Language：English   Publisher：Journal of Vascular Surgery  

Objective: This study aimed to compare the influence of inframalleolar (IM) P0/P1 on wound healing in bypass surgery vs endovascular therapy (EVT) in patients with chronic limb-threatening ischemia (CLTI). Methods: We retrospectively analyzed the multicenter data of patients who underwent infra-inguinal revascularization for CLTI between 2015 and 2022. IM P represents target artery crossing into foot, with intact pedal arch (P0) and absent or severely diseased pedal arch (P1). The endpoints were wound healing, limb salvage (LS), and postoperative complications. Results: We analyzed 66 and 189 propensity score-matched pairs in the IM P0 and IM P1 cohorts, respectively. In the IM P0 cohort, the 1-year wound healing rates were 94.5% and 85.7% in the bypass surgery and EVT groups, respectively (P = .092), whereas those in the IM P1 cohort were 86.2% and 66.2% in the bypass surgery and EVT groups, respectively (P < .001). In the IM P0 cohort, the 2-year LS rates were 96.7% and 94.1% in the bypass surgery and EVT groups, respectively (P = .625), and those in the IM P1 cohort were 91.8% and 81.5% in the bypass surgery and EVT groups, respectively (P = .004). No significant differences were observed between the bypass surgery and EVT in terms of postoperative complication rates in either the IM P0 or P1 cohorts. Conclusions: Bypass surgery facilitated better wound healing and LS than EVT in patients with IM P1. Conversely, no differences in wound healing or LS were observed between groups in patients with IM P0. Bypass surgery should be considered a better revascularization strategy than EVT in patients with tissue loss and IM P1 disease.

DOI： 10.1016/j.jvs.2024.04.040

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Language：English   Publisher：Annals of Surgical Oncology  

Background: Signal-regulatory protein alpha (SIRPα) is an immune checkpoint molecule expressed on macrophages that functions to inhibit phagocytosis by binding to CD47 expressed on tumor cells. SIRPα has attracted increasing attention as a novel target for cancer immunotherapy; however, the expression and immune function of SIRPα in lung squamous cell carcinoma (LUSC) remain unclear. Therefore, this study aimed to identify the clinical importance of SIRPα expression in LUSC and to explore the factors that elevate SIRPα expression. Patients and Methods: Primary LUSC specimens surgically resected from 172 patients underwent immunohistochemical evaluation of the association of SIRPα expression on tumor-associated macrophages with clinicopathological features and clinical outcomes. Furthermore, we analyzed the association of SIRPα expression with tumor-infiltrating lymphocytes and the expression of programmed cell death ligand 1 (PD-L1). In vitro, monocytes were treated with cytokines, and SIRPα protein expression was assessed by flow cytometry. Results: There were no differences in SIRPα expression and clinicopathological factors. High SIRPα expression was significantly associated with PD-L1-positive expression, and high CD8, PD-1, and CD163 expression. The high SIRPα expression group showed significantly shorter recurrence-free survival (RFS) and overall survival (OS). On multivariate analysis, high SIRPα expression was an independent poor prognostic factor for RFS and OS. The expression of SIRPα protein in monocytes was upregulated by treatment with IFNγ. Conclusion: Our analysis revealed that high SIRPα expression significantly predicts poor prognosis in patients with surgically resected LUSC.

DOI： 10.1245/s10434-024-15649-3

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DOI： 10.1007/s00595-024-02930-x

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DOI： 10.1245/s10434-024-16065-3

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Language：English   Publisher：Surgery Today  

Purpose: We aimed to define borderline resectable colorectal liver metastases (CRLM) based on the analysis of risk factors for early surgical failure and investigate the efficacy of neoadjuvant chemotherapy in these patients. Methods: This was a retrospective analysis of a multi-institutional cohort of patients diagnosed with technically resectable CRLM. Early surgical failure within 6 months of liver surgery was defined as ESF6. We classified CRLM into three grades (A, B, and C) according to the definition of the Japanese Society for Cancer of the Colon and Rectum. Results: Among the 249 patients with technically resectable CRLM, 46 (18.5%) developed ESF6. The survival rate of these patients was significantly lower than that of the patients without ESF6. In the multivariate analysis of synchronous CRLM patients, no neoadjuvant chemotherapy, Grade B/C, and Charlson comorbidity index ≥ 3 were independent predictors of ESF6. Among patients with synchronous and Grade B/C CRLM, ESF6 rates, surgical failure-free survival, and overall survival in the neoadjuvant chemotherapy group were significantly better relative to the upfront surgery group. Conclusions: Patients with synchronous and Grade B/C CRLM are at a high risk of early surgical failure, have a poor long-term prognosis, and can be defined as borderline resectable and good candidates for neoadjuvant chemotherapy.

DOI： 10.1007/s00595-024-02920-z

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Language：English   Publisher：Surgery Today  

Purpose: Infectious complications, particularly post-transplant sepsis, have a critical impact on postoperative outcomes. This study examined the effects of perioperative synbiotic treatment on postoperative outcomes in patients receiving early enteral nutrition. Methods: We reviewed 210 living-donor liver transplantation procedures and retrospectively analyzed the postoperative outcomes with and without perioperative synbiotic treatment (live lactic acid bacteria, bifidobacteria, and oligosaccharides) 5 days before and after living-donor liver transplantation. Results: The synbiotic group (n = 34) had significantly fewer male donors (38.2% vs. 61.9%, p = 0.011) and a higher proportion of ABO-incompatible grafts (52.9% vs. 25.6%, p = 0.021) than the non-synbiotic group (n = 176). The incidence of sepsis was significantly lower in the synbiotic group than in the non-synbiotic group (0% vs. 7.4%, p = 0.029), with a lower incidence rate of sepsis due to bacteremia with intestinal bacteria (0% vs. 4.6%, p = 0.089). There were no significant differences in the proportions of acute rejection, small-for-size graft syndrome, or postoperative liver function between the two groups. Furthermore, there was no significant difference in the graft survival rates after LDLT between two groups. (p = 0.24). Conclusion: Perioperative synbiotic treatment prevents post-transplant sepsis, even with early enteral nutrition.

DOI： 10.1007/s00595-024-02918-7

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DOI： 10.1245/s10434-024-15960-z

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Language：English   Publisher：Annals of Surgical Oncology  

DOI： 10.1245/s10434-024-15177-0

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Publisher：American Journal of Transplantation  

The excess mortality of coronavirus disease 2019 (COVID-19) solid organ transplant recipients (SOTRs) throughout the pandemic remains unclear. This prospective cohort study based on the Japanese nationwide registry included 1632 SOTRs diagnosed with COVID-19 between February 1, 2020, and July 31, 2022, categorized based on dominant phases of variants of concern (VOCs): Waves 1 to 3 (Beta), 4 (Alpha), 5 (Delta), 6 (Omicron BA.1/BA.2), and 7 (Omicron BA.5). Excess mortality of COVID-19-affected SOTRs was analyzed by calculating standardized mortality ratios (SMRs). Overall, 1632 COVID-19-confirmed SOTRs included 1170 kidney, 408 liver, 25 lung, 20 heart, 1 small intestine, and 8 multiorgan recipients. Although disease severity and all-cause mortality decreased as VOCs transitioned, SMRs of SOTRs were consistently higher than those of the general population throughout the pandemic, showing a U-shaped gap that peaked toward the Omicron BA.5 phase; SMR (95% CI): 6.2 (3.1-12.5), 4.0 (1.5-10.6), 3.0 (1.3-6.7), 8.8 (5.3-14.5), and 21.9 (5.5-87.6) for Waves 1 to 3 (Beta), Wave 4 (Alpha), Wave 5 (Delta), Wave 6 (Omicron BA.1/2), and Wave 7 (Omicron BA.5), respectively. In conclusion, COVID-19 SOTRs had greater SMRs than the general population across the pandemic. Vaccine boosters, immunosuppression optimization, and other protective measures, particularly for older SOTRs, are paramount.

DOI： 10.1016/j.ajt.2024.03.016

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Language：English   Publisher：Journal of Thoracic Disease  

Background: The preoperative serum creatine kinase (CK) concentration is a prognostic factor for malignant diseases. We investigated the significance of CK in surgically resected thymic epithelial tumors and the relationship between CK and clinicopathological factors. Methods: We retrospectively evaluated the relationship between preoperative CK levels and prognosis in 120 patients with thymic epithelial tumors who underwent surgical resection at two centers. The cutoff for CK was determined by the standard value in our institution (<62 IU/L for men and <45 IU/L for women). The paravertebral muscle at the Th12 level was used to assess skeletal muscle area to investigate sarcopenia. Results: Eighteen patients (15.0%) were categorized into the low CK group. The CK level was not associated with age, sex, performance status, myasthenia gravis, and pathological findings. Preoperative serum albumin and total cholesterol concentrations were significantly lower in the low CK group than in the normal CK group (both P<0.001). Moreover, the Th12 muscle index was lower in the low CK group (P=0.03), indicating that low CK was related to sarcopenia. Kaplan-Meier curve analysis illustrated that patients in the low CK group had significantly shorter disease-free survival (DFS) and overall survival (OS) than those in the normal CK group (P=0.03 and P=0.002, respectively). Multivariate analysis identified low CK as an independent prognostic factor for DFS (P=0.03) and OS (P=0.005). Conclusions: Preoperative serum CK might reflect the host nutritional status in patients with resected thymic epithelial tumors; therefore, CK could be a biomarker of postoperative prognosis.

DOI： 10.21037/jtd-23-1797

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: The eighth edition of lung cancer N staging assignment includes the location of lymph node metastasis, but does not include single-N and multiple-N descriptors. RESEARCH QUESTION: Do the single-N and multiple-N statuses stratify the prognosis of patients with non-small cell lung cancer (NSCLC)? STUDY DESIGN AND METHODS: Using the National Cancer Database, we analyzed patients with pathologically staged N1 and N2 NSCLC. N descriptors were classified into pathological single N1 (pSingle-N1), pathological multiple N1 (pMulti-N1), pathological single N2 (pSingle-N2), and pathological multiple N2 (pMulti-N2). Survival analysis was performed using the Kaplan-Meier method and multivariable Cox regression models. RESULTS: In the general analysis cohort, 24,531, 22,256, 8,528, and 21,949 patients with NSCLC demonstrated pSingle-N1, pMulti-N1, pSingle-N2, and pMulti-N2 disease, respectively. Patients with pMulti-N1 and pMulti-N2 disease showed a shorter survival than those with pSingle-N1 and pSingle-N2 disease, respectively (hazard ratio [HR], 1.22 [P < .0001] for N1 and 1.39 [P < .0001] for N2). After adjusting age, sex, and histologic findings, the HR for pSingle-N2 compared with pMulti-N1 disease was 1.05 (P = .0031). Patients with pN1 disease were categorized by metastatic lymph node count (1, 2, 3, ≥ 4), showing significant prognostic differences among groups (P < .0001). In the sensitivity analysis cohort (limited to R0 resection, lobectomy, or more; survival ≥ 30 days; ≥ 10 examined lymph nodes; and without neoadjuvant therapy; n = 34,904) and the external validation cohort (n = 708), analyses supported these results. INTERPRETATION: Patients with NSCLC with one metastatic lymph node, whether in N1 or N2 stations, showed better survival than those with more than one lymph node involved. Patients with NSCLC with a single-skip N2 lymph node metastasis showed survival similar to patients with multiple N1 lymph nodes, and the number of lymph nodes involved in N1 resections up to four or more was sequentially prognostic.

DOI： 10.1016/j.chest.2024.06.3797

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Language：English   Publisher：Annals of Gastroenterological Surgery  

Aim: There is limited evidence regarding the feasibility of living-donor liver transplantation (LDLT) for patients aged over 70. The aims of this study were to assess postoperative outcomes in elderly recipients and to ascertain the potential feasibility and acceptability of LDLT. Methods: Data were collected from 762 recipients, including 26 in the elderly group (aged ≥70) and 736 in the younger group (aged <70), and reviewed even by propensity score matching (PSM). Results: No significant differences were observed in the frequency of postoperative complications between the two groups. Additionally, both groups exhibited a comparable 30-day mortality rate after LDLT (3.9% in both) and similar hospital stays (36 days vs. 40 days). The 1-, 3-, and 5-year graft survival rates in the elderly group were 92.0%, which was comparable to those in the younger group (p = 0.517), as confirmed by PSM. Notably, all donors for elderly patients were the children of the recipients, with an average age of 41.6 years, and grafts from donors aged ≥50 years were not utilized, signifying the use of high-quality grafts. Our inclusion criterion for elderly recipients was strictly defined as an ECOG-PS score of 0–2, which played a pivotal role in achieving favorable postoperative outcomes. Conclusion: LDLT can be performed safely for elderly patients aged 70 years or older, provided they have a preserved PS and receive high-quality grafts from younger donors, inevitably all children of elderly recipients. This approach yields acceptable long-term outcomes. Consequently, age alone should not serve as an absolute contraindication for LDLT.

DOI： 10.1002/ags3.12769

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Language：English   Publisher：Surgery Today  

Purpose: To evaluate the short term-outcomes of venous reconstruction using a round ligament-covered prosthetic vascular graft and assess its effectiveness in the prevention of prosthetic vascular graft migration in right‑lobe living donor liver transplantation (LDLT). Methods and results: Thirty patients underwent reconstruction of the middle hepatic vein (MHV) tributaries during right lobe LDLT between January, 2021 and October, 2022. These patients were divided into the autologous vascular graft group (A group, n = 24) and the round ligament-covered prosthetic vascular graft group (RP group, n = 6). The computed tomography (CT) density ratio of the drainage area in the posterior segment of patent grafts was significantly higher in the RP group than in the A group (0.91 vs. 1.06, p = 0.0025). However, the patency rates of reconstructed MHV tributaries in the A and RP groups were 61% and 67%, respectively, with no significant difference between the groups (p = 0.72). Prosthetic vascular graft migration did not occur in the RP group. Conclusion: Venous reconstruction using round ligament-covered prosthetic vascular grafts is a feasible and simple method to prevent prosthetic vascular graft migration in right-lobe LDLT.

DOI： 10.1007/s00595-024-02793-2

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Language：English   Publisher：Hepatology Research  

Aim: The Japanese indication criteria for liver transplantation (LT) for hepatocellular carcinoma (HCC) have been updated based on living donor LT data to include either the Milan criteria (MC) or the 5-5-500 rule, which requires a nodule size of ≤5 cm, ≤5 nodules, and an alpha-fetoprotein (AFP) level ≤500 ng/mL. We aimed to validate the 5-5-500 rule and the MC for deceased donor LT (DDLT). Methods: Using national registry data from the United States from 2010 to 2014, we separated DDLT patients into four groups based on the MC and the 5-5-500 rule. The AFP values were stratified into categories: ≤100, 101–300, 301–500, and >500 ng/mL. Results: The 5-year survival rate was significantly lower for patients in the groups within MC/beyond 5-5-500 (56.3%) or beyond MC/5-5-500 (60.7%) than for patients in the groups within MC/5-5-500 (76.2%) and beyond MC/within 5-5-500 (72.3%) (p < 0.01). Hepatocellular carcinoma recurrence at 5 years was highest for the within MC/beyond 5-5-500 (25.4%) group, followed by the beyond MC/within 5-5-500 (13.1%), beyond MC/5-5-500 (9.6%), and within MC/5-5-500 (7.4%) groups. The stratified 5-year survival rates after DDLT were 76.5%, 72.4%, 58.4%, and 55.6% in the AFP ≤100, 101–300, 301–500, and >500 categories, respectively (p < 0.01). Conclusion: The 5-5-500 rule guides the appropriate selection of patients with HCC for DDLT. Patients with AFP levels from 300 to 500 ng/mL had inferior outcomes even when they met the 5-5-500 rule, so further investigation is needed to guide their treatment.

DOI： 10.1111/hepr.14017

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Language：English   Publisher：Journal of Gastrointestinal Surgery  

Purpose: Although the incidence of recipients and donors with overweight and obesity is increasing worldwide, few reports have focused on outcomes of preoperative weight reduction (WR) in living-donor liver transplantation (LDLT). Therefore, we examined the outcomes and the impact of WR on the postoperative course. Methods: We analyzed 217 consecutive LDLT procedures performed from 2017 to 2022. We divided the recipients and donors into a WR group and non-WR group. Results: Twenty-two recipients (10.1%) achieved WR (preoperative recipient WR [RWR] group), reducing their weight by 6.8% ± 6.0% within 2.2 ± 1.4 months with a significant decrease in body mass index (BMI) (P < .0001). The RWR group showed no significant differences in short-term postoperative outcomes (operative factors, postoperative liver function tests, amount of ascites, and morbidity) or in the graft survival rate as a long-term outcome (P = .24) compared with the non-RWR group. Forty-one donors (18.9%) achieved WR (preoperative donor WR [DWR] group), reducing their weight by 9.7% ± 6.3% within 3.2 ± 5.8 months with a significant decrease in BMI (P < .0001). Compared with the non-DWR group, the DWR group showed no significant differences in short-term postoperative outcomes between themselves and recipients or in the graft survival rate (P = .49). Furthermore, WR resulted in an increase to 32 donor-eligible and 6 recipient-eligible patients. Conclusion: WR in LDLT recipients and donors had no harmful effect on postoperative outcomes and should lead to increase recipients’ chance of undergoing LDLT and to expand the donor pool.

DOI： 10.1016/j.gassur.2024.04.010

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Language：English   Publisher：Journal of Vascular Surgery  

Objective: This study aimed to evaluate treatment outcomes after bypass surgery or endovascular therapy (EVT) in average- and high-risk patients with chronic limb-threatening ischemia (CLTI). Methods: We retrospectively analyzed multicenter data of patients who underwent infra-inguinal revascularization for CLTI between 2015 and 2022. A high-risk patient was defined as one with estimated 30-day mortality rate ≥5% or 2-year survival rate ≤50%, as determined by the Surgical Reconstruction vs Peripheral Intervention in Patients With Critical Limb Ischemia (SPINACH) calculator. The amputation-free survival (AFS), limb salvage (LS), wound healing, and 30-day mortality were compared separately for the average- and high-risk patients between the bypass and EVT with propensity score matching. Results: We analyzed 239 and 31 propensity score-matched pairs in the average- and high-risk patients with CLTI. In the average-risk patients, the 2-year AFS and LS rates were 78.1% and 94.4% in the bypass group and 63.0% and 87.7% in the EVT group (P <.001 and P =.007), respectively. The 1-year wound healing rates were 88.6% in the bypass group and 76.8% in the EVT group, respectively (P <.001). The 30-day mortality was 0.8% in the bypass surgery and 0.8% in the EVT group (P =.996). In the high-risk patients, there was no differences in the AFS, LS, and wound healing between the groups (P =.591, P =.148, and P =.074). The 30-day mortality was 3.2% in the bypass group and 3.2% in the EVT group (P =.991). Conclusions: Bypass surgery is superior to EVT with respect to the AFS, LS, and wound healing in the average-risk patients. EVT is a feasible first-line treatment strategy for high-risk patients with CLTI undergoing revascularization, based on the lack of significant differences in the 2-year AFS rate, between the bypass surgery and EVT cohorts.

DOI： 10.1016/j.jvs.2024.03.025

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Language：English   Publisher：Surgery Today  

Some patients with refractory esophagogastric varices require surgery, such as gastric devascularization and splenectomy (Hassab’s procedure). However, these patients are at risk of perioperative morbidities when undergoing devascularization to develop collateral vessels. We performed a more simplified procedure, splenectomy, and en bloc gastropancreatic fold division (GPFD) with hand-assisted laparoscopic surgery. Four patients with refractory esophagogastric varices and portal hypertension underwent splenectomy and GPFD. We reviewed patients’ perioperative laboratory and morphological data, operative variables, and postoperative outcomes. Esophagogastric varices improved in 3 (75%) of the 4 patients. In one patient, esophageal varices (F1RC0) were observed 3 years after surgery, but they required no treatment and only received follow-up. Treatment with splenectomy and GPFD is not only less invasive than Hassab’s procedure but also provides effective outcomes for refractory esophagogastric varices.

DOI： 10.1007/s00595-023-02780-z

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Language：English   Publisher：Surgery Today  

Living-donor liver transplantation (LDLT) is an established treatment for patients with end-stage liver disease or acute liver failure, and outflow reconstruction is considered one of the most vital techniques in LDLT. To date, many strategies have been reported to prevent outflow obstruction, which can be refractory to liver dysfunction and can cause life-threatening graft loss or mortality. In addition, in this era of laparoscopic hepatectomy in donor surgery, especially LDLT using a left liver graft, it has been predicted that cutting the hepatic vein with automatic linear staplers will lead to more outflow-related problems than with conventional open hepatectomy because of the short neck of the anastomosis orifice. We herein review 10 cases of venoplasty performed with a novel venous cuff system using a donor’s round ligament around the hepatic vein in LDLT with a left lobe graft, which makes anastomosis of the hepatic vein sterically easy for postoperative venous patency.

DOI： 10.1007/s00595-023-02791-w

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Language：English   Publisher：Anticancer Research  

Background/Aim: Osteopenia, the loss of bone mineral density (BMD), was recently reported as a prognostic factor in various cancers. However, the prognostic significance of preoperative osteopenia in breast cancer remains unclear. This study aimed to clarify the clinical significance of preoperative osteopenia in breast cancer. Patients and Methods: We retrospectively analyzed the relationship between osteopenia and clinical factors and prognosis in 532 patients with pathological Stage I-III primary breast cancer between 2009 and 2017. Osteopenia was assessed by measuring the average pixel density (Hounsfield unit) in the midvertebral core of the 11th thoracic vertebra on enhanced preoperative computed tomography. Results: Osteopenia was diagnosed in 186 (35.0%) patients. The recurrence-free survival (RFS) rate was significantly worse in the osteopenia group than in the non-osteopenia group (p=0.0275), but there was no significant difference in overall survival (OS) between the two groups. When evaluated by menopausal status, RFS and OS were significantly worse in the osteopenia group than in the non-osteopenia group (p=0.0094 and p=0.0264, respectively) in premenopausal patients. However, there were no significant differences in RFS and OS between the two groups among postmenopausal patients. In premenopausal patients, osteopenia was an independent prognostic factor for RFS in a multivariate analysis (p=0.0266). Conclusion: Preoperative osteopenia was independently associated with recurrence of breast cancer.

DOI： 10.21873/anticanres.17074

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Evidence regarding the application of the multispectral camera for blood flow measurement is insufficient, and its performance has not been compared with the conventional indocyanine green (ICG) method. Therefore, we retrospectively compared the effectiveness of a new multispectral camera for non-invasive, real-time, quantitative imaging of tissue oxygen (O2) saturation and hemoglobin (Hb) levels and commercially available ICG fluorescence imaging in hemodynamic assessment of gastric tubes in esophagectomy. METHODS: Thirty patients who underwent thoracoscopic esophagectomy and gastric tube reconstruction for esophageal cancer were included in this study. The multispectral camera was used to measure tissue O2 saturation and Hb levels. The ICG fluorescence imaging, with the analysis software tool Lumi view, was employed to record ICG luminance changes, with values measured at the anastomotic site. Furthermore, the usefulness of each assessment device was examined using the arterial and venous blood flow indices as cutoff lines for cases with anastomotic failure. RESULTS: In the evaluation of arterial perfusion, anastomotic leak occurred in three of the five (60 %) patients with arterial insufficiency as assessed by the ICG imaging, while anastomotic leakage occurred in all three patients (100 %) who were assessed as having arterial insufficiency by the multispectral camera. In the evaluation of venous perfusion, anastomotic leakage occurred in three of the nine (33.3 %) patients diagnosed with venous stasis by the IC imaging and in three of the five (60 %) patients assessed by the multispectral camera. CONCLUSION: The multispectral camera assessed gastric tube blood flow more accurately than the ICG fluorescence method.

DOI： 10.1016/j.sopen.2024.03.005

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DOI： 10.1016/j.ejso.2024.108374

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Language：English   Publisher：European Journal of Vascular and Endovascular Surgery  

Objective: This study aimed to evaluate three survival prediction models: the JAPAN Critical Limb Ischaemia Database (JCLIMB), Surgical Reconstruction Versus Peripheral Intervention in Patients With Critical Limb Ischaemia (SPINACH), and Vascular Quality Initiative (VQI) calculators. Methods: Multicentre data of patients who underwent infrainguinal revascularisation for chronic limb threatening ischaemia between 2018 and 2021 were analysed retrospectively. The prediction models were validated using a calibration plot analysis with the intercept and slope. The discrimination was evaluated using area under the curve (AUC) analysis. The observed two year overall survival (OS) was evaluated by the Kaplan – Meier method. The two year OS predicted by each model at < 50%, 50 – 70%, and > 70% was defined as high, medium, and low risk, respectively. Results: A total of 491 patients who underwent infra-inguinal revascularisation were analysed. The rates of surgical revascularisation, endovascular therapy, and hybrid therapy were 26.5%, 70.1%, and 5.5%, respectively. The average age was 75.6 years, and the percentages of patients with diabetes mellitus and dialysis dependent end stage renal disease were 66.6% and 44.6%, respectively. The tissue loss rate was 85.7%. The intercept and slope were −0.13 and 1.18 for the JCLIMB, 0.11 and 0.82 for the SPINACH, and −0.15 and 1.10 for the VQI. The AUC for the two year OS of JCLIMB, SPINACH, and VQI were 0.758, 0.756, and 0.740, respectively. The observed two year OS rates of low, medium, and high risk using the JCLIMB calculator were 80.1%, 61.1%, and 28.5%, respectively (p < .001), using the SPINACH calculator were 81.0%, 57.0%, and 38.1%, respectively (p < .001), and using the VQI calculator were 77.8%, 45.8%, and 49.6%, respectively (p < .001). Conclusion: The JCLIMB, SPINACH, and VQI survival calculation models were useful, although the OS predicted by the VQI model appeared to be lower than the observed OS.

DOI： 10.1016/j.ejvs.2023.12.023

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Language：English   Publisher：eBioMedicine  

Background: Cell–cell interaction factors that facilitate the progression of adenoma to sporadic colorectal cancer (CRC) remain unclear, thereby hindering patient survival. Methods: We performed spatial transcriptomics on five early CRC cases, which included adenoma and carcinoma, and one advanced CRC. To elucidate cell–cell interactions within the tumour microenvironment (TME), we investigated the colocalisation network at single-cell resolution using a deep generative model for colocalisation analysis, combined with a single-cell transcriptome, and assessed the clinical significance in CRC patients. Findings: CRC cells colocalised with regulatory T cells (Tregs) at the adenoma–carcinoma interface. At early-stage carcinogenesis, cell–cell interaction inference between colocalised adenoma and cancer epithelial cells and Tregs based on the spatial distribution of single cells highlighted midkine (MDK) as a prominent signalling molecule sent from tumour epithelial cells to Tregs. Interaction between MDK-high CRC cells and SPP1+ macrophages and stromal cells proved to be the mechanism underlying immunosuppression in the TME. Additionally, we identified syndecan4 (SDC4) as a receptor for MDK associated with Treg colocalisation. Finally, clinical analysis using CRC datasets indicated that increased MDK/SDC4 levels correlated with poor overall survival in CRC patients. Interpretation: MDK is involved in the immune tolerance shown by Tregs to tumour growth. MDK-mediated formation of the TME could be a potential target for early diagnosis and treatment of CRC. Funding: Japan Society for the Promotion of Science (JSPS) Grant-in-Aid for Science Research; OITA Cancer Research Foundation; AMED under Grant Number; Japan Science and Technology Agency (JST); Takeda Science Foundation; The Princess Takamatsu Cancer Research Fund.

DOI： 10.1016/j.ebiom.2024.105102

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Language：English   Publisher：Liver Transplantation  

Elevated Protein Induced by Vitamin-K Absence-II (PIVKA-II) has been shown to be an adverse prognostic factor in HCC patients undergoing liver transplantation (LT). No definitive data are available about the impact of PIVKA-II concerning post-LT recurrence in patients not secreting (≤ 20 ng/mL) alpha-fetoprotein (AFP). An observational retrospective study of the East-West HCC-LT consortium is reported. Between 2000 and 2019, 639 HCC patients were enrolled in 5 collaborative European and Japanese centers. To minimize the initial selection bias, an inverse probability therapy weighting method was adopted to analyze the data. In the post-inverse probability therapy weighting population, PIVKA-II (HR = 2.00; 95% CI: 1.52-2.64; p < 0.001) and AFP (HR=1.82; 95% CI: 1.48-2.24; p < 0.001) were the most relevant independent risk factors for post-LT recurrence. A sub-Analysis focusing only on patients who are AFP non-secreting confirmed the negative role of PIVKA-II (HR=2.06, 95% CI: 1.26-3.35; p=0.004). When categorizing the entire population into 4 groups according to the AFP levels (≤ or > 20 ng/mL) and PIVKA (≤ or > 300 mUA/mL) at the time of LT, the lowest recurrence rates were observed in the low AFP-PIVKA-II group (5-year recurrence rate = 8.0%). Conversely, the high AFP-PIVKA-II group had the worst outcome (5-year recurrence rate = 35.1%). PIVKA-II secretion is a relevant risk factor for post-LT HCC recurrence. The role of this marker is independent of the AFP status. Combining both tumor markers, especially in the setting of LT, should be of great relevance for adding information about predicting the post-LT risk of tumor recurrence and selecting these patients for transplantation.

DOI： 10.1097/LVT.0000000000000259

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Language：English   Publisher：Liver Transplantation  

DOI： 10.1097/LVT.0000000000000308

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Language：English   Publisher：シュプリンガー・ジャパン(株)  

Language：English   Publishing type：Research paper (scientific journal)  

PURPOSES: End-stage liver and kidney disease is an indication for simultaneous liver and kidney transplantation. However, in countries where deceased donor transplantation is not well established, living donor liver transplantation (LDLT) is a realistic option for patients on hemodialysis (HD). We investigated the outcomes of LDLT for patients on HD. METHODS: We conducted a retrospective multicenter survey of patients on chronic HD who underwent LDLT in East Asian countries. The characteristics of donors and recipients and the short and long-term outcomes were analyzed. RESULTS: Between 2001 and 2021, 45 patients on HD underwent LDLT and 11 of these patients also underwent kidney transplantation (KT). The overall survival rate at 5 years of the 34 patients who underwent only LDLT was 44.5%. Multivariate analysis identified a low graft recipient weight ratio (< 1%) (p = 0.048) and long HD duration (≥ 10 years) (p = 0.046) as independent predictors of poor overall survival. The major complication was posttransplant bleeding, which occurred in12 patients (35%). CONCLUSION: It is important to establish the indications for LDLT, taking into consideration graft size and HD duration in candidate patients on HD.

DOI： 10.1007/s00595-023-02751-4

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Publisher：日本メディカルセンター  

DOI： 10.19020/cg.0000003026

CiNii Research

Language：English   Publishing type：Research paper (scientific journal)  

PURPOSE: Few studies have investigated the impact of the surgical proximal and distal margins on colon cancer recurrence. We conducted this study to investigate the effect of resection margins on the prognosis of resectable colon cancer. METHODS: We analyzed data on 1458 patients who underwent colorectal resection in our institute between January, 2004 and March, 2020, including 579 patients with resectable colon cancer. The association between the resection margin and recurrence for each oncological status was assessed and the value of the resection length that influenced recurrence was analyzed. RESULTS: Patients who had pT4 colon cancer with margins of more than 7 cm had a trend of fewer recurrences and longer relapse-free survival (RFS) than those with colon cancer of other stages (P = 0.033; hazard ratio [HR], 0.42; 95% confidence interval [CI], 0.20-0.89). Multivariate analysis identified a margin of < 7 cm as an independent risk factor for RFS in patients with pT4 colon cancer (P = 0.023; HR, 2.65; 95% CI 1.013-6.17). No correlation was found between resection margins and recurrence, depending on the extent of lymph node metastasis and tumor location. CONCLUSION: A resection margin of at least 7 cm should be maintained for patients with pT4 colon cancer.

DOI： 10.1007/s00595-024-02836-8

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Language：Japanese   Publisher：The Japan Broncho-esophagological Society  

DOI： 10.2468/jbes.75.144

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1245/s10434-024-15246-4

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Language：Others   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.ajt.2024.04.016

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Language：English   Publisher：Surgery Today  

Purpose: To verify the usefulness of haptic feedback in telesurgery and improve the safety of telerobotic surgery. Methods: The surgeon's console was installed at two sites (Fukuoka and Beppu; 140 km apart), and the patient cart was installed in Fukuoka. During the experiment, the surgeon was blinded to the haptic feedback levels and asked to grasp the intestinal tract in an animal model. The surgeon then performed the tasks at each location. Results: No marked differences in task accuracy or average grasping force were observed between the surgeon locations. However, the average task completion time was significantly longer, and the system usability scale (SUS) was significantly lower rating for remote operations than for local ones. No marked differences in task accuracy or task completion time were observed between the haptic feedback levels. However, with haptic feedback, the organ was grasped with a significantly weaker force than that without it. Furthermore, with haptic feedback, experienced surgeons in robotic surgery tended to perform an equivalent task with weaker grasping forces than inexperienced surgeons. Conclusion: The haptic feedback function is a tool that allows the surgeon to perform surgery with an appropriate grasping force, both on site and remotely. Improved safety is necessary in telesurgery; haptic feedback will thus be an essential technology in robotic telesurgery going forward.

DOI： 10.1007/s00595-023-02732-7

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Language：English   Publisher：シュプリンガー・ジャパン(株)  

Language：English   Publisher：(一社)日本外科学会  

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Publisher：金原出版  

DOI： 10.18888/op.0000003803

CiNii Research

Language：English  

DOI： 10.1186/s40792-024-01856-3

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Glutathione peroxidase 2 (GPX2) is an antioxidant enzyme with an important role in tumor progression in various cancers. However, the clinical significance of GPX2 in lung adenocarcinoma has not been clarified. METHODS: Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to analyze GPX2 mRNA expression. Then, we conducted immunohistochemistry (IHC) to assess GPX2 expression in specimens acquired from 351 patients with lung adenocarcinoma who underwent surgery at Kyushu University from 2003 to 2012. We investigated the association between GPX2 expression and clinicopathological characteristics and further analyzed the prognostic relevance. RESULTS: qRT-PCR revealed that GPX2 mRNA expression was notably higher in tumor cells than in normal tissues. IHC revealed that high GPX2 expression (n = 175, 49.9%) was significantly correlated with male sex, smoking, advanced pathological stage, and the presence of pleural, lymphatic, and vascular invasion. Patients with high GPX2 expression exhibited significantly shorter recurrence-free survival (RFS) and overall survival. Multivariate analysis identified high GPX2 expression as an independent prognostic factor of RFS. CONCLUSIONS: GPX2 expression was significantly associated with pathological malignancy. It is conceivable that high GPX2 expression reflects tumor malignancy. Therefore, high GPX2 expression is a significant prognostic factor of poor prognosis for completely resected lung adenocarcinoma.

DOI： 10.1245/s10434-024-15116-z

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Language：Japanese   Publisher：(一社)日本腹部救急医学会  

食道ステント脱落は一般的なステント合併症だが,胃より遠位に移動することはほとんどなく,脱落したステントが原因で小腸閉塞をきたす症例は珍しい。ステント脱落のリスクとして化学療法の腫瘍縮小効果に伴う食道癌部内圧の低下や,カバードステントなど滑りやすい材質の使用が報告されている。とくに,近年食道癌での使用が可能となった免疫チェックポイント阻害薬(immune checkpoint inhibitors:以下,ICI)は,従来の殺細胞性抗腫瘍薬より高い腫瘍縮小効果が期待できることから,ステント併用時の脱落のリスクが懸念される。今回,われわれは進行食道癌部ステント留置後にICI併用化学療法を行い,ステント脱落から小腸閉塞をきたし手術を要した1例を経験したので報告する。(著者抄録)

Language：English   Publisher：Springer Berlin Heidelberg  

Language：English   Publisher：John Wiley & Sons Australia, Ltd  

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Recent advancements in systemic therapy for hepatocellular carcinoma (HCC) necessitate the establishment of resectability criteria for advanced HCC. METHODS: A questionnaire survey sought to clarify the perspectives of Japanese expert hepatobiliary surgeons regarding surgical indications for HCC. Thirty-one questions were used to determine when surgery is strongly recommended (resectable: R) or not recommended (unresectable: UR). RESULTS: A total of 351 responses were obtained. While 64.7% of the respondents considered solitary tumors as being R, irrespective of size, opinions diverged on the upper limit of the number of tumors/tumor size for R: (1) up to three nodules with no size limit (27.9%), (2) up to three nodules ≤5 cm in diameter each (21.4%) and (3) up to three nodules ≤3 cm in diameter each (19.4%). Vp1, Vp2, Vp3, and Vp4 were considered as being R by 90.9%, 70.7%, 39.0%, and 8.0% of respondents, respectively. Half of the respondents indicated they would consider resection even for cases with extrahepatic spread under limited conditions. CONCLUSIONS: The current views of Japanese expert surgeons on the resectability criteria for HCC were clarified for the first time. The findings could serve as a basis for preparing expert consensus statements on the resectability criteria for HCC.

DOI： 10.1002/jhbp.1408

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Language：English   Publisher：Journal of Gastroenterology and Hepatology (Australia)  

Aim: Pretreatment peripheral blood markers have value in predicting the treatment outcome of various cancers. In particular, the eosinophil count has recently gained attention. However, no study has reported the influence of the pretreatment eosinophil count on the outcomes of atezolizumab plus bevacizumab (ATZ/BEV), which is the recommended first-line systemic therapy for unresectable hepatocellular carcinoma (u-HCC). Methods: We enrolled 114 patients with u-HCC treated with ATZ/BEV (n = 48) or lenvatinib (n = 66). The patients receiving ATZ/BEV or lenvatinib were divided into two groups by calculating the cutoff value of the pretreatment eosinophil count. The groups were compared regarding the clinicopathological characteristics, outcomes, and incidence of adverse events (AEs). Results: Twenty-three of 48 patients (47.9%) who received ATZ/BEV therapy were categorized as the ATZ/BEV-eosinophil-high group, which had better responses than the ATZ/BEV-eosinophil-low group (P = 0.0090). Kaplan–Meier curves revealed a trend toward significantly better progression-free survival (PFS) in the ATZ/BEV-eosinophil-high group than the ATZ/BEV-eosinophil-low group (the median PFS: 4.7 months in the ATZ/BEV-eosinophil-low group vs 12.6 months in the ATZ/BEV-eosinophil-high group; P = 0.0064). Multivariate analysis showed that a low eosinophil count was an independent risk factor for worse PFS after ATZ/BEV therapy (P = 0.0424, hazard ratio: 2.24, 95% confidence interval: 1.02–4.89). AEs (≥ grade 3) were significantly more likely to occur in the ATZ/BEV-eosinophil-high group (P = 0.0285). The outcomes did not significantly differ between the LEN-eosinophil-high group and the LEN-eosinophil-low group. Conclusion: A high pretreatment eosinophil count predicted a better response to ATZ/BEV therapy for u-HCC and was associated with the incidence of AEs (≥ grade 3).

DOI： 10.1111/jgh.16441

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND/AIM: The efficacy of neoadjuvant chemotherapy (NAC) for colon cancer remains unestablished. This study aimed to investigate the outcomes of NAC in patients with locally advanced T4b or obstructive T4a colon cancers (LACC). PATIENTS AND METHODS: Data of patients with LACC who underwent colon surgery between 2010 and 2022 after NAC at our institution were retrospectively reviewed. Patient characteristics, surgical outcomes, tumor features, and prognosis were analyzed. RESULTS: Among 800 patients with LACC who underwent radical resection, 11 received NAC because of cT4b or cT4a with mechanical obstruction. NAC, administered as a doublet regimen, had a median duration of three months, without grade ≥3 adverse events. R0 resection was achieved in all patients and downstaging was observed in eight patients. One patient developed a postoperative abdominal abscess, and adjuvant chemotherapy was administered to eight patients. Four patients experienced recurrence: liver metastasis in two, and local recurrence in two. Among these, three patients underwent resection of recurrent tumors. Median follow-up was 30 months. CONCLUSION: NAC is feasible for T4b or obstructive T4a colon cancer and may be a treatment option for LACC. Further large-scale studies are required to confirm the efficacy of NAC in these patients.

DOI： 10.21873/anticanres.16923

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Language：English   Publisher：The Japanese Society of Balneology, Climatology and Physical Medicine  

DOI： 10.11390/onki.87_1.3

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Language：English   Publishing type：Research paper (scientific journal)  

Many methods have been developed to measure the neutralizing capacity of antibodies to SARS-CoV-2. However, these methods are low throughput and can be difficult to quickly modify in response to emerging variants. Therefore, an experimental system for rapid and easy measurement of the neutralizing capacity of antibodies against various variants is needed. In this study, we developed an experimental system that can efficiently measure the neutralizing capacity of sera by using a GFP-carrying recombinant SARS-CoV-2 with spike proteins of multiple variants (B.1.1, BA.5, or XBB.1.5). For all 3 recombinant chimeric genomes generated, neutralizing antibody titers determined by measuring GFP fluorescence intensity correlated significantly with those calculated from viral RNA levels measured by RT-qPCR in the supernatant of infected cells. Furthermore, neutralizing antibody titers determined by visually assessing GFP fluorescence using microscopy were also significantly correlated with those determined by RT-qPCR. By using this high-throughput method, it is now possible to quickly and easily determine the neutralizing capacity of antibodies against SARS-CoV-2 variants.

DOI： 10.1016/j.jviromet.2024.114894

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BACKGROUND: Laparoscopic gastrectomy is widely used as a curative treatment for gastric cancer. Although delta-shaped anastomosis is commonly used for Billroth I anastomosis after totally laparoscopic distal gastrectomy (TLDG), it has some drawbacks. The book-binding technique (BBT) was developed as an alternative, and this study aimed to examine its short-term results in 188 consecutive cases. STUDY DESIGN: This retrospective study included patients who underwent BBT reconstruction after TLDG for gastric malignancy between 2011 and 2020. BBT is a technique for intracorporeal gastroduodenostomy, which is a triangular anastomosis with a linear stapler that does not require additional dissection or rotation of the duodenum. The short-term outcomes of BBT reconstruction and postoperative endoscopic findings were analyzed. RESULTS: This study evaluated 188 patients who underwent TLDG and BBT reconstruction. Anastomotic stenosis and leakage occurred in 1.1% and 0.5% of the patients, respectively. The median time to the first diet was 3.1 days, and the median postoperative hospital stay was 11.9 days. BBT anastomoses were performed by 19 surgeons and took an average of 32.8 minutes to complete, with completion times decreasing as the surgical team became more proficient. On endoscopy performed 1 year postoperatively, 5.2% had reflux esophagitis (grade A or higher), 67.8% had gastritis (grade 1 or higher), 37.4% had residual food (grade 1 or higher), and 37.4% had bile reflux (grade 1). CONCLUSIONS: BBT is a safe and feasible method for intracorporeal gastroduodenostomy in TLDG for patients with gastric malignancy and demonstrates good surgical outcomes.

DOI： 10.1097/XCS.0000000000000891

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Language：English   Publisher：Journal of Vascular Surgery  

Objective: To examine limb salvage (LS) and wound healing in dialysis-dependent and -independent patients with chronic limb-threatening ischemia (CLTI) after infrainguinal bypass surgery or endovascular therapy (EVT). Methods: We retrospectively analyzed the multi-center data of patients who underwent infrainguinal revascularization for CLTI with Wound, Ischemia, and foot Infection (WIfI) stage 2 to 4 between 2015 and 2020. The primary endpoint was LS. The secondary endpoint included wound healing, amputation-free survival (AFS), periprocedural complications, and 2-year survival. Comparison of these outcomes were made after propensity score matching. Results: We analyzed 252 dialysis-dependent (318 limbs) and 305 dialysis-independent (354 limbs) patients. Propensity score matching extracted 202 pairs with no significant differences in characteristics. The LS rate in bypass surgery was better than that in EVT in dialysis-dependent patients (P <.001). There was no significant difference in the LS rates between bypass surgery and EVT in dialysis-independent patients (P =.168). The wound healing rate of bypass surgery was better than that of EVT both dialysis-dependent and -independent patients with CLTI. The AFS rate of bypass surgery was better than that of EVT in dialysis-dependent patients (P <.001). There was no significant difference in the AFS rates between bypass surgery and EVT in dialysis-independent patients (P =.099). There was no significant difference in the occurrence of Clavien-Dindo ≥ IV and V between bypass surgery and EVT in dialysis-dependent and -independent patients. Age ≥75 years, serum albumin levels <3.5 g/dL, and non-ambulatory status were risk factors for 2-year mortality in dialysis-dependent patients. The 2-year survival rates in dialysis-dependent patients with risk factors of 0, 1, 2, and 3 were 82.5%, 67.1%, 49.5%, and 10.2%, respectively (P <.001). Conclusions: For LS and wound healing, bypass surgery was preferred for revascularization in dialysis-dependent patients with WIfI stage 2 to 4. Although dialysis dependency was one of the risk factors for 2-year mortality, dialysis-dependent patients, who have 0 to 1 risk factors, may benefit from bypass surgery, as 2-year survival of >50% is expected.

DOI： 10.1016/j.jvs.2023.09.035

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND/AIM: This study examined the clinical significance of very high preoperative carbohydrate antigen 19-9 (CA19-9) levels in patients with early-stage colorectal cancer (CRC). PATIENTS AND METHODS: We retrospectively analyzed the clinicopathological data of patients who underwent curative resection for primary CRC (c-Stage I-III) between 2004 and 2022 in our facility. The patients were classified into three groups according to the preoperative CA19-9 level: normal (≤37.0 U/ml), high (>37.0 to ≤100.0 U/ml), and very high (>100.0 U/ml). RESULTS: Of 971 patients, 885 (91.1%), 67 (6.9%), and 19 (2.0%) had normal, high, and very high CA19-9 levels, respectively. Overall survival (very high vs. normal: p<0.0001, very high vs. high: p=0.01) and recurrence-free survival (very high vs. normal: p<0.0001, very high vs. high: p=0.18) were significantly worse in the very high group. On multivariate analysis including TNM stage, very high preoperative CA19-9 levels were independently associated with worse overall (odds ratio=4.54; 95% confidence interval=2.03-10.16; p=0.0002) and recurrence-free survival (odds ratio=3.49; 95% confidence interval=1.82-6.69; p=0.0002). CONCLUSION: High preoperative CA19-9 levels were associated with poor survival in early-stage CRC. Careful intraoperative observation and close follow-up might be necessary.

DOI： 10.21873/anticanres.16871

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Publisher：金原出版  

DOI： 10.18888/op.0000003667

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Language：English  

DOI： 10.1186/s40792-024-01807-y

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Language：English  

Surgical treatment for a pneumothorax involves resection of the pulmonary pleural fistula, and closure of the fistula or coverage of the fistula using pericardial fat pads or an intercostal muscle flap. In some cases, however, these treatments are difficult because of thickened pleura or dense pleural adhesions in the thoracic cavity. We report two cases of refractory secondary pneumothorax due to lung cancer that were successfully treated using free subcutaneous fat pads to cover the pulmonary pleural fistulas. Both patients had advanced lung cancer, and each developed a pneumothorax after chemotherapy or the administration of osimertinib. Each had a prolonged air leak despite chest tube drainage. We harvested a free subcutaneous fat pad around the thoracotomy site and sutured it to cover the fistula. After the operation, the air leak disappeared immediately, and the chest tube was removed from each patient on postoperative day 2. Computed tomography at 2 or 4 months postoperatively demonstrated that the free subcutaneous fat pads were still present with no sign of pneumothorax. Application of free subcutaneous fat pads to cover a persistent pulmonary pleural fistula is useful for the treatment of secondary pneumothorax due to lung cancer.

DOI： 10.1510/mmcts.2023.085

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Language：Others   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

Abstract

Background &amp; Aims

Recently, the association between hepatocellular carcinoma (HCC) and ferroptosis has been the focus of much attention. The expression of long chain fatty acyl‐CoA ligase 4 (ACSL4), a marker of ferroptosis, in tumour tissue is related to better prognosis in various cancers. In HCC, ACSL4 expression indicates poor prognosis and is related to high malignancy. However, the mechanism remains to be fully understood.

Methods

We retrospectively enrolled 358 patients with HCC who had undergone hepatic resection. Immunohistochemistry (IHC) for ACSL4 was performed. Factors associated with ASCL4 expression were investigated by spatial transcriptome analysis, and the relationships were investigated by IHC. The association between ACSL4 and the tumour immune microenvironment was examined in a public dataset and investigated by IHC.

Results

Patients were divided into ACSL4‐positive (n = 72, 20.1%) and ACSL4‐negative (n = 286, 79.9%) groups. ACSL4 positivity was significantly correlated with higher α‐fetoprotein (p = .0180) and more histological liver fibrosis (p = .0014). In multivariate analysis, ACSL4 positivity was an independent prognostic factor (p &lt; .0001). Spatial transcriptome analysis showed a positive correlation between ACSL4 and cancer‐associated fibroblasts; this relationship was confirmed by IHC. Evaluation of a public dataset showed the correlation between ACSL4 and exhausted tumour immune microenvironment; this relationship was also confirmed by IHC.

Conclusion

ACSL4 is a prognostic factor in HCC patients and its expression was associated with cancer‐associated fibroblasts and anti‐tumour immunity.

DOI： 10.1111/liv.15839

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TP53-induced glycolysis and apoptosis regulator (TIGAR) is an important gene that encodes a regulatory enzyme of glycolysis and reactive oxygen species (ROS) detoxification and is associated with worse prognosis in various cancers. Ferroptosis is a recently identified type of programmed cell death that is triggered by iron-dependent lipid peroxidation. There are no reports on the prognostic impact of TIGAR on intrahepatic cholangiocarcinoma (ICC), and its role in ferroptosis is unclear. Ninety ICC patients who had undergone hepatic resection were enrolled. Immunohistochemical staining for TIGAR was performed. The regulation of malignant activity by TIGAR and the association between ferroptosis and TIGAR were investigated in vitro. Twenty-two (24.4%) patients were categorized into TIGAR-high and -low groups by immunohistochemical staining. There were no noticeable differences in background factors between the two groups, but TIGAR positivity was an independent prognostic factor in disease-free survival (hazard ratio [HR], 2.00; 95% confidence interval [CI], 1.04-3.85, p = 0.0378) and overall survival (HR, 2.10; 95% CI, 1.03-4.30, p = 0.00422) in a multivariate analysis. In vitro, TIGAR knockdown (KD) decreased cell motility (cell proliferation/migration/invasion/colony-forming capabilities) and elevated ROS and lipid peroxidation. This indicated that TIGAR KD induced ferroptosis. TIGAR KD-induced ferroptosis was suppressed using liproxstatin. TIGAR KD decreased the expression of glutathione peroxidase 4, known as factor-suppressing ferroptosis. The combination of TIGAR KD with cisplatin significantly induced more ferroptosis. In conclusion, TIGAR is associated with poor outcomes in ICC patients and resistance to ferroptosis.

DOI： 10.1111/cas.15981

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BACKGROUND: There is limited published information regarding the expression of mechanistic target of rapamycin (mTOR) in vessels that encapsulate tumor cluster (VETC)-positive hepatocellular carcinoma (HCC). The mTOR inhibitor, everolimus, has been approved as an immunosuppressant for use in HCC patients after living donor liver transplantation (LDLT). METHODS: Using a database of 214 patients who underwent LDLT for HCC, we examined the mTOR protein and angiopoietin-2 (Ang-2) in VETC-positive HCC by immunohistochemical staining. The presence of VETC and mTOR expression were evaluated in both primary and recurrent HCC lesions. RESULTS: Forty-three of the 214 patients (20.1%) were VETC-positive, and 29 of these 43 patients (67.4%) expressed mTOR. Relative Ang-2 expression was significantly higher in the mTOR-positive than in the mTOR-negative group (p = 0.037). Thirty-four of the 214 patients experienced HCC recurrence after LDLT; 20 of these were operable. The primary lesions of six of these 20 patients were VETC-positive; five of these six patients also had VETC-positive recurrent lesions (p < 0.001). The expression of mTOR was significantly higher in the VETC-positive lesions (p = 0.0018). CONCLUSIONS: We showed that mTOR expression was higher in the VETC-positive primary and recurrent lesions than in the VETC-negative ones.

DOI： 10.1002/ags3.12735

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Language：English   Publisher：Springer Berlin Heidelberg  

Language：English   Publisher：シュプリンガー・ジャパン(株)  

Language：English   Publisher：John Wiley & Sons Australia, Ltd  

Language：English   Publisher：John Wiley & Sons Australia, Ltd  

Language：English   Publisher：Hepatology Research  

Aim: To investigate the prognostic value of the preoperative albumin–lymphocyte–platelet–C-reactive protein (ALPC) index in patients with hepatocellular carcinoma (HCC) undergoing curative hepatectomy. We also evaluated the relationship between the ALPC index and the phosphorylated nuclear factor erythroid 2-related factor 2 (p-Nrf2) levels. Methods: Data were analyzed retrospectively from 256 patients who underwent resection for HCC. For cross-validation, patients were divided into the training and testing cohort. We assessed eight combinations of inflammatory markers for predictive value for recurrence. We examined the associations of the ALPC index with recurrence-free survival and overall survival in univariate and multivariate analyses (Cox proportional hazards model). Immunohistochemical staining of p-Nrf2 was performed on tumor samples of 317 patients who underwent hepatic resection for HCC. Results: A high preoperative ALPC index correlated with a high serum albumin concentration, small tumor size, low rate of poor differentiation, solitary tumor, early Barcelona Clinic Liver Cancer stage, and low rate of microscopic intrahepatic metastasis in the training dataset. A high preoperative ALPC index correlated with a high serum albumin concentration, high serum alpha-fetoprotein concentration, small tumor size, a low rate of poor differentiation and a low rate of microscopic intrahepatic metastasis in the testing dataset. A higher preoperative ALPC index was an independent predictor of longer recurrence-free survival and overall survival in the training and testing datasets. A high ALPC index was associated with negative p-Nrf2 expression in HCC tumor cells. Conclusions: We showed that a high ALPC index was an independent prognostic factor for patients with HCC undergoing curative hepatic resection.

DOI： 10.1111/hepr.13958

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Language：English   Publisher：American Journal of Transplantation  

There are exceedingly uncommon but clearly defined situations where intraoperative abortions are inevitable in living-donor liver transplantation (LDLT). This study aimed to summarize the cases of aborted LDLT and propose a strategy to prevent abortion or minimize donor damage from both recipient and donor sides. We collected data from a total of 43 cases of aborted LDLT out of 13 937 cases from 7 high-volume hospitals in the Vanguard Multi-center Study of the International Living Donor Liver Transplantation Group and reviewed it retrospectively. Of the 43 cases, there were 24 recipient-related abortion cases and 19 donor-related cases. Recipient-related abortions included pulmonary hypertension (n = 8), hemodynamic instability (n = 6), advanced hepatocellular carcinoma (n = 5), bowel necrosis (n = 4), and severe adhesion (n = 1). Donor-related abortions included graft steatosis (n = 7), graft fibrosis (n = 5), primary biliary cholangitis (n = 3), anaphylactic shock (n = 2), and hemodynamic instability (n = 2). Total incidence of aborted LDLT was 0.31%, and there was no remarkable difference between the centers. A strategy to minimize additional donor damage by delaying the donor's laparotomy or trying to open the recipient's abdomen with a small incision should be effective in preventing some causes of aborted LDLT, such as pulmonary hypertension, advanced cancer, and severe adhesions.

DOI： 10.1016/j.ajt.2023.07.011

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Language：English   Publisher：John Wiley & Sons Australia, Ltd  

腫瘍クラスターを被包する血管(VETC)陽性の肝細胞癌(HCC)におけるmTOR発現に関する報告は少ない。mTOR阻害物質であるエベロリムスが、生体肝移植(LDLT)後のHCC患者に対する免疫抑制剤として認可された。HCCに対してLDLTを施行した214例のデータを用いて、VETC陽性HCCにおけるmTOR蛋白質およびアンギオポエチン-2(Ang-2)の発現を免疫組織化学的染色により検討した。VETCおよびmTOR発現の有無を原発性および再発性HCC病変の両方で評価した。214例中43例(20.1%)はVETC陽性で、この43例中29例(67.4%)はmTORを発現していた。相対的Ang-2発現は、mTOR発現例でmTOR陰性例よりも有意に多かった(P=0.037)。214例中34例でLDLT後にHCCの再発が認められ、うち20例は手術適応であった。これら20例のうち6例の原発巣はVETC陽性で、この6例中5例は再発巣でもVETC陽性であった(P<0.001)。以上より、mTORの発現はVETC陽性病変で有意に多かった。VETC陽性の原発および再発病変において、VETC陰性病変と比較してmTOR発現高いことが示された。

Language：Japanese   Publisher：The Japan Society for Transplantation  

<p><b>【Objective】</b> Postoperative prolonged ascites is a common complication after living-donor liver transplantation (LDLT). However, there is little evidence regarding the circulatory indicators as risk factors for ascites after LDLT. The aim was to evaluate the impact of trans tricuspid pressure gradient (TRPG) on postoperative prolonged ascites.</p><p><b>【Design】</b> Case-series.</p><p><b>【Method】</b> We collected data from 268 recipients who underwent LDLT for liver failure between 2008 and 2022. We excluded 7 recipients who died within 30 days after LDLT and divided the remainer into two groups by TRPG value.</p><p><b>【Results】</b> Of the 261 patients with liver failure, 98 (37.7%) were classified as the high TRPG group and 163 (62.3%) comprised the low TRPG group. There was a significant difference in the rate of intractable ascites between the two groups, but no significant difference in overall survival (OS). After PSM, univariate analysis detected two risk factors, high TRPG value and ascites at laparotomy ≥5000 mL. In the multivariate analysis, high TRPG value (<i>P</i>=0.0345, OR=11.4, 95% CI 1.19-108) and ascites at laparotomy ≥5000 (mL) (<i>P</i>=0.0067, OR=10.2, 95% CI 1.91-54.8) were identified as independent risk factors.</p><p><b>【Conclusion】</b> Preoperative TRPG elevation is a risk for prolonged ascites after LDLT, and it can be valuable to measure TRPG in the preoperative condition assessment.</p>

DOI： 10.11386/jst.59.1_37

CiNii Research

Language：English   Publisher：Transplantation  

Background. The consensus that portal venous pressure modulation, including splenectomy (Spx), prevents portal hypertension-related complications after living-donor liver transplantation (LDLT) has been established. However, little evidence about the risk factors for graft loss after simultaneous Spx during LDLT is available. This study aimed to identify the independent predictors of graft loss after simultaneous Spx during LDLT. Methods. Data of 655 recipients who underwent LDLT between 1997 and 2021 were collected and separated into the simultaneous Spx group (n=461) and no-Spx group (n=194). Results. The simultaneous Spx group had significantly lower serum total bilirubin levels, drained ascites volumes, and prothrombin time-international normalized ratios on postoperative day 14 than the no-Spx group (P<0.001 for each). Incidences of small-for-size graft syndrome (P<0.001), acute cellular rejection (P=0.002), and sepsis (P=0.007) were significantly lower in the Spx group. Graft survival of the Spx group was significantly better than that of the no-Spx group (P<0.001; hazard ratio [HR], 1.788; 95% confidence interval, 1.214-2.431). A multivariate analysis revealed that 3 variables, platelet count ≤4.0×104/mm3 (P=0.029; HR, 2.873), donor age ≥60 y old (P=0.013; HR, 6.693), and portal venous pressure at closure ≥20 mm Hg (P=0.010; HR, 3.891), were independent predictors of graft loss within 6 mo after simultaneous Spx during LDLT. Conclusions. Spx is a safe inflow modulation procedure with a positive impact on both postoperative complications and prognosis for most patients. However, patients with the 3 aforementioned independent factors could experience graft loss after LDLT.

DOI： 10.1097/TP.0000000000004952

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Language：English   Publisher：Liver Transplantation  

Liver transplantation is the definitive treatment for advanced liver cirrhosis with portal hypertension. In Japan, the scarcity of deceased donors leads to reliance on living donors, often resulting in smaller grafts. Managing portal venous pressure (PVP) is critical to prevent fatal posttransplant complications. This study explored the possibility of predicting intraoperative PVP. We analyzed 475 living donor liver transplant cases from 2006 to 2023, excluding those with acute liver failure or prior splenectomy or splenic artery embolization. Patients were divided into a training group (n=425) and a test group (n=50). We evaluated the correlation between preoperative factors and PVP at laparotomy, to predict PVP at laparotomy and closure. The predictive model was validated with the test group data. PVP at laparotomy could be predicted using correlated preoperative factors: prothrombin time (p<0.001), predicted splenic volume (p<0.001), and presence of a portosystemic shunt (p=0.002), as follows: Predicted PVP at laparotomy (mmHg)=25.818 - 0.077×[prothrombin time (%)]+0.004×[predicted splenic volume (ml)] - 2.067×[1: with a portosystemic shunt] (p<0.001; R=0.346). Additionally, PVP at closure could be predicted using correlated operative factors, including measured PVP at laparotomy, as follows: predicted PVP at closure (mmHg)=14.268+0.149×[measured PVP at laparotomy (mmHg)] - 0.040×[GV/SLV (%)] - 0.862×[1: splenectomy (if yes)] - 3.511×[1: splenic artery ligation without splenectomy (if yes)] (p<0.001; R=0.339).This study demonstrated the feasibility of predicting intraoperative PVP using preoperative factors in liver transplant patients with decompensated cirrhosis. This predictive approach could refine surgical planning, potentially improving patient outcomes.

DOI： 10.1097/LVT.0000000000000433

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Publisher：Liver Cancer  

Recent advances in systemic therapy for hepatocellular carcinoma (HCC) have led to debates about the feasibility of combination therapies, such as systemic therapy combined with surgery or transarterial chemoembolization, for patients with advanced HCC. However, a lack of consensus on the oncological resectability criteria has hindered discussions of "conversion therapy"and the optimal management in patients with HCC. To address this issue, the Japan Liver Cancer Association (JLCA) and the Japanese Society of Hepato-Biliary-Pancreatic Surgery (JSHBPS) established a working group and discussed the concept of borderline resectable HCC. Herein, we present a consensus statement from this expert panel on the resectability criteria for HCC from the oncological standpoint under the assumption of technically and liver-functionally resectable situations. The criteria for oncological resectability in HCC are classified into three grades: resectable, representing an oncological status for which surgery alone may be expected to offer clearly better survival outcomes as compared with other treatments; borderline resectable 1, representing an oncological status for which surgical intervention as a part of multidisciplinary treatment may be expected to offer survival benefit; and borderline resectable 2, representing an oncological status for which the efficacy of surgery is uncertain and the indication for surgery should be determined carefully under the standard multidisciplinary treatment. These criteria aim to provide a common language for discussing and analyzing the treatment strategies for advanced HCC. It is also expected that these criteria will be optimized, modified, and updated based on further advancements in systemic therapies and future validation studies.

DOI： 10.1159/000538627

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Language：English   Publisher：Surgery Today  

Purposes: Polyglycolic acid (PGA) sheets, fibrin glue, and staple line reinforcement are frequently used to prevent air leakage during lung resection. However, the optimal staple-line reinforcement method remains unclear. Methods: Cranial lung lobes of pigs were used to evaluate different staple line reinforcement methods (n = 6). Ventilator-assisted manometry was used to measure the maximum resistance pressure at the time of rupture of the lung tissue after stapling. Results: The mean maximum resistance pressures at the time of lung tissue rupture after using the stapler alone, stapler with PGA sheet and fibrin glue, and stapler with reinforcement were 38.0 cmH2O, 51.3 cmH2O, and 62.7 cmH2O, respectively. A significant increase in the maximum resistance pressure was observed with stapler reinforcement (P < 0.001), while the differences between the other groups were not statistically significant (P = 0.055, P = 0.111). A histological assessment revealed disruption of alveolar structures near the needle-stitching site in the stapler alone, and in the stapler with PGA sheet and fibrin glue groups. Pleural rupture near the staple line was observed in the stapler with reinforcement group. Conclusions: The maximum resistance pressure before air leakage was significantly higher when using a stapler with reinforcement than when using a stapler alone.

DOI： 10.1007/s00595-024-02858-2

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Language：English   Publisher：American Journal of Transplantation  

Decreasing the graft size in living donor liver transplantation (LDLT) increases the risk of early allograft dysfunction. Graft-to-recipient weight ratio (GRWR) of 0.8 is considered the threshold. There is evidence that smaller volume grafts may also provide equally good outcomes, the cut-off of which remains unknown. In this retrospective multicenter study, 92 adult LDLTs with a final GRWR ≤0.6 performed at 12 international liver transplant centers over a 3-year period were included. Perioperative data including preoperative status, portal flow hemodynamics (PFH) and portal flow modulation, development of small for size syndrome (SFSS), morbidity, and mortality was collated and analyzed. Thirty-two (36.7%) patients developed SFSS and this was associated with increased 30-day, 90-day, and 1-year mortality. The preoperative model for end-stage liver disease and inpatient status were independent predictors for SFSS (P <.05). Pre-liver transplant renal dysfunction was an independent predictor of survival (hazard ratio 3.1; 95% confidence intervals 1.1, 8.9, P =.035). PFH or portal flow modulation were not predictive of SFSS or survival. We report the largest ever multicenter study of LDLT outcomes using ultralow GRWR grafts and for the first time validate the International Liver Transplantation Society-International Living donor liver transplantation study group-Liver Transplantation Society of India consensus definition and grading of SFSS. Preoperative recipient condition rather than GRWR and PFH were independent predictors of SFSS. Algorithms to predict SFSS and LT outcomes should incorporate recipient factors along with GRWR.

DOI： 10.1016/j.ajt.2024.06.013

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Language：English   Publisher：Hepatology Research  

Aim: Sarcopenia is reportedly associated with a poor prognosis in patients who undergo living-donor liver transplantation (LDLT), most of whom are not able to tolerate muscle strengthening exercise training. Myostatin is one of the myokines and a negative regulator of skeletal muscle growth. The clinical feasibility of an electrical muscle stimulation (EMS) system, which exercises muscle automatically by direct electrical stimulation, has been reported. In this study, we aimed to determine the effect of perioperative application of SIXPAD, which is a type of EMS system, with reference to the serum myostatin and sarcopenia in LDLT patients. Method: Thirty patients scheduled for LDLT were divided into a SIXPAD group (n = 16) and a control group (n = 14). In the SIXPAD group, EMS was applied to the thighs twice daily. The serum myostatin was measured in samples obtained before use of SIXPAD and immediately before LDLT. The psoas muscle index (PMI) at the level of the third lumbar vertebra and the quadriceps muscle area were compared on computed tomography images before use of SIXPAD and 1 month after LDLT. Results: The preoperative serum myostatin was found to be higher in LDLT patients than in healthy volunteers and EMS significantly reduced the serum myostatin. Electrical muscle stimulation prevented a postoperative reduction not only in the area of the quadriceps muscles but also in the PMI despite direct stimulation of the thigh muscles. Conclusion: Stimulation of muscles by EMS decreases the serum myostatin and helps to maintain skeletal muscle in patients who have undergone LDLT.

DOI： 10.1111/hepr.14027

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Language：English   Publisher：Annals of Thoracic Surgery  

Background: Cluster of differentiation (CD) 155 is a transmembrane protein that belongs to the nectin-like molecule family, which is widely overexpressed in several types of cancer. However, the clinical significance of CD155 in pathologic stage I lung adenocarcinoma remains poorly understood. Methods: We analyzed 320 patients diagnosed with pathologic stage I lung adenocarcinoma who underwent surgical treatment at Kyushu University Hospital between 2006 and 2015. The number of tumor cells expressing CD155 was assessed by immunohistochemistry, and patients were categorized into high and low CD155 expression groups. We compared the clinical and pathologic characteristics and clinical outcomes between these groups. Results: Mutation status of the epidermal growth factor receptor gene (EGFR) was determined in 237 patients. A total of 106 patients (33.1%) had EGFR wild-type, and 131 patients (40.9%) had EGFR mutant-type. CD155 expression was classified as high in 77 patients (24.1%) and as low in 243 (75.9%) as low. Multivariate analysis identified pleural invasion and EGFR wild-type as independent predictors of high CD155 expression. The Kaplan-Meier plot demonstrated significantly poorer recurrence-free survival and overall survival in the high CD155 group compared with the low CD155 group. Multivariate analysis showed high CD155 expression was an independent poor prognostic factor for recurrence-free and overall survival. Subgroup analyses revealed that a prognostic difference related to CD155 expression was observed only in patients with EGFR wild-type but not in those with EGFR mutant-type. Conclusions: Our findings suggest that high expression of CD155 is associated with EGFR wild-type and could serve as a valuable prognostic marker in pathologic stage I lung adenocarcinoma, particularly in cases without EGFR mutation.

DOI： 10.1016/j.athoracsur.2024.05.042

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Language：English   Publisher：Surgery Today  

Purpose: Treatment outcomes are predicted by analyzing peripheral blood markers such as serum lactate dehydrogenase (LDH). We conducted this study to investigate whether serum LDH levels can predict the prognosis of patients treated with atezolizumab plus bevacizumab (ATZ/BEV) therapy for hepatocellular carcinoma (HCC) and whether LDH levels correlate with metabolic changes. Methods: We enrolled 66 HCC patients treated with ATZ/BEV. Based on the change in serum LDH levels before and after treatment, the patients were divided into two groups, and the prognosis of each group was examined. Moreover, the association of LDH levels with tumor metabolism was analyzed by fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT). Results: There were 32 patients categorized as the LDH-decrease group. Kaplan–Meier survival analysis indicated worse progression-free survival (PFS) in the LDH-increase group than in the LDH-decrease group (p = 0.0029). Multivariate analysis showed that an increase in the LDH level was an independent risk factor for worse PFS (p = 0.0045). The baseline LDH level correlated significantly with a high maximum standardized uptake value of 18F-FDG, according to the PET/CT findings. Transcriptomic analyses of specimens resected after ATZ/BEV therapy showed downregulated mitochondria-related pathways. Conclusion: Serum LDH levels are a potential prognostic marker and an indicator of tumor metabolism.

DOI： 10.1007/s00595-024-02914-x

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Language：English   Publisher：Annals of Surgical Oncology  

DOI： 10.1245/s10434-024-15839-z

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND/AIM: Recent research has demonstrated that laparoscopic multivisceral resection (MVR) for advanced colorectal cancer is safe, practicable, and yields satisfactory oncological results, which is in line with the growing usage of laparoscopic surgery. The effectiveness of laparoscopic MVR is still debatable, though. The goal of this study was to compare the short- and long-term results of patients with advanced colorectal cancer treated with open MVR with laparoscopic procedures. PATIENTS AND METHODS: Data on 3,571 consecutive patients hospitalized at the Kyushu University National Kyushu Cancer Center for colorectal cancer surgery between 2004 and 2020 were gathered retrospectively. In the end, 84 individuals with advanced colorectal cancer who had a colectomy with MVR were examined. We evaluated invasiveness in terms of complications, blood loss, and operating time. Recurrence-free survival rates and overall 5-year survival were among the oncological outcomes. RESULTS: Of the 84 patients examined, 29 underwent laparoscopic treatment, and 55 underwent open treatment. The laparoscopic surgery group experienced shorter hospital stays (15 vs. 18 days, p<0.05) and much less blood loss (median volume: 167 vs. 1,058 g, p<0.005) than the open surgery group. Following the exclusion of patients with stage IV colorectal cancer from the study (groups undergoing laparoscopic surgery, n=25; open surgery, n=38), the groups displayed comparable pathologic results and no discernible variations in either the 5-year overall survival (p=0.87) or recurrence-free survival (p=0.86). CONCLUSION: In certain individuals with advanced colorectal cancer, a laparoscopic method of manipulation with MVR may be less invasive than an open method without compromising the prognosis.

DOI： 10.21873/cdp.10302

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Language：Japanese   Publisher：The Japan Society for Transplantation  

<p><b>【Introduction】</b> Therapeutic strategies for antibody mediated rejection (AMR) after liver transplantation are gradually being established; however, the efficacy of intravenous immunoglobulin (IVIg) therapy as a treatment for AMR after liver transplantation is not clear. The purpose of this multicenter, retrospective, observational study was to clarify the actual status of AMR treatment using IVIg in Japan, and the efficacy and safety of IVIg therapy.</p><p><b>【Methods】</b> Sixty-one liver transplant recipients diagnosed with AMR and treated with IVIg between April 2001 and March 2022 were analyzed. Sixty-one patients in the secondary survey who were treated with IVIG were analyzed for efficacy and safety in a retrospective study.</p><p><b>【Results】</b> Acute AMR was observed in 86.0% of adult cases, and 94.4% of pediatric cases. Acute T cell-mediated rejection (TCMR) was also concomitant with AMR in 48.8% of adult patients and 22.2% of pediatric patients. When AMR develops after liver transplantation, IVIg + PE and IVIg + steroid pulse therapy was the most common treatment in adult patients (27.9%). In pediatric cases, IVIg therapy alone was the most commonly used, at 38.9%. Patient survival and graft survival rates at 6 months after AMR treatment including IVIg in adult patients were 69.8% and 69.8%, respectively and were 94.4% and 88.9% in pediatric patients, respectively.</p><p>Serious adverse events, including those with unknown causal relationship, were observed in 7.0% of adult cases and 5.6% of pediatric cases.</p><p><b>【Conclusion】</b> AMR treatment including IVIg is safe and has sufficient therapeutic effect and may be one of the effective treatment modalities for the development of AMR after liver transplantation.</p>

DOI： 10.11386/jst.59.1_15

CiNii Research

Language：Japanese   Publisher：The Japan Society of Hepatology  

<p>Since April 2022, robot-assisted liver resection has been covered by insurance, and strict institutional standards and guidelines from the Japanese Society of Hepato-Biliary-Pancreatic Surgery and the Japanese Society of Endoscopic Surgery have been proposed for its safe introduction, setting forth the criteria for proctors certified by the societies. Robotic precision surgical techniques are expected to enable safer liver resection. However, several issues must be addressed for widespread use of robot-assisted liver resection, such as overcoming the learning curve of the robotic technique and establishing evidence through prospective case registries in terms of short- and long-term outcomes.</p>

DOI： 10.2957/kanzo.64.595

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CiNii Research

Language：English   Publishing type：Research paper (scientific journal)  

PURPOSE: Transferrin receptor (TFR), a membrane protein that has a critical role in the transport of iron into cells, is known to be a ferroptosis-related marker. Although TFR is reported to be abundantly expressed in tumor cells, its relationship with ferroptosis inducers in hepatocellular carcinoma (HCC) remains unclear. METHODS: The authors performed immunohistochemical staining of TFR and divided 350 HCC patients into two groups according to its expression. They analyzed the association between TFR expression and prognosis or clinicopathologic factors. In addition, the regulation of malignant activity and its effect on the efficacy of ferroptosis inducers were investigated in vitro. RESULTS: For this study, 350 patients were divided into TFR-positive (n =180, 51.4%) and TFR-negative (n = 170, 48.6%) groups. The TFR-positive group had more hepatitis B surface antigen (HBs-Ag) (p = 0.0230), higher α-fetoprotein (AFP) levels (p = 0.0023), higher des-gamma-carboxyprothrombin (DCP) levels (p = 0.0327), a larger tumor size (p = 0.0090), greater proportions of Barcelona Clinic Liver Cancer (BCLC) stage B or C (p = 0.0005), poor differentiation (p < 0.0001), and microscopic intrahepatic metastasis (p = 0.0066). In the multivariate analyses, TFR expression was an independent prognostic factor in disease-free survival (p = 0.0315). In vitro, TFRC knockdown decreased cell motility. In addition, TFRC knockdown abolished artesunate (AS)-, lenvatinib-, and sorafenib-induced ferroptosis in HCC cell lines. The study demonstrated that simultaneous treatment of AS with multi-kinase inhibitor augmented the ferroptosis-inducing effects of AS in HCC cell lines. CONCLUSION: TFR expression is a poor prognostic factor in HCC, but its expression increases sensitivity to ferroptosis-inducing agents.

DOI： 10.1245/s10434-023-14053-7

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BACKGROUND: In telementoring, differences in teaching methods affect local surgeons' comprehension. Because the object to be operated on is a three-dimensional (3D) structure, voice or 2D annotation may not be sufficient to convey the instructor's intention. In this study, we examined the usefulness of telementoring using 3D drawing annotations in robotic surgery. METHODS: Kyushu University and Beppu Hospital are located 140 km apart, and the study was conducted using a Saroa™ surgical robot by RIVERFIELD Inc. using a commercial guarantee network on optical fiber. Twenty medical students performed vertical mattress suturing using a swine intestinal tract under surgical guidance at the Center for Advanced Medical Innovation Kyushu University. Surgical guidance was provided by Beppu Hospital using voice, 2D, and 3D drawing annotations. All robot operations were performed using 3D images, and only the annotations were independently switched between voice and 2D and 3D images. The operation time, needle movement, and performance were also evaluated. RESULTS: The 3D annotation group tended to have a shorter working time than the control group (25.6 ± 63.2 vs. - 36.7 ± 65.4 min, P = 0.06). The 3D annotation group had fewer retries than the control group (1.3 ± 1.7 vs. - 1.1 ± 0.7, P = 0.006), and there was a tendency for fewer needle drops (0.4 ± 0.7 vs. - 0.5 ± 0.9, P = 0.06). The 3D annotation group scored significantly higher than the control group on the Global Evaluate Assessment of Robot Skills (16.8 ± 2.0 vs. 22.8 ± 2.4, P = 0.04). The 3D annotation group also scored higher than the voice (13.4 ± 1.2) and 2D annotation (16.2 ± 1.8) groups (3D vs. voice: P = 0.03, 3D vs. 2D: P = 0.03). CONCLUSION: Telementoring using 3D drawing annotation was shown to provide good comprehension and a smooth operation for local surgeons.

DOI： 10.1007/s00464-023-10521-z

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OBJECTIVE: To clarify the surgical outcomes of esophagectomy in Japan and comprehensively evaluate trends over time. It is important to analyze data from a large number of consecutive patients from a single institution. METHODS: We evaluated the treatment outcomes, complications, and prognosis of 1500 consecutive patients who underwent esophagectomy during 5 periods: group A (n = 284), 1964-1984; group B (n = 345), 1985-1993; group C (n = 253), 1994-2002; group D (n = 297), 2003-2012; and group E (n = 321), 2013-March 2020. RESULTS: The incidences of squamous cell carcinoma and adenocarcinoma were 93.8% and 3.3%, respectively. The proportion of adenocarcinoma cases has gradually increased over time. The in-hospital mortality rates for groups A, B, C, D, and E were 12%, 4.6%, 1.2%, 2.9%, and 1.5%, respectively. Group A had a significantly higher mortality rate than the other groups (P < 0.0001). Three-year survival rates were 22.2%, 47.8%, 53.4%, 69.9%, and 72.6% in groups A-E, respectively, 5-year survival rates were 17.2%, 41.3%, 49.2%, 63.9%, and 68.4%, respectively (P < 0.0001, group A vs groups D and E). The prognosis improved over time. Multivariate analysis revealed that depth of invasion, lymph node metastasis, the extent of lymph node resection, curative resection, pulmonary complications, and anastomotic leakage were significant independent prognostic factors. However, for recent surgeries (groups D and E), only the depth of invasion, lymph node metastasis, and curative resection were significant independent prognostic factors. CONCLUSIONS: Valuable changes in background and prognostic factors occurred over time. These findings will help optimize esophageal cancer management and improve patient outcomes.

DOI： 10.1097/AS9.0000000000000347

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Language：English   Publisher：シュプリンガー・ジャパン(株)  

Language：English   Publisher：JGH Open  

Background and Aim: Many recent studies have shown a relationship between various systemic diseases and the gut microbiota (GM), with the gut–liver axis receiving particular attention. In contrast, no report has comprehensively shown the effects of GM on the pathophysiology of patients undergoing living donor liver transplantation (LDLT). Method: We enrolled 16 recipients who underwent LDLT for liver cirrhosis, and 17 donors constituted the reference group. We examined the differences in GM between recipients and donors. We also examined the relationships between GM, short-chain fatty acids, and portal vein pressure (PVP) in recipients. Results: There was no significant difference in alpha-diversity between the recipients and donors, but there was variation in beta-diversity among the recipients. The abundance of the phylum Bacteroidetes was significantly higher in recipients than in donors (P = 0.016), and it was positively correlated with PVP (r = 0.511, P = 0.043). Propionic acid, which is a component of short-chain fatty acids, was positively correlated with PVP (r = 0.544, P = 0.0295), the phylum Bacteroidetes (r = 0.677, P = 0.004), and total bilirubin concentration (r = 0.501, P = 0.048). Propionic acid was negatively correlated with serum albumin concentration (r = −0.482, P = 0.043). Conclusion: Our findings suggest relationships between fecal Bacteroidetes levels, propionic acid concentrations, and PVP in patients with liver cirrhosis undergoing LDLT.

DOI： 10.1002/jgh3.13018

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DOI： 10.1245/s10434-023-14202-y

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Language：English   Publisher：Annals of Surgical Oncology  

DOI： 10.1245/s10434-023-14054-6

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Systemic sclerosis (SSc) is an autoimmune disease characterized by frequent esophageal involvement. However, there are few reports on esophagectomy for esophageal strictures associated with SSc. Herein, we present a case of successful treatment of an esophageal stricture associated with SSc through subtotal esophagectomy. CASE PRESENTATION: A 53-year-old female patient was diagnosed with SSc, interstitial pneumonia, and gastroesophageal reflux disease (GERD). The patient developed an esophageal ulcer and benign stricture that required a subtotal esophagectomy 10 years after the diagnosis. Histopathological findings revealed thinning of the muscle layer, a characteristic feature of SSc. The patient was free of dysphagia or regurgitation. CONCLUSIONS: An esophagectomy is a valuable option for treating esophageal strictures in SSc. Therefore, surgical approaches should be established for patients with SSc.

DOI： 10.1186/s40792-023-01727-3

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BACKGROUND: Osimertinib is an irreversible EGFR tyrosine kinase inhibitor approved for the first-line treatment of patients with metastatic NSCLC harboring EGFR exon 19 deletions or L858R mutations. Patients treated with osimertinib invariably develop acquired resistance by mechanisms involving additional EGFR mutations, MET amplification and other pathways. There is no known involvement of the oncogenic MUC1-C protein in acquired osimertinib resistance. METHODS: H1975/EGFR(L858R/T790M) and patient-derived NSCLC cells with acquired osimertinib resistance were investigated for MUC1-C dependence in studies of EGFR pathway activation, clonogenicity and self-renewal capacity. RESULTS: We demonstrate that MUC1-C is upregulated in H1975 osimertinib drug tolerant persister (DTP) cells and is necessary for activation of the EGFR pathway. H1975 cells selected for stable osimertinib resistance (H1975-OR) and MGH700-2D cells isolated from a patient with acquired osimertinib resistance are shown to be dependent on MUC1-C for induction of (i) p-EGFR, p-ERK and p-AKT, (ii) EMT, and (iii) the resistant phenotype. We report that MUC1-C is also required for p-EGFR, p-ERK and p-AKT activation and self-renewal capacity in acquired osimertinib-resistant (i) MET amplified MGH170-1D #2 cells, and (ii) MGH121 Res#2/EGFR(T790M/C797S) cells. Importantly, targeting MUC1-C in these diverse models reverses osimertinib resistance. In support of these results, high MUC1 mRNA and MUC1-C protein expression is associated with a poor prognosis for patients with EGFR mutant NSCLCs. CONCLUSIONS: Our findings demonstrate that MUC1-C is a common effector of osimertinib resistance and is a potential target for the treatment of osimertinib resistant NSCLCs.

DOI： 10.1016/j.jtho.2023.10.017

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BACKGROUND: Comprehensive genomic profiling (CGP) has become generally accepted practice in cancer care since CGP has become reimbursed by national healthcare insurance in Japan in 2019. However, its usefulness for cancer patients is insufficient for several reasons. METHODS: In an observational clinical study of FoundationOne® CDx, potential biomarkers were explored and the cause of testing failure was investigated. A total of 220 cancer patients were enrolled in the study during the period from 2018 to 2019 at Kyushu University Hospital. RESULTS: The primary tumor sites of the 220 cases were breast (115), colon (29), stomach (19), and pancreas (20). The present dataset suggested that homologous recombination repair (HRR) gene alterations were positively associated with tumor mutational burden-high (TMB-high) (p = 0.0099). A public dataset confirmed that patients with HRR gene alterations had a higher TMB and showed significantly longer survival of immunotherapy. In the present study, 18 cases failed sequencing. A lower percentage of tumor cell nuclei was the most common reason for testing failures (p = 0.037). Cases that received neoadjuvant chemotherapy before sampling tended to fail testing. CONCLUSIONS: HRR gene alterations can be a potential biomarker predicting TMB-high and a good response to immunotherapy. For successful sequencing, samples with lower percentages of tumor cell nuclei and previous neoadjuvant chemotherapy should be avoided.

DOI： 10.3390/cancers15235608

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BACKGROUND/AIM: Recent advances in surgery, such as thoracoscopic surgery, have made it possible to treat patients with chronic obstructive pulmonary disease (COPD) more safely than before. This study evaluated the short- and long-term prognosis of lobectomy in non-small cell lung cancer (NSCLC) patients with COPD. PATIENTS AND METHODS: This retrospective, propensity-matched, cohort analysis was conducted from January 2014 to December 2018. Among 441 patients who underwent lobectomy for NSCLC, 158 (35.8%) had a preoperative diagnosis of COPD. Propensity-matched analysis, incorporating preoperative variables, was used to compare postoperative hospital stay and complications, and long-term prognosis between the groups. RESULTS: Propensity matching estimated 145 patients in each group. There was no difference between the two groups for length of postoperative hospital stay (12 vs. 11 days, p=0.306). Postoperative complications were more frequent in the COPD group (24.1%) than in the non-COPD group (16.6%), but the difference was not significant (p=0.108). The 5-year overall survival rate was 86.2% in the COPD group and 82.1% in the non-COPD group after matching (p=0.580). The corresponding 5-year recurrence-free survival rate was 72.8% in the COPD group and 67.2% in the non-COPD group after matching (p=0.601). CONCLUSION: In case of Global Initiative for Chronic Obstructive Lung Disease (GOLD) I/II classification, COPD did not significantly worsen the prognosis of patients with NSCLC after lobectomy.

DOI： 10.21873/anticanres.16723

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Language：English   Publisher：Transplantation Proceedings  

Background: This study aimed to elucidate the effect of early enteral nutrition on graft loss within 12 h after living-donor liver transplantation (LDLT) using propensity score-matching analysis and subsequently examine the risk factors for graft loss after LDLT. Methods: We retrospectively reviewed the data of 467 LDLT patients who were assigned to the early and non-early groups based on the optimal cutoff value of 12 h for the starting time of early enteral nutrition after LDLT to predict graft loss. Results: The 1-year graft survival rate of the early group before propensity score-matching was 92.1%, whereas the 1-year graft survival rate of the non-early group was 86.2%. There was no significant difference between the 2 groups (P = .067). The incidences of early allograft dysfunction (EAD), small-for-size graft (SFSG) syndrome, acute cellular rejection (ACR), and sepsis were not statistically different between the 2 groups (P = .12, .91, .46, and .056, respectively). After propensity score-matching, the 1-year graft survival rate of the early group was 94.4%, whereas the 1-year graft survival rate of the non-early group was 85.4% (P = .034). The incidences of EAD, SFSG syndrome, and ACR were not statistically different between the 2 groups (P = .43, .81, and .24, respectively). However, the incidence of sepsis was statistically different between the 2 groups (non-early: 10.7% vs early: 3.6%, P = .038). Conclusion: Early enteral nutrition within 12 h after LDLT may contribute to better graft survival in LDLT patients by preventing sepsis.

DOI： 10.1016/j.transproceed.2023.07.029

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Language：English   Publisher：シュプリンガー・ジャパン(株)  

切除後の膵癌患者に対するS-1による術後補助化学療法の効果を投与期間で比較するため、6ヵ月を標準期間として12ヵ月と比較する多施設共同無作為化非盲検第II相試験を実施した。組織学的に浸潤性膵管癌が証明され、病理学的病期がI-III期で、局所残存腫瘍または顕微鏡的残存腫瘍のない患者を適格とし、6ヵ月群82例(60歳以上70例)と12ヵ月群82例(60歳以上76例)を比較した。その結果、レジメン完了率は6ヵ月群が64.7%、12ヵ月群が44.0%であった。2年生存率(OS)は6ヵ月群が71.5%、12ヵ月群が65.4%であった(ハザード比[HR]1.143;80%CI 0.841～1.553;P=0.5758)、2年無病生存率(DFS)はそれぞれ46.4%と44.9%であった(HR 1.069、95%CI 0.727～1.572、P=0.6448)。レジメンを完了した患者の2年DFSは56.5%(6ヵ月群)、75.0%(12ヵ月群)であった。5%以上の頻度で認められたグレード3以上の有害事象は、食欲不振(6ヵ月群で10.5%)および下痢(6ヵ月群と12ヵ月群でそれぞれ5.3%と5.1%)であった。以上より、切除された膵癌患者において、S-1による12ヵ月の術後補助化学療法は、OSとDFSに関して6ヵ月の治療より優れていなかった。

Language：English   Publisher：Springer Berlin Heidelberg  

症例は53歳女性。全身性硬化症(SSc)に罹患しており、食道狭窄の精査加療目的に当科紹介となった。15年前に胃食道逆流症(GERD)および間質性肺炎と診断され、プロトンポンプ阻害剤(PPI)、ミコフェノール酸モフェチル、タクロリムス、プレドニゾロンを処方されていた。5年前、逆流症状と咳嗽を呈して入院となり、内視鏡検査で軽度逆流性食道炎と食道裂孔ヘルニアを認め、食道内圧検査にて平均積算弛緩圧は14.3mmHgを示し蠕動の全欠損がみられた。さらに3年前、嚥下障害の増悪をきたし、食道造影で食道無蠕動ならびに液体通過に障害がみられ、内視鏡検査で中等度の逆流性食道炎を検出、PPIを増量して退院となった。しかし、1年前にGERD症状の悪化を呈し、内視鏡検査で重度逆流性食道炎と潰瘍形成を認め、radical incision and cuttingを行うも拘縮再発がみられたため手術目的に当科へ紹介された。受診時、重度嚥下障害、食道逆流、皮膚硬化、顔面と手指の拘縮が認められ、内視鏡検査で重度逆流性食道炎と食道狭窄、食道造影にて食道拘縮が検出された。胸腔鏡下食道亜全摘術と腹腔鏡下胃管再建術を施行し、術後の組織病理所見では筋層の菲薄化および断裂、筋組織への線維性組織への置換がみられた。タクロリムスの用量調整目的に1ヵ月の入院を要し、状態の安定を得た後に退院となった。術後6ヵ月、GERDや食道拘縮の所見は認めていない。

DOI： 10.1016/j.annonc.2023.10.762

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Language：Japanese   Publisher：血管外科症例検討会  

症例1は75歳、男性。閉塞した腋窩-両大腿動脈バイパスのstump syndromeにより、右下肢急性動脈閉塞症を発症した。緊急で右下肢の血栓除去術を行い、待機的にグラフト末梢吻合部の離断を行う方針とした。しかし、翌日に対側の下肢にも急性動脈閉塞が発生したため、対側の血栓除去術に加え、バイパスの末梢吻合部の離断を行った。症例2は71歳、男性。閉塞した大腿-大腿動脈交叉バイパスのstump syndromeにより、左下肢急性動脈閉塞を発生した。血栓除去術と左側の吻合部の離断を行った。非解剖学的バイパスの閉塞に伴う急性動脈閉塞症に対しては、血栓除去術に加えて、閉塞したバイパスの吻合部の離断も検討するべきである。(著者抄録)

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: NASH is an increasingly common cause of chronic liver disease and can progress to cirrhosis and HCC. Although exercise suppresses inflammation during acute hepatitis, its impact on the progression of chronic liver disease remains unclear. Here, we investigated the effects of exercise on disease progression and intrahepatic immune cell composition in a mouse model of NASH. METHOD: Mice were assigned to 4 groups: 2 control groups (normal diet) and 2 NASH groups (western diet and low-dose carbon tetrachloride injection). One of each group remained sedentary and one was exercised on a treadmill for 12 weeks (60 min/d, 5 times/wk). All mice were then analyzed for liver histomorphology, steatosis, inflammation, and fibrosis; liver, adipose tissue, and skeletal muscle expression of genes related to metabolism and inflammation; and intrahepatic immune cell composition. RESULT: Compared with the normal diet mice, NASH mice exhibited enhanced liver steatosis, inflammation, and fibrosis; upregulated expression of liver lipogenesis-related and inflammation-related genes; and increased frequencies of intrahepatic F4/80int CD11bhi bone marrow-derived macrophages and programmed death receptor-1 (PD-1)+ CD8+ T cells. Expression of inflammatory cytokines and the frequencies of bone marrow-derived macrophages and PD-1+ CD8+ T cells correlated positively with liver steatosis, inflammation, and fibrosis. Exercise was shown to reduce NASH-induced hepatic steatosis, liver inflammation, and fibrosis; induce alterations in metabolism-related genes and inflammatory cytokines in the liver; and suppress accumulation of liver bone marrow-derived macrophages and PD-1+ CD8+ T cells. In addition, we showed that exercise induced increased expression of IL-15 in muscle and its deficiency exacerbated the pathology of NASH. CONCLUSIONS: Exercise alters the intrahepatic immune cell profile and protects against disease progression in a mouse model of NASH.

DOI： 10.1097/HC9.0000000000000236

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Language：English   Publisher：John Wiley & Sons Australia, Ltd  

腹腔鏡下胆嚢摘出術が施行された急性胆嚢炎患者189例を対象に、臨床転帰を評価する新たな複合指標であるtextbook outcome(TO)を検討した。TOは、開腹手術への移行、術中合併症、Clavien-Dindo分類でGrade II以上の術後合併症、10日以上の在院期間の延長、術後30日以内の再入院がない腹腔鏡下胆嚢摘出術と定義した。TOは154例で達成した。開腹手術への移行は10例、術中合併症は1例、術後合併症は5例で発生し、29例で在院期間が10日以上であった。患者をTO達成群154例(男性107例、女性47例、年齢中央値63歳)と非達成群35例(男性23例、女性12例、年齢中央値74歳)に分類した。医療費はTO達成群が有意に低かった。多変量解析の結果、70歳以上、ヘモグロビン濃度11.9g/dL未満、白血球数18000/μL以上がTOの非達成を予測する独立因子であった。

Language：English   Publisher：Asian Journal of Endoscopic Surgery  

Purpose: Textbook outcome (TO) is a novel composite measure of clinical outcomes that can be used to measure the quality of surgical outcomes. The aim of this cohort study was to propose TO criteria for laparoscopic cholecystectomy for acute cholecystitis and to identify reasons for TO failure and individual patient factors that predispose to failure. Methods: We retrospectively analyzed data for 189 patients with acute cholecystitis who underwent laparoscopic cholecystectomy. TO was defined as laparoscopic cholecystectomy without conversion to open cholecystectomy, intraoperative complications, postoperative complications (Clavien–Dindo classification ≥2), prolonged length of stay (≥10 days), readmission within 30 days, or mortality. Results: TO was achieved in 154 of 189 patients who underwent laparoscopic cholecystectomy for acute cholecystitis. Medical costs were lower in the TO-achieved group than in the TO-failure group. Factors associated with TO failure on multivariate analysis were age > 70 years, hemoglobin <11.9 g/dL, and white blood cells >18 000 / μL (all P <.05). Conclusions: Applying TO to patients with acute cholecystitis allowed us to evaluate the overall quality of care related to hospitalization. TO may provide better assessment of the quality of care and help determine the treatment choice and reduce costs.

DOI： 10.1111/ases.13238

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DOI： 10.1007/s13691-023-00618-6

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Language：English   Publisher：Transplantation  

Small-for-size syndrome (SFSS) is a well-recognized complication following liver transplantation (LT), with up to 20% developing this following living donor LT (LDLT). Preventing SFSS involves consideration of factors before the surgical procedure, including donor and recipient selection, and factors during the surgical procedure, including adequate outflow reconstruction, graft portal inflow modulation, and management of portosystemic shunts. International Liver Transplantation Society, International Living Donor Liver Transplantation Group, and Liver Transplant Society of India Consensus Conference was convened in January 2023 to develop recommendations for the prediction and management of SFSS in LDLT. The format of the conference was based on the Grading of Recommendations, Assessment, Development, and Evaluation system. International experts in this field were allocated to 4 working groups (diagnosis, prevention, anesthesia, and critical care considerations, and management of established SFSS). The working groups prepared evidence-based recommendations to answer-specific questions considering the currently available literature. The working group members, independent panel, and conference attendees served as jury to edit and confirm the final recommendations presented at the end of the conference by each working group separately. This report presents the final statements and evidence-based recommendations provided by working group 2 that can be implemented to prevent SFSS in LDLT patients.

DOI： 10.1097/TP.0000000000004769

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Language：English   Publisher：シュプリンガー・ジャパン(株)  

症例は55歳女性。腹痛を主訴に受診し、上部消化管内視鏡検査で十二指腸第3部にBorrmann 2型腫瘍が認められ、生検により高頻度マイクロサテライト不安定性(MSI-H)と高分化型から中分化型の腺癌が明らかになった。上部消化管造影とCTでも十二指腸に腫瘍が認められ、ステージIV十二指腸腺癌と診断した。腫瘍は左腎静脈に近接しており、小腸の腸間膜リンパ節転移も認められたため、ペムブロリズマブによる術前治療を開始した。2コース終了後に十二指腸狭窄のため緊急入院となり、上部消化管内視鏡検査で十二指腸内腔に微小な穴が認められた。CTでは、腫瘍の著しい退縮と十二指腸狭窄が認められた。リンパ節も著明に縮小していたことから、根治切除が可能であると判断し、腹腔鏡下十二指腸部分切除術とリンパ節郭清を行った。術後経過は順調で、病理学的完全奏効を達成した。生検でMSI-Hが検出されたこと、子宮癌の既往があること、近親者に癌の既往があることから、Lynch症候群(LS)が疑われた。患者の末梢血を用いて遺伝子検査を行ったところ、MSH2遺伝子のNM_000251.3:c.211+1G>Cに変異が認められ、LSと診断した。

Language：English   Publisher：John Wiley & Sons Australia, Ltd  

肺癌におけるCD155発現を転写後レベルで調節している可能性があるマイクロRNA(miR)の同定を試みた。標的予測プログラムを用いた網羅的miRスクリーニングを行い、さらに二重ルシフェラーゼレポーターアッセイを施行した。その結果、CD155 mRNAの3'-UTRに結合するmiRとして4種(miR-346、miR-328-3p、miR-326、miR-330-5p)が同定された。これらのmiRを複数の肺癌細胞株で強制発現させるとCD155の発現が抑制された。肺腺癌患者57名の組織検体でCD155を標的とする免疫組織化学解析を行った。その結果、CD155の腫瘍割合スコアの中央値は68%となった。これらの組織検体のうちCD155発現レベルが低い検体では高い検体よりもmiR-326が豊富に存在していた(p<0.005)。本研究結果から、肺腺癌ではmiR-326はCD155発現を負方向へ調節していることが示唆された。CD155発現の亢進はPD-1/PD-L1阻害剤耐性の機序になっていることから、miR-326はその耐性の出現に際して何らかの役割を果たしていると考えられた。

Language：English   Publisher：シュプリンガー・ジャパン(株)  

症例は90歳女性。非B非C型肝炎であり、18ヵ月前に原発性肝細胞癌に対して腹腔鏡下肝切除術が施行された。術後6ヵ月、肝細胞癌再発に対して経カテーテル的肝動脈化学塞栓療法(TACE)が施行されたが、その1年後に2回目の再発が認められた。レンバチニブ(LEN)8mg/日投与を開始したところ、1週間後に極度の疲労や食欲不振などの重篤な有害事象(AE)が出現し、投与量を4mg/日に減量したがAEの管理は困難であった。そこで、LEN導入から1ヵ月後に化学療法をアテゾリズマブ+ベバシズマブ併用療法に変更した。その結果、副作用はほとんど認められず、腫瘍の退縮が認められた。本レジメンを8ヵ月間、10サイクル続け、最終的に完全奏効(CR)を達成した。CR達成後1年経過しても再発はみられていない。

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Language：English   Publisher：Journal of Hepato-Biliary-Pancreatic Sciences  

Purpose: To evaluate the prognostic impact of dynamic gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) in patients with hepatocellular carcinoma (HCC). Methods: We retrospectively reviewed the data of 206 patients with HCC who underwent preoperative Gd-EOB-DTPA-enhanced MRI and hepatectomy and quantitatively evaluated the signal intensity ratio of the tumor to the surrounding liver tissue in the portal phase (SIRPP). We verified the survival rates and assessed the prognostic factors associated with overall survival (OS) and recurrence-free survival (RFS) using SIRPP. Results: Multivariate analysis revealed that the independent predictive factors for poorly-differentiated HCC were α-fetoprotein > 20 ng/mL (hazard ratio [HR]: 3.1909, 95% confidence interval [CI]: 1.3464–7.5622, p =.0084) and SIRPP ≤ 0.85 (HR: 3.7155, 95% CI: 1.521–9.076, p =.004). The 5-year OS and RFS rates in the high and low SIRPP groups were 83.2 and 52.1%, respectively (p <.0001) and 49.7 and 18.5%, respectively (p =.0003). Multivariate analysis revealed that SIRPP ≤ 0.68 was an independent prognostic factor related to OS (HR: 4.4537, 95% CI: 1.6581–11.9626, p =.003). Conclusion: The SIRPP of preoperative Gd-EOB-DTPA-enhanced MRI might predict the histological differentiation and prognosis of HCC.

DOI： 10.1002/jhbp.1345

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Language：English   Publisher：John Wiley & Sons Australia, Ltd  

肝後上区域(PS)の3cm以下の単純結節型肝細胞癌(HCC)に対する腹腔鏡下肝切除(LLR)の有効性を検討した。2010年1月～2018年12月に九州肝臓外科研究会の18施設で3cm以下の単純結節型HCCに対し肝部分切除を受けた患者を後ろ向きに調べた。傾向スコアマッチングを行ってLLRと開腹肝切除(OLR)の短期転帰を比較し、PSと前外側区域(AL)のサブグループ解析も行った。LLR-PSとLLR-AL間の転帰も比較した。患者473例(LLR 328例、OLR 145例)を特定し、マッチング後のLLR群、OLR群各140例を解析した。失血量(中央値55対287mL)、術後合併症(0.71対8.57%)、術後の在院日数(中央値9対14日)に有意な群間差がみられた。PSとALのサブグループ解析の結果も同等であった。LLR-PSとLLR-AL間でも短期転帰に有意差は認められなかった。以上より、PSの3cm以下の単純結節型HCCに対する腹腔鏡下部分切除術は好ましい選択肢である可能性が示された。

Language：English   Publisher：シュプリンガー・ジャパン(株)  

70歳以上の局所進行胃癌(LAGC)患者に対する術前補助化学療法(NAC)としてのS-1+オキサリプラチン(SOX)の安全性と有効性を評価するため、第II相試験(KSCC1801)を行った。オキサリプラチン(130mg/m2、1日目に静脈内投与)とS-1(40～60mg、1日2回、14日間経口投与)(SOX130)を用いる3コースのNACを3週毎に実施した後、胃切除とリンパ節郭清を行った。対象患者は26例(男性73.1%、年齢中央値74.5歳)で、主要評価項目の用量強度中央値はS-1で97.2%、オキサリプラチンで98.3%であった。24例が胃切除を受けた。R0切除率は92.3%、病理学的奏効率は62.5%であった。全例が少なくとも1件の有害事象を経験した。主なグレード3以上の有害事象は好中球減少症(20.0%)と血小板減少症(11.5%)であった。1件の治療関連死が発生した。2年全生存率は89.7%、2年無再発生存率は58.6%であった。

Language：English   Publisher：John Wiley & Sons Australia, Ltd  

肝細胞癌(HCC)患者におけるダイナミックGd-EOB-DTPA造影MRI所見と予後との関連を検討した。Gd-EOB-DTPA造影MRIの施行後に肝切除を受けたHCC患者206例を対象に後ろ向きレビューを行い、門脈相における肝組織周囲に対する腫瘍の信号強度比(SIRPP)を算出し、全生存率(OS)、無再発生存率(RFS)との関連を評価した。58例(28.2%)に未分化成分が検出され、多変量解析では未分化型HCCの独立予測因子としてAFP 20ng/mL超およびSIRPP 0.85以下が抽出された。患者生存を評価したROC解析ではSIRPPのカットオフ値は0.68と算出され、この値をもとにSIRPP高値群166例とSIRPP低値群40例に分類すると、高値群にはF3またはF4の組織学的肝硬変が多く、SIRPP低値群にはBCLCステージBまたはC、腹腔鏡下肝切除の施行、未分化型HCC、被膜形成、顕微的被膜浸潤・脈管浸潤・胆管浸潤を多く認めた。また、AFP、AFP-L3、DCP、手術時間、術中出血量、腫瘍サイズはSIRPP低値群の方が有意に高値を示しており、5年OSはSIRPP高値群が83.2%、低値群が52.1%、5年RFSはSIRPP高値群が49.7%、低値群が18.5%と有意差が認められた。多変量解析ではOSの独立予測因子としてDCP 100mAU/mL以上、SIRPP 0.68以下、RFSの独立予測因子として腫瘍数2個以上が示された。ダイナミックGd-EOB-DTPA造影MRIによりHCCの組織学的分化度と予後を予測できうると思われた。

Language：English   Publisher：Journal of Surgical Case Reports  

Surgical therapy following lenvatinib (LEN) plus transarterial chemoembolization (TACE) is a useful therapeutic option for intermediate-stage hepatocellular carcinoma (HCC). A 66-year-old man with a history of hepatitis C was detected four masses in the caudate lobe and segment 6/7 of the liver, with a maximum lesion diameter of 14 cm by computed tomography. The patient was diagnosed with intermediate-stage HCC and received LEN plus TACE. After resuming LEN for 8 weeks, computed tomography showed weakened stained areas of the tumors, and no new lesions. Thus, the patient was evaluated as having a partial response in the modified Response Evaluation Criteria in Solid Tumors. The patient underwent hepatic caudate lobectomy, partial hepatectomy of S6/7, and S6 microwave coagulation therapy for radical resection. The patient is currently alive and recurrence-free at 12 months postoperatively. In patients with multiple HCC lesions, hepatic resection combined with local therapy might be an effective treatment option.

DOI： 10.1093/jscr/rjad485

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BACKGROUND: Six-month adjuvant chemotherapy with S-1 is standard care for resected pancreatic cancer in Japan; however, the optimal duration has not been established. We aimed to evaluate the impact of duration of adjuvant chemotherapy with S-1. METHODS: We performed a multicenter, randomized, open-label, phase II study. Patients with histologically proven invasive pancreatic ductal carcinoma, pathological stage I-III, and no local residual or microscopic residual tumor were eligible. Patients were randomized 1:1 to receive 6- or 12-month adjuvant chemotherapy with S-1. The primary endpoint was 2-year overall survival (OS). Secondary endpoints were disease-free survival (DFS) and feasibility. RESULTS: A total of 170 patients were randomized (85 per group); the full analysis set was 82 in both groups. Completion rates were 64.7% (6-month group) and 44.0% (12-month group). Two-year OS was 71.5% (6-month group) and 65.4% (12-month group) (hazard ratio (HR): 1.143; 80% confidence interval CI 0.841-1.553; P  =  0.5758). Two-year DFS was 46.4% (6-month group) and 44.9% (12-month group) (HR: 1.069; 95% CI 0.727-1.572; P = 0.6448). In patients who completed the regimen, 2-year DFS was 56.5% (6-month group) and 75.0% (12-month group) (HR: 0.586; 95% CI 0.310-1.105; P  = 0.0944). Frequent (≥ 5%) grade ≥ 3 adverse events comprised anorexia (10.5% in the 6-month group) and diarrhea (5.3% vs. 5.1%; 6- vs. 12-month group, respectively). CONCLUSIONS: In patients with resected pancreatic cancer, 12-month adjuvant chemotherapy with S-1 was not superior to 6-month therapy regarding OS and DFS.

DOI： 10.1007/s10147-023-02399-7

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Language：Others   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.celrep.2023.112899

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Treatment with immune checkpoint inhibitors induces a durable response in some patients with non-small-cell lung cancer, but eventually gives rise to drug resistance. Upregulation of CD155 expression is implicated as one mechanism of resistance to programmed death receptor-1 (PD-1)/PD-1 ligand (PD-L1) inhibitors, and it is therefore important to characterize the mechanisms underlying regulation of CD155 expression in tumor cells. The aim of this study was to identify microRNAs (miRNAs) that might regulate CD155 expression at the posttranscriptional level in lung cancer. Comprehensive miRNA screening with target prediction programs and a dual-luciferase reporter assay identified miR-346, miR-328-3p, miR-326, and miR-330-5p as miRNAs that bind to the 3'-UTR of CD155 mRNA. Forced expression of these miRNAs suppressed CD155 expression in lung cancer cell lines. Immunohistochemical staining of CD155 in tissue specimens from 57 patients with lung adenocarcinoma revealed the median tumor proportion score for CD155 to be 68%. The abundance of miR-326 in these specimens with a low level of CD155 expression was significantly greater than in specimens with a high level (p < 0.005). Our results thus suggest that miR-326 negatively regulates CD155 expression in lung adenocarcinoma and might therefore play a role in the development of resistance to PD-1/PD-L1 inhibitors.

DOI： 10.1111/cas.15921

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DOI： 10.1245/s10434-023-14037-7

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DOI： 10.1245/s10434-023-14085-z

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Language：English   Publisher：シュプリンガー・ジャパン(株)  

肝細胞癌(HCC)を発症したFontan手術関連肝疾患の3例を報告した。症例1は28歳女性で、4歳時にFontan手術(FO)を受けた。HCC(cT4aN0M0、Stage IVA、UICC第8版)と診断され、拡大右葉後区域切除およびS2の肝部分切除を受けた。術後12ヵ月目に腹膜播種再発が認められ、手術後18ヵ月の時点で存命中である。症例2は43歳男性で、FOを3歳時に受けた。HCC(cT2N0M0、Stage II)と診断され、腹腔鏡補助下S3部分切除を受けた。術後17ヵ月間HCCの再発は認められていない。症例3は21歳女性で、FOを3歳時に受けた。HCC(cT3N0M0、Stage III)と診断され、腹腔鏡補助下S2およびS4肝部分切除を受けた。術後30ヵ月間、HCCの再発は認められていない。Fontan関連肝疾患由来のHCCは、本報の3例を含めこれまで18例報告があり、術前AFP高値がHCC再発の予知因子である可能性が示唆された。

Language：English   Publisher：John Wiley & Sons Australia, Ltd  

日本の単一施設の肝細胞癌(HCC)患者64例の腫瘍データ80件を後ろ向きに評価し、術中インドシアニングリーン(ICG)蛍光画像(FI)パターン、術前Gd-EOB-DTPA造影MRI所見、術前MRI拡散強調画像(DWI)、組織学的分化の臨床的関連性を評価した。ICG FIでrim陽性であった患者では、rim陰性患者に比べて低分化HCC率とGd-EOB-DTPA造影MRI肝胆道相(HBP)の低信号率が有意に高く、Gd-EOB-DTPA造影MRI門脈相の周囲肝組織に対する腫瘍のシグナル強度比(SIRPP)とMRI DWI見かけの拡散係数(ADC)が有意に低値であった。ICG FIで癌性に分類された患者は、非癌性患者に比べて中分化HCC率、Gd-EOB-DTPA造影MRI HBPの高信号率とSIRPP、MRI DWI ADCが有意に高値であった。多変量解析において、SIRPP低値、ADC低値、HBPの低信号率はrim陽性HCCの有意な予測因子であり、SIRPP高値、ADC高値、HBPの高信号率は癌性HCCの有意な予測因子であった。

Language：English   Publisher：シュプリンガー・ジャパン(株)  

治癒的肝切除を受けた肝内胆管癌(ICC)患者におけるヘモグロビン、アルブミン、リンパ球、血小板(HALP)スコアのバイオマーカーとしての予後予測能およびサルコペニアや免疫微小環境との関連を後ろ向きに検討した。1998～2018年に当院でICCに対して外科的切除を受けた患者95例(年齢33～87歳)を対象とした。HALPスコアのカットオフ値25.2に基づきICC患者をHALP高値と低値の2群に分けた。その結果、患者95例中22例がHALP低値であった。HALP低値群では、有意にアルブミン値が低く、ヘモグロビン値が低く、血小板数が多く、リンパ球数が少なく、CA19-9値が高く、リンパ節転移が多かった。多変量解析の結果、無病生存率の独立した予後因子は、最大腫瘍径(5.0cm以上)、微小血管浸潤、HALPスコア(25.2以下)であり、全生存率の予後因子は、リンパ節転移、HALPスコア(25.2以下)であった。HALP低値群にはサルコペニアを有する患者が有意に多かった。さらに免疫組織化学的には、CD陽性腫瘍浸潤リンパ球数はHALP低値群で有意に少なかった。以上より、HALPスコアの低さは、治癒的肝切除を受けるICC患者の独立した予後因子であり、サルコペニアおよび免疫微小環境と関連していた。

Publisher：Renal Replacement Therapy  

Backgrounds: Therefore, reports on the risk of HTLV-1-related diseases in organ transplantation have increased in recent years, and the management of HTLV in renal transplantation remains a challenge. Patients and methods: We retrospectively analyzed four HTLV-1-positive recipients or donors among 89 renal transplantation cases from 2006 to 2021. Results: Among the four HTLV-1-positive recipients, two patients developed adult T cell leukemia/lymphoma (ATL) derived from recipients at approximately 3 years (1016 days and 1195 days) after renal transplantation. Case 1 developed lymphoma-type ATL (an extranodal primary cutaneous variant), including skin and pulmonary lesions. The patient achieved CR with FK tapering and CHOP therapy following cord blood stem cell transplantation. However, the patient died 101 days after ATL development because of a severe fungal infection. Case 2 developed acute-type ATL with an unusual phenotype of CD4+8+30+. The patient was treated with FK tapering and palliative therapy because of poor PS. Notably, in case 1, histopathological findings showed high numbers of PD-1-positive TIL cells in ATL, suggesting exhausted T cells and a correlation with the early onset of ATL. Furthermore, in Case 2, histopathological findings revealed CD 30 expression in ATL cells, suggesting the importance of CD 30 in ATL development. Importantly, case 2 showed typical driver mutations, including CCR4 truncation mutations of the C-terminal, TBL1XR1 mutation, and TP53 mutation in the splice site. Notably, our present study and our previous study on renal transplantation strongly indicated that two out of two and one out of 59 “recipient” positive cases developed ATL, respectively. Furthermore, our previous nationwide study 4 out of 10 “donor” positive cases developed HAM. These findings showed that ATL may be derived from HTLV-I+ recipient cells and HAM may be derived from HTLV-1+ donor cells, although the precise mechanism remains unknown. Conclusions: Thus, early onset and rapid progression of ATL with poor outcomes should be considered in HTLV-1 endemic areas. Furthermore, immunological or genetic mechanisms may be related to the development of ATL after renal transplantation. We believe that the mechanism of onset of ATL after transplantation may be important when considering the immune environment of ATL itself.

DOI： 10.1186/s41100-023-00480-5

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BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) often recurs early after radical resection, and such early recurrence (ER) is associated with a poor prognosis. Predicting ER is useful for determining the optimal treatment. METHODS: One hundred fifty-three patients who underwent pancreatectomy for PDAC were divided into an ER group (n = 54) and non-ER group (n = 99). Clinicopathological factors were compared between the groups, and the predictors of ER and prognosis after PDAC resection were examined. RESULTS: The ER group had a higher platelet count, higher platelet-to-lymphocyte ratio (PLR), higher preoperative CA19-9 concentration, higher SPan-1 concentration, larger tumor diameter, and more lymph node metastasis. The receiver operating characteristic (ROC) curve analysis identified cut-off values for PLR, carbohydrate antigen 19-9 (CA19-9), SPan-1, and tumor diameter. In the multivariate analysis, a high PLR, high CA19-9, and tumor diameter of >3.1 cm were independent predictors of ER after resection (all p < 0.05). When the parameter exceeded the cut-off level, 1 point was given, and the total score of the three factors was defined as the ER prediction score. Next, our new ER prediction model using PLR, CA19-9 and tumor diameter (Logit(p) = 1.6 + 1.2 × high PLR + 0.7 × high CA19-9 + 0.5 × tumor diameter > 3.1cm) distinguished ER with an area under the curve of 0.763, a sensitivity of 85.2%, and a specificity of 55.6%. CONCLUSIONS: ER after resection of PDAC can be predicted by calculation of a score using the preoperative serum CA19-9 concentration, PLR, and tumor diameter.

DOI： 10.1371/journal.pone.0288033

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Publisher：南江堂  

DOI： 10.15106/j_geka85_863

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Abstract

Background

Because the robotic arm is located on the dorsal side of the patient, when the esophagus is pulled dorsally for the left recurrent nerve lymph node (LRLN) dissection, the robotic arm interferes with the surgical field. This made it difficult to prepare for the left recurrent lymph node dissection. We developed LRLN dissection in robotic surgery with natural space creation by physiological organ movement and evaluated the short-term results.

Methods

In this retrospective study, we analyzed 102 cases of robot-assisted thoracoscopic subtotal esophagectomy (RATE) among radical subtotal esophagectomies performed between December 2018 and December 2022 using medical records. LRLN dissection is preceded by a dissection of the esophagus from the trachea. Leaving the esophagus on the vertebral side and away from the trachea resulted in a physiological elevation of the esophagus, providing space between the trachea and esophagus.

Results

The thoracic surgery time in RATE was 181 (115–394) min. The number of LRLNs dissected was 4 (1–14). Six patients (6%) had a postoperative recurrence in the mediastinal lymph nodes. Seven patients (7%) had grade ≥ 1 left recurrent nerve palsy.

Conclusions

LRLN dissection with RATE using natural space creation was performed safely with a sufficient number of dissected lymph nodes and little left recurrent nerve palsy.

DOI： 10.1186/s12957-023-03117-3

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Autoimmune encephalitis after liver transplantation (LT) is a rare disorder. This is because patients are usually in an immunosuppressed state after LT. Here, we report a rare case of autoantibody-negative autoimmune-encephalitis-induced coma after living-donor (LD) LT. A 45-year-old woman who underwent LDLT for primary biliary cholangitis (PBC) was brought to our hospital with the chief complaint of cognitive deficiency and an episode of memory loss. Physical examination, laboratory tests, and cerebrospinal fluid analysis revealed no significant findings. However, diffusion-weighted magnetic resonance imaging showed hyperintensity in the bilateral hippocampus. No autoantibodies associated with autoimmune encephalitis were detected. The diagnosis of antibody-negative autoimmune encephalitis was made on the basis of low immunosuppressive drug levels in the blood (indicative of poor adherence) and the presence of PBC as the autoimmune disease. The patient regained consciousness after intravenous methylprednisolone pulse therapy and plasma exchange. This case highlights that when examining patients with impaired consciousness after LDLT, it is important to consider autoimmune encephalitis as a potential diagnosis.

DOI： 10.1016/j.transproceed.2023.07.005

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DOI： 10.1007/s13691-023-00622-w

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DOI： 10.1245/s10434-023-13864-y

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Language：English   Publisher：BioMed Central  

ヒトT細胞白血病ウイルス1型(HTLV-1)陽性の腎移植レシピエントで成人T細胞白血病/リンパ腫(ATL)が早期発症し迅速に進行した症例に遭遇したことから、自験例を後ろ向きに調査した。2006～2021年に当院で経験した腎移植レシピエント患者89名のうち、ドナーまたはレシピエントがHTLV-1陽性であった例は4名おり、うち2名がATLを発症していた。症例1は60歳男性で、元からHTLV-1陽性であり、ドナーは陰性であった。腎移植から1016日後にリンパ腫型ATLを発症した。タクロリムス、CHOP化学療法、臍帯血幹細胞移植術にてCRを達成したが、ATL発症101日後に重症の真菌感染症のため死亡した。症例2は75歳女性で、ドナーのみHTLV-1陽性であった。移植1195日後にCD4、8、30陽性とunusualな表現型のATLを発症した。タクロリムスで加療したがパフォーマンスステータスが不良であったことから同薬は減量してゆき緩和医療を提供した。そうした治療の転帰はPDと判定され、ATLと診断してから5日後に死亡した。HTLV-1が流行している地域では、腎移植後にATLが早期に発症して迅速に進行して転帰不良となる可能性を考慮するべきであった。本ATL発症例をさらに解析するなどした結果から、腎移植後のATL発症には免疫学的機序と遺伝学的機序が関係していると考えられた。

Language：English   Publishing type：Research paper (scientific journal)  

Angiosarcoma is a malignant vascular endothelial neoplasm with various histological patterns. Despite its highly malignant potential, histological prognostic prediction has not been adopted for angiosarcoma. This study aimed to establish a method of predicting the prognosis of primary angiosarcoma. Formalin-fixed, paraffin-embedded samples from 104 primary angiosarcomas were prepared. All the cases were reviewed based on histological examinations with H&E staining. Because the French Fédération Nationale des Centres de Lutte Contre Le Cancer system (FNCLCC) is not adopted for angiosarcoma, we experimentally established a modified version of FNCLCC. Immunohistochemical staining for ERG, CD31, CD34, D2-40, HHV-8, p16, C-MYC, and p53 was performed. Fluorescence in situ hybridization (FISH) was performed for 31 cases to assay c-MYC gene amplification. Multivariate analysis revealed that age (> 70 years old) (p = 0.0011), non-cutaneous angiosarcoma (p = 0.0265), metastasis on diagnosis (p < 0.0001), size ≥ 5 cm (p = 0.0388), no taxane chemotherapy (p = 0.0388), strong nuclear atypia (p = 0.0087), and the presence of luminal structure in ≥ 50% of the tumor volume (p = 0.0009) were independent poor prognostic factors. Among angiosarcomas with luminal formation, mFNCLCC scores were significantly correlated with a poorer prognosis. The overexpression of p16 was associated with less luminal formation (p = 0.0192). Immunohistochemical analysis of C-MYC showed a moderate level of concordance with FISH (Kappa value = 0.45). This study suggested that luminal formation and nuclear atypia may be poor histological prognostic factors of angiosarcoma and that mFNCLCC would be useful for predicting the prognosis of angiosarcoma with luminal formation.

DOI： 10.1007/s00428-023-03572-z

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BACKGROUND: Pancreatic metastases from other primary malignancies are rare. There is no clear evidence for a treatment strategy for this condition. The purpose of this study was to assess the clinical outcomes, including prognostic factors for pancreatic resection of metastatic tumors in the pancreas, through a retrospective review. METHODS: Data of 35 patients who underwent pancreatic resection for pancreatic metastasis between 2005 and 2020 in eight Japanese institutions were included in this study. Survival analyses were performed using the Kaplan-Meier method, and comparisons were made using the Cox proportional hazards model. RESULTS: The median follow-up period was 35 months (range, 5-102 months). Median duration from resection for primary tumor to resection for metastatic pancreatic tumor was 10.6 years (range, 0.6-29.2 years). The 3- and 5-year survival rates after resection for metastatic tumors in the pancreas were 89% and 69%, respectively. In contrast, the 3- and 5-year disease-free survival rates after resection for metastatic tumors in the pancreas were 48% and 21%, respectively. Performance status ≥1 at the time of resection for metastatic tumors in the pancreas (HR: 7.56, p = 0.036) and pancreatic metastasis tumor diameter >42 mm (HR: 6.39, p = 0.02) were significant poor prognostic factors only in the overall survival. CONCLUSIONS: The prognosis of pancreatic resection for metastatic tumors in the pancreas is relatively good for selected patients. However, because it is prone to recurrence after radical surgery, it should only be considered in patients with good PS.

DOI： 10.1016/j.suronc.2023.101942

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Abstract

Background

Intramural metastasis (IM) of esophageal cancer is classified as distant metastasis according to the Japanese Classification of Esophageal Cancer, and it is well-known to be associated with a poor prognosis. We herein report a case of perforated gastric IM of esophageal cancer that was successfully controlled with nonradical surgery and subsequent immune checkpoint inhibitor (ICI) treatment.

Case presentation

A 72-year-old woman was referred to our department for the treatment of esophageal cancer and perforated gastric ulcer. A histological examination of the main tumor and gastric ulcer lesion revealed squamous cell carcinoma. Since the gastric wall tumor had invaded the celiac artery, complete resection was considered impossible. Chemotherapy was administered but led to severe adverse events, so palliative resection was performed. Two months after surgery, computed tomography revealed enlargement of the residual tumor around the celiac artery. However, after nivolumab monotherapy was started, the tumor diminished remarkably, and the quality of life of the patient dramatically improved. Nine months after nonradical surgery, she is surviving without any disease concern.

Conclusions

With the increased availability of ICIs, multidisciplinary treatment with surgery and ICIs can potentially lead to long-term survival, even in cases expected to have a poor prognosis.

DOI： 10.1186/s40792-023-01703-x

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PURPOSE: To clarify the Japan criteria (JC), as proposed in 2019, in order to identify the most appropriate treatment methods for hepatocellular carcinoma (HCC) recurrence and assess the feasibility of pre-living donor liver transplantation (LDLT) downstaging within these criteria. METHODS: The subjects of this study were 169 LDLT patients with HCC recurrence. We performed univariate and multivariate analyses of the factors contributing to HCC recurrence after LDLT and clarified the post-transplant outcomes of pre-LDLT downstaging. RESULTS: Univariate and multivariate analysis identified beyond the JC (p = 0.0018) and a neutrophil-to-lymphocyte ratio > 2.01 (p = 0.029) as independent risk factors. Patients who met the JC had significantly higher recurrence-free and overall survival rates after LDLT (p < 0.0001) than those who did not (p = 0.0002). The post-transplant outcomes of patients within the JC after downstaging were significantly better than those of patients beyond the JC (p = 0.034) and equivalent to those within the JC without downstaging. CONCLUSION: Even for HCC recurrence, the JC could play an important role in deciding on the best treatment strategy, and downstaging within the JC had good post-transplant outcomes.

DOI： 10.1007/s00595-023-02710-z

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PURPOSE: Analyzing the gut microbiome is essential for planning treatment strategies to manage esophageal squamous cell carcinoma. This study aimed to characterize the gut microbiome of patients with esophageal squamous cell carcinoma and to identify alterations in its composition during treatment. METHODS: We observed alterations in the gut microbiome in 21 consecutive patients with esophageal squamous cell carcinoma at five different time points, from neoadjuvant treatment to postoperative surgery. Ten healthy individuals were used as a non-cancer control group. Fecal samples were collected and analyzed using 16S ribosomal ribonucleic acid sequencing. RESULTS: Before treatment, participants with esophageal squamous cell carcinoma had different alpha and beta diversity in comparison to healthy controls. The number of Streptococcus, a facultative anaerobic bacterium, was significantly higher, whereas that of Faecalibacterium, an obligate anaerobic bacterium, was significantly lower. Both alpha and beta diversity remained unchanged during neoadjuvant treatment, but the alterations were pronounced after surgery. The increase in the relative abundance of Streptococcus and the decrease in that of Faecalibacterium also tended to be more pronounced after surgery. CONCLUSIONS: The gut microbiome in patients with esophageal squamous cell carcinoma is altered with surgical intervention.

DOI： 10.1007/s00595-022-02607-3

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DOI： 10.1016/j.xjtc.2023.03.002

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AIM: The hemoglobin, albumin, lymphocyte, and platelet (HALP) score reflects the immune system and the nutritional status of patients, and prognosis in various cancers. However, the HALP score in hepatocellular carcinoma has not been reported. METHODS: Data were analyzed retrospectively from Child-Pugh A patients undergoing hepatic resection for single hepatocellular carcinoma ≤5 cm. For cross-validation, patients were divided into the training (332 patients) and validation cohort (210 patients). In the training cohort, we divided patients into two groups by appropriate cut-off value of the HALP score, and univariable and multivariable analyses were conducted for disease-free and overall survival (OS) between two groups. In the validation cohort, we examined OS by Kaplan-Meier analysis in the same cut-off value of the HALP score in the training cohort. RESULTS: The HALP-low group was significantly older (p = 0.0003), had fewer hepatitis B surface antigen-positive patients (p = 0.0369), higher prothrombin time (p = 0.0141), lower fibrosis-4 index (p = 0.0206), bigger maximum tumor size (p = 0.0196), and less histological liver fibrosis (p = 0.0077). Multivariate analysis showed that the independent prognostic factors for disease-free survival were fibrosis-4 index ≥2.67 (p = 0.0008), simple nodular type with extranodular growth or confluent multinodular type (p = 0.0221), and intrahepatic metastasis (p = 0.0233), and that for OS were fibrosis-4 index ≥2.67 (p = 0.0020), HALP ≤45.6 (p = 0.0228), and poor differentiation (p = 0.0305). In the validation cohort, Kaplan-Meier analysis revealed the trend toward significantly impaired OS (p = 0.0220) in the HALP-low group. CONCLUSION: We showed that a low HALP score is the independent prognostic factor for Child-Pugh A patients undergoing curative hepatic resection for single and small hepatocellular carcinoma.

DOI： 10.1111/hepr.13885

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BACKGROUND: Gastrectomy with D2 dissection and adjuvant chemotherapy is the standard treatment for locally advanced gastric cancer (LAGC) in Asia. However, administering chemotherapy with sufficient intensity after gastrectomy is challenging. Several trials demonstrated the efficacy of neoadjuvant chemotherapy (NAC). However, limited studies explored the feasibility of NAC-SOX for older patients with LAGC. This phase II study (KSCC1801) evaluated the safety and efficacy of NAC-SOX in patients with LAGC aged ≥ 70 years. METHODS: Patients received three cycles of SOX130 (oxaliplatin 130 mg/m2 on day 1, oral S-1 40-60 mg twice daily for two weeks every three weeks) as NAC, followed by gastrectomy with lymph node dissection. The primary endpoint was the dose intensity (DI). The secondary endpoints were safety, R0 resection rate, pathological response rate (pRR), overall survival, and relapse-free survival. RESULTS: The median age of 26 enrolled patients was 74.5 years. The median DI in NAC-SOX130 was 97.2% for S-1 and 98.3% for oxaliplatin. Three cycles of NAC were administered in 25 patients (96.2%), of whom 24 (92.3%) underwent gastrectomy with lymphadenectomy. The R0 resection rate was 92.3% and the pRR (≥ grade 1b) was 62.5%. The major adverse events (≥ grade 3) were neutropenia (20.0%), thrombocytopenia (11.5%), anorexia (11.5%), nausea (7.7%), and hyponatremia (7.7%). Postoperative complications of abdominal infection, elevated blood amylase, and bacteremia occurred in one patient each. Severe diarrhea and dehydration caused one treatment-related death. CONCLUSIONS: NAC-SOX130 is a feasible therapy for older patients, although systemic management and careful monitoring of adverse events are necessary.

DOI： 10.1007/s10147-023-02373-3

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Language：Others   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

Abstract

Background

We aimed to clarify the genomic characteristics of HER2‐positive and negative gastric cancer cases that potentially affect tumor progression and treatment response in a prospective trial.

Methods

We collected 80 formalin‐fixed paraffin‐embedded (FFPE) samples (49 HER2+ and 31 HER2‐) from gastric cancer patients who participated in the TROX‐A1 trial (UMIN000036865). We queried a 435‐gene panel (CANCERPLEX‐JP) to generate comprehensive genomic profiling data, including the tumor mutation burden, somatic mutations, and copy number variations. In addition, the genomic differences between HER2+ and HER2‐ gastric cancer patients were analyzed.

Results

Mutational analyses showed that TP53 was the most frequently mutated gene regardless of HER2 status. ARID1A mutation was significantly enriched in HER2‐negative patients. The number of total mutations in HER2‐negative patients with ARID1A mutation was remarkably higher than that in HER2‐positive patients. Next, copy number variation analyses showed that the number of amplified genes (such as CCNE1, PGAP3, and CDK12) in HER2‐positive cases was significantly higher than that in HER2‐negative cases. Moreover, PTEN deletion was more common in HER2‐positive cases. Finally, we found that, compared with HER2‐positive patients, HER2‐negative patients tended to have a higher tumor mutation burden, particularly in patients with ARID1A mutation. Pathway analyses of the gene alterations showed an enrichment of several immune‐related pathways in HER2‐negative patients.

Conclusions

According to the genomic profiling of HER2‐positive and negative gastric cancer, several gene alterations in the HER2 pathway may be the potential mechanism underlying trastuzumab resistance. Relative to HER2‐positive gastric cancer, HER2‐negative gastric tumors with ARID1A mutation may be sensitive to immune checkpoint inhibitors.

DOI： 10.1002/cam4.6269

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INTRODUCTION: Sleeve gastrectomy is the most common surgical procedure to reduce weight and treat metabolic complications in patients with moderate-to-severe obesity; however, it affects the musculoskeletal system. Dual-energy X-ray absorptiometry (DXA), which is commonly used to measure bone mineral density (BMD), may be affected by excess fat tissue around the bones, interrupting BMD measurement. Due to the strong correlation between DXA and the Hounsfield units (HU) obtained from computed tomography (CT) scans, BMD assessment using clinical abdominal CT scans has been useful. To date, there has been no report of detailed CT evaluation in patients with severe obesity after sleeve gastrectomy. OBJECTIVE: This study investigated the effect of sleeve gastrectomy in severely obese patients on bone and psoas muscle density, and cross-sectional area using retrospective clinical CT scans. METHODS: This was a retrospective observational study that included 86 patients (35 males and 51 females) who underwent sleeve gastrectomy between March 2012 and May 2019. Patients' clinical data (age at the time of surgery, sex, body weight, body mass index (BMI), comorbidities, and preoperative and postoperative blood test results, HU of the lumbar spine and psoas muscle and psoas muscle mass index (PMI)) were evaluated. RESULTS: The mean age at the time of surgery was 43 years, and the body weight and BMI significantly reduced (p < 0.01) after surgery. The mean hemoglobin A1c level showed significant improvement in males and females. Serum calcium and phosphorus levels remained unchanged before and after surgery. In CT analysis, HU of the lumbar spine and psoas muscle showed no significant decrease, but PMI showed a significant decrease (p < 0.01). CONCLUSIONS: Sleeve gastrectomy could dramatically improve anthropometric measures without causing changes in serum calcium and phosphorus levels. Preoperative and postoperative abdominal CT revealed no significant difference in the bone and psoas muscle density, and the psoas muscle mass was significantly decreased after sleeve gastrectomy.

DOI： 10.1016/j.bonr.2023.101661

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DOI： 10.1245/s10434-023-13396-5

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BACKGROUND: Many inflammatory and nutritional markers have been used to predict prognosis in lung cancer. The C-reactive protein (CRP)-to-lymphocyte ratio (CLR) is a useful prognostic factor in various cancers. However, the prognostic value of preoperative CLR in patients with non-small cell lung cancer (NSCLC) remains to be established. We examined the significance of the CLR compared with known markers. METHODS: A total of 1380 surgically resected NSCLC patients treated at two centers were recruited and divided into derivation and validation cohorts. After CLRs were calculated, patients were classified into high and low CLR groups based on the cutoff value determined by receiver operating characteristics curve analysis. Subsequently, we determined the statistical associations of the CLR with clinicopathological factors and prognosis and further analyzed its prognostic impact by propensity-score matching. RESULTS: Of all the inflammatory markers examined, CLR yielded the highest area-under-the-curve value. The prognostic impact of CLR remained significant after propensity-score matching. Prognosis was significantly worse in the high-CLR group than in the low-CLR group (5-year, disease-free survival [DFS]: 58.1% vs. 81.9%, P < 0.001; 5-year overall survival [OS]: 72.1% vs. 91.2%, P < 0.001). The results were confirmed in the validation cohorts. Multivariable analysis also showed high CLR as an independent factor for both DFS and OS (DFS: hazard ratio [HR] 1.42, P = 0.027; OS: HR 1.95, P = 0.0037). CONCLUSIONS: Preoperative CLR is a useful marker for predicting the prognosis of NSCLC patients who have undergone surgery.

DOI： 10.1245/s10434-023-13250-8

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DOI： 10.1245/s10434-022-12974-3

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症例は72歳女性。胸部食道癌と胃潰瘍穿孔の診断で加療を目的に当院へ紹介された。CTで腹水および小彎近くの胃壁に胃潰瘍穿孔による膿瘍の形成を認めた。PET/CTで同部位にFDGの集積亢進を認めた。生検で胃壁の潰瘍性病変と食道癌はいずれも腺癌と診断された。腫瘍は腹腔動脈を囲むように位置しており、浸潤が疑われた。根治手術は困難と診断し、食道癌と胃癌に対してドセタキセル、シスプラチン、5-FUの3剤を併用した化学療法を開始した。15日後に好中球減少症が出現し、ドセタキセルを中止した。1サイクル終了後に発熱性好中球減少症と下痢の有害事象により化学療法の中止を余儀なくされ、ロボット支援手術を施行した。Open laparotomy法によりカメラポートを作製し、ポート挿入後に食道切除術を施行した。膿瘍病変は腹腔動脈浸潤のため完全切除できず、ドレナージを施行した。病理組織学的検査で胃壁の潰瘍性病変は食道腺癌の胃壁内転移と診断した。2ヵ月後に残存腫瘍の増大を認め、2次治療としてニボルマブ療法を開始した。3サイクル終了後に腫瘍径は著明に縮小し、QOLは改善した。9ヵ月後現在、無病生存中である。

Language：English   Publisher：John Wiley & Sons Australia, Ltd  

単発小型肝細胞癌に対する根治的肝切除を受ける患者におけるヘモグロビン・アルブミン・リンパ球・血小板(HALP)スコアの予後予測能を評価した。5cm以下の単発肝細胞癌に対し肝切除を受け、Child-Pugh分類がAの患者を後ろ向きに調べた。患者を訓練コホート(332例)と検証コホート(210例)に分け、訓練コホートでは全生存期間(OS)からHALPスコアの適切なカットオフ値を求めて患者を低群、高群に分け、無病生存期間(DFS)と全生存期間(OS)について単変量解析と多変量解析を実施した。検証コホートでは、訓練コホートで求めたカットオフ値を用いて、カプラン・マイヤー解析でOSを調べた。訓練コホートの多変量解析で、DFSの独立予後因子は、Fibrosis-4 index 2.67以上(p=0.0008)、単純結節周囲増殖型または多結節癒合型(p=0.0221)、肝内転移(p=0.0233)、OSの独立予後因子はFibrosis-4 index 2.67以上(p=0.0020)、HALP 45.6以下(p=0.0228)、低分化型(p=0.0305)であった。検証コホートでは、HALP低群でOSが有意に短い傾向が認められた(p=0.0220)。以上より、単発小型肝細胞癌に対する根治的肝切除を受けるChild-Pugh分類Aの患者において、HALPスコアはOSの予測因子であることが示された。

Language：English   Publisher：シュプリンガー・ジャパン(株)  

食道扁平上皮癌患者の腸内微生物叢の特徴と治療時における組成の変化について検討した。食道扁平上皮癌連続患者21例(患者群)と健常者10例(対照群)の便検体を採取し、16S rRNAシーケンシングにより腸内微生物叢の解析を行った。患者の便検体は、ネオアジュバント療法から食道切除術後までの期間中5時点で採取した。治療前の患者群と対照群では、腸内微生物叢のα多様性とβ多様性に違いがみられ、患者群では対照群に比べて通性嫌気性菌のStreptococcus属が有意に多く、偏性嫌気性菌のFaecalibacterium属が有意に少なかった。ネオアジュバント療法中、腸内微生物叢のα/β多様性には変化がみられなかった。食道切除術後、腸内微生物叢の多様性は変化し、Streptococcus属の相対存在量が有意に増加し、Faecalibacterium属の相対存在量は有意に減少した。

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INTRODUCTION: We examined the neutralizing antibody production efficiency of the second and third severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine doses (2nd- and 3rd-dose) and neutralizing activity on mutant strains, including, the Ancestral, Beta and Omicron strains using green fluorescent protein-carrying recombinant SARS-CoV-2, in living-donor liver transplantation (LDLT) recipients. METHODS: The patients who were administered vaccines other than Pfizer- BioNTechBNT162b2 and who had coronavirus disease 2019 in this study period were excluded. We enrolled 154 LDLT recipients and 50 healthy controls. RESULT: The median time were 21 days (between 1st and 2nd vaccination) and 244 days (between 2nd and 3rd vaccination). The median neutralizing antibody titer after 2nd-dose was lower in LDLT recipients than in controls (0.46 vs 1.00, P<0.0001). All controls had SARS-CoV-2 neutralizing antibodies, whereas 39 LDLT recipients (25.3%) had no neutralizing antibodies after 2nd-dose; age at vaccination, presence of ascites, multiple immunosuppressive treatments, and mycophenolate mofetil treatment were significant risk factors for nonresponder. The neutralizing activities of recipient sera were approximately 3-fold and 5-fold lower than those of control sera against the Ancestral and Beta strains, respectively. The median antibody titer after 3rd-dose was not significantly different between recipients and controls (1.02 vs 1.22, p=0.0758); only 5% recipients was non-responder. The neutralizing activity after third dose to Omicron strains were enhanced and had no significant difference between two groups. CONCLUSION: Only the 2nd-dose was not sufficiently effective in recipients; however, 3rd-dose had sufficient neutralizing activity against the mutant strain and was as effective as that in healthy controls.

DOI： 10.3389/fcimb.2023.1197349

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BACKGROUND: Long-term survival can be achieved with radical local therapy in some cases of postoperative recurrence of non-small cell lung cancer (NSCLC). Here, we evaluated post-recurrence survival (PRS) after treatment of postoperative recurrent epidermal growth factor receptor (EGFR) mutated NSCLC and examined the effectiveness of radical local therapy. METHODS: This multicenter prospective cohort study was conducted in 14 hospitals. The inclusion criteria for this study were patients with recurrence after radical resection for NSCLC. Information about the patient characteristics at recurrence, tumor-related variables, primary surgery, and treatment for recurrence was collected. After registration, follow-up data (e.g., treatment and survival outcomes) were obtained and analyzed. RESULTS: From 2010 to 2015, 505 patients with recurrent NSCLC were enrolled into the study, and 154 EGFR mutation-positive cases were included. As the initial treatment for recurrence, 111 patients (72%) received chemotherapy, 14 (9%) received chemoradiotherapy, 14 (9%) received definitive radiotherapy, and seven (5%) received surgical resection. The remaining eight patients (5%) received supportive care. The median PRS and 5-year survival rates for all cases were 64 months and 53.2%, respectively. The 5-year survival rate according to the initial treatment was as follows: supportive care, 0%; chemotherapy, 53.3% and radical local therapy, 60.1%. The six patients who received radical local treatment remained recurrence-free for more than 3 years after recurrence with only initial treatment. CONCLUSIONS: Although radical local therapy may be curative in some patients, chemotherapy including EGFR-TKI treatment is expected to provide long-term survival comparable to that of radical local therapy.

DOI： 10.1111/1759-7714.14911

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BACKGROUND: Although several studies on telesurgery have been reported globally, a clinically applicable technique has not yet been developed. As part of a telesurgical study series conducted by the Japan Surgical Society, this study describes the first application of a double-surgeon cockpit system to telesurgery. METHODS: Surgeon cockpits were installed at a local site and a remote site 140 km away. Three healthy pigs weighing between 26 and 29 kg were selected for surgery. Non-specialized surgeons performed emergency hemostasis, cholecystectomy, and renal vein ligation with remote assistance using the double-surgeon cockpits and specialized surgeons performed actual telesurgery. Additionally, the impact of adding internet protocol security (IPsec) encryption to the internet protocol-virtual private network (IP-VPN) line on communication was evaluated to address clinical security concerns. RESULTS: The average time required for remote emergency hemostasis with the double-surgeon cockpit system was 10.64 s. A non-specialized surgeon could safely perform cholecystectomy or renal vein ligation with remote assistance. Global Evaluative Assessment of Robotic Skills and System Usability Scale scores were higher for telesurgical support-assisted surgery by a non-specialized surgeon using the double-surgeon cockpits than for telesurgery performed by a specialized surgeon without the double-cockpit system. Adding IPsec encryption to the IP-VPN did not have a significant impact on communication. CONCLUSION: Telesurgical support through our double-surgeon cockpit system is feasible as first step toward clinical telesurgery.

DOI： 10.1007/s00464-023-10061-6

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BACKGROUND: The hemoglobin-albumin-lymphocyte-platelet (HALP) score is a combination index that assesses nutritional status and systemic inflammatory response and is reported to predict prognosis in several cancer types. However, researches about the usefulness of the HALP score in intrahepatic cholangiocarcinoma (ICC) are limited. METHODS: This was a single-center, retrospective study of 95 patients who underwent surgical resection for ICC between 1998 and 2018. We divided patients into two groups by calculating the cutoff value of the HALP score and examined clinicopathological characteristics, prognosis, and sarcopenia. Tumor-infiltrating lymphocytes (TILs), CD8 + TILs, and FOXP3 + TILs were evaluated by immunohistochemical staining of resected tumors. RESULTS: Of 95 patients, 22 were HALP-low. The HALP-low group had significantly lower hemoglobin (p = 0.0007), lower albumin (p = 0.0013), higher platelet counts (p < 0.0001), fewer lymphocytes (p < 0.0001), higher CA19-9 levels (p = 0.0431), and more lymph node metastasis (p = 0.0013). Multivariate analysis revealed that the independent prognostic factors for disease-free survival were maximum tumor size (≥ 5.0 cm) (p = 0.0033), microvascular invasion (p = 0.0108), and HALP score (≤ 25.2) (p = 0.0349), and that factors for overall survival were lymph node metastasis (p = 0.0020) and HALP score (≤ 25.2) (p = 0.0014). The HALP-low group contained significantly more patients with sarcopenia (p = 0.0015). Immunohistochemistry showed that counts of CD8 + TILs were significantly lower in the HALP-low group (p = 0.0075). CONCLUSIONS: We demonstrated that low HALP score is an independent prognostic factor for ICC patients undergoing curative hepatic resection and is associated with sarcopenia and the immune microenvironment.

DOI： 10.1007/s10147-023-02358-2

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AIM: Laparoscopic liver resection (LLR) for hepatocellular carcinoma (HCC) located in the posterosuperior segments (PS) have generally been considered more difficult than those for HCC in anterolateral segments (AL), but may be safe and feasible for selected patients with accumulated experience. In the present study, we investigated the effectiveness of LLR for single nodular HCCs ≤3 cm located in PS. METHODS: In total, 473 patients who underwent partial liver resection for single nodular HCCs ≤3 cm at the 18 institutions belonging to the Kyusyu Study Group of Liver Surgery from January 2010 to December 2018 were enrolled. The short-term outcomes of laparoscopic partial liver resection and open liver resection (OLR) for HCCs ≤3 cm, with subgroup analysis of PS and AL, were compared using propensity score-matching analysis. Furthermore, results were also compared between LLR-PS and LLR-AL. RESULTS: The original cohort of patients with HCC ≤3 cm included 328 patients with LLR and 145 with OLR. After matching, 140 patients with LLR and 140 with OLR were analyzed. Significant differences were found between groups in terms of volume of blood loss (median, 55 vs. 287 ml, p < 0.001), postoperative complications (0.71 vs. 8.57%, p = 0.003), and postoperative hospital stay (median, 9 vs. 14 days, p < 0.001). The results of subgroup analysis of PS were similar. Short-term outcomes did not differ significantly between LLR-PS and LLR-AL after matching. CONCLUSIONS: Laparoscopic partial resection could be the preferred option for single nodular HCCs ≤3 cm located in PS.

DOI： 10.1111/hepr.13929

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OBJECTIVES: In non-small cell lung cancer (NSCLC), T factor plays an important role in determining staging. The present study aimed to determine the validity of preoperative evaluation of clinical T (cT) factor by comparing radiological and pathological tumor sizes. METHODS: Data for 1,799 patients with primary NSCLC who underwent curative surgery were investigated. The concordance between cT and pathological T (pT) factors was analyzed. Furthermore, we compared groups with an increase or decrease of ≥ 20% and groups with an increase or decrease of < 20% in the size change between preoperative radiological and pathological diameters. RESULTS: The mean sizes of the radiological solid components and the pathological invasive tumors were 1.90 cm and 1.99 cm, respectively, correlation degree = 0.782. The group with increased pathological invasive tumor size (≥ 20%) compared with the radiologic solid component was significantly more likely female, consolidation tumor ratio (CTR) ≤ 0.5, and within cT1. Multivariate logistic analysis identified CTR < 1, cT ≤ T1, and adenocarcinoma as independent risk factors for increased pT factor. CONCLUSION: The radiological invasive area of tumors with cT1, CTR < 1, or adenocarcinoma on preoperative CT may be underestimated compared with pathological invasive diameter.

DOI： 10.1007/s11748-023-01938-3

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BACKGROUND: Immunotherapy has become a standard-of-care for patients with non-small-cell lung cancer (NSCLC). Although several biomarkers, such as programmed cell death-1, have been shown to be useful in selecting patients likely to benefit from immune checkpoint inhibitors (ICIs), more useful and reliable ones should be investigated. The prognostic nutritional index (PNI) is a marker of the immune and nutritional status of the host, and is derived from serum albumin level and peripheral lymphocyte count. Although several groups reported its prognostic role in patients with NSCLC receiving a single ICI, there exist no reports which have demonstrated its role in the first-line ICI combined with or without chemotherapy. MATERIALS AND METHODS: Two-hundred and eighteen patients with NSCLC were included in the current study and received pembrolizumab alone or chemoimmunotherapy as the first-line therapy. Cutoff value of the pretreatment PNI was set as 42.17. RESULTS: Among 218 patients, 123 (56.4%) had a high PNI (≥42.17), while 95 (43.6%) had a low PNI (<42.17). A significant association was observed between the PNI and both the progression-free survival (PFS; hazard ratio [HR] =  0.67, 95% confidence interval [CI]: 0.51-0.88, p =  0.0021) and overall survival (OS; HR = 0.46, 95% CI: 0.32-0.67, p < 0.0001) in the entire population, respectively. The multivariate analysis identified the pretreatment PNI as an independent prognosticator for the PFS (p =  0.0011) and OS (p  < 0.0001), and in patients receiving either pembrolizumab alone or chemoimmunotherapy, the pretreatment PNI remained an independent prognostic factor for the OS (p = 0.0270 and 0.0006, respectively). CONCLUSION: The PNI might help clinicians appropriately identifying patients with better treatment outcomes when receiving first-line ICI therapy.

DOI： 10.1002/cam4.6110

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DOI： 10.1016/j.ejvs.2023.01.048

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BACKGROUND/AIM: Tumour lysis syndrome (TLS) is a life-threatening oncological emergency. TLS is rare and associated with a higher mortality rate in solid tumours than in haematological malignancies. Our case report and literature review aimed to identify the distinctive features and hazards of TLS in breast cancer. CASE REPORT: A 41-year-old woman complained of vomiting and epigastric pain and was diagnosed with HER2-positive, hormone-receptor-positive breast cancer with multiple liver and bone metastases and lymphangitis carcinomatosis. She had several risk factors for TLS: high tumour volume, high sensitivity to antineoplastic treatment, multiple liver metastases, high lactate dehydrogenase levels, and hyperuricaemia. To prevent TLS, she was treated with hydration and febuxostat. One day after the first course of trastuzumab and pertuzumab, she was diagnosed with disseminated intravascular coagulation (DIC). After 3 further days of observation, she was relieved of DIC and administered a reduced dose of paclitaxel without life-threatening complications. The patient achieved a partial response after four cycles of anti-HER2 therapy and chemotherapy. CONCLUSION: TLS in solid tumours is a lethal situation and can be complicated by DIC. Early recognition of patients who are at risk of TLS and initiation of therapy is essential to avoid fatal situations.

DOI： 10.21873/anticanres.16403

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BACKGROUND: The present study aimed to determine the preferred initial revascularization procedure between bypass surgery and endovascular therapy (EVT) in patients with chronic limb-threatening ischemia (CLTI) categorized as indeterminate according to the Global Vascular Guidelines (GVG). METHODS: We retrospectively analyzed the multicenter data of patients who underwent infrainguinal revascularization for CLTI categorized as indeterminate according to the GVG between 2015 and 2020. The end point was the composite of relief from rest pain, wound healing, major amputation, reintervention, or death. RESULTS: A total of 255 patients with CLTI and 289 limbs were analyzed. Of the 289 limbs, 110 (38.1%) and 179 (61.9%) underwent bypass surgery and EVT, respectively. The 2-year event-free survival rates with respect to the composite end point were 63.4% and 28.7% in the bypass and EVT groups, respectively (P < 0.01). Multivariate analysis revealed that increased age (P = 0.03); decreased serum albumin level (P = 0.02); decreased body mass index (P = 0.02); dialysis-dependent end-stage renal disease (P < 0.01); increased Wound, Ischemia, and foot Infection (WIfI) stage (P < 0.01); Global Limb Anatomic Staging System (GLASS) III (P = 0.04); increased inframalleolar grade (P < 0.01); and EVT (P < 0.01) were independent risk factors for the composite end point. In the WIfI-GLASS 2-III and 4-II subgroups, bypass surgery was superior to EVT with regard to 2-year event-free survival (P < 0.01). CONCLUSIONS: Bypass surgery is superior to EVT in terms of the composite end point in patients classified as indeterminate according to the GVG. Bypass surgery should be considered an initial revascularization procedure, especially in the WIfI-GLASS 2-III and 4-II subgroups.

DOI： 10.1016/j.avsg.2023.05.014

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根治的肝切除が施行された肝内胆管細胞癌患者92例を対象とした後ろ向き研究を実施し、FGFR2発現の臨床的意義および予後を評価した。評価項目は臨床病理学的特徴、転帰などとした。患者をFGFR2陽性群18例(男性16例、年齢中央値65歳)、陰性群74例(男性46例、年齢中央値66歳)に分けて検討した。その結果、FGFR2陽性群では男性が多く、血清アルブミン低値であり、癌胎児性抗原が高値であった(p<0.0001、p=0.0355、p=0.0099)。多変量解析の結果、FGFR2陽性群は無病生存率が不良であることが明らかになった(p=0.0002)。最大腫瘍径(≧5cm)、腫瘍局在(傍肝門型)、FGFR2陽性が無病生存の独立した予測因子であった(p=0.0011、p=0.0180、p=0.0029)。両群間で腫瘍浸潤リンパ球に有意差は認められなかった。以上から、FGFR2高発現は肝切除施行原発性胆管癌患者の再発の独立した予測因子であることが示された。

Publisher：南江堂  

DOI： 10.15106/j_geka85_489

CiNii Research

Language：Japanese   Publisher：The Japan Broncho-esophagological Society  

DOI： 10.2468/jbes.74.118

CiNii Research

Language：English   Publisher：BMC Research Notes  

Objective: A centrifugation-assisted peptide-mediated gene transfer (CAPT) method was recently developed as an efficient system for gene delivery into plant cells. However, the gene transfer efficiency of CAPT into plant cells was not entirely satisfactory for detecting transient expression of a transgene driven into mitochondria. Here, we report a new gene delivery system using a method called particle bombardment-assisted peptide-mediated gene transfer (PBPT). Results: We investigated various parameters of the PBPT method to increase transient gene expression efficiency in Brassica campestris. The optimal conditions for PBPT were a single bombardment with gold particles coated with a DNA‒peptide complex (6 µg of DNA and 2 µg of peptide) at an acceleration pressure of 5 kg/cm2 and a target distance of 12.5 cm. Moreover, bombardment under the optimal conditions successfully transferred the transgene into the cells of other plant species, namely B. juncea and tomato. Thus, we developed a PBPT method for highly efficient delivery of a DNA‒peptide complex into plant mitochondria.

DOI： 10.1186/s13104-023-06320-3

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MAIN PROBLEMS: In non-small-cell lung cancer, ground-glass opacity on computed tomography imaging reflects pathological noninvasiveness and is a favorable prognostic factor. However, the significance of pathological noninvasive areas (NIAs) has not been fully revealed. In this study, we aimed to elucidate the prognostic impact of NIAs on lung adenocarcinoma. METHODS: We analyzed 402 patients with pathological stage (p-Stage) IA lung adenocarcinoma who underwent surgery in 2013-2016 at two institutions and examined the association of the presence of NIAs with clinicopathological factors and prognosis. Furthermore, after using propensity-score matching to adjust for clinicopathological factors, such as age, sex, smoking history, pathological invasive area size, pathological T factor (p-T), p-Stage, and histological subtype (lepidic predominant adenocarcinoma [LPA] or non-LPA), the prognostic impact of NIAs was evaluated. RESULTS: Patients were divided into NIA-present (N = 231) and NIA-absent (N = 171) groups. Multivariable analysis showed that NIA-present was strongly associated with earlier p-T, earlier p-Stage, LPA, and epidermal growth factor receptor mutation. Kaplan-Meier survival analysis showed that the NIA-present group displayed a better prognosis than the NIA-absent group in disease-free survival (DFS) and overall survival (OS) (5-year DFS 94.6% vs. 87.2%, 5-year OS 97.2% vs. 91.1%). However, after adjusting for clinicopathological factors by propensity score matching, no significant differences in prognosis were identified between the NIA-present and NIA-absent groups (5-year DFS 92.4% vs 89.6%, 5-year OS 95.6% vs 94.3%). CONCLUSIONS: Our current study suggests that the prognostic impact of the presence of NIAs on lung adenocarcinoma is due to differences in clinicopathological factors.

DOI： 10.1111/1759-7714.14910

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OBJECTIVE: The aim of this study was to examine outcomes between bypass surgery and endovascular therapy (EVT) in patients with chronic limb-threatening ischemia (CLTI), classified as bypass-preferred according to the Global Vascular Guidelines (GVG). METHODS: We retrospectively analyzed the multi-center data of patients who underwent infrainguinal revascularization for CLTI with Wound, Ischemia, and foot Infection (WIfI) Stage 3 to 4 and Global Limb Anatomical Staging System (GLASS) Stage III, which is classified as bypass-preferred category by the GVG between 2015 and 2020. The endpoints were limb salvage and wound healing. RESULTS: We analyzed 301 patients and 339 limbs following 156 bypass surgeries and 183 EVTs. The 2-year limb salvage rates were 92.2% in the bypass surgery group and 76.3% in the EVT group, respectively (P < .01). The 1-year wound healing rates were 86.7% in the bypass surgery group and 67.8% in the EVT group (P < .01). Multivariate analysis shows decreased serum albumin level (P < .01), increased wound grade (P = .04), and EVT (P < .01) were risk factors for major amputation. Decreased serum albumin level (P < .01), increased wound grade (P < .01), GLASS infrapopliteal grade (P = .02), inframalleolar (IM) P grade (P = .01), and EVT (P < .01) were risk factors for impaired wound healing. Subgroup analysis of limb salvage in patients after EVT, decreased serum albumin level (P < .01), increased wound grade (P = .03), increased IM P grade (P = .04), and congestive heart failure (P < .01) were risk factors for major amputation. According to scoring by existence of these risk factors, 2-year limb salvage rates following EVT were 83.0% and 42.8% for the total score of 0 to 2 and of 3 to 4, respectively (P < .01). CONCLUSIONS: Bypass surgery provides better limb salvage and wound healing in patients with WIfI Stage 3 to 4 and GLASS Stage III, which is classified as bypass-preferred category by the GVG. In patients after EVT, serum albumin level, wound grade, IM P grade, and congestive heart failure were related to major amputation. Although bypass surgery may be considered as initial revascularization procedure in patients classified as bypass-preferred category, in case that EVT has to be selected, relatively acceptable outcomes can be expected in patients with less of these risk factors.

DOI： 10.1016/j.jvs.2023.04.006

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Introduction The proportion of gastroduodenal ulcers caused by drugs is increasing. However, the risk of gastroduodenal ulcer from drugs other than non-steroidal anti-inflammatory drugs (NSAIDs) and low-dose aspirin (LDA) is unclear. An association between immunosuppressive drugs and gastroduodenal ulcers has been suggested. We aimed to identify the immunosuppressive drugs and clinical characteristics associated with gastroduodenal ulcers in post-liver transplant patients. Methods The study investigated 119 patients who underwent esophagogastroduodenoscopy after liver transplantation and two patients were excluded. Clinical characteristics, medications, and endoscopic images were retrospectively reviewed. Results Among 117 post-living donor liver transplant recipients, gastroduodenal ulcers were found in 10 (9.2%) patients. The ulcer group had endoscopically gastritis more frequently (40%) compared with the non-ulcer group (10%). Logistic regression analysis revealed gastritis, NSAIDs use and mycophenolate mofetil were risk factors in the post-liver transplant patients. Among 103 patients not on NSAIDs, eight (7.8%) had peptic ulcer. The most common ulcer site and ulcer shape were the gastric antrum and a circular shape, respectively. All patients in the ulcer group were taking mycophenolate mofetil, which was the only immunosuppressive drug that showed a significant difference between the two groups. Five out of eight ulcer patients (63%) were taking gastric acid suppressants, and gastroduodenal ulcers in post-liver transplant recipients were suggested to be refractory. Conclusion Patients treated with immunosuppressive drugs after liver transplantation can develop gastroduodenal ulcers, even with gastric acid suppressant medication. Mycophenolate mofetil may increase the risk of gastroduodenal ulcers compared with other immunosuppressive drugs.

DOI： 10.1159/000530472

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BACKGROUND: Antiangiogenic tyrosine kinase inhibitors (TKIs) provide one of the few therapeutic options for effective treatment of hepatocellular carcinoma (HCC). However, patients with HCC often develop resistance toward antiangiogenic TKIs, and the underlying mechanisms are not understood. The aim of this study was to determine the mechanisms underlying antiangiogenic TKI resistance in HCC. METHODS: We used an unbiased proteomic approach to define proteins that were responsible for the resistance to antiangiogenic TKIs in HCC patients. We evaluated the prognosis, therapeutic response, and serum insulin-like growth factor-binding protein-1 (IGFBP-1) levels of 31 lenvatinib-treated HCC patients. Based on the array of results, a retrospective clinical study and preclinical experiments using mouse and human hepatoma cells were conducted. Additionally, in vivo genetic and pharmacological gain- and loss-of-function experiments were performed. RESULTS: In the patient cohort, IGFBP-1 was identified as the signaling molecule with the highest expression that was inversely associated with overall survival. Mechanistically, antiangiogenic TKI treatment markedly elevated tumor IGFBP-1 levels via the hypoxia-hypoxia inducible factor signaling. IGFBP-1 stimulated angiogenesis through activation of the integrin α5β1-focal adhesion kinase pathway. Consequently, loss of IGFBP-1 and integrin α5β1 by genetic and pharmacological approaches re-sensitized HCC to lenvatinib treatment. CONCLUSIONS: Together, our data shed light on mechanisms underlying acquired resistance of HCC to antiangiogenic TKIs. Antiangiogenic TKIs induced an increase of tumor IGFBP-1, which promoted angiogenesis through activating the IGFBP-1-integrin α5β1 pathway. These data bolster the application of a new therapeutic concept by combining antiangiogenic TKIs with IGFBP-1 inhibitors.

DOI： 10.1002/cac2.12411

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We herein describe three patients with Fontan-associated liver disease who developed hepatocellular carcinoma (HCC). The first patient was a 28-year-old woman who had undergone the Fontan operation (FO) at the age of 4 years. She was diagnosed with HCC (cT4aN0M0, Stage IVA, UICC 8th edition), for which she underwent extended posterior right sectionectomy and partial hepatectomy of S2. She developed recurrence of peritoneal dissemination after 12 months, and she was alive 18 months after surgery. The second patient was a 43-year-old man who had undergone the FO at the age of 3 years. He was diagnosed with HCC (cT2N0M0, Stage II), for which he underwent laparoscopic-assisted partial hepatectomy of S3. He remained free from recurrent HCC for 17 months. The third patient was a 21-year-old woman who had undergone the FO at the age of 3 years. She was diagnosed with HCC (cT3N0M0, Stage III), for which she underwent laparoscopic-assisted partial hepatectomy of S2 and S4. She remained free from recurrent HCC for 30 months. We reviewed 18 surgical cases of HCC arising from Fontan-associated liver disease, including our 3 cases, and found that a high preoperative alpha-fetoprotein concentration might be a predictor of HCC recurrence.

DOI： 10.1007/s12328-023-01795-w

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A combined therapy of atezolizumab and bevacizumab (atezo/bev) is used as the first-line treatment for unresectable hepatocellular carcinoma (HCC). In this study, we report the case of curative hepatic resection in a 77-year-old man who initially had unresectable advanced-stage HCC with lung metastases. This rare hepatectomy conversion was owing to the administration of atezo/bev. Notwithstanding the side effects of immune-related adverse event hepatitis and intratumoral hemorrhage developed during atezo/bev treatment; after seven treatment cycles, the patient's tumor markers normalized, the tumor shrank markedly, and the metastasis disappeared. Subsequently, conversion therapy with hepatic resection was performed, and pathology confirmed complete tumor necrosis. No cancer recurrence was observed at the 8-month postoperative follow-up, and the patient remained drug free.

DOI： 10.1007/s12328-022-01744-z

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The identification of actionable targets in oncogene-addicted non-small cell lung cancer (NSCLC) has fueled biomarker-directed strategies, especially in advanced stage disease. Despite the undeniable success of molecular targeted therapies, duration of clinical response is relatively short-lived. While extraordinary efforts have defined the complexity of tumor architecture and clonal evolution at the genetic level, not equal interest has been given to the dynamic mechanisms of phenotypic adaptation engaged by cancer during treatment. At the clinical level, molecular targeted therapy of EGFR-mutant and ALK-rearranged tumors often results in epithelial-to-mesenchymal transition (EMT) and histological transformation of the original adenocarcinoma without the acquisition of additional genetic lesions, thus limiting subsequent therapeutic options and patient outcome. Here we provide an overview of the current understanding of the genetic and non-genetic molecular circuits governing this phenomenon, presenting current strategies and potentially innovative therapeutic approaches to interfere with lung cancer cell plasticity.

DOI： 10.1016/j.critrevonc.2023.103966

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BACKGROUND: Left renal vein division (LRVD) is a maneuver performed during open surgical repair for abdominal aortic aneurysms. Even so, the long-term effects of LRVD on renal remodeling are unknown. Therefore, we hypothesized that interrupting the venous return of the left renal vein might cause renal congestion and fibrotic remodeling of the left kidney. METHODS: We used a murine left renal vein ligation model with 8-week-old to 12-week-old wild-type male mice. Bilateral kidneys and blood samples were harvested postoperatively on days 1, 3, 7, and 14. We assessed the renal function and the pathohistological changes in the left kidneys. In addition, we retrospectively analyzed 174 patients with open surgical repairs between 2006 and 2015 to assess the influence of LRVD on clinical data. RESULTS: Temporary renal decline with left kidney swelling occurred in a murine left renal vein ligation model. In the pathohistological assessment of the left kidney, macrophage accumulation, necrotic atrophy, and renal fibrosis were observed. In addition, Myofibroblast-like macrophage, which is involved in renal fibrosis, was observed in the left kidney. We also noted that LRVD was associated with temporary renal decline and left kidney swelling. LRVD did not, however, impair renal function in long-term observation. Additionally, the relative cortical thickness of the left kidney in the LRVD group was significantly lower than that of the right kidney. These findings indicated that LRVD was associated with left kidney remodeling. CONCLUSIONS: Venous return interruption of the left renal vein is associated with left kidney remodeling. Furthermore, interruption in the venous return of the left renal vein does not correlate with chronic renal failure. Therefore, we suggest careful follow-up of renal function after LRVD.

DOI： 10.1016/j.avsg.2023.03.035

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Language：English   Publisher：シュプリンガー・ジャパン(株)  

当初肺転移を伴う切除不能進行肝細胞癌であった77歳男性に対する治癒的肝切除例を報告した。この稀なコンバージョン肝切除術は、アテゾリズマブとベバシズマブの併用療法(atezo/bev)によるものであった。atezo/bev中に有害事象として免疫関連肝炎と腫瘍内出血が認められたが、7サイクルの治療後、腫瘍マーカーは正常化し、腫瘍は著明に縮小し、転移は消失した。その後、コンバージョン肝切除術が行われ、病理検査で腫瘍の完全壊死が確認された。術後8ヵ月の経過観察で癌の再発は認められず、薬物投与なしで経過している。

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OBJECTIVE: This study aimed to evaluate the influence of change in ambulatory status on the prognosis of patients with chronic limb-threatening ischemia (CLTI) undergoing infrainguinal bypass surgery or endovascular therapy (EVT). METHODS: We retrospectively analyzed data from two vascular centers for patients who underwent revascularization for CLTI between 2015 and 2020. The primary endpoint was overall survival (OS), and the secondary endpoints were changes in ambulatory status and postoperative complications. RESULTS: Throughout the study, 377 patients and 508 limbs were analyzed. In the preoperative nonambulation cohort, the average body mass index (BMI) was lower in the postoperative nonambulatory group than in the postoperative ambulatory group (P < .01). The percentage of cerebrovascular disease (CVD) was higher in the postoperative nonambulatory group than in the postoperative ambulatory group (P = .01). In the preoperative ambulation cohort, the average controlling nutritional status (CONUT) score was higher in the postoperative nonambulatory group than in the postoperative ambulatory group (P < .01). There was no difference in the bypass percentage and the EVT in the preoperative nonambulation (P = .32) and ambulation (P = .70) cohorts. According to the change in ambulatory status before and after revascularization, the 1-year OS rates were 86.8% in the ambulatory → ambulatory group, 81.1% in the nonambulatory → ambulatory group, 54.7% in the nonambulatory → nonambulatory group, and 23.9% in the ambulatory → nonambulatory group (P < .01). On multivariate analysis, increased age (P = .04), higher Wound, Ischemia, and foot Infection stage (P = .02), and increased CONUT score (P < .01) were independent risk factors for the decline in ambulatory status in patients with preoperative ambulation. In patients with preoperative nonambulation, increased BMI (P < .01) and absence of CVD (P = .04) were independent factors related to the improved ambulatory status. The percentages of postoperative complications were 31.0% and 17.0% in the preoperative nonambulation and the preoperative ambulation in the overall cohort (P < .01). Preoperative nonambulatory status (P < .01), CONUT score (P < .01), and bypass surgery (P < .01) were risk factors for postoperative complications. CONCLUSIONS: Improved ambulatory status is associated with better OS in patients with preoperative nonambulatory status after infrainguinal revascularization for CLTI. Although patients with preoperative nonambulatory status have a risk of postoperative complication, some may benefit from revascularization if they have no factors such as low BMI and CVD, improving their ambulatory status.

DOI： 10.1016/j.jvs.2023.03.024

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Prof. Setsuro Fujii achieved significant results in the field of drug discovery research in Japan. He developed nine well-known drugs: FT, UFT, S-1 and FTD/TPI are anticancer drugs, while cetraxate hydrochloride, camostat mesilate, nafamostat mesilate, gabexate mesilate and pravastatin sodium are therapeutic drugs for various other diseases. He delivered hope to patients with various diseases across the world to improve their condition. Even now, drug discovery research based on Dr. Fujii's ideas is continuing.

DOI： 10.1007/s10147-023-02326-w

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AIM: We aimed to evaluate the association between the intraoperative indocyanine green (ICG) fluorescence imaging (FI) pattern, preoperative magnetic resonance imaging (MRI) findings using gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA), preoperative diffusion-weighted imaging (DWI) of MRI, and histological differentiation of hepatocellular carcinoma (HCC). METHODS: We retrospectively reviewed the data for 80 tumors of 64 patients. Intraoperative ICG FI patterns were classified into cancerous or rim-positive type. We evaluated the signal intensity ratio of the tumor and the surrounding liver tissue in the portal phase (SIRPP) and intensity in the hepatobiliary phase (HBP) of Gd-EOB-DTPA-enhanced MRI, the apparent diffusion coefficient (ADC) in the DWI of MRI, and clinicopathologic factors. RESULTS: In the rim-positive group, the rate of poorly differentiated HCC and hypointensity type in HBP were significantly higher, and SIRPP and ADC were significantly lower than the rim-negative group. In the cancerous group, the rate of well or moderately differentiated HCC and hyperintensity type in HBP, SIRPP, and ADC were significantly higher than the noncancerous group. Multivariate analysis identified low SIRPP, low ADC, and hypointensity type in HBP as the significant predictive factors for rim-positive HCC and high SIRPP, high ADC, and hyperintensity type in HBP as the significant predictive factors for cancerous HCC. The positive rate of programmed cell death 1-ligand 1 and vessels that encapsulate tumor clusters status of the rim-positive HCC and HCC with low SIRPP were significantly higher than the control group. CONCLUSIONS: The intraoperative ICG FI pattern of HCC closely correlated with histological differentiation, preoperative SIRPP and intensity type in the Gd-EOB-DTPA MRI, and preoperative ADC in the DWI of MRI.

DOI： 10.1111/hepr.13902

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The development of liver cancer in patients with hepatitis B is a major problem, and several models have been reported to predict the development of liver cancer. However, no predictive model involving human genetic factors has been reported to date. For the items incorporated in the prediction model reported so far, we selected items that were significant in predicting liver carcinogenesis in Japanese patients with hepatitis B and constructed a prediction model of liver carcinogenesis by the Cox proportional hazard model with the addition of Human Leukocyte Antigen (HLA) genotypes. The model, which included four items-sex, age at the time of examination, alpha-fetoprotein level (log10AFP) and presence or absence of HLA-A*33:03-revealed an area under the receiver operating characteristic curve (AUROC) of 0.862 for HCC prediction within 1 year and an AUROC of 0.863 within 3 years. A 1000 repeated validation test resulted in a C-index of 0.75 or higher, or sensitivity of 0.70 or higher, indicating that this predictive model can distinguish those at high risk of developing liver cancer within a few years with high accuracy. The prediction model constructed in this study, which can distinguish between chronic hepatitis B patients who develop hepatocellular carcinoma (HCC) early and those who develop HCC late or not, is clinically meaningful.

DOI： 10.3390/ijms24054761

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OBJECTIVE: This study aimed to analyse the influence of the Global Anatomic Staging System (GLASS) and inframalleolar (IM) disease on the treatment outcomes of patients with chronic limb threatening ischaemia (CLTI) who undergo endovascular treatment (EVT) METHODS: Data of patients who underwent infrainguinal endovascular therapy (EVT) for CLTI between 2015 and 2019 at two centres were analysed retrospectively. The endpoints were major amputation, major adverse limb events (MALE), and wound healing. RESULTS: Overall, 276 patients and 340 limbs were analysed. The number of revascularisations for an infrapopliteal lesion was 48 (70.6%), 63 (63.0%), and 142 (82.6%) in the GLASS I, GLASS II, and GLASS III stages, respectively (p < .001). There was no statistically significant difference in limb salvage among the GLASS stages (p = .78). The limb salvage rates at one year were 94.6%, 88.0%, and 70.0% in the IM P0 P1, and P2 groups, respectively (p < .001). Multivariable analysis showed that Wound, Ischemia, and foot Infection (WIfI) stage, and IM grade were risk factors for major amputation. The freedom from MALE rates at two years were 60.5%, 45.3%, and 41.1% in the GLASS I, II, and III stages, respectively (p = .003) and 64.1%, 43.5%, and 18.4% in the IM P0, P1, and P2 groups, respectively (p < .001). Multivariable analysis demonstrated that WIfI stage, GLASS stage, IM grade, and infrapopliteal revascularisation were risk factors for MALE. There was no significant difference in wound healing among GLASS I - III (p = .75). The wound healing rates at 365 days were 78.6%, 68.6%, and 42.0% in the IM P0, P1, and P2 groups, respectively (p = .065). Multivariable analysis showed that WIfI stage and IM P2 were risk factors for incomplete wound healing. CONCLUSION: GLASS IM was associated with major amputation, MALE, and wound healing, while GLASS stage was associated with only MALE.

DOI： 10.1016/j.ejvs.2022.11.023

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The association between tumor microenvironment (TME) and cancer-associated fibroblasts (CAFs) in intrahepatic cholangiocarcinoma (ICC) progression is poorly understood. This study aimed to reveal whether specific microRNAs (miRNAs) in extracellular vesicles (EVs) derived from CAFs were involved in ICC progression. Conditioned medium (CM) and EVs in the CM of CAFs and normal fibroblasts (NFs) derived from ICC specimens were used to investigate the effects on tumor cell lines. miRNA microarray assay was used to examine the miRNAs of EVs derived from CAFs and NFs in ICC, and the effects of miR-493-5p on tumor cell lines were examined. Additionally, databases were used to identify miR-493-5p targets, and the relationship between prognosis of ICC patients and cocaine- and amphetamine-regulated transcript propeptide (CARTPT), one of the targets of miR-493-5p, expression in ICC tissues was retrospectively analyzed. Compared with NF-derived CM and EVs, CAF-derived CM and EVs promoted cell lines in proliferation, scratch, migration, and invasion assays. miRNA microarray analysis revealed that miR-493-5p was significantly increased in CAF-derived EVs compared to NF-derived EVs. Tumor cell lines transfected with miR-493-5p were promoted in proliferation and scratch assays. Immunohistochemical staining was performed on 76 ICC specimens; both overall and recurrence-free survival rates were significantly worse in the CARTPT-negative group. Univariate and multivariate analyses showed that low CARTPT expression was an independent poor prognostic factor for overall and recurrence-free survival. Overall, our data suggest that CAFs in the ICC TME suppress CARTPT in tumor cells and promote tumor cells via miR-493-5p in EVs.

DOI： 10.1111/cas.15644

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Background: This study aims to clarify the perioperative risk factors and short-term prognosis of central bisectionectomy (CB) for hepatocellular carcinoma (HCC). Methods: Surgical data from 142 selected patients out of 171 HCC patients who underwent anatomical CB (H458) between 2005 and 2020 were collected from 17 expert institutions in a single-arm retrospective study. Results: Morbidities recorded by the International Study Group of Liver Surgery (ISGLS) from grade BC post-hepatectomy liver failure (PHLF) and bile leakage (PHBL), or complications requiring intervention were observed in 37% of patients. A multivariate analysis showed that increased blood loss (iBL) &gt; 1500 mL from PHLF (risk ratio [RR]: 2.79), albumin level &lt; 4 g/dL for PHBL (RR, 2.99), involvement of segment 1, a large size &gt; 6 cm, or compression of the hepatic venous confluence or cava by HCC for all severe complications (RR: 5.67, 3.75, 6.51, and 8.95, respectively) (p &lt; 0.05) were significant parameters. Four patients (3%) died from PHLF. HCC recurred in 50% of 138 surviving patients. The three-year recurrence-free and overall survival rates were 48% and 81%, respectively. Conclusions: Large tumor size and surrounding tumor involvement, or compression of major vasculatures and the related iBL &gt; 1500 mL were independent risk factors for severe morbidities in patients with HCC undergoing CB.

DOI： 10.3390/cancers15061740

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BACKGROUND: To evaluate limb salvage outcomes and risk factors for major amputation in chronic limb-threatening ischemia (CLTI) patients classified as stage 4 per the wound, ischemia, and foot infection (WIfI) classification following infrainguinal revascularization. METHODS: We retrospectively analyzed multicenter data of patients who had undergone infrainguinal revascularization for CLTI between 2015 and 2020. The endpoint was secondary major amputation defined as an above- or below-knee amputation following infrainguinal revascularization. RESULTS: We analyzed 243 patients with CLTI and 267 limbs. Bypass surgery was performed in 14 (25.5%) and 120 (56.6%) limbs from the secondary major amputation and limb salvage groups, respectively (P < 0.01). Endovascular therapy (EVT) was performed in 41 limbs (74.5%) in the secondary major amputation group and 92 limbs (43.4%) in the limb salvage group (P < 0.01). The average serum albumin levels were 3.0 ± 0.6 and 3.4 ± 0.5 g/dL in the secondary major amputation and limb salvage groups, respectively (P < 0.01). The percentage of congestive heart failure (CHF) was 36.4% and 14.2% in secondary major amputation and limb salvage groups, respectively (P < 0.01). The number of limbs with infra-malleolar (IM) P0, P1, and P2 were 4 (7.3%), 37 (67.3%), and 14 (25.5%), respectively, in the secondary major amputation group and 58 (27.4%), 140 (66.0%), and 14 (6.6%), respectively, in the limb salvage group (P < 0.01). Limb salvage rates at 1 year were 91.0% and 68.6% in the bypass and EVT groups, respectively (P < 0.01). Limb salvage rates at 1 year in patients with IM P0, P1, and P2 were 91.8%, 79.9%, and 53.1%, respectively (P < 0.01). Multivariate analysis revealed that serum albumin level [hazard ratio (HR), 0.56; 95% confidence interval (CI), 0.36-0.89; P = 0.01], hypertension (HR, 0.39; 95% CI, 0.21-0.75; P < 0.01), CHF (HR, 2.10; 95% CI, 1.09-4.05; P = 0.03), wound grade (HR, 1.72; 95% CI, 1.03-2.88; P = 0.04), IM P (HR, 2.08; 95% CI, 1.27-3.42; P < 0.01), and EVT (HR, 3.31; 95% CI, 1.77-6.18; P < 0.01) as independent risk factors for secondary major amputation being required. CONCLUSIONS: Among CLTI patients with WIfI stage 4, the limb salvage rate was poor in those with IM P1-2 following infrainguinal EVT. Low serum albumin levels, CHF, high wound grade, IM P1-2, and EVT were independent risk factors for CLTI patients requiring major amputation.

DOI： 10.1016/j.avsg.2023.02.010

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肝内胆管癌(ICC)の腫瘍微小環境(TME)における癌関連線維芽細胞(CAF)および正常線維芽細胞(NF)由来の細胞外小胞(EV)におけるmiRNAプロファイルの差異について検討した。その結果、NF由来のCMおよびEVと比較して、CAF由来のCMおよびEVは、胆管癌細胞株の増殖、遊走、浸潤を促進した。miRNAマイクロアレイ解析により、NF由来のEVと比較してCAF由来のEVでmiR-493-5pが著しく増加していた。miR-493-5pのトランスフェクションは、胆管癌細胞株の増殖、遊走、浸潤を促進した。免疫組織化学染色を76例のICC標本で実施した。その結果、全生存率、無再発生存率ともにコカイン・アンフェタミン調節転写産物プロペプチド(CARTPT)陰性群で有意に悪化していた。単変量解析と多変量解析により、CARTPTの低発現は、全生存率および無再発生存率の独立した予後不良因子であることが示された。以上より、ICCのTMEにおけるCAFは、腫瘍細胞のCARTPTを抑制し、EVのmiR-493-5pを介して腫瘍細胞を促進することが示唆された。

Publisher：株式会社医学書院  

DOI： 10.11477/mf.1407214044

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BACKGROUND: Currently, segmentectomy is the procedure of choice in approximately 10% of lung cancer surgeries in Japan. However, complications are often observed in that procedure. In particular, residual pulmonary congestion after segmentectomy often leads to surgical intervention. CASE DESCRIPTION: We report a case of improved congestion in the residual lung after left upper trisegmentectomy (LUTS) with conservative treatment under careful observation. A 65-year-old man was diagnosed with bilateral lung cancer and initially underwent LUTS. On the next day after surgery, blood sputum was observed. Computed tomography (CT) showed consolidation in the lingual region of the left lung and stenosis of V4+5 in the left lung. The cause of the congestion was thought to be an isolated segment with part of the remaining S3 and a thin V4+5 with poor flow. Because pulmonary torsion or necrosis of the residual lung was not observed, conservative treatment with antibiotics under careful follow-up by CT was chosen. The pulmonary congestion and inflammatory reaction gradually improved, and the patient was discharged home on the 26th day after surgery. CONCLUSIONS: We experienced a case of residual pulmonary congestion after LUTS that resolved with conservative treatment. Careful follow-up of the patient's general condition and imaging studies are considered to be important.

DOI： 10.21037/tcr-22-2104

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INTRODUCTION: This study aimed to compare the prognostic impact of laparoscopic left hepatectomy (LLH) with that of open left hepatectomy (OLH) on patient survival after resection of left hepatocellular carcinoma (HCC). METHODS: Among the 953 patients who received initial treatment for primary HCC that was resectable by either LLH or OLH from 2013 to 2017 in Japan and Korea, 146 patients underwent LLH and 807 underwent OLH. The inverse probability of treatment weighting approach based on propensity scoring was used to address the potential selection bias inherent in the recurrence and survival outcomes between the LLH and OLH groups. RESULTS: The occurrence rate of postoperative complications and hepatic decompensation was significantly lower in the LLH group than in the OLH group. Recurrence-free survival (RFS) was better in the LLH group than in the OLH group (hazard ratio, 1.33; 95% confidence interval, 1.03-1.71; p = 0.029), whereas overall survival (OS) was not significantly different. Subgroup analyses of RFS and OS revealed an almost consistent trend in favor of LLH over OLH. In patients with tumor sizes of ≥4.0 cm or those with single tumors, both RFS and OS were significantly better in the LLH group than in the OLH group. CONCLUSIONS: LLH decreases the risk of tumor recurrence and improves OS in patients with primary HCC located in the left liver.

DOI： 10.1159/000527294

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OBJECTIVES: Sarcopenia correlates with poor prognosis in various malignancies. However, the prognostic significance of sarcopenia remains to be determined in patients with non-small-cell lung cancer who undergo surgery after receiving neoadjuvant chemoradiotherapy (NACRT). METHODS: We retrospectively reviewed the patients with stage II/III non-small-cell lung cancer who underwent surgery following NACRT. The paravertebral skeletal muscle area (SMA) (cm2) at the 12th thoracic vertebra level was measured. We calculated the SMA index (SMAI) as SMA/squared height (cm2/m2). Patients were divided into low and high SMAI groups, and the association of SMAI with clinicopathological factors and prognosis was assessed. RESULTS: The patients' [men, 86 (81.1%)] median age was 63 (21-76) years. There were 106 patients including 2 (1.9%), 10 (9.4%), 74 (69.8%), 19 (17.9%) and 1 (0.9%) patients with stage IIA, IIB, IIIA, IIIB and IIIC, respectively. Of the patients, 39 (36.8%) and 67 (63.2%) were classified in the low and the high SMAI groups, respectively. Kaplan-Meier analysis showed that the low group had a significantly shorter overall survival and disease-free survival than the high group. Multivariable analysis identified low SMAI as an independent poor prognostic factor for overall survival. CONCLUSIONS: Pre-NACRT SMAI correlates with poor prognosis; therefore, assessing sarcopenia based on pre-NACRT SMAI may help determine optimal treatment strategies and suitable nutritional and exercise interventions.

DOI： 10.1093/icvts/ivad020

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DOI： 10.1245/s10434-023-13182-3

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肝切除後の造血幹細胞/M2BPGi/クッパー細胞軸の肝再生について検討した。まず、M2BPGiがヒト肝細胞およびクッパー細胞へ及ぼす影響を調べた。次に、in vitroおよびマウス肝切除モデルを用いて、M2BPGi関連分泌タンパク質であるグルコース調整タンパク質78(GRP78)が肝再生へ与える効果について検討した。その結果、M2BPGiは肝細胞促進作用を有さないが、M2BPGiはクッパー細胞におけるGRP78産生を促進させていた。クッパー細胞由来GRP78は肝細胞増殖を促進していた。70%肝切除後マウスに対するGRP78投与により肝再生が促進された。90%肝切除後マウスに対するGRP78投与により、生存率上昇も認められた。以上から、M2BPGiにより活性化されたクッパー細胞はGRP78を分泌し、肝再生を促進し、マウスモデルの生存率を向上させることが示された。

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DOI： 10.18888/op.0000003119

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Language：Japanese   Publisher：The Japan Society of Hepatology  

<p>To organize the current status and understanding of liver resection in the treatment of hepatocellular carcinoma, a questionnaire survey was conducted. The Kyushu Liver Surgery Study Group was sponsoring 15 institutions including hepatologists and liver surgeons. Regarding the excision borderline, hepatologists felt limited by numbers and Vps, while surgeons felt limited by Vvs. In the case of BCLC-B, hepatologists had few choices for resection even if the treatment succeeded. Surgeons chose treatment for the conversion surgery attempt in the case of portal vein proximity, but hepatologists chose resection as a result after successful treatment. For the conversion attempt, most hepatologists hoped to use drug therapy or local treatment. It has become clear that hepatologists and surgeons must further change their mindset to perform hepatic resection and local or systemic therapy in the treatment of hepatocellular cancer.</p>

DOI： 10.2957/kanzo.64.1

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OBJECTIVE: Postoperative limb infection is associated with a poor prognosis and a low amputation-free survival rate after surgical revascularization in patients with critical limb-threatening ischemia. The Global Vascular Guidelines 2019 recommend antibiotic therapy for patients with deep space foot infection or wet gangrene; however, no study is cited as evidence for this recommendation. The present study was performed to offer new evidence supporting the use of perioperative therapeutic antibiotics in patients with critical limb-threatening ischemia (CLTI) undergoing surgical revascularization. METHODS: This single-center retrospective study was performed in Kyushu University Hospital and involved patients with CLTI who underwent surgical revascularization from 2003 to 2021. Ampicillin/sulbactam and cefazolin were defined as preventive antibiotics, and other types were defined as therapeutic antibiotics. Postoperative limb-associated infection was defined as an increased foot infection (fI) score in the Wound, Ischemia, and foot Infection (WIfI) classification system after surgical revascularization. The association between perioperative antibiotic therapy and postoperative limb-associated infection was assessed. RESULTS: Among 286 limbs of 263 patients with CLTI, 27 (9%) limbs developed postoperative limb-associated infection after surgical revascularization. The fI scores were significantly higher in the patients with than without postoperative limb-associated infection (1.0 ± 0.2 vs 0.4 ± 0.1, respectively; p = 0.0033), indicating that an fI score of ≥1 was a risk factor for postoperative limb-associated infection. Perioperative therapeutic antibiotics significantly reduced the incidence of postoperative limb-associated infection compared with preventive antibiotics (0.0% vs. 44.8%, respectively; p = 0.0028) in the patients with CLTI who had an fI score of ≥1 after bypass surgery, although perioperative therapeutic antibiotics were not effective for patients with an fI score of 0. CONCLUSION: Perioperative therapeutic antibiotics for patients with an fI score of ≥1 are beneficial for reducing the incidence of postoperative limb-associated infection after surgical revascularization.

DOI： 10.1177/17085381231154608

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Macrophages play crucial roles in abdominal aortic aneurysm (AAA) formation through the inflammatory response and extracellular matrix degradation; therefore, regulating macrophages may suppress AAA formation. Interleukin-38 (IL-38) is a member of the IL-1 family, which binds to IL-36 receptor (IL1RL2) and has an anti-inflammation effect. Because macrophages express IL1RL2, we hypothesized that IL-38 suppresses AAA formation by controlling macrophages. We assessed a C57BL6/J mouse angiotensin II-induced AAA model with or without IL-38 treatment. RAW 264.7 cells were cultured with tumor necrosis factor-α and treated with or without IL-38. Because p38 has important roles in inflammation, we assessed p38 phosphorylation in vitro and in vivo. To clarify whether the IL-38 effect depends on the p38 pathway, we used SB203580 to inhibit p38 phosphorylation. IL1RL2+ macrophage accumulation along with matrix metalloproteinase (MMP)-2 and -9 expression was observed in mouse AAA. IL-38 reduced the incidence of AAA formation along with reduced M1 macrophage accumulation and MMP-2 and -9 expression in the AAA wall. Macrophage activities including inducible nitric oxide, MMP-2, and MMP-9 production and spindle-shaped changes were significantly suppressed by IL-38. Furthermore, we revealed that inhibition of p38 phosphorylation diminished the effects of IL-38 on regulating macrophages to reduce AAA incidence, indicating the protective effects of IL-38 depend on the p38 pathway. IL-38 plays protective roles against AAA formation through regulation of macrophage accumulation in the aortic wall and modulating the inflammatory phenotype. Using IL-38 may be a novel therapy for AAA patients.

DOI： 10.14814/phy2.15581

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Hepatocellular carcinoma (HCC) is a common cause of cancer-related deaths worldwide, and the mortality rate of patients with unresectable HCC is very high. Microsatellite instability (MSI) is an essential biomarker for response to immune checkpoint inhibitors (ICI) in various tumors. However, the frequency of MSI in HCC is low (1.11%). There is only one case report of MSI-high HCC, and it is not well understood how high MSI affects the tumor microenvironment of HCC. Hence, we describe an interesting patient with unresectable MSI-high HCC, including the evaluation of immune status in the tumor microenvironment. A 68-year-old man presented to our department with HCC in liver segment 1. Contrast-enhanced CT revealed a liver tumor of 6.0 cm in maximum size. The patient underwent extended left and caudate lobectomy of the liver for HCC. Four months after surgical resection, contrast-enhanced computed tomography (CECT) detected 13 recurrent nodules. The patient was diagnosed with unresectable hepatocellular carcinoma recurrence, and we decided to administer systematic chemotherapy. Lenvatinib was administered over approximately 2 years as a first-line treatment, which resulted in intrahepatic tumor shrinkage. However, follow-up CECT showed new lesions, hepatogastric mesentery lymph node swelling, and peritoneal dissemination. After MSI-high status was identified, the patient began to receive pembrolizumab (200 mg, every 3 weeks). Eleven cycles of pembrolizumab therapy were administered over approximately 8 months, during which the diameter of the hepatogastric mesentery lymph node swelling and peritoneal dissemination showed shrinkage but later re-increased. As the third- and fourth-line therapy has been administered, the tumors and lymph nodes have shrunk. We report a rare case in which multikinase inhibitors were effectively used to treat MSI-high HCC.

DOI： 10.1007/s13691-022-00585-4

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AIM: Although the survival rate after living-donor liver transplantation (LDLT) is improving, sepsis still limits the prognosis. Immune dysfunction and sarcopenia are often observed in LDLT patients, and increase susceptibility to infection. Brain-derived neurotrophic factor (BDNF) is a myokine produced by immune cells and skeletal muscle. We aimed to determine whether serum BDNF could be a feasible biomarker for sepsis of LDLT patients. METHODS: We measured serum samples from 124 patients who underwent LDLT and 9 healthy volunteers for BDNF. We examined its correlation with incidence rate of sepsis. To clarify the source of BDNF, we examined its expression in lymphocytes, skeletal muscle cells, and hepatocytes. RESULTS: Patients who experienced sepsis showed worse short-term survival. Preoperative serum BDNF was lower in LDLT patients compared with healthy volunteers, and was also lower in Child-Pugh C compared with Child-Pugh A or B. Serum BDNF was inversely correlated with Model for End-Stage Liver Disease and controlling nutritional status (CONUT) scores, but had a weak positive correlation with skeletal muscle mass index (SMI). Multivariate analysis revealed that serum BDNF was independently associated with sepsis. Preoperative serum BDNF was a better predictor of sepsis in LDLT patients than CONUT score or SMI. Serum BDNF was positively correlated with lymphocyte counts, especially T cells. In vitro, T cells and skeletal muscle cells produced BDNF. CONCLUSIONS: Preoperative serum BDNF could be a predictive biomarker for sepsis after LDLT, by reflecting the systemic condition including hepatic function, nutritional status, and immune status.

DOI： 10.1111/hepr.13834

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BACKGROUND: Signal regulatory protein alpha (SIRPα), expressed in the macrophage membrane, inhibits phagocytosis of tumor cells via CD47/SIRPα interaction, which acts as an immune checkpoint factor in cancers. This study aimed to clarify the clinical significance of SIRPα expression in hepatocellular carcinoma (HCC). METHODS: This study analyzed SIRPα expression using RNA sequencing data of 372 HCC tissues from The Cancer Genome Atlas (TCGA) and immunohistochemical staining of our 189 HCC patient cohort. The correlation between SIRPα expression and clinicopathologic factors, patient survival, and intratumor infiltration of immune cells was investigated. RESULTS: Overall survival (OS) was significantly poorer with high SIRPα expression than with low expression in both TCGA and our cohort. High SIRPα expression correlated with lower recurrence-free survival (RFS) in our cohort. High SIRPα expression was associated with higher rates of microvascular invasion and lower serum albumin levels and correlated with greater intratumor infiltration of CD68-positive macrophages and myeloid-derived suppressor cells (MDSCs). Multivariate analysis showed that SIRPα expression and high infiltration of CD8-positive T cells and MDSCs were predictive factors for both RFS and OS. Patients with high SIRPα expression and infiltration of CD8-positive T cells and MDSCs had significantly lower RFS and OS rates. In spatial transcriptomics sequencing, SIRPα expression was significantly correlated with CD163 expression. CONCLUSIONS: High SIRPα expression in HCC indicates poor prognosis, possibly by inhibiting macrophage phagocytosis of tumor cells, promoting MDSC infiltration and inducing antitumor immunity. Treatment alternatives using SIRPα blockage should be considered in HCC as inhibiting macrophage antitumor immunity and MDSCs.

DOI： 10.1245/s10434-022-13058-y

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Recurrence of hepatocellular carcinoma (HCC) after living donor liver transplant (LDLT) is an essential factor defining prognosis, and surgical resection is the only curative treatment. However, the factors that define whether surgical resection is possible remain unclear. Here, we compared resectable and unresectable HCC recurrence cases after LDLT and examined factors that determine whether surgical resection is possible. Resectable (n = 17) and unresectable (n = 14) groups among 264 patients who underwent LDLT for HCC from January 1999 to March 2020 were compared and examined for recurrence type, prognosis, and clinicopathologic factors. Overall survival after LDLT (median, 8.5 vs 1.7 years, P < .01) was significantly longer in the resectable group. In univariate analysis, female recipient rate, lymphocyte to monocyte ratio (LMR) ≥2.75, and tumor size ≤5.0 cm were significantly higher in the resectable group. Younger donors, lower Model for End-Stage Liver Disease scores, lower graft volume, and lower graft volume to standard liver volume ratio were evident in the resectable group. In multivariate analysis, female recipient rate (P = .0034) and LMR ≥2.75 (P = .0203) were independent predictive factors for resectable HCC recurrence after LDLT. Female recipient and LMR ≥2.75 before transplant could predict the surgically resectable type of HCC recurrence after LDLT.

DOI： 10.1016/j.transproceed.2022.09.031

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Language：English   Publisher：John Wiley & Sons Australia, Ltd  

喫煙歴とSARS-Cov-2感染性との関係性について検討した。2013年1月～2019年12月までの期間内に、著者等の医療施設で外科治療で採取した肺組織試料を用い、喫煙者、喫煙歴ありの非喫煙者、非喫煙者肺から検出されるアンジオテンシン変換酵素2(ACE2)の遺伝子発現を調査した。その結果、禁煙期間6ヵ月未満の患者ではACE2遺伝子発現量が、非喫煙者や禁煙期間6ヵ月以上の患者から検出された発現量に比べ高発現であった。また、SARS-Cov-2の感染効率はACE2発現量に依存して亢進し、喫煙者肺のRNA-seq解析では、炎症シグナル伝達に関与する遺伝子発現がACE2遺伝子発現と相関することが明らかにされた。なかでも、過去に喫煙歴がある患者では、禁煙期間が長いほどACE2遺伝子発現量のみならず、炎症シグナル伝達に関与する遺伝子発現量でも低下が認められた。以上より、喫煙はACE2遺伝子と炎症シグナル伝達に関与する遺伝子発現量を亢進させ、SARS-Cov-2への感染効率は、喫煙を介したACE2遺伝子発現量のアップレギュレーションにより増強されることが示唆された。

Language：English   Publisher：シュプリンガー・ジャパン(株)  

症例は68歳男性で、肝S1の肝細胞癌について造影CTで最大径6.0cmの腫瘤を認めた。拡大肝左葉切除術と尾状葉切除術を施行した。病理診断では中・低分化型肝細胞癌で、脈管侵襲や肝内転移は認めなかった。手術標本ではプログラム細胞死リガンド-1の高発現とCD8陽性T細胞の存在を認め、腫瘍浸潤性マクロファージが多数観察された。切除4ヵ月後、造影CTで13個の再発結節を認めた。切除不能な肝細胞癌の再発と診断し、系統的な化学療法を行うことにした。一次治療としてレンバチニブを約2年間投与し、肝内腫瘍の縮小を認めた。しかし、経過観察の造影CTで新たな病変、肝胃腸間膜リンパ節腫脹、腹膜播種を認めた。高頻度マイクロサテライト不安定性(MSI-high)が検出されたため、ペムブロリズマブ(200mg、3週ごと)の投与を開始した。約8ヵ月間で11サイクルのペムブロリズマブ療法を施行した結果、肝胃腸間膜リンパ節腫脹と腹膜播種径は縮小したが、その後に再び増加した。三次治療としてソラフェニブを投与したところ、病変は一旦縮小したが、皮疹(グレード3)を認めたため、治療を中止した。さらに、四次治療としてカボザンチニブを8ヵ月間投与した。その結果、腫瘍とリンパ節腫脹が縮小した。MSI-highの肝細胞癌に対してマルチキナーゼ阻害剤が有効であった。

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND/AIM: Peritoneal metastasis (PM) of gastric cancer (GC) leads to poor clinical outcomes. Tumor-derived exosomes promote metastasis via communication between tumor cells and host cells. In this study, we investigated the effect of Rab27, which is required for exosome secretion, on the PM of GC. MATERIALS AND METHODS: We established a stable knockdown of two Rab27 homologs, Rab27a and Rab27b, in human GC cells (58As9) with a high potential of PM. We examined the level of exosome secretion from Rab27-knockdown 58As9 cells by Western blotting and the ability of Rab27b knockdown to suppress PM in 58As9 cells using a mouse xenograft model. In vitro proliferation and invasion assays were performed in the Rab27b-knockdown cells. Next, Rab27b expression was evaluated in human GC tissues by immunohistochemistry. Finally, we assessed the clinicopathological and prognostic significance of Rab27b expression by RT-qPCR in both our and other TCGA datasets of GC. RESULTS: Rab27a and Rab27b knockdown in 58As9 cells decreased the secretion of exosomes, characterized by the endocytic marker CD63. Rab27b knockdown decreased PM in vivo without affecting the in vitro proliferation or invasion ability of 58As9 cells. In human GC tissues, Rab27b was overexpressed in tumor cells. The overall and recurrence-free survival rates were significantly lower in GC patients with high compared to low Rab27b mRNA expression in our and other TCGA datasets. CONCLUSION: Rab27b expression potentially serves as a poor prognostic biomarker, possibly affecting PM via exosome secretion from GC cells.

DOI： 10.21873/cgp.20362

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生体肝移植(LDLT)患者の血清脳由来神経栄養因子(BDNF)を評価し、LDLT後の敗血症や生存率を予測するバイオマーカーになり得るかについて検討した。LDLTを受けた末期肝疾患患者を後ろ向きに調べ、健常者を対照群とした。BDNFと敗血症発生率との関連を調べた。患者124例(男性53例、女性71例、年齢17～76歳)と健常者9例を解析した。11例(8.9%)で敗血症が発症し、敗血症患者では短期生存率が非敗血症患者より不良であった。術前血清BDNFは対照群より患者群で低く、Child-Pugh分類AまたはBの患者よりCの患者で低かった。血清BDNFは、末期肝疾患モデル(MELD)スコアおよびControlling Nutritional Status(CONUT)スコアと逆相関を示したが、骨格筋量指数(SMI)と弱い正の相関を示した。多変量解析では、血清BDNFが敗血症と独立に関連した。LDLT患者の敗血症について、術前血清BDNFの予測能はCONUTスコアやSMIより高かった。以上より、術前の血清BDNFは、LDLT後の敗血症の予測バイオマーカーとなり得ることが示唆された。

Language：Japanese   Publisher：(一社)日本肝臓学会  

肝癌に対する肝切除における内科医と外科医の現状と肝切除に対する考え方を整理することを目的にアンケートを実施した.九州肝臓外科研究会世話人施設15施設の内科医および外科医を対象とした.切除のボーダーラインに関して内科医は個数とVpに関して制限を,外科医はVvに制限を感じていた.イメージ症例に対してBCLC-B・up to 7 outは内科医・外科医ともにICIを選択し,内科医は奏功しても切除の選択は少なかった.門脈近接症例に対して外科医はConversion企図の治療選択であったが,内科医は治療奏功後に結果として切除を選択していた.内科医としての切除前後での関わりに関してはConversionを企図した薬物療法・局所治療の選択を希望していた.今後さらに複雑化する肝癌治療において肝切除と薬物治療・局所治療をシームレスに行うためにより一層内科医と外科医の意識改革が必要であることが明らかとなった.(著者抄録)

Language：Japanese   Publisher：一般社団法人 日本移植学会  

<p>【目的】　移植後患者は新型コロナウイルス感染症（COVID-19）の重症化群であり、健常者よりCOVID-19への感染への恐怖が強いことが報告されている。本研究は、COVID-19禍における移植後患者の身体活動量と恐怖、感染予防行動との関連を明らかにすることを目的とする。【方法】対象者は2021年3～4月に当院通院中で肝、腎移植後6ヶ月以上の20歳以上の患者とした。身体活動量はInternational Physical Activity Questionnaireを用いて不活発群と活発群に分類した。COVID-19への恐怖と感染予防行動は、先行研究に基づき自記式質問紙で調査した。身体活動量と恐怖、感染予防行動との関連は活発群・不活発群の2群を従属変数としてロジスティック回帰分析を用いて分析した。【結果】対象者は204名で（肝136名、腎68名）、男性は98名（48%）、平均年齢は59.1±11.8歳、平均BMIは22.6±3.6kg/m²、平均移植後年数は6.6±5.5年であった。不活発群は113名（55.4%）であり、移植臓器による身体活動量に相違はなかった。不活発群は活発群と比較し、免疫抑制剤の内服が感染を悪化させることへの恐怖が強く（OR=1.48, p=0.08）、運動習慣（OR =0.35, p ＜ 0.001）や外出頻度が少なかった（OR=1.50 , p=0.009）。【考察】COVID-19禍で移植後患者の半数以上は不活発であることが示された。過度な恐怖は身体活動量の低下を招くため、医療者による正しい情報提供の必要性が示唆された。</p>

DOI： 10.11386/jst.58.supplement_s328_1

CiNii Research

Language：Japanese   Publisher：一般社団法人 日本移植学会  

<p>【背景・目的】肝移植後のsmall-for-size syndrome (SFSS)は予後不良の病態であり、周術期のportal modulation介入が必須である。2023年1月、ILTS consensus conference (India)においてSFSSの新基準及び重症度分類が提唱された。重症度分類(Grade A/B/C)では、特にportal hypertensive phaseであるSFSS Grade Bにおいてportal modulationを含めた周術期管理が重要とされている。当院におけるSFSS Grade B[(T-Bil＞10mg/dL or INR＞1.6(POD7)、もしくはT-Bil＞10mg/dL and腹水1L/日(POD14)]の成績につき考察する。</p><p>【対象・方法】当科施行の成人間生体肝移植(LDLT)783例を対象(2022年12月まで)。SFSSの重症度分類で特にGrade Bにおける臨床因子及び予後因子について検討を行った。</p><p>【結果】SFSS新基準においてSFSSを442例(56.4%)認めた。Grade A/B/Cの割合は60.0%/26.0%/14.0%であり、術後グラフト生存率(Grade A/B/C )は1年生存率90.2%/88.7%/46.2%であり、Grade Cが有意に予後不良であった(P＜0.05)。また、前期・後期に分類した場合、Grade A/Bのグラフト1年生存率は、前期 89.2%/80.3%(P＜0.05)、後期91.0%/91.3%(P=NS)と前期のみGrade Bのグラフト生存率が有意に低値であった。</p><p>【まとめ】SFSS新基準による重症度分類によって予後の層別化可能であった。Grade Bに関して、high volume centerにおける周術期管理の習熟、portal modulation介入による時代後期の予後改善が示唆された。</p>

DOI： 10.11386/jst.58.supplement_s207_2

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Language：English   Publisher：The Japan Society for Transplantation  

<p>The aim of this study was to examine the influence of machine perfusion (MP) and normothermic regional perfusion (NRP) on the utilization and outcomes of liver transplantation (LT). Using US national data, 4642 donation after circulatory death (DCD) donors between 2016 and 2021 were analyzed. 4542 were with static cold storage(SCS), 79 were with MP(1.7%), and 21 were with NRP(0.5%).The utilization rates of liver in DCD with MP or NRP were significantly higher (P=0.001; 92.4% or 95.2% vs 70.4%). There were no graft failure with primary nonfunction or ischemic cholangiopathy after LT with MP or NRP. MP or NRP significantly increased the utilization rate of livers with favorable outcomes after LT. Increasing use of MP or NRP should be considered in low utilization donors to expand donor pool.</p>

DOI： 10.11386/jst.58.supplement_s127_1

CiNii Research

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Rendu-Osler-Weber disease (Osler's disease) is the most common cause of pulmonary arteriovenous fistula. We report a case of pulmonary arteriovenous fistula associated with Osler's disease that was treated by lobectomy. CASE REPORT: A 44-year-old man with Osler's disease presented with respiratory distress. Computed tomography showed a pulmonary arteriovenous fistula, which had a 26-mm-long diameter in S6 of the left lung. Transcatheter treatment had a high risk of recurrence, and surgery was indicated. The pulmonary arteriovenous fistula was found at the beginning of A6. A6 and the basilar artery were cut together with a stapler. The postoperative course was uneventful, and respiratory distress symptoms improved with no recurrence. CONCLUSION: We report a case of pulmonary arteriovenous fistula caused by Osler's disease treated by lobectomy. Although transcatheter treatment is the mainstream treatment for pulmonary arteriovenous fistulas, surgical resection may be effective depending on the size of the lesion.

DOI： 10.21873/invivo.13402

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Language：Japanese   Publisher：一般社団法人 日本移植学会  

<p>【背景・目的】生体肝移植術(LDLT)において術前運動耐容能と術後自立歩行獲得日数との関連性は明らかではない.今回,術前運動耐容能が術後自立歩行にどの程度影響しているか検討し,機能予後の予測因子となりえるか明らかにする.【方法】対象は,当院で施行したLDLT105例.術前運動耐容能は,6分間歩行距離(6MD)を指標とした.(1)術後自立歩行獲得日数により早期群と遅延群に分類し,以下の臨床因子(年齢,性別,BMI,MELDscore,GNRI,腹水量,手術時間,出血量,グラフト体重比,人工呼吸器装着日数,術後せん妄及び術後敗血症合併の有無,術後端坐位及び歩行開始到達日数,術後在院日数)を2群間で比較検討した.(2)遅延群に関するリスク因子をロジスティック回帰分析にて検討した.【結果】(1)術前運動耐容能を測定し得た解析可能症例は42例であった.術後自立歩行獲得日数は,中央値9(6-14)日であり,歩行早期群19例及び歩行遅延群23例に分類された.両群間の比較にて,遅延群において術前因子では,6MDが低値,MELDscoreが高値,術後因子では,せん妄,敗血症合併,人工呼吸器装着日数,術後在院日数が有意に延長を認めた.(2)歩行遅延群のリスク因子として,6MD(OR1.02,95%CI:0.97-0.99,p＜0.05;カットオフ350m)が同定され,術前6MDは術後自立歩行獲得日数に有意に逆相関した.【結論】LDLTにおいて術前運動耐容能は術後の自立歩行獲得日数の指標となり,LDLT後の機能予後予測因子となることが示唆された.</p>

DOI： 10.11386/jst.58.supplement_s274_3

CiNii Research

Language：Japanese   Publisher：一般社団法人 日本移植学会  

<p>【はじめに】肝移植では多様な重篤である術後合併症により非常に難渋する症例を経験する。</p><p>【症例】57歳男性、11年前にC型非代償性肝硬変、肝細胞癌に対し生体肝移植術施行。術後吻合部胆管狭窄から二次性非代償性胆汁うっ滞性肝硬変、肝腎症候群に伴う維持透析導入となり4ヶ月前に脳死登録。脳死肝腎移植術施行、著明な凝固機能障害、肝周囲中心の腹腔内癒着のため、手術時間1100分、出血量約27L。術後7日目に横行結腸穿孔に対し腹腔内洗浄ドレナージ、人工肛門造設術施行、以後ドレーン管理継続。術後23日目に肝酵素上昇、US・CTにて肝動脈閉塞症が疑われた。血管造影にて、固有肝動脈遠位での血流途絶を認めた(肝内動脈本幹は著明な血流低下認めるが遅延性に描出)。肝動脈再建施行も肝内動脈血流改善認めず、肝内動脈血確保目的に総肝動脈-肝円索吻合を行った。術後門脈圧亢進に伴う大量水様便等を認め水分・電解質補正、ドレーン管理継続。術後54日目にドレーン排液血性変化、CTで吻合部肝円索側の仮性瘤形成を認めた。緊急血管造影で仮性瘤より末梢血流は途絶、また以前の側副血行路の発達を認め良好な肝内動脈血流を認めたため仮性瘤はコイル塞栓施行。翌日より水様便減少し良好に経過した。リハビリを継続し、最終的に自宅退院となった。</p><p>【まとめ】綿密な術後管理と肝内動脈血確保の姑息的手段として総肝動脈-肝円索吻合により救命し得た症例を経験した。</p>

DOI： 10.11386/jst.58.supplement_s140_2

CiNii Research

Language：Japanese   Publisher：一般社団法人 日本移植学会  

<p>将来は専門に偏らず、様々な急患手術にも対応ができるような外科医になりたい、そんな夢を胸に医学部に入学した私が、肝移植の分野に興味を持ったのはベッドサイド実習で見学した生体肝移植の手術がきっかけだった。しかし、実際に肝移植を志すきっかけとなったのは、医師4年目に担当した2人の肝移植を受けた患者さんとの出会いであった。生体肝移植はドナーとなる家族が、そして脳死肝移植も提供を決意してくれたドナーやその家族がいてこそ成り立つ医療である。そのため、患者本人だけでなく、その家族とも深く関わる機会も多く、患者の回復には家族の支えが不可欠であることを痛感する。だからこそ、死を目前にしていた患者が、笑顔で家族と退院した時の感動が、肝移植の一番の魅力ではないかと思う。ただ、医師の働き方改革が進められる中、肝移植の分野では医師の負担もまだ大きく、家庭を有する女性医師が両立できるような体制が整っているとは言えない。だが、女性医師の割合が増加している現在、女性医師を敬遠してしまう環境では、肝移植分野の継続した発展は難しいのではないかとも考えられる。移植医療は、移植コーディネーターを始めとした多数の職種が協力することが不可欠な分野でもあることから、多職種のチーム体制を確立させ、より分業化することが、将来的に医師の多様な働き方に対応できるような環境づくりの一歩となるのではないかと考える。</p>

DOI： 10.11386/jst.58.supplement_s218_1

CiNii Research

Language：Japanese   Publisher：一般社団法人 日本移植学会  

<p>【背景】三尖弁逆流圧較差(TRPG)は肺動脈圧をある程度反映するとされ、肺高血圧症のスクリーニングとして使用される。これまでに、TRPGと生体肝移植術後腹水量との関係を示した報告はない。【目的】TRPG値と術後遷延する腹水量との関係を評価する。【対象と方法】当院で2001年8月から2022年1月までに生体肝移植術を施行した症例の内、TRPG値を取得可能な268症例を対象とした。術後30日目腹水量500ml以上を術後遷延腹水と定義した。傾向スコアマッチングを用い、TRPG高値群(n=50)とTRPG低値群(n=50)について多変量解析を行った。 【結果】多変量解析では、TRPG高値(p=0.0307)、術中大量出血(p=0.0237)が独立に相関する因子であり、TRPG高値群において術中の出血量を抑えると術後遷延腹水の割合が減少することが示された(p＜0.01)。【考察】肝硬変患者では、末梢血管抵抗の減少、心拍出量の増大をきたす、Hyperdynamic circulation の状態にある。TRPG高値群で術後遷延腹水が多い理由として、TRPG高値が循環血漿量過多を示しており、これが術後遷延する腹水量に関与している可能性が考えられた。【結語】TRPG高値は生体肝移植術後の遷延腹水のリスク因子であった。術中の出血量を抑えることで、術後腹水の遷延を回避できる可能性が示唆された。</p>

DOI： 10.11386/jst.58.supplement_s275_2

CiNii Research

Language：English   Publishing type：Research paper (scientific journal)  

Inflammation plays a part in the development of abdominal aortic aneurysm (AAA), and the gut microbiota affects host inflammation by bacterial translocation. The relationship between abdominal aortic aneurysm and the gut microbiota remains unknown. This study aimed to detect bacterial translocation in the aneurysmal wall and blood of patients with abdominal aortic aneurysm, and to investigate the effect of the gut microbiota on abdominal aortic aneurysm. We investigated 30 patients with abdominal aortic aneurysm from 2017 to 2019. We analysed the aneurysmal wall and blood using highly sensitive reverse transcription-quantitative polymerase chain reaction, and the gut microbiota was investigated using next-generation sequencing. In the 30 patients, bacteria were detected by reverse transcription- quantitative polymerase chain reaction in 19 blood samples (detection rate, 63%) and in 11 aneurysmal wall samples (detection rate, 37%). In the gut microbiota analysis, the Firmicutes/Bacteroidetes ratio was increased. The neutrophil-lymphocyte ratio was higher (2.94 ± 1.77 vs 1.96 ± 0.61, P < 0.05) and the lymphocyte-monocyte ratio was lower (4.02 ± 1.25 vs 5.86 ± 1.38, P < 0.01) in the bacterial carrier group than in the bacterial non-carrier group in blood samples. The volume of intraluminal thrombus was significantly higher in the bacterial carrier group than in the bacterial non-carrier group in aneurysmal wall samples (64.0% vs 34.7%, P < 0.05). We confirmed gut dysbiosis and bacterial translocation to the blood and aneurysmal wall in patients with abdominal aortic aneurysm. There appears to be a relationship between the gut microbiota and abdominal aortic aneurysm.

DOI： 10.1371/journal.pone.0278995

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The recipient muscle status is closely associated with postoperative poor survival in recipients of living donor liver transplantation (LDLT). However, it is uncertain whether LDLT donor muscle quality and quantity affect graft quality. Hence, we analyzed the correlation between donor muscle status and graft function. We measured the skeletal muscle mass index (SMI) and intramuscular adipose tissue content (IMAC) of 380 LDLT donors. We examined the correlation between donor SMI or IMAC and graft mortality, the occurrence rates of small-for-size graft (SFSG) syndrome, and 6-month graft survival rates. The donor SMI had no effect on the occurrence of SFSG syndrome and graft survival, while a high IMAC in both male and female donors was significantly correlated with the rate of SFSG syndrome [high vs low: (male donors) 15.8% vs. 2.5%, p = 0.0003; (female donors) 12.8% vs. 3.1%, p = 0.0234] and 6-month graft survival rates [(male donors) 87.7% vs 95.9%, p = 0.02; (female donors) 83.0% vs. 99.0%, p < 0.0001]. Multivariate analysis revealed that a high donor IMAC (HR; 5.42, CI; 2.13-13.8, p = 0.0004) was an independent risk factor for 6-month graft survival, and the donor IMAC is useful for donor selection for high-risk recipients.

DOI： 10.3389/ti.2022.10723

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Publisher：南江堂  

DOI： 10.15106/j_geka84_1362

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Although there have been a few liver transplantations (LTs) between identical twins, to our knowledge hepatic damage after LT in an immunosuppressant-free patient has not been reported. Autoimmune liver disease recurrence after LT is also a postoperative problem. In this follow-up to our previous report, we present the case of a 57-year-old man with acute liver failure who underwent living donor liver transplantation (LDLT) from an identical twin. Six months after LDLT, the patient was free from immunosuppressive medication and showed good liver function. However, 1 year after LDLT, he developed liver damage and was diagnosed with autoimmune hepatitis by liver biopsy. His liver function was improved with steroid pulse therapy and the resumption of immunosuppressive medications. Even after LDLT from an identical twin, careful management is required for patients to remain free of immunosuppressive medications, considering the background liver disease.

DOI： 10.1016/j.transproceed.2022.09.022

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AIMS: The fibroblast growth factor receptor 2 (FGFR2) fusion gene is frequently found as a genetic abnormality in the FGFR pathway in patients with intrahepatic cholangiocarcinoma (ICC). The FGFR fusion protein, produced from the FGFR fusion gene, is thought to cause tumor cell growth. To date, there have been few reports on the relationship between pathologic FGFR2 expression and prognosis in patients who have undergone hepatectomy for ICC, and on the relationship between FGFR2 and tumor-infiltrating lymphocytes (TILs). METHODS AND RESULTS: We enrolled 92 patients who underwent hepatectomy for ICC and performed immunohistochemical staining for FGFR2 and cluster of differentiation 8, and hematoxylin and eosin staining for evaluating TILSs. The relationships between the FGFR2 and clinicopathological characteristics and outcomes were analyzed, and patients were classified into positive (n = 18) and negative (n = 74) FGFR2 groups. The FGFR2-positive group contained more men (p < 0.0001) and had lower serum albumin (p = 0.0355) and higher carcinoembryonic antigen (p = 0.0099). Furthermore, multivariable analyses revealed that the FGFR2-positive group had worse disease-free survival (DFS) (p = 0.0002). Multivariate analysis showed that the independent prognostic factors for DFS were maximum tumor size (≥5 cm) (p = 0.0011), tumor localization (perihilar type) (p = 0.0180), and FGFR2 positivity (p = 0.0029). There was no significant difference in TILs count between the two groups. CONCLUSION: We showed that FGFR2 high expression was an independent prognostic factor for recurrence of resected ICC.

DOI： 10.1111/hepr.13875

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Background / Regular physical activity (PA) is important for maintaining mental and physical health after liver transplantation (LT); however, the fluctuations in routine PA during COVID-19 and its putative impacts are currently unknown. This study examined the changes in PA during the COVID-19 pandemic and explored its association with fear and depression during the pandemic. / Material/Methods / This longitudinal study included 83 LT patients whose PA was measured using the short form of the International Physical Activity Questionnaire before and during COVID-19. Fear of COVID-19 was estimated based on previous studies, and depression was assessed using the Patient Health Questionnaire-9. Participants were also asked about important sources of information on COVID-19. PA was classified as inactive or active depending on the changes in PA, and logistic regression analyses with PA as a dependent variable were conducted to explore the associations among PA, depression, and fear of COVID-19. / Results / Moderate and high PA exhibited decreasing trends before and during the COVID-19 pandemic, especially in males. Fear of being infected with SARS-CoV-2, the virus that causes COVID-19, while shopping was significantly higher in females and was significantly independent of inactivity during the COVID-19 pandemic. Only 1 patient reported that their transplant center was their main source of information about COVID-19. Only 4.9% of the LT participants were depressed. / Conclusions / Our study results indicate the need to support the provision of accurate information about COVID-19 by health care professionals in transplant centers, especially for patients with low PA, to prevent PA decline in LT patients.

DOI： 10.12659/AOT.938239

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

BACKGROUND: To develop an artificial intelligence-based model to predict recurrence after curative resection for stage I-III colorectal cancer from digitized pathological slides. PATIENTS AND METHODS: In this retrospective study, 471 consecutive patients who underwent curative resection for stage I-III colorectal cancer at our institution from 2004 to 2015 were enrolled, and 512 randomly selected tiles from digitally scanned images of hematoxylin and eosin-stained tumor tissue sections were used to train a convolutional neural network. Five-fold cross-validation was used to validate the model. The association between recurrence and the model's output scores were analyzed in the test cohorts. RESULTS: The area under the receiver operating characteristic curve of the cross-validation was 0.7245 [95% confidence interval (CI) 0.6707-0.7783; P < 0.0001]. The score successfully classified patients into those with better and worse recurrence free survival (P < 0.0001). Multivariate analysis revealed that a high score was significantly associated with worse recurrence free survival [odds ratio (OR) 1.857; 95% CI 1.248-2.805; P = 0.0021], which was independent from other predictive factors: male sex (P = 0.0238), rectal cancer (P = 0.0396), preoperative abnormal carcinoembryonic antigen (CEA) level (P = 0.0216), pathological T3/T4 stage (P = 0.0162), and pathological positive lymph node metastasis (P < 0.0001). CONCLUSIONS: The artificial intelligence-based prediction model discriminated patients with a high risk of recurrence. This approach could help decision-makers consider the benefits of adjuvant chemotherapy.

DOI： 10.1245/s10434-022-12926-x

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Other Link： https://link.springer.com/article/10.1245/s10434-022-12926-x/fulltext.html

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BACKGROUND: A comparison between atezolizumab plus bevacizumab (ATEZO/BEVA) and lenvatinib (LEN) for the treatment of hepatocellular carcinoma (HCC) remains unclear. OBJECTIVE: This study aimed to compare the therapeutic effects and safety of ATEZO/BEVA and LEN as first-line therapies for HCC. PATIENTS AND METHODS: This study was a retrospective analysis of 810 patients with HCC who underwent ATEZO/BEVA (n = 186) or LEN (n = 624) as first-line systemic therapy between March 2018 to March 2022 at 14 facilities. After propensity score matching, 304 patients (ATEZO/BEVA group: n = 152; LEN group: n = 152) were analyzed. RESULTS: After propensity score matching, although there was no significant difference in objective response rates (ORRs) between the ATEZO/BEVA and LEN groups (ORR 44.8% vs. 46.7%, p = 0.644), the median progression-free survival (PFS) and median overall survival (OS) in the ATEZO/BEVA group were significantly higher than those in the LEN group (median PFS: 8.3 months vs. 6.0 months, p = 0.005; median OS: not reached vs. 20.2 months, p = 0.039). The rates of appetite loss, fatigue, and proteinuria of grade 3 or higher in the ATEZO/BEVA group were lower than those in the LEN group. However, the rate of bleeding of grade 3 or higher in the ATEZO/BEVA group was higher than that in the LEN group. The conversion rate was higher in the ATEZO/BEVA group than that in the LEN group (8.6% vs. 1.9%, p = 0.007). CONCLUSIONS: ATEZO/BEVA showed superiority to LEN in terms of prognosis and conversion rate as first-line therapy. Moreover, ATEZO/BEVA had a lower rate of severe adverse events, except for bleeding, than LEN.

DOI： 10.1007/s11523-022-00921-x

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The polybromo-1 (PBRM1) chromatin-targeting subunit of the SWI/SNF PBAF chromatin remodeling complex drives DNA damage resistance and immune evasion in certain cancer cells through mechanisms that remain unclear. STAT1 and IRF1 are essential effectors of type I and II interferon (IFN) pathways. Here, we report that MUC1-C is necessary for PBRM1 expression and that it forms a nuclear complex with PBRM1 in TNBC cells. Analysis of global transcriptional (RNA-seq) and chromatin accessibility (ATAC-seq) profiles further demonstrated that MUC1-C and PBRM1 drive STAT1 and IRF1 expression by increasing chromatin accessibility of promoter-like signatures (PLSs) on their respective genes. We also found that MUC1-C, PBRM1, and IRF1 increase the expression and chromatin accessibility on PLSs of the (i) type II IFN pathway IDO1 and WARS genes and (ii) type I IFN pathway RIG-I, MDA5, and ISG15 genes that collectively contribute to DNA damage resistance and immune evasion. In support of these results, targeting MUC1-C in wild-type BRCA TNBC cells enhanced carboplatin-induced DNA damage and the loss of self-renewal capacity. In addition, MUC1-C was necessary for DNA damage resistance, self-renewal, and tumorigenicity in olaparib-resistant BRCA1-mutant TNBC cells. Analysis of TNBC tumors corroborated that (i) MUC1 and PBRM1 are associated with decreased responsiveness to chemotherapy and (ii) MUC1-C expression is associated with the depletion of tumor-infiltrating lymphocytes (TILs). These findings demonstrate that MUC1-C activates PBRM1, and thereby chromatin remodeling of IFN-stimulated genes that promote chronic inflammation, DNA damage resistance, and immune evasion. Implications: MUC1-C is necessary for PBRM1-driven chromatin remodeling in chronic activation of IFN pathway genes that promote DNA damage resistance and immunosuppression.

DOI： 10.1158/1541-7786.MCR-22-0772

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BACKGROUND: There is little evidence concerning survival after surgery in patients with hepatocellular carcinoma who have received lenvatinib treatment. The aim of this study was to evaluate whether post-lenvatinib surgical treatment in patients with hepatocellular carcinoma improves overall survival. METHODS: The cohort of this retrospective study comprised 55 patients with hepatocellular carcinoma who had undergone lenvatinib treatment. We classified them into two groups according to post-lenvatinib surgical treatment status and compared clinicopathologic factors and prognosis between the two groups with the aim of identifying predictors of overall survival. RESULTS: The median duration of lenvatinib administration was 5.8 months (range, 0.4-24.0 months). Twelve of the 55 patients underwent surgery after receiving lenvatinib. There was no significant difference in assessed clinicopathological factors between patients who did and did not undergo surgery after being treated with lenvatinib. Multivariate analysis revealed that older age was associated with a significantly worse overall survival (hazard ratio: 2.332; 95% confidence interval 1.062-5.168; P = 0.0369) and that surgery after treatment with lenvatinib achieved better overall survival than other forms of treatment (hazard ratio: 0.121; 95% confidence interval 0.016-0.901; P = 0.0393). CONCLUSIONS: Surgical treatment after lenvatinib administration may be a useful therapeutic option for select patients with hepatocellular carcinoma.

DOI： 10.1007/s10147-022-02229-2

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Language：English   Publisher：シュプリンガー・ジャパン(株)  

レンバチニブ投与後に手術を受けた肝細胞癌(HCC)患者の生存率を調査した。レンバチニブ投与期間の中央値は5.8ヵ月(範囲0.4～24.0ヵ月)であった。レンバチニブ投与を受けたHCC患者55例のうち、12例(年齢41～77歳)はレンバチニブ投与後に手術(肝切除術8例、転移病変切除3例、生体肝移植1例)を受け、43例(年齢36～88歳)は手術を受けなかった。手術例と非手術例の間で臨床病理学的因子に有意差はなかった。多変量解析の結果、高齢は全生存率の有意な低下と関連し(ハザード比2.332、95%CI 1.062～5.168、P=0.0369)、レンバチニブ投与後の手術は他の治療方法よりも全生存率が優れていた(ハザード比0.12、95%CI 0.016～0.901、P=0.0393)。以上より、レンバチニブ投与後の手術は、一部の肝細胞癌患者にとって有用な治療選択肢となる可能性があった。

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BACKGROUND: Extrapulmonary tuberculosis commonly affects the lymphatic system, nervous system, and gastrointestinal system. Tuberculous infection in the muscle is very rare. Moreover, tuberculous infection in the diaphragm is extremely rare. We herein report a case of tuberculomas in the diaphragm and posterior mediastinum that were successfully diagnosed and treated. CASE PRESENTATION: We encountered a 62-year-old woman with a tuberculoma in the diaphragm. The patient presented with mild dyspnea. Computed tomography showed a mass in the left diaphragm, focal thickening of the posterior mediastinum, and multiple nodules in the lungs. Positron emission tomography-computed tomography showed increased uptake in the left diaphragm mass and thickening of the posterior mediastinum; therefore, we considered the masses to be malignant and planned surgical resection. However, the patient was diagnosed with tuberculosis from a sputum culture, and she was treated with anti-tuberculous therapy. The masses in the diaphragm and posterior mediastinum had become enlarged after 6 months of anti-tuberculous therapy; therefore, the patient underwent resection of both masses. Tuberculous infection was histologically confirmed in each lesion. She was pathologically diagnosed with tuberculous abscesses in the diaphragm and posterior mediastinum and began treatment with anti-tuberculosis drugs. CONCLUSIONS: Preoperative diagnosis of a tuberculoma in the diaphragm is usually difficult, and surgical intervention is important for both diagnosis and treatment.

DOI： 10.1186/s40792-022-01554-y

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Smoking is one of the risk factors most closely related to the severity of coronavirus disease 2019 (COVID-19). However, the relationship between smoking history and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectivity is unknown. In this study, we evaluated the ACE2 expression level in the lungs of current smokers, ex-smokers, and nonsmokers. The ACE2 expression level of ex-smokers who smoked cigarettes until recently (cessation period shorter than 6 months) was higher than that of nonsmokers and ex-smokers with a long history of nonsmoking (cessation period longer than 6 months). We also showed that the efficiency of SARS-CoV-2 infection was enhanced in a manner dependent on the angiotensin-converting enzyme 2 (ACE2) expression level. Using RNA-seq analysis on the lungs of smokers, we identified that the expression of inflammatory signaling genes was correlated with ACE2 expression. Notably, with increasing duration of smoking cessation among ex-smokers, not only ACE2 expression level but also the expression levels of inflammatory signaling genes decreased. These results indicated that smoking enhances the expression levels of ACE2 and inflammatory signaling genes. Our data suggest that the efficiency of SARS-CoV-2 infection is enhanced by smoking-mediated upregulation of ACE2 expression level.

DOI： 10.1111/1348-0421.13034

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BACKGROUND: Congenital portosystemic shunt is an infrequent abnormal connection between the portal vascular system and the systemic circulation. Portosystemic shunts are common findings in patients with cirrhosis, causing gastroesophageal varices, hepatic encephalopathy, and others. However, there is no consensus or literature describing how to manage asymptomatic patients with portosystemic shunts and normal liver. CASE PRESENTATION: The patient was a 39-year-old female who underwent donor right hepatectomy for living donor liver transplantation. The patient was healthy by nature, however, developed hepatic encephalopathy after the surgery due to a development of portosystemic shunt. Portosystemic shunt stole portal blood flow, and imaging modalities revealed narrowing of the portal trunk, representing prolonged depletion of portal blood flow. Balloon-occluded retrograde transvenous obliteration (B-RTO) was performed for occlusion of the portosystemic shunt. B-RTO increased portal blood flow, and hepatic encephalopathy with hyperammonemia was successfully resolved without the outbreak of any other symptom of portal hypertension. CONCLUSIONS: A congenital portosystemic shunt itself is not a contraindication for donor hepatectomy, but perioperative endovascular shunts occlusion or intraoperative ligature of these shunts should be considered.

DOI： 10.1186/s40792-022-01533-3

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The case is a 78-year-old female. A giant liver cyst was pointed out by abdominal echo from 7 years ago, but because the size of the cyst tended to increase, it was decided to operate taking into account the risk of the cyst rupturing. Laparoscopic surgery was started, and the cyst contents did not fluorescent when observed by the indocyanine green (ICG) fluorescence method. Laparoscopic liver cyst fenestration was performed using the ICG fluorescence method, paying attention to the damage to the bile duct excluded by the cyst. The opened cyst was filled with the greater omentum. In this report, we describe that the ICG fluorescence method can evaluate the presence or absence of bile leakage from the hepatic dissection and the running of the bile duct on the inner wall of the cyst, and is considered to contribute to safer laparoscopic liver cyst fenestration.

DOI： 10.1093/jscr/rjac479

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PURPOSE: This study evaluated the reliability, validity, and responsiveness of the Japanese version of the European Organization for Research and Treatment of Cancer (EORTC) QLQ-ELD14 and measured the health-related quality of life (HRQOL) of elderly Japanese patients with cancer aged ≥ 60 and ≥ 70 years. METHODS: The study recruited elderly Japanese patients with cancer aged ≥ 60 (≥ 70) years (n = 1803 [n = 1236]). The EORTC QLQ-ELD14 was evaluated for reliability, validity, responsiveness, and correlations of changes in score between the EORTC QLQ-ELD14 and the EORTC QLQ-C30 before and after the commencement of the COVID-19 pandemic. RESULTS: In both age groups, the proportion of missing items was low (< 3%). Cronbach's α was good at ≥ 0.70, except for two of the seven items. All the intraclass coefficient constants were good at ≥ 0.70. The concurrent validity was good but correlation with the EORTC QLQ-C30 was not strong, except for the hypothesis items. Regarding the assessment of responsiveness, only one item ("maintaining purpose") of the EORTC QLQ-ELD14 worsened (- 6.14 ± 29.20, standard response of mean > 0.2) after the commencement of the COVID-19 pandemic. The changes in score between the EORTC QLQ-ELD14 and the "global health status/QOL" and "summary score" of the EORTC QLQ-C30 had moderate-to-high negative correlations for all items, except two. Hypotheses to evaluate construct validity were accepted at 90%, while responsiveness was accepted at 80%. CONCLUSION: The Japanese version of the EORTC QLQ-ELD14 questionnaire appears to have acceptable reliability, validity, and responsiveness to evaluate HRQOL in elderly Japanese people with cancer.

DOI： 10.1007/s00432-022-04414-2

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

BACKGROUND AND AIM: The risk of hepatocellular carcinoma (HCC) persists in a condition of sustained virologic response (SVR) after hepatitis C virus (HCV) eradication. Comprehensive molecular analyses were performed to test the hypothesis that epigenetic abnormalities present after an SVR play a role in hepatocarcinogenesis. METHODS: Whole-genome methylome and RNA sequencing were performed on HCV, SVR, and healthy liver tissue. Integrated analysis of the sequencing data focused on expression changes in transcription factors and their target genes, commonly found in HCV and SVR. Identified expression changes were validated in demethylated cultured HCC cell lines and an independent validation cohort. RESULTS: The coincidence rates of the differentially methylated regions between the HCV and SVR groups were 91% in the hypomethylated and 71% in the hypermethylated regions in tumorous tissues, and 37% in the hypomethylated and 36% in the hypermethylated regions in non-tumorous tissues. These results indicate that many epigenomic abnormalities persist even after an SVR was achieved. Integrated analysis identified 61 transcription factors and 379 other genes that had methylation abnormalities and gene expression changes in both groups. Validation cohort specified gene expression changes for 14 genes, and gene ontology pathway analysis revealed apoptotic signaling and inflammatory response were associated with these genes. CONCLUSION: This study demonstrates that DNA methylation abnormalities, retained after HCV eradication, affect the expression of transcription factors and their target genes. These findings suggest that DNA methylation in SVR patients may be functionally important in carcinogenesis, and could serve as biomarkers to predict HCC occurrence.

DOI： 10.1002/jgh3.12833

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Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/jgh3.12833

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PURPOSE: To investigate whether the iodine density of liver parenchyma in the equilibrium phase and extracellular volume fraction (ECV) measured by deep learning-based spectral computed tomography (CT) can enable noninvasive liver fibrosis staging. METHOD: We retrospectively analyzed 63 patients who underwent dynamic CT using deep learning-based spectral CT before a hepatectomy or liver transplantation. The iodine densities of the liver parenchyma (I-liver) and abdominal aorta (I-aorta) were independently measured by two radiologists using iodine density images at the equilibrium phase. The iodine-density ratio (I-ratio: I-liver/I-aorta) and CT-ECV were calculated. Spearman's rank correlation analysis was used to evaluate the relationship between the I-ratio or CT-ECV and liver fibrosis stage, and receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic performances of the I-ratio and CT-ECV. RESULTS: The I-ratio and CT-ECV showed significant positive correlations with liver fibrosis stage (ρ = 0.648, p < 0.0001 and ρ = 0.723, p < 0.0001, respectively). The areas under the ROC curve for the CT-ECV were 0.882 (F0 vs ≥ F1), 0.873 (≤F1 vs ≥ F2), 0.848 (≤F2 vs ≥ F3), and 0.891 (≤F3 vs F4). CONCLUSIONS: Deep learning-based spectral CT may be useful for noninvasive assessments of liver fibrosis.

DOI： 10.1016/j.ejrad.2022.110461

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症例は39歳女性で、生体移植のためにドナー肝切除を施行された。合併症はなく、術前MD-CTでは残肝容積は429mL(40.5%)を示し、先天性門脈体循環シャントの拡張が認められた。シャント径は9cmに及び、左胃静脈(LGV)から左腎静脈(LRV)への流入を認めたが、臨床検査所見に異常はなかった。術中所見では肝臓の外観は正常であり、手術時間は320分、推定出血量は245mLで術後経過は良好であった。しかし、術後9日目、活動量低下と記憶障害をきたし、軽度脳症と全身性血中アンモニア高値が検出された。MD-CTでは明らかな門脈血栓はみられなかったが、門脈幹の狭小化と門脈血流の低下を認め、先天性門脈体循環シャントへの盗血が疑われた。さらに、プロトロンビン時間-国際標準化比(PT-INR)とD-ダイマーの上昇が確認されたことから、門脈血流不良による門脈微小血栓の存在が示唆された。このため、右大腿静脈アプローチによるバルーン閉塞下逆行性経静脈的塞栓術(B-RTO)を行うこととし、門脈圧を13mmHgに設定してLGV-LRVシャントを閉塞した。術後、肝性脳症と高アンモニア血症の改善が得られ、PT-INRも正常化しB-RTO施行後9日目に退院となった。6ヵ月後のMD-CTでは門脈幹の拡大と残肝の再生促進が得られていた。

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症例は62歳女性で、軽度の呼吸困難をきたし、胸部X線で両肺野に小結節がみられ、血液検査では異常所見はなく、胸部CTにて左横隔膜の嚢胞性病変、左第11胸椎領域の石灰化を伴う後縦隔胸膜の肥厚、両肺の多発小結節を認めた。悪性疾患の可能性を考慮して左横隔膜と後縦隔の腫瘤に対する切除術を予定したが、喀痰培養で結核菌が検出されたため抗結核治療を開始した。6ヵ月後に培養結果は陰性となったが、横隔膜腫瘤は軽度増大し、後縦隔厚も増加していた。このため、悪性の可能性が高いと判断して手術目的に入院となった。術中所見では横隔膜腫瘤と左下葉との癒着が強固であり、左下葉に対する楔状切除を施行、さらに横隔膜病変周囲の健常筋辺縁を残して単純縫合による再建術を行い、続いて楔状切除とともに後縦隔病変切除術を行った。左横隔膜に生じた膿性液のPCR検査では結核陽性であり、腫瘤を結核腫と診断した。術後経過は良好であり、7日目からイソニアジド、リファンピシン、エタンブトール、ピラジナミドの抗結核治療を開始、10日目に退院となった。その後6ヵ月、無症状で経過し再発は認めていない。

Language：English   Publisher：John Wiley & Sons Australia, Ltd  

ドナー肝でのシンタキシン17(STX17)の発現と移植片の生着率および機能との関連について検討した。2005年10月～2019年4月に生体ドナー肝移植(LDLT)を受けた患者を後ろ向きに調べた。右葉移植片レシピエント143例を対象とし、移植片でのSTX17の発現を調べ、発現量の中央値をカットオフ値として患者を2群に分けた。STX17ノックダウン肝細胞株を用いて、STX17の発現、ミトコンドリア膜電位、細胞増殖の関連を評価した。STX17が低発現の移植片レシピエント(低群73例)は、高発現の移植片レシピエント(高群70例)よりも移植片生着率が有意に低かった(88.9%対100%、p<0.01)。多変量解析で、LDLTの重度合併症である過小グラフト症候群の独立予測因子はSTX17の低発現および脾臓摘出術非施行であった。STX17ノックダウン肝細胞株では脱分極損傷ミトコンドリアの割合が増加し、マイトファジーとATP合成の減少が示唆された。STX17ノックダウン肝細胞株での細胞増殖は有意に減少した。以上より、STX17は肝細胞のマイトファジーとミトコンドリア機能の維持に寄与し、移植片機能障害の予測因子である可能性が考えられた。

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BACKGROUND: Preoperative maximum standardized uptake value (SUVmax) of 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography and serum carcinoembryonic antigen (CEA) have been reported as prognostic factors for lung adenocarcinoma. However, the significance of combined SUVmax and CEA in early-stage lung adenocarcinoma is not well known. METHODS: We retrospectively evaluated the relationship between the combination of SUVmax and CEA and the prognosis of 410 patients with clinical stage IA lung adenocarcinoma who underwent resection. The cutoff values for SUVmax and CEA were determined by receiver operating characteristic curve analysis, and patients were categorized into high SC (SUVmax and CEA) group (SUVmax ≥2.96 and CEA ≥5.3), moderate SC group (either SUVmax <2.96 and CEA ≥5.3 or SUVmax ≥2.96 and CEA <5.3) and low SC group (SUVmax <2.96 and CEA <5.3). RESULTS: Kaplan-Meier curve analysis showed that patients with clinical stage IA lung adenocarcinoma in the high SC group had significantly shorter overall survival (OS) and recurrence-free survival (RFS) than the other groups (p = 0.011 and p < 0.0001, respectively). Multivariate analysis showed that high SC was an independent prognostic factor of OS (p = 0.029) and RFS (p < 0.0001). CONCLUSIONS: High values of SUVmax and CEA were associated with poor OS and RFS in patients with stage IA lung adenocarcinoma. Simultaneous evaluation of SUVmax and CEA may be an effective prognostic marker to determine the optimal treatment strategy of early-stage lung adenocarcinoma.

DOI： 10.1111/1759-7714.14599

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BACKGROUND: Systemic artery to pulmonary vessel fistula (SAPVF) is an uncommon abnormal vascular communication between systemic arteries and the lung parenchyma. It has been reported that the appropriate treatment for SAPVF is embolization or surgical resection. However, in patients such as ours, who have many aberrant vessels or multiple lesions, surgery should be considered as the first-choice treatment. CASE PRESENTATION: This case report describes multiple SAPVFs and huge bullae at the apex of the left lung in a 43-year-old man that were resected completely with the video-assisted thoracoscopic surgery (VATS). The patient had an uneventful postoperative recovery without any complications and was discharged 9 days postoperatively. He had heavy smoking history, and the giant bullae and the diffuse emphysematous change were found in the lung. Therefore, the chronic inflammation may have been present in the thoracic cavity, which caused multiple SAPVFs. CONCLUSIONS: We describe the clinical course and management of the patient with multiple SAPVFs who had no obvious history of surgery, trauma, or various inflammatory or infection diseases. VATS should be the first-choice treatment in patients with many abnormal vessels or multiple lesions.

DOI： 10.1186/s40792-022-01540-4

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AIM: This study aimed to clarify the clinical effects of the indocyanine green (ICG)-fluorescence imaging (FI) technique for determination of liver transection lines during laparoscopic partial liver resection for liver tumors. METHODS: This was a retrospective study including 112 patients who underwent laparoscopic partial liver resection for liver tumors. These enrolled patients were divided into an ICG-FI group (n = 55) and a non-ICG-FI group (n = 57) according to the availability of the ICG-FI. The clinicopathological characteristics of patients between two groups were compared before and after propensity score matching. RESULTS: The ICG-FI and non-ICG-FI groups differed at baseline in terms of ICG retention rate at 15 min. After propensity score matching, two comparable groups of 32 patients each were obtained. The negativity rated of the pathological surgical margins were comparable between the two groups before and after propensity score matching. However, the surgical margins were significantly wider in the ICG-FI group before and after propensity score matching (P = .039 and P = .047, respectively). CONCLUSION: The ICG-fluorescence imaging technique may offer clinical benefits in terms of a secure surgical margin in laparoscopic partial liver resection.

DOI： 10.1002/ags3.12563

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症例は43歳男性。重度の喫煙歴があり現喫煙者でもあった。背部痛と呼吸困難から受診した。経皮的酸素飽和度はroom airで97%であった。胸部造影CTを行ったところ、左肺上葉前区域内で一連なりの拡張血管が腫瘤様構造物を形成しており、全身動脈-肺血管瘻(SAPVF)の所見が示された。またSAPVF近くの肺尖には巨大なブラも存在していた。造影検査では5～15mm大の動脈瘤性構造物が描出され、過剰に発達した血管が左内胸動脈、外側胸動脈、最上胸動脈から起始し、左上肺動脈・静脈に注いでいた。異常血管の数が多く塞栓術は困難と考えられたため胸腔鏡手術を施行した。SAPVFは胸壁に癒着していた。異常血管を胸壁から切り離し、ブラも含めた領域を楔状切除した。また舌区にも別のSAPVFがみられ、これも楔状切除した。術後経過は良好で呼吸困難は少しだけ改善した。6ヵ月後の経過観察でも症状はみられなかった。

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検討対象は肝腫瘍に対して腹腔鏡下肝部分切除を施行した112例で、インドシアニングリーン蛍光画像(ICG-FI)を使用した55例(ICG-FI群)と使用しなかった57例(非ICG-FI群)を後方視的に比較検討した。2群の臨床病理学的因子を、傾向スコアマッチ前後の両方で比較した。ICG-FI群と非ICG-FI群には、ICG15分停滞率に差が認められた。傾向スコアマッチング法により各群より32例を検討対象とした。病理学的断端陰性率は、傾向スコアマッチ前後ともに、両群とも同等であった。傾向スコアマッチ前後ともに、切除断端距離はICG-FI群の方が非ICG-FI群と比較して有意に大きかった(P=0.039、P=0.047)。ICG-FIは、より確実に切除断端陰性とすることに貢献する可能性がある。

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The association of Jumonji domain-containing 6 (JMJD6) with the prognosis of various types of cancer has been demonstrated, except in intrahepatic cholangiocarcinoma (ICC). The present study aimed to clarify the impact of JMJD6 on ICC. The liver specimens of 51 patients who underwent surgery for ICC were analyzed for JMJD6 expression using immunohistochemistry staining. The relationship between clinicopathological factors and JMJD6 expression was investigated. The cellular activity was also evaluated in JMJD6 knocked down cells with Transwell migration assay and viability assay. In the immunohistochemistry staining of clinical samples, high expression of JMJD6 was seen in 32 of 51 samples. High expression was also associated with improved overall survival (OS) and recurrence-free survival (RFS) (P=0.0033 and 0.048, respectively). Further analyses revealed that higher JMJD6 expression was one of the improved independent prognostic factors of OS and RFS. Expression of JMJD6 was knocked down in commercial culture cell lines of ICC, and RNA and protein were extracted to analyze the downstream gene expression using RNA-sequencing and western blotting. JMJD6 knockdown was associated with higher programmed death-ligand 1 (PD-L1) expression in RNA-sequencing and western blotting. In addition, PD-L1 expression was higher in JMJD6 low expression clinical samples when measured using immunohistochemistry staining. In conclusion, high expression of JMJD6 was an independent favorable prognostic factor of ICC. JMJD6 may influence the prognosis of ICC through the regulation of PD-L1 expression.

DOI： 10.3892/mco.2022.2564

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INTRODUCTION: Recently, several meta-analyses have investigated the association between sex and the efficacy of immune checkpoint inhibitors (ICIs) in non-small-cell lung cancer (NSCLC). However, this issue remains controversial, because the results have been inconsistent. Moreover, the effect of sex on outcomes in patients with NSCLC receiving combination chemoimmunotherapy as a first-line therapy is poorly understood. The aim of this study was to examine the association between sex and outcomes in patients with NSCLC receiving combination chemoimmunotherapy as a first-line therapy. METHODS: We searched PubMed and Scopus from database inception to Feb 18, 2022 and performed a systematic review and meta-analysis of randomized and controlled clinical trials investigating ICI+non-ICI vs non-ICI as a first-line therapy in NSCLC. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) for overall survival (OS) and progression-free survival (PFS) in male and female patients were calculated using common and random-effects models. RESULTS: We analyzed 5,830 patients, comprising 4,137 (71.0%) males and 1,693 (29.0%) females, from nine randomized clinical trials. The pooled HR (95%CI) for OS comparing ICI+non-ICI vs non-ICI was 0.80 (0.72-0.87) for males and 0.69 (0.54-0.89) for females. The pooled HR (95%CI) for PFS comparing ICI+non-ICI vs non-ICI was 0.60 (0.55-0.66) for males and 0.56 (0.44-0.70) for females. CONCLUSIONS: In patients with NSCLC receiving combination chemoimmunotherapy as a first-line therapy, a greater improvement in OS and PFS was observed in female patients than in male patients.

DOI： 10.1186/s40001-022-00789-7

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DOI： 10.18888/op.0000002887

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BACKGROUND: Consolidation tumor ratio (CTR) is associated with cancer progression and histological invasiveness in lung adenocarcinoma (LAD). However, little is known about the association between CTR and immune-related factors, including tumor-infiltrating lymphocytes (TILs) density or tumor expression of programmed death ligand 1 (PD-L1) and indoleamine 2,3-dioxygenase 1 (IDO1) in small-sized LAD. METHODS: This study included 258 patients with LAD (<3 cm) who underwent surgery. Patients were assigned to four groups: CTR = 0; 0 < CTR <0.5; 0.5 ≤ CTR <1 (ground-glass opacity [GGO] group); and CTR = 1 (pure-solid group). CD4+ , CD8+ , and FoxP3+ TIL density and PD-L1 and IDO1 tumor expression were assessed by immunohistochemistry. RESULTS: Among the GGO group, CD8+ and FoxP3+ TIL density increased significantly with increasing CTR (p < 0.001 and p < 0.001, respectively). Moreover, PD-L1 and IDO1 expression was significantly higher in the pure-solid group than in the GGO group (p < 0.001 and p < 0.001, respectively). CONCLUSIONS: CTR was correlated with the abundance of CD8+ and FoxP3+ TILs in the GGO group. PD-L1 and IDO1 positivity rates were significantly higher in the pure-solid group than in the GGO group. Increased CTR may be correlated with immunosuppressive condition.

DOI： 10.1111/1759-7714.14524

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Background and Aim: Sarcopenia has received much attention as a poor prognostic factor in various fields, and has also been reported to worsen prognosis in patients with hepatocellular carcinoma (HCC) treated with sorafenib or lenvatinib (LEN). Atezolizumab/bevacizumab (ATZ/BEV) is recommended as first-line drug therapy for unresectable-HCC, but the effect of sarcopenia on patients treated with ATZ/BEV is unknown. Methods: We enrolled 98 patients treated with ATZ/BEV or LEN. Computed tomography performed before the initiation of drug therapy was used to diagnose sarcopenia in accordance with the criteria proposed by the Japanese Society of Hepatology. Patients were divided into two groups based on the presence or absence of sarcopenia in each regimen, and patient characteristics, adverse events, and prognosis were compared. Results: In ATZ/BEV therapy, 57.1% of patients had sarcopenia. The sarcopenia group had significantly more women (P = 0.0125) and more macroscopic vascular invasion (P = 0.0270). Sarcopenia had no significant effect on progression-free survival (PFS) and overall survival (OS). In LEN therapy, 63.4% of patients had sarcopenia. The sarcopenia group was significantly older (P = 0.0064) and had a higher number of women (P = 0.0003), a higher neutrophil-lymphocyte ratio (P = 0.0222), worse albumin-bilirubin grade (P = 0.0087), and worse best response (P = 0.0255). PFS (P = 0.0091) and OS (P = 0.0006) were worse in the sarcopenia group. In multivariate analysis, age (P = 0.0362), lymphocyte-monocyte ratio (P = 0.0365), and sarcopenia (P = 0.0268) were independent prognostic factors for OS. Conclusion: In ATZ/BEV therapy, sarcopenia does not determine prognosis, and therapeutic efficacy can be expected even in cases of sarcopenia.

DOI： 10.1002/jgh3.12777

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The quality and size of liver grafts are critical factors that influence living-donor liver transplantation (LDLT) function and safety. However, the biomarkers used for predicting graft quality are lacking. In this study, we sought to identify unique graft quality markers, aside from donor age, by using the livers of non-human primates. Hepatic gene microarray expression data from young and elderly cynomolgus macaques revealed a total of 271 genes with significantly increased expression in the elderly. These candidate genes were then narrowed down to six through bioinformatics analyses. The expression patterns of these candidate genes in human donor liver tissues were subsequently examined. Importantly, we found that grafts exhibiting up-regulated expression of these six candidate genes were associated with an increased incidence of liver graft failure. Multivariable analysis further revealed that up-regulated expression of LRRN2 (encoding leucine-rich repeat protein, neuronal 2) in donor liver tissue served as an independent risk factor for graft failure (odds ratio 4.50, confidence interval 2.08-9.72). Stratification based on graft expression of LRRN2 and donor age was also significantly associated with 6-month graft survival rates. Conclusion: Up-regulated LRRN2 expression of liver graft is significantly correlated with graft failure in LDLT. In addition, combination of graft LRRN2 expression and donor age may represent a promising marker for predicting LDLT graft quality.

DOI： 10.1002/hep4.2033

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