記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Recently, endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) procedures have been gradually established; nonetheless, some adverse events (AEs) have been reported. Dilation procedures using a non-cautery or cautery device increase the incidence of AEs in EUS-HGS. AIMS: We evaluated EUS-HGS procedures without dilation and the factors associated with dilation. METHODS: We enrolled 79 patients who underwent EUS-HGS between July 2015 and March 2021 at two centers, 72 of whom had technical success (72/79, 91&#37;). During the EUS-HGS procedures, we defined patients without dilation procedures as the dilation (-) group. We divided the patients into two groups: the dilation (+) (35 patients) and dilation (-) (37 patients) groups. We performed a propensity score matching analysis to adjust for confounding bias between the two groups. Multivariable logistic regression analysis was conducted to identify factors associated with dilation. RESULTS: There was no difference in clinical success rate between the dilation (+) and dilation (-) groups (91&#37; vs. 95&#37;, P = 0.545). The AE rate (P = 0.013) and long procedure time (P = 0.017) were significantly higher in the dilation (+) group than in the dilation (-) group before and after propensity score matching. Factors associated with dilation were plastic stent placement (odds ratio [OR], 6.96; 95&#37; confidence interval [CI], 1.68-28.7; P = 0.007) and puncture angle of ≤ 90° (OR, 44.6; 95&#37; CI, 5.1-390; P < 0.001). CONCLUSIONS: A dilation procedure in EUS-HGS may not always be necessary. However, patients with an angle of ≤ 90° between the needle and intrahepatic biliary tract or plastic stent deployment require dilation procedures.

DOI： 10.1007/s10620-022-07555-z

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Endoscopic duodenal stent (DS) placement for malignant gastric outlet obstruction (GOO) is rapidly increasing in clinical practice; however, the most suitable patient candidates for DS placement have not been determined. One hundred and thirty-five patients with GOO who underwent DS placement in three Japanese referral centers between January 2010 and October 2019 were retrospectively evaluated. Overall survival (OS) after DS placement, technical/clinical success rates, adverse events, and predictive factors affecting OS after DS placement were also analyzed. The median OS after DS placement of all patients was 81 (7-901) days. Technical and clinical success rates were 99.3&#37; and 83.7&#37;, respectively. The GOO Scoring System score significantly increased before and after DS placement (0.9 vs. 2.7, P < 0.001). The procedure-related complication rate was 6.0&#37;. All 19 patients (14.1&#37;) with stent occlusion underwent endoscopic re-intervention successfully. Multivariate analyses revealed chemotherapy after DS placement (P = 0.01), stricture site in D3 (distal part of the papilla) (P = 0.01), and a Glasgow Prognostic Score (GPS) of 0-1 before duodenal stent placement (P < 0.001) were factors significantly associated with prolonged OS. In conclusion, patients with a GPS of 0-1 and D3 stricture who are tolerant of chemotherapy are suitable candidates for DS placement.

DOI： 10.1038/s41598-022-13209-x

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.pan.2020.04.003

記述言語：日本語  

DOI： 10.3109/00365521.2015.1083050

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Endoscopy  

DOI： 10.1055/a-2253-1069

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記述言語：英語  

DOI： 10.1055/a-2445-8419

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Endoscopy  

DOI： 10.1055/a-2334-0926

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記述言語：英語   出版者・発行元：Digestive Diseases and Sciences  

Background: Almost all previous reports on endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) involve malignant distal bile duct strictures. However, the feasibility of EUS-HGS for malignant hilar biliary obstruction (MHBO) remains unclear. Aims: This study aimed to evaluate the efficacy and safety of EUS-HGS for MHBO and identify the risk factors associated with technical failure. Methods: In this multicenter retrospective study, we reviewed consecutive patients who underwent EUS-HGS between April 2017 and March 2023 at five institutions. We assessed the overall feasibility and efficacy of EUS-HGS for MHBO, including the factors associated with technical failure, using multivariable logistic regression analysis. Results: A total of 85 patients were enrolled (mean age, 72 years; 36.4% female). Thirty-six patients (42.3%) had surgically altered anatomy, and 43 (50.6%) underwent biliary stenting by transpapillary or percutaneous biliary drainage before EUS-HGS. The rates of technical success, clinical success, and adverse events were 87.0% (74/85), 76.4% (65/85), and 11.8% (10/85), respectively. Multivariable analysis demonstrated that a bile duct diameter ≤ 4 mm was the only independent risk factor for technical failure (odds ratio, 6.12; 95% confidence interval, 1.02–36.6; P = 0.047). The most common reason for technical failure was cholangiography failure (45.4%), followed by inappropriate guidewire position (36.4%). Conclusions: EUS-HGS is a challenging but promising treatment option for MHBO. Patients with a bile duct diameter ≤ 4 mm or inappropriate guidewire position should be careful as these factors can lead to the technical failure of EUS-HGS for MHBO.

DOI： 10.1007/s10620-024-08652-x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Preoperative vascular embolization is an effective strategy for managing meningiomas, neck paragangliomas, renal cell carcinomas, and bone metastasis by reducing the intraoperative bleeding volume and operation time. Although hypervascular tumors also occur in the pancreas, preoperative embolization for these tumors is not commonly practiced. We herein present a case of a giant serous cystic neoplasm (SCN) of the pancreas with significant arterial vascularity that was managed with preoperative interventional radiology and subsequently resected via pancreaticoduodenectomy. CASE PRESENTATION: A 60-year-old man presented with an 8-cm hypervascular tumor located at the head of the pancreas, identified as an SCN on pathologic examination. The tumor had increased by 13 mm over 5 years, necessitating surgical intervention. Computed tomography revealed a substantial blood supply to the tumor from the dorsal pancreatic artery and gastroduodenal artery, both branches of the superior mesenteric artery. To mitigate the risk of severe intraoperative bleeding from this giant hypervascular tumor, branches of the dorsal pancreatic artery and gastroduodenal artery were embolized using metallic coils and further secured using a gelatin sponge 1 day prior to pancreatectomy. During the laparotomy, the tumor appeared to have decreased in size, likely because of reduced distension and congestion. Despite significant adhesions to surrounding tissues secondary to prolonged compression and inflammation, the pancreaticoduodenectomy was completed successfully in 5 h and 15 min with blood loss of 763 mL. The patient was discharged on postoperative day 15 without complications. CONCLUSIONS: Preoperative arterial embolization for hypervascular pancreatic tumors might control the risk of massive intraoperative bleeding, contributing to a favorable postoperative outcome. Utilizing interventional radiology for preoperative inflow control is one of the beneficial strategies for pancreatectomy in patients with a giant SCN.

DOI： 10.1186/s40792-024-02009-2

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Journal of Hepato-Biliary-Pancreatic Sciences  

Background: One advantage of endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) is that it is difficult for reflux cholangitis, caused by duodenal pressure increasing due to duodenal obstruction, to occur. In addition, since stent deployment is performed away from the malignant stricture site, longer stent patency than with endoscopic retrograde cholangiopancreatography (ERCP) may be obtained. However, no study has previously compared EUS-HGS and ERCP for patients without duodenal obstruction or surgically altered anatomy. The aim of the present study was to compare clinical outcomes between EUS-HGS and ERCP in normal anatomy patients without duodenal obstruction. Method: In the ERCP group, patients who initially underwent biliary drainage were included. In the EUS-HGS group, patients who underwent EUS-HGS due to failed biliary cannulation were included. Patients with an inaccessible papilla, such as with surgically altered anatomy or duodenal obstruction, were excluded. Results: A total of 314 patients who underwent ERCP and EUS-HGS were enrolled in this study. Of the 314 patients, 289 underwent biliary stenting under ERCP guidance, and 25 patients underwent biliary stenting under EUS-HGS. After propensity score-matching analysis, the adverse event rate tended to be lower in the EUS-HGS group than in the ERCP group. Although overall survival was not significantly different between the EUS-HGS and ERCP groups (p =.228), stent patency was significantly longer in the EUS-HGS group (median 366.0 days) than in the ERCP group (median 76.5 days). Conclusions: EUS-HGS had a lower adverse event rate, shorter procedure time, and longer stent patency than ERCP in cases of normal anatomy without duodenal obstruction.

DOI： 10.1002/jhbp.12055

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記述言語：英語   出版者・発行元：Clinical Endoscopy  

Background/Aims: Although endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) is performed globally, the procedure remains challenging. Guidewire manipulation is the most difficult step, and there are few reports on the factors associated with unsuccessful guidewire manipulation. This study aimed to assess the significance of the puncture angle on EUS images and identify the most effective guidewire rescue method for patients with unsuccessful guidewire manipulation. Methods: We retrospectively enrolled 115 patients who underwent EUS-HGS between May 2016 and April 2022 at two centers. The puncture angle between the needle and the intrahepatic bile duct was measured through EUS movie records. Results: Guidewire manipulation was unsuccessful in 28 patients. Receiver operating characteristic (ROC) curves identified an optimal puncture angle cutoff value of 85° (cutoff value, 85°; area under the ROC curve, 0.826; sensitivity, 85.7%; specificity, 81.6%). Multivariate analysis demonstrated that a puncture angle <85° was a significant risk factor for unsuccessful guidewire manipulation (odds ratio, 19.8; 95% confidence interval, 6.42-61.5; p<0.001). Among the 28 unsuccessful cases, 24 patients (85.7%) achieved successful guidewire manipulation using various rescue methods. Conclusions: The puncture angle observed on EUS is crucial for guidewire manipulation. A puncture angle of <85° was associated with unsuccessful guidewire manipulation.

DOI： 10.5946/ce.2023.244

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Clinical Journal of Gastroenterology  

Pancreatic acinar cell carcinoma (PACC) is a very rare subtype of pancreatic cancer. Due to small number of patients, no standard chemotherapy protocol has been established. We experienced an extremely rare case of PACC with liver metastasis that showed a pathological complete response after modified FOLFIRINOX (mFFX) therapy. A 42-year-old man who underwent distal pancreatectomy for an 80 mm tumor at the pancreatic tail 3 years ago was referred to our hospital in September 2017 for the treatment of a recurrent liver tumor. Percutaneous biopsy revealed an acinar-neuroendocrine carcinoma, similar to the surgical specimen. He received eight cycles of irinotecan plus cisplatin chemotherapy. However, the tumor increased in size, and treatment was switched to mFFX therapy. The tumor in the liver shrank remarkably after nine cycles of mFFX therapy. Conversion surgery was selected, and the patient underwent hepatic left and caudate lobectomy 8 months after administration of mFFX. The resected specimen showed no viable tumor cells, indicating a pathological complete response. The histological diagnosis was reconsidered, and PACC was finally diagnosed via an additional immunohistological review. The patient has remained well with no recurrence for 6 years after surgery. This study is the first to report a case of pathological complete response with mFFX therapy for the recurrence of PACC.

DOI： 10.1007/s12328-024-01983-2

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Digestive Endoscopy  

DOI： 10.1111/den.14798

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記述言語：その他   掲載種別：研究論文（学術雑誌）   出版者・発行元：Journal of Gastroenterology  

Abstract

Background

Recently, two molecular subtypes of pancreatic ductal adenocarcinoma (PDAC) have been proposed: the “Classical” and “Basal-like” subtypes, with the former showing better clinical outcomes than the latter. However, the “molecular” classification has not been applied in real-world clinical practice. This study aimed to establish patient-derived organoids (PDOs) for PDAC and evaluate their application in subtype classification and clinical outcome prediction.

Methods

We utilized tumor samples acquired through endoscopic ultrasound-guided fine-needle biopsy and established a PDO library for subsequent use in morphological assessments, RNA-seq analyses, and in vitro drug response assays. We also conducted a prospective clinical study to evaluate whether analysis using PDOs can predict treatment response and prognosis.

Results

PDOs of PDAC were established at a high efficiency (> 70&#37;) with at least 100,000 live cells. Morphologically, PDOs were classified as gland-like structures (GL type) and densely proliferating inside (DP type) less than 2 weeks after tissue sampling. RNA-seq analysis revealed that the “morphological” subtype (GL vs. DP) corresponded to the “molecular” subtype (“Classical” vs. “Basal-like”). The “morphological” classification predicted the clinical treatment response and prognosis; the median overall survival of patients with GL type was significantly longer than that with DP type (P < 0.005). The GL type showed a better response to gemcitabine than the DP type in vitro, whereas the drug response of the DP type was improved by the combination of ERK inhibitor and chloroquine.

Conclusions

PDAC PDOs help in subtype determination and clinical outcome prediction, thereby facilitating the bench-to-bedside precision medicine for PDAC.

DOI： 10.1007/s00535-024-02103-0

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その他リンク： https://link.springer.com/article/10.1007/s00535-024-02103-0/fulltext.html

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Japanese Journal of Clinical Oncology  

BACKGROUND: Streptozocin has been used to treat neuroendocrine tumors in Europe and the USA; however, its actual status in Japan has not been fully clarified owing to the rarity of this disease and the relatively recent approval of streptozocin in Japan. METHODS: We retrospectively analyzed 53 patients with gastroenteropancreatic neuroendocrine tumors who were treated with streptozocin-based chemotherapy at two Japanese hospitals between January 2004 and June 2023. RESULTS: The overall response and disease control rates were 27.7 and 74.5&#37;, respectively, and the median progression-free survival and overall survival were 7.1 and 20.3 months, respectively. Performance status ≥1 showed a significant negative correlation with progression-free survival, and performance status ≥1 and liver tumor burden ≥25&#37; showed a significant negative correlation with overall survival. No significant differences were observed in the treatment response between pancreatic and gastrointestinal neuroendocrine tumors. No treatment-related serious adverse events were observed; however, 87.7&#37; of patients expressed a decrease in the estimated glomerular filtration rate, which negatively correlated with the duration of streptozocin treatment (r = 0.43, P = 0.0020). In the streptozocin re-administration group (n = 5), no differences were found in efficacy between the initial and second streptozocin treatments. CONCLUSIONS: Although streptozocin is a safe, streptozocin-induced renal dysfunction is a dilemma in streptozocin responders. Streptozocin may benefit patients with gastroenteropancreatic neuroendocrine tumors, especially those with a good performance status; however, in some cases, planned streptozocin withdrawal or switching to other drugs should be considered.

DOI： 10.1093/jjco/hyae026

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Pancreatic neuroendocrine tumors (PanNETs) are rare malignant tumors that occur in the pancreas. They are divided into functioning and non-functioning tumors based on the presence or absence of their specific hormonal hyper-expression symptoms. Adrenocorticotropic hormone (ACTH)-producing PanNETs are rare, functional tumors, and their clinical characteristics and outcomes have not been well reported.Here, we report the cases of two patients with PanNETs who presented with ectopic ACTH syndrome (EAS) during the course of their disease. Case 1 involved a non-functioning PanNET at the time of surgery. During treatment for recurrent liver metastases, the patient presented with EAS and tumor-associated hypercalcemia, probably due to ACTH and parathyroid hormone-related peptide (PTHrP) production from the liver tumor. Case 2 was a gastrinoma, and similar to Case 1, this patient presented with EAS during the treatment of recurrent liver metastases.It is not uncommon for patients with PanNETs to have multiple hormones and develop secondary hormone secretion during their disease course, although tumor phenotypes differ between primary and metastatic sites. In patients with functioning PanNETs, symptom control with anti-hormonal therapy is essential, in addition to anti-tumor therapy, especially for EAS, which is an endocrine emergency disease that requires prompt diagnosis and treatment.

DOI： 10.1007/s12328-023-01908-5

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND/OBJECTIVES: The association between autoimmune pancreatitis (AIP) and pancreatic cancer (PC) remains controversial. This study aimed to clarify the long-term prognosis and risk of malignancies in AIP patients in Japan. METHODS: We conducted a multicenter retrospective cohort study on 1364 patients with type 1 AIP from 20 institutions in Japan. We calculated the standardized incidence ratio (SIR) for malignancies compared to that in the general population. We analyzed factors associated with overall survival, pancreatic exocrine insufficiency, diabetes mellitus, and osteoporosis. RESULTS: The SIR for all malignancies was increased (1.21 [95 &#37; confidence interval: 1.05-1.41]) in patients with AIP. Among all malignancies, the SIR was highest for PC (3.22 [1.99-5.13]) and increased within 2 years and after 5 years of AIP diagnosis. Steroid use for ≥6 months and ≥50 months increased the risk of subsequent development of diabetes mellitus and osteoporosis, respectively. Age ≥65 years at AIP diagnosis (hazard ratio [HR] = 3.73) and the development of malignancies (HR = 2.63), including PC (HR = 7.81), were associated with a poor prognosis, whereas maintenance steroid therapy was associated with a better prognosis (HR = 0.35) in the multivariate analysis. Maintenance steroid therapy was associated with a better prognosis even after propensity score matching for age and sex. CONCLUSIONS: Patients with AIP are at increased risk of developing malignancy, especially PC. PC is a critical prognostic factor for patients with AIP. Although maintenance steroid therapy negatively impacts diabetes mellitus and osteoporosis, it is associated with decreased cancer risk and improved overall survival.

DOI： 10.1016/j.pan.2024.01.008

記述言語：英語   出版者・発行元：Gastrointestinal Endoscopy  

Background and Aims: EUS-guided biliary drainage (EUS-BD) has shown promising procedural outcomes in high-volume centers. Although inferior procedural outcomes were reported in inexperienced centers during the early days of EUS-BD, the current outcomes are unknown. This study aimed to clarify the feasibility and safety of EUS-BD in centers that recently introduced EUS-BD. Methods: This multicenter retrospective study was conducted at 22 centers that introduced EUS-BD between 2017 and 2022. A maximum of 20 initial EUS-BD cases at each center were evaluated. The clinical outcomes and experience of 84 endoscopists who performed these procedures were examined. Primary outcomes were the rate of technical success and adverse events (AEs), whereas secondary outcomes were risk factors associated with technical failure and procedure-related AEs. Results: Two hundred fifty-five patients were enrolled. The technical success rate was 91.4% (233/255). Among 22 technical failure cases, guidewire manipulation failure was the most common cause (n = 12) followed by tract dilation failure (n = 5). The AE rate was 10.2% (26/255). Multivariate analysis identified a puncture target diameter of <5 mm (odds ratio, 3.719; 95% CI, 1.415-9.776; P = .008) and moderate ascites extending to the liver surface (odds ratio, 3.25; 95% CI, 1.195-8.653; P = .021) as independent risk factors for technical failure and procedure-related AEs, respectively. Endoscopists’ procedural experience was not a risk factor for technical failure or procedure-related AEs. Conclusions: The feasibility and safety of EUS-BD were maintained during the induction phase at inexperienced centers. These data will be helpful to better understand the current status of EUS-BD. (Clinical trial registration number: UMIN 000053615.)

DOI： 10.1016/j.gie.2024.09.014

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記述言語：その他   掲載種別：研究論文（学術雑誌）   出版者・発行元：Gastroenterology Report  

DOI： 10.1093/gastro/goad071

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Endoscopy  

DOI： 10.1055/a-2072-5740

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記述言語：英語   出版者・発行元：Endoscopy  

DOI： 10.1055/a-1959-1500

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記述言語：その他   掲載種別：研究論文（学術雑誌）   出版者・発行元：Digestive Endoscopy  

Objectives

For preoperative biliary drainage (PBD) of malignant hilar biliary obstruction (MHBO), current guidelines recommend endoscopic nasobiliary drainage (ENBD) due to the higher risk of cholangitis after endoscopic biliary stenting (EBS) during the waiting period before surgery. However, few studies have supported this finding. Therefore, we aimed to compare the outcomes of preoperative ENBD and EBS in patients with MHBO.

Methods

Patients with MHBO who underwent laparotomy for radical surgery after ENBD or EBS were included from retrospectively collected data from 13 centers (January 2014 to December 2018). We performed a 1:1 propensity score matching between the ENBD and EBS groups. These patients were compared for the following: cholangitis and all adverse events (AEs) after endoscopic biliary drainage (EBD) until surgery, time to cholangitis development after EBD, postsurgical AEs, and in‐hospital death after surgery.

Results

Of the 414 patients identified, 355 were analyzed in this study (226 for ENBD and 129 for EBS). The matched cohort included 63 patients from each group. The proportion of cholangitis after EBD was similar between the two groups (20.6&#37; vs. 25.4&#37;, P = 0.67), and no significant difference was observed in the time to cholangitis development. The proportions of surgical site infections, bile leaks, and in‐hospital mortality rates were similar between the groups.

Conclusion

For PBD of MHBO, the proportion of AEs, including cholangitis, after EBD until surgery was similar when either ENBD or EBS was used.

DOI： 10.1111/den.14712

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Digestive Endoscopy  

DOI： 10.1111/den.14642

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記述言語：日本語  

膵癌と糖尿病には密接な関連がある。糖尿病は膵癌のリスク因子として古くから知られているが、膵癌発症の結果として糖尿病が出現することがあり、その関連性は双方向である。長期罹患糖尿病ではインスリン抵抗性とそれに伴う高インスリン血症が膵癌発症の機序であると考えられている。一方で膵癌患者ではインスリン抵抗性に加え、膵癌による膵島細胞機能不全によって糖尿病が新規発症するとされている。糖尿病が膵癌発見の契機となることや膵癌治療の予後に影響を与えること、糖尿病治療薬が膵癌発症や予後に影響を与えることも報告されており、膵癌の診断・治療において糖尿病の存在を常に意識することが重要である。(著者抄録)

記述言語：その他   掲載種別：研究論文（学術雑誌）   出版者・発行元：Ovid Technologies (Wolters Kluwer Health)  

DOI： 10.1097/eus.0000000000000006

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記述言語：日本語  

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：European Journal of Radiology  

PURPOSE: To clarify the relationship between extracellular volume (ECV) measured by dual-energy CT (DECT) and efficacy of preoperative neoadjuvant chemotherapy (NAC) in patients with pancreatic ductal adenocarcinoma (PDAC), as compared with single-energy CT (SECT). METHODS: We enrolled 67 patients with PDAC who underwent dynamic contrast-enhanced CT with a dual-energy CT system prior to NAC. Attenuation values were measured on unenhanced and the equilibrium-phase 120-kVp equivalent CT images for PDAC and the aorta. ΔHU-tumor, ΔHU-tumor/ΔHU-aorta, and SECT-ECV were calculated. Iodine densities of the tumor and aorta were measured in the equilibrium phase, and DECT-ECV of the tumor was calculated. Response to NAC was evaluated and the correlation between imaging parameters and response to NAC was statistically assessed. RESULTS: Tumor DECT-ECVs were significantly lower in the response group (n = 7) than in the non-response group (n = 60), with most significant difference (p = 0.0104). DECT-ECV showed highest diagnostic value with an Az value of 0.798. When using the optimal cut off value of DECT-ECV (<26.0 &#37;), sensitivity, specificity, accuracy, positive predictive value, and negative value for predicting response group were 71.4 &#37;, 85.0 &#37;, 83.6 &#37;, 35.7 &#37; and 96.2 &#37;, respectively. CONCLUSION: PDAC with lower DECT-ECV can potentially show better response to NAC. DECT-ECV might be a useful biomarker for predicting response to NAC in patients with PDAC.

DOI： 10.1016/j.ejrad.2023.110756

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Japanese Journal of Clinical Oncology  

Abstract

Objective

JCOG1106, a randomized phase II trial conducted to compare chemoradiotherapy (S-1 concurrent radiotherapy) with (Arm B) or without (Arm A) induction chemotherapy using gemcitabine in patients with locally advanced pancreatic cancer, showed a more favorable long-term survival in Arm A. This study was aimed at exploring whether some subgroups classified by the systemic inflammatory response might derive greater benefit from either treatment.

Methods

All subjects eligible for JCOG1106 were included in this analysis (n = 51/49 in Arm A/B). This exploratory subgroup analysis was performed by Cox regression analysis to investigate the impact of the systemic inflammatory response, as assessed based on the serum C-reactive protein, serum albumin (albumin), Glasgow Prognostic Score and derived neutrophil–lymphocyte ratio, at the baseline on overall survival. P values &amp;lt;0.1 for the interaction were regarded as denoting significant association.

Results

Glasgow prognostic score showed significant treatment interactions for overall survival. Hazard ratios of Arm B to Arm A were 1.35 (95&#37; confidence interval, 0.82–2.23) in the Glasgow Prognostic Score 0 (C-reactive protein ≤10 mg/L and albumin ≥35 g/L) (n = 44/34 in Arm A/B) and 0.59 (95&#37; confidence interval, 0.24–1.50) in the Glasgow Prognostic Score 1/2 (C-reactive protein &amp;gt;10 mg/L and/or albumin &amp;lt;35 g/L) (n = 7/15) (P-interaction = 0.06). C-reactive protein alone and albumin alone also showed significant treatment interactions for overall survival.

Conclusions

Survival benefits of induction chemotherapy in chemoradiotherapy for locally advanced pancreatic cancer were observed in patients with elevated Glasgow Prognostic Score, high C-reactive protein and low albumin. These results suggest that systemic inflammatory response might be considered to apply induction chemotherapy preceding chemoradiotherapy.

DOI： 10.1093/jjco/hyad044

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/den.14535

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Langenbeck's Archives of Surgery  

PURPOSE: The frequency of pancreaticoduodenectomy is increasing in oldest old patients owing to population aging. We aimed to clarify the clinical significance of pancreaticoduodenectomy in patients aged ≥ 80 years with multiple underlying diseases. METHODS: A total of 649 consecutive patients who underwent pancreaticoduodenectomy from April 2010 to March 2021 in our institute were divided into two groups according to their age: ≥ 80 years (51) and ≤ 79 years (598). We compared mortality and morbidity between the groups. The age-related prognosis was analyzed in 302 patients who underwent pancreaticoduodenectomy for pancreatic ductal adenocarcinoma treatment. RESULTS: There were no significant differences in morbidity (Clavien-Dindo classification grade III or higher; P = 0.1300), mortality (P = 0.0786), or postoperative hospital stay (P = 0.5763) between the groups. Patients aged ≥ 80 years, who underwent pancreaticoduodenectomy for pancreatic ductal adenocarcinoma, had shorter overall survival than those aged ≤ 79 years (median survival time, 16.7 months vs. 32.7 months; P = 0.0206). However, the overall survival of patients aged ≥ 80 years who received perioperative chemotherapy was comparable to that of patients aged ≤ 79 years (P = 0.9795). In the multivariate analysis, the absence of perioperative chemotherapy was identified as an independent prognostic factor, while age ≥ 80 years was not. Perioperative chemotherapy was the sole independent prognostic factor in patients aged ≥ 80 years who underwent pancreaticoduodenectomy for pancreatic ductal adenocarcinoma. CONCLUSIONS: Pancreaticoduodenectomy is safe for patients aged ≥ 80 years. The survival benefits of pancreaticoduodenectomy for patients with pancreatic ductal adenocarcinoma aged ≥ 80 years might be limited to those who can receive perioperative chemotherapy.

DOI： 10.1007/s00423-023-02843-2

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Journal of Gastrointestinal Surgery  

PURPOSE: To evaluate the clinical significance of 18F-fluorodeoxyglucose positron emission tomography/computed tomography in patients with pancreatic ductal adenocarcinoma who underwent neoadjuvant therapy. METHODS: Among 285 consecutive patients who underwent pancreatic resection for pancreatic ductal adenocarcinoma between 2015 and 2021, 86 who underwent preoperative 18F-fluorodeoxyglucose positron emission tomography/computed tomography after completion of neoadjuvant treatment were reviewed. Among preoperative factors, including post-treatment maximum standardized uptake value, predictors of early recurrence and poor prognosis were identified using multivariate analysis for decision making in surgery. RESULTS: Nineteen (22&#37;) patients with pancreatic ductal adenocarcinoma demonstrated high maximum standardized uptake (≥ 4.5). High post-treatment maximum standardized uptake (≥ 4.5) predicted early recurrence within 6 months after surgery and correlated with shorter recurrence-free survival. Elevated post-treatment CA19-9 level (> 37 U/ml) and maximum standardized uptake ≥ 4.5 were independent prognostic factors. Post-treatment, a high maximum standardized uptake value indicated a poorer prognosis than a low maximum standardized uptake value in both patients with elevated CA19-9 and normal CA19-9 levels. The median overall survival in patients with elevated post-treatment CA19-9 and high maximum standardized uptake was only 17 months; 67&#37; experienced early recurrence. Dynamic changes in maximum standardized uptake during neoadjuvant therapy were correlated with pathological response to neoadjuvant therapy, but not with radiological response or change in CA19-9 level. CONCLUSIONS: Post-treatment assessment using maximum standardized uptake value is useful for stratifying patients with pancreatic ductal adenocarcinoma who will benefit from surgery. Instead of subsequent curative resection, additional neoadjuvant therapy should be considered in patients with a persistently high maximum standardized uptake value.

DOI： 10.1007/s11605-023-05591-2

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出版者・発行元：The Lancet  

Background: S-1 has shown promising efficacy with a mild toxicity profile in patients with advanced biliary tract cancer. The aim of this study was to evaluate whether adjuvant S-1 improved overall survival compared with observation for resected biliary tract cancer. Methods: This open-label, multicentre, randomised phase 3 trial was conducted in 38 Japanese hospitals. Patients aged 20–80 years who had histologically confirmed extrahepatic cholangiocarcinoma, gallbladder carcinoma, ampullary carcinoma, or intrahepatic cholangiocarcinoma in a resected specimen and had undergone no local residual tumour resection or microscopic residual tumour resection were randomly assigned (1:1) to undergo observation or to receive S-1 (ie, 40 mg, 50 mg, or 60 mg according to body surface area, orally administered twice daily for 4 weeks, followed by 2 weeks of rest for four cycles). Randomisation was performed by the minimisation method, using institution, primary tumour site, and lymph node metastasis as adjustment factors. The primary endpoint was overall survival and was assessed for all randomly assigned patients on an intention-to-treat basis. Safety was assessed in all eligible patients. For the S-1 group, all patients who began the protocol treatment were eligible for a safety assessment. This trial is registered with the University hospital Medical Information Network Clinical Trials Registry (UMIN000011688). Findings: Between Sept 9, 2013, and June 22, 2018, 440 patients were enrolled (observation group n=222 and S-1 group n=218). The data cutoff date was June 23, 2021. Median duration of follow-up was 45·4 months. In the primary analysis, the 3-year overall survival was 67·6% (95% CI 61·0–73·3%) in the observation group compared with 77·1% (70·9–82·1%) in the S-1 group (adjusted hazard ratio [HR] 0·69, 95% CI 0·51–0·94; one-sided p=0·0080). The 3-year relapse-free survival was 50·9% (95% CI 44·1–57·2%) in the observation group compared with 62·4% (55·6–68·4%) in the S-1 group (HR 0·80, 95% CI 0·61–1·04; two-sided p=0·088). The main grade 3–4 adverse events in the S-1 group were decreased neutrophil count (29 [14%]) and biliary tract infection (15 [7%]). Interpretation: Although long-term clinical benefit would be needed for a definitive conclusion, a significant improvement in survival suggested adjuvant S-1 could be considered a standard of care for resected biliary tract cancer in Asian patients. Funding: The National Cancer Center Research and the Ministry of Health, Labour, and Welfare of Japan.

DOI： 10.1016/S0140-6736(22)02038-4

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記述言語：その他   掲載種別：研究論文（学術雑誌）   出版者・発行元：Endoscopic Ultrasound  

DOI： 10.4103/eus-d-21-00213

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND AND OBJECTIVES: Although the use of a long metal stent is favored for EUS-guided hepaticogastrostomy (EUS-HGS) for the relief of malignant biliary obstruction (MBO), endoscopic reintervention (E-RI) at the time of recurrent biliary obstruction (RBO) is challenging due to a long intragastric portion. This study evaluated the feasibility and safety of E-RI after a long partially covered metal stent (L-PCMS) placement during EUS-HGS. MATERIALS AND METHODS: We performed a multicenter retrospective study between January 2015 and December 2019 examining patients with MBO who underwent E-RI for RBO through the EUS-HGS route after the L-PCMS placement. Technical and clinical success rates, details of E-RI, adverse events (AEs), stent patency, and survival time were evaluated. RESULTS: Thirty-three patients at eight referral centers in Japan who underwent E-RI through the EUS-HGS route were enrolled. The location of MBO was distal in 54.5&#37;. The median intragastric length of the L-PCMS was 5 cm. As the first E-RI attempt, E-RI via the distal end of the existing L-PCMS was successful in 60.6&#37;. The overall technical and clinical success rates of E-RI were 100&#37; and 81.8&#37;, respectively. Liver abscess was noted in one patient. A proximal biliary stricture was associated with the clinical ineffectiveness of E-RI in multivariable analysis (odds ratio, 12.5, P = 0.04). The median survival and stent patency duration after E-RI were 140 and 394 days, respectively. CONCLUSIONS: Our study findings suggest that E-RI for RBO after EUS-HGS with a L-PCMS is technically feasible and clinically effective, without any severe AEs, especially for patients with distal MBO.

DOI： 10.4103/EUS-D-22-00029

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：European Journal of Cancer  

AIM: We compared the efficacy of modified 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin (mFOLFIRINOX) with that of gemcitabine plus nab-paclitaxel (GnP) for locally advanced pancreatic cancer (LAPC). METHODS: Patients with untreated LAPC were randomly assigned (1:1) to receive mFOLFIRINOX or GnP. One-year overall survival (OS) was the primary endpoint. The major secondary end-points included progression-free survival (PFS), response rate (RR), carbohydrate antigen 19-9 (CA19-9) response, and adverse events. The sample size was 124 patients to select a more effective regimen with a minimum probability of 0.85 and to examine the null hypothesis of the 1-year OS <53&#37;. RESULTS: Of the 126 patients enrolled from 29 institutions, 125 were deemed eligible. The 1-year OS was 77.4&#37; (95&#37; CI, 64.9-86.0) and 82.5&#37; (95&#37; CI, 70.7-89.9) in the mFOLFIRINOX and GnP arms, respectively. The median PFS was 11.2 (95&#37; CI, 9.9-15.9) and 9.4 months (95&#37; CI, 7.4-12.8) in the mFOLFIRINOX and GnP arms, respectively. The RR and CA19-9 response rate were 30.9&#37; (95&#37; CI, 19.1-44.8) and 57.1&#37; (95&#37; CI, 41.0-72.3) and 42.1&#37; (95&#37; CI 29.1-55.9) and 85.0&#37; (95&#37; CI, 70.2-94.3) in the mFOLFIRINOX and GnP arms, respectively. Grade 3-4 diarrhoea and anorexia were predominant in the mFOLFIRINOX arm. CONCLUSION: GnP was considered the candidate for a subsequent phase III trial because of its better RR, CA19-9 response, and mild gastrointestinal toxicities. Both regimens displayed higher efficacy in the 1-year survival than in the historical data of gemcitabine monotherapy.

DOI： 10.1016/j.ejca.2022.12.014

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND AND OBJECTIVES: Although the use of a long metal stent is favored for EUS-guided hepaticogastrostomy (EUS-HGS) for the relief of malignant biliary obstruction (MBO), endoscopic reintervention (E-RI) at the time of recurrent biliary obstruction (RBO) is challenging due to a long intragastric portion. This study evaluated the feasibility and safety of E-RI after a long partially covered metal stent (L-PCMS) placement during EUS-HGS. MATERIALS AND METHODS: We performed a multicenter retrospective study between January 2015 and December 2019 examining patients with MBO who underwent E-RI for RBO through the EUS-HGS route after the L-PCMS placement. Technical and clinical success rates, details of E-RI, adverse events (AEs), stent patency, and survival time were evaluated. RESULTS: Thirty-three patients at eight referral centers in Japan who underwent E-RI through the EUS-HGS route were enrolled. The location of MBO was distal in 54.5&#37;. The median intragastric length of the L-PCMS was 5 cm. As the first E-RI attempt, E-RI via the distal end of the existing L-PCMS was successful in 60.6&#37;. The overall technical and clinical success rates of E-RI were 100&#37; and 81.8&#37;, respectively. Liver abscess was noted in one patient. A proximal biliary stricture was associated with the clinical ineffectiveness of E-RI in multivariable analysis (odds ratio, 12.5, P = 0.04). The median survival and stent patency duration after E-RI were 140 and 394 days, respectively. CONCLUSIONS: Our study findings suggest that E-RI for RBO after EUS-HGS with a L-PCMS is technically feasible and clinically effective, without any severe AEs, especially for patients with distal MBO.

DOI： 10.4103/EUS-D-22-00029

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Nature Communications  

MHC class I-related protein 1 (MR1) is a metabolite-presenting molecule that restricts MR1-reactive T cells including mucosal-associated invariant T (MAIT) cells. In contrast to MAIT cells, the function of other MR1-restricted T cell subsets is largely unknown. Here, we report that mice in which a T cell-specific transcription factor, B-cell lymphoma/leukemia 11B (Bcl11b), was ablated in immature thymocytes (Bcl11b∆iThy mice) develop chronic inflammation. Bcl11b∆iThy mice lack conventional T cells and MAIT cells, whereas CD4+IL-18R+ αβ T cells expressing skewed Traj33 (Jα33)+ T cell receptors (TCR) accumulate in the periphery, which are necessary and sufficient for the pathogenesis. The disorders observed in Bcl11b∆iThy mice are ameliorated by MR1-deficiency, transfer of conventional T cells, or germ-free conditions. We further show the crystal structure of the TCR expressed by Traj33+ T cells expanded in Bcl11b∆iThy mice. Overall, we establish that MR1-reactive T cells have pathogenic potential.

DOI： 10.1038/s41467-022-34802-8

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Gastrointestinal Endoscopy  

INTRODUCTION: Endoscopic ultrasound guided fine-needle aspiration/biopsy (EUS-FNA/B) is the gold standard for diagnosing subepithelial lesions (SELs); however, its diagnostic ability for SELs <20 mm is low. We developed a new diagnostic method to differentiate between gastrointestinal stromal tumor (GIST) and non-GIST by measuring high-frequency impedance (H-impedance) using an EUS-FNB needle. METHODS: The H-impedance of gastric epithelial neoplasms from 16 cases were measured using a conventional impedance probe to confirm whether H-impedance is clinically useful for assessing cell density (Study 1). The H-impedance values of exposed SELs from 25 cases using the conventional probe (Study 2) and non-exposed SELs from 20 cases using the EUS-FNB needle probe (Study 3) were measured to determine the diagnostic ability of H-impedance for differentiating GISTs from non-GISTs. RESULTS: H-impedance significantly positively correlated with cell density (P=0.030) (Study 1). The H-impedance of GIST (99.5) measured using conventional probe was significantly higher than those of the muscular layer (82.4) and leiomyoma (89.2) (P<0.01) (Study 2). The H-impedance of GIST measured using the EUS-FNB needle was also significantly higher than that of leiomyoma (GIST: 80.2 vs. leiomyoma: 71.8, P=0.015). The diagnostic yield of the impedance method for differentiating GISTs from non-GISTs had 94.4&#37; accuracy, 88.9&#37; sensitivity, 100&#37; specificity, and 0.95 area under the curve. Diagnostic ability was not affected by lesion size (P=0.86) (Study 3). CONCLUSION: Auxiliary differential diagnosis between gastric GISTs and non-GISTs by the H-impedance measurement during EUS-FNB could be a good option especially when the lesion is smaller than 20 mm.

DOI： 10.1016/j.gie.2022.11.022

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Endoscopy  

DOI： 10.1055/a-1937-9781

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記述言語：その他   掲載種別：研究論文（学術雑誌）   出版者・発行元：Digestive Diseases and Sciences  

Background: The appropriate method of preoperative endoscopic biliary drainage (EBD) for cholangiocarcinoma with hilar biliary obstruction remains controversial. The inside-stent technique is a method of placing plastic stents entirely inside the bile duct. Several studies of patients with unresectable stage have reported longer stent patency compared with conventional endoscopic biliary stenting (EBS). Inside-stent techniques have been introduced as a bridge-to-surgery option and as an alternative to conventional EBS. Aims: We aimed to evaluate the clinical outcomes of inside stent use and conventional EBS. Methods: During this retrospective multicenter study, we reviewed consecutive patients with cholangiocarcinoma who underwent radical surgery after conventional EBS or inside-stent insertion. Adverse event (AE) rates after EBD and post-surgical AEs were compared. A multivariable analysis was performed to identify factors affecting cholangitis after EBD. Results: Conventional EBS and inside-stent procedures were performed for 56 and 73 patients, respectively. Patient backgrounds were similar between groups, except for percutaneous transhepatic portal vein embolization. The waiting time before surgery was similar between groups (28.5 days vs. 30 days). There were no significant differences in the cholangitis rate (21.4% vs. 26.0%; P = 0.68) and all AEs (25.0% vs. 30.1%; P = 0.56) between groups. The post-surgical AE rate was similar between the groups. The multivariable analysis found that preprocedural cholangitis was a risk factor for cholangitis after EBD (odds ratio: 5.67; 95% confidence interval: 1.61–19.9). Conclusions: The outcomes of inside-stent techniques and conventional EBS for the management of preoperative EBD are comparable for patients with cholangiocarcinoma.

DOI： 10.1007/s10620-022-07718-y

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その他リンク： https://link.springer.com/article/10.1007/s10620-022-07718-y/fulltext.html

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background/Aims: Patients with acute cholecystitis (AC) after metallic stent (MS) placement for malignant biliary obstruction (MBO) have a high surgical risk. We performed percutaneous transhepatic gallbladder aspiration (PTGBA) as the first treatment for AC. We aimed to identify the risk factors for AC after MS placement and the poor response factors of PTGBA. Methods: We enrolled 401 patients who underwent MS placement for MBO between April 2011 and March 2020. The incidence of AC was 10.7&#37;. Of these 43 patients, 37 underwent PTGBA as the first treatment. The patients' responses to PTGBA were divided into good and poor response groups. Results: There were 20 patients in good response group and 17 patients in poor response group. Risk factors for cholecystitis after MS placement included cystic duct obstruction (p<0.001) and covered MS (p<0.001). Cystic duct obstruction (p=0.003) and uncovered MS (p=0.011) demonstrated significantly poor responses to PTGBA. Cystic duct obstruction is a risk factor for cholecystitis and poor response factor for PTGBA, whereas covered MS is a risk factor for cholecystitis and an uncovered MS is a poor response factor of PTGBA for cholecystitis. Conclusions: The onset and poor response factors of AC after MS placement were different between covered and uncovered MS. PTGBA can be a viable option for AC after MS placement, especially in patients with covered MS.

DOI： 10.5946/ce.2021.244

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Scientific Reports  

Gastrointestinal stromal tumors (GISTs) are common subepithelial lesions (SELs) and require treatment considering their malignant potential. We recently developed an endoscopic ultrasound-based artificial intelligence (EUS-AI) system to differentiate GISTs from non-GISTs in gastric SELs, which were used to train the system. We assessed whether the EUS-AI system designed for diagnosing gastric GISTs could be applied to non-gastric GISTs. Between January 2015 and January 2021, 52 patients with non-gastric SELs (esophagus, n = 15; duodenum, n = 26; colon, n = 11) were enrolled. The ability of EUS-AI to differentiate GISTs from non-GISTs in non-gastric SELs was examined. The accuracy, sensitivity, and specificity of EUS-AI for discriminating GISTs from non-GISTs in non-gastric SELs were 94.4&#37;, 100&#37;, and 86.1&#37;, respectively, with an area under the curve of 0.98 based on the cutoff value set using the Youden index. In the subanalysis, the accuracy, sensitivity, and specificity of EUS-AI were highest in the esophagus (100&#37;, 100&#37;, 100&#37;; duodenum, 96.2&#37;, 100&#37;, 0&#37;; colon, 90.9&#37;, 100&#37;, 0&#37;); the cutoff values were determined using the Youden index or the value determined using stomach cases. The diagnostic accuracy of EUS-AI increased as lesion size increased, regardless of lesion location. EUS-AI based on gastric SELs had good diagnostic ability for non-gastric GISTs.

DOI： 10.1038/s41598-022-20863-8

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Journal of Hepato-Biliary-Pancreatic Sciences  

BACKGROUND: We attempted to determine the indications and limitations of steroid therapy as the 1st line therapy in patients with autoimmune pancreatitis (AIP) with cyst formation (ACF). METHODS: This Japanese multicenter survey was conducted to examine the merits/demerits of steroid treatment as the initial therapy for ACF. RESULT: Data of a total of 115 patients with ACF were analyzed. Complete remission was achieved in 86&#37; (86/100) of patients who had received steroid treatment, but only 33.3&#37; (5/15) of patients who had not received steroids. Relapse after the remission (n=86) occurred in 7.6&#37; (6/86) of patients who had received steroid therapy, but 40&#37; (2/5) of patients who had not received steroid therapy. Multivariate analysis identified adoption of the wait&watch approach without steroid treatment (odds ratio=0.126, p<0.001) as a significant and independent negative predictor of remission of ACF. As for predictors of relapse, the presence of varix (odds ratio=5.83, p=0.036) was identified as an independent risk factor. CONCLUSION: Steroid therapy plays an important role as 1st line therapy in AIP patients with pancreatic cyst formation, however, varix formation, besides the diameter of the cyst(s), is a risk factor for refractoriness to steroid therapy.

DOI： 10.1002/jhbp.1227

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Mucosal incision-assisted biopsy (MIAB) is a valuable alternative to endoscopic ultrasound-guided fine-needle aspiration/biopsy (EUS-FNAB) for sampling gastric subepithelial lesions (SELs). This study aimed to evaluate the potential risk of dissemination and impact on postoperative prognosis associated with MIAB, which has not yet been investigated. METHODS: Study 1: A prospective observational study was conducted to examine the presence or absence and growth rate of tumor cells in gastric juice before and after the procedure in patients with SELs who underwent MIAB (n = 25) or EUS-FNAB (n = 22) between September 2018 and August 2021. Study 2: A retrospective study was conducted to examine the impact of MIAB on postoperative prognosis in 107 patients with gastrointestinal stromal tumors diagnosed using MIAB (n = 39) or EUS-FNAB (n = 68) who underwent surgery between January 2001 and July 2020. RESULTS: In study 1, although no tumor cells were observed in gastric juice in MIAB before the procedure, they were observed in 64&#37; of patients after obtaining samples (P < 0.001). In contrast, no tumor cells were observed in the gastric juice in EUS-FNAB before and after the procedure. In study 2, there was no significant difference in 5-year disease-free survival between MIAB (100&#37;) and EUS-FNAB (97.1&#37;) (P = 0.27). CONCLUSION: MIAB is safe, with little impact on postoperative prognosis, although the procedure releases some tumor cells after damaging the SEL's pseudocapsule.

DOI： 10.1007/s00464-022-09419-z

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：一般社団法人 日本内分泌学会  

VIPomas are generally rare functioning pancreatic neuroendocrine tumors (PanNETs) that cause watery diarrhea, hypokalemia, and achlorhydria. Due to their extreme rarity, the clinicopathological features and outcomes of VIPomas have not been well reported. This study aimed to determine the diagnostic and therapeutic characteristics and prognosis of VIPomas and to compare them with other PanNETs at a Japanese reference hospital. Medical records of 293 patients with PanNETs were collected. Patient and tumor characteristics and outcomes were retrospectively reviewed. This cohort had only 1.4&#37; (four patients) of patients with VIPomas, and three of these patients changed from non-functioning (NF-) PanNETs during their disease course. Recurrences of hormonal symptoms were observed in all patients despite the initial controls, and all of them died from their disease, more specifically mainly from hormonal symptoms. Compared to the other PanNETs, VIPomas were all located at the pancreatic tail, were larger, and had a higher Ki-67 index and more metastasis. The median survival time was significantly shorter for patients with VIPoma than for those with NF-PanNET (5.9 vs. 26.7 years, p < 0.0001), insulinoma (21.8 years, p < 0.0001), and gastrinoma (12.3 years, p = 0.0325). This study presents the possibility of shifting from non-symptomatic to symptomatic VIPomas as they grow or of transforming from NF-PanNETs to VIPomas. VIPomas should be considered in patients with relatively large NF-PanNETs, especially those located in the pancreatic tail, when diarrhea is continuously observed. As hormonal symptoms are an important cause of death in VIPomas, long-term symptomatic control, which is relatively difficult, is of great significance.

DOI： 10.1507/endocrj.EJ22-0111

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Therapeutic Advances in Gastroenterology  

Background: Several studies have suggested that elderly patients, as well as younger patients, can be safely treated using endoscopic retrograde cholangiopancreatography (ERCP). However, endoscopic ultrasound-guided biliary drainage (EUS-BD) has not been clinically evaluated for very elderly patients. The present multicenter, retrospective study aimed to determine the safety of EUS-BD for advanced elderly patients. Method: Patients who underwent EUS-BD during this period were retrospectively enrolled, and they were divided into two groups based on age: group A (age  < 75 years) and group B (age ⩾ 75). In this study, capnographic monitoring was used only for elderly patients (age ⩾ 75 years). Results: A total of 271 patients who underwent EUS-BD were enrolled in this study (group A = 177, group B = 94). The types of adverse events that were associated with EUS-BD was observed in 38 patients, and they did not differ significantly between two groups (p = 0.855). This result was confirmed after propensity score matching (p = 0.510). Adverse events were associated with sedation after propensity score matching; hypoxemia (p = 0.012) and severe hypoxemia (p = 0.003) were significantly higher in group A compared with group B. According to logistic regression analysis, monitoring (non-capnography) was also only risk factor (odds ratio: 0.317, 95&#37; confidence interval: 0.143-0.705; p = 0.005) for sedation-related adverse events. Conclusion: In conclusion, EUS-BD could be safety performed in advanced elderly patients, the same as in younger patients. Also, capnographic monitoring might be helpful in case of sedation by a gastroenterologist in a non-intubated patient. Further prospective, randomized studies are needed to confirm these conclusions.

DOI： 10.1177/17562848221092612

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記述言語：英語  

DOI： 10.1111/den.14283

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Digestive Endoscopy  

OBJECTIVES: Endoscopic ultrasound-guided tissue acquisition (EUS-TA) plays a crucial role in the diagnosis of pancreatic tumors. The present study aimed to investigate the current status of needle tract seeding (NTS) after EUS-TA of pancreatic tumors based on a nationwide survey in Japan. METHODS: Patients who underwent surgical resection of primary pancreatic tumors after EUS-TA performed between April 2010 and March 2018 were surveyed. The incidence rates of NTS were determined, and compared in patients with pancreatic ductal adenocarcinomas (PDACs) and other tumors, and in patients who underwent transgastric and transduodenal EUS-TA of PDACs. The detailed features and prognosis of patients with NTS were also assessed. RESULTS: A total of 12,109 patients underwent surgical resection of primary pancreatic tumors after EUS-TA. The overall incidence rate of NTS was 0.330&#37;, and the NTS rate was significantly higher in patients with PDAC than in those with other tumors (0.409&#37; vs. 0.071&#37;, P=0.004). NTS was observed in 0.857&#37; of patients who underwent transgastric EUS-TA, but in none of those who underwent transduodenal EUS-TA. Of the patients with NTS of PDACs, the median time from EUS-TA to occurrence of NTS and median patient survival were 19.3 and 44.7 months, respectively, with 97.4&#37; of NTS located in the gastric wall and 65.8&#37; of NTS resected. The patient survival was significantly longer in patients who underwent NTS resection than in those without NTS resection (P=0.037). CONCLUSIONS: NTS appeared only after transgastric not after transduodenal EUS-TA. Careful follow-up provides an opportunity to remove localized NTS lesions by gastrectomy.

DOI： 10.1111/den.14346

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Digestive Diseases  

BACKGROUND: Neuroendocrine neoplasms of the ampulla of Vater (ampullary NEN) have features of both gastrointestinal and pancreato-biliary (PB) NEN. However, the limited number of studies examining ampullary NEN makes it difficult to clarify their unique characteristics. This study aimed to elucidate the clinical characteristics of ampullary NEN. METHODS: We enrolled 162 patients with PB-NEN diagnosed at Kyushu University Hospital between 2011 and 2020. Clinical features, pathological diagnoses, treatments, and prognoses were retrospectively analyzed. We also compared ampullary NEN with pancreatic NEN (PanNEN). RESULTS: We analyzed 10 ampullary NEN cases and 149 PanNEN cases. The ampullary NEN cases consisted of four cases of NET G1 (neuroendocrine tumor Grade 1), one NET G2 (Grade 2), and five NECs (neuroendocrine carcinoma). The incidences of NEC and cholangitis were significantly higher in ampullary NEN than in PanNEN. All ampullary NETs had a submucosal tumor-like appearance, as identified by endoscopic ultrasound-guided fine needle aspiration. We treated small NET G1 (<10 mm) with endoscopic papillectomy and large NET G1 with pancreaticoduodenectomy. There were no cases of recurrence after resection. All ampullary NECs presented with the characteristic endoscopic finding of a ''crater sign" similar to deep-mining ulcers seen in gastric malignant lymphoma. Four cases underwent surgical resection, and one case was unresectable. Two patients who underwent multidisciplinary treatment were maintained without recurrence for over 2 years. CONCLUSIONS: Endoscopic findings showed identifiable distinctions between ampullary NETs and NECs.

DOI： 10.1159/000525013

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Discover Oncology  

BACKGROUND/AIMS: Recently neoadjuvant chemotherapy (NAC) for pancreatic cancer has been shown to be superior to upfront surgery, but it remains a matter of debate for resectable cases. In clinical practice, some resectable cases may become unresectable after NAC. This study aimed to reveal the outcomes after NAC and to clarify the characteristics of unresected cases. METHODS: The medical records of 142 patients who underwent NAC between 2016 and 2020 were retrospectively reviewed. Patient characteristics, effectiveness of NAC, and outcomes were compared between the surgical group and non-surgical group (NSG). Furthermore, the risk of recurrence limited to in the patients who received NAC with gemcitabine plus nab-paclitaxel, which were mostly administered in this cohort, following R0/R1 resection was assessed. RESULTS: The overall and R0 resection rates after NAC were 89.1&#37; and 79.7&#37;, respectively. The neutrophil to lymphocyte ratio (NLR) > 2.78 (p = 0.0120) and anatomical borderline resectable pancreatic cancer (p = 0.0044) revealed a statistically significantly correlation with the NSG. On the other hand, NAC week < 8 (p = 0.0285), radiological response, stable disease or progression disease (p = 0.0212), and pathological stage > IIA (P = 0.0003) were significantly associated with recurrence. The tumor response rate was approximately 26.1&#37;, and three patients with ≥ 30&#37; reduction of primary tumor lost excision opportunities because of metastasis, interstitial pneumonia, and vascular invasion. CONCLUSIONS: This study shows incomplete tumor shrinkage benefits, but pre-NAC NLR is a predictive factor for predicting operability after NAC. The NLR can be easily calculated by normal blood test, and can be considered as a suitable marker of operability.

DOI： 10.1007/s12672-021-00462-1

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記述言語：その他   掲載種別：研究論文（学術雑誌）  

<title>Abstract</title><sec>
<title>Background</title>
The pathological conditions of UC and CD involved in inflammatory bowel disease-unclassified (IBD-U), UC with primary sclerosing cholangitis (PSC-UC), and UC with autoimmune pancreatitis type 2 (AIP-UC) remain unclear. Therefore, it is difficult to decide the appropriate treatments for these subtypes of UC. Our aim was to examine whether the discriminant equation using the mucosally expressed mediators designed as our previous study for IBD, could characterize IBD-U, PSC-UC, or AIP-UC.


</sec><sec>
<title>Methods</title>
A total of 56 patients including UC (n = 24), CD (n = 15), IBD-U (n = 10), PSC-UC (n = 4), and AIP-UC (n = 3), along with 9 control patients were enrolled in this study. Mucosally expressed inflammatory mediators related to Th1, Th2, Th17, and Treg were measured using quantitative PCR in endoscopic biopsies from the inflamed intestines of the patients. The IBD-U, PSC-UC or AIP-UC were characterized using discriminant analysis and principle component analysis.


</sec><sec>
<title>Results</title>
Through discriminant analyses, combinations of 3 to 7 inflammatory mediators were used to discriminate between UC and CD. Moreover, the identified 3 markers could diagnose patients with IBD-U as UC or CD with high accuracy. The distribution graph of inflammatory mediators using the principal component analysis revealed that PSC-UC and AIP-UC exhibited CD-like and UC-like features, respectively.


</sec><sec>
<title>Conclusions</title>
The discriminant equation using mucosally expressed mediators of IL-13, IL-21 and T-bet can be used as a universal diagnostic tool not only for IBD-U but also to assess pathological conditions in PSC-UC and AIP-UC.


</sec>

DOI： 10.1186/s12876-021-01656-1

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1055/a-1711-4161

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Neuroendocrine neoplasms (NENs) are rare neoplasms that occur in various organs and present with diverse clinical manifestations. Pathological classification is important in the diagnosis of NENs. Treatment strategies must be selected according to the status of differentiation and malignancy by accurately determining whether the neoplasm is functioning or nonfunctioning, degree of disease progression, and presence of metastasis. The newly revised Clinical Practice Guidelines for Gastroenteropancreatic Neuroendocrine Neoplasms (GEP-NENs) comprises 5 chapters-diagnosis, pathology, surgical treatment, medical and multidisciplinary treatment, and multiple endocrine neoplasia type 1 (MEN1)/von Hippel-Lindau (VHL) disease-and includes 51 clinical questions and 19 columns. These guidelines aim to provide direction and practical clinical content for the management of GEP-NEN preferentially based on clinically useful reports. These revised guidelines also refer to the new concept of "neuroendocrine tumor" (NET) grade 3, which is based on the 2017 and 2019 WHO criteria; this includes health insurance coverage of somatostatin receptor scintigraphy for NEN, everolimus for lung and gastrointestinal NET, and lanreotide for GEP-NET. The guidelines also newly refer to the diagnosis, treatment, and surveillance of NEN associated with VHL disease and MEN1. The accuracy of these guidelines has been improved by examining and adopting new evidence obtained after the first edition was published.

DOI： 10.1007/s00535-021-01827-7

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Endoscopic Ultrasound  

DOI： 10.4103/EUS-D-21-00067

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PubMed

記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIM: The aim of this study was to describe the long-term safety and efficacy of lanreotide in Japanese patients with neuroendocrine tumors. METHODS: The final analyses of a 48-week open-label phase II study (n = 32) and its extension study (n = 17) were conducted. Patients received 4-weekly subcutaneous injections of lanreotide autogel 120 mg. Safety was evaluated by adverse events. Efficacy endpoints included tumor response by RECIST and change in tumor size. Post hoc analyses including tumor growth rate were performed. RESULTS: The median (range) of lanreotide exposure in the safety analysis set (n = 17) and efficacy analysis set (n = 28) were 151.4 (52-181) and 52.7 (12-181) weeks, respectively. Sixteen patients developed adverse drug reaction; of these, upper abdominal pain and urticaria were not reported before 48 weeks. No patient discontinued lanreotide or died from an adverse event. Two serious events of bile duct stones in one patient were drug-related. Partial response was observed in 2 patients (7.1&#37;; at 60 and 108 weeks), stable disease in 20 (71.4&#37;) and progressive disease in 6 (21.4&#37;). The mean of the greatest change from baseline in the sum of diameters of target lesions was -5.5&#37;. The mean (standard deviation) tumor growth rate before treatment and from baseline to last observation was 25.3&#37; (35.7&#37;)/month and 6.4&#37; (9.6&#37;)/month, respectively. CONCLUSION: Lanreotide treatment had an acceptable safety profile and was effective over long-term treatment in Japanese patients with neuroendocrine tumors. No unexpected serious adverse events developed during prolonged use of lanreotide.

DOI： 10.1111/ajco.13371

記述言語：日本語  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.4103/EUS-D-21-00043

記述言語：その他   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/den.13981

記述言語：その他   掲載種別：研究論文（学術雑誌）  

DOI： 10.1097/mpa.0000000000001729

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.vgie.2020.08.009

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background. Endoscopic ultrasound-guided transluminal drainage (EUS-TD) is generally performed 4 weeks after disease onset for evacuating pancreatic fluid collections. However, the optimal timing for conducting the procedure in those diagnosed with postoperative pancreatic fistula (POPF) has not been established. We aimed to elucidate the efficacy and safety of early EUS-TD procedures for treating POPF. Methods. We retrospectively reviewed patients diagnosed with POPF who underwent EUS-TD in the Kyushu University Hospital between 2008 and 2019. Clinical features were comparatively analyzed between the two patient groups who underwent either early (≤15 days postoperatively) or late (>15 days postoperatively) EUS-TD. Factors prolonging hospital stay were also analyzed using Cox proportional hazard models. Results. Thirty patients (median age, 64.5 years) were enrolled. The most common initial operation was distal pancreatectomy with splenectomy (60.0&#37;). Median size of POPF was 69.5 (range, 38–145) mm, and median time interval between surgery and EUS-TD was 17.5 (range, 3–232) days. Totally, 47&#37; patients underwent early EUS-TD. Rates of technical success, clinical success, and complications were 100&#37;, 97&#37;, and 6.9&#37;, respectively. No recurrence of POPF occurred during a median follow-up period of 14 months. Clinical characteristics and outcomes were comparable between the early and late drainage patient groups, except for the rates of infection and nonencapsulation of POPF, which were significantly higher in the early drainage group. Performing simultaneous internal and external drainage (hazard ratio (HR): 0.31; 95&#37; confidence interval (CI): 0.11–0.93, <inline-formula>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="M1">
<mi>p</mi>
<mo>=</mo>
<mn>0.04</mn>
</math>
</inline-formula>) and conducting ≥2 treatment sessions (HR: 0.26; 95&#37; CI: 0.08–0.84, <inline-formula>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="M2">
<mi>p</mi>
<mo>=</mo>
<mn>0.02</mn>
</math>
</inline-formula>) were significantly associated with prolonged hospitalization after EUS-TD. Conclusions. EUS-TD is a safe and effective method for managing POPF, regardless of when it is performed in the postoperative period. Once infected POPF occurs, clinicians should not hesitate to perform EUS-TD even within 15 days of the initial operation.

DOI： 10.1155/2021/6691705

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1055/a-1167-7861

記述言語：英語   掲載種別：研究論文（学術雑誌）  

A 55-year-old man was diagnosed with pancreatic cancer of the uncus and received chemotherapy (modified FOLFIRINOX). Ten months later, he was admitted to our hospital with massive lower gastrointestinal bleeding. Contrast-enhanced CT showed ascending colon varices caused by the occlusion of the superior mesenteric vein (SMV) due to pancreatic cancer invasion. Colonoscopy revealed tortuous varices with red spots in the ascending colon. The patient received blood transfusions and was discharged; however, he was hospitalized for recurrent massive lower gastrointestinal bleeding 3 months later. During this readmission, we performed the transileocolic vein obliteration method due to SMV stenosis and the absence of an obvious shunt. He experienced an uneventful post-operative recovery, and contrast-enhanced CT after 2 months revealed no recurrence of colonic varices. Ectopic varices are portosystemic venous collaterals resulting from portal hypertension occurring in any locations other than the esophagogastric region. Colonic varices have rarely been reported before. Patients with pancreatic cancer may present with gastrointestinal bleeding caused by tumor bleeding or esophagogastric varices; however, ectopic varices such as colon varices, a rare complication of pancreatic cancer, should be considered in patients with obscure gastrointestinal bleeding.

DOI： 10.1007/s12328-020-01225-1

記述言語：日本語  

記述言語：日本語  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

A 54-year-old man with pancreatic head tumor had undergone pancreaticoduodenectomy and was diagnosed with pancreatic neuroendocrine tumor (P-NET) associated with sporadic multiple endocrine neoplasm type 1. Five years after the resection, P-NET recurred and liver metastases were observed. He was treated with a somatostatin analog. Eleven years after the resection, computed tomography revealed a new pancreatic hypodense and hypovascular mass adjacent to the P-NET that was diagnosed as pancreatic adenocarcinoma via endoscopic ultrasound-guided fine-needle aspiration. He underwent a total remnant pancreatectomy. Pathological examination showed that the lesion was constituted by a pancreatic ductal adenocarcinoma (PDAC) and a neuroendocrine tumor. Additionally, the invasive ductal carcinoma collided with the neuroendocrine tumor. Both PDAC and P-NET cells were observed in the collision area. We could observe the onset of PDAC during the treatment of P-NET. Moreover, we are the first to report the case of a collision of pancreatic endocrine and exocrine tumors diagnosed preoperatively.

DOI： 10.1007/s12328-020-01234-0

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: Endoscopic treatment for malignant biliary obstruction (MBO) in patients bearing surgically altered anatomy (SAA) is not well-established. Although endoscopic ultrasound-guided biliary drainage (EUS-BD) has emerged as a new treatment option for MBO, limited data are available regarding the efficacy and safety of EUS-BD in patients with SAA. We conducted a multicenter prospective registration study to evaluate the efficacy and safety of EUS-BD in this population. Methods: This study involved 10 referral centers in Japan. Patients with SAA who were scheduled to receive EUS-BD for unresectable MBO between May 2016 and September 2018 were prospectively registered. The primary endpoint was technical success and the secondary outcomes were clinical success, procedure time, procedure-related adverse events (AEs), stent patency, and overall survival. Results: In total, 40 patients were prospectively enrolled. The surgical reconstruction methods were gastrectomy with Roux-en-Y reconstruction (47.5&#37;), gastrectomy with Billroth-II reconstruction (15&#37;), pancreaticoduodenectomy (27.5&#37;), and hepaticojejunostomy with Roux-en-Y reconstruction (10&#37;). EUS-BD was performed for primary biliary drainage in 31 patients and for rescue biliary drainage in nine patients. Transmural stenting alone (60&#37;), antegrade stenting alone (5&#37;), and a combination of the two techniques (35&#37;) were selected for patients treated with EUS-BD. Technical and clinical success rates were 100&#37; (95&#37; confidence interval, 91.2-100.0&#37;) and 95&#37; (95&#37; confidence interval, 83.1-99.4&#37;), respectively. Mean procedure time was 36.5 min. Early AEs were noted in six patients (15&#37;): three self-limited bile leak, one bile peritonitis, and two pneumoperitonea. Late AEs occurred in six patients (15&#37;): one jejunal ulcer and five stent occlusions. Stent patency rate after 3 months of survival was 95.7&#37; (22/23). Median overall survival was 96 days. Conclusion: EUS-BD for MBO in patients with SAA appears to be effective and safe not only as a rescue drainage technique after failed endoscopic retrograde cholangiography but also as a primary drainage technique. Clinical Trial Registration: UMIN000022101.

DOI： 10.1177/1756284820930964

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: To provide updates on clinical practice of acute pancreatitis (AP) in Japan, we conducted a nationwide epidemiological survey. Methods: This study consisted of a two-staged survey; the number of AP patients was estimated by the first-stage survey and their clinical features were examined by the second-stage survey. We surveyed AP patients who had visited hospitals in 2016. Results: The estimated number of AP patients in 2016 was 78,450, with an overall incidence of 61.8 per 100,000 persons. We obtained detailed clinical information of 2994 AP patients, including 706 (23.6&#37;) severe cases classified according to the Japanese severity criteria. The male-to-female sex ratio was 2.0, and the mean age at onset was 59.9 years in males and 66.5 years in females. Alcohol was the most common etiology (42.8&#37;) in males and gallstones in females (37.7&#37;). The AP-associated mortality was 6.1&#37; in severe AP cases, which was decreased by 40&#37; compared to the 2011 survey. Antibiotics were administered to most cases, with carbapenem being frequently used. Enteral nutrition was given in 31.8&#37; of severe cases, but majority cases received after 48 h. Among the 107 patients who received intervention for walled-off necrosis, five patients received surgery-first approach, 66 received endoscopic ultrasound-guided transluminal drainage, and 19 underwent step-up approach. Conclusions: We clarified the current status of AP in Japan including the significant reduction of mortality in severe cases, shift to endoscopic approaches for walled-off necrosis, and poor compliance of the recommendations in the guidelines including management of enteral nutrition and antibiotic administration.

DOI： 10.1016/j.pan.2020.04.013

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background/Objectives: This single-center study aimed to evaluate treatment outcomes and long-term prognosis of patients with pancreatic neuroendocrine neoplasms (PanNENs) based on the World Health Organization (WHO) 2017 classification. Methods: We enrolled 245 patients with PanNENs treated at Kyushu University Hospital between January 1987 and March 2018. PanNENs were categorized according to the WHO 2017 classification or further subdivisions of Ki-67 index. Clinicopathological features, median survival time (MST), and prognostic factors were retrospectively analyzed. Results: The number of PanNENs, especially non-functioning PanNENs, has increased over the last decade. The mean MST of all patients was 202 months; which was longest in patients with NET G1 (n = 145, MST = 261 months) relative to NET G2 (n = 72, 132 months), NET G3 (n = 3, 34 months) and NEC G3 (n = 17, 9 months). Prognosis in patients with surgery as the first-line treatment was significantly better than in those with drug therapy. However, 26&#37; of patients who underwent curative resection developed recurrence after a median time of 28.7 months. In unresectable PanNENs (n = 97), the MST and 5-year survival rate were 78 months and 55.8&#37;, respectively. Poor differentiation, Ki-67 index of >10&#37; and presence of liver metastasis were significant unfavorable predictors. Response to first-line therapy (stable disease/partial response) and three or more treatment regimens were significant favorable predictors for unresectable PanNENs according to multivariate analyses (p < 0.01). Conclusions: We demonstrated the utility of the WHO 2017 classification for PanNENs in the real clinical setting. For better prognosis in PanNENs, the use of three or more regimens should be considered.

DOI： 10.1016/j.pan.2020.04.003

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: It is clinically necessary to validate a new non-invasive and reliable imaging method to detect early chronic pancreatitis. Intravoxel incoherent motion magnetic resonance imaging (MRI) is useful for quantitative assessment in abdominal solid organs. Purpose: To investigate the usefulness of intravoxel incoherent motion MRI parameters in the diagnosis of chronic pancreatitis. Material and Methods: Sixty patients with early chronic pancreatitis (n = 44) and chronic pancreatitis (n = 16) were assessed with intravoxel incoherent motion imaging. For comparison, a control group of 71 individuals without chronic pancreatitis was also enrolled. The perfusion fraction (f), pseudo-diffusion coefficient (D*), true diffusion coefficient (D), and apparent diffusion coefficient of pancreatic parenchyma were calculated. These measurements were compared between the three groups. The diagnostic accuracy of imaging parameters was assessed. Results: The f values of the early chronic pancreatitis group and the chronic pancreatitis group were significantly lower than those of the control group (P < 0.001 and P < 0.001, respectively). The D* value of the chronic pancreatitis group was significantly lower than that of the early chronic pancreatitis group (P = 0.0025). The D values of the early chronic pancreatitis group and the chronic pancreatitis group were significantly higher than those of the control group (P = 0.001 and P = 0.001, respectively). The perfusion fraction showed the highest diagnostic performance with an Az value of 0.76 for discriminating the control group from the early chronic pancreatitis and chronic pancreatitis groups. Conclusion: Intravoxel incoherent motion MRI parameters may reflect the minimal histological changes in early chronic pancreatitis.

DOI： 10.1177/0284185119872687

記述言語：その他   掲載種別：研究論文（学術雑誌）  

A 75-year-old man presented with upper abdominal pain. CT and MRI showed cystic lesions 27 mm in size with no malignant findings in the head of the pancreas. Under the diagnosis of intraductal papillary mucinous neoplasm (IPMN), the patient was followed-up with imaging studies. Six years after the initial presentation, a contrast CT scan showed an enhanced mural nodule 10 mm in size in the cyst, and the patient was referred to our hospital for further examination. CT and MRI revealed the cysts had shrunk compared to previous imaging findings. Pancreatic juice cytology showed no malignant cells. Based on detailed examination, a diagnosis of IPMN with high risk stigmata was made and laparoscopy-assisted pancreatoduodenectomy was performed. A histopathological examination revealed a cystic lesion consisting of IPMN with low-grade dysplasia, inflammatory infiltrates with lymphoplasmacytes corresponded to nodules in cysts, obliterative phlebitides, and storiform fibrosis. Immunohistochemical staining demonstrated that the infiltrating lymphoplasmacytes were positive for IgG4 and that IgG4+/IgG+ plasm cell ratio was over 40&#37;. Finally, we diagnosed branch duct type IPMN associated with autoimmune pancreatitis type-1, mimicking an enhanced mural nodule. We encountered a rare case of IPMN associated with autoimmune pancreatitis. It can be suggested that serological and histological examinations, including blood IgG4 testing and ultrasound-guided fine-needle aspiration, should be considered in patients with IPMN that show rapid appearance of enhanced nodules and shrinkage of cysts.

DOI： 10.5833/jjgs.2019.0044

記述言語：日本語  

症例は75歳の男性で,上腹部痛を自覚し受診した前医で膵頭部に27mmの嚢胞性病変を指摘されたが,明らかな悪性所見はなく,分枝型膵管内乳頭粘液性腫瘍(intraductal papillary mucinous neoplasm;以下,IPMNと略記)として定期的に画像評価を行っていた.6年2ヵ月後,嚢胞内部に10mm大の造影される壁在結節が出現した.High-risk stigmataを伴うIPMNと診断し,腹腔鏡補助下亜全胃温存膵頭十二指腸切除術を施行した.病理組織学的に,嚢胞性病変は低異形度IPMNであった.IPMNの結節に一致してIgG4陽性形質細胞の浸潤を伴う炎症細胞の集簇,花むしろ状繊維化,閉塞性静脈炎を認めた.免疫染色検査で強拡1視野当たり100個以上の集簇したIgG4陽性形質細胞を認め,IPMNに1型自己免疫性膵炎が合併したために壁在結節状の所見を呈したと考えられた.(著者抄録)

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/den.13637

記述言語：英語  

Background: To further clarify the clinico-epidemiological features of autoimmune pancreatitis (AIP) in Japan, we conducted the fourth nationwide epidemiological survey. Methods: This study consisted of two stage surveys; the number of AIP patients was estimated by the first survey and their clinical features were assessed by the second survey. We surveyed the AIP patients who had visited hospitals in 2016. Results: The estimated number of AIP patients in 2016 was 13,436, with an overall prevalence rate of 10.1 per 100,000 persons. The estimated number of newly diagnosed patients was 3984, with an annual incidence rate of 3.1 per 100,000 persons. Compared to the 2011 survey, both numbers more than doubled. We obtained detailed clinical information of 1474 AIP patients. The male-to-female sex ratio was 2.94, the mean age was 68.1, and mean age at diagnosis was 64.8. At diagnosis, 63&#37; patients were symptomatic and nearly half of them presented jaundice. Pancreatic cysts were found in 9&#37; of the patients and calcifications in 6&#37;. Histopathological examination was performed in 64&#37;, mainly by endoscopic ultrasonography-guided fine needle aspiration. Extra-pancreatic lesions were detected in 60&#37; of the patients. Eighty-four &#37; patients received the initial steroid therapy, and 85&#37; received maintenance steroid therapy. Kaplan–Meier analysis revealed that the relapsed survival was 14&#37; at 3 years, 25&#37; at 5 years, 40&#37; at 10 years, and 50&#37; at 15 years. Mortality was favorable, but pancreatic cancer accounted for death in one quarter of fatal cases. Conclusion: We clarified the current status of AIP in Japan.

DOI： 10.1007/s00535-019-01658-7

記述言語：英語  

DOI： 10.1002/lt.25707

記述言語：英語  

DOI： 10.1055/a-0992-8900

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/den.13476

記述言語：日本語  

症例は42歳、男性。20XX年アルコール性急性膵炎に対し前医で保存的加療を行ったが、症状改善せず、歩行困難となったため、当院へ転院となった。予後因子6点、造影CT Grade 2の重症急性膵炎と診断した。また、CK、Cre、LDH、ミオグロビンは高値であることから、横紋筋融解症、急性腎不全の合併を認めた。保存的加療を開始するも全身状態の改善が乏しかったため、持続血液濾過透析を中心とする集学的治療にて上記の改善を認めた。リハビリテーションを行った後、第37病日当院退院となった。重症急性膵炎に横紋筋融解症、急性腎不全を合併した場合の成因はアルコールが考えられ、また合併例は予後が不良である可能性があり、早急かつ積極的な集学的治療が必要であると考えられた。(著者抄録)

記述言語：日本語  

記述言語：英語  

記述言語：日本語  

記述言語：日本語  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Accumulation of evidence suggests that neoadjuvant chemotherapy improves the outcomes of borderline resectable pancreatic cancer (BRPC). Gemcitabine plus nab-paclitaxel (GnP) has been widely accepted as systemic chemotherapy for unresectable pancreatic cancer and reportedly results in remarkable tumor shrinkage. This study was performed to evaluate the safety and efficacy of neoadjuvant chemotherapy using neoadjuvant GnP for BRPC. METHODS: The medical records of 57 patients who underwent treatment of BRPC from 2010 to 2017 were retrospectively reviewed. The patient characteristics and short- and intermediate-term outcomes were compared between the GnP and upfront surgery (UFS) groups. RESULTS: The GnP group comprised 31 patients and the UFS group comprised 26 patients. The patient characteristics were comparable with the exception of a higher prevalence of arterial involvement in the GnP group. Twenty-seven of the 31 patients (87&#37;) in the GnP group and all 26 patients in the UFS group underwent resection. The GnP group showed a significantly shorter operation time (429 vs. 509.5 min, p = 0.0068), less blood loss (760 vs. 1324 ml, p = 0.0115), and a higher R0 resection rate (100&#37; vs. 77&#37;, p = 0.0100) than the UFS group. Postoperative complications and hospital stay were comparable between the two groups, and no treatment-related mortality occurred in either group. Both the disease-free survival and overall survival times were significantly longer in the GnP group (p = 0.0018 and p = 0.0024, respectively). CONCLUSIONS: Neoadjuvant GnP is a safe and effective treatment strategy for BRPC. It potentially improves patients' prognosis and facilitates surgical procedures.

DOI： 10.1245/s10434-019-07309-8

記述言語：日本語  

症例は10歳男児。上腹部痛・嘔吐で発症し、前医で重症急性膵炎と診断され、当院に搬送された。集中治療により膵炎鎮静化が得られ、発症2ヵ月後に合併した感染性嚢胞に対して嚢胞空腸吻合術が奏効した。しかし、その後も膵炎を反復し、その誘因と考えられた主膵管狭窄に対して、内視鏡的膵管ステント留置、続いて副乳頭切開を行い、一時的に寛解したが、その後も再燃したため、発症9ヵ月後にFrey手術を施行した。5年後現在まで膵炎の再燃なく、膵内外分泌機能も温存されている。膵機能温存や長期予後が重視される小児例においては、内視鏡治療の限界も考慮しつつ、外科治療のタイミングを逸さない慎重な経過観察が必要である。(著者抄録)

記述言語：日本語  

30歳、男性。急性膵炎の診断で前医に入院し、第2病日に低血糖が出現したが、第4病日より高血糖となりCTで膵全体にまだらな低吸収域が出現した。第8病日に当院に転院となり、ケトアシドーシス発症を契機に劇症1型糖尿病と診断されたが、その際のCTでは低吸収域は消失していた。膵生検では膵島は認められなかった。急性膵炎と低血糖が先行し、膵CT所見の経時的変化を観察しえた非常にまれな劇症1型糖尿病の1例を経験した。(著者抄録)

記述言語：その他   掲載種別：研究論文（学術雑誌）  

DOI： 10.11405/nisshoshi.116.161

記述言語：日本語  

症例は50代男性。肝転移・腹膜播種・十二指腸狭窄を伴う膵頭部癌に対して、胆管metallic stentを留置後に、化学療法を導入したが、急性膵炎を発症したため、胆管plastic stent(PS)へ交換、内視鏡的膵管ステント(endoscopic pancreatic stent:EPS)を留置した。EPS抜去後に、化膿性膵管炎を発症し、ENPDチューブを留置した。十二指腸下行脚狭窄があり、ENPDチューブを胃内でカットして内瘻化した。約1ヵ月後に胆管炎を発症し、胆管PSを交換したが、処置後7日目に突如ショックバイタルとなった。CT検査をしたところカットしたENPDチューブ近位端が十二指腸球部前壁を貫いており、free airと腹腔内膿瘍を認めた。腹腔内膿瘍に対して緊急CTガイド下ドレナージ後、上部消化管内視鏡でENPDチューブを抜去し、穿孔部位をクリップで閉鎖した。その後、経口摂取可能となったが、以後はBSCとなり、治療開始約8ヵ月後に原病死された。(著者抄録)

記述言語：英語  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: Accumulation of evidence suggests that neoadjuvant chemotherapy improves the outcomes of borderline resectable pancreatic cancer (BRPC). Gemcitabine plus nab-paclitaxel (GnP) has been widely accepted as systemic chemotherapy for unresectable pancreatic cancer and reportedly results in remarkable tumor shrinkage. This study was performed to evaluate the safety and efficacy of neoadjuvant chemotherapy using neoadjuvant GnP for BRPC. Methods: The medical records of 57 patients who underwent treatment of BRPC from 2010 to 2017 were retrospectively reviewed. The patient characteristics and short- and intermediate-term outcomes were compared between the GnP and upfront surgery (UFS) groups. Results: The GnP group comprised 31 patients and the UFS group comprised 26 patients. The patient characteristics were comparable with the exception of a higher prevalence of arterial involvement in the GnP group. Twenty-seven of the 31 patients (87%) in the GnP group and all 26 patients in the UFS group underwent resection. The GnP group showed a significantly shorter operation time (429 vs. 509.5 min, p = 0.0068), less blood loss (760 vs. 1324 ml, p = 0.0115), and a higher R0 resection rate (100% vs. 77%, p = 0.0100) than the UFS group. Postoperative complications and hospital stay were comparable between the two groups, and no treatment-related mortality occurred in either group. Both the disease-free survival and overall survival times were significantly longer in the GnP group (p = 0.0018 and p = 0.0024, respectively). Conclusions: Neoadjuvant GnP is a safe and effective treatment strategy for BRPC. It potentially improves patients’ prognosis and facilitates surgical procedures.

DOI： 10.1245/s10434-019-07309-8

記述言語：日本語  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Pancreatic cancer is a malignant neoplasm that originates from acinar cells. Acinar cells get reprogrammed to become duct cells, resulting in pancreatic cancer. Pancreatitis is an acinar cell inflammation, leading to "impaired autophagy flux". Pancreatitis promotes acinar-to-ductal transdifferentiation. Expression of amylase gets eliminated during the progression of pancreatic cancer. Amylase is considered as an acinar cell marker; however, its function in cells is not known. Thus, we investigated whether amylase affects the acinar cell autophagy and whether it plays any role in development of pancreatitis. Here, we knocked out ATG12 in a pancreatic cancer cells and acinar cells using CRISPR/Cas9. Autophagy inhibition led to an increase in the expression of duct cell markers and a simultaneous decrease in that of acinar cell markers. It also caused an increase in cell viability and changes in mitochondrial morphology. Next, we knocked out amylase in acinar cells. Amylase deficiency decreased autophagy induced by pancreatitis. Our results suggest that amylase controls pancreatitis-induced autophagy. We found that eliminating amylase expression contributes to pancreatic cancer etiology by decreasing autophagy. Furthermore, our results indicate that amylase plays a role in selective pancreatitis-induced autophagy of pancreatic enzyme vesicles.

DOI： 10.1155/2018/8719397

記述言語：英語  

記述言語：英語  

記述言語：日本語  

DOI： 10.1007/s00280-017-3482-7

記述言語：日本語  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVES: This study aimed to evaluate the usefulness of the 48-hour fasting test and insulin surrogates followed by a glucagon stimulatory test (GST) for the diagnosis of insulinoma. METHODS: Thirty-five patients with suspected insulinoma who underwent 48-hour fasting test and GST were retrospectively included in our study: 15 patients with surgically proven insulinomas and 20 patients in whom insulinoma was clinically ruled out. We determined the duration of the fasting test, plasma glucose levels, serum levels of immunoreactive insulin and C-peptide, and insulin surrogates (serum levels of β-hydroxybutyrate, free fatty acid, and response of plasma glucose to intravenous glucagon [ΔPG]) at the end of the fast. RESULTS: The sensitivity and specificity of the 48-hour fasting test were 100.0&#37; and 80.0&#37;, respectively, for the diagnosis of insulinoma. When the 48-hour fasting test and immunoreactive insulin, C-peptide, or insulin surrogates were combined, the combination with GST showed the best results. The sensitivity, specificity, and accuracy rate were 93.3&#37;, 95.0&#37;, and 94.3&#37;, respectively, with 1 false-negative case and 1 false-positive case occurring. CONCLUSIONS: A more accurate and less invasive diagnosis of insulinoma was possible by combining the 48-hour fasting test with the GST, compared with the existing method.

DOI： 10.1097/MPA.0000000000000772

記述言語：日本語  

記述言語：日本語  

DOI： 10.1093/jjco/hyv143

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

The standard chemotherapy for the treatment of unresectable advanced and recurrent biliary tract cancers is considered gemcitabine plus cisplatin (Gc) on the basis of favorable results reported in the ABC-02 study from the UK and the BT22 study from Japan. However, the GC cohort of the BT22 study consisted of only 42 patients, and we considered it necessary to confirm the effectiveness and safety of GC chemotherapy in a multicenter prospective observational study in Fukuoka. Thirty- seven patients were enrolled in this study, including two patients with recurrent disease. The median patient age was 67.5 years (range, 43-84 years). Twelve patients had intrahepatic cholangiocarcinoma, 13 patients had extrahepatic cholangiocarcinoma, and 12 patients had gallbladder cancer. The median survival time (MST) was 14.9 months, the 1-year survival rate was 54.5&#37;, and the median progression free survival (PFS) was 7.7 months. No chemotherapy-related deaths occurred, and Grade 3/4 adverse events were mainly hematological events including leucopenia in 13 (35.1&#37;) patients and neutropenia in 12 (32.4&#37;). The MST, 1-year survival rate, median PFS, and rate of Grade 3/4 adverse events in our study were similar to those of the BT22 study. In conclusion, this multicenter prospective observational study confirms the effectiveness and safety of GC chemotherapy for the treatment of unresectable advanced and recurrent biliary tract cancers.

記述言語：日本語  

切除不能進行・再発胆道癌に対する標準化学療法は、英国のABC-02試験と日本のBT22試験の良好な結果から、ゲムシタビン+シスプラチン(GC療法)とされるが、BT22試験のGC群は42例にすぎず、さらに症例を重ねて有効性と安全性を検討する必要があると考えられた。そこで、福岡・北九州地区においてGC療法の安全性・有効性を多施設前向き観察研究にて確認した。登録症例は再発例2例を含む37例。年齢の中央値は67.5(43～84)歳、肝内胆管癌12例、肝外胆管癌13例、胆嚢癌12例であった。生存期間中央値(median survival time:MST)は14.9ヵ月、1年生存率は54.5%であり、無増悪生存期間(progression free survival:PFS)の中央値は7.7ヵ月であった。治療関連死亡は認めず、Grade3以上の有害事象は白血球減少13例(35.1%)、好中球減少12例(32.4%)など血液毒性が主であった。MST、1年生存率、PFS、有害事象発生状況などはBT22試験と同様であり、本多施設前向き観察研究により、切除不能進行・再発胆道癌に対するGC療法の有効性と安全性が確認された。(著者抄録)

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIM: To investigate the relationship between the iron-metabolism-related gene expression profiles and efficacy of antiviral therapy in chronic hepatitis C patients. METHODS: The hepatic expression profile of iron-metabolism-related genes was analyzed and its association with virological response to pegylated-interferon plus ribavirin combination therapy was evaluated. A hundred patients with chronic hepatitis C (genotype1b, n = 50; genotype 2, n = 50) were enrolled and retrospectively analyzed. Liver biopsy samples were subjected to quantitative polymerase chain reaction for iron-metabolism-related genes and protein expression (Western blotting analysis) for ferroportin. As a control, normal liver tissue was obtained from 18 living donors of liver transplantation. Serum hepcidin level was measured by sensitive liquid chromatography/electrospray ionization tandem mass spectrometry. RESULTS: Iron overload is associated with liver damage by increasing oxidative stress and hepatitis C virus (HCV) is reported to induce iron accumulation in hepatocytes in vivo. Conversely, iron administration suppresses HCV replication in vitro. Therefore, the association between HCV infection and iron metabolism remains unclear. Compared with controls, patients had significantly higher gene expression for transferrin, iron-regulatory proteins 1 and 2, divalent metal transporter 1, and ferroportin, but similar for transferrin receptors 1 and 2, and hepcidin. When the expression profiles were compared between sustained virological response (SVR) and non-SVR patients, the former showed significantly lower transcription and protein expression of hepcidin and ferroportin. Expression of hepcidin-regulating genes, BMPR1, BMPR2, and hemojuvelin, was significantly increased, whereas BMP2 was decreased in HCV-infected liver. BMPR2 and hemojuvelin expression was significantly lower in the SVR than non-SVR group. HCV infection affects the expression of iron-metabolism-related genes, leading to iron accumulation in hepatocytes. CONCLUSION: Decreased expression of hepcidin and ferroportin in SVR patients indicates the importance of hepatocytic iron retention for viral response during pegylated-interferon plus ribavirin treatment.

DOI： 10.3748/wjg.v21.i11.3291

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Although chromogranin A (CGA) is a useful marker for pancreatic neuroendocrine tumors (pNET) in the West, its usefulness in Japanese populations is unclear. To assess this, we evaluated the serum CGA levels in 189 patients with various pancreatic diseases, including proven pNET (n = 69), pancreatic cancer (PC) (n = 50), chronic pancreatitis (CP) (n = 50) and autoimmune pancreatitis (AIP) (n = 20), and 112 normal controls (controls) using an ELISA kit. The mean CGA level of patients with pNET was significantly higher than any of the other groups (407.8 ± 984.6 ng/mL [pNET] vs 91.8 ± 101.8 ng/mL [PC], 93.6 ± 57.5 ng/mL [CP], 69.9 ± 52.4 ng/mL [AIP] and 62.5 ± 48.3 ng/mL [controls]). Limiting the analysis to patients not using proton pump inhibitors (PPI), the CGA level of patients with PC or CP was not significantly different compared with the controls. Discriminant analysis revealed that the best cut-off value of CGA to distinguish patients with pNET from the controls was 78.7 ng/mL, with a sensitivity and specificity of 53.6&#37; and 78.6&#37;, respectively. In patients with pNET, significant factors associating with elevated CGA levels were tumor classification, tumor size, and the presence of liver metastases in univariate analysis as well as PPI use and the presence of liver metastases in multivariate analysis. We show that CGA is a useful marker for diagnosing pNET in Japanese populations and for distinguishing patients with pNET from patients with other pancreatic diseases. The increased use of CGA in Japan will likely be a helpful tool in managing these patients, as found in the West.

DOI： 10.1111/cas.12533

記述言語：日本語  

記述言語：日本語  

DOI： 10.1016/j.pan.2014.02.009

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIM: To clarify the efficacy and safety of an endoscopic approach through the minor papilla for the management of pancreatic diseases. METHODS: This study included 44 endoscopic retrograde cholangiopancreatography (ERCP) procedures performed in 34 patients using a minor papilla approach between April 2007 and March 2012. We retrospectively evaluated the clinical profiles of the patients, the endoscopic interventions, short-term outcomes, and complications. RESULTS: Of 44 ERCPs, 26 were diagnostic ERCP, and 18 were therapeutic ERCP. The most common cause of difficult access to the main pancreatic duct through the major papilla was pancreas divisum followed by distortion of Wirsung's duct. The overall success rate of minor papilla cannulation was 80&#37; (35/44), which was significantly improved by wire-guided cannulation (P = 0.04). Endoscopic minor papillotomy (EMP) was performed in 17 of 34 patients (50&#37;) using a needle-knife (13/17) or a pull-type papillotome (4/17). EMP with pancreatic stent placement, which was the main therapeutic option for patients with chronic pancreatitis, recurrent acute pancreatitis, and pancreatic pseudocyst, resulted in short-term clinical improvement in 83&#37; of patients. Mild post-ERCP pancreatitis occurred as an early complication in 2 cases (4.5&#37;). CONCLUSION: The endoscopic minor papilla approach is technically feasible, safe, and effective when the procedure is performed in a high-volume referral center by experienced endoscopists.

DOI： 10.4253/wjge.v5.i3.81

記述言語：英語   掲載種別：研究論文（学術雑誌）  

The clinical course of chronic pancreatitis (CP) worsens with drinking, and pancreatic stellate cells (PSCs) have an important role in the pathogenesis of alcoholic CP. Chemokines recruit inflammatory cells, resulting in chronic pancreatic inflammation. Although serum levels of fractalkine (CX3CL1) are significantly elevated in patients with alcoholic CP, the mechanism of this elevation remains unclear. This study aims to determine the effects of cytokines, pathogen-associated molecular patterns (PAMPs), and ethanol and its metabolites on CX3CL1 secretion by PSCs. Male Wistar/Bonn Kobori (WBN/Kob) rats aged 15 to 20 weeks were used as rodent models of CP in vivo. PSCs were isolated from 6-week-old male Wistar rats. The effects of cytokines, PAMPs, and ethanol and its metabolites on chemokine production and activation of signaling pathways in PSCs in vitro were examined by real-time reverse transcription-polymerase chain reaction (RT-PCR), western blotting, and enzyme-linked immunosorbent assay. Expression of CX3CL1 and matrix metalloprotease (MMP)-2 was increased in the pancreas of WBN/Kob rats. The rat PSCs expressed CX3CL1, MMP-2, and a disintegrin and metalloprotease domain (ADAM) 17. Cytokines and PAMPs induced CX3CL1 release and activated extracellular signal-regulated kinase (ERK), MMP-9, and ADAM17. CX3CL1 release was suppressed by specific inhibitors of ERK, MMP, and ADAM, and ERK was associated with CX3CL1 transcription. Ethanol and phorbol myristate acetate synergistically increased CX3CL1 release. Real-time PCR and western blotting confirmed the synergistic activation of ERK and ADAM17. Ethanol synergistically increased CX3CL1 release via ERK and ADAM17 activation in PSCs. In conclusion, we demonstrated for the first time that ethanol synergistically increased CX3CL1 release from PSCs at least in part through activation of ERK mitogen-activated protein kinase and ADAM17. This might be one of the mechanisms of serum CX3CL1 elevation and disease progression in patients with alcoholic CP.

DOI： 10.1038/labinvest.2012.156

記述言語：英語  

Multiple endocrine neoplasia type 1 (MEN1) is an inherited autosomal dominant disease presenting with pancreatic neuroendocrine tumors (pNETs), parathyroid tumors, or pituitary tumors. Using the PubMed database, we reviewed the literature on information regarding the proper diagnosis and treatment of MEN1-associated pNET. Many cases of MEN1-associated pNET are functioning pNETs. Gastrinomas and insulinomas tend to occur frequently in the duodenum and pancreas, respectively. In addition to diagnostic imaging, the selective arterial secretagogue injection test (SASI test) is useful for localizing functioning pNET. The standard treatment is surgical resection. However, in the case of a functioning pNET, the tumor should first be accurately located using the SASI test before an appropriate surgical method is selected. In cases of a MEN1-associated non-functioning pNET that exceeds 2 cm in diameter, the incidence of distant metastasis is significantly increased, and surgery is recommended. In cases of unresectable pNET, a somatostatin analog has been shown to demonstrate antitumor effects and is considered to be a promising treatment. In addition, molecular-targeted drugs have recently been found to be effective in phase III clinical trials. (Gut Liver 2012;6:287-294)

DOI： 10.5009/gnl.2012.6.3.287

記述言語：その他   掲載種別：研究論文（学術雑誌）  

Pancreatitis is an inflammatory disease of unknown causes. There are many triggers causing pancreatitis, such as alcohol, common bile duct stone, virus and congenital or acquired stenosis of main pancreatic duct, which often involve tissue injuries. Pancreatitis often occurs in sterile condition, where the dead/dying pancreatic parenchymal cells and the necrotic tissues derived from self-digested-pancreas were observed. However, the causal relationship between tissue injury and pancreatitis and how tissue injury could induce the inflammation of the pancreas were not elucidated fully until now. This study demonstrates that cytosolic double-stranded DNA increases the expression of several inflammatory genes (cytokines, chemokines, type I interferon, and major histocompatibility complex) in rat pancreatic stellate cells. Furthermore, these increase accompanied the multiple signal molecules genes, such as interferon regulatory factors, nuclear factor-kappa B, low-molecular-weight protein 2, and transporter associated with antigen processing 1. We suggest that this phenomenon is a plausible mechanism that might explain how cell damage of the pancreas or tissue injury triggers acute, chronic, and autoimmune pancreatitis; it is potentially relevant to host immune responses induced during alcohol consumption or other causes.

DOI： 10.1155/2012/504128

記述言語：日本語  

膵神経内分泌腫瘍は比較的稀な疾患であるが，近年注目されている領域である．最近行われた本邦の全国疫学調査では人口10万人当たりの有病患者数は約2.23人で，欧米と比較すると種々の疫学的相違点が明らかとなった．本腫瘍の治療方針を決定する上で，正確な診断（存在診断・局在診断）が極めて重要である．そのためには各腫瘍の症候や診断modality，組織分類などについて十分理解しておく必要がある．

DOI： 10.2169/naika.101.100

記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVES: We hoped to clarify the possible role of CpG DNA as a trigger factor for overt pancreatic inflammation of pancreatic stellate cells (PSCs). METHODS: Pancreatic stellate cells were isolated from the male Lewis rat. The expression of Toll-like receptor 9 (TLR9) messenger RNA and protein were evaluated by reverse transcription-polymerase chain reaction and immunofluorescent cytochemistry. Internalization of CpG DNA was analyzed by confocal laser scanning microscopy. Pancreatic stellate cells were incubated with CpG DNA, and then cell proliferation and migration were assessed. RESULTS: Constitutive expression of TLR9 occurs at the messenger RNA and protein levels. After several minutes of CpG DNA administration, CpG DNA was observed on the cell membrane surface and in the cytoplasm and found to be translocating into the perinucleus of PSCs. Pancreatic stellate cells migrated and proliferated in dose- and time-dependent manners in response to simulation by CpG DNA. Proliferation of PSCs was observed 3 hours after administration (earlier than platelet-derived growth factor-induced proliferation), suggesting that PSCs respond readily to provide innate immunity. Endosomal acidification inhibitors attenuated CpG DNA-induced signaling, leading to suppression of DNA synthesis by PSCs. CONCLUSIONS: Our findings demonstrate that bacterial DNA promotes migration and proliferation of PSCs and suggest that bacterial DNA can initiate and sustain pancreatic inflammation and fibrosis by means of TLR9.

DOI： 10.1097/MPA.0b013e318224a501

記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVES: There have been few epidemiological studies on pancreatic diabetes. In this study, we determined the incidence and pathology of pancreatic diabetes in Japan. METHODS: We examined the epidemiology of pancreatic diabetes in Japan in 2005 by using a nationwide stratified random-sampling method. Especially, we focused on newly developed diabetes in association with the occurrence of pancreatic disease (true pancreatic diabetes). RESULTS: A total of 19,500 individuals received treatment for true pancreatic diabetes, accounting for 0.8&#37; of patients with diabetes. Prevalence was estimated to be 15.2 per 100,000 with an annual onset incidence of 1.1 per 100,000. With regard to the complications in true pancreatic diabetes, the incidence of retinopathy was lower than that in types 1 and 2 diabetes. Among true pancreatic diabetes with chronic pancreatitis, alcoholic pancreatitis was found in the largest sector. Furthermore, as many as 53.7&#37; were continuous drinkers, and 66.7&#37; received insulin therapy. The frequency of hypoglycemia was high in regular drinkers treated with insulin. Hypoglycemia was a major cause of death in patients who were on insulin and continuous drinkers. CONCLUSION: We clarified the epidemiology of pancreatic diabetes in Japan. Patients with chronic pancreatitis-associated pancreatic diabetes should receive lifestyle guidance focused on drinking cessation.

DOI： 10.1097/MPA.0b013e3181ca3da4

記述言語：英語  

A 77-year-old man was referred to our hospital for further investigation of pancreatic masses. Imaging studies revealed hypovascular masses in the pancreatic head and body. Total pancreatectomy was performed under the diagnosis of double primary pancreatic carcinomas. Macroscopic examination revealed 3 nodules: one each in the pancreatic head, body, and tail. Microscopically, all 3 lesions showed similar carcinoma cells, which communicated with each other via the intraductal component, indicating a single large tumor. Incidentally, we also identified an adenocarcinoma of the common bile duct (CBD). The final diagnosis was synchronous double cancer involving the whole pancreas and the CBD.

DOI： 10.2169/internalmedicine.49.3347

記述言語：日本語  

自己免疫性膵(AIP)は,その成因と病態の進展に自己免疫的機序が関与している膵の炎症性疾患と理解されている.近年の症例の蓄積により,ステロイド治療経過中/中止後に再燃をきたす症例が報告されるようになり,ステロイドの維持療法の重要性も指摘されてきている.長期的には膵内外分泌機能低下,さらには膵の萎縮,膵石を合併する症例も経験されるようになった.一方,非ステロイド投与下に自然軽快する症例も報告されてきているが,再燃例も認め慎重な検討が必要である.2006年の本邦のAIP改訂基準では,「長期予後は不明であるが,膵石合併の報告がある」とされているが,近年,膵癌合併の症例報告も散見されてきている.AIPが膵癌のリスクファクターになりうるかどうかも含め,AIPの長期予後についてはさらなる症例の蓄積が必要である.(著者抄録)

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Context Lipomatous pseudohypertrophy of the pancreas is an extremely rare disease, and is characterized by the replacement of pancreatic acinar cells with adipose tissue, although the pancreatic duct and islets are preserved. Case report We report the case of a 64-year-old female who was undergoing treatment for Hashimoto's disease at a nearby clinic. For the previous two years, she had experienced an unpleasant feeling in the upper abdominal area after eating oily foods. For the previous six months, she had also suffered from lower-back pain, and presented at our hospital. Abdominal computed tomography and magnetic resonance imaging revealed marked fat replacement over the entire pancreas. Endoscopic retrograde cholangiopancreatography revealed no anatomical abnormality or narrowing of the main pancreatic duct
the main pancreatic duct was normal up to the pancreatic tail and the branchesof the pancreatic duct did not show any abnormalities. While the serum levels of the pancreatic enzymes were considerably low, according to the data of the pancreatic exocrine function test (N-benzoyl-tyrosyl-p-aminobenzoic acid test), endocrine function was maintained. On the basis of the abovementioned findings, we diagnosed lipomatous pseudohypertrophy of the pancreas. Conclusions Lipomatous pseudohypertrophy of the pancreas is a very rare disease characterized by the disappearance of pancreatic exocrine tissue due to adipose tissue replacement, although the pancreatic duct and islets remain intact. Even though it has been suggested that the diagnosis of lipomatous pseudohypertrophy of the pancreas should be based on histological findings, this case indicated the possibility that lipomatous pseudohypertrophy of the pancreas may be diagnosed solely by typical imaging findings and serological data.

記述言語：日本語  

Lipomatous pseudohypertrophy of the pancreas(LPP)の一症例

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：日本語  

慢性膵炎の治療は病期で異なり，代償期では，反復する再燃と疼痛予防が主体であり，過度の膵刺激を避ける食事療法，蛋白分解酵素薬を中心とした薬物療法が重要である．非代償期では消化吸収障害および膵性糖尿病のコントロールが重要であり，低栄養状態を避けるため，適切な量の脂肪摂取をさせた上で，十分量の消化酵素薬を投与する．そのうえで糖尿病に対するインスリン量などを決定する必要がある．

DOI： 10.2169/naika.99.56

記述言語：日本語  

66歳男性。患者は上腹部不快感、体重減少を主訴に近医を受診、膵腫瘍が指摘され、精査加療目的に今回、著者らの施設へ紹介となった。入院時、血中NSE値の上昇がみられ、腹部CTでは膵体部に5cm大の腫瘍が認められた。超音波内視鏡下腫瘍生検の結果、膵原発小細胞癌と診断され、全身化学療法を選択、初期治療としてGemcitabineとS-1併用療法を開始したものの治療効果は認められず、PE療法へ変更した。以後、4コース終了後には原発巣の縮小とNSEの低下を認め、5コース時に放射線療法を追加し、PE療法は計6コース行なわれた。目下、PE療法終了後7ヵ月経過で腫瘍の増大はみられず、経過は良好である。

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Camostat mesilate (CM), an oral protease inhibitor, has been used clinically for the treatment of chronic pancreatitis in Japan. However, the mechanism by which it operates has not been fully understood. Our aim was to evaluate the therapeutic efficacy of CM in the experimental pancreatic fibrosis model induced by dibutyltin dichloride (DBTC), and we also determined the effect of CM on isolated monocytes and panceatic stellate cells (PSCs). In vivo, chronic pancreatitis was induced in male Lewis rats by single administration of 7 mg/kg DBTC and a special diet containing 1 mg/g CM was fed to the DBTC+CM-treated group from day 7, while the DBTC-treated group rats were fed a standard diet. At days 0, 7, 14 and 28, the severity of pancreatitis and fibrosis was examined histologically and enzymologically in both groups. In vitro, monocytes were isolated from the spleen of a Lewis rat, and activated with lipopolysaccharide stimulation. Thereafter, the effect of CM on monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-alpha (TNF-alpha) production from monocytes was examined. Subsequently, cultured rat PSCs were exposed to CM and tested to see whether their proliferation, MCP-1 production and procollagen alpha1 messenger RNA expression was influenced by CM. In vivo, the oral administration of CM inhibited inflammation, cytokines expression and fibrosis in the pancreas. The in vitro study revealed that CM inhibited both MCP-1 and TNF-alpha production from monocytes, and proliferation and MCP-1 production from PSCs. However, procollagen alpha1 expression in PSCs was not influenced by CM. These results suggest that CM attenuated DBTC-induced rat pancreatic fibrosis via inhibition of monocytes and PSCs activity.

開催年月日： 2023年4月

記述言語：英語   会議種別：口頭発表（一般）  

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開催年月日： 2020年9月

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開催地：九州大学（福岡市）   国名：日本国  

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記述言語：英語   会議種別：口頭発表（一般）  

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開催年月日： 2019年5月 - 2019年6月

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記述言語：日本語   会議種別：口頭発表（一般）  

開催地：京都   国名：日本国  

開催年月日： 2018年6月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：和歌山   国名：日本国  

開催年月日： 2018年6月

記述言語：日本語   会議種別：口頭発表（一般）  

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開催地：福岡   国名：日本国  

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MACHINE LEARNING-BASED MODEL FOR PREDICTION AND FEATURE ANALYSIS OF RECURRENCE IN PANCREATIC NEUROENDOCRINE TUMORS G1/G2

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APPROACH TO PRECISION MEDICINE FOR PANCREATIC DUCTAL ADENOCARCINOMA USING PATIENT- DERIVED ORGANOIDS

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Current status and future strategies for the treatment of advanced gastroenteropancreatic neuroendocrine neoplasms

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Diagnostic Approach of Pancreatic Tumor: Role of EUS-FNA and FNB

記述言語：英語  

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Current status of EUS-BD ～Beyond the ERCP～

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Current status and future perspectives of early detection and management of pancreatic cancer in Japan

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Predictive factors of recurrence after curative resection in patients with PanNET; A multicenter retrospective study

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Current status of EUS-BD ～Can we perform EUS-HGS without dilation?～

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開催地：京都   国名：日本国  

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記述言語：英語  

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記述言語：英語  

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DOI： 10.15106/j_naika130_502

記述言語：その他  

DOI： 10.15106/j_naika130_77

記述言語：その他  

記述言語：その他  

記述言語：日本語  

近年、腫瘍領域においてliquid biopsyが注目を集めているが、神経内分泌腫瘍(NEN)においてもmRNAを用いたliquid biopsyであるNETestが発明明された。NENは非常にheterogenousな腫瘍であるため、これまで汎用性の高いbiomarkerは存在していなかったが、NETestは診断、モニタリング、予後の予測において高い有効性を示している。また、NETestは腫瘍の分子生物学的プロファイルを得ることができるが、従来の組織学的検査とは異なり、intertumoral/intratumoral heterogeneityが問題となることはなく、容易にリアルタイムの病状を把握することができる。さらなるエビデンスの蓄積とともに、本邦でも導入が期待される検査と考えられる。(著者抄録)

記述言語：日本語  

膵癌を含む多くの固形がんにおいて、末梢血や尿などの体液からサンプルを抽出するliquid biopsyが急速に広がりつつある。血中遊離DNA(cell-free DNA:cfDNA)や血中循環腫瘍DNA(circulating-tumor DNA:ctDNA)を用いた解析はliquid biopsyの一つであり、組織採取が難しい膵癌ではとくに期待される領域である。膵癌における術前・術後のctDNA検出や、cfDNA(ctDNA)中のKRAS mutation陽性が、予後不良と関連するとした報告が多い。これらの予後不良例には、術前・術後治療や切除後サーベイランスの方法を変えるという戦略が今後確立される可能性もあり、さらなる研究の発展が期待される。(著者抄録)

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

異所性膵は胃角部から前庭部に多く発生する消化管粘膜下腫瘍として見つかることが多い疾患である。多くの異所性膵は良性で経過し診断がつけば基本的には経過観察が可能である。診断は上部消化管内視鏡検査ならびに超音波内視鏡を用いた画像診断や病理学的評価が有用とされている。超音波内視鏡による画像診断は非常に有用であるが、内部の性状だけでなく病変の由来層の確認が極めて重要である。また超音波内視鏡下吸引穿刺細胞診/生検以外の診断法として近年報告が増えている粘膜切開生検が、EUS-FNABで診断困難な症例における新たな診断オプションとして期待される。(著者抄録)

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

専門性が高い胆膵疾患の診療では診療科横断的チーム医療が不可欠である。とくに外科の立場からは、術前・術中・術後、すべての局面で内科・放射線科・病理の診断や治療が重要となっている。九州大学病院の胆膵チームは各週の手術症例を中心に画像診断の確認を行うWeeklyカンファレンス、各科の新患患者の情報共有を行う月1回の胆嚢・膵臓部会、年3回行われる症例検討である胆膵カンファレンスを行っている。これらを通じた患者の情報共有が各科の連携を円滑にし、正確な術前診断と適切な治療の選択、周術期の安全性向上、長期的な患者予後改善に寄与していると考えられる。今後も患者のアウトカムを検証しながら、チーム医療によるよりよい診療を継続して行くことが重要である。(著者抄録)

記述言語：日本語  

専門性が高い胆膵疾患の診療では診療科横断的チーム医療が不可欠である。とくに外科の立場からは、術前・術中・術後、すべての局面で内科・放射線科・病理の診断や治療が重要となっている。九州大学病院の胆膵チームは各週の手術症例を中心に画像診断の確認を行うWeeklyカンファレンス、各科の新患患者の情報共有を行う月1回の胆嚢・膵臓部会、年3回行われる症例検討である胆膵カンファレンスを行っている。これらを通じた患者の情報共有が各科の連携を円滑にし、正確な術前診断と適切な治療の選択、周術期の安全性向上、長期的な患者予後改善に寄与していると考えられる。今後も患者のアウトカムを検証しながら、チーム医療によるよりよい診療を継続して行くことが重要である。(著者抄録)

記述言語：日本語  

専門性が高い胆膵疾患の診療では診療科横断的チーム医療が不可欠である。とくに外科の立場からは、術前・術中・術後、すべての局面で内科・放射線科・病理の診断や治療が重要となっている。九州大学病院の胆膵チームは各週の手術症例を中心に画像診断の確認を行うWeeklyカンファレンス、各科の新患患者の情報共有を行う月1回の胆嚢・膵臓部会、年3回行われる症例検討である胆膵カンファレンスを行っている。これらを通じた患者の情報共有が各科の連携を円滑にし、正確な術前診断と適切な治療の選択、周術期の安全性向上、長期的な患者予後改善に寄与していると考えられる。今後も患者のアウトカムを検証しながら、チーム医療によるよりよい診療を継続して行くことが重要である。(著者抄録)

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語   掲載種別：記事・総説・解説・論説等（学術雑誌）  

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Medical Treatment of Chronic Pancreatitis

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Medical treatment of unresectable malignant insulinoma in an elderly patient

記述言語：日本語  

＜文献概要＞慢性膵炎の診断基準が改訂され,新たな概念としてmechanistic definitionが取り入れられた.アルコール性と,特発性,遺伝性,家族性などの非アルコール性に分類されており,成因や病期を考慮した慢性膵炎診療が重要となる.本邦では定期的に慢性膵炎の疫学調査が行われており,成因として男性ではアルコール性,女性では特発性が最多である.慢性膵炎の進展には飲酒継続や喫煙が関連しており,断酒・禁煙などの生活習慣改善が重要であるとともに,膵癌発症の高リスクであることを念頭に置いた診療が必要である.

記述言語：日本語  

記述言語：日本語  

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記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

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記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

慢性膵炎の原因として代表的な因子である飲酒・喫煙は介入可能であるにもかかわらず,成因によっては解決に至らず,就業不能に至るケースや家族や友人といったコミュニティーの協力も得られないケースをしばしば経験する.当院では対応に難渋した症例を踏まえ,多職種連携の重要性を再認識することとなった.医師・看護師の慢性膵炎に対する知識や患者支援の状況をアンケートを用いて把握するとともに,現状の問題点の抽出を行った.その結果,職種間の連携が不十分であることや各職種での知識も不足していることが抽出された.その対応策として多職種で患者アンケートを作成し,各職種間での情報共有や問題意識を醸成することができた.慢性膵炎患者が抱える問題は患者の自助努力だけでは解決できないことも多く,多職種連携の介入さらには周囲のコミュニティーを巻き込んだ患者サポートも検討する必要がある.(著者抄録)

記述言語：日本語  

慢性膵炎の原因として代表的な因子である飲酒・喫煙は介入可能であるにもかかわらず,成因によっては解決に至らず,就業不能に至るケースや家族や友人といったコミュニティーの協力も得られないケースをしばしば経験する.当院では対応に難渋した症例を踏まえ,多職種連携の重要性を再認識することとなった.医師・看護師の慢性膵炎に対する知識や患者支援の状況をアンケートを用いて把握するとともに,現状の問題点の抽出を行った.その結果,職種間の連携が不十分であることや各職種での知識も不足していることが抽出された.その対応策として多職種で患者アンケートを作成し,各職種間での情報共有や問題意識を醸成することができた.慢性膵炎患者が抱える問題は患者の自助努力だけでは解決できないことも多く,多職種連携の介入さらには周囲のコミュニティーを巻き込んだ患者サポートも検討する必要がある.(著者抄録)

記述言語：日本語  

記述言語：日本語  

膵性糖尿病は、二次性糖尿病の中で膵炎や膵癌、膵切除後などの膵疾患に伴う糖尿病と位置付けられる。β細胞減少によるインスリン分泌低下に加えて、α細胞減少によるグルカゴン分泌低下も伴っており、血糖コントロールが不安定になることが多い。膵外分泌機能を適切に評価し、十分なエネルギー摂取と消化剤の補充後に血糖コントロールを行うことが重要である。膵性糖尿病の治療として経口血糖降下薬のエビデンスは乏しく、インスリン療法が主体となるが、膵内外分泌機能も含めた症例ごとの検討が必要である。一般の糖尿病に比べて低血糖のリスクが大きく、比較的緩やかな血糖コントロールが推奨されている。(著者抄録)

記述言語：日本語  

＜文献概要＞ポイント ◆GEP-NETの治療法は多様化しており,適切な治療選択のために正確な画像診断とgrade分類が必須である.◆CT,MRI,EUS,SRSが基本的な画像検査となり,症例に応じてSASIテストやERCPを組み合わせて診断する.◆原発巣(消化管,膵)からの内視鏡下生検(通常生検とEUS-FNA)と肝転移巣に対する肝腫瘍生検が組織学的確定診断に有用である.WHO分類に基づいたgrade分類を併せて評価する必要がある.

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

膵・消化管神経内分泌腫瘍(GEP-NEN)に対する新たな治療薬が近年相次いで登場し、GEP-NENに対する治療戦略は多様化している。そのなかで、肝転移を制御することを目的とした局所療法として経動脈的塞栓療法(TAE)、経動脈的化学塞栓療法(TACE)、ラジオ波焼灼術(RFA)などが古くから施行されている。いずれも良好な治療成績が報告されており、とくに機能性腫瘍に対する有用性(症状改善効果)が示唆される。治療選択肢が多様化した現在においても、重要な治療オプションの一つとして念頭に置く姿勢が重要である。今後は他治療薬との比較や治療選択順などを検討し、GEP-NENの治療全体における肝局所療法の位置付けをより明確にしていく必要がある。本稿ではGEP-NEN肝転移に対するTAE、TACE、RFAの文献的報告を中心に解説し、さらに今後の展望・課題について言及する。(著者抄録)

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

癌の緩和医療の中でも、癌の進行・転移による消化管閉塞に対する治療の選択肢は、これまで限られていた。本邦において、悪性腫瘍による消化管閉塞に対して、従来はバイパス術や人工肛門造設術が行われてきた。しかし、QOL改善のために手術を行うことへの抵抗感は否めず、消化管の閉塞解除を少ない負担で行える方法は長らく望まれていた。近年、内視鏡技術の急速な進歩によって、消化管狭窄には自己拡張型金属ステント(self-expandable metallic stent:SEMS)留置術が開発され、全消化管に臨床導入可能となった。本稿では、食道、胃十二指腸、大腸に分けて、最近の消化管ステントの現状を概説する。(著者抄録)

記述言語：日本語  

癌の緩和医療の中でも、癌の進行・転移による消化管閉塞に対する治療の選択肢は、これまで限られていた。本邦において、悪性腫瘍による消化管閉塞に対して、従来はバイパス術や人工肛門造設術が行われてきた。しかし、QOL改善のために手術を行うことへの抵抗感は否めず、消化管の閉塞解除を少ない負担で行える方法は長らく望まれていた。近年、内視鏡技術の急速な進歩によって、消化管狭窄には自己拡張型金属ステント(self-expandable metallic stent:SEMS)留置術が開発され、全消化管に臨床導入可能となった。本稿では、食道、胃十二指腸、大腸に分けて、最近の消化管ステントの現状を概説する。(著者抄録)

記述言語：日本語  

自己免疫性膵炎(AIP)の概念が初めて報告されて10数年が経過したが、この間各国からそれぞれの疾患概念や診断体系に合わせて診断基準が提唱された。日本は世界に先駆けて診断基準を提唱したが、主にLPSPと呼ばれる組織型を膵癌と誤診することなく確実に診断することが基本的理念であった。一方欧米ではIDCPと呼ばれる別の組織型も報告されており、国際的なコンセンサスを作る必要性が生じてきた。2011年国際コンセンサス診断基準(ICDC)が提唱され、AIPはtype 1、type 2に大別された。ICDCに齟齬をなくすべく日本の診断基準も最近改訂された。今後新しい診断基準の問題点について検証していく必要がある。(著者抄録)

記述言語：日本語  

自己免疫性膵炎(AIP)の概念が初めて報告されて10数年が経過したが、この間各国からそれぞれの疾患概念や診断体系に合わせて診断基準が提唱された。日本は世界に先駆けて診断基準を提唱したが、主にLPSPと呼ばれる組織型を膵癌と誤診することなく確実に診断することが基本的理念であった。一方欧米ではIDCPと呼ばれる別の組織型も報告されており、国際的なコンセンサスを作る必要性が生じてきた。2011年国際コンセンサス診断基準(ICDC)が提唱され、AIPはtype 1、type 2に大別された。ICDCに齟齬をなくすべく日本の診断基準も最近改訂された。今後新しい診断基準の問題点について検証していく必要がある。(著者抄録)

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

再発性膵炎は、日常診療のなかで比較的よく経験する。当科における再発性膵炎症例28例の膵管像の検討では、胆石性以外の症例で膵管狭窄や膵管走行異常に伴う膵液流出障害を高率に認めた。膵液流出障害を認めた症例で、乳頭切開などの内視鏡的治療を施行した23例中、半数以上の症例で比較的長期にわたり膵炎の再発なく経過していた。内視鏡的治療を施行しても膵炎が再発した症例の多くは飲酒継続例であった。再発性膵炎症例のうち、膵液流出障害がある症例では患者への侵襲の大きさなども考慮して、内視鏡的治療が第一選択となりうると考えられる。しかし、内視鏡的治療だけでは改善がみられず、外科的治療が必要となる症例が存在し、個々の症例において適応を考慮する必要がある。飲酒継続症例では治療後の再発例が多く、断酒が絶対必要であると考えられた。(著者抄録)

記述言語：日本語  

再発性膵炎は、日常診療のなかで比較的よく経験する。当科における再発性膵炎症例28例の膵管像の検討では、胆石性以外の症例で膵管狭窄や膵管走行異常に伴う膵液流出障害を高率に認めた。膵液流出障害を認めた症例で、乳頭切開などの内視鏡的治療を施行した23例中、半数以上の症例で比較的長期にわたり膵炎の再発なく経過していた。内視鏡的治療を施行しても膵炎が再発した症例の多くは飲酒継続例であった。再発性膵炎症例のうち、膵液流出障害がある症例では患者への侵襲の大きさなども考慮して、内視鏡的治療が第一選択となりうると考えられる。しかし、内視鏡的治療だけでは改善がみられず、外科的治療が必要となる症例が存在し、個々の症例において適応を考慮する必要がある。飲酒継続症例では治療後の再発例が多く、断酒が絶対必要であると考えられた。(著者抄録)

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

当科で経験した小膵癌6症例の検討

記述言語：日本語  

記述言語：日本語  

Life style and pancreatic cancer

記述言語：日本語  

記述言語：日本語  

膵内分泌腫瘍(PNET)はまれな疾患であり,ホルモン産生能や症状の有無から機能性と非機能性に分類される.本邦初の疫学調査では非機能性腫瘍が最多であり,インスリノーマ,ガストリノーマの順に多い結果であった.PNET診断においては正確な存在診断と各種modalityを組み合わせた局在診断が重要である.血清クロモグラニンA測定やソマトスタチンレセプターシンチグラフィーは診断や治療効果判定に有用であるが,本邦では保険収載されていない.外科的切除が第一選択であるが,切除不能例には全身化学療法,ソマトスタチンアナログ,肝動脈塞栓術などを組み合わせた集学的治療が行われる.RAD001(everolimus)に代表される新規分子標的薬の有効性が報告されており,今後本領域における標準治療となる可能性が高い.(著者抄録)

記述言語：日本語  

膵内分泌腫瘍(PNET)はまれな疾患であり,ホルモン産生能や症状の有無から機能性と非機能性に分類される.本邦初の疫学調査では非機能性腫瘍が最多であり,インスリノーマ,ガストリノーマの順に多い結果であった.PNET診断においては正確な存在診断と各種modalityを組み合わせた局在診断が重要である.血清クロモグラニンA測定やソマトスタチンレセプターシンチグラフィーは診断や治療効果判定に有用であるが,本邦では保険収載されていない.外科的切除が第一選択であるが,切除不能例には全身化学療法,ソマトスタチンアナログ,肝動脈塞栓術などを組み合わせた集学的治療が行われる.RAD001(everolimus)に代表される新規分子標的薬の有効性が報告されており,今後本領域における標準治療となる可能性が高い.(著者抄録)

記述言語：日本語  

膵神経内分泌腫瘍(pNET)の治療は、手術療法が原則であるが、切除不能例においては腫瘍増殖を抑制し生命予後を向上させることと、臨床症状の改善の両方を目的とした治療が必要である。機能性腫瘍では、腫瘍浸潤・転移による症状のみならず、ホルモン過剰症状によって患者のQuality of lifeが阻害される。ソマトスタチンアナログ、中でもオクトレオチドは機能性NETのホルモン過剰症状に対する有効性が以前から報告され、現在では徐放剤が開発された。最近のPROMID試験の結果により、進行した中腸由来NET患者におけるオクトレオチド徐放剤の腫瘍安定化効果が指摘された。ソマトスタチンアナログは、切除不能膵神経内分泌腫瘍における内科的治療においても重要な役割を演じてきているが、非機能性pNETに対する抗腫瘍効果の評価には更なる検討が必要である。新規ソマチスタチンアナログ製剤の開発や、新規薬剤との併用療法の臨床試験も進んでおり、今後に期待される。(著者抄録)

記述言語：日本語  

膵神経内分泌腫瘍(pNET)の治療は、手術療法が原則であるが、切除不能例においては腫瘍増殖を抑制し生命予後を向上させることと、臨床症状の改善の両方を目的とした治療が必要である。機能性腫瘍では、腫瘍浸潤・転移による症状のみならず、ホルモン過剰症状によって患者のQuality of lifeが阻害される。ソマトスタチンアナログ、中でもオクトレオチドは機能性NETのホルモン過剰症状に対する有効性が以前から報告され、現在では徐放剤が開発された。最近のPROMID試験の結果により、進行した中腸由来NET患者におけるオクトレオチド徐放剤の腫瘍安定化効果が指摘された。ソマトスタチンアナログは、切除不能膵神経内分泌腫瘍における内科的治療においても重要な役割を演じてきているが、非機能性pNETに対する抗腫瘍効果の評価には更なる検討が必要である。新規ソマチスタチンアナログ製剤の開発や、新規薬剤との併用療法の臨床試験も進んでおり、今後に期待される。(著者抄録)

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

自己免疫性膵(AIP)は,その成因と病態の進展に自己免疫的機序が関与している膵の炎症性疾患と理解されている.近年の症例の蓄積により,ステロイド治療経過中/中止後に再燃をきたす症例が報告されるようになり,ステロイドの維持療法の重要性も指摘されてきている.長期的には膵内外分泌機能低下,さらには膵の萎縮,膵石を合併する症例も経験されるようになった.一方,非ステロイド投与下に自然軽快する症例も報告されてきているが,再燃例も認め慎重な検討が必要である.2006年の本邦のAIP改訂基準では,「長期予後は不明であるが,膵石合併の報告がある」とされているが,近年,膵癌合併の症例報告も散見されてきている.AIPが膵癌のリスクファクターになりうるかどうかも含め,AIPの長期予後についてはさらなる症例の蓄積が必要である.(著者抄録)

記述言語：日本語  

膵傷害が起こると局所の傷害された腺房細胞や内皮細胞から炎症性サイトカインが産生され、それを契機に遺伝的背景もしくは環境要因により膵局所から全身炎症となる。重症化に重要なサイトカインにはTumor necrosis factor(TNF)-αとInterleukin(IL)-6、IL-8などがあり、サイトカインが炎症の進展・重症化に深くかかわっている。一方、慢性膵炎では頻回もしくは慢性の炎症刺激を契機に線維化が進展することが想定される。遊走した炎症細胞とともに、その線維化の中心的役割を果たすpancreatic stellate cell(PSC)は局所にて産生されたサイトカイン・ケモカインを介して活性化し、細胞増殖、細胞外マトリックスの産生を促し、線維化を進展させる。(著者抄録)

記述言語：日本語  

膵傷害が起こると局所の傷害された腺房細胞や内皮細胞から炎症性サイトカインが産生され、それを契機に遺伝的背景もしくは環境要因により膵局所から全身炎症となる。重症化に重要なサイトカインにはTumor necrosis factor(TNF)-αとInterleukin(IL)-6、IL-8などがあり、サイトカインが炎症の進展・重症化に深くかかわっている。一方、慢性膵炎では頻回もしくは慢性の炎症刺激を契機に線維化が進展することが想定される。遊走した炎症細胞とともに、その線維化の中心的役割を果たすpancreatic stellate cell(PSC)は局所にて産生されたサイトカイン・ケモカインを介して活性化し、細胞増殖、細胞外マトリックスの産生を促し、線維化を進展させる。(著者抄録)

記述言語：日本語  

記述言語：日本語  

慢性膵炎は、アルコール摂取やその他の原因により引き起こされる非可逆性で進行性の慢性炎症性疾患である。通常反復する上腹部痛・背部痛で始まり、進展に伴って膵内外分泌機能が低下し、膵外分泌機能障害および耐糖能障害が出現してくる。長期予後として、悪性腫瘍が指摘されている。慢性膵炎はその病期により代償期、移行期、非代償期に分類されるが、代償期の前には膵炎症状に乏しい潜在期の時期も想定されている。2009年に慢性膵炎臨床診断基準の改訂案が提案された。慢性膵炎はアルコール性と非アルコール性に大別され、自己免疫性膵炎、閉塞性慢性膵炎は別個として扱われる。さらに早期慢性膵炎が規定された。慢性膵炎の特殊型としてGroove膵炎、腫瘤形成性膵炎があげられる。診断困難例が存在し、特に膵臓癌との鑑別が重要である。(著者抄録)

記述言語：日本語  

記述言語：日本語  

慢性膵炎は、アルコール摂取やその他の原因により引き起こされる非可逆性で進行性の慢性炎症性疾患である。通常反復する上腹部痛・背部痛で始まり、進展に伴って膵内外分泌機能が低下し、膵外分泌機能障害および耐糖能障害が出現してくる。長期予後として、悪性腫瘍が指摘されている。慢性膵炎はその病期により代償期、移行期、非代償期に分類されるが、代償期の前には膵炎症状に乏しい潜在期の時期も想定されている。2009年に慢性膵炎臨床診断基準の改訂案が提案された。慢性膵炎はアルコール性と非アルコール性に大別され、自己免疫性膵炎、閉塞性慢性膵炎は別個として扱われる。さらに早期慢性膵炎が規定された。慢性膵炎の特殊型としてGroove膵炎、腫瘤形成性膵炎があげられる。診断困難例が存在し、特に膵臓癌との鑑別が重要である。(著者抄録)

記述言語：日本語  

慢性膵炎臨床診断改訂基準の有用性を検討する目的にて、現行の診断基準と改訂基準とを慢性膵炎疑いの当科で経験した125症例を用いて比較検討した。現行基準で確診78例中71例(91.0%)は改訂基準でも確診であった。準確診への移行は7例(9.0%)のみであった。一方、現行基準で準確診27例中4例(14.8%)が確診へ、19例(70.4%)が早期慢性膵炎へ移行した。その19例は現行基準で膵外分泌の異常が有り準確診に分類されていた。慢性膵炎現行基準で疑診例11例中9例(81.8%)、異常なしの9例中5例(55.6%)が早期慢性膵炎に移行した。今回の検討で慢性膵炎の診断において改訂基準の妥当性が確認できた。また、早期の慢性膵炎の拾い上げにも有用であった。(著者抄録)

記述言語：日本語  

慢性膵炎臨床診断改訂基準の有用性を検討する目的にて、現行の診断基準と改訂基準とを慢性膵炎疑いの当科で経験した125症例を用いて比較検討した。現行基準で確診78例中71例(91.0%)は改訂基準でも確診であった。準確診への移行は7例(9.0%)のみであった。一方、現行基準で準確診27例中4例(14.8%)が確診へ、19例(70.4%)が早期慢性膵炎へ移行した。その19例は現行基準で膵外分泌の異常が有り準確診に分類されていた。慢性膵炎現行基準で疑診例11例中9例(81.8%)、異常なしの9例中5例(55.6%)が早期慢性膵炎に移行した。今回の検討で慢性膵炎の診断において改訂基準の妥当性が確認できた。また、早期の慢性膵炎の拾い上げにも有用であった。(著者抄録)

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

The current chemotherapy for advanced pancreatic cancer : including the result of phase II study of irinotecan (CPT-11)

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

種別：大会・シンポジウム等 

種別：大会・シンポジウム等 

種別：査読等 

外国語雑誌　査読論文数：29

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種別：大会・シンポジウム等 

種別：大会・シンポジウム等 

種別：大会・シンポジウム等 

種別：大会・シンポジウム等 

種別：大会・シンポジウム等 

種別：大会・シンポジウム等 

種別：大会・シンポジウム等 

種別：大会・シンポジウム等 

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種別：大会・シンポジウム等 

種別：大会・シンポジウム等 

種別：大会・シンポジウム等 

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外国語雑誌　査読論文数：29

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種別：大会・シンポジウム等 

種別：大会・シンポジウム等 

種別：大会・シンポジウム等 

種別：大会・シンポジウム等 

種別：大会・シンポジウム等 

種別：大会・シンポジウム等 

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種別：大会・シンポジウム等 

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外国語雑誌　査読論文数：1