Language：English   Publisher：Liver International  

Background: Patatin-like phospholipase domain 3 (PNPLA3) I148M (rs738409 C>G) variant has been reported as a risk factor for metabolic dysfunction-associated steatotic liver disease/steatohepatitis and contributes to hepatic fibrosis and hepatocellular carcinoma (HCC); however, its role in recurrence after liver resection remains unclear. This study aimed to evaluate the effect of PNPLA3 variants on HCC recurrence after liver resection. Methods: One hundred sixteen patients with non-viral HCC who underwent curative liver resection were retrospectively analysed. PNPLA3 rs738409 genotype was identified using blood-derived genomic DNA. Recurrence-free survival (RFS) was compared across genotypes, and multivariate analysis was performed to identify the independent risk factors for recurrence. Postoperative changes in fibrosis indexes over 2 years were also evaluated according to genotype. Results: The number of patients in each PNPLA3 genotype group was as follows: CC (n = 20), CG (n = 55) and GG (n = 41). The CG/GG group showed significantly poorer RFS than the CC group, and multivariate analysis identified the PNPLA3 CG/GG genotype as an independent risk factor, especially for late recurrence. To better evaluate the effect on the remnant liver, patients with early recurrence were excluded from the study. In the CG/GG group, the fibrosis indices worsened over the 2 years following surgery, whereas they remained stable in the CC group. Among the patients with CG/GG, those with worsening fibrosis had a significantly higher rate of late recurrence. Conclusions: Patients with the PNPLA3 CG/GG genotype, especially those with progressive fibrosis, have a high risk of recurrence after liver resection. PNPLA3 genotyping may help identify patients at high risk of late recurrence who require careful long-term surveillance.

DOI： 10.1111/liv.70531

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Language：English   Publisher：Surgery Today  

Purpose: To investigate the independent predictors of progression-free survival (PFS) after gemcitabine, cisplatin, and durvalumab (GCD) therapy for advanced biliary tract cancer (BTC), including the thyroid-stimulating hormone (TSH) ratio pre- and post-GCD. Methods: The subjects of this retrospective analysis were 29 patients receiving GCD for advanced BTC. The cutoff TSH ratios were determined by a receiver operating characteristic (ROC) curve for PFS. The independent predictors of PFS after GCD were determined by univariate and multivariate analyses. Results: The median PFS was 4.9 (range, 0.9–16.8) months. The objective response and disease control rates were 13.0% and 52.2%, respectively. The cutoff values of the TSH ratio after one and two cycles were 0.97 [area under the ROC curve (AUROC): 0.86, 95% confidence interval (CI): 0.70–1.00], p = 0.02] and 1.2 (AUROC: 0.820, 95% CI: 0.664–0.976), respectively. Multivariate analysis identified pretreatment neutrophil-to-lymphocyte ratio (NLR) ≥ 5 [hazard ratio (HR): 6.27, 95% CI: 1.83–21.5, p = 0.004] and TSH ratio after two cycles of < 1.2 (HR: 3.25, 95% CI: 1.25–8.46, p = 0.02) as independent predictors of PFS. Conclusion: The TSH ratio after two GCD cycles of < 1.2 and a pretreatment NLR ≥ 5 are potential prognostic factors for poor PFS.

DOI： 10.1007/s00595-025-03227-3

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Language：English   Publisher：Transplantation Proceedings  

Background: Living donor liver transplantation is the definitive treatment for decompensated cirrhosis. While the prognosis for high Model for End-Stage Liver Disease (MELD) patients is well-studied, risk factors in low MELD patients remain unclear. This study aimed to identify prognostic risk factors for low MELD cases. Methods: We analyzed 838 adult living donor liver transplantation patients from September 1998 to April 2024 and divided them into low MELD (≤15) and high MELD (>15) groups. The low MELD group was further categorized into early and non-early graft loss subgroups. The risk factors for recipient survival were analyzed. Results: Of the 838 patients, 408 (48.7%) were in the low MELD group, and 430 (51.3%) were in the high MELD group. The survival rates were significantly higher in the low MELD group than in the high MELD group. In the low MELD group, 5.1% (21 patients) experienced early graft loss, and 94.9% (387 patients) were classified as non-early graft loss. Independent risk factors for early graft loss included donor body mass index ≥25 kg/m², absence of simultaneous splenectomy, and postoperative complications. One year survival rates were significantly lower in patients with more risk factors. Conclusion: Donor body mass index, absence of simultaneous splenectomy, and postoperative complications were identified as independent risk factors for poor prognosis in living donor liver transplantation patients with low MELD. Surgeons must focus on performing meticulous surgeries to minimize the risk of complications.

DOI： 10.1016/j.transproceed.2025.12.005

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PubMed

Language：English   Publisher：Hepatology Research  

Background: Complications associated with the Fontan circulation have become evident in recent years. Fontan-associated liver disease (FALD) has attracted particular attention. However, many aspects of this condition including FALD-associated hepatocellular carcinoma (FALD-HCC) remain unclear. Patients and Methods: Since 2018, 12 liver resections for FALD-HCC were performed in 9 patients at our institution. These 12 procedures were reviewed, and 9 cases of primary HCC were compared with 216 cases of primary HCC resection performed during the same period in non-FALD patients in terms of short- and long-term outcomes. Results: Among 12, nine were initial and three were recurrences. Approaches included open (n = 6), laparoscopic (n = 4), and robotic surgery (n = 2). Compared with non-FALD patients, FALD group was younger (37 vs. 69 years, p < 0.0001), had lower BMI (19.0 vs. 24.1, p = 0.0002) and showed advanced fibrosis/cirrhosis (F3–4) more frequently (p = 0.03). Intraoperative blood loss was greater in the FALD group (1695 vs. 520 mL, p = 0.0003). Factors associated with blood loss > 1000 mL included CVP > 12 mmHg, tumor size > 2 cm, tumor depth > 3 cm from the liver surface. Among nine patients under regular post-Fontan imaging surveillance, tumors tended to be smaller and blood loss lower. With a mean follow-up period of 32.1 months in the FALD group, recurrence-free survival did not differ between the groups. Conclusion: Long-term outcomes seem comparable between FALD and non-FALD HCC. In particular, FALD-HCC ≤ 2 cm and close to the liver surface with CVP ≤ 12 mmHg could be potential candidates for surgical resection, including minimally invasive approaches. Post-Fontan surveillance may be crucial.

DOI： 10.1111/hepr.70150

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PubMed

Language：English   Publisher：Jci Insight  

Genetic variants in lipid metabolism influence the risk of developing metabolic dysfunction–associated steatotic liver disease (MASLD), cirrhosis, and end-stage liver disease (ESLD). The mechanisms by which these variants drive disease are poorly understood. Because of the PNPLA3-I148M variant’s strong correlation with all stages of the MASLD spectrum and the lack of tractable therapeutic targets, we sought to understand its impact on cellular function and liver metabolism. Primary human hepatocytes (HAHs) and induced pluripotent stem cell–derived (iPSC-derived) hepatocytes (iHeps) from healthy individuals possessing the PNPLA3-I148M mutation were characterized for changes in lipid metabolism, cellular stress, and survival. Using lipidomics, metabolomics, stable isotope tracing, and flux propensity analysis, we created a comprehensive metabolic profile of the changes associated with the PNPLA3-I148M variant. Functional analysis showed that the presence of the PNPLA3-I148M variant increased endoplasmic reticulum stress, mitochondrial dysfunction, and peroxisomal β-oxidation, ultimately leading to cell death via ferroptosis. Nutritional interventions, ferroptosis-specific inhibitors, and genetic approaches modulating GPX4 activity in PNPLA3-I148M HAHs and iHeps decreased programmed cell death. Our findings indicate that therapies targeting ferroptosis in patients carrying the PNPLA3-I148M variant could affect the development of MASLD and ESLD and highlight the utility of iPSC-based models for the study of genetic contributions to hepatic disorders.

DOI： 10.1172/jci.insight.193805

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Authorship：Lead author   Language：English   Publisher：Journal of Surgical Research  

Introduction: Clinically relevant postoperative pancreatic fistula (CR-POPF) after pancreaticoduodenectomy (PD) is one of the most life-threatening complications. Early drain removal after PD is recommended in the clinical setting; however, the risk stratification for CR-POPF to guide drain removal is not widely recognized. Methods: This single-center retrospective study included patients who underwent PD between 2013 and 2024. In total, 280 patients were divided into training (n = 196) and validation (n = 84) cohorts by random sampling. The predictive impact of CR-POPF was evaluated using receiver operating characteristic curves of perioperative factors in the training cohort. Based on a probability formula, a predictive model of CR-POPF was established. Results: CR-POPF occurred in 29.1% of 196 patients in the training cohort. Postoperative day 5 C-reactive protein and drain fluid amylase levels were the strongest diagnostic values in patients with CR-POPF (area under the receiver operating characteristic curve, area under the ROC curve: 0.787 and 0.750, respectively). Logistic regression analysis provided the prediction index (10.5 × C-reactive protein [mg/dL] + 0.01 × drain fluid amylase [IU/L] ± 21.8 [add if the pancreas is soft; subtract if it is hard]) was defined as a new prognostic model for the probability of CR-POPF. A higher CR-POPF prediction index was an independent prognostic factor in the multivariate analysis. Finally, the clinical feasibility of the CR-POPF prediction index was confirmed in the validation cohort. Conclusions: The CR-POPF index could guide safe early drain removal, which may help surgeons to implement appropriate drain management after PD.

DOI： 10.1016/j.jss.2025.06.028

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PubMed

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

Language：English   Publisher：International Journal of Clinical Oncology  

Background: Ferroptosis, a form of programmed cell death, is a potential target for cancer therapy. Metazoan SpoT Homolog 1 (MESH1) possesses intracellular NADPH phosphatase activity, which has been linked to ferroptosis. However, the molecular effects on the ferroptosis in hepatocellular carcinoma (HCC) remain unclear. This study aimed to investigate the relationship between MESH1 expression and the prognosis of patients with HCC, as well as its impact on ferroptosis in HCC cells. Methods: We used resected specimens from patients to assess the relationship between MESH1 expression and prognosis. HCC cell lines were used to evaluate the impact of MESH1 expression on the cell phenotype and ferroptosis through various assays, RNA sequencing, and an animal experiment with xenograft mice model. Results: We found that high MESH1 expression correlated with good outcomes. Further investigation demonstrated that MESH1 also exhibits NADPH phosphatase activity in HCC, contributing to increased sensitivity to ferroptosis when the ferroptosis inducer was used. Similar results were observed with other ferroptosis inducers, sorafenib and lenvatinib. Notably, RNA sequencing analysis of cells with MESH1 KD revealed a correlation between intracellular iron homeostasis and MESH1 levels. These results suggested that MESH1 also can affect ferroptosis sensitivity through changing intracellular iron levels. Tumors derived from MESH1 KD cells in xenograft mice showed reduced sensitivity to sorafenib and lenvatinib, further supporting the role of MESH1 ferroptosis regulation. Conclusion: This study suggests that MESH1 influences intracellular redox and iron regulatory pathways, both of which are linked to cellular processes associated with ferroptosis.

DOI： 10.1007/s10147-025-02818-x

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Language：English   Publisher：Annals of Surgical Oncology  

Background: Signal-regulatory protein alpha (SIRPα) has recently garnered attention for its role in the immune system, commonly referred to as the “don’t eat me” signal. However, the relationship between SIRPα expression in tumor cells and prognosis in patients undergoing hepatectomy for intrahepatic cholangiocarcinoma (ICC) has been scarcely reported. Patients and Methods: A total of 117 patients who underwent hepatectomy for ICC were enrolled in this study. Immunohistochemical staining was performed to evaluate SIRPα, programmed cell death-ligand 1 (PD-L1), and cluster of differentiation 8 (CD8). The relationships between SIRPα expression, clinicopathological characteristics, and patient outcomes were analyzed. Results: The macrophage-SIRPα-positive group exhibited a higher rate of lymph node metastasis (p = 0.0013). The tumor-cell-SIRPα-positive group showed lower carcinoembryonic antigen levels (p = 0.0068) and fewer cases of the perihilar type (p = 0.0165). In multivariate analysis, SIRPα positivity in tumor cells was identified as an independent prognostic factor for both disease-free survival (p = 0.0198) and overall survival (p = 0.0089). Notably, SIRPα positivity in tumor cells showed no significant correlation with PD-L1 expression or CD8-positive tumor-infiltrating T cells in ICC. Conclusions: Our findings demonstrate that SIRPα expression in tumor cells is more critical than its expression in macrophages for predicting the prognosis of patients with ICC following hepatic resection.

DOI： 10.1245/s10434-025-17813-9

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Authorship：Lead author   Language：Japanese   Publisher：南江堂  

DOI： 10.15106/j_geka87_518

CiNii Research

Language：Japanese   Publisher：南江堂  

DOI： 10.15106/j_geka87_353

CiNii Research

Language：Japanese   Publisher：(株)南江堂  

＜文献概要＞肝癌の中でも,特に肝細胞癌は慢性肝炎や肝硬変を背景肝に有するためサルコペニアの合併率が高いことが知られている.肝細胞癌に対する肝切除術において,サルコペニアの合併は予後不良因子であることから,初診時の握力や検査結果をもとにしたわれわれの術前介入のプロトコールを紹介する.加えて,全身薬物療法におけるサルコペニアの影響に関して薬物による相違点を検討する.

Authorship：Lead author   Language：Japanese   Publisher：(株)南江堂  

＜文献概要＞・肝細胞癌患者の背景肝は障害を伴うことが多く,肝障害の進行に伴って肝硬変にいたり,その結果,門脈圧亢進症を呈することも少なくない.・欧米のガイドラインでは門脈圧亢進症の存在は,肝切除ではなく肝移植を適応としているが,本邦では肝予備能が保たれていれば門脈圧亢進症を伴っていても肝切除を行うことがある.・肝硬変が進行すると,肝予備能の低下だけではなく血小板減少や難治性食道静脈瘤,難治性胸腹水など複雑な病態を呈し,周術期を通して肝細胞癌に対する肝切除に難渋することが多い.・門脈圧亢進症の病態を的確に把握し術前・術後管理に十分対策していれば,万一の合併症に迅速に対応することができる.

Language：Japanese   Publisher：南江堂  

DOI： 10.15106/j_geka87_182

CiNii Research

Language：Japanese   Publisher：(株)南江堂  

＜文献概要＞移植医療は多岐に及ぶ知識や技術,経験が求められるが,レシピエントを助けたいと願うドナーがいてはじめて成り立つ医療である.だからこそ,われわれ医療者もその思いに応えられる熱意が必要であり,疲弊することなくその熱意を持続できる環境づくりが不可欠となる.多職種のチーム体制を確立させ,分業化をよりすすめることが,将来的に医師の多様な働き方に対応できるような環境づくりの一歩となるのではないかと考える.

Authorship：Lead author   Language：English   Publisher：Surgery Today  

Purpose: Hepatocellular carcinoma (HCC) frequently recurs after radical resection, resulting in a poor prognosis. This study assessed the prognostic value of Mac-2 binding protein glycosylation isomer (M2BPGi) for early recurrence (ER) in patients with HCC. Methods: Patients who underwent radical resection for HCC between 2015 and 2021. HCC recurrence within one year after curative resection was defined as ER. Results: The 150 patients were divided into two groups: non-ER (116, 77.3%) and ER (34, 22.7%). The ER group had a lower overall survival rate (p < 0.0001) and significantly higher levels of M2BPGi (1.06 vs. 2.74 COI, p < 0.0001) than the non-ER group. High M2BPGi levels (odds ratio [OR] 1.78, 95% confidence interval [CI] 1.31–2.41, p < 0.0001) and a large tumor size (OR 1.31, 95% CI, 1.05–1.63; p = 0.0184) were identified as independent predictors of ER. M2BPGi was the best predictor of ER according to a receiver operating characteristic (ROC) analysis (area under the ROC curve 0.82, p < 0.0001). Conclusions: M2BPGi can predict ER after surgery and is useful for risk stratification in patients with HCC.

DOI： 10.1007/s00595-024-02885-z

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PubMed

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

肝細胞癌(HCC)に根治的切除を行った患者の早期再発(ER)とMac-2結合蛋白糖鎖修飾異性体(M2BPGi)との関連を検討した。2015～2021年に当院で初発HCCに対して肝切除を行い、かつ術前にM2BPGiを測定していた150例を対象とした。根治的切除後1年以内のHCC再発をERと定義し、患者をER群34例(22.7%)と非ER群116例(77.3%)に分けた。その結果、全生存率は非ER群と比較してER群で有意に低かった。M2BPGi値は非ER群と比較してER群が有意に高かった(1.06vs2.74 cutoff index)。多変量解析では、M2BPGi高値と腫瘍径大はERの独立予測因子であった。ROC解析では、M2BPGiはER予測能は他の因子と比較して最良であった(AUC=0.82)。以上より、M2BPGiは術後ERの有用な予測因子であると考えられた。

Language：English  

DOI： 10.1097/SP9.0000000000000048

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PubMed

Language：Japanese   Publisher：The Japan Society for Transplantation  

<p>【背景】高齢レシピエントはサルコペニアや様々な合併症を有し、生体肝移植適応基準は各施設に委ねられている。当院ではPS良好であれば70歳代の症例においても生体肝移植を検討し、術前筋肉電気刺激装置(EMS)による介入をおこなっており、その治療成績、妥当性について明らかとする。【対象・方法】2025年1月までの成人間生体肝移植840例を対象。(1)高齢群(70歳以上, n=30)と非高齢群（70歳未満, n=810）の背景因子・術後成績、(2)プロペンシティスコアマッチング（両群n=30）を用いて妥当性を検討した。【結果】(1)高齢群平均年齢は71.3歳、最高齢は76歳だった。背景因子では、高齢群は肝癌(p＜0.01)やCKD(p＜0.01)の合併率が高く、急性肝不全(p=0.046)やドナー50歳以上(p=0.021)は少なく、手術時間(p=0.03)は短かった。その他の因子（レシピエント性別、BMI、MELD、術前入院、ドナー性別、ABOi、GV/SLV、冷/温虚血時間、出血量）に有意差は認めなかった。術後成績は、敗血症、SFSG、門脈血栓症、胆管狭窄、術後在院日数、術後30日死亡率は両群間で同等、移植後生存率も同等だった。高齢群術後1年以内死亡症例は、術前PS不良で術後リハビリ不良の敗血症症例とSFSGによるグラフト不全症例だった。(2)PSM後は高齢群、非高齢群の術後成績、移植後生存率は同等だった。【まとめ】70歳以上高齢レシピエントにおいても、術前PS良好、周術期リハビリやEMS導入により安全な肝移植が可能である。</p>

DOI： 10.11386/jst.60.supplement_s157_2

CiNii Research

Language：Japanese   Publisher：The Japan Society for Transplantation  

<p>臓器移植法改正以降、脳死下臓器提供はコロナ禍中に減少したものの、徐々に増加傾向にある。しかし、臓器移植待機患者が減少することはなく、肝臓・腎臓においては未だに生体ドナーからの移植が主流である。一方、心停止後臓器提供は手術室を持つ医療施設であれば可能であるが、その数は激減し、2024年はわずか8件に留まった。これは、本邦ではuncontrolled DCDが主であるため、摘出時間が不確定で死戦期が長いために、腎臓と角膜の提供に留まること、提供施設・摘出医・移植医の負担が大きいことが要因と考えられる。一方、欧米においては心停止後臓器提供が著増している。これは、controlled DCDが主であり、生命維持装置停止後30分以内の心停止のみの摘出により臓器機能が担保されること、さらに体内での人工心肺(ECMO)による灌流(NRP)あるいは、臓器を摘出後に体外灌流装置を用いて恒温(NMP)あるいは低温(HOPE)で灌流する方法である。NMPでは移植前に臓器の機能を評価することが可能である。一方、HOPEはDCDに特徴的な虚血性胆管障害を低減させるとされている。本邦で終末期医療の選択肢としての生命維持装置停止によるcontrolled DCDガイドラインの策定、機械灌流のコストの問題などがクリアされれば、心停止ドナーは増加傾向に転じるものと予想される。</p>

DOI： 10.11386/jst.60.supplement_s143_1

CiNii Research

Language：Japanese   Publisher：The Japan Society for Transplantation  

<p>【背景・目的】プレバイミスは腎移植後のサイトメガロウイルス(CMV)感染症発症抑制効果が、バルガンシクロビル(VGCV)に対して非劣性、かつ骨髄抑制が少ないことが報告されている。従来のVGCV投与量(900mg/日)では骨髄抑制の副作用が多く、当科では、重篤な患者の多い肝移植後は減量(450mg/日x週3回)し投与を行ってきたが、2024年6月以降、プレバイミスを導入しており、本検討ではその有効性と安全性について検討する。【対象・方法】2023年11月から2024年5月の生体肝移植(LDLT)症例をVGCV群(n=20)、2024年6月から2025年4月のLDLT症例をプレバイミス群(n=26, 480mg/日x毎日)とした。LDLT後1ヶ月以内にCMVpp65抗原陽性細胞を検出した割合と副作用の頻度、タクロリムス(TAC)血中濃度の変化を比較検討した。【結果】CMV感染症の発症はなく、CMVpp65抗原陽性細胞の検出割合は、プレバイミス群で有意に低かった(VGCV群35% vsプレバイミス群3.8%, p＜0.05)。VGCV減量投与を行っている本検討では両群共に骨髄抑制の発症率に差はなく、副作用によるプレバイミスの中止症例は認めなかった。TACの血中濃度を同等に維持(10 ng/ml)するために必要なプログラフの内服量は、プレバイミス群で約半分に減量された(VGCV群4.0mg vs プレバイミス群 2.1mg, p＜0.05)。【まとめ】プレバイミスは肝移植後CMV再活性化予防として有効、かつ安全に投与可能なことが示された。</p>

DOI： 10.11386/jst.60.supplement_s283_1

CiNii Research

Language：Japanese   Publisher：The Japan Society for Transplantation  

<p>【背景・目的】 生体肝移植(LDLT)は、一般に「too sick for transplant」とされるHigh MELD患者において、適応や治療意義がいまだ議論されている。近年、手術手技や周術期管理の進歩により、この「too sick」な病態に対しても挑戦的治療が可能となりつつある。本研究では、High MELD患者に対するLDLTの妥当性およびその治療戦略の有効性を再評価する。</p><p>【方法】2024年12月までに施行された成人LDLT 852例を対象に、MELDによりL群(＜20, n=642),M群(20-29, n=160),H群(≧30, n=50)に分類し術後成績を比較検討した。</p><p>【結果】 Grade B以上の過小グラフト症候群（SFSS）はH群で最も高頻度（L群24.3%、M群36.3%、H群51.5%、p＜0.01）。敗血症の発症率やグラフト生存率には有意差なしだが、時代後期(2015年-)では1年生存率の改善がみられ、特にH群における改善が顕著（76.0%→80.0%、p＜0.05）であった。また、H群では左葉グラフトの1年生存率が右葉に比して有意に低値（61.0% vs. 89.2%、p＜0.05）、特に50歳未満ドナーからの右葉グラフトを用いた症例では良好な成績であった。</p><p>【結論】 High MELD患者、すなわち“too sick”とされる症例に対しても、生体肝移植は適切なグラフト選択と周術期戦略により、近年その成績が著しく改善している。とりわけ右葉グラフトの選択は、十分な肝容積を確保しうる有効な戦略であり、この極めて重篤な病態における治療の鍵を握る。</p>

DOI： 10.11386/jst.60.supplement_s219_2

CiNii Research

Language：English   Publisher：Annals of Gastroenterological Surgery  

Background: The role of anatomical resection (AR) in hepatocellular carcinoma (HCC) remains controversial, particularly for tumors ≤ 5 cm without vascular invasion. We aimed to evaluate the long-term outcomes of AR versus non-anatomical resection (NAR) in solitary HCC presumed negative for microvascular invasion (MVI) and intrahepatic metastasis (IM). Methods: We retrospectively analyzed 303 patients with solitary HCC who underwent hepatectomy between 2002 and 2019. Predictive factors for MVI and IM were identified, and 214 patients with solitary HCC ≤ 5 cm and predicted absence of MVI and IM were further analyzed. We compared the perioperative and oncological outcomes between the AR (n = 94) and NAR (n = 120) groups. Subsequently, we conducted propensity score matching (n = 41 per group) and performed subgroup analyses based on tumor size. Results: Des-γ-carboxy prothrombin > 150 mAU/mL was identified as an independent predictor for MVI and IM. Compared with the NAR group, the AR group had a significantly longer operative time, greater blood loss, and higher rate of complications, but showed no significant differences in recurrence-free survival and overall survival. Recurrence-free survival and overall survival remained comparable between the two groups after propensity score matching. Subgroup analyses by tumor size (0–2.0 and 2.1–5.0 cm) showed no prognostic advantage for AR over NAR. Conclusions: For solitary HCC ≤ 5 cm without predicted MVI and IM, NAR and AR result in comparable long-term outcomes. The resection strategy should prioritize remnant liver function over anatomical extent.

DOI： 10.1002/ags3.70157

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PubMed

Language：Japanese   Publisher：The Japan Society for Transplantation  

<p>【背景・目的】肝移植は肝細胞癌（HCC）に対する有力な治療法だが、日本の肝癌診療ガイドラインでは、Child Cのみが適応とされている。一方、欧米では腫瘍条件が適合すればChild Aにも肝移植が選択されている。現在日本でもChild B肝硬変に対する肝移植は保険適応となったが、HCCに関しては併存条件が記載されているに留まっており、Child AのHCCに対する移植報告は極めて限定的である。本研究では、Child A及びBのHCCに対する生体肝移植(LDLT)と肝切除（HR）の成績を比較し、適応拡大の可能性を検討した。</p><p>【方法】 今回、改正臓器移植法施行後かつDAAが保険適応となった2011年以降の症例を対象。当院で施行されたLDLT (n=159, total n=309)及び初発HCCに対するHR (n=208)を対象とし、術後成績について比較検討。</p><p>【結果】(1) 日本基準内HCCに対するHRではChild Aの1y/5y-OSが99.3/79.8%、Child Bが80.3/62.5%と肝機能により予後が層別化された（P＜0.05）。一方、LDLT群ではChild A～C間でOSに有意差は認めなかった。(2) Child BではLDLTがHRよりRFS・OSともに有意に良好だったが、Child Aでは有意差なし。ただしICG-R15＞15%のChild Aでは、HRがLDLTより有意に予後不良（P＜0.05）。Child BのLDLTではDCP＞300が独立予後不良因子。</p><p>【まとめ】2010年代以降の症例においてもChild B及びICG高値のChild Aに対するLDLTはHRより良好な成績を示し、移植適応拡大の可能性を示唆する結果となった。</p>

DOI： 10.11386/jst.60.supplement_s217_1

CiNii Research

Publisher：南江堂  

DOI： 10.15106/j_geka86_1288

CiNii Research

Language：Japanese   Publisher：(株)南江堂  

＜文献概要＞再肝切除に対するロボット支援や腹腔鏡下手術といった低侵襲手術では,前回手術内容の把握や,術前3Dシミュレーションをもとにした精密な術前準備が重要である.低侵襲再肝切除は,適切なポート配置による癒着剥離,肝十二指腸靱帯のテーピング,インドシアニングリーン(ICG)蛍光法を用いた腫瘍の同定により安全に施行が可能である.再肝切除においても低侵襲手術は有用であり,合併症の軽減と良好な治療成績が期待される.

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

症例は78歳女性で、C型肝炎ウイルス抗体陽性を示して紹介受診となった。超音波検査で肝S8に13mmの等エコー病変を認めた。病変は、造影CTではarterial hyperintensityおよび後期相でwashoutを示し、ethoxybenzyl MRIでは動脈相で増強効果の亢進、肝細胞相で低信号を示した。腫瘍マーカーはいずれも正常であったが、CTおよびMRIにおける造影パターンは肝細胞癌と一致していたことから、S8亜区域切除を施行した。切除検体の病理組織検査において、胚中心の拡張を伴うさまざまなサイズおよび形状のdense lymphoid tissueを認めた。免疫組織化学染色ではCD3、CD10(胚中心)、CD20陽性、bcl-2(胚中心)およびEpstein-Barrウイルス陰性を示した。IgH遺伝子再構成のPCR解析ではpolyclonalityを認めた。これらの所見から肝reactive lymphoid hyperplasiaと診断した。術後経過に問題はなく、術後10日目に退院に至った。術後のQOLは良好で、4ヵ月時点で肝結節の再発は認めていない。

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

膵管腺癌(PDAC)の根治手術を行った127例を対象とした後向き単施設研究において、至適治療を評価するスコアリングモデルを作成した。術後12ヵ月以内の再発を早期再発(ER)と定義し、術前パラメータによるERの予測能をROC曲線により評価した。全体の43例でERが認められ、ER群では非ER群に比べて予後が有意に不良であった。糖鎖抗原(CA)19-9値、リンパ球-単球比(LMR)が最も強力な診断因子であった。至適カットオフ値を用いてER予測スコアを算出した結果、CA19-9+LMRスコア高値は、全生存、無再発生存の短縮と有意に関連した。多変量解析では、ERの独立した予測因子はCA19-9+LMRスコア高値であった。CA19-9+LMRスコアリングモデルは、切除可能なPDAC患者のリスク層別化に適用可能であると考えられた。

Authorship：Lead author   Language：English   Publisher：Surgery Today  

Purpose: Pancreatic ductal adenocarcinoma (PDAC) often recurs early after radical resection, which causes a poor prognosis. This study aimed to establish a scoring model to assess the optimal treatment in patients who underwent surgery for PDAC. Methods: This single-center retrospective study included 127 patients who underwent radical resection for PDAC between 2005 and 2021. Early recurrence (ER) was defined as recurrence within 12 months after resection. The predictive effect for ER was evaluated using receiver operating characteristic (ROC) curves of preoperative parameters. Results: ER occurred in 43 (33.9%) patients. The ER group had a significantly worse prognosis than the non-ER group (p < 0.0001). The carbohydrate antigen 19-9 (CA19-9) level and lymphocyte-to-monocyte ratio (LMR) were the strongest diagnostic factors (areas under the ROC curves: 0.74 and 0.68, respectively). The ER prediction score was calculated using optimal cutoff values. A higher CA19-9-LMR score was associated with a worse prognosis in terms of the overall and recurrence-free survival (p = 0.0017 and p < 0.0001, respectively). A multivariate analysis identified a high CA19-9-LMR score as an independent predictor of ER. Conclusions: The CA19-9-LMR scoring model can predict ER after surgery and is applicable for risk stratification in the assessment of patients with resectable PDAC.

DOI： 10.1007/s00595-023-02675-z

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PubMed

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

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

Language：English   Publisher：Hepatology Research  

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

DOI： 10.1111/hepr.13875

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PubMed

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

症例は74歳男性で、膵体部から尾部を占める膵管内乳頭粘液性腫瘍(IPMN)で14年間経過観察されていた。発熱と無痛性閉塞性黄疸のため当科に紹介された。患者は17年前に胃癌で噴門側胃切除術を受けていた。腹部造影CTでは、膵頭部に境界明瞭な約30mmの門脈相を増強した結節を認め、肝内・肝外胆管の著明な拡張を伴っていた。磁気共鳴胆管膵管造影により膵実質に多数の嚢胞性腫瘤と主膵管拡張を認めた。組織学的に膵頭部の膵管腺癌(PDAC)(cT2N0M0、cStage IB)と診断し、膵体部と膵尾部のIPMNを伴っていた。その後、21日サイクルでゲムシタビン+S-1による術前補助化学療法(NAC)を受けたが、全身性NACの影響により全身状態が低下した。手術治療計画は、幽門部を温存する膵全摘術(TP)を継続し、残胃への血液供給を温存する試みであった。TPを残存胃血流の部分的流入・流出部として脾動脈と静脈を温存しながら行い、その後修正Child法を用いて再建を行った。切除標本の病理組織学的検査では膵頭部に浸潤性乳管腺癌(最大径20mm)、膵体部と膵尾部にIPMNを認め、リンパ節転移はなく、手術断端は陰性であった。術後補助化学療法としてS-1単剤療法を受け、8ヵ月間再発を認めなかった。

Authorship：Lead author   Language：English   Publisher：Anticancer Research  

Background/Aim: Hepatic resection for Barcelona Clinic Liver Cancer (BCLC) stage B (intermediate-stage) hepatocellular carcinoma (HCC) is not recommended by BCLC treatment algorithms. We sought to develop a new prognostic model for determining appropriate treatment strategies in patients with intermediate-stage HCC. Patients and Methods: This single-center retrospective study included patients who underwent hepatic resection for HCC between 2000 and 2018. A total of 498 patients were classified according to the BCLC staging system (0, n=116; A, n=319; B, n=63). The predictive impact for surgical outcomes was evaluated using receiver operating characteristic (ROC) curves. Based on a survival outcome probability formula, a new predictive model was established. Results: The preoperative albumin level and platelet count were the strongest diagnostic values in patients with intermediate-stage HCC (areas under the ROC curves, AUCs: 0.710 and 0.676, respectively). Logistic regression analysis provided the albumin–platelet index [API; 156.2×albumin (g/dl)+platelet count (×10⁹/l)] was defined as a new prognostic model for the probability of poor survival. The optimal cutoff value (781.2; AUC 0.755) divided patients with BCLC-B into B1 (>781.2, n=27) and B2 (≤781.2, n=36) categories. Patients in substage B2 had a significantly worse prognosis than patients in other stages (p<0.0001), whereas there was no difference in prognosis between patients in substage B1 and those in other stages. Conclusion: The API stratifies prognosis in patients with intermediate-stage HCC. For subgroup B1, hepatic resection can be considered a radical treatment, even for intermediate-stage HCC.

DOI： 10.21873/anticanres.16337

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PubMed

Authorship：Lead author   Language：English  

DOI： 10.1007/s13691-023-00596-9

PubMed

Language：Japanese   Publisher：大道学館出版部  

症例は40歳代女性で、マンモグラフィ検診で異常を指摘され当院を受診した。CT検査、骨シンチの結果、cT1cN0M0 Stage 1の乳癌にて右乳房部分切除+センチネルリンパ節生検を施行した。術後3年6ヵ月が経過し、右上肢痛を訴えたためCT検査を施行した。その結果、腋窩リンパ節は腫大しており、US、MRI検査にて腫大リンパ節が腋窩静脈に浸潤している可能性が疑われた。化学療法先行ではなく手術を行うこととし、腫大したリンパ節が腋窩静脈に強固に癒着しており鈍的鋭的に切離した。腋窩郭清範囲はレベルIII、鎖骨下リンパ節まで郭清した。病理結果では広範囲にinvasive carcinomaを認め、scirrhous typeであった。その後、右腋窩から鎖骨上リンパ節領域にかけて放射線照射を行い、放射線照射終了後に術後補助化学療法としてTC療法を施行し経過観察を行った。

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

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

Language：English   Publisher：Cancer Science  

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

DOI： 10.1111/cas.15644

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PubMed

Authorship：Lead author   Language：English   Publisher：World Journal of Surgical Oncology  

Background: Posthepatectomy liver failure (PHLF) is a life-threatening complication following hepatic resection. The aspartate aminotransferase-to-platelet ratio index (APRI) is a non-invasive model for assessing the liver functional reserve in patients with hepatocellular carcinoma (HCC). This study aimed to establish a scoring model to stratify patients with HCC at risk for PHLF. Methods: This single-center retrospective study included 451 patients who underwent hepatic resection for HCC between 2004 and 2017. Preoperative factors, including non-invasive liver fibrosis markers and intraoperative factors, were evaluated. The predictive impact for PHLF was evaluated using receiver operating characteristic (ROC) curves of these factors. Results: Of 451 patients, 30 (6.7%) developed severe PHLF (grade B/C). Multivariate logistic analysis indicated that APRI, model for end-stage liver disease (MELD) score, operating time, and intraoperative blood loss were significantly associated with severe PHLF. A scoring model (over 0–4 points) was calculated using these optimal cutoff values. The area under the ROC curve of the established score for severe PHLF was 0.88, which greatly improved the predictive accuracy compared with these factors alone (p < 0.05 for all). Conclusions: The scoring model-based APRI, MELD score, operating time, and intraoperative blood loss can predict severe PHLF in patients with HCC.

DOI： 10.1186/s12957-022-02714-y

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PubMed

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

症例は76歳男性で、2型糖尿病、高血圧、高脂血症の既往があった。転移リンパ節を有する膵頭部の切除可能な膵管腺癌(PDAC)と診断した。同時に膵尾部から約2cmの嚢胞性腫瘤を認め、仮性嚢胞であることが判明した。PDACに対する術前化学療法後、呼吸困難と左下胸部痛を呈した。胸部X線検査で大量の左胸水を認め、胸水検査でアミラーゼ値が非常に高いことが判明した。CTにより、膵尾部仮性嚢胞と左横隔膜を直接つなぐ瘻孔を確認したことから、膵尾部から左胸膜への膵胸膜瘻が示唆された。胸腔ドレナージ、内視鏡的膵管ドレナージ、抗生剤の内科的治療が無効であったため、PDACに対する膵頭十二指腸切除術の前に膵尾部切除術、瘻孔閉鎖術、胸腔鏡下胸膜剥離術を施行した。術後、胸水は消失し、症状は直ちに改善した。

Authorship：Lead author   Language：English  

DOI： 10.1007/s13691-022-00555-w

PubMed

Language：English   Publisher：Molecular and Clinical Oncology  

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

DOI： 10.3892/mco.2022.2564

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PubMed

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

肝細胞癌(HCC)患者の予後予測に有用な種々の術前マーカーの組み合わせを検討した。肝切除を施行されたHCC患者454例を対象に単施設後ろ向き研究を実施し、トレーニングコホート334例と検証コホート120例に分類して、術前マーカーの組み合わせと手術成績との関連を評価した。全生存期間(OS)中央値はトレーニングコホートが9.6年、検証コホートが8.9年、無病生存期間(DFS)中央値はトレーニングコホート、検証コホート共に2.4年であった。予後予測能を評価したROC解析では、さまざまな炎症性マーカー、栄養関連マーカーのうちPrognostic Nutritional Index(PNI)が最も優れていた(曲線下面積[AUC] 0.627)。肝線維化関連マーカーのうちアスパラギン酸アミノトランスフェラーゼ/血小板比指数(APRI)が最も優れていた(AUC 0.646)。PNIとAPRIを組み合わせたPNI-APRIスコアは検証コホートのDFS不良の予測に関して最も精度が高かった。多変量Cox回帰分析では、検証コホートにおいてPNI-APRI高値がOSおよびDFS不良の独立予測因子であった。以上より、PNI-APRIスコアはHCC患者の術後転帰予測に有用であることが示された。

Authorship：Lead author   Language：English   Publisher：Surgery Today  

Purpose: Inflammation-, nutrition-, and liver fibrosis-related markers are recognized as prognostic for hepatocellular carcinoma (HCC) patients. This study, therefore, assessed the preoperative prognostic utility of the combination of these markers in patients with HCC. Methods: This single-center retrospective study included patients who underwent hepatic resection for HCC between 2004 and 2017. A total of 454 patients were divided into training (n = 334) and validation (n = 120) cohorts by random sampling. The predictive impact on surgical outcomes was evaluated using receiver operating characteristic (ROC) curves of these prognostic values in the training cohort. Results: The prognostic nutritional index (PNI) and aspartate aminotransferase-to-platelet ratio index (APRI) were the strongest diagnostic values (areas under the ROC curves: 0.627 and 0.646, respectively). A scoring system (over 0–2 points) was developed using optimal cutoff values (for PNI < 46.5 scored as 1 point; for APRI > 0.98 scored as 1 point). An increased PNI-APRI score was an independent prognostic factor for both the overall and disease-free survival in HCC patients. Finally, the clinical feasibility of the PNI-APRI score was confirmed in the validation cohort. Conclusions: The PNI-APRI score is a useful marker for predicting surgical outcomes of HCC patients.

DOI： 10.1007/s00595-021-02440-0

Scopus

PubMed

Language：English   Publisher：Hepatology Communications  

We examined phosphorylated nuclear factor erythroid 2–related factor 2 (P-NRF2) expression in surgically resected primary hepatocellular carcinoma (HCC) and investigated the association of P-NRF2 expression with clinicopathological features and patient outcome. We also evaluated the relationship among NRF2, cancer metabolism, and programmed death ligand 1 (PD-L1) expression. In this retrospective study, immunohistochemical staining of P-NRF2 was performed on the samples of 335 patients who underwent hepatic resection for HCC. Tomography/computed tomography using fluorine-18 fluorodeoxyglucose was performed, and HCC cell lines after NRF2 knockdown were analyzed by array. We also analyzed the expression of PD-L1 after hypoxia inducible factor 1α (HIF1A) knockdown in NRF2-overexpressing HCC cell lines. Samples from 121 patients (36.1%) were positive for P-NRF2. Positive P-NRF2 expression was significantly associated with high alpha-fetoprotein (AFP) expression, a high rate of poor differentiation, and microscopic intrahepatic metastasis. In addition, positive P-NRF2 expression was an independent predictor for recurrence-free survival and overall survival. NRF2 regulated glucose transporter 1, hexokinase 2, pyruvate kinase isoenzymes L/R, and phosphoglycerate kinase 1 expression and was related to the maximum standardized uptake value. PD-L1 protein expression levels were increased through hypoxia-inducible factor 1α after NRF2 overexpression in HCC cells. Conclusions: Our large cohort study revealed that P-NRF2 expression in cancer cells was associated with clinical outcome in HCC. Additionally, we found that NRF2 was located upstream of cancer metabolism and tumor immunity.

DOI： 10.1002/hep4.1838

Web of Science

Scopus

PubMed

Authorship：Lead author   Language：English   Publisher：Annals of Surgical Oncology  

Background: Hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) can recur even after achievement of a sustained virologic response (SVR). Mac-2-binding protein glycosylation isomer (M2BPGi) is a newly identified biomarker correlated with liver fibrosis. This study aimed to clarify outcomes for patients with an SVR and to assess the prognostic value of M2BPGi. Methods: This single-center retrospective study analyzed patients who underwent surgical resection for primary HCV-related HCC between 2008 and 2018. The study enrolled 81 patients whose M2BPGi could be evaluated after an SVR. The relationship between liver fibrosis-related factors and scores (including M2BPGi) and HCC recurrence, was evaluated. Results: Of the 81 patients, 57 (70.4%) with HCV-related HCC obtained an SVR, whereas 24 patients (29.6%) did not. The patients with an SVR had a significantly more favorable recurrence-free survival (RFS) than the patients with no SVR (P < 0.0001, log-rank). Among the SVR groups, M2BPGi predicted a shorter RFS after hepatic resection with a higher degree of accuracy than other markers and scores in the SVR group. The high-M2BPGi group had worse liver function, RFS, and overall survival (OS) (P = 0.0014 and 0.0006, log-rank, respectively). In the multivariate analysis, high M2BPGi was significantly associated with worse RFS and OS. Conclusions: Even after achievement of an SVR, the risk of HCC recurrence cannot be eliminated. Measurement of M2BPGi after an SVR can be applied for risk stratification in the assessment of patients with HCV-related HCC.

DOI： 10.1245/s10434-021-11011-z

Scopus

PubMed

Language：English   Publisher：Oncology Letters  

The clinicopathological features of myeloid-derived suppressor cell (MDSC) and CD8+ T-cell infiltration in hepatocellular carcinoma (HCC) are poorly understood. The present study examined MDSC and CD8+ T-cell infiltration in surgically resected primary HCC specimens and investigated the association of MDSC and CD8+ T-cell infiltration with clinicopathological features and patient outcomes. Using a database of 466 patients who underwent hepatic resection for HCC, immunohistochemical staining of CD33 (an MDSC marker) and CD8 was performed. High infiltration of MDSCs within the tumor was observed in patients with a poorer Barcelona Clinic Liver Cancer stage, larger tumor size, more poorly differentiated HCC, and greater presence of portal venous thrombosis, microscopic vascular thrombosis and macroscopic intrahepatic metastasis. MDSC infiltration and CD8+ T-cell infiltration were independent predictors of recurrence-free survival and overall survival, respectively. Stratification based on the MDSC and CD8+ T-cell status of the tumors was also associated with recurrence-free survival (10 year-recurrence-free survival; MDSChighCD8+ T-cellLow, 3.68%; others, 25.7%) and overall survival (10 year-overall survival; MDSChighCD8+ T-cellLow, 12.0%; others, 56.7%). In conclusion, the present large cohort study revealed that high MDSC infiltration was associated with a poor clinical outcome in patients with HCC. Furthermore, the combination of the MDSC and tumor-infiltrating CD8+ T-cell status enabled further classification of patients based on their outcomes.

DOI： 10.3892/ol.2022.13213

Web of Science

Scopus

PubMed

Authorship：Lead author   Language：English   Publisher：Journal of Gastrointestinal Surgery  

Background: Systemic inflammation-related factors, either independently or in combination, are recognized as prognostic factors for various cancers. The ratio of lymphocyte count to C-reactive protein concentration (lymphocyte–CRP ratio; LCR) is a recently identified prognostic marker for several cancers. Here, we examined the prognostic value of the LCR in patients with hepatocellular carcinoma (HCC). Methods: This was a single-center retrospective study of patients who underwent surgical resection for HCC between 2004 and 2017. Patients were divided into high- and low-LCR status groups, and the relationships between LCR status, prognosis, and other clinicopathological characteristics were analyzed. Results: A total of 454 patients with HCC were enrolled and assigned to the high- (n=245) or low- (n=209) LCR groups. Compared with the high-LCR group, patients in the low-LCR group had a significantly lower serum albumin level (median 4.1 vs. 3.9 g/dL, P <0.0001), lower platelet count (median 14.0 vs. 12.0 ×10⁴/μL, P=0.0468), lower prothrombin time (median 93.2 vs. 89.6 %, P=0.0006), and larger tumor size (median 2.3 vs. 2.5 cm, P=0.0056). Patients with low-LCR status had significantly worse outcomes of overall survival and disease-free survival than patients with high-LCR status (P=0.0003 and P=0.0069, respectively). Low-LCR status was significantly associated with worse overall survival in multivariate analysis (hazard ratio 1.57, 95% confidence interval 1.14–2.17, P=0.0058). Conclusions: Low-LCR status may predict worse outcomes in patients with HCC. Measurement of LCR is routine and can easily be applied for risk stratification in the assessment of patients with HCC.

DOI： 10.1007/s11605-021-05085-z

Scopus

PubMed

Authorship：Lead author   Language：English   Publishing type：Doctoral thesis  

収集根拠 : 博士論文（送信）

DOI： 10.1016/j.ejso.2020.08.002

CiNii Research

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Language：Japanese   Publisher：(株)南江堂  

＜文献概要＞再肝切除に対するロボット支援や腹腔鏡下手術といった低侵襲手術では,前回手術内容の把握や,術前3Dシミュレーションをもとにした精密な術前準備が重要である.低侵襲再肝切除は,適切なポート配置による癒着剥離,肝十二指腸靱帯のテーピング,インドシアニングリーン(ICG)蛍光法を用いた腫瘍の同定により安全に施行が可能である.再肝切除においても低侵襲手術は有用であり,合併症の軽減と良好な治療成績が期待される.