周術期の体組成評価:―サルコペニアの観点より―

周術期の体組成評価:―サルコペニアの観点より―

The Japanese Journal of Surgical Metabolism and Nutrition


Loss of Fbxw7 expression is a predictor of recurrence in colorectal liver metastasis.

Fbxw7 is a tumor suppressor through ubiquitination and degradation of multiple oncoproteins. Loss of Fbxw7 is frequently observed in various human cancers. In this study, we examined the role of Fbxw7 expression in colorectal liver metastasis (CRLM) and its mechanism. Fifty-six patients with CRLM who undergo curative resection were enrolled. Fbxw7 in tumor tissue was determined by immunohistochemistry. Patients were divided into two groups, the Fbxw7 high and low groups. Clinicopathological factors including miR-223 expression were compared between the high (n = 32) and low Fbxw7 groups (n = 24). Fbxw7 expression in tumor tissues was significantly lower than that in normal tissues. The disease-free survival in the low Fbxw7 group was significantly worse than that in the high Fbxw7 group, and 3 years disease-free survival of the low and high Fbxw7 groups were 12.5% and 47.0%, respectively (P = 0.023). On multivariate analysis, loss of Fbxw7 was detected as one of the independent risk factors for recurrence of CRLM (hazard ratio: 2.390, P = 0.017). Likewise, Fbxw7 expression inversely correlated to miR-223 expression (P = 0.017). Loss of Fbxw7 in tumor tissues could be a reliable predictor of recurrence after hepatectomy in patients with CRLM, and miR-223 might be a possible regulator of Fbxw7.

Journal of Hepato-Biliary-Pancreatic Sciences


Treatment strategy of conversion hepatectomy for colorectal liver metastasis

【Conversion Surgery-進行消化器がんのトータル治療戦略】がん種別Conversion Surgeryの戦略 転移性肝癌


【どこをどう切る?どうつなぐ?なぞって覚える!消化器外科術式理解イラストノート】 肝臓・胆道の手術 肝切除術


Evidence and topics of surgical treatment for hepatocellular carcinoma

【肝細胞癌 診断・治療におけるエビデンスとトピックス】 肝細胞癌に対する外科的治療のエビデンスとトピックス

肝細胞癌に対する外科的治療のエビデンスとして，ガイドライン(2013年版)における，手術(外科的治療)に関係するClinical Questionの中で，CQ21 腫瘍条件からみた肝切除の適応は?，CQ22 肝切除後の予後因子は何か?，CQ24 系統的切除は予後に寄与するか?，CQ31 肝細胞癌に対する肝移植の適応基準は何か?，について概説する．また，今後エビデンス構築が期待されるトピックスとして，腹腔鏡下肝切除の治療適応，BCLC Stage Bに対する外科的治療選択，Conversion Hepatectomyに関しても言及する．

The Japanese Journal of Gastro-enterology


【胆膵進行癌に対する外科治療戦略】 閉塞性黄疸に対する最新の術前減黄戦略

【胆膵進行癌に対する外科治療戦略】 閉塞性黄疸に対する最新の術前減黄戦略


Effective stepwise training and procedure standardization for young surgeons to perform laparoscopic left hepatectomy.

Laparoscopic hepatectomy remains one of the most difficult procedures for young surgeons to perform. We recently developed a new training method and standardization procedure for teaching young surgeons to perform laparoscopic left hepatectomy (Lap-LHx). The aim of this study was to assess the effectiveness of our method. In 2004, we standardized a laparoscopic procedure for Lap-LHx, using a laparoscopy-assisted method as a stepping stone. The laparoscopic training method comprised the following three steps: (1) training in fundamental procedures using a dry box and checking by mentors; (2) detailed preoperative simulation using Vincent three-dimensional software for each patient; and (3) self-assessment including understanding of relevant anatomy and completion grade for each procedure using a check sheet and feedback by both mentors and a professor. Twenty-three Lap-LHx procedures performed during the study period were divided into two groups: those performed by young non-board-certified surgeons (n = 9) and those performed by senior board-certified surgeons (n = 14). The blood loss and operative time were similar in the young surgeon (194 g and 336 min, respectively) and senior surgeon groups (208 g and 322 min, respectively). Our standardized Lap-LHx procedure and stepwise training to perform it enable young surgeons to perform Lap-LHx as confidently and safely as more experienced surgeons.


Liver regeneration after splenectomy in patients with liver cirrhosis.

Splenectomy is a well-known procedure to improve thrombocytopenia and liver function in patients with liver cirrhosis (LC). However, the effect of splenectomy on liver regeneration remains unclear. The aim of this study is to investigate the effect of splenectomy on liver regeneration. Twenty patients with LC who underwent splenectomy were included in this study. Liver and splenic volumes were measured by a 3-D simulation imaging system. Liver volume (LV) and clinicopathological data were compared before and 6 months after splenectomy. Thereafter, patients were divided into two groups: the elevated LV group and the reduced LV group. Patient characteristics were compared between the two groups. Postoperative LV was increased in 14 patients compared with the preoperative state. Thrombocytopenia, leukopenia, total bilirubin and prothrombin time were improved after splenectomy. In the elevated LV group, four patients exhibited improved Child-Pugh grades after splenectomy, whereas no patients demonstrated improvement in the reduced LV group. The elevated LV group exhibited high albumin level, good indocyanine green retention rate at 15 min and large splenic volume compared with the same measurements in the decreased group. Patients with larger spleen volumes and higher albumin values before splenectomy showed increased rates of LV after splenectomy. Splenectomy for patients with LC improved pancytopenia and liver function. Especially, in patients with large spleen and high albumin levels, considerable increases in LV and improved liver function were observed.


内分泌·糖尿病·代謝内科


Epithelial-mesenchymal transition-related genes are linked to aggressive local recurrence of hepatocellular carcinoma after radiofrequency ablation.

We reported that poor prognoses of hepatocellular carcinoma (HCC) patients after radiofrequency ablation (RFA) are owing to up-regulation of expression of hypoxia-inducible factor-1 and epithelial cell adhesion molecule. We investigated aggressive progression in residual liver tumors (RLTs) after RFA to focus on expression of epithelial-mesenchymal transition (EMT)-related genes and miRNAs. Ten patients with recurrent HCC post-RFA who underwent hepatectomy (RFA group) and 78 patients with HCC without prior RFA (non-RFA group) were enrolled. We examined expression of transforming growth factor (TGF)-β, Twist, vimentin, and Snail-1 mRNAs in tumor tissues, and expression of miR-34a and miR-200c. Expression of TGF-β, Twist and Snail-1 in the RFA group was significantly higher than that in the non-RFA group (P < 0.05); vimentin expression in the RFA group was higher than that in the non-RFA group (P = 0.07). Expression of miR-200c and miR-34a in the RFA group was significantly lower than that in the non-RFA group (miR-200c: P = 0.04; miR-34a: P < 0.01). Increased expression of EMT markers through down-regulation of miRNA expression in RLTs after RFA may be related to poor prognoses of HCC patients with aggressive local recurrence after RFA.


【最新 肝胆膵高難度外科手術アトラス】 高難度外科手術手技 肝臓 肝下部下大静脈再建を伴う肝切除


【外科領域におけるサルコペニア】 周術期サルコペニア発生の予防法

【外科領域におけるサルコペニア】 周術期サルコペニア発生の予防法


High NEK2 Expression Is a Predictor of Tumor Recurrence in Hepatocellular Carcinoma Patients After Hepatectomy.

Better prognosis of cancer including hepatocellular carcinoma (HCC) remains unsatisfactory due to recurrence and chemoresistance. In this respect it is important to identify molecular targets specific to the disease in order to design effective therapeutic strategies. In the present study, we investigated the prognostic role of Never-in-mitosis-A-related kinase 2 (NEK2) in HCC. Fifty HCC patients who underwent hepatectomy were enrolled in the study. NEK2 gene and protein expression was examined by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry, respectively. Higher expression of NEK2 was detected in HCC tumoral compared to adjacent non-tumor tissues (p<0.001), and protein expression was also relatively high in tumor than corresponding non-tumor tissues. Furthermore, high NEK2 expression was positively correlated with hepatic venous invasion (p=0.047), des-gammacarboxy prothrombin (p=0.003), and alpha-fetoprotein (AFP) (p=0.024). Patients with high NEK2 expression had significantly poor recurrence-free survival (p=0.042) and early recurrence. Overall, these results suggest that NEK2 could be a promising biomarker for HCC recurrence.


Loss of SFRP1 Expression Is Associated with Poor Prognosis in Hepatocellular Carcinoma.

Secreted frizzled-related protein-1 (SFRP1) is a well-known inhibitor of the wingless type (WNT)-β-catenin signaling pathway and its inactivation plays an important role in the development and progression of various types of cancer. However, the clinical significance of SFRP1 expression in patients with hepatocellular carcinoma (HCC) remains unknown. A total of 63 patients with HCC who underwent hepatectomy at our Institution were enrolled in this study. A quantitative real-time polymerase chain reaction (RT-PCR) was performed to determine the SFRP1 mRNA expression level in both the tumorous and non-tumorous tissues of HCC. The patients were divided into low and high gene-expression groups based on the SFRP1 gene expression level in their tumor tissues. We analyzed the differences in clinicopathological characteristics between these two groups of patients. The expression level of SFRP1 was significantly lower in tumor tissue than in non-tumor tissue (p<0.0001). Significant correlations were observed between a high expression of SFRP1 in tumor tissue and older than 65 years (p=0.030), tumor size less than 5 cm (p=0.011); and no vascular invasion (p=0.004). Patients with high SFRP1 expression in tumor tissue had a significantly better overall survival rate (p=0.040). However, the SFRP1 expression level was not defined as an independent risk factor for patient survival based on results of multivariate analysis. SFRP1 may play a role in the development and progression of HCC. Therefore, more studies are required to investigate a potential role of SFRP1 in HCC prognosis.


Epigallocatechin gallate hinders human hepatoma and colon cancer sphere formation.

The long-term survival of patients with hepatocellular carcinoma remains unsatisfactory because of the presence of cancer stem cells (CSCs), which are responsible for tumor recurrence and chemoresistance after hepatectomy. Drugs that selectively target CSCs thus offer great promise for cancer treatment. Although the antitumor effects of epigallocatechin gallate (EGCG) have been reported in some cancer cells, its effects on CSCs remain poorly studied. In this study, we investigated the effects of EGCG on human hepatoma and colon CSCs. HepG2 and HCT-116 cell lines were enriched by sphere formation, and their gene-expression profiles were analyzed by quantitative real-time polymerase chain reaction. EGCG-induced growth inhibition in the parental cells was determined by WST-8 assay, and protein expression was assessed by western blotting. Cell cycle profile and apoptosis analysis was performed using flow cytometer. Sphere-derived cells grown in serum-free, nonadherent cultures showed increased expression of stem cell markers, Nek2, and ATP-binding cassette transporter genes, compared with parental cells grown in conventional culture. EGCG induced growth inhibition in the parental cells in a dose-dependent manner. EGCG also inhibited self-renewal in hepatoma and colon CSCs, attenuated the expression of stem cell markers and ATP-binding cassette transporter genes, which are putative molecules associated with treatment resistance in CSCs, and decreased the transcription of Nek2 and p-Akt, resulting in the inhibition of Akt signaling. EGCG also altered cell cycle profile and apoptosis, which may in part play an important role in EGCG-induced cancer cell death. Overall, these results suggest that EGCG could be a useful chemopreventive agent for targeting hepatocellular carcinoma and colon CSCs, in combination with standard chemotherapies.

Journal of Gastroenterology and Hepatology


Complication of portal vein thrombosis after right hemihepatectomy in a patient lacking the portal vein bifurcation.

Absence of portal vein bifurcation is a rare anomaly. We report a patient with this anomaly who underwent right hemihepatectomy for treatment of hepatocellular carcinoma. Although the procedure was carefully performed with a preoperative three-dimensional simulation and intraoperative cholangiography, postoperative portal vein thrombosis occurred. J. Med. Invest. 63: 315-318, August, 2016.

The Journal of Medical Investigation : JMI


CKDにおけるサルコペニア・フレイル対策 CKD患者のサルコペニア・フレイルに対する栄養サポート


栄養療法のピットフォール・よりよい栄養ケアのために Part1.栄養アセスメント Rapid turnover protein値とその解釈


肝胆膵手術例の術前栄養管理

肝胆膵手術例の術前栄養管理


【膵・胆管合流異常の診断基準の改訂をめぐって】 膵・胆管合流異常の診断の最前線 胆汁中アミラーゼ値


【肝胆膵・術後病態を學ぶ】 膵胆管合流異常・先天性胆道閉鎖症術後 膵胆管合流異常術後発癌の特徴


【各種デバイスを応用した私の手術―使用法と工夫】各種デバイスを応用した肝・胆手術


High expressions of cancer stem cell markers in cholangiolocellular carcinoma.

Cholangiolocellular carcinoma (CLC) is an extremely rare malignant liver tumor. It is thought to originate from the ductules and/or canals of Hering, where hepatic stem cells (HpSC) are located, but there are few reports on cancer stem cell markers in CLC. Thus, we evaluated the significance of cancer stem cell markers, including CD133, CD44, and EpCAM, in CLC. The subjects of this study were three patients with CLC and one patient with an intermediate type of combined hepatocellular cholangiocarcinoma (CHC). The cancer cell markers, CK7, CK19, and EMA, were evaluated immunohistochemically. Histological examination of the CLC revealed morphologically cholangiolar features and immunohistochemical examination revealed positivity for CD133, CD44, and EpCAM. On the other hand, in the intermediate type of CHC, only CD44 was positive, whereas CD133 and EpCAM were negative. CLC may have stronger features derived from HpSCs than an intermediate type of CHC.


The protective effect of adipose-derived stem cells against liver injury by trophic molecules.

In this study we investigated whether adipose-derived stem cells (ADSCs) had any beneficial protective effects on liver injury and regeneration in vivo. Moreover, we examined whether ADSCs protect hepatocytes via trophic molecules. We transplanted ADSCs into mice after 70% hepatectomy and ischemia-reperfusion, and observed liver injury and regeneration after reperfusion. We co-cultured hepatocytes with ADSCs using a Transwell system for 7 d and evaluated the viabilities of hepatocytes and the cytokine levels in the culture medium. Bevacizumab was used to confirm the effect of vascular endothelial growth factor (VEGF) on hepatocytes. ADSCs improved serum liver function at 6 h after reperfusion in a nonlethal model and stimulated liver regeneration at 24 h after reperfusion in a lethal model. VEGF levels in the culture medium were increased by co-culture ADSCs with hepatocytes. ADSCs improved the viabilities of hepatocytes. The inhibited production of VEGF by bevacizumab did not affect the viability of hepatocytes. ADSCs were able to ameliorate liver injury and stimulate liver regeneration in subsequent hepatectomy and ischemia-reperfusion-injured model mice. Furthermore, hepatocytes were protected by the trophic molecules of the ADSCs. However, such protective effects might be provided by mechanisms other than VEGF signaling.


【膵・胆管合流異常診療ガイドラインを巡る残された問題点】 非拡張型膵・胆管合流異常の胆管癌発生頻度を巡る問題点


Changes of immunological parameters with administration of Japanese Kampo medicine (Juzen-Taihoto/TJ-48) in patients with advanced pancreatic cancer.

The prognosis of pancreatic cancer is extremely poor regardless of various combination therapies. Immunoaugumentation against tumor cells was recently A focus. We reported that the population of Foxp3(+)CD25(+)CD4(+) regulatory T cells (Foxp3(+)Treg) was the new parameter for the estimation of host immunity and had correlation with tumor aggressiveness. Here we show the immunoaugumentation effects of Japanese Kampo medicine, Juzen-Taihoto/TJ-48, empirically considered as an immunoaugumentation drug, with investigation of Treg and other immunological parameters. Peripheral Foxp3(+) Treg populations, CD4/CD8 ratio, and CD57(+) cells (NK cells) populations in advanced pancreatic cancer patients (n = 30, stage VI A and B according to TNM classification) were estimated after TJ-48 administration for 14 days before the anti-cancer therapy. Treg populations were significantly increased compared to healthy donors (Mann-Whitney U test, P < 0.001). Administration of Juzen-Taihoto/TJ-48 significantly decreased Treg populations (Mann-Whitney U test, P < 0.001) and increased the CD4/CD8 ratio (Mann-Whitney U test, P < 0.01), even though CD57(+) cell populations did not change significantly. Juzen-Taihoto/TJ-48 increased regulatory activities in T cells through decreasing Foxp3(+) Treg populations in advanced pancreatic cancer patients. This effect can lead to immunoaugumentation for various combination therapies.

International Journal of Clinical Oncology


Regulatory T cells in the blood: a new marker of surgical stress.


Hepatic epithelioid angiomyolipoma with arterioportal venous shunting mimicking hepatocellular carcinoma : report of a case.

A patient with hepatic epithelioid angiomyolipoma (Epi-AML) with arterioportal venous shunting, who was successfully treated by a laparoscopic left lateral sectionectomy, is presented herein. AML is an uncommon benign neoplasm of the liver. Tumors composed predominantly of epithelioid cells have been subcategorized into Epi-AML, and the treatment strategy for Epi-AML is currently undetermined. There are no reports describing Epi-AML with arterioportal venous shunting to date. An arterioportal venous shunting of the liver tumor was suggested to be one of the malignant signs of the liver tumor. It would be important to differentiate Epi-AML with arterioportal venous shunting from hepatocellular carcinoma and hypervascular metastatic tumors. Minimally invasive resection, such as laparoscopic hepatectomy, for patients having Epi-AML with arterioportal venous shunting may be recommended.

The Journal of Medical Investigation : JMI


Hilar cholangiocarcinoma accompanied by pancreaticobiliary maljunction without bile duct dilatation 20 years after cholecystectomy: report of a case

Pancreaticobiliary maljunction (PBM) is associated with the occurrence of biliary cancer due to pancreatobiliary reflux. From the perspective of carcinogenesis, the treatment for PBM is controversial. We herein report a case of hilar cholangiocarcinoma 20 years after the occurrence of gallbladder cancer. A 75-year-old man was referred to our hospital regarding an obstructive jaundice and bile duct tumor. A cholecystectomy was performed for cholelithiasis on this patient 20 years ago, and cancer in situ was detected. Computed tomography (CT) and endoscopic retrograde cholangiopancreatography (ERCP) revealed a tumor of the portal hepatic region and PBM without dilatation of the bile duct. Adenocarcinoma was detected from bile cytology, and we diagnosed hilar cholangiocarcinoma. Despite the biliary decompression, jaundice was prolonged and the patient passed away. Our case suggests that not only cholecystectomy but also biliary diversion is needed for PBM regardless of the existence of bile duct dilatation.


Role of CD44 expression in non-tumor tissue on intrahepatic recurrence of hepatocellular carcinoma.

CD44 is well known to be one of the cancer stem cell markers and is a cell-surface glycoprotein involved in cell-cell interactions, cell adhesion, and cell migration. We investigated the role of CD44 expression in both tumor and non-tumor tissues on recurrence of hepatocellular carcinoma (HCC). Forty-eight patients with HCC who underwent hepatic resection at our institution were enrolled in this study. CD44 expressions in both tumor and non-tumor tissues were examined using real time reverse transcription-polymerase chain reaction. The patients were divided into two groups: high and low gene-expression group, based on the CD44 expression level. We compared the clinicopathological factors between the high expression and low expression groups in both tumor and non-tumor tissues. In the tumor tissues, the gene-expression levels of CD44 did not correlate with any clinicopathological parameters. The disease-free survival rate showed no significant difference between the two groups. In non-tumor tissues, although there was no significant relationship between the CD44 expression levels and clinicopathological factors, disease-free survival rate in the CD44 low expression group was significantly better than that in the CD44 high expression group (P < 0.05). In multivariate analysis, the risk factors in tumor recurrence were presence of microscopic portal invasion and high expression level of CD44. The CD44 expressions in the non-tumor tissues may predict HCC recurrence.