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Mitofusin-2 mediated mitochondrial Ca2+ uptake 1/2 induced liver injury in rat remote ischemic perconditioning liver transplantation and alpha mouse liver-12 hypoxia cell line models

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World Journal of Gastroenterology 2017年第38期23卷 6995-7008页

作者： Ruo-Peng Liang Jun-Jun Jia Jian-Hui Li Ning He Yan-Fei Zhou Li Jiang Tao Bai Hai-Yang Xie Lin Zhou Yu-Ling Sun Department of hepatobiliary and Pancreatic Surgery The First Affiliated Hospital of Zhengzhou University Institute of hepatobiliary and Pancreatic Diseases Zhengzhou University Key Lab of Combined Multi-Organ Transplantation Ministry of Public Health Division of hepatobiliary and Pancreatic Surgery Department of Surgery First Affiliated Hospital Zhejiang University School of Medicine Collaborative Innovation center for Diagnosis and Treatment of Infectious Diseases

AIM To investigate the protective mechanism of mitofusin-2 (Mfn2) in rat remote ischemic perconditioning (RIC) models and revalidate it in alpha mouse liver-12 (AML-12) hypoxia cell lines. METHODS Sprague-Dawley rats were divided into three groups (n = 6 each): sham, orthotopic liver transplantation and RIC. After operation, blood samples were collected to test alanine aminotransferase and aspartate aminotransferase. The liver lobes were harvested for histopathological examination, western blotting (WB) and quantitative real-time (qRT)-PCR. AML-12 cell lines were then subjected to normal culture, anoxic incubator tank culture (hypoxia) and anoxic incubator tank culture with Mfn2 knockdown (hypoxia + Si), and data of qRT-PCR, WB, mitochondrial membrane potential (Delta psi m), apoptosis, endoplasmic reticulum Ca2+ concentrations and mitochondrial Ca2+ concentrations were collected. RESULTS Both sham and normal culture groups showed no injury during the experiment. The RIC group showed amelioration of liver function compared with the orthotopic liver transplantation group (P < 0.05). qRTPCR and WB confirmed that Mfn2-mitochondrial Ca2+ uptake 1/2 (MICUs) axis was changed (P < 0.005). In AML-12 cell lines, compared with the hypoxia group, the hypoxia + Si group attenuated the collapse of..m and apoptosis (P < 0.005). The endoplasmic reticulum Ca2+ decrease and mitochondrial Ca2+ overloading observed in the hypoxia group were also attenuated in the hypoxia + Si group (P < 0.005). Finally, qRT-PCR and WB confirmed the Mfn2-MICUs axis change in all the groups (P < 0.005). CONCLUSION Mfn2 participates in liver injury in rat RIC models and AML-12 hypoxia cell lines by regulating the MICUs pathway.

关键词： Remote ischemic per-conditioning Ischemia-reperfusion injury Ca2+ Mitofusin-2 Mitochondrial Ca2+ uniporter

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Advancements and challenges in treating advanced gastric cancer in the West

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World Journal of Gastrointestinal Oncology 2019年第9期11卷 652-664页

作者： Jennifer L Leiting Travis E Grotz Division of hepatobiliary and Pancreas Surgery Mayo Clinic

Gastric cancer is a leading cause of cancer incidence and death *** with advanced gastric cancer benefit from a multi-modality treatment *** oncologic resection with negative margins and complete lymphadenectomy plays a crucial role in long-term survival for patients with resectable *** utilization of minimally invasive techniques for gastric cancer has been slowly increasing and is proving to be both technically and oncologically *** chemotherapy is the current standard of care for advanced gastric cancer.A variety of chemotherapy regimens have been used with the combination of docetaxel,oxaliplatin,5-fluorouracil,and leucovorin being the current recommendation given its superior ability to induce a complete pathologic response and prolong *** use of radiation has been more controversial with its optimal place in the treatment sequence being *** are current ongoing studies assessing the impact of radiation as an adjunct or in place of *** treatments(e.g.,trastuzumab for human epidermal growth factor receptor 2 positive tumors and pembrolizumab for programmed death-ligand 1 positive tumors)are showing promise and are part of a continued emphasis on individualized *** chemotherapy may also play a role in preventing peritoneal recurrences for patients with high risk *** treatment of patients with advanced gastric cancer in the West continues to advance and improve with a better understanding of optimal treatment sequences and the utilization of personalized treatment regimens.

关键词： Gastric cancer D2 lymphadenectomy Minimally invasive surgery Neoadjuvant chemotherapy Chemoradiation Targeted treatments

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Profiling of hepatocellular carcinoma neoantigens reveals immune microenvironment and clonal evolution related patterns

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Chinese Journal of Cancer Research 2021年第3期33卷 364-378页

作者： Zhenli Li Geng Chen Zhixiong Cai Xiuqing Dong Lei He Liman Qiu Yongyi Zeng Xiaolong Liu Jingfeng Liu The United Innovation of Mengchao hepatobiliary Technology Key Laboratory of Fujian Province Mengchao Hepatobiliary Hospital of Fujian Medical UniversityFuzhou 350025China Mengchao Med-X center Fuzhou UniversityFuzhou 350116China Liver Disease center the First Affiliated Hospital of Fujian Medical UniversityFuzhou 350005China

Objective: Neoantigens derived from tumor-specific genomic alterations have demonstrated great potential for immunotherapeutic interventions in cancers. However, the comprehensive profile of hepatocellular carcinoma(HCC) neoantigens and their complex interplay with immune microenvironment and tumor evolution have not been fully ***: Here we integrated whole exome sequencing data, transcriptome sequencing data and clinical information of 72 primary HCC patients to characterize the HCC neoantigen profile, and systematically explored its interactions with tumor clonal evolution, driver mutations and immune ***: We observed that higher somatic mutation/neoantigen load was associated with better clinical outcomes and HCC patients could be further divided into two subgroups with distinct prognosis based on their neoantigen expression patterns. HCC subgroup with neoantigen expression probability high(NEP-H) showed more aggressive pathologic features including increased incidence of tumor thrombus(P=0.038), higher recurrence rate(P=0.029),more inclined to lack tumor capsule(P=0.026) and with more microsatellite instability sites(P=0.006). In addition,NEP-H subgroup was also characterized by higher chance to be involved in tumor clonal evolution [odds ratio(OR)=46.7, P<0.001]. Gene set enrichment analysis revealed that upregulation of MYC and its targets could suppress immune responses, leading to elevated neoantigen expression proportion in tumor cells. Furthermore, we discovered an immune escape mechanism that tumors could become more inconspicuous by evolving subclones with less immunogenicity. We observed that smaller clonal mutation clusters with higher immunogenicity in tumor were more likely to involve in clonal evolution. Based on identified neoantigen profiles, we also discovered series of neoantigenic hotspot genes, which could serve as potential actionable targets in ***: Our results revealed the landscape of HCC

关键词： Immune microenvironment immune escape MYC regulation neoantigen tumor clonal evolution

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Role of hepatectomy for recurrent or initially unresectable hepatocellular carcinoma

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World Journal of Hepatology 2014年第12期6卷 836-843页

作者： Yoji Kishi Kazuaki Shimada Satoshi Nara Minoru Esaki Tomoo Kosuge hepatobiliary and Pancreatic Surgery Division National Cancer Center Hospital Tokyo 104-0045 Japan

As a result of donor shortage and high postoperative morbidity and mortality after liver transplantation,hepatectomy is the most widely applicable and reliable option for curative treatment of hepatocellular carcinoma(HCC).Because intrahepatic tumor recurrence is frequent after loco-regional therapy,repeated treatments are advocated provided background liver function is *** treatments including local ablation and transarterial chemoembolization,hepatectomy provides the best long-term outcomes,but studies comparing hepatectomy with other nonsurgical treatments require careful review for selection *** patients with initially unresectable HCC,transarterial chemo-or radio-embolization,and/or systemic chemotherapy can down-stage the tumor and conversion to resectable HCC is achieved in approximately 20%of ***,complete response is rare,and salvage hepatectomy is essential to help prolong patients’*** counter the short recurrence-free survival,excellent overall survival is obtained by combining and repeating different *** is important to recognize hepatectomy as a complement,rather than a contraindication,to other nonsurgical treatments in a mul-tidisciplinary approach for patients with HCC,including recurrent or unresectable tumors.

关键词： Hepatocellular carcinoma Hepatectomy Repeat hepatectomy Conversion therapy Multidisciplinary treatment

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Borderline resectable giant hepatic cavernous hemangioma and coexisting hemangiomatosis should be a new indication for living donor liver transplantation:A report of two cases

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hepatobiliary & Pancreatic Diseases International 2024年第6期23卷 653-657页

作者： Sung-Min Kim Deok-Bog Moon Young-In Yoon Sung-Gyu Lee Division of hepatobiliary Surgery and Liver Transplantation Department of SurgeryUniversity of Ulsan College of MedicineAsan Medical CenterSeoulKorea

To the Editor:Hemangioma is a benign liver tumor that rarely requires treatment if the patient is asymptomatic[1].However,great cavernous hemangioma(GCH)can lead to symptoms due to its mass effect and Kasabach-Merritt syndrome(KMS)[2].GCH treatment options vary;therefore,tailoring treatment to individual patients according to their condition,such as symptoms,tumor location,and liver function,is ***,GCH is associated with hemangiomatosis,and its boundaries with normal tissue are unclear[3],leading to a lack of consensus on the initial therapeutic approach,with literature primarily comprising case reports or series[4].This study presented two cases of GCH and coexisting hemangiomatosis;the patients underwent liver resection of the main mass to relieve symptoms but ultimately required liver transplantation(LT).We aimed to describe the role of LT in these patients.

关键词： hemangioma cases donor

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Integrin αvβ6 sustains and promotes tumor invasive growth in colon cancer progression

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World Journal of Gastroenterology 2015年第24期21卷 7457-7467页

作者： Guang-Yun Yang Sen Guo Cong-Ying Dong Xian-Qiang Wang Bing-Yang Hu Yang-Feng Liu Yong-Wei Chen Jun Niu Jia-Hong Dong hepatobiliary Department PLA General Hospital hepatobiliary Department Qilu Hospital Shandong University The Second People’s Hospital of Huangdao

AIM: To detect the mechanism by which colon tumor escapes the growth constraints imposed on normal cells by cell crowding and dense pericellular ***: An immunohistochemical study of integrin αvβ6 and matrix metalloproteinase-9(MMP-9) was performed on tissue microarrays of 200 spots, including 100 cases of colon tumors. RESULTS: High immunoreactivity for αvβ6(73.7%; 28/38) and MMP-9(76.5%; 52/68) was observed in invasive tumor portions. Furthermore, the effects of integrin αvβ6 on tumor invasive growth in nude mice were detected. Tumor invasive growth and high expression of both αvβ6 and MMP-9 were only seen in tumors resulting from Wi Dr cells expressing αvβ6 in the tumorigenicity assay. Flow cytometry was applied to analyze αvβ6 expression in colon cancer Wi Dr and SW480 cells. The effects of cell density on αvβ6 expression and MMP-9 secretion were also detected by Biotrak MMP-9 activity assay and gelatin zymography assay. High cell density evidently enhanced αvβ6 expression and promoted MMP-9 secretion compared with low density. CONCLUSION: Integrin αvβ6 sustains and promotes tumor invasive growth in tumor progression via a selfperpetuating mechanism. Integrin ανβ6-mediated MMP-9 secretion facilitates pericellular matrix degradation at high cell density, which provides the basis of invasive growth.

关键词： Colonic neoplasms Integrin αvβ6 Matrixmetalloproteinase-9 Invasive growth

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“Wrapping the gastroduodenal artery stump” during pancreatoduodenectomy reduced the stump hemorrhage incidence after operation

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Chinese Journal of Cancer Research 2014年第3期26卷 299-308页

作者： Chang Xu Xinwei Yang Xiangji Luo Feng Shen Mengchao Wu Weifeng Tan Xiaoqing Jiang Eastern hepatobiliary Surgery Hospital Second Military Medical University

Objective： After pancreaticoduodenectomy （PD）, the postoperative gastroduodenal artery stump （GDAS） hemorrhage is one of the most serious complications. The purpose of this study is to determine whether wrapping the GDAS during PD could decrease the postoperative GDAS hemorrhage incidence. Methods： A retrospective review involving 280 patients who underwent PD from 2005 to 2012 was performed. Wrapping the GDAS during PD was defined as ＂Wrapping the GDAS using the teres hepatis ligamentum during PD＂. A total of 140 patients accepted the ＂wrapping＂ procedure （wrapping group）. The other 140 patients didn＇t apply the procedure （non-wrapping group）. Age, sex, preoperative data, estimated intraoperative blood loss, postoperative complications, pathologic parameters and hospitalization time were compared between two groups. ResultsI There were no significant differences in patient characteristics between two groups. After wrapping, the incidence of postoperative GDAS bleeding decreased significantly （1/140 vs. 9/140, P=0.01）. The rates of the other complications （such as intra-abdominal infection pancreatic fistula, billiary fistula, gastrointestinal bleeding, et aL） showed no significant differences. Conclusions： Wrapping the GDAS during PD significantly reduced the postoperative GDAS hemorrhage incidence. And the ＂wrapping＂ had no obvious influence on other complications.

关键词： Pancreaticoduodenectom (PD) wrapping the gastroduodenal artery stump (GDAS) GDAShemorrhage

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Combined hepatocellular and cholangiocarcinoma originating from the same clone:a pathomolecular evidence-based study

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Chinese Journal of Cancer 2016年第11期35卷 585-595页

作者： Qian Zhao Wen-Long Yu Xin-Yuan Lu Hui Dong Yi-Jin Gu Xia Sheng Wen-Ming Cong Meng-Chao Wu Department of Pathology Eastern Hepatobiliary Surgery HospitalSecond Military Medical University Department of Biliary Surgery Eastern Hepatobiliary Surgery HospitalSecond Military Medical University Department of Hepatic Surgery Eastern Hepatobiliary Surgery HospitalSecond Military Medical University

Background:Combined hepatocellular and cholangiocarcinoma(CHC) is a unique subtype of liver cancer comprising both hepatocellular carcinoma(HCC) and intrahepatic cholangiocarcinoma(ICC);however,its cellular origin remains *** purpose of this study was to investigate the clinicopathologic features and the clonal relationship between HCC and ICC in 34 patients with ***:The clinicopathologic features and prognosis of the 34 CHC patients were compared with those of 29 patients with separated HCC and ICC(5HC).Loss of heterozygosity(LOH) at 10 highly polymorphic microsatellite markers was detected in 16 CHC and 10 SHC tissues for determination of the clonal origin of *** of hepatocyte markers[hepatocyte paraffin 1(Hep Par 1) and glypican 3(GPC3)]and cholangiocyte markers[cytokeratin(CK)7 and 19]in tumor tissues was examined by immuno histochemical ***:In the 16 CHC specimens,the difference in LOH patterns between HCC and ICC was less than 30%,suggesting the same clonal origin of HCC and *** with this finding,immunohistochemical analysis revealed that hepatocyte markers(Hep Par 1 and GPC3) and cholangiocyte markers(CK7 and CK19) were simultaneously expressed in both the HCC and ICC components in 52.9%of CHC specimens,suggesting that the two components shared a similar phenotype with hepatic progenitor cells(HPCs).On the contrary,in all 10 SHC cases,the difference in LOH patterns between the HCC and ICC components was greater than 30%,suggesting different clonal origins of HCC and *** survival and disease-free survival were shorter for patients with CHC than for patients with SHC(P < 0.05).Conclusions:Our results suggest that the HCC and ICC components of CHC may originate from the same clone,having the potential for dual-directional differentiation similar to *** tended to exhibit the biological behaviors of both HCC and ICC,which may enhance the infiltrative capacity of tumor cells,leading to poor clinical ou

关键词： Combined hepatocellular and cholangiocarcinoma Hepatocellular carcinoma Intrahepatic cholangiocellular carcinoma Loss of heterozygosity Clonal origin Prognosis

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Novel model combining contrast-enhanced ultrasound with serology predicts hepatocellular carcinoma recurrence after hepatectomy

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World Journal of Clinical Cases 2021年第24期9卷 7009-7021页

作者： Hai-Bin Tu Li-Hong Chen Yu-Jie Huang Si-Yi Feng Jian-Ling Lin Yong-Yi Zeng Department of Ultrasound Mengchao Hepatobiliary Hospital of Fujian Medical UniversityFuzhou 350025Fujian ProvinceChina Department of hepatobiliary Surgery Mengchao Hepatobiliary Hospital of Fujian Medical UniversityFuzhou 350025Fujian ProvinceChina

BACKGROUND Surgery is the primary curative option in patients with hepatocellular carcinoma(HCC).However,recurrence within 2 years is observed in 30%–50%of patients,being a major cause of *** To construct and verify a non-invasive prediction model combining contrastenhanced ultrasound(CEUS)with serology biomarkers to predict the early recurrence of *** Records of 744 consecutive patients undergoing first-line curative surgery for HCC in one institution from 2016–2018 were reviewed,and 292 local patients were selected for *** characteristics including gender and age,CEUS liver imaging reporting and data system(LIRADS)parameters including wash-in time,wash-in type,wash-out time,and wash-out type,and serology biomarkers including alanine aminotransferase,aspartate aminotransferase,platelets,and alpha-fetoprotein(AFP)were *** analysis and multivariate Cox proportional hazards regression model were used to evaluate the independent prognostic factors for tumor *** a nomogram called CEUS model was *** CEUS model was then used to predict recurrence at 6 mo,12 mo,and 24 mo,the cut-off value was calculate by X-tile,and each C-index was *** Kaplan-Meier curve was compared by logrank *** calibration curves of each time were *** A nomogram predicting early recurrence(ER),named CEUS model,was formulated based on the results of the multivariate Cox regression *** nomogram incorporated tumor diameter,preoperative AFP level,and LIRADS,and the hazard ratio was 1.123(95%confidence interval[CI]:1.041-1.211),1.547(95%CI:1.245-1.922),and 1.428(95%CI:1.059-1.925),*** cut-off value at 6 mo,12 mo,and 24 mo was 100,80,and 50,and the C-index was 0.748(95%CI:0.683-0.813),0.762(95%CI:0.704-0.820),and 0.762(95%CI:0.706-0.819),*** model showed satisfactory results,and the calibration at 6 mo was desirable;however,the calibration at 12 and 24 mo should be improv

关键词： Hepatocellular carcinoma Recurrence Prediction Contrast-enhanced ultrasound Liver imaging reporting and data system Alpha-fetoprotein

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How do we manage post-OLT redundant bile duct?

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World Journal of Gastroenterology 2013年第16期19卷 2501-2506页

作者： Victor Torres Nicholas Martinez Gabriel Lee Jose Almeda Glenn Gross Sandeep Patel Laura Rosenkranz Division of Gastroenterology and Nutrition Department of Medicine University of Texas Health Science Center at San Antonio Department of Pancreatic and hepatobiliary Surgery University of Texas Health Science Center at San Antonio

AIM: To address endoscopic outcomes of post-Orthotopic liver transplantation (OLT) patients diagnosed with a "redundant bile duct" (RBD). METHODS: Medical records of patients who underwent OLT at the Liver Transplant center, University Texas Health Science center at San Antonio Texas were retrospectively analyzed. Patients with suspected biliary tract complications (BTC) underwent endoscopic retrograde cholangiopancreatography (ERCP). All ERCP were performed by experienced biliary endoscopist. RBD was defined as a looped, sigmoid-shaped bile duct on cholangiogram with associated cholestatic liver biomarkers. Patients with biliary T-tube placement, biliary anastomotic strictures, bile leaks, bile-duct stonessludge and suspected sphincter of oddi dysfunction were excluded. Therapy included single or multiple biliary stents with or without sphincterotomy. The incidence of RBD, the number of ERCP corrective sessions, and the type of endoscopic interventions were recorded. Successful response to endoscopic therapy was defined as resolution of RBD with normalization of associated cholestasis. Laboratory data and pertinent radiographic imaging noted included the pre-ERCP period and a follow up period of 6-12 mo after the last ERCP intervention. RESULTS: One thousand two hundred and eighty-two patient records who received OLT from 1992 through 2011 were reviewed. Two hundred and twenty-four patients underwent ERCP for suspected BTC. RBD was reported in each of the initial cholangiograms. Twentyone out of 1282 (1.6%) were identified as having RBD. There were 12 men and 9 women, average age of 59.6 years. Primary indication for ERCP was cholestatic pattern of liver associated biomarkers. Nineteen out of 21 patients underwent endoscopic therapy and 2/21 required immediate surgical intervention. In the endoscopically managed group: 65 ERCP procedures were performed with an average of 3.4 per patient and 1.1 stent per session. Fifteen out of 19 (78.9%) patients were successfully

关键词： Redundant bile duct Orthotopic liver transplantation Biliary complications Biliary stent Endoscopic retrograde cholangiopancreatography

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