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胰腺移植的现状与展望

中华消化外科杂志 2020年第12期19卷 1243-1247页

作者：石宜铭中国台北荣民总医院普通外科

目前胰腺移植是治疗1型糖尿病最可靠,可实现永久性治疗效果的外科手术。胰腺功能重度障碍导致的血糖水平长期控制不良或重度糖尿病是发生心脏病、中风、尿毒症、失明等疾病的危险因素,患者生命质量通常极差。胰腺移植可使受者血糖浓度... 详细信息

目前胰腺移植是治疗1型糖尿病最可靠,可实现永久性治疗效果的外科手术。胰腺功能重度障碍导致的血糖水平长期控制不良或重度糖尿病是发生心脏病、中风、尿毒症、失明等疾病的危险因素,患者生命质量通常极差。胰腺移植可使受者血糖浓度恢复正常水平,改善受者糖尿病并发症,包括肾脏病变、神经性病变、视网膜病变等,降低受者的病残率和病死率。笔者结合中国台北荣民总医院临床实践经验,探讨胰腺移植治疗1型糖尿病的手术方式、适应证与禁忌证、供者与受者选择、手术流程与术后并发症、免疫抑制剂及其相关并发症、术后排斥反应及其处理、疗效及预后相关因素,旨在为广大同道提供参考。

关键词：器官移植胰腺 1型糖尿病移植物排斥经验

Characterization of pancreatic stem cells derived from adult human pancreas ducts by fluorescence activated cell sorting

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World Journal of Gastroenterology 2006年第28期12卷 4529-4535页

作者： Han-Tso Lin Shih-Hwa Chiou Chung-Lan Kao yi-ming shyr Chien-Jen Hsu yin-Wen Tarng Larry L-T Ho Ching-Fai Kwok Hung-Hai Ku Department of Medical Research and Education Taipei Veterans General HospitalTaipei11217TaiwanChina Department of Medical Research and Education Taipei Veterans General Hospitaland Institute of Clinical MedicineNational Yang-Ming UniversityTaipei11221TaiwanChina Department of Physical Medicine and Rehabilitation Taipei Veterans General HospitalTaipei11217TaiwanChina Department of Surgery Taipei Veterans General HospitalTaipei11217TaiwanChina Department of Orthopedics Kaohsiung Veterans General Hospital Kaohsiung 81346TaiwanChina Division of Endocrinology and Metabolism Department of Internal MedicineTaipei Veterans General HospitalTaipei11217TaiwanChina Institute of Anatomy and Cell Biology National Yang-Ming UniversityTaipeiDepartment of Education and ResearchTaipei City Hospital11221TaiwanChina

AIM： To isolate putative pancreatic stem cells （PSCs） from human adult tissues of pancreas duct using serumfree, conditioned medium. The characterization of surface phenotype of these PSCs was analyzed by flow cytometry. The potential for pancreatic lineage and the capability of β-cell differentiation in these PSCs were evaluated as well. METHODS： By using serum-free medium supplemented with essential growth factors, we attempted to isolate the putative PSCs which has been reported to express nestin and pdx-1. The MatrigelTM was employed to evaluate the differential capacity of isolated cells. Dithizone staining, insulin content/secretion measurement, and immunohistochemistry staining were used to monitor the differentiation. Fluorescence activated cell sorting （FACS） was used to detect the phenotypic markers of putative PSCs. RESULTS： A monolayer of spindle-like cells was cultivated. The putative PSCs expressed pdx-1 and nestin. They were also able to differentiate into insulin-, glucagon-, and somatostatin-positive cells. The spectrum of phenotypic markers in PSCs was investigated; a similarity was revealed when using human bone marrow-derived stem cells as the comparative experiment, such as CD29, CD44, CD49, CD50, CD51, CD62E, PDGFR-α, CD73 （SH2）, CD81, CD105（SH3）. CONCLUSION： In this study, we successfully isolated PSCs from adult human pancreatic duct by using serumfree medium. These PSCs not only expressed nestin and pdx-1 but also exhibited markers attributable to mesenchymal stem cells. Although work is needed to elucidate the role of these cells, the application of these PSCs might be therapeutic strategies for diabetes mellitus.

关键词： Putative pancreas stem cell Nestirr, pdx-1 Phenotypic marker

Experience with Open and Laparoscopic Surgery for Primary Gastric Stromal Tumors in a Single Institute

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Surgical Science 2017年第6期8卷 229-239页

作者： yi-Hsuan Hu Kuo-Hung Huang Yuan-Tzu Lan Jen-Hao Chen Su-Shun Lo Anna Fen-Yau Li Shih-Hwa Chiou Chew-Wun Wu yi-ming shyr Wen-Liang Fang Division of General Surgery Department of Surgery Taipei Veterans General Hospital Taiwan Division of General Surgery Department of Surgery Cardinal Tien Hospital Taiwan Division of Colon & Rectal Surgery Department of Surgery Taipei Veterans General Hospital Taiwan Department of Pathology Taipei Veterans General Hospital Taiwan National Yang-ming University Taiwan Institute of Clinical Medicine School of Medicine National Yang-Ming University Taiwan Cheng Hsin General Hospital Taiwan National Yang-ming University Hospital Taiwan Department of Medical Research and Education Taipei Veterans General Hospital Taiwan Institute of Pharmacology National Yang-Ming University Taiwan

Laparoscopic surgery has become increasingly popular in the management of gastric gastrointestinal stromal tumors (GISTs) in recent years. One hundred and forty-five patients underwent curative resections of primary gastric stromal tumors between September 2002 and March 2012 were assigned to either an open surgery group (n = 99) or a laparoscopic surgery group (n = 46). In the open surgery group, there was a significantly higher number of samples with a mitotic index ≥ 10 (16.1% vs. 0%), more tumors located in the gastric cardia (13.1% vs. 6.5%), greater operative blood loss (80 mL vs. 50 mL) and a longer postoperative hospital stay (10 days vs. 6 days) than in the laparoscopic group. The surgical morbidity and mortality were 6.1% and 0% in the open group, whereas no complication or mortality in the laparoscopic group. Ten patients in the open group had tumor recurrences and no recurrence in the laparoscopic group. Multivariate analysis showed that tumor size and mitotic index were two independent risk factors associated with tumor recurrence. The 3-year disease-free survival rates and 5-year overall survival rates were similar between the two groups. The laparoscopic approach is a safe alternative procedure for gastric GISTs.

关键词： GIST Open Laparoscopic Tumor Size Mitotic Index

International consensus statement on robotic pancreatic surgery

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Hepatobiliary Surgery and Nutrition 2019年第4期8卷 345-360页

作者： Rong Liu Go Wakabayashi Chinnusamy Palanivelu Allan Tsung Kehu Yang Brian KPGoh Charing Ching-Ning Chong Chang Moo Kang Chenghong Peng Eli Kakiashvili Ho-Seong Han Hong-Jin Kim Jin He Jae Hoon Lee Kyoichi Takaori Marco Vito Marino Shen-Nien Wang Tiankang Guo Thilo Hackert Ting-Shuo Huang yiengpruksawan Anusak Yuman Fong Yuichi Nagakawa yi-ming shyr Yao-ming Wu Yupei Zhao Department of Hepatopancreatobiliary Surgical Oncology Chinese People’s Liberation Army(PLA)General HospitalBeijing 100853China Center for Advanced Treatment of Hepatobiliary and Pancreatic Diseases Ageo Central General HospitalAgeoJapan Division of Gastrointestinal Surgery and Minimal Access Surgery GEM Hospital and Research CentreCoimbatoreIndia Division of Surgical Oncology Gastrointestinal Disease Specific Research GroupThe Ohio State University Wexner Medical Center Department of SurgeryColumbusOHUSA Evidence-Based Medicine Center School of Basic Medical SciencesLanzhou UniversityLanzhou 730000China Department of Hepatopancreatobiliary and Transplant Surgery Singapore General HospitalSingapore Department of Surgery Division of Hepatobiliary and Pancreatic SurgeryPrince of Wales Hospitalthe Chinese University of Hong KongHong KongChina Division of HBP Surgery Yonsei University College of MedicinePancreatobiliary Cancer CenterYonsei Cancer CenterSeverance HospitalSeoulKorea Pancreatic Disease Centre Ruijin HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200025China Department of General Surgery Galilee Medical CenterNahariyaIsrael Department of Surgery Seoul National University College of MedicineSeoul National University Bundang HospitalSeoulKorea Department of Surgery Yeungnam University HospitalDaeguKorea Department of Surgery The Johns Hopkins HospitalBaltimoreMDUSA Division of Hepatobiliary&Pancreas Surgery Department of SurgeryAsan Medical CenterSeoulKorea Department of Surgery Kyoto University HospitalShogoinSakyo-KuKyotoJapan Department of General Surgery Azienda OspedalieraOspedali Riuniti Villa Sofia-CervelloPalermoItaly Division of General and Digestive Surgery Department of SurgeryKaohsiung Medical University HospitalKaohsiung Department of General Surgery Gansu Provincial HospitalLanzhou 730030China Department of General Visceral and Transplantation SurgeryHeidelberg University HospitalHeidelbergGermany Division of General Surge

The robotic surgical system has been applied to various types of pancreatic surgery. However, controversies exist regarding a variety of factors including the safety, feasibility, efficacy, and cost-effectiveness of robotic surgery. This study aimed to evaluate the current status of robotic pancreatic surgery and put forth experts' consensus and recommendations to promote its development. Based on the WHO Handbook for Guideline Development, a Consensus Steering Group* and a Consensus Development Group were established to determine the topics, prepare evidence-based documents, and generate recommendations. The GRADE Grid method and Delphi vote were used to formulate the recommendations. A total of 19 topics were analyzed. The first 16 recommendations were generated by GRADE using an evidence-based method (EBM) and focused on the safety, feasibility, indication, techniques, certification of the robotic surgeon, and cost-effectiveness of robotic pancreatic surgery. The remaining three recommendations were based on literature review and expert panel opinion due to insufficient EBM results. Since the current amount of;evidence was low/meager as evaluated by the GRADE method, further randomized controlled trials (RCTs) are needed in the future to validate these recommendations.

关键词： Robotic surgery consensus statement pancreatectomy pancreaticoduodenectomy pancreatic enucleation

Balthazar computed tomography severity index is superior to Ranson criteria and APACHE Ⅱ scoring system in predicting acute pancreatitis outcome

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World Journal of Gastroenterology 2005年第38期11卷 6049-6052页

作者： Ting-Kai Leung Chi-ming Lee shyr-yi Lin Hsin-Chi Chen Hung-Jung Wang Li-Kuo Shen Ya-Yen Chen Department of Diagnostic Radiology Taipei Medical University Hospital Taipei TaiwanChina Department of Internal Medicine Taipei Medical University Hospital Taipei Taiwan China

AIM： Acute pancreatitis （AP） is a process with variable involvement of regional tissues or organ systems. Multifactorial scales included the Ranson, Acute Physiology and Chronic Health Evaluation （APACHE Ⅱ） systems and Balthazar computed tomography severity index （CTSI）. The purpose of this review study was to assess the accuracy of CTSI, Ranson score, and APACHE II score in course and outcome prediction of AP. METHODS： We reviewed 121 patients who underwent helical CT within 48 h after onset of symptoms of a first episode of AP between 1999 and 2003. Fourteen inappropriate subjects were excluded; we reviewed the 107 contrastenhanced CT images to calculate the CTSI. We also reviewed their Ranson and APACHE Ⅱ score. In addition, complications, duration of hospitalization, mortality rate, and other pathology history also were our comparison parameters. RESULTS： We classified 85 patients （79%） as having mild AP （CTSI 〈5） and 22 patients （21%） as having severe AP （CTSI ≥5）. In mild group, the mean APACHE II score and Ranson score was 8.6±1.9 and 2.4±1.2, and those of severe group was 10.2±2.1 and 3.1±0.8, respectively. The most common complication was pseudocyst and abscess and it presented in 21 （20%） patients and their CTSI was 5.9±1.4. A CTSI ≥5 significantly correlated with death, complication present, and prolonged length of stay. Patients with a CTSI ≥5 were 15 times to die than those CTSI 〈5, and the prolonged length of stay and complications present were 17 times and 8 times than that in CTSI 〈5, respectively. CONCLUSION： CTSI is a useful tool in assessing the severity and outcome of AP and the CTSI ≥5 is an index in our study. Although Ranson score and APACHE II score also are choices to be the predictors for complications, mortality and the length of stay of AP, the sensitivity of them are lower than CTSI.

关键词： Acute pancreatitis Ranson score APACHE Ⅱ score Balthazar computed tomography severity index

Influence of iron on the severity of hepatic fibrosis in patients with chronic hepatitis C

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World Journal of Gastroenterology 2006年第30期12卷 4897-4901页

作者： Tsung-Jung Lin Li-ying Liao shyr-yi Lin Chih-Lin Lin Ting-An Chang Department of Gastroenterology Ren-Ai Branch Taipei City Hospital TaipeiTaiwan China Graduate Institute of Medical Sciences Taipei Medical University Taipei Taiwan China Department of Pathology Ren-Ai Branch Taipei City Hospital Taipei Taiwan China

AIM： To evaluate the association among hepatic fibrosis, serum iron indices, and hepatic iron stores in patients with Chronic Hepatitis C （CHC）. METHODS： Thirty-two CHC patients were included in our study. The histological degree of fibrosis and inflammation activity was assessed according to the Metavir system. The serum iron indices including ferritin, iron and transferrin saturation were measured. Hepatic iron deposition was graded by Perls＇ stain. RESULTS： The CHC patients with severe hepatic fibrosis （n = 16） were significantly older than CHC patients with mild fibrosis （n = 16）（P = 0.024）. The serum iron indices, increased serum iron store and positive hepatic iron stain were not significantly different between the two groups. In multivariate logistic regression analysis, the age at biopsy was an independent predictor of severe hepatic fibrosis （Odds ratio = 1.312; P = 0.035）. The positive hepatic iron stain was significantly associated with the values of alanine aminotransferase （ALT）（P = 0.017）, ferritin （P = 0.008）, serum iron （P = 0.019） and transferrin saturation （P = 0.003）. The ferritin level showed significant correlation with the value ofALT （r = 0.531; P = 0.003）, iron （r = 0.467; P = 0.011） and transferrin saturation （r = 0.556; P = 0.002）. CONCLUSION： Our findings suggest that the severity of hepatitis C virus （HCV）-related liver injury is associated with patient age at biopsy. Both serum iron indices and hepatic iron deposition show correlation with serum indices of chronic liver disease but are not related to grade and stage of liver histology.

关键词： Chronic hepatitis C Hepatitis C virus Hepatic iron Serum iron Hepatic fibrosis

Molecular mechanisms of denbinobin-induced anti-tumorigenesis effect in colon cancer cells

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World Journal of Gastroenterology 2005年第20期11卷 3040-3045页

作者： Kuo-Ching Yang yih-Huei Uen Fat-Moon Suk Yu-Chih Liang ying-Jan Wang Yuan-Soon Ho I-Hsuan Li shyr-yi Lin Department of Internal Medicine Shin Kong Wu Ho-Su Memorial Hospital Taipei Taiwan Department of Internal Medicine Taipei Medical University Taipei Taiwan China Department of Surgery Chi-Mei Foundational Medical Center Yung-Kane City Tainan Taiwan China Department of Internal Medicine Taipei Medical University Hospital Taipei Taiwan China School of Medical Technology Taipei Medical University Taipei Taiwan China Department of Environmental and Occupational Health National Cheng Kung University Medical College TainanTaiwan China Department of Internal Medicine School of Medicine Taipei Medical University Taipei Taiwan China Department of Internal Medicine School of Medicine and Department of Internal Medicine Taipei Medical University Hospital Taipei Medical University Taipei Taiwan China

AIM: To explore both the in vitro and in vivo effects of denbinobin against colon cancer cells and clarify its underlying signal pathways. METHODS: We used COLO 205 cancer cell lines and nude mice xenograft model to study the in vitro and in vivo anti-cancer effects of denbinobin. RESULTS: Denbinobin at concentration of 10-20 μmol/L dose-dependently suppressed COLO 205 cell proliferation by MTT test. Flow cytometry analysis and DNA fragmentation assay revealed that 10-20 μmol/L denbinobin treatment induced COLO 205 cells apoptosis. Western blot analysis showed that caspases 3,8,9 and Bid protein were activated by denbinobin treatment to COLO 205 cells accompanied with cytochrome c and apoptosis-inducing factor (AIF) translocation. Pretreatment of MEK 1 inhibitor (U10126), but not p38 inhibitor (SB203580) and JNK inhibitor (SP600125), reversed denbinobin-induced caspase 8, 9 and Bid activation in COLO 205 cells suggesting that extracellular signal-regulated kinase were involved in the denbinobin-induced apoptosis in COLO 205 cells. Significant regression of tumor up to 68% was further demonstrated in vivo by treating nude mice bearing COLO 205 tumor xenografts with denbinobin 50 mg/kg intraperitoneally. CONCLUSION: Our findings suggest that denbinobin could inhibit colon cancer growth both in vitro and in vivo. Activation of extrinsic and intrinsic apoptotic pathways and AIF were involved in the denbinobin-induced COLO 205 cell apoptosis.

关键词： Denbinobin Colon cancer Nude mice Apoptosis ERK pathway

Involvement of fatty acid-CoA ligase 4 in hepatocellular carcinoma growth: Roles of cyclic AMP and p38 mitogen-activated protein kinase

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World Journal of Gastroenterology 2005年第17期11卷 2557-2563页

作者： Yu-Chih Liang Chih-Hsiung Wu Jan-Show Chu Chung-Kwe Wang Ling-Fang Hung ying-Jan Wang Yuan-Soon Ho Jan-Gowth Chang shyr-yi Lin School of Medical Technology Taipei Medical University TaipeiTaiwanChina Department of Surgery Taipei Medical University Hospital Taipei Medical UniversityTaipeiTaiwanChina Department of Pathology School of Medicine Taipei Medical UniversityTaipeiTaiwanChina Department of Internal Medicine Taipei Municipal Jen-Ai Hospital TaipeiTaiwanChina Department of Environmental and Occupational Health National Cheng Kung University Medical College TainanTaiwanChina Department of Molecular Medicine and Laboratory Medicine China Medical University Hospital TaiwanChina Department of Internal Medicine School of Medicine Department of Internal Medicine Taipei Medical University HospitalTaipei Medical UniversityTaipeiTaiwanChina

AIM: Fatty acid-CoA ligase 4 (FACL4) is an arachidonatepreferring enzyme which has been shown to be up-regulated in human colon cancer tissues and implicated in the colon tumorigenesis. The purpose of this study was to investigatethe role of FACL4 in the human hepatocellular carcinoma (HCC) tumorigenesis and the specific signal pathways involved in this ***: We investigated the expression and regulation of FACL4 in HCC, adjacent non-tumorous liver tissues, and cell ***: In HCC patients, we demonstrated that FACL4 gene expression was markedly elevated in the cancerous tissues than in the adjacent non-cancerous liver *** addition, several human hepatoma cell lines, including Hep3B and HepG2, expressed high levels of FACL4. Stable overex-pression of FACL4 knockdown plasmids (small interfering RNA, siRNA) to Hep3B cells significantly decreased FACL4 expression and subsequently limited the cell proliferation. Treatment of Hep3B cells with 8bromo-cAMP and SB203508 (p38 MAPK inhibitor) significantly suppressed the FACL4 expression. CONCLUSION: FACL4 is involved in the HCC tumorigenesis and both cAMP and p38 MAPK pathways are associated with the regulation of FACL4 in HCC.

关键词： FACL-4 HCC

Shanghai Score： A Prognostic and Adjuvant Treatment-evaluating System Constructed for Chinese Patients with Hepatocellular Carcinoma after Curative Resection

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Chinese Medical Journal 2017年第22期130卷 2650-2660页

作者： Hui-Chuan Sun Lu Xie Xin-Rong Yang Wei Li Jian Yu Xiao-Dong Zhu Yong Xia Ti Zhang Yang Xu Bo Hu Li-Ping Du Ling-Yao Zeng Jian Ouyang Wei Zhang Tian-Qiang Song Qiang Li ying-Hong Shi Jian Zhou Shuang-Jian Qiu Qian Liu yi-Xue Li Zhao-You Tang Yu shyr Feng Shen Jia Fan Department of Liver Surgery Liver Cancer Institute Zhongshan Hospital Fudan University Key Laboratory of Carcinogenesis and Cancer Invasion Ministry of Education Shanghai 200032 China Shanghai Center for Bioinformation Technology Shanghai Academy of Science and Technology Shanghai 201203 China Britton Chance Center for Biomedical Photonics Wuhan National Laboratory for Optoelectronics Huazhong University of Science and Technology Wuhan Hubei 430074 China Key Laboratory of Computational Biology CAS-MPG Partner Institute for Computational Biology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai 200031 China Department of Hepatic Surgery Eastern Hepatobiliary Surgery Hospital The Second Military Medical University Shanghai 200438 China Department of Hepatobiliary Surgery Tianjin Medical University Cancer Institute and Hospital Tianjin 300040 China Center for Quantitative Sciences Vanderbilt University School of Medicine Nashville TN 37232 USA

Background： For Chinese patients with hepatocellular carcinoma （HCC）, surgical resection is the most important treatment to achieve long-term survival for patients with an early-stage tumor, and yet the prognosis after surgery is diverse. We aimed to construct a scoring system （Shanghai Score） for individualized prognosis estimation and adjuvant treatment evaluation. Methods： A multivariate Cox proportional hazards model was constructed based on 4166 HCC patients undergoing resection during 2001-2008 at Zhongshan Hospital. Age, hepatitis B surface antigen, hepatitis B e antigen, partial thromboplastin time, total bilirubin, alkaline phosphatase, y-glutamyltransferase, a-fetoprotein, tumor size, cirrhosis, vascular invasion, differentiation, encapsulation, and tumor number were finally retained by a backward step-down selection process with the Akaike information criterion. The Harrell＇s concordance index （C-index） was used to measure model performance. Shanghai Score is calculated by summing the products of the 14 variable values times each variable＇s corresponding regression coefficient. Totally 1978 patients from Zhongshan Hospital undergoing resection during 2009-2012, 808 patients from Eastern Hepatobiliary Surgery Hospital during 2008-2010, and 244 patients from Tianjin Medical University Cancer Hospital during 2010-2011 were enrolled as external validation cohorts. Shanghai Score was also implied in evaluating adjuvant treatment choices based on propensity score matching ***： Shanghai Score showed good calibration and discrimination in postsurgical HCC patients. The bootstrap-corrected C-index （confidence interval [CI]） was 0.74 for overall survival （OS） and 0.68 for recurrence-free survival （RFS） in derivation cohort （4166 patients）, and in the three independent validation cohorts, the CIs for OS ranged 0.70 0.72 and that for RFS ranged 0.63 0.68. Furthermore, Shanghai Score provided evaluation for adjuvant treatment choices （transcatheter arteri

关键词： Adjuvant Treatment Hepatocellular Carcinoma Prognosis Shanghai Score