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Platelets in liver disease, cancer and regeneration

World Journal of Gastroenterology 2017年第18期23卷 3228-3239页

作者： Tomohiro Kurokawa Nobuhiro Ohkohchi department of Surgery Division of Gastroenterological and Hepatobiliary Surgery and Organ Transplantation Faculty of Medicine University of Tsukuba

Although viral hepatitis treatments have evolved over the years, the resultant liver cirrhosis still does not completely heal. Platelets contain proteins required for hemostasis, as well as many growth factors required for organ development, tissue regeneration and repair. Thrombocytopenia, which is frequently observed in patients with chronic liver disease(CLD) and cirrhosis, can manifest from decreased thrombopoietin production and accelerated platelet destruction caused by hypersplenism; however, the relationship between thrombocytopenia and hepatic pathogenesis, as well as the role of platelets in CLD, is poorly understood. In this paper, experimental evidence of platelets improving liver fibrosis and accelerating liver regeneration is summarized and addressed based on studies conducted in our laboratory and current progress reports from other investigators. In addition, we describe our current perspective based on the results of these studies. Platelets improve liver fibrosis by inactivating hepatic stellate cells, which decreases collagen production. The regenerative effect of platelets in the liver involves a direct effect on hepatocytes, a cooperative effect with liver sinusoidal endothelial cells, and a collaborative effect with Kupffer cells. Based on these observations, we ascertained the direct effect of platelet transfusion on improving several indicators of liver function in patients with CLD and liver cirrhosis. However, unlike the results of our previous clinical study, the smaller incremental changes in liver function in patients with CLD who received eltrombopag for 6 mo were due to patient selection from a heterogeneous population. We highlight the current knowledge concerning the role of platelets in CLD and cancer and anticipate a novel application of platelet-based clinical therapies to treat liver disease.

关键词： Platelet Liver cirrhosis Liver regeneration Cancer Thrombopoietin Thrombopoietin agonist Eltrombopag

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Anticoagulation and delayed bowel resection in the management of mesenteric venous thrombosis

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World Journal of Gastroenterology 2013年第30期19卷 5025-5028页

作者： Hyung-Kee Kim Jae Min Chun Seung Huh Division of transplantation and Vascular Surgery Department of SurgeryKyungpook National University School of Medicine

Acute mesenteric venous thrombosis is potentially lethal because it can result in mesenteric ischemia and,ultimately,bowel infarction requiring surgical *** anticoagulation for the prevention of thrombus propagation is a well-recognized treatment modality and the current mainstay therapy for patients with acute mesenteric venous ***,the decision between prompt surgical exploration vs conservative treatment with anticoagulation is somewhat difficult in patients with suspected bowel *** we describe a patient with acute mesenteric venous thrombosis who presented with bowel ischemia and was treated with anticoagulation and delayed short-segment bowel resection.

关键词： Thrombosis Mesenteric vein Anticoagulation Small intestine Resection

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Malaria after living donor liver transplantation:report of two cases

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Hepatobiliary & Pancreatic Diseases International 2008年第2期7卷 210-213页

作者： Durgatosh Pandey Kan-Hoe Lee Sin-Yew Wong Kai-Chah Tan department of Hepatobiliary Surgery and Liver transplantation Asian Centre for Liver Diseases and transplantation Gleneagles Hospital Singapore department of Respiratory medicine and Intensive Care Asian Centre for Liver Diseases and transplantation Gleneagles Hospital Singapore department of Infectious Diseases Asian Centre for Liver Diseases and transplantation Gleneagles Hospital Singapore

BACKGROUND:Infectious complications are common during the postoperative course of a liver transplant recipient. Malaria, however, is a rare complication in such a setting. METHOD:We report post-transplantation malaria causing elevation of liver enzymes in two recipients. RESULTS:Both patients who had undergone living donor liver transplantation showed elevated levels of liver enzymes and fever during the postoperative course. Investigations (including liver biopsy in one patient) were initially inconclusive in determining the cause of liver dysfunction. The diagnosis of malaria was established in both cases by peripheral blood smear. Liver function transiently worsened with antimalarial treatment but subsequently became normal. CONCLUSION:This report highlights the importance of excluding such uncommon causes of post-transplantation liver dysfunction, especially when either the recipient or the donor comes from a region endemic for malaria.

关键词： liver transplantation malaria recipient

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Epithelial turnover in duodenal familial adenomatous polyposis: A possible role for estrogen receptors?

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World Journal of Gastroenterology 2016年第11期22卷 3202-3211页

作者： Alfredo Di Leo Gabriella Nesi Mariabeatrice Principi Domenico Piscitelli Bruna Girardi Maria Pricci Giuseppe Losurdo Andrea Iannone Enzo Ierardi Francesco Tonelli Gastroenterology Section Department of Emergency and Organ TransplantationUniversity of Bari Pathology Section Department of Surgery and Translational MedicineUniversity of Florence Pathology Section Department of Emergency and Organ TransplantationUniversity of Bari General Surgery Section Department of Surgery and Translational MedicineUniversity of Florence

AIM: To investigate estrogen receptors expression in duodenal familial adenomatous polyposis (FAP) and any relationship with epithelial proliferation/apoptosis ***: Twenty-two patients affected by FAP undergoing duodenal resection for malignancies were recruited. Controls were 15 healthy subjects undergoing endoscopy for dyspeptic symptoms. ER-α, ER-α, Ki-67, TUNEL and caspase 3 expression (labeling index: percentage of positive cells) were evaluated by immunohistochemistry or immunofluorescence and examined by light or confocal microscopy. Samples were assigned to four groups: normal tissue, low (LGD) and high-grade dysplasia (HGD), adenocarcinoma (AC). One-way analysis of variance, corrected by Bonferroni’s test, and Pearson’s correlation test were applied for statistical ***: ER-beta showed a progressive decline: normal tissue (23.5 ± 4.9), LGD (21.1 ± 4.8), HGD (9.3 ± 3.5), AC (7.1 ± 3.1). The normal tissue of FAP subjects expressed ER-beta like the controls (23.9 ± 6.2). Conversely, ER-α showed a progressive increase from normal tissue (24.8 ± 5.6) to AC (52.0 ± 8.2); the expression in normal tissue was similar to controls (22.5 ± 5.3). Ki67 demonstrated a statistically significant progressive increase at each disease stage up to AC. TUNEL did not reveal differences between controls and normal tissue of FAP subjects, but progressive decreases were observed in LGD, through HGD to AC. Pearson’s correlation test showed a direct relationship between ER-β and TUNEL LI (r = 0.8088, P < 0.0001). Conversely, ER-α was inversely correlated with TUNEL LI (r = - 0.7257, P < 0.0001). The co-expression of ER-β and caspase 3 declined progressively from normal to neoplastic ***: This study confirmed that ER-β is strongly decreased in duodenal FAP carcinomas, declining in a multiple

关键词： Familial adenomatous polyposis Duodenal cancer Estrogen receptors Immunohistochemistry Confocal microscopy Dysplasia

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COVID-19 and Liver transplantation:Challenges and Opportunities

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Journal of Clinical and Translational Hepatology 2023年第3期11卷 521-522页

作者： Georgios Tsoulfas department of transplantation Surgery Aristotle University School of MedicineThessalonikiGreece

Coronavirus disease 2019(COVID-19)has presented hu-manity with a significant global challenge that has neces-sitated changes and adaptations at all *** transplant(LT)activity could not have been an exception,as it was impacted both by changes in the urgency of the use of medi-cal resources,including shortage of hospital and intensive care unit beds,problems in outpatient follow-up,redefining the urgency of a LT among *** addition to the fact that the quarantines placed and the resulting emotional isolation have led to increased alcohol use and abuse.1,2 An effort by several transplant associations and the Centers for Medicare and Medicaid led to issuing guidance and recommendations regarding transplantation surgery during COVID-19.3,4 In the paper“Impact of COVID-19 on Liver Transplant Activity in the USA:Variation by Etiology and Cirrhosis Complications”by Kuo et al.,5 the authors provide us with a thorough evalu-ation of the impact of the COVID-19 pandemic on LT activity based on etiology in the USA,by analysing data from the United Network of Organ Sharing(UNOS)database(2018-2021).The authors looked at two different time periods,one in the pre-COVID era between April 2018 and February 2020.

关键词： Liver alcohol unit

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Role of surgery and transplantation in the treatment of hepatic metastases from neuroendocrine tumor

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World Journal of Gastroenterology 2014年第39期20卷 14348-14358页

作者： Sayee Sundar Alagusundaramoorthy Roberto Gedaly Division of transplantation Department of Surgery University of Kentucky College of Medicine Lexington KY 40536 United States

Neuroendocrine tumors(NET) are a heterogeneous group of cancers, with indolent behavior. The most common primary origin is the gastro-intestinal tract but can also appear in the lungs, kidneys, adrenals, ovaries and other organs. In general, NET is usually discovered in the metastatic phase(40%-80%). The liver is the most common organ involved when metastases occur(40%-93%), followed by bone(12%-20%) and lung(8%-10%).A number of different therapeutic options are available for the treatment of hepatic metastases including surgical resection, transplantation, ablation, trans-arterial chemoembolization, chemotherapy and somatostatin analogues. Recently, molecular targeted therapies have been used, usually in combination with other treatment options, to improve outcomes in patients with metastases. This article emphasizes on the role of surgery in the treatment of liver metastases from NET.

关键词： Neuroendocrine tumors Liver metastases Hepatectomy Liver transplantation

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Nasogastric tube syndrome induced by an indwelling long intestinal tube

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World Journal of Gastroenterology 2016年第15期22卷 4057-4061页

作者： Naoki Sano Masayoshi Yamamoto Kentaro Nagai Keiichi Yamada Nobuhiro Ohkohchi department of Surgery Tsukuba Medical Center Hospital department of Surgery and Organ transplantation Faculty of Medicine University of Tsukuba

The nasogastric tube(NGT) has become a frequently used device to alleviate gastrointestinal symptoms. Nasogastric tube syndrome(NTS) is an uncommon but potentially life-threatening complication of an indwelling NGT. NTS is characterized by acute upper airway obstruction due to bilateral vocal cord paralysis. We report a case of a 76-year-old man with NTS, induced by an indwelling long intestinal tube. He was admitted to our hospital for treatment of sigmoid colon cancer. He underwent sigmoidectomy to release a bowel obstruction, and had a long intestinal tube inserted to decompress the intestinal tract. He presented acute dyspnea following prolonged intestinal intubation, and bronchoscopy showed bilateral vocal cord paralysis. The NGT was removed immediately, and tracheotomy was performed. The patient was finally discharged in a fully recovered state. NTS be considered in patients complaining of acute upper airway obstruction, not only with a NGT inserted but also with a long intestinal tube.

关键词： Nasogastric tube syndrome Nasogastric tube Long intestinal tube Acute upper airway obstruction Tracheotomy

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Endothelial dysfunction in the kidney transplant population:Current evidence and management strategies

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World Journal of transplantation 2025年第1期15卷 24-43页

作者： Arun Prabhahar Akshey Batta Juniali Hatwal Vivek Kumar Raja Ramachandran Akash Batta department of Telemedicine(Internal medicine and Nephrology) Post Graduate Institute of Medical Education and ResearchChandigarh 160012India department of Urology and Renal Transplant Neelam HospitalRajpura 140401PunjabIndia department of Internal medicine Post Graduate Institute of Medical Education and ResearchChandigarh 160012India department of Nephrology Post Graduate Institute of Medical Education and ResearchChandigarh 160012India department of Cardiology Dayanand Medical College and HospitalLudhiana 141001PunjabIndia

The endothelium modulates vascular homeostasis owing to a variety of vasoconstrictors and *** dysfunction(ED),characterized by impaired vasodilation,inflammation,and thrombosis,triggers future cardiovascular(CV)*** kidney disease,a state of chronic inflammation caused by oxidative stress,metabolic abnormalities,infection,and uremic toxins damages the *** is also associated with a decline in estimated glomerular filtration *** kidney transplantation,endothelial functions undergo immediate but partial restoration,promising graft longevity and enhanced CV ***,the anticipated CV outcomes do not happen due to various transplant-related and unrelated risk factors for ED,culminating in poor CV health and graft *** in kidney transplant recipients is an underrecognized and poorly studied *** diseases are the leading cause of death among kidney transplant candidates with functioning *** contributes to the pathogenesis of many of the CV *** biomarkers and vasoreactivity tests are available to study endothelial *** an increasing number of transplants happening every year,and improved graft rejection rates due to the availability of effective immunosuppressants,the focus has now shifted to endothelial protection for the prevention,early recognition,and treatment of CV diseases.

关键词： Endothelial dysfunction Endothelium Cardiovascular disease Kidney transplantation Chronic kidney disease Nitric oxide Flow-mediated dilatation Nitro-glycerine-mediated dilatation Biomarkers

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Risk factors for new onset diabetes mellitus after liver transplantation: A meta-analysis

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World Journal of Gastroenterology 2015年第20期21卷 6329-6340页

作者： Da-Wei Li Tian-Fei Lu Xiang-Wei Hua Hui-Juan Dai Xiao-Lan Cui Jian-Jian Zhang Qiang Xia department of Liver Surgery and Liver transplantation Center Renji HospitalSchool of MedicineShanghai Jiaotong University

AIM: To determine the risk factors for new-onset diabetes mellitus(NODM) after liver transplantation by conducting a systematic review and ***: We electronically searched the databases of MEDLINE, EMBASE and the Cochrane Library from January 1980 to December 2013 to identify relevant studies reporting risk factors for NODM after liver transplantation. Two authors independently assessed the trials for inclusion and extracted the data. Discrepancies were resolved in consultation with a third reviewer. All statistical analyses were performed with the Rev Man5.0 software(The Cochrane Collaboration, Oxford, United Kingdom). Pooled odds ratios(OR) or weighted mean differences(WMD) with 95% confidence intervals(CIs) were calculated using either a fixed effects or a random effects model, based on the presence(I2 50%) of significant heterogeneity. RESULTS: Twenty studies with 4580 patients were included in the meta-analysis, all of which were retrospective. The meta-analysis identified the following significant risk factors: hepatitis C virus(HCV) infection(OR = 2.68; 95%CI: 1.92-3.72); a family history of diabetes(OR = 1.69, 95%CI: 1.09-2.63, P transplantation.

关键词： Diabetes mellitus Meta-analysis Risk factor Liver transplantation Hepatitis C virus

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Liver transplantation for hepatocellular carcinoma on cirrhosis:Strategies to avoid tumor recurrence

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World Journal of Gastroenterology 2011年第43期17卷 4741-4746页

作者： Marco Vivarelli Andrea Risaliti department of Surgery and transplantation University of BolognaS Orsola Hospital department of Hepatobiliopancreatic and transplantation Surgery Polytechnic University of MarcheOspedali Riuniti

Hepatocellular carcinoma(HCC) is one of the most frequent neoplasms worldwide and in most cases it is associated with chronic liver *** transplantation(LT) is potentially the optimal treatment for those patients with HCC who have a poor functional hepatic reserve due to their underlying chronic liver ***,due to the limited availability of donors,only those patients whose oncologic profile is favorable can be considered for *** the careful selection of candidates based on strict rules,10 to 20%of liver transplant recipients who have HCC in the native cirrhotic liver develop tumor recurrence after *** selection criteria presently employed to minimize the risk of recurrence are based on gross tumor characteristics defined by imaging techniques;unfortunately,the accuracy of imaging is far from being ***,microscopic tumor features that are strictly linked with prognosis can not be assessed prior to ***-transplantation tumor downstaging may allow transplantation in patients initially outside the selection criteria and seems to improve the prognosis;it also provides information on tumor *** peculiarity of the transplantation setting,when this is compared with other modalities of treatment,is the need for pharmacological immunosuppression:this is based on drugs that have been demonstrated to increase the risk of tumor *** HCC is an aggressive malignancy,immunosuppression has to be handled carefully in patients who have HCC at the time of transplantation and new categories of immunosuppressive agents should be *** chemotherapy following transplantation has failed to show any significant *** aim of the present study is to review the possible strategies to avoid recurrence of HCC after liver transplantation based on the current clinical evidence and the more recent developments and to discuss possible future directions.

关键词： Chemotherapy Hepatocellular carcinoma Immunosuppression Liver transplantation Tumor recurrence

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