Ex vivo liver resection and auto-transplantation as an alternative for the treatment of liver malignancies: Progress and challenges

Hepatectomy is still the major curative treatment for patients with liver malignancies.However,it is still a big challenge to remove the tumors in the central posterior area,especially if their location involves the retrohepatic inferior vena cava and hepatic veins.Ex vivo liver resection and auto-transplantation(ELRA),a hybrid technique of the traditional liver resection and transplantation,has brought new hope to these patients and therefore becomes a valid alternative to liver transplantation.Due to its technical difficulty,ELRA is still concentrated in a few hepatobiliary centers that have experienced surgeons in both liver resection and liver transplantation.The efficacy and safety of this technique has already been demonstrated in the treatment of benign liver diseases,especially in the advanced alveolar echinococcosis.Recently,the application of ELRA for liver malignances has gained more attention.However,standardization of clinical practice norms and international consensus are still lacking.The prognostic impact in these oncologic patients also needs further evaluation.In this review,we summarized the principles and recent progresses on ELRA.

A 26-year clinical observation of splenic auto-transplantation and oesophageal transection anastomosis:a new treatment strategy in patients with portal hypertension

Background Surgical treatment options for patients with cirrhosis and portal hypertension are complicated. In this study we evaluated the effectiveness of a new treatment strategy, splenic auto-transplantation and oesophageal transection anastomosis. We report results from clinical observations, splenic immune function and portal dynamics in 274 patients. Methods From 1979 to 2005, 274 cirrhosis patients with portal hypertension underwent the new treatment strategy, and were followed up to compare results with those patients who underwent traditional surgical treatment. From 1999 to 2002 a randomized controlled trial （RCT） was performed on 40 patients to compare their post-operative immune function. From 1994 to 2006, another RCT enrolled 28 patients to compare portal dynamics using three-dimensional dynamic contrast-enhanced magnetic resonance angiography （3D DEC MRA） investigation post operation. Results Among 274 patients （mean age 41.8 years）, the emergency operative mortality （4.4%）, selective operative mortality （2.2%）, complication rate （17.9%）, prevalence of hepatic encephalopathy （〈1%）, rate of portal hypertension gastritis （PHG） bleeding （9.1%）, and morbidity of hepatic carcinoma （8%） were similar to those patients undergoing traditional operation; the spleen immunology function （Tuftsin, IgM） decreased in both groups 2 months post operation, but this decrease did not reach statistical significance. Through 3D DCE MRA, the cross sectional area and the velocity and volume of blood flow of the main portal vein decreased significantly after operation in both groups. The velocity and volume of blood flow in the auto-transplantation group was significantly lower than that in the control group. Conclusions Splenic auto-transplantation and esophageal transection anastomosis is a safe, effective, and reasonable treatment strategy for patients with portal hypertension with varicial bleeding. It not only can correct hypersplenism, but may also achieve complete hemostasis. Spleens auto-transplanted into the retroperitoneal space can preserve immune function and establish broad collateral circulation.

Histomorphological observation in arterial remodeling following New Zealand rabbit auto-extremity artery transplantation

Objective： To investigate the histomorphological change in auto-extremity artery following transplantation. Methods： 50 New Zealand rabbits were randomly divided into 5 groups（postoperative 1 d, 3 d, 7 d, 14 d, 56 d, n = 10）. Femoral artery was harvested and end-to-side anastomosed with carotid in order to build the auto-extremity arterial graft animal model. On the postoperative 1^st, 35^nd, 7^th, 14th and 56^th days, grafts for morphometric analysis under the Image analysis system were obtained; and electron microscope was scanned to observe endothelial cells. In addition, Immunostaining of sections were performed with the mouse monoclonal antibody of the a -smooth muscle isoform of actin and proliferating cell nuclear antigen antibody. Results： Overall patency rate for all conduits was 86%.The intimal hyperplasia was first observed in the 7^th day group, and continued to increase in the 56^th day group（183.21 ± 111.74） μ m, P 〈 0.01. Additionally, the luminal narrowed（32.43 ± 18.28）% in the 56^th day group. Smooth muscle cells were the mainly hyperplastic components. The most active proliferation of cells was detected in the 14^th day group, where the extracellular matrix gradually deposited in the intima. Conclusion： Moderate intimal hyperplasia occurred in arterial conduits and vascular structure experienced constrictive remodeling after auto-transplantation.

The establishment of pancreatic islet isolation in India-an update on human pancreatic islet transplantation

Background:Diabetes is a widespread disease with increasing prevalence.Transplantation of islets of Langerhans is a viable treatment for a selected group of patients with repeated hypoglycemic episodes in type 1 diabetes.The countries where islet transplantation has not been explored suffer from insufficient knowledge concerning key elements of the isolation process.Donor and organ procurement parameters impact human islet yield,although for research purposes,islet yield may be secondary in importance to islet function.This paper will analyze the feasibility of research-only human islet isolation and signify parameters underlying a successful yield in the Indian population.This eventually can make islet transplantation a clinical reality in India.Method:After receiving the consent for procuring brain-dead pancreas from the first-degree of relatives,samples were collected and transported in a transportation buffer at 4℃.The procedure consists of a mechanically enhanced enzymatic digestion of the pancreas,after which it was taken for purification using Ficoll method,followed by islet quality testing.Results:Through 15 isolations done over a span of approximately 2 years during the COVID pandemic in India,we confirm that ischemic time and glycated hemoglobin,each have a negative impact on isolation purity and yield.Notably,extending cold ischemic tim beyond the typical clinical isolation cutoff of 12 hours(to≥18 h)had a huge impact on islet function and yield.Age had a negative correlation with islet yield;however other biological parameters(specifically body mass index)and isolation variables appear to make a significant contribution to the heterogeneity of human islet yield.Our current work demonstrates the feasibility of extending acceptable cold ischemic time for research-focused human islet isolation and highlights the biological variation in isolation of human islets from donors with and without diabetes.Conclusion:India requires establishment of an islet transplant program using the current standard methods of“islet isolation”and donor program and process.Research should focus on improving standards in the islet preparation process to increase the number of successful preparations,shorten the isolation time,and increase patient safety so that the theoretical risk involved can become a practical reality.

Auto-intestine transplantation for pancreatic tumors with mesenteric root involvement:a systematic review and survival-based analysis

To analyze a long-term survival outcome of an auto-intestine transplantation(aINTx)for the patients with locally advanced pancreatic tumor and identify the potential prognostic factors,databases were carefully searched for the studies reporting the patients with a locally advanced pancreatic tumor which typically underwent aINTx.We performed a database search using PubMed,the Cochrane Library,EMBASE,and MEDLINE to identify multiple case series of the patients who had pancreatic tumors with mesenteric root involvement and underwent aINTx,to evaluate the treatment outcomes,and calculated the patient survival using the Kaplan–Meier method and Cox proportional hazard regression analysis to properly identify an independent predictor of the survival.A total of 9 retrospective studies with a total of 29 patients were included in our study.The calculated 1-,2-,and 3-year survival rates for the patients with pancreatic cancer and benign or low grade pancreatic tumors were 49.64%,22.06%,and 0%versus 100%,100%,and 80%,respectively.The corresponding median survival time was 13.4months and 84months,respectively.Moreover,when stratifying the pancreatic cancer patients undergoing aINTx on the basis of neoadjuvant chemotherapy(aINTx+neoadjuvant vs aINTx-neoadjuvant)there was a significant difference in the survival(P=0.01).The 1-and 2-year survival rates were 75%and 75%versus 34.1%and 0%,respectively.Corresponding median survival times were 24months and 10months,respectively.Our analysis shows the long-term survival benefit with acceptable morbidity and mortality of pancreatoduodenectomy and aINTx for the pancreatic tumors with the mesenteric root involvement that are otherwise unresectable by the conventional surgical techniques.However,from an oncological point of view,a larger study with the control group is required to determine its safety compared to less aggressive surgical treatment.