Objective To investigate the immunological rejection after hepatocyte transplantation for acute liver failure (ALF) in mice.Methods The hepatocytes were isolated from pig,BALB/c and C57BL/6 mice livers were conducted and then transplanted into C57BL/6 mice.CCl4 was used to make ALF mice model.The experimental animals were randomly divided into three groups, including syngenic group,allogeneic group,and xenogenic group.The survival statuses of all the mice were recorded. The alteration of T lymphocyte subsets,immune globulin,and cytokine were determined.Results ①The survival ratio was 8/10,6/10, and 3/10 in the syngenic group, allogeneic group, and xenogenic group, respectively.The survival ratio in the syngenic group was significantly higher than that in the other two groups (P<0.05).②The CD4+ and CD8+ T cells of the peripheral blood in the syngenic group did not change significantly on week one after transplantation.The CD4+ T cells in the allogeneic group reached the peak on day 3 after hepatocyte transplantation (P<0.05), while CD8+ T cells did not change much in one week.The CD4+ and CD8+ T cells in the xenogenic group increased and reached the peak on day 3 after transplantation (P<0.05).③There were no significantly differences of IgM and IgG in the syngenic group among 0.5, 1, and 3 d after transplantation. IgM of the allogeneic group and xenogenic group reached the peak on day 1 (P<0.05) and IgG reached the peak on day 3 (P<0.05) after transplantation.④The concentrations of IFN-γ, TNF-ɑ, and IL-2 in the allogeneic group and xenogenic group were significantly higher than those in the syngenic group (P<0.05).The concentration of IL-6 of the xenogenic group was higher than that of the other two groups (P<0.05). Conclusions CD4+ and CD8+ T cells play an important role in immune response to both allogeneic and xenogenic hepatocyte transplantation, as well as induce humoral immune response early after hepatocyte transplantation.
Objective To investigate the changes of indocyanine green retention rate at 15 minutes (ICGR15) of autologous peripheral blood CD34+ hematopoietic stem cells transplantation in end-stage liver disease (end-stage liver, disease, ESLD) patients with different Child-Pugh grades during before and after transplantation of 3, 6, 12, 36, and 60 months. Methods The CD34+ hematopoietic stem cells transplantation were performed in 60 cases of advanced liver cirrhosis with different Child-Pugh grades who were ineffectively treated with strictly conservative treatment and complied with the criterion of liver transplantation. The ICGR15 were performed before transplantation and in 3, 6, 12, 36 and 60 months after transplantation. And the results of each time point in each Child-Pugh classification group were compared, and the rate of change of ICGR15 value were compared between each Child-Pugh classification group. Results The ICGR15 values of the Child-Pugh grading groups all decreased with time. In Child A group, there were respectively significant differences between the 6 months, 12 months, 36 months, and 60 months groups after transplantation and preoperative and 3 months groups after transplantation (P<0.05), but there was no significant difference between preoperative and 3 months group after transplantation (P>0.05), and there was significant difference between the 12 months and the 60 months group after transplantation (P<0.05). As same as Child A group, there were also significant differences between that time groups in the Child B group (P<0.05), but there were also significant differences between the 3 months group after transplantation and preoperative (P<0.05), and there were respectively significant differences between the 6 months and 12 months, 36 months, and 60 months group after transplantation in the Child B group (P<0.05). Also in the Child C group, there were significant differences between that time groups (P<0.05), but there was no significant difference between preoperative and 3 months group after transplantation (P>0.05), and there were respectively significant differences between the 6 months and 12 months, 36 months, and 60 months group after transplantation (P<0.05). There was no significant difference in the rate of ICGR15 between Child-Pugh classification groups. Conclusion Autologous peripheral blood CD34+ hematopoietic stem cells transplantation can effectively improve the liver function reserve capacity of ESLD patients and improve the safety of operation for a long time.
On January 7, 2022, the University of Maryland Medical Center reported that the world’s first gene-edited pig heart was successfully transplanted into a 57-year-old man with end-stage heart disease, causing a global attention. The first gene-edited pig heart transplanted into a human successfully survived for 59 d without showing early signs of rejection, creating a history of xenotransplantation and marking a key step forward the clinical development of xenotransplantation. This article focuses on the role of gene editing in alleviating immune rejection, summarizes the case of xenotransplantation at the Maryland Medical Center, and outlines the current status of xenotransplantation and the unresolved issues of xenotransplantation. It is expected that xenotransplantation can successfully enter the clinic in the near future.
Objective To investigate the appropriate indication about removing abdominal drainage after pancreaticoduodenectomy. Method The clinical data of 156 patients who underwent pancreaticoduodenectomy in our hospital from January 2014 to June 2016 were analyzed retrospectively. The patients were divided into two groups, with 76 patients in the enhanced recovery after surgery (ERAS) group and 80 patients in the control group according to the type of indications about removing abdominal drainage. The time of removing abdominal drainage, hospital stay, incidence of postoperative complications, and readmission rate during 30 days after surgery were compared between the2 groups. Results Compared with the control group, the time of removing abdominal drainage 〔(6.2±2.5) dvs. (10.8±2.2) d,P<0.001〕and hospital stay〔(11.8±3.4) dvs. (15.7±3.6) d,P<0.001〕 of the ERAS group were both shorter, incidence of abdominal infection was lower〔1.3% (1/76)vs. 10.0% (8/80), P=0.020〕 , but there was no significant difference in the incidence of postoperative pancreatic fistula 〔18.4% (14/76) vs. 21.3% (17/80)〕 , delayed gastric emptying〔1.4% (1/76) vs. 7.5% (6/80)〕 , and the readmission rate during 30 days after surgery〔5.3% (4/76) vs. 3.8% (3/80)〕 , P>0.05. Conclusions Indications about removing abdominal drainage after pancreaticoduodenectomy by authors are safe.
Objective To summarize the feasibility and safety of the islet cells co-transplantation with bone marrow mesenchymal stem cells (BMSCs) in the treatment of diabetes. Methods The latest progress and new achievements of islet cells transplantation and BMSCs transplantation in treatment of diabetes in the world were analyzed and reviewed. Results At present, the pancreas transplantation and the islet cells transplantation were mainly treatments for diabetes, the pancreas transplantation had disadvantages of large trauma and high mortality; the islet cells transplantation was safe, but had disadvantages of strong rejection, and the survival time of islets cells were short which affected the treatment effect of diabetes. The BMSCs co-transplanted with the islet cells could prolong the survival time of islet cells and could alleviate the rejection in body, so the co-transplantation can be more effective in treatment of diabetes. Conclusion The BMSCs co-transplant with the islet cells could reduce the rejection in vivo, reduce the inflammation in vivo, prolong the survival time of islet cells, extend the time of normal glucose, which may become the new treatment method for the diabetes.
ObjectiveTo explore the clinical application of variant associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) combined with inferior vena cava reconstruction for end stage hepatic alveolar echinococcosis (HAE).MethodThe clinical data of one case with HAE who treated in Organ Transplantation Center of Sichuan Provincial People’s Hospital in November 2017 was analyzed retrospectively.ResultsComputed tomography revealed that the three hepatic veins and retrohepatic inferior vena cava were invaded by multiple and giant hydatid lesions. Only the segment 6 retained the complete portal vein and hepatic vein return branch. Remnant liver volume/standard liver volume (RLV/SLV) of this patient was 24.9%. Surgical exploration was performed after preoperative examination. In the first stage, ligation of the left portal vein and the right anterior lobe portal vein were performed to increase portal blood supply at S6 while partial split of the liver. The patient recovered well after operation without complications such as bile leakage and infection. Six months after the first stage surgery, the second stage surgery was performed, and RLV/SLV measured before surgery was 48.3%. S1–5/S7–8 were completely removed and the hepatic inferior vena cava was reconstructed with artificial blood vessels. The patient was discharged on 10 days after operation, and there was no complications and relapses occurred during the 18 months follow-up period.ConclusionsVariant ALPPS combined with inferior vena cava reconstruction is an effective attempt to treat end stage HAE with multiple and giant hydatid lesions and insufficient RLV.
Objective To explore the effect of ex-vivo liver resection and autologous liver transplantation (ERAT) combined with complicated hepatic venous reconstruction for end stage hepatic alveolar echinococcosis (AE). Method Theclinical data of one case with hepatic AE who treated in Organ Transplantation Center of Sichuan Provincial People’s Hospital in December 2017 was analyzed retrospectively. Results Pre-operative examination and intraoperative exploration revealed the hepatic vein (HV) and retrohepatic inferior vena cava (RHIVC) were invaded widely. We successfully initiated operation through vivo and ex-vivo hepatic AE resection, portal vein reconstruction, right/short/right inferior HV reconstruction into a wide mouth outflow with the assist of autogenous saphenous vein, and then piggyback autologous liver transplantation by wide mouth outflow-artificial inferior vena cava anastomosis (side to side). The operative time was 16 hours, and blood loss was 1 000 mL approximately. The patient was admitted routine treatment after hepatectomy. The inject low-molecular-weight heparin sodium was admitted for anticoagulant therapy 24 hours after operation. This patient recovered smoothly without bile leakage, bleeding, infection and liver failure, and so on. The patient was discharged uneventfully 14 days after operation, and there was no special situation during the6 months follow-up period. Conclusions ERAT is an ideal surgical method for end stage hepatic AE. Hepatic parenchymal transection and individual duct reconstruction, especially hepatic outflow reconstruction, are the key steps for ERAT.
ObjectiveTo explore value of partial liver preservation in situ for ex-vivo liver resection and auxiliatry autologous liver transplantation in end-stage hepatic alveolar echinococcosis.MethodsThe clinical data of one patient with end-stage hepatic alveolar echinococcosis treated with auxiliatry autologous liver transplantation combined partial liver preservation in situ were analyzed retrospectively. This patient was admitted on January 2019. During the auxiliatry autologous liver transplantation procedure, the S1, S4-S8 segments of the liver were resected for mass dissection, whereas the S2 and S3 segments of left liver were preserved in situ.ResultsThe preoperative evaluation and intraoperative exploration indicated that the mass located in the S4, S5, S8 segments, which was adjacent to the first hepatic portal and involved the anterior wall of posterior inferior vena cava, middle hepatic veins, the opening of right hepatic veins and the right wall of left hepatic veins. Based on the " in situ first” principle, the left lesion was slit using the anterior approach, the left hepatic vein was repaired and the S2 and S3 segments were preserved in situ. Then, the right lesion to involved hepatic vein was slit along the right interlobar fissure. The right hepatic artery, right portal vein and right bile duct were divided separately. The S1 and S4-S8 segments were removed completely. Next, the mass was resected, the out flow of the right liver was reconstructed using the allogeneic veins during the ex-vivo liver resection. Then, the auxiliatry autologous right liver transplantation was initiated by the wide-caliber hepatic vein-artificial inferior vena cava anastomosis. The surgical procedures lasted for 12 h, and the intraoperative bleeding was approximately 800 mL. The patient was routinely treated and smoothly recovered after the operation.ConclusionsProcedure of auxiliatry autologous liver transplantation preserved part functional liver in situ during ex-vivo resection, which could maintain stability of systemic and portal vein circulation, hold part liver function during operation, preserve functional liver furthest, and reduce risk of hepatic failure, is an effective attempt for end stage hepatic alveolar echinococcosis.
ObjectiveTo explore the effect of hepatic outflow reconstruction with allograft vascular in ex-vivo liver resection and autologous liver transplantation.MethodThe clinical data of a patient with end-stage hepatic alveolar echinococcosis admitted to the Organ Transplantation Center of Sichuan Provincial People’s Hospital in August 2019 who underwent the ex-vivo liver resection and autologous liver transplantation combined with hepatic vein reconstruction with allograft vascular were analyzed retrospectively.ResultsThe patient, a 44-year-old female, was admitted to Sichuan Provincial People’s Hospital for “pain in the right abdomen accompanied by skin and sclera yellow staining for 6+ months and aggravated for 20+ d”. When the patient was admitted, the general condition was poor, such as hyperbilirubin and hypoproteinemia. The body mass was 45 kg and the standard liver volume was 852 mL. The hydatid lesions corroded the first and second hilum of the liver, the right hepatic vein and the posterior inferior vena cava. It was difficult to reconstruct the outflow tract of the hepatic vein in vivo, and it was extremely difficult to completely remove the hydatid lesions in vivo. After admission, the patient was generally in a good condition after the PTCD treatment, then after discussion and rigorous evaluation, the ex-vivo hepatectomy combined with autologous liver transplantation was required. The operative time was 15 h and the intraoperative blood loss was approximately 2 000 mL. After the operation, the routine treatment was performed, the antiviral treatment was continued, the international standardized ratio value was monitored at 1.5–2.5, and the anti-immune rejection drugs were not needed. The patient was transferred to the general ward on the 4th day after the operation, and there were no bile leakage, bleeding, infection and other complications. the result of postoperative pathological diagnosis was the alveolar echinococcosis. The re-examination of enhanced CT on 1 week after the operation suggested that the hepatic outflow tract of allograft vascular reconstruction was unobstructed, no stenosis and no thrombosis occurred. The patient was following-up at present.ConclusionsIn treatment of end-stage hepatic alveolar echinococcosis by autologous liver transplantation, reconstruction of hepatic outflow should be individualized. Allograft venous vessels could be used as ideal materials due to their advantages of matched tube diameter and length, no anti-rejection, and low risk of infection.