Systematic evaluation on PD-1 monoclonal antibody in the treatment of malignant tumor after solid organ transplantation / 器官移植

Objective To investigate the efficacy and safety of programmed cell death protein-1 (PD-1) monoclonal antibody on the treatment of malignant tumor after solid organ transplantation (SOT). Methods The relevant literatures in 7 databases were searched. The data on 54 cases of recipients with malignant tumors treated with PD-1 monoclonal antibody after SOT were collected, and the clinical effects and rejection of SOT recipients treated with PD-1 monoclonal antibody were analyzed. Results Total 32 acceptable articles including 54 SOT recipients were incorporated, including 43 males and 11 females aged 14-79 years old. There are 29 renal transplant recipients, 19 liver transplant recipients and 6 heart transplant recipients. The types of PD-1 monoclonal antibody agent used by SOT recipients included pembrolizumab for 28 patients and nivolumab for 26 patients. The overall remission rate, disease progression rate and fatality rate of PD-1 monoclonal antibody for postoperative malignant tumors of SOT recipients were 32% (17/54), 44% (24/54) and 36% (19/54), respectively. After treatment with PD-1 monoclonal antibody for postoperative malignant tumors of SOT recipients, the incidence of rejection was 39% (21/54), indicating no significant correlation between rejection and type of PD-1 monoclonal antibody (P > 0.05). Conclusions PD-1 monoclonal antibody can effectively treat postoperative malignant tumors of SOT recipients, and may induce rejection during the treatment. But rejection is not the most common cause for death of recipients.

Liver transplantation in acute-on-chronic liver failure patients:a single center experience of 159 consecutive cases / 中华器官移植杂志

Objective To evaluate the outcome of 1iver transplantation for acute-on-chronic liver failure (ACLF) patients .Methods We included 453 consecutive patients with previously cirrhosis who underwent liver transplantation between January 2013 and December 2017 .Patients were categorized as no ACLF (n=294) and ACLF(n=159) according to EASL-CLIF consortium criteria .Furthermore ,we used ACLF grades to categorize the ACLF patients .Their clinical data were reviewed and their 90-days survival outcomes were compared .Results Compared with the no ACLF group ,the length of stay in the ICU was significantly prolonged for all patients with ACLF ,and the 90-days survival rate after transplantation was significantly reduced in ACLF group .The length of stay in the ICU was shorter in Grade 1 and Grade 2 group when compared to Grade 3 group .The 90-days survival rate of no ACLF ,Grade 1 ,Grade 2 and Grade 3 group were 93 .20％ ,92 .59％ ,93 .33％ and 73 .68％ ,respectively .There were no statistically significant differences in 90-days survival rate among the no ACLF ,Grade 1 and Grade 2 group .However , the 90-days survive rate of Grade 3 group was lower than that of other groups .Conclusions Liver transplantation has been shown to be safe and effective with good outcome in patients with ACLF and should be offered in early course of ACLF before onset of multi-organ failure .

Effect of donor risk index on early prognosis of liver transplantation for acute-on-chronic liver failure: experience of 159 cases in one single center / 器官移植

Objective To evaluate the effect of donor risk index (DRI) on the early prognosis of liver transplantation for acute-on-chronic liver failure (ACLF). Methods Clinical data of 159 ACLF recipients undergoing liver transplantation were retrospectively analyzed. According to the calculation formula of DRI, all recipients were divided into DRI < 1.65 group (n=96) and DRI≥1.65 group (n=63). Based on the Chronic Liver Failure Consortium acute-on-chronic liver failure score (CLIF-C ACLFs), all recipients were divided into CLIF-C ACLFs < 48 group (n=78) and CLIF-C ACLFs≥48 group (n=81). The early prognosis indexes including the length of intensive care unit (ICU) stay and the length of postoperative hospital stay of the recipients in each group were observed after liver transplantation. The 90 dsurvival rate of the recipients after liver transplantation was analyzed by Kaplan-Meier survival curve. The risk factors affecting the early prognosis of ACLF recipients after liver transplantation were analyzed by Cox's hazards regression model. Results The length of ICU stay and the length of postoperative hospital stay did not significantly differ between the DRI < 1.65 group and DRI≥1.65 group (both P > 0.05). The length of postoperative hospital stay did not significantly differ between the CLIF-C ACLFs < 48 group and CLIF-C ACLFs≥48 group (P > 0.05). The length of ICU stay in the CLIF-C ACLFs < 48 group was 4 (3-14) d, significantly shorter than 7 (1-33) d in the CLIF-C ACLFs≥48 group (P < 0.05). The CLIF-C ACLFs was a risk factor of the early prognosis of ACLF recipients after liver transplantation (P < 0.05). The postoperative 90 d survival rate did not significantly differ between the DRI < 1.65 group and DRI≥1.65 group (P > 0.05). The postoperative 90 d survival rate in the CLIF-C ACLFs < 48 group was 94%, significantly higher than 79% in the CLIF-C ACLFs≥48 group (P < 0.05). Conclusions The early prognosis of ACLF recipients after liver transplantation is correlated with the severity of the disease rather than the DRI. Liver transplantation should be performed early and promptly.

Establishment and troubleshooting of orthotopic mouse liver transplantation model / 中华器官移植杂志

Objective To construct the orthotopic mouse liver transplantation model and cover troubleshooting,in order to provide experimental techniques support for organ transplantation pathology and immunology studies.Methods Male C57BL/6 mice,10-12 weeks,were selected as the allograft donors.Male C3H mice with same age were selected as the allograft recipients.The orthotopic mouse liver transplantation model consisted of 3 stages,including harvesting the donor liver,back-table preparation of the liver graft and transplantation of the donor liver into the recipient.The average time for harvesting the donor livers was (40 ± 8.8) min,(23 ± 4.7) min for preparing the donor livers and (75 ± 9.6) min for transplanting the donor livers into the recipient.Results Seventy pairs of mice were used for the preliminary experiments.For the formal experiments,the allograft transplantation was established on 220 pairs with 90.4％ successful rate.Conclusion It is the skillful and high quality microsurgical technique that is the guarantee of establishing the orthotopic mouse liver transplantation model successfully.

Expression and significance of CD39 on regulatory T cells in the peripheral blood of patients following liver transplantation / 中华肝胆外科杂志

Objective To study the clinical significance of CD39 on regulatory T (Treg) cells in the peripheral blood (PB) of patients following liver transplantation and to evaluate the relationship between the levels of CD39+ Treg cells in the PB and acute rejection.Methods A prospective study was conducted to compare the CD39+ Treg cells from 76 liver transplant patients with those coming from 20 age-matched healthy individuals.The PB samples were collected within one year at different time points post-transplant.Blood samples and liver biopsies were collected at the time when acute rejection was diagnosed.The percentages of CD39 within the CD4+ CD25+ T cells were measured by using flow cytometry.The liver transplant patients were classified into two groups:the rejection group which consisted of 17 patients who an episode of acute rejection,and the non-rejection group consisted of the remaining 59 patients who had no acute rejection episodes.The percentages of CD39 within the CD4 + CD25 + T cells and the inhibition function of the CD39+ Treg cells were compared between the two liver transplant groups.Results The percentages of CD39 within the CD4+ CD25+ cells were significantly lower in the rejection group during acute rejection as compared to the non-rejection group (P ＜ 0.05).The percentages of CD39 within the CD4 + CD25 + cells were negatively correlated with the Rejection Activity Index (r =-0.86,P ＜ 0.05).The inhibition rate regarding the CD4+ CD25+ CD39+ Treg cells in patients with acute rejection was significantly lower than those without rejection (P ＜ 0.05).Conclusions The percentages of CD39 within the CD4+ CD25+ T cells were significantly lower in the rejection group during acute rejection and were negatively correlated with the RAI.The inhibition rate regarding the CD4+ CD25+ CD39+ Treg cells in patients with acute rejection was significantly lower than those without rejection.

Protective effect of minocycline on hepatic ischemia-reperfusion injury in rats / 中南大学学报(医学版)

Objective: To explore the protective effect of minocycline on hepatic ischemia-reperfusion injury (IRI) in rats and the underlying mechanisms. Methods: A total of 54 male Sprague-Dawley rats were randomly divided into 3 groups: the sham-operated group (control group), the ischemic–reperfusion (IR group), and the minocycline preconditioning group (n=18 per group). The rats in the minocycline preconditioning group were given minocycline (45 mg/kg) by gastric irrigation at 36 h before operation and then were subsequently administered with minocycline (22.5 mg/kg) at every 12 h. hTe rats were sacriifcedat 2, 6, 24 h after reperfusion. The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) were measured. HE staining of liver tissues was performed to detect the histological changes, and the degree of liver IRI according to Suzuki score were calculated. hTe levels of malondialdehyde (MDA) and myeloperoxidase (MPO) were determined by spectrophotometer; the mRNA expression of tumor necrosis factor-α (TNF-α) and interleukin-1 beta (IL-1β) in the liver were measured by real-time PCR; Dickkopf-1 (DKK-1) and beta-catenin (β-catenin) protein expression in the liver were detected by Western blot. Results: Atfer 2, 6, 24 h reperfusion, compared with the IR group, the liver function (ALT, AST and LDH) in the minocycline group was signiifcantly improved (allP<0.05); the Suzuki’s scores and the levels of hepatic TNF-α and IL-1β mRNA were signiifcantly decreased (allP<0. 05); the MDA and MPO levels the liver were decreased (bothP<0.05); the protein expression of hepatic DKK-1 was decreased (P<0.05), while the protein expression of β-catenin was increased (P<0.05). Conclusion: Minocycline can alleviate the ischemic-reperfusion injury mainly through reducing oxidative stress and inhibiting the release of pro-inlfammatory cytokines depends on the activation of the Wnt/β-catenin signaling pathway in the liver.

IL-17 in the early diagnosis of acute renal allograft rejection in mice / 中南大学学报(医学版)

ObjectiveTo investigate the expression of T helper (Th) 17 cells and the related interleukin 17 (IL-17) in acute renal allograft rejection in mice and its significance.Methods We established a mouse renal allograft model,in which mice were randomly divided into a renal isograft group and an acute renal allograft rejection group.Three and 7 d after the transplantation,the serum interferon (IFN)-γand IL-17 levels in the mice were determined by enzyme-linked immunosorbent assay,the percentage of Th1 and Th17 cells in the total kidney-infiltrating lymphocytes was investigated by flow cytometry,and the transplanted kidney species were given routine pathological examination after fixation with 10％ formalin.ResultsCompared with the isograft group,the allograft mice showed a significantly higher content of IL-17 (P ＜0.05 ) but not IFN-γ in the serum 3 d after transplantation,and showed significantly higher serum IL-17 and IFN-γcontents 7 d after transplantation (P ＜ 0.05 ).Also,compared with the isograft group,the allograft mice exhibited significantly higher percentage of Th1 and Th17 cells on both day 3 and day 7 ( P ＜ 0.05 ).In the allograft group,the contents of serum IFN-γand IL-17 and the percentage of Th1 and Th17 cells were significantly higher on day 7 than on day 3 (P ＜ 0.05 ).Routine pathological examination indicated that,as time passed,the allograft mice showed gradually stronger rejection responses.ConclusionTh17 cells might play an important role in the development of acute renal allograft rejection,and IL-17 can be used as an early indicator of acute rejection.

Mouse model of orthotopic small bowel transplantation / 中南大学学报(医学版)

ObjectiveTo investigate the surgical procedures of orthotopic small bowel transplantation (SBT) model in mice to study the function and rejection of SBT.MethodsWe established a mouse SBT allograft model as follows: the donor portal vein was anastomosed end by side with the recipient inferior vena cava; the donor superior mesenteric artery with aorta patch was anastomosed end by side with recipient abdominal aorta.After an appropriate length of the recipient's small bowel was removed,the donor's small bowel and the recipient's small bowel were end-to-end anastomosed discontinuously.The mice were fasted for 4 d after the operation,free access to water and subcutaneously injection of 2 mL of 5％ glucose saline twice daily.Operation success was regarded as survival for more than 5 d.There is no antibiotic and immunosuppressor.ResultsA total of 30 transplantations were done,the 5 d survival rate was 60％ ( 18/30),and 12 died within 5 d.Among the dead recipients,5 died of arterial anastomotic stenosis and anastomotic thrombosis,2 of hemorrhagic shock caused by anastomotic bleeding,and the other 5 of intra-abdominal infection caused by postoperative intestinal fistula.The donors' operative time was (40 ± 4.5 ) min,warm ischemia time was about 0.5 min,donor preparation time was about 3 min,and cold preservation time was (30 ±7.5) min.The recipients' operative time was (95 ±8.0) min,among which,the abdominal aorta and inferior vena cava clamping time was ( 38 ± 3.5 ) min,the venous anastomotic time was (10 ±2.0) min and the arterial anastomotic time was (15 ± 3.0) min.The mean intraoperative blood loss of the surviving recipient mice was about 0.2 mL.ConclusionHigh quality vascular anastomosis,and rehydration of donors and recipients are crucial factors for improving the success rate of SBT.

Emergency orthotopic liver transplantation for acute hepatic failure:a report of 8 cases / 中国普通外科杂志

Objective To study the efficacy of emergency orthotopic liver transplantation(EOLT) for acute(hepatic) failure(ALT).Methods A retrospective review was undertaken on the clinical data of 8 patients undergoing emergency liver transplantation for ALT.Results The 8 patients completely regained consciousness in 12 to 72 hours after operation.No case developed central nervous complications.One case of severe(hepatitis) complicated by acute renal failure died of respiratory infection and ARDS on postoperative day 7.One case who refused to take medication died from chronic rejection 12 months after operation.One case was(complicated) by bile duct stricture and biliary sludge at 14 months postoperatively and survived for 18 months.Four of the other 5 cases were followed up for 17 months and 1 cases for 14 months,and thir quality of life was excellent.3 of them have returned to work.Conclusions Emergency orthotopic liver thansplantation is an effective means to treat ALF.Intensive care and effective treatment preoperatively are pre-requisite(conditions) to ensure the success of EOLT.

A new acute pancreatitis mice model / 中国普通外科杂志

Objective To develop a new severe but sublethal acute pancreatitis mice model. Methods The animals were divided into two groups: the bile acid injection group and the control group. In the bile acid injection group, acute necrotizing pancreatitis was induced by intraductal administration of 0.1 ml of 1.0 % bile acid under 30 cm H 2O pressure, while the controls underwent the sham operation. The structural and functional features of the pancreas were examined at 24 hours after surgery. Results Pancreatic edema, bleeding, acinar cell necrosis and inflammation accompanied with increased serum amylase and MPO were found in the bile acid injection animals. Conclusions The sublethal acute pancreatitis mice model is ideal for pathogenetic and therapeutic study of acute necrotizing pancreatitis.

Analysis of outcome of breast conserving treatment of breast ductal carcinoma in situ / 中国普通外科杂志

Objective To study the clinical outcome of breast conserving treatment of breast ductal carcinoma in situ(DCIS).Methods The data of 62 patients with pathologically proven DCIS who underwent breast conserving operation and adjuvant radiotherapy were retrospectively compared with 62 concurrent cases of stageⅠ or Ⅱ infiltrating ducatl carcinoma who received breast conserving operation and adjuvant readotherapy.Results The recurrence rate in DCIS cases was 6.4%(4/62),among them,3 cases belonged to comedo type;the recurrence rate in early infiltrating type of ductal breast carcinoma was 19.3%(11/62)(P

Study of the arterial blood supply of the pancreas head and the gastroduodenal artery reconstruction of pancreatic graft / 中国普通外科杂志

Objective To investigate the arterial blood supply of the pancreas head and provide a theoretical basis for the gastroduodenal artery reconstruction in pancreatic transplantation(PT).Methods Photograms of digital subtraction artery(DSA)which performing on 300 patients were analyzed to recognize the aberrations of arterial blood supply of pancreatic head.Results In 300 DSA photograms,the gastroduodenal artery(GD.a)was identified in 131 cases,and the anterior superior pancreaicduodenal artery(ASPD.a)and posterior superior pancreaicduodenal artery(PSPD.a)in 79 cases.The rate of aberrant origin of pancreatic transverse artery(PT.a)from GD.a was 12.98℅.There are some minor sources of blood supply to the pancreas head from GD.a.The rate of absence of an ASPD.a-AIPD.a anastomosis and PSPD.a-PIPD.a anastomosis was 15.19℅and 24.05℅,respectively.Conclusions The reconstruction of gastroduodenal artery can ensure a complete blood supply to the pancreatic head and duodenum in PT.

Surgical treatment of rectal carcinoid:a report of 36 cases / 中国普通外科杂志

Objective To investigate the rational method of treatment of rectal carcinoid and its outcome.Methods The clinical data of 36 cases of rectal carcinoid were retrospectively analysed.Results During a follow-up of 82.6+/-63.4 months,there were no cases with recurrence among the 20 patients with tumor size2cm.Conclusions Tumor diametar can be used to estimate the degree of malignancy of rectal carcinoid.TNM staging is simpler and practical for deciding the method of surgical treatment.