Individualized management of immunosuppressants in liver transplant recipients by using a novel immune score system.

BACKGROUND: There is no reliable means to evaluate the immune status of liver transplant recipients. We proposed a novel score model, namely Mingdao immune cell analysis and Mingdao immune score system, to quantify the immunity. METHODS: Data from those who underwent a single liver transplant between January 2017 and June 2020 at Beijing Chaoyang Hospital, were collected. In addition, healthy volunteers were also enrolled. The score model was based on the immune cell populations determined by flow cytometry. RESULTS: There were a total of 376 healthy controls with 376 tests and 148 liver transplant recipients with 284 tests in this study. Evaluated by Mingdao immune cell analysis and Mingdao immune score system, the mean scores of healthy controls were near zero suggesting a balanced immune system. In contrast, the mean scores of liver transplant recipients were negative both before and after surgery indicating a compromised immune system. When liver transplant recipients were given a reduced or routine first dose according to their preoperative score, they had similar recovery of liver function. Moreover, liver transplant recipients with increased scores ≥ 5 were associated with elevated aspartate transaminase and alanine amiotransferase. Finally, on multivariate analysis the score model was the only significant independent risk factor for clinical acute rejection (P = 0.021; Odds ratio, 0.913; 95% confidence interval, 0.845-0.987). CONCLUSION: The novel score model could be used as an indicator to reflect immunity and to regulate immunosuppressants in liver transplant recipients after surgery.

Impact of metabolic dysfunction-associated fatty liver disease on liver transplant recipients with hepatitis B virus-related hepatocellular carcinoma.

BACKGROUND: Metabolic dysfunction-associated fatty liver disease was proposed by international consensus to redefine the metabolic abnormal condition. However, its impact on liver transplant recipients with hepatitis B virus-related hepatocellular carcinoma has not been explored. METHODS: A two-center retrospective cohort study on liver transplant recipients with hepatitis B virus-related hepatocellular carcinoma was performed to analyze the impact of metabolic dysfunction-associated fatty liver disease on the clinicopathologic parameters and prognosis. RESULTS: There were 201 liver transplant recipients enrolled from two hospitals in our study. The pre- and post-transplant prevalences of metabolic dysfunction-associated fatty liver disease were 9.95% and 28.86%, respectively. The clinicopathological parameters revealed a similarity between patients with and without pre-transplant metabolic dysfunction-associated fatty liver disease. In contrast, the group with post-transplant metabolic dysfunction-associated fatty liver disease was linked with older age, a higher hepatitis recurrence rate and incidence of cardiovascular disease, usage of calcineurin inhibitors, a greater body mass index and waist circumference, lower albumin and high-density lipoprotein cholesterol levels, and poorer tumor-free survival and overall survival. The multivariate analysis showed the largest tumor size >4 cm (95% confidence intervals: 0.06~0.63, p = 0.006), microvascular invasion (95% confidence intervals: 1.61~14.92, p = 0.005), post-transplant metabolic dysfunction-associated fatty liver disease (95% confidence intervals: 1.40~10.60, p = 0.009), and calcineurin inhibitors-based regimen (95% confidence intervals: 0.33~0.96, p = 0.036) were the independent risk factors for recurrent hepatocellular carcinoma. CONCLUSIONS: Our study suggests that post-transplant metabolic dysfunction-associated fatty liver disease is more closely to metabolic abnormalities and that it can help identify liver transplant recipients at high risk of recurrent hepatocellular carcinoma.

Treatment of retrogastric pancreatic pseudocysts by laparoscopic transgastric cystogastrostomy.

This paper discusses variations of laparoscopic transgastric cystogastrostomy in management of retrogastric pancreatic pseudocysts for 8 patients with symptom or pseudocysts (larger than 6 cm) companied with clinical manifestations. Using a Harmonic scalpel, two 3-5-cm incisions were made in the anterior and posterior gastric wall respectively. In the last step, the anterior gastrotomy was closed with an Endo-GIA stapler. All cases were successfully treated without large blood loss and without conversion to open surgery. The mean operative time was 114.29±19.24 min, blood loss was 157.14±78.70 mL, and mean hospital stay was 8.29±2.98 days. Gastric fistula occurred in one case on the postoperative day 7, and closed 1 month later. No bleeding was seen in all patients during the perioperative follow-up period. CT scans, given one month after the surgeries, displayed that the pancreatic pseudocysts disappeared or decreased in size, and ultrasounds showed no fluid or food residue in stomas at the third and fifth month following surgery. No patient experienced a recurrence during the follow-up period. Transgastric laparoscopic cystogastrostomy is a minimally invasive surgical procedure with a high rate of success and a low rate of recurrence, accompanied by rapid recovery. It is easy to master, safe to perform and may be the preferred option to treat retrogastric pancreatic pseudocysts.

Protective role of berberine and Coptischinensis extract on T2MD rats and associated islet Rin­5f cells.

The aim of the present study was to compare the different effects of berberine (Ber) and Coptischinensis extract (CCE) on a rat model of type 2 diabetes mellitus (T2DM), and the islet Rin­5f cell line was used to examine the differences between Ber and CCE and the underlying mechanisms. CCE was extracted and purified prior to analysis. Male Sprague­Dawley rats were provided with a high­fat diet to induce insulin resistance prior to injecting with streptozotocinto establish the T2DM model, the T2DM rats were treated with Ber and CCE, and blood samples and pancreatic tissues were obtained and compared to examine T2DM metabolic syndromes among the groups of rats, which included healthy rats, model rats, and model rats treated with Ber and CCE at different doses between 0 and 8 weeks. The protective effects of Ber and CCE on the Rin­5f islet cell line were also evaluated. The effects on Rin­5f cell proliferation and cell cycle, glucose­stimulated insulin release test (GSIS), the anti­apoptotic effects caused by fat induction, and protein expression levels of poly ADP­ribose polymerase (PARP­1) were evaluated. The results showed that the content of the prepared CCE was 96.07% for five alkaloids. When it was used for treatment of the T2DM rats, compared with Ber, metformin and rosiglitazone, the fasting blood glucose, glucosylated serum protein (GSP) and glucose infusion rate indicesin the fasting rats were ameliorated, compared with those in the T2MD rats, with no significant differences between treatment with Ber or CCE and metformin or rosiglitazone. The indices of mean optical density and fasting ß­cell function index (FBCI) were different following treatment with Ber and CCE, compared with those in the model rats, which may have stimulated the pancreatic secretion of insulin. When Ber and CCE were used to examine the protective effects on Rin­5F cells, it was found that the Rin­5f cell GSIS, cell cycle, lipotoxic islet cell proliferation and protein expression of PARP­1 were altered and improved, which may have protected pancreatic islet ß­cells by improving islet ß­cell proliferation and the protein expression of PARP­1. CCE and Ber exerted similar effects when used for the treatment of T2MD rats, and may have stimulated the pancreatic secretion of insulin through the protective effect on islet ß­cells via improving islet ß­cell proliferation and the protein expression of PARP­1.

Bilioenteric anastomotic stricture in patients with benign and malignant tumors: prevalence, risk factors and treatment.

BACKGROUND: Stricture formation at the bilioenteric anastomosis is a rare but important postoperative complication. However, information on this complication is lacking in the literature. In the present study, we aimed to assess its prevalence and predictive factors, and report our experience in managing bilioenteric anastomotic strictures over a ten-year period. METHODS: A total of 420 patients who had undergone bilioenteric anastomosis due to benign or malignant tumors between February 2001 and December 2011 were retrospectively reviewed. Univariate and multivariate modalities were used to identify predictive factors for anastomotic stricture occurrence. Furthermore, the treatment of anastomotic stricture was analyzed. RESULTS: Twenty-one patients (5.0%) were diagnosed with bilioenteric anastomotic stricture. There were 12 males and 9 females with a mean age of 61.6 years. The median time after operation to anastomotic stricture was 13.6 months (range, 1 month to 5 years). Multivariate analysis identified that surgeon volume (≤30 cases) (odds ratio: -1.860; P=0.044) was associated with the anastomotic stricture while bile duct size (>6 mm) (odds ratio: 2.871; P=0.0002) had a negative association. Balloon dilation was performed in 18 patients, biliary stenting in 6 patients, and reoperation in 4 patients. Five patients died of tumor recurrence, and one of heart disease. CONCLUSIONS: Bilioenteric anastomotic stricture is an uncommon complication that can be treated primarily by interventional procedures. Bilioenteric anastomosis may be performed by a surgeon in his earlier training period under the guidance of an experienced surgeon. Bile duct size >6 mm may play a protective role.

Treatment of Retrogastric Pancreatic Pseudocysts by Laparoscopic Transgastric Cystogastrostomy / 华中科技大学学报（医学）（英德文版）

This paper discusses variations of laparoscopic transgastric cystogastrostomy in management of retrogastric pancreatic pseudocysts for 8 patients with symptom or pseudocysts (larger than 6 cm) companied with clinical manifestations.Using a Harmonic scalpel,two 3-5-cm incisions were made in the anterior and posterior gastric wall respectively.In the last step,the anterior gastrotomy was closed with an Endo-GIA stapler.All cases were successfully treated without large blood loss and without conversion to open surgery.The mean operative time was 114.29±19.24 min,blood loss was 157.14±78.70 mL,and mean hospital stay was 8.29±2.98 days,Gastric fistula occurred in one case on the postoperative day 7,and closed 1 month later.No bleeding was seen in all patients during the perioperative follow-up period.CT scans,given one month after the surgeries,displayed that the pancreatic pseudocysts disappeared or decreased in size,and ultrasounds showed no fluid or food residue in stomas at the third and fifth month following surgery.No patient experienced a recurrence during the follow-up period.Transgastric laparoscopic cystogastrostomy is a minimally invasive surgical procedure with a high rate of success and a low rate of recurrence,accompanied by rapid recovery.It is easy to master,safe to perform and may be the preferred option to treat retrogastric pancreatic pseudocysts.

Effect of preoperative injection of carbon nanoparticle suspension on the outcomes of selected patients with mid-low rectal cancer.

BACKGROUND: Carbon nanoparticles show significant lymphatic tropism and can be used to identify lymph nodes surrounding mid-low rectal tumors. In this study, we analyzed the effect of trans anal injection of a carbon nanoparticle suspension on the outcomes of patients with mid-low rectal cancer who underwent laparoscopic resection. METHODS: We collected the data of 87 patients with mid-low rectal cancer who underwent laparoscopic resection between November 2014 and March 2015 at Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College. For 35 patients in the experimental group, the carbon nanoparticle suspension was injected transanally into the submucosa of the rectum around the tumor 30 min before the operation; 52 patients in the control group underwent the operation directly without the injection of carbon nanoparticle suspension. We then compared the operation outcomes between the two groups. RESULTS: In the experimental group, the rate of incomplete mesorectal excision was lower than that in the control group, but no significant difference was found (2.9% vs. 7.7%, P = 0.342). The distance between the tumor and the circumferential resection margin was 5.8 ± 1.4 mm in the experimental group and 4.8 ± 1.1 mm in the control group (P = 0.001). The mean number of lymph nodes removed was 28.2 ± 9.4 in the experimental group and 22.7 ± 7.3 in the control group (P = 0.003); the mean number of lymph nodes smaller than 5 mm in diameter was 10.1 ± 7.5 and 4.5 ± 3.7, respectively (P < 0.001). Three patients in the experimental group received lateral lymph node resection. Among the three patients, we retrieved three nodes (one stained node) from the first patient, three nodes (two stained nodes) from the second patient, and two nodes (no stained nodes) from the third patient. CONCLUSIONS: Injecting a carbon nanoparticle suspension improved the outcomes of patients who underwent laparoscopic resection for mid-low rectal cancer; it also improved the accuracy of pathologic staging. Moreover, for selected patients, this technique narrowed the scope of lateral lymph node dissection.

Resection of portal and/or superior mesenteric vein and reconstruction by using allogeneic vein for pT3 pancreatic cancer.

BACKGROUND AND AIM: There is still controversy on the outcomes of portal vein (PV) and/or superior mesenteric vein (SMV) resection in pancreatic cancer, and there are few reports about pancreaticoduodenectomy (PD) with PV/SMV resection and reconstruction by using allogeneic vein. This study is to explore the outcomes of PD with PV/SMV resection and reconstruction by using allogeneic vein for pT3 pancreatic cancer with venous invasion. METHODS: Clinicopathological data of patients underwent PD with en bloc resection of PV/SMV and reconstruction by using internal iliac from August 20, 2013 to July 25, 2015 were collected and the data of patients with pT3 stage pancreatic head cancer with PV/SMV invasion were analyzed. The short- and long-term outcomes were presented. RESULTS: Thirty patients met the criteria of this study. PV resection and reconstruction were performed for 12 patients, SMV for 9 patients, and PV + SMV for 9 patients, respectively. The median operation time was 460 min, and the median intraoperative blood loss was 450 mL. R0 resection rate was 93.3%, total incidence of complications was 23.3%, and incidence of pancreatic fistula was 10%. The 1-year and 2-year overall survival rates were 68.6% and 39.2%, 1-year and 2-year disease free survival rates were 44.8% and 17.1%. CONCLUSIONS: PD with en bloc resection of PV/SMV and reconstruction by using allogeneic vein was safe and feasible for patients with pT3 stage pancreatic head cancer with PV/SMV invasion. A large-scale research with longer follow-up time is required to draw a significant conclusion.

Segmental portal/superior mesenteric vein resection and reconstruction with the iliac vein after pancreatoduodenectomy.

Objective The results of segmental venous resection (VR) combined with pancreatoduodenectomy (PD) are controversial but may be promising. Few studies have described reconstruction of the portal/superior mesenteric vein (PV/SMV) with the iliac vein harvested from donation after cardiac death (DCD). Methods From January 2014 to April 2016, PD combined with segmental excision of the PV/SMV (VR group) was performed in 21 patients with adenocarcinoma of the head of the pancreas (ADHP). The authors established a new technique of venous reconstruction using the iliac vein from DCD and analysed patients' long-term survival. Results The tumour dimensions and tumour staging were greater and the operation time was longer in the VR than PD group; however, no differences in the resection degree, blood loss, complications, reoperation rate, or mortality rate were found. The median survival was similar between the VR and PD groups. The long-term patency of the donor iliac vein was 90%. The degree of resection was a strong predictor of long-term survival. Conclusion Segmental PV/SMV resection combined with PD is applicable to selective patients with venous invasion by ADHP if R0 resection has probably been achieved. An iliac vein obtained by DCD provides an effective graft for venous reconstruction.

Predictors of incidental gallbladder cancer in elderly patients.

BACKGROUND: At the time of diagnosis, most patients with gallbladder cancer are in advanced stage and the cancer is unresectable. Long-term survivors are usually seen in a small number of patients with incidental gallbladder cancer. This study aimed to identify preoperative predictors of incidental gallbladder cancer in elderly patients. METHODS: A total of 4014 patients of more than 44 years old who had undergone cholecystectomy at our department from January 2000 to December 2010 were retrospectively reviewed. Univariate and multivariate modalities were used to identify the predictive factors of incidental gallbladder cancer. RESULTS: Twenty-nine of the 4014 patients who had undergone cholecystectomy for benign gallbladder diseases were histologically diagnosed as having incidental gallbladder cancer. Multivariate analysis identified that elevated carbohydrate antigen 19-9 combined with carcinoembryonic antigen and/or carbohydrate antigen 125 (P=0.045), a gallbladder polyp greater than or equal to 1.2 cm (P=0.043) and focal gallbladder wall thickening of more than or equal to 5 mm (P=0.002) were predictive factors of incidental gallbladder cancer. CONCLUSION: Cholecystectomy is suggested for patients with these predictive factors and intraoperative frozen section should be considered to rule out carcinoma.

Association between four common microRNA polymorphisms and the risk of hepatocellular carcinoma and HBV infection.

microRNAs (miR/miRNAs) have been demonstrated to function as tumor suppressors and oncogenes, and miRNA polymorphisms may have a role in cancer development. The present study aimed to investigate the association between the miR-146aG>C, miR-149C>T, miR-196a2C>T and miR-499A>G polymorphisms and the risk of hepatocellular carcinoma (HCC) and hepatitis B virus (HBV) infection. A total of 271 patients with HCC and 532 healthy control participants were enrolled in the present study. miR-146aG>C, miR-149C>T, miR-196a2C>T and miR-499A>G polymorphisms were genotyped using the polymerase chain reaction-restriction fragment length polymorphism method. A significant difference was identified in the genotype frequency of miR-196a2C>T in the patients in the case group compared with the control group (χ2=6.88; P=0.032). Compared with the CC genotype, the miR-196a2 TT genotype was associated with a significantly reduced risk of HCC [odds ratio (OR), 0.62; 95% confidence interval (CI), 0.38-0.99], and a significantly reduced risk was also found in the dominant (OR, 0.69; 95% CI, 0.49-0.98) and recessive (OR, 0.70; 95% CI, 0.46-1.02) models. Moreover, individuals with HBV who were carrying the miR-196a2 CT and TT genotypes had a significantly reduced risk of HCC (OR, 0.62; 95% CI, 0.41-0.95; and OR, 0.39; 95% CI, 0.20-0.73, respectively). In conclusion, the present study found that the miR-196a2C>T polymorphism has a protective effect in patients with HCC, particularly in those with HBV infection.

[Clinical significance for monitoring of serum ghrelin in acute pancreatitis severity assessment].

OBJECTIVE: To explore the value of altered serum level of Ghrelin for severity assessment in patients with acute pancreatitis (AP). METHODS: Peripheral blood samples were collected from 47 AP patients at admission, 48 hours post-admission and at discharge. According to the criteria of APACHEII score ≥ 8, RANSON ≥ 3, CT ≥ 4, they were divided into mild (n = 17) and severe (n = 30) groups. Enzyme-linked immunosorbent assay (ELISA) was used to measure the serum level of Ghrelin. And correlation analysis was made with the score of APACHEII and the level of C reactive protein (CRP). Also the serum level of Ghrelin was analyzed with receiver operating characteristic (ROC) curve. RESULTS: The serum levels of Ghrelin after 24 h were 358.6 ± 119.3 vs 212.1 ± 42.7 ng/L (P < 0.001); after 48 hours, 253.1 ± 71.2 vs 275.5 ± 73.6 ng/L (P = 0.572); at discharge, 327.8 ± 103.8 vs 319.4 ± 87.1 ng/L respectively (P = 0.816). And serum level of Ghrelin was positively correlated with APACHEII and CRP. ROC area under curve was 0.841 ± 0.057 and 95% confidence interval 0.729-0.952 (P < 0.001). CONCLUSION: The serum level of Ghrelin during early-stage AP has significant differences between two groups. And it may become an early predictor of pancreatic necrosis and a degree marker of clinical severity.

Increase of peripheral Th17 lymphocytes during acute cellular rejection in liver transplant recipients.

BACKGROUND: Although many human inflammatory and autoimmune diseases were previously considered to be mediated by T helper type 1 (Th1) cells, the recently described Th17 cells play dominant roles in several of these diseases. We and others speculated that allograft rejection after organ transplantation may also involve Th17 cells. Episodes of acute rejection occur in 30% of liver transplants. This study aimed to determine the frequency of circulating Th17 cells in patients who had received liver transplants for benign end-stage liver disease and to identify any association between acute rejection episodes and levels of Th17 cells in the peripheral blood. METHODS: A prospective study compared Th17 cells from 76 consecutive benign end-stage liver disease patients who had undergone orthotopic liver transplantation from 2007 to 2011 with those from 20 age-matched healthy individuals. Peripheral blood samples were collected at different time points within one year after transplant. Blood samples and liver biopsies were also collected at the diagnosis of acute rejection. Percentages of circulating CD4+IL-17+ cells were measured by flow cytometry. The transplant patients were classified into two groups: a rejection group consisting of 17 patients who had an episode of acute rejection, and a non-rejection group comprising the remaining 59 patients with no acute rejection episodes. Percentages of circulating Th17 cells were compared between the two groups and controls. RESULTS: The levels of circulating CD4+IL-17+ T cells in the rejection group were higher during acute rejection than those in the non-rejection group (2.56+/-0.43% versus 1.79+/-0.44%, P<0.001). The frequency of CD4+IL-17+ cells in peripheral blood was positively correlated with the rejection activity index (r=0.79, P=0.0002). CONCLUSION: Circulating Th17 cells may be useful as a surrogate marker for predicting acute rejection in liver transplant recipients.

Sirolimus as primary immunosuppressant for calcineurin inhibitor-related renal insufficiency after liver transplantation.

BACKGROUND: Calcineurin inhibitor-related renal toxicity affects patient and graft survival in transplant recipients. This study aimed to determine whether sirolimus is effective and safe in treating renal insufficiency related to tacrolimus after liver transplantation. METHODS: Tacrolimus for primary immunosuppression was used in 16 patients after liver transplantation. Patients with a creatinine level higher than 132.6 micromol/L were eligible for conversion to sirolimus. Simultaneously, the dose of tacrolimus was decreased to half. Blood urea nitrogen, creatinine, tacrolimus level, liver function and rejection episodes were monitored dynamically. RESULTS: All patients showed improvement of renal function after conversion to sirolimus. Blood creatinine level was reduced from 146.8+/-92.4 to 105.3+/-71.3 micromol/L (P<0.05). One patient had an acute rejection episode that was successfully treated with pulsed corticosteroids and low-dose tacrolimus. The side-effects of sirolimus included hyperlipidemia (4 patients) and leukocytopenia (2). CONCLUSION: Sirolimus can be safely used in liver transplant recipients suffering from tacrolimus-related renal insufficiency.

[Classification and clinical study of plasma cell mastitis under breast duct endoscope].

OBJECTIVE: To evaluate the clinical significance of breast duct endoscope for plasma cell mastitis. METHODS: Breast duct endoscope was performed on 250 patients with nipple discharge. The characters of 95 cases of plasma cell mastitis under the breast duct endoscope were analyzed and studied. RESULTS: Among the 95 cases with plasma cell mastitis, 21 were in type I, 43 in type II, 18 in type III and 13 in type IV. Eighty-three cases were treated with no-operation treatment, and 45 completely released, 38 partly released. There were 5 cases with middle to serious atypical hyperplasia in 12 cases treated with operation, that were all confirmed by pathological examination. CONCLUSION: In patients with plasma cell mastitis, clear diagnosis can be made through breast duct endoscope, and the breast duct with lesions could be positioned. It is a necessary assistant method for patients to avoid biopsy or decrease the biopsy range.