Circ_0005075 promotes hepatocellular carcinoma progression by suppression of microRNA-335.

Accumulating evidence suggests that noncoding RNAs play a vital role in cancer biology. Circular RNAs (circRNAs), a newly defined class of endogenously widespread noncoding RNAs, have been intensively reported to influence cell function and development, and even cancer prognosis by sponging microRNAs in various types of cancer. Nevertheless, the circRNAs research in hepatocellular carcinoma (HCC) still remains far insufficient. Herein, we investigated the role of a newly defined circRNAs, circ_0005075, in HCC development. We found circ_0005075 was upregulated in HCC tissues. HCC progression was suppressed by downregulation of circ_0005075 in vitro and in vivo, and the suppression was partially reversed by inhibition of microRNA-335 (miR-335) expression. Further, we found the expression of mitogen-activated protein kinase 1 (MAPK1) was substantially regulated by circ_0005075 and miR-335. Mechanically, it was demonstrated that circ_0005075 could directly bind to miR-335 and miR-335 could bind to MAPK1. Our data provide evidence that circ_0005705 promotes the HCC progression by sponging miR-335 and further regulating MAPK1 expression.

Biliary reconstruction with a pedicled gallbladder flap in patients during pancreaticoduodenectomy.

BACKGROUND: Stricture formation at the biliary-enteric anastomosis can cause serious complications after pancreaticoduodenectomy while the anastomotic size is reported to significantly affect stricture formation. In this study, we aimed to determine the effect of a pedicled gallbladder flap used as an alternative to biliary reconstruction during pancreaticoduodenectomy in patients with a nondilated extrahepatic bile duct. METHODS: Data of patients with a nondilated extrahepatic bile duct, who underwent pancreaticoduodenectomy between October 2012 and July 2015 at the Department of Hepatobiliary and Pancreaticosplenic Surgery at Beijing Chaoyang Hospital, were collected. A pedicled gallbladder flap for biliary reconstruction was consecutively performed in patients with morphologically normal gallbladder, whereas patients with abnormal gallbladder morphology accept conventional biliary reconstruction. RESULTS: A total of 29 patients were enrolled in this study with 17 patients using a pedicled gallbladder flap and 12 patients using the conventional technique. Patients of the two groups had similar preoperative and operative parameters as well as similar early complication rates. No patients in the former group experienced biliary stricture or transient episodes of cholangitis over the follow-up period. While in the latter group, one patient had biliary stricture in the 14th month which was cured by intervene treatment. Another two patients had intermittently mild-to-moderate elevations in liver enzymes level from the 11th month and the 18th month, respectively, and were treated with medication. CONCLUSIONS: Biliary reconstruction with a pedicled gallbladder graft can be used as an alternative in patients with a nondilated extrahepatic bile duct during pancreaticoduodenectomy.

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.

Inferior Infracolic 'Superior Mesenteric Artery First' Approach with a No-Touch Isolation Surgical Technique in Patients with a Borderline Resectable Cancer of the Pancreatic Head.

BACKGROUND: Early diagnosis of superior mesenteric artery (SMA) involvement is vital for patients with a borderline resectable cancer of the pancreatic head to achieve an R0 resection. We aimed to detect the effect of the inferior infracolic 'superior mesenteric artery first' approach with a no-touch isolation surgical technique in these patients. METHODS: The data of 21 patients who were consecutively diagnosed with a borderline resectable cancer of the pancreatic head and treated with our technique between July 2014 and September 2015 were analyzed. RESULTS: During the exploration, five patients were confirmed to have invasion to the SMA. Fourteen patients underwent a pancreaticoduodenectomy, and two patients underwent a total pancreatectomy due to a positive margin at the pancreatic neck on frozen sections. Ten men and six women, with a mean age of 64.1 years, were included in the study. Pathologic stage was T1, T2, and T3 in 1, 3, and 12 patients, respectively. Venous resection was performed in 8 patients, and an R0 resection was achieved in all patients (16/16). The mean intraoperative blood loss was 532 ml (range 200-1800 ml). At median follow-up time after surgery (12.8 months; range 4.5-18 months), two patients had a recurrence in the liver. The 1-year survival rate was 75 %, and the 1-year tumor-free survival rate was 62.5 %. CONCLUSIONS: Our technique facilitates early diagnosis of arterial involvement and the achievement of an R0 resection. This technique allows the tumor to be resected in situ, and removed en bloc, and is associated with decreased blood loss.

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.

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.

[Clinical predictors of cytomegalovirus infection after liver transplantation].

OBJECTIVE: To investigate the clinical predictors of cytomegalovirus (CMV) infection after liver transplantation. METHODS: The clinical data of 182 patients (146 male and 36 female with a mean age of (50 ± 7) years) receiving liver transplantation in Beijing Chaoyang Hospital between January 2004 and December 2008 were retrospectively analyzed.All patients were divided into two groups, namely the CMV infection group (n=24) and the control group (n=158). Logistic regression was used to identify the predictive factors of postoperative CMV infection. RESULTS: According to univariate analysis results, the factors for CMV infection were acute liver failure (P=0.032), MELD score ≥ 30 (P=0.001), liver retransplantation (P=0.002), acute rejection (P=0.000) and delayed graft function (P=0.022). According to multi-analysis results, MELD score ≥ 30 (P=0.037, 95%CI:1.194-271.461) and acute rejection (P=0.033, 95%CI:1.179-51.863) were proved to be independent predictors by multivariate analysis. CONCLUSION: The study indicates that MELD score ≥ 30 and acute rejection are the independent predictors of CMV infection.

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.

[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.

MiR-1301-3p Inhibits Epithelial-Mesenchymal Transition via Targeting RhoA in Pancreatic Cancer.

Micro(mi)RNAs play an essential role in the epithelial-mesenchymal transition (EMT) process in human cancers. This study aimed to uncover the regulatory mechanism of miR-1301-3p on EMT in pancreatic cancer (PC). The miRNA profilings from Gene Expression Omnibus data sets (GSE31568, GSE41372, and GSE32688) demonstrated the downregulation of miR-1301-3p in PC tissues, which was validated with 72 paired PC tissue samples through qRT-PCR detection. The low level of miR-1301-3p was associated with a poor prognosis for PC patients from the PC cohort of The Cancer Genome Atlas and the validation cohort. Gene Ontology analyses indicated that the target genes of miR-1301-3p were involved in cell cycle and adherent junction regulation. In vitro assays revealed that miR-1301-3p suppressed the proliferation and migration abilities of PC cells. Western blotting and luciferase reporter assays suggested that miR-1301-3p inhibited RhoA expression by targeting its 3'-untranslated region; RhoA upregulated N-cadherin and vimentin levels; however, it downregulated the E-cadherin level. In conclusion, our study showed that miR-1301-3p could serve as a prognostic biomarker for PC and suppress PC cell malignancy by targeting the RhoA-induced EMT process.

Single-cell transcriptomics reveals heterogeneous progression and EGFR activation in pancreatic adenosquamous carcinoma.

Pancreatic adenosquamous carcinoma (PASC) - a rare pathological pancreatic cancer (PC) type - has a poor prognosis due to high malignancy. To examine the heterogeneity of PASC, we performed single-cell RNA sequencing (scRNA-seq) profiling with sample tissues from a healthy donor pancreas, an intraductal papillary mucinous neoplasm, and a patient with PASC. Of 9,887 individual cells, ten cell subpopulations were identified, including myeloid, immune, ductal, fibroblast, acinar, stellate, endothelial, and cancer cells. Cancer cells were divided into five clusters. Notably, cluster 1 exhibited stem-like phenotypes expressing UBE2C, ASPM, and TOP2A. We found that S100A2 is a potential biomarker for cancer cells. LGALS1, NPM1, RACK1, and PERP were upregulated from ductal to cancer cells. Furthermore, the copy number variations in ductal and cancer cells were greater than in the reference cells. The expression of EREG, FCGR2A, CCL4L2, and CTSC increased in myeloid cells from the normal pancreas to PASC. The gene sets expressed by cancer-associated fibroblasts were enriched in the immunosuppressive pathways. We demonstrate that EGFR-associated ligand-receptor pairs are activated in ductal-stromal cell communications. Hence, this study revealed the heterogeneous variations of ductal and stromal cells, defined cancer-associated signaling pathways, and deciphered intercellular interactions following PASC progression.

Enhanced recovery after surgery pathways benefit patients with soft pancreatic texture following pancreaticoduodenectomy.

BACKGROUND: We aimed to compare the enhanced recovery after surgery pathway with the standard perioperative care protocol concerning complications, postoperative length of stay and 1-year survival rate. METHODS: Using a before-after cohort study design, data from patients with pancreatic head cancer, who consecutively underwent pancreaticoduodenectomy, were retrospectively collected. RESULTS: Compared to the control group, patients with soft pancreas in the enhanced recovery after surgery group had a lower incidence of delayed gastric emptying (36.7% vs 13.3%, P = 0.026) and respiratory complications (46.7% vs 20.0%, P = 0.028), and shorter postoperative length of stay (All: 10.9 ±â€¯3.4 d vs13.5 ±â€¯3.8 d, P = 0.002; Soft: 11.2 ±â€¯3.8 d vs14.0 ±â€¯4.5 d, P = 0.001). The 1-year survival rates were similar between the groups. CONCLUSION: The enhanced recovery after surgery pathways can significantly reduce the incidence of certain surgical complications and decrease the postoperative length of stay. It does not affect 1-year survival.

Proposed Chaoyang vascular classification for superior mesenteric-portal vein invasion, resection, and reconstruction in patients with pancreatic head cancer during pancreaticoduodenectomy - A retrospective cohort study.

BACKGROUND: Patients with pancreatic head cancer involving the superior mesenteric-portal vein can benefit from vascular resection and reconstruction. We aimed to propose our vascular classification and assess its effect in this study. MATERIAL AND METHODS: Data of consecutive patients, who were diagnosed with pancreatic head cancer, and underwent radical pancreaticoduodenectomy combined with superior mesenteric-portal vein resection and reconstruction at our institute between October 2013 and August 2016, were retrospectively collected. On a scale of one to four, our classification was proposed. Perioperative parameters were then analyzed among the four types. RESULTS: There were a total of 52 patients with 11 in type Ⅰ, 15 in type Ⅱ, 18 in type Ⅲ, 8 in type Ⅳ. The respective operative time and estimated blood loss of types Ⅲ (425-990 min, 265-1820 mL) and Ⅳ (480-1036 min, 330-1690 mL) were greater than those of types Ⅰ (300-824 min, 200-1255 mL) and Ⅱ (369-875 min, 305-1400 mL) (p < 0.05). Type Ⅳ had larger tumors (4-7 cm) than type Ⅰ (1.5-4 cm) (p < 0.05). Percentage of tunica intima involvement and the median survival time of type Ⅰ (9.1%, 22 months) were lower and longer than those of types Ⅱ (46.7%, 17 months) and Ⅲ (44.4%, 16 months; p < 0.05), and even lower and longer than those of type Ⅳ (87.5%, 10 months; p < 0.01), respectively. CONCLUSIONS: Our classification can provide a system to grade patients with venous invasion in order of surgical difficulty and survival.

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.

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.

Isolated hepatic tuberculosis in the caudate lobe mimicking intrahepatic carcinoma.

Although tuberculosis (TB) remains a worldwide epidemic, isolated hepatic TB is an extremely rare entity and poorly described in the literature. Isolated hepatic TB may pose a diagnostic dilemma due to the non-specific clinical symptoms and imaging features. We present a case of a 54-year-old female with an isolated caseating granulomatous lesion at the caudate lobe of liver involving the pancreatic head.