Abstract:Objective: To investigate the risk factors associated with gallbladder cancer, and provide a theoretical basis for the prevention and treatment of this condition. Methods: Using a case-control design, 316 patients admitted and diagnosed as gallbladder cancer from January 2009 to December 2017 in Xiangya Hospital of Central South University and 316 cases admitted for other diseases with similar age distribution and sex ratio to the former during the same period were selected. The risk factors associated with the occurrence of gallbladder cancer was analyzed. Results: Of the 316 patients with gallbladder cancer, the mean age was (60.2±10.6) years, cases over 50 years of age accounted for 82.28%, the male to female ratio was 1:1.95, and 156 cases (49.4%) had concomitant gallstones, of whom 30 cases were gallbladder filling type stones. Univariate and multivariate analysis showed that gallstone was the only risk factor for gallbladder cancer (OR=6.72, 95% CI=4.52–10.02, P<0.01). The number of cases with gallbladder cancer and concomitant gallstones showed a first rising and then declining trend during the studied period, and its proportion accounting for the total number of cases of gallbladder cancer each year did not significantly change; the proportion of cases with concomitant gallstones in female patients was higher than that in male patients (P<0.01). The proportions of gallbladder cancer patients with concomitant gallstones who did not undergo radical surgery and had TNM stage IIIB and IV diseases were higher than those of gallbladder cancer patients without gallstones (both P<0.05). The relative risks to gallbladder cancer were increased in patients with large-diameter gallstones and gallbladder filling type stones (both P<0.05). Conclusion: Gallstones may be one of the major risk factors for gallbladder cancer. The risk for gallbladder cancer is increased with the increase of the diameter and number of the gallstones. The gallbladder cancer patients with concomitant gallstones always have a relatively late stage. Timely surgical treatment is recommended for those with types of stones that are relatively possible to develop gallbladder cancer.

Abstract:Objective: To investigate the clinicopathologic features, diagnosis and treatment as well as prognosis of primary non-Hodgkin’s lymphoma (NHL) of the common bile duct. Methods: The data of a patient with primary NHL of the common bile duct treated in the Affiliated Tumor Hospital of Guangxi Medical University, and together with the data of 34 cases of primary NHL of the common bile duct reported from 1982 to 2017 at home and abroad were analyzed. Results: The patient was an 81-year-old male, who was diagnosed as primary NHL (diffuse large B cell lymphoma) of the common bile duct by postoperative pathological findings after undergoing pancreatoduodenectomy. No adjuvant anti-tumor therapy such as systemic chemotherapy and regional radiotherapy was performed after operation, and no recurrence was noted 4 months later. Of this patient plus the reported 34 patients, 21 cases (60.0%) were males and 14 cases (40.0%) were females; the age at onset ranged from 4 to 81 years, with a median age of 57 years; the clinical manifestations included jaundice (88.6%) and abdominal pain (40.0%), enlarged superficial lymph nodes (11.4%) and concomitant fever (11.4%); imaging manifestations in some cases showed space occupying lesion in the common bile duct or thickening and stenosis of the common bile duct wall; four cases underwent systemic chemotherapy, 10 cases underwent surgical resection, 16 cases underwent surgical resection combined with systemic chemotherapy, 1 case underwent surgical resection combined with local radiotherapy, 3 cases underwent surgical resection combined with systemic chemotherapy and local radiotherapy, and treatment regimen in 1 case was unknown. The majority of cases had a passable prognosis after treatment, and one case survived more than 72 months; there were no significant differences in survival times between patients undergoing surgical resection alone and those undergoing chemotherapy alone or other combined treatments (all P>0.05). Conclusion: Primary NHL of the common bile duct is a rare condition in clinical practice, lacks typical clinical manifestations, and the laboratory tests and imaging examinations have no obvious specificity. So, its clinical diagnosis is difficult, and definite diagnosis depends on postoperative pathology and immunohistochemistry. Selection of appropriate treatment options is critical for improving the survival of the patients.

Abstract:Objective: To compare the clinical efficacy of robotic-assisted cholecystectomy (RAC) and traditional laparoscopic cholecystectomy (TLC) in treatment of benign gallbladder diseases. Methods: After systematic retrieval in literature databases, the eligible literature of studies was screened out according to the inclusion and exclusion criteria. After data extraction, Meta-analysis was performed by using RevMan 5.3 software. Results: Twenty-six studies were finally included, involving 4 004 patients, of whom, 1 833 cases underwent RAC and 2 171 cases underwent TLC. The results of Meta-analysis showed that RAC had prolonged operative time (MD=13.14, 95% CI=4.79–21.50, P=0.002) and increased incidence of incisional hernia (RR=3.59, 95% CI=1.77–7.28, P=0.0004), but reduced intraoperative conversion rate (RR=0.60, 95% CI=0.40–0.92, P=0.02) compared with TLC. However, no significant differences were found in intraoperative complications, postoperative complications, 30 d readmission rate, length of hospital stay and blood loss between the two procedures (all P>0.05). Conclusion: Current evidence suggests that RAC has similar safety and effectiveness as TLC, but no advantage over TLC.

Abstract:Objective: To evaluate the feasibility, safety and clinical efficacy of laparoscopic cholecystectomy combined with intraoperative endoscopic retrograde cholangiopancreatography (IOERCP) for elderly patients with concomitant cholelithiasis and choledocholithiasis.
Methods: Eighty-two elderly patients (≥60 years of age) with concomitant cholelithiasis and choledocholithiasis admitted in the Third Hospital of Mianyang from May 2015 to October 2017 were enrolled. The patients were randomly assigned to two groups by a random number table, and underwent combined treatment of LC and IOERCP (LC plus IOERCP group, 42 cases) and combined treatment of LC and laparoscopic common bile duct exploration (LCBDE) (LC plus LCBDE group, 40 cases). The main clinical variables between the two groups of patients were compared.
Results: The baseline data of the two groups of patients were comparable. There were no significant differences in operative time, intraoperative blood loss and rate of open conversion between the two groups (all P>0.05). The stone residual rate in LC plus IOERCP group was significantly lower than that in LC plus LCBDE group (0 vs. 15.4%, P<0.05). The overall incidence of postoperative complications and incidence of each specific complication showed no significant difference between the two groups (all P>0.05). The hospitalization cost was increased but the length of postoperative hospital stay was reduced in LC plus IOERCP group compared with LC plus LCBDE group (both P<0.05).
Conclusion: LC simultaneously combined with IOERCP is safe and feasible for elderly patients with concomitant cholelithiasis and choledocholithiasis, with advantages such as rapid postoperative recovery, shortened hospital stay, and lower residual stone rate.

Abstract:Objective: To investigate the efficacy and safety of using “three-step method” to determine the timing for laparoscopic cholecystectomy (LC) following endoscopic sphincterotomy (EST) in treatment of simultaneous cholecystolithiasis and choledocholithiasis. Methods: Patients who had been definitely diagnosed with concomitant gallbladder and common bile duct stones during December 2012 to December 2017 were selected and randomly allocated into study group and control group. Patients in both groups underwent endoscopic retrograde cholangiopancreaticography (ERCP) and EST after completion of the preoperative preparation. Time interval for following LC in study group was determined by using the “three-step method” in study group, while LC was performed after the complete disappearance of clinical symptoms and the full recovery of all laboratory test results in control group. Results: A total of 116 patients were consented for the study, with 58 patients each in both groups. The baseline data were comparable between the two groups. In study group compared with control group, the length of hospital stay [12.0 (11.0–15.0) d vs. 16.5 (13.0–19.8) d, P<0.01] and total hospitalization cost [ (28 000±7 000) yuan vs. (32 000±8 000) yuan, P=0.004]were significantly reduced (both P<0.05), but the LC conversion rate, operative time, intraoperative blood loss and incidence of postoperative complication showed no significant differences (all P>0.05). Conclusion: Using “three-step method” to determine the optimal timing for LC according to the intra- and postoperative conditions of ERCP/EST can effectively reduce the length of hospital stay and hospitalization cost, and meanwhile, it has similar efficacy and safety to those by conventional method.

Abstract:Objective: To investigate the related factors for stone recurrence in patients with gallbladder stones after gallbladder-preserving cholecystolithotomy. Methods: The clinical and follow-up data of 400 patients with gallbladder stones undergoing gallbladder-preserving cholecystolithotomy from May 2010 to May 2014 were collected. The factors for postoperative stone recurrence of the patients were analyzed. Results: In the 400 patients, the average follow-up time was (34.2±3.6) months, and gallbladder stone recurrence occurred in 42 cases (10.5%). The results of univariate analysis showed that having a family history of gallstones, degree of gallbladder wall thickness, number of stones and triacylglycerol level were significantly associated with postoperative stone recurrence (all P<0.05); multivariate Logistic regression analysis revealed that having a family history of gallstones (OR=10.231, 95% CI= 6.344–48.343, P=0.008), gallbladder wall thickness ≥4 mm (OR=2.312, 95% CI=1.223–12.156, P=0.023), multiple gallstones (OR=4.568, 95% CI=3.213–15.328, P=0.015) and triacylglycerol level ≥1.71 mmol/L (OR=2.556, 95% CI=1.643–15.312, P=0.041) were independent risk factors for postoperative stone recurrence. Conclusion: Having a family history of gallstones, gallbladder wall thickness ≥4 mm, multiple gallstones and triglyceride level ≥1.71 mmol/L are risk factors for postoperative stone recurrence in gallstone patients after gallbladder-preserving stone extraction. For patients with these factors, the appropriate preventive measures should be considered or gallbladder-preserving procedure should not be performed.

Abstract:Objective: To determine the risk factors for conversion to open surgery in patients undergoing laparoscopic cholecystectomy (LC) combined with laparoscopic common bile duct exploration (LCBDE) in treatment of gallbladder stones with common bile duct stones and perform the relevant clinical analysis. Methods: The clinical data of 197 patients undergoing LC plus LCBDE from January 2014 to June 2018 were retrospectively analyzed. The risk factors for conversion to open surgery were screened, and the perioperative variables and postoperative complications between patients undergoing completed laparoscopic surgery and those converted to open surgery were compared. Results: Fifteen cases (7.6%) of the 197 patients were converted to open surgery. Univariate and multivariate analyses showed that serum total bilirubin>17.1 μmol/L (OR=5.156, P=0.032), gallbladder wall thickness >6 mm (OR=7.971, P=0.012), jaundice (OR=10.715, P=0.002) and stone incarceration in the lower part of the common bile duct (OR=20.203, P=0.003) were independent risk factors for open conversion. For predicting open conversion, the regression equation established by integration of the above 4 factors showed an area under ROC of 0.891, with a sensibility of 80.0% and specificity of 98.9%. In patients undergoing completed laparoscopic surgery compared with those undergoing open conversion, the operative time, intraoperative blood loss, number of postoperative analgesic use, time period of postoperative antibiotic use, time to first postoperative anal gas passage, length of hospital stay, hospitalization cost and incidence of complications were significantly reduced (all P<0.05). Conclusion: For patients undergoing LC plus LCBDE, the above 4 independent risk factors should be carefully evaluated, which has important significance for optimal preoperative preparation, operative procedure selection, reducing open conversion rate and improvement of the patient outcomes.

Abstract:Objective: To detect the expression of miR-362-3p in gallbladder cancer and its functions. Methods: The expressions of miR-362-3p in the surgical specimens from 44 gallbladder cancer patients were determined by qRT-PCR, and the relations of miR-362-3p expression with clinicopathological characteristics and prognosis of the patients were analyzed. In gallbladder cancer cells after transfection with miR-362-3p mimics, the changes in proliferation, migration and invasion were examined by MTT colorimetry, wound healing assay, and Transwell assay respectively. The target gene of miR-362-3p was analyzed by bioinformatics analysis and dual luciferase reporter gene assay, and then was verified through recovery tests. Results: The expression of miR-362-3p was significantly decreased in gallbladder cancer tissue compared with tumor adjacent tissue (P<0.05). The decreased miR-362-3p expression was significantly associated with tumor TNM stage, lymph node metastasis and distant metastasis (all P<0.05). The overall survival rate in patients with low miR-362-3p expression was significantly lower than that in patients with high miR-362-3p expression (P<0.05). The abilities of proliferation, migration and invasion were significantly reduced in gallbladder cancer cells after transfection with miR-362-3p mimics (all P<0.05). Nemo like kinase (NLK) was found potentially to be the target gene of miR-362-3p. After transfection with NLK overexpression vectors, the above effects exerted by miR-362-3p mimics in gallbladder cancer cells were significantly reversed (all P<0.05). Conclusion: The expression of miR-362-3p is down-regulated in gallbladder cancer, and the down-regulated miR-362-3p expression may reduce the inhibition on its target gene NLK, and thereby promote the proliferation, migration and invasion of gallbladder cancer cells.

Abstract:Objective: To investigate the expression of the adaptor protein CARMA3 in cholangiocarcinoma cells and its function. Methods: The expressions of CARMA3 mRNA in cholangiocarcinoma HUCCT1 and RBE cells as well as in normal biliary epithelia cell line HIBEC were determined by qRT-PCR. After silencing the expression of CARMA3 with siRNA technique, the changes in proliferation, apoptosis, cell cycle and abilities of migration and invasion in HUCCT1 and RBE cells were examined by CCK-8 assay, flow cytometry and Transwell assay, respectively. Results: The expression levels of CARMA3 mRNA were significantly increased in both cholangiocarcinoma cell lines compared with normal biliary epithelia cell line HIBEC (HUCCT1 vs. HIBEC: t=5.321, P=0.011; RBE vs. HIBEC: t=5.932, P=0.008). In both cholangiocarcinoma cell lines after silencing the expression of CARMA3, the abilities of proliferation, metastasis and invasion were significantly inhibited, and the G1-phase arrest and apoptosis rates were significantly increased (all P<0.05). Conclusion: CARMA3 is up-regulated in cholangiocarcinoma cells, and its actions may be associated with promoting cell proliferation, migration and invasion, and inhibiting cell apoptosis.

Abstract:Objective: To investigate the inhibitory effect of paclitaxel on hepatic fibrosis induced by bovine serum albumin (BSA) in rats and its mechanism.
Methods: Wistar rats after the formation of immunological liver fibrosis induced by BSA, were injected with normal saline (model group) or 10 μg/g paclitaxel (paclitaxel treatment group) via tail vein respectively, and another 10 normal rats administered with normal saline with the same fashion were served as control group. Injection was performed once daily, and the rats were sacrificed and their blood samples and liver specimens were obtained 28 d later, and then histopathological observations were performed, the serum biochemical parameters for liver function and the collagen-related variables in the serum and liver tissue, and the expressions of α-SMA and TGF-β1 in the liver tissue were measured; the hepatic stellate cells (HSCs) were isolated, and then the protein and mRNA expressions of molecules related to TGF-β/Smad signaling pathway in them were determined.
Results: In model group compared with control group, significant liver fibrosis was present, the levels of serum transaminases were significantly increased with significantly decreased albumin level, the collagen-related variables in the serum and liver tissue were significantly augmented, the expression rates of α-SMA and TGF-β1 in the liver tissue were significantly elevated, and the protein and mRNA expressions of molecules related to TGF-β/Smad signaling pathway in the HSCs were significantly up-regulated (all P<0.05). The changing amplitudes of all above variables in paclitaxel treatment group were significantly lower than those in model group (all P<0.05), and some of them showed no significant differences with control group (partial P<0.05).
Conclusion: Paclitaxel has inhibitory effect on immunological liver fibrosis induced by BSA in rats, and the mechanism may probably associated with its suppressing the activity of the TGF-β/Smad signaling pathway.

Abstract:Objective: To evaluate the application value of biliary water injection test in laparoscopic common bile duct exploration (LCBDE). Methods: Using a prospective cohort design, 95 patients undergoing LCBDE and stone extraction from January 2016 to October 2017 in Chifeng Clinical Medical School of Inner Mongolia Medical University were enrolled and randomly designated to study group (46 cases) and control group (49 cases). Performance of primary closure of the common bile duct or T-tube drainage was decided by observation of the status of the sphincter of Oddi (SO) through choledochoscopic biliary water injection test in study group, while that was judged by conventional methods in control group. The relevant clinical variables were compared between the two groups of patients. Results: There were no significant differences in preoperative general data between the two groups (all P>0.05). The operative time showed no significant difference between the two groups (P>0.05), but the primary choledochal closure rate in study group was significantly higher than that in control group (26.1% vs. 10.2%, χ2=4.074, P=0.044). No death or severe complications occurred in the two groups, and both the overall incidence of complications and incidence of each complication also showed no significant differences between the two groups (all P>0.05). No significant differences were noted in hospitalization costs, length of postoperative hospital stay and abdominal drainage time between the two groups (all P>0.05). No stone recurrence occurred within half a year in both groups. Conclusion: The biliary water injection test can safely and effectively evaluate the SO function and reduce the T-tube placement, and thereby avoid the discomfort and pain caused by unnecessary T-tube indwelling and the associated complications, which is in accordance with the current concept of enhanced recovery after surgery.

Abstract:Objective: To investigate the preoperative evaluation, diagnosis and surgical approach of cholecystoduodenal fistula with gallstone ileus. Methods: The clinical data of a patient with cholecystoduodenal fistula and gallstone ileus were analyzed retrospectively, and the relevant literature was reviewed. Results: The patient was considered to have gallbladder stone and gallstone bowel obstruction by preoperative CT examinations. Intraoperative exploration found incarceration of a 40 cm stone at the ileocecal junction. Then, enterotomy and stone removal, duodenal fistula repair and cholecystectomy were successfully performed. The patient was discharged after postoperative recovery, and no related complications were observed up to the present time. Conclusion: Cholecystoduodenal fistula with gallstone ileus is a rare condition in clinical practice, early diagnosis and accurate assessment are critical, and appropriate surgical approach should be chosen according to the specific characteristics of individuals.

Abstract:Objective: To investigate the diagnosis and treatment methods for cholecystoduodenal fistula complicated with gallstone ileus. Methods: The clinical data of 16 patients with cholecystoduodenal fistula and gallstone ileus undergoing surgical treatment from January 2013 to June 2017 were analyzed retrospectively. Results: Of the 16 patients, 8 cases were diagnosed before operation, and 8 cases were diagnosed during operation; 7 cases were diagnosed having concomitant gallstone cholecystitis, and 5 cases were diagnosed having concomitant duodenal ulcer and gastric ulcer before operation. All of the 16 patients underwent surgical treatment, which included small bowel enterotomy and stone extraction plus gastrectomy (Billroth II operation) and Braun’s anastomosis in 7 cases, small bowel enterotomy and stone extraction plus gastrectomy (Billroth II operation) in 3 cases, gastric antrotomy and stone extraction combined with gastrectomy (Billroth II operation) and Braun’s anastomosis in 2 cases, and small bowel enterotomy and stone extraction, cholecystectomy and duodenal fistula repair plus duodenostomy and jejunostomy in 4 cases. The operative average time was 115 min, the average length of hospital stay was 8 d, and liquid food intake started on average postoperative day 9. After the operation, pulmonary infection occurred in 4 cases, duodenal leakage occurred in 2 cases, anastomotic bleeding occurred in 1 case, and wound infection occurred in 3 cases, respectively. All the 16 patients were discharged after a complete cure. Conclusion: Preoperative examinations such as CT and B ultrasound are very important for diagnosis of this condition. For patients with severe inflammatory adhesion of the gallbladder, especially with concomitant duodenal ulcers and gastric ulcers, gastrectomy (Billroth II operation) plus Braun’s anastomosis is effective, while cholecystectomy plus duodenal fistula repair and jejunostomy can be considered for those with mild cholecystitis, and gastric antrotomy and stone removal can be performed in cases with duodenal bulb stone obstruction.

Abstract:Objective: To compare the effects of sufentanil and remifentanil respectively combined with propofol for intravenous anesthesia in laparoscopic cholecystectomy (LC). Methods: Ninety patients undergoing LC from March 2017 to March 2018 were enrolled, equally randomized into two groups, and received intravenous anesthesia with sufentanil and propofol (sufentanil group) or remifentanil and propofol (remifentanil group). The hemodynamic parameters and serum stress indicators at predefined time points during anesthesia, times to recovery of spontaneous breathing, eye opening and extubation, scores of postoperative visual analogue scale (VAS), and pre- and postoperative scores of mini-mental state examination (MMSE) as well as incidence of adverse reactions were compared between the two groups. Results: In sufentanil group compared with remifentanil group, the heart rate and mean arterial pressure as well as serum levels of cortisol and norepinephrine were significantly decreased at the moment immediately after tracheal intubation and anesthesia induction, 5 min after CO2 pneumoperitoneum, and the moment immediately after tube removal (all P<0.05); the times to recovery of spontaneous breathing, eye opening and extubation were all significantly prolonged (all P<0.05); the VAS scores were significantly decreased at 2, 6 and 12 h after operation (all P<0.05); the MMSE score on the first postoperative day was significantly increased (P<0.05); the overall incidence of adverse reactions was significantly reduced (P<0.05). Conclusion: Compared to anesthesia using remifentanil combined with propofol, using sufentanil combined with propofol for LC is more helpful in maintaining the hemodynamic stability, weakening stress responses, lessening the severity of postoperative pain, quickening the recovery of cognitive function, and reducing the adverse reactions.

Abstract:Gallbladder cancer is a common biliary malignancy and one of the most aggressive tumors of the digestive system. Surgical treatment is effective for early stage gallbladder cancer, but radical surgery is always difficult or impossible for advanced stage gallbladder cancer, due to the spread of tumor cells to the lymph nodes, hepatic hilar area, or other organs, resulting in poor prognosis and short survival. The authors address the current research status and progress in treatment of gallbladder cancer for reference use in clinical practice.

Abstract:Cholangiocarcinoma is a malignant tumor with a low resection rate and dismal prognosis. At present, the effective markers or targets for early diagnosis and treatment of cholangiocarcinoma remain absent. Recent investigations have found that there are certain links between the occurrence and development of cholangiocarcinoma and the abnormal expressions of non-coding RNAs (ncRNAs) in cancer cells. ncRNAs are a family of RNAs that do not encode proteins, and they can not only affect multiple biological processes such as proliferation, differentiation, apoptosis of the tumor cells, but also play important roles in the occurrence and development of tumors as well as in the invasion and metastasis processes of tumor cells, through participating in the regulation of gene expressions. Studies of the abnormal expressions of ncRNAs in cholangiocarcinoma cells may promote the development of molecular diagnosis and targeted therapy for cholangiocarcinoma. Here, the authors review and briefly analyze the research progress on the relationship between ncRNAs and cholangiocarcinoma and the related mechanisms, so as to provide clues for further investigation and new ideas for the treatment of cholangiocarcinoma.