Abstract:Despite considerable progress, the surgical treatment of hilar cholangiocarcinoma remains one of the most difficult challenges for surgeons. There are still many disputes concerning the definition, staging, imaging evaluation, preoperative pretreatment, surgical procedures and adjuvant therapy of this disease. So, it requires the joint efforts of multiple disciplines to achieve the best treatment effect.

Abstract:Objective: To evaluate the effectiveness, safety and economic value between laparoscopic cholecystectomy (LC) plus laparoscopic common bile duct exploration (LCBDE) and endoscopic sphincterotomy (EST) plus LC in treatment of common bile duct stones. Methods: Using a prospective, randomized controlled approach, patients with confirmed choledocholithiasis were randomly assigned in a 1:1 ratio to two groups to undergo LC+LCBD and EST+LC, respectively. Six-month postoperative follow-up was conducted. The main clinical variables between the two groups of patients were compared. Results: One hundred and ten patients were enrolled. In LC+LCBD group, the average operative time was (103.9±18.0) min, the average intraoperative blood loss was (15.3±29.5) mL, 3 cases (5.5%) had open conversion, the average length of hospital stay was (12.02±5.8) d and the average hospitalization cost was (32 116± 6 503) yuan, and no residual stone was found during follow-up. In EST+LC group, the average operative was (175.2±10.5) min, the average intraoperative blood loss was (6.8±7.0) mL, 2 cases (3.6%) had open conversion, the average length of hospital stay was (11.9±3.0) d, the average hospitalization cost was (37 571± 5 017) yuan, and residual stone was found in one case during follow-up. Between the two groups, the operative time, intraoperative blood loss and hospitalization cost had statistical difference (all P<0.05), while no statistical difference was noted in the remaining variables (all P>0.05). Conclusion: The two combined minimally invasive procedures show no obvious difference in effectiveness and safety. However, LC+LCBDE is preferentially recommended for its low costs.

Abstract:Objective: To investigate clinical efficacy of percutaneous transhepatic endoscopy (PTES) combined with different lithotripsy methods for precision treatment of complicated hepatolithiasis and summarize relevant experiences. Methods: The clinical data of 49 patients with complicated hepatolithiasis undergoing PTES plus holmium laser lithotripsy or electrohydraulic lithotripsy were retrospectively analyzed. Results: The surgical successful rate was 93.9% (46/49). The average operative time was (107.5±8.9) min and blood loss was (43.6±10.4) mL. The incidence of residual stones was 8.7% (4/46) and complications occurred 18 times. The short- and long-term recurrence rate was 6.5% and 13.6%, respectively. Conclusion: PTES combined with different lithotripsy methods shows favorable efficacy in precision treatment of complicated hepatolithiasis. This method is recommended as the first choice of options for patients with no lobar atrophy, and the stones confined to one segment or one lobe of the liver as well as those without tolerance to an open surgery due to repeated biliary operation history.

Abstract:Objective: To evaluate the application value of percutaneous transhepatic cholangial drainage (PTCD) in laparoscopic common bile duct exploration (LCBDE) with primary closure. Methods: The clinical data of 65 patients with gallbladder stones and concomitant bile duct stones undergoing LCBDE and primary closure in the Third Division of Hepatopancreatobiliary Surgery of the Second Affiliated Hospital, Kunming Medical University from June 2015 to June 2016 were retrospectively analyzed. Of the patients, 33 cases received preoperative PTCD treatment and retention of the PTCD tube for postoperative drainage (PTCD group), and 32 cases did not receive PTCD treatment (non-PTCD group). The main clinical variables between the two groups of patients were compared. Results: Operation was successfully performed in all the 65 patients, without any open conversion. In PTCD group compared with non-PTCD group, the average operative time (119.5 min vs. 136.6 min), intraoperative blood loss (44.70 mL vs. 62.81 mL), time to first gas passage (9.52 h vs. 11.13 h), length of postoperative hospital stay (11.85 d vs. 13.53 d), and hospitalization cost (12 800 yuan vs. 14 400 yuan) were all significantly reduced (all P<0.05). The direct bilirubin levels in both group were decreased compared with their preoperative values, but the pre- and postoperative direct bilirubin levels showed no significant difference between the two groups (both P>0.05). There was no significant difference in incidence of postoperative complications between PTCD group and no-PTCD group (3.0% vs. 15.6%, P=0.087). Conclusion: In patients with gallbladder stones and concomitant bile duct stones undergoing LCBDE and primary closure, as long as the diameter of the bile duct is greater than 1.0 cm, even if there is no severe liver injury, PTCD placement is recommended, which may be helpful for liver function recovery, and reducing the length and cost of hospitalization.

Abstract:Objective: To evaluate the safety and feasibility of laparoscopic common bile duct exploration (LCBDE) with primary closure of the common bile duct. Methods: The clinical data of patients undergoing LCBDE in Foshan Hospital affiliated to Southern Medical University from June 2013 to September 2016 were retrospectively analyzed. Of the patients, 62 cases received intraoperative primary closure of the common bile duct (study group), and 38 cases had T-tube drainage (control group). The main clinical variables between the two groups of patients were compared. Results: There were no significant differences in gender, BMI and diameter of the common bile duct between the two groups of patients (all P>0.05). In study group compared with control group, the mean operative time was significantly prolonged (113.92 min vs. 95.92 min, P=0.032), but the residual stone rate was significantly reduced (0 vs. 6.0%, P=0.002), while the length of postoperative hospital stay showed no significant difference (4.00 d vs. 5.11 d, P=0.088). The overall incidence of postoperative complications showed no significant difference between the two groups (8.1 vs. 5.3%, P=0.701), and grade A and B biliary fistula occurred in one and two cases respectively in study group, which were all resolved by conservative treatment. No open conversion was required and on death occurred in either of the groups. Follow-up was performed in both groups of patients for at least 12 months, and no stone recurrence or symptomatic stricture of the common bile duct was noted. Conclusion: In selected patients, LCBDE with primary closure of the common bile duct has favorable short- and long-term efficacy, and can improve the patients’ quality of life and avoid the complications associated with use of T-tube.

Abstract:Objective: To investigate the value of using enhanced recovery after surgery (ERAS) programs in liver resection for hepatolithiasis. Methods: The clinical data of 178 patients undergoing liver resection for hepatolithiasis with ERAS management (ERAS group) from January 2013 to December 2016 and 218 patients undergoing liver resection for hepatolithiasis with conventional perioperative management (conventional group) from January 2009 to December 2012 were retrospectively analyzed. The main clinical variables between the two groups of patients were compared. Results: In ERAS group compared with conventional group, the recovery of liver function parameters after surgery was faster (partial P<0.05), the length of postoperative hospital stay was significantly shortened, the time to first flatulence was significantly reduced, the postoperative body weight loss was significantly decreased and the total hospitalization cost was significantly reduced (all P<0.05). There were no statistical differences either in incidence of overall postoperative complications or incidence of specific complication between the two group (all P>0.05). No death occurred in either of the groups. Conclusion: Using ERAS protocol in liver resection for hepatolithiasis is safe and feasible. It can effectively promote the postoperative recovery of the patients, and reduce the length of hospital stay and medical cost.

Abstract:Objective: To investigate the efficacy and safety of primary closure of the common bile duct plus nasobiliary drainage via antegrade transabdominal approach in treatment of common bile duct stones. Methods: One hundred and thirty-eight patients with gallstones and concomitant choledocholithiasis admitted in the Department of Hepatobiliary Surgery of Hunan Provincial People’s Hospital from August 2015 to February 2017 were enrolled. Of the patients, 45 cases underwent laparoscopic cholecystectomy, common bile duct exploration and endoscopic nasobiliary drainage with primary choledochal closure (nasobiliary drainage group), and 93 cases underwent laparoscopic cholecystectomy and common bile duct exploration plus T-tube drainage (T-tube drainage group). The main clinical variables between the two groups of patients were compared. Results: Operations were successfully completed in all the 138 patients, and no serious surgical complication occurred. In nasobiliary drainage group compared with T-tube drainage group, the operative time, intraoperative blood loss and volume of bile drainage on the first postoperative day showed no significant difference (all P>0.05), but the time to postoperative bowel function recovery, retention of the bile drainage tube, length of hospital stay and hospitalization cost as well as the amount of postoperative fluid infusion, and the volume of bile drainage on the second and third postoperative day were all significantly reduced (all P<0.05). There was no significant difference in overall incidence of postoperative complications between the two groups (P>0.05), but the incidence of symptoms of electrolyte imbalance such as nausea and vomiting in nasobiliary drainage group was significantly lower than that in the T-tube drainage group (P<0.05). Conclusion: Nasobiliary drainage extends the indications for primary closure of the common bile duct, and can shorten the tube retention time and length of hospital stay, and reduce the fluid and electrolyte disorders, with no increase of complications such as bile leakage and biliary stricture. It has certain superiority to T-tube drainage, but its indications should be followed.

Abstract:Objective: To investigate the application value of intrabiliary contrast-enhanced ultrasonography (CEUS) in residual stone detection following choledochal surgery. Methods: Forty-one patients readmitted after undergoing open or laparoscopic common bile duct exploration and stone extraction with choledochal T-tube drainage, and 10 patients undergoing stone extraction through sinus tract dilation after percutaneous transhepatic cholangial drainage (PTCD) from August 2016 to January 2018 were enrolled. All patients underwent intrabiliary CEUS and X-ray cholangiography before choledochoscopic exploration through T-tube sinus tract or dilated PTCD sinus tract after admission. The length and diameter of the common bile duct before and after CEUS combined with saline injection were recorded. Using the results of choledochoscopic exploration as a golden standard for residual stones, the accuracies of the other two methods for residual stone detection were analyzed. Results: All the three examinations were completed in these patients. The full length of the common bile duct was exposed in 92.2% (47/51) patients under CEUS combined with saline injection. Using the results of choledochoscopic exploration as a standard, the coincidence rate of residual stone detection was 88.2% (45/51) for CEUS, with a sensitivity of 78.3%, specificity of 96.4% and κ value for the consistency of 0.76; the coincidence rate of residual stone detection was 82.4% (42/51) for X-ray cholangiography, with a sensitivity of 60.9%, specificity of 100% and κ value for the consistency of 0.63. Conclusion: Intrabiliary CEUS for residual stone detection after T-tube placement or PTCD sinus tract dilation can effectively observe the full length of the common bile duct and the residual stones inside, and its residual stone detection rate can be improved by combination with X-ray cholangiography.

Abstract:Objective: To establish a reliable, convenient and high resolution method for bile proteomic analysis. Methods: Gallbladder bile samples were drawn from 3 gallbladder cancer patients and 3 gallstone patients for protein extraction and purification, and then the protein samples were identified and quantified using a high-resolution proteomic method named isobaric tags for relative and absolute quantification (iTRAQ), and then were analyzed by bioinformatics methods. Results: After concentration and integrity test, all of the extracted protein samples met the concentration and integrity requirements of the iTRAQ experiment. Following identification, a total of 1 323 proteins were detected, which was remarkably higher than that by traditional methods. In bile from gallbladder cancer patients compared with that from gallstone patients, 173 proteins were significantly up-regulated and 345 proteins were significantly down-regulated (fold change>1.5, P<0.05). Conclusion: A reliable method for bile protein isolation, purification, identification and analysis is established, which has the ability to detect many more proteins and greater potential to find key proteins associated with specific diseases compared with traditional methods, and may lay a foundation for proteomic analysis of bile and other body fluids in the future.

Abstract:Objective: To investigate the expressions of mucin-3 (MUC3) and -4 (MUC4) in tissues of intrahepatic cholangiocarcinoma (ICC) associated with hepatolithiasis and their clinical significance. Methods: The MUC3 and MUC4 expressions in the 24 specimens of normal bile duct tissue, 44 specimens of bile duct tissue from hepatolithiasis patients, and 38 specimens of hepatolithiasis-associated ICC were determined by immunohistochemical staining. The relations of MUC3 and MUC4 expressions with clinical factors and prognosis of the patients with hepatolithiasis-associated ICC were analyzed. Results: The positive expression rates of both MUC3 and MUC4 were significantly different in the three different tissues (both P<0.05); in normal bile duct tissue, bile duct tissue from hepatolithiasis patients and hepatolithiasis-associated ICC tissue, the positive MUC3 expression rates were ranked in a decreasing order (79.2%, 56.8% and 36.8%), while the opposite was true for MUC4 (29.2%, 79.5% and 86.8%). In patients with hepatolithiasis-associated ICC, both MUC3 and MUC4 expressions were significantly related to the tumor histological differentiation and the presence or absence of lymph node metastasis, and MUC4 expression was also significantly related to the presence or absence of portal vein invasion (all P<0.05). In patients with hepatolithiasis-associated ICC, the postoperative survival rate in patients with positive MUC3 expression was significantly higher than that in patients with negative MUC3 expression, and in patients with positive MUC4 expression was significantly lower than that in patients with negative MUC4 expression (all P<0.05). Conclusion: The MUC3 expression is decreased and the MUC4 expression is increased in hepatolithiasis-associated ICC tissue, and the changes of their expressions are closely related to the development, invasion and metastasis of hepatolithiasis-associated ICC.

Abstract:Objective: To investigate the expression of targeting protein for xenopus kinesin-like protein 2 (TPX2) in cholangiocarcinoma tissue and its clinical significance. Methods: The cancer tissues together with their adjacent tissues from 60 patients with cholangiocarcinoma were collected. The positive expression rates of TPX2 protein in these tissues were determined by immunohistochemical staining, and the TPX2 protein expression levels were detected by Western blot in 4 pairs of randomly selected tissues. The relations of TPX2 protein expression with the clinical factors and prognosis of the patients were analyzed. Results: In cholangiocarcinoma tissue compared with adjacent tissue, the positive expression rate (46.7% vs. 8.3%, P<0.05) and expression level of TPX2 protein were increased. The TPX2 protein expression was significantly associated with the TNM stage, lymph node metastasis and survival of the patients (all P<0.05). The postoperative survival rates in patients with positive TPX2 protein expression were significantly lower than those in patients with its negative expression (2-year survival rate: 27.6% vs. 78.4%; 3-year survival rate: 14.3% vs. 59.5%, both P<0.05). Conclusion: High TPX2 expression may possibly be associated with postoperative recurrence and metastasis in cholangiocarcinoma patients. It may be a potential biological indicator for the early diagnosis and estimation of prognosis and a therapeutic target of cholangiocarcinoma.

Abstract:Objective: To investigate the role of leptin in gallbladder cholesterol stone formation through analysing the relations of leptin with gallbladder bile components and blood lipids in patients with gallbladder cholesterol stones. Methods: Thirty patients with gallbladder cholesterol stones undergoing elective laparoscopic cholecystectomy (gallstone group) and 22 patients undergoing elective laparoscopic cholecystectomy for gallbladder polyps (polyp group) during the same period were selected. In these patients, the serum levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL) and leptin as well as the concentrations of bile TC and total bile acid (TBA) in gallbladder and the mRNA expression of leptin receptor in the tissues of gallbladder wall were determined. Results: In gallstone group compared with polyp group, the serum levels of TC, TG, LDL and leptin as well as the bile TC/TBA ratio in the gallbladder and mRNA expression level of leptin receptor in the gallbladder tissue were all significantly increased, while the serum level of HDL was significantly decreased (all P<0.05). In gallstone group, the serum leptin level had significantly positive correlation with serum TG and TC levels and bile TC content (r=0.633, P=0.002; r=0.224, P=0.025; r=0.384, P=0.000), and significant negative correlation with HDL level and TBA content (r=-0.205, P=0.014; r=-0.548, P=0.024); in polyp group, the serum leptin level showed no significant correlation with all above variables (all P>0.05). Conclusion: Leptin participates in gallbladder cholesterol stone formation. The increased levels of leptin and its receptor may be closely related to abnormal cholesterol metabolism and gallbladder bile component imbalance.

Abstract:Objective: To investigate the role of intrahepatic stem/progenitor cells in liver regeneration after the first stage of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS). Methods: Seventy-two SD rats were equally randomized into ALPPS group, portal vein ligation (PVL) group and sham operation group, and then underwent the first stage of ALPPS, PVL alone and sham operation, respectively. The serum levels of transaminases and inflammatory factors and the hepatic regeneration rate (HRR) of the right middle lobe of the liver were determined, and the expressions of cell proliferation index Ki-67 and OV-6, the biomarker of oval cells (stem/progenitor cells), were also examined in each group of rats at postoperative day (POD) 1, 2, 3 and 7, respectively. Results: Compared with sham operation group, the serum levels of transaminases and inflammatory factors were significantly increased in both ALPPS group and PVL group on POD 1 to 2, and their increasing amplitudes in ALPPS group were all significantly higher than those in PVL group (all P<0.05); the HRR of the right middle lobe of the liver and positive Ki-67 rate in the liver tissue were significantly increases in both ALPPS group and PVL group, but the HRR was significantly higher on POD 3 and 7, the positive Ki-67 rate was significantly higher on POD 2 and 3 in ALPPS group than those in PVL group (all P<0.05); obvious OV-6 expression was seen in either ALPPS group or PVL group, but its expression levels in ALPPS group were significantly higher than those in PVL group on POD 2 and 3 (both P<0.05). Conclusion: The first stage of ALPPS is superior to single PVL for inducing liver regeneration, and the mechanism is probably related to higher inflammatory status after ALPPS which may cause the mobilization and activation of the intrahepatic stem/progenitor cells, and thereby promote the rapid liver regeneration.

Abstract:Objective: To investigate the clinical efficacy of hepatic arterial infusion (HAI) of 5-fluorouracil (5-FU) and cisplatin combined with systemic intravenous chemotherapy of gemcitabine in treatment of advanced intrahepatic cholangiocarcinoma (ICC). Methods: Seventy-nine patients with advanced ICC and measurable lesions were enrolled and designated to study group (39 cases) and control group (40 cases) by use of a random number table. Patients in study group underwent HAI of 5-FU+cisplatin combined with intravenous gemcitabine chemotherapy, and those in control group underwent systemic intravenous chemotherapy of gemcitabine and cisplatin. Patients in either group received two repeated courses of treatment, with one month per course. Results: There was no statistical difference in response rate between study group and control group (38.46% vs. 20.00%, P>0.05), but the benefit rate in study group was significantly higher than that in control group (79.49% vs. 60.00%, P<0.05). The levels of tumor biomarkers were significantly decreased in both groups after treatment compared with their pretreatment levels, but their decreasing amplitudes were significantly greater in study group than those in control group (all P<0.05). The 1- and 2-year survival rates showed no statistical difference between study group and control group (63.16% vs. 39.47%; 55.00% vs. 22.50%, both P>0.05), but the 3-year survival rate in study group was significantly higher than that in control group (23.68% vs. 7.50%, P<0.05). There was no statistical difference in incidence of each toxic and adverse reaction during chemotherapy (all P>0.05). Conclusion: HAI combined with systemic intravenous gemcitabine chemotherapy for advanced intrahepatic cholangiocarcinoma patients can achieve relatively good short-term effects and increased long-term survival.

Abstract:Objective: To investigate the choice of surgical timing for acute severe cholecystitis (ASC). Methods: The clinical data of 156 ASC patients undergoing emergency laparoscopic cholecystectomy (LC) or elective LC after percutaneous transhepatic gallbladder drainage (PTGBD) were retrospectively analyzed. Of the patients, 21 cases underwent emergency LC, 89 cases underwent LC within 2 months after PTGBD, and 46 cases underwent LC more than 2 months after PTGBD. The main clinical variables were compared between patients with different surgical timings. Results: In patients undergoing emergency LC compared with those undergoing elective LC after PTGBD, the number of open conversion and total hospitalization cost showed no statistical difference (both P>0.05), but intraoperative blood loss, operative time, length of postoperative hospital stay, time period for postoperative antibiotic administration, number of cases requiring postoperative analgesics and incidence of postoperative complications were all significantly decreased (all P<0.05). No significant differences were noted in all above variables between patients undergoing elective LC at different times after PTGBD (all P<0.05). Conclusion: For ASC, performing early emergency LC is inadvisable, while elective LC within or more than 2 months after PTGBD may be more appropriate.

Abstract:Objective: To investigate the appropriate methods of diagnosis and treatment for biliary tract obstruction secondary to juxtapapillary duodenal diverticula (JPPD). Methods: The clinical data of 22 patients with JPPD caused biliary tract obstruction treated in the First Affiliated Hospital of Kunming Medical University in recent years were analyzed, along with literature review. Results: Of the 22 patients, 14 cases were definitely diagnosed by endoscopic retrograde cholangiopancreatography (ERCP), 8 cases were confirmed by magnetic resonance cholangiopancreatography (MRCP); one case underwent diverticulum resection alone, 2 cases underwent diverticulum resection and choledochostomy with T-tube drainage, 15 cases underwent Billroth II gastrectomy and choledochostomy with T-tube drainage, 3 cases underwent Roux-en-Y choledochojejunostomy, and one case underwent pancreaticoduodenectomy. Twenty patients were followed up for 1.5 to 10 years, and all recovered well. Conclusion: For JPPD caused biliary tract obstruction, MRCP is the best diagnostic method at present; simple diverticulum resection is the most ideal surgical approach, Billroth II gastrectomy and choledochostomy with T-tube drainage is a simple, safe and effective approach and is most widely used, and Roux-en-Y choledochojejunostomy can be performed for those with stenosis of the sphincter of Oddi.

Abstract:B ultrasound-guided percutaneous transhepatic gallbladder drainage (PTGBD) has gradually become the first choice for treatment of acute edematous cholecystitis. The PTGBD technique has been developed with the continued improvement of the surgical instruments and surgeons’ proficiency. At present, the reported literature concerning PTGBD is mostly limited to acute cholecystitis in elderly patients, but no systematic reports are available on its specific advantages, indications and timing for subsequent cholecystectomy. In this article, the authors address the above three aspects to provide indications for clinical practice.