Management of anastomotic biliary stricture through utilizing percutaneous transhepatic cholangioscopy.

AIM: Occurrence of anastomotic biliary stricture (AS) remains an essential issue following hepatobiliary surgeries, and percutaneous transhepatic cholangioscopy (PTCS) has great therapeutic significance in handling refractory AS for patients with altered gastrointestinal anatomy after cholangio-jejunostomy. This present study aimed to investigate feasibility of PTCS procedures in AS patients for therapeutic indications. MATERIALS AND METHODS: This study was a single-center, retrospective cohort study with a total number of 124 consecutive patients who received therapeutic PTCS due to AS. Clinical success rate, required number, and adverse events of therapeutic PTCS procedures as well as patients survival state were reviewed. RESULTS: These 124 patients previously underwent choledochojejunostomy or hepatico-jejunostomy, and there was post-surgical altered gastrointestinal anatomy. Overall, 366 therapeutic PTCS procedures were performed for these patients through applying rigid choledochoscope, and the median time of PTCS procedures was 3 (1-11). Among these patients, there were 34 cases (27.32%) accompanied by biliary strictures and 100 cases (80.65%) were also combined with biliary calculi. After therapeutic PTCS, most patients presented with relieved clinical manifestations and improved liver functions. The median time of follow-up was 26 months (2-86 months), and AS was successfully managed through PTCS procedures in 104 patients (83.87%). During the follow-up period, adverse events occurred in 81 cases (65.32%), most of which were tackled through supportive treatment. CONCLUSION: PTCS was a feasible, safe and effective therapeutic modality for refractory AS, which may be a promising alternative approach in clinical cases where the gastrointestinal anatomy was changed after cholangio-jejunostomy.

Efficiency of percutaneous transhepatic cholangioscopy in the treatment of biliary complications after liver transplantation.

BACKGROUND: Percutaneous transhepatic cholangioscopy (PTCS) has provided an alternative therapeutic option for handling refractory biliary complications in liver transplanted recipients. This study aimed to evaluate short-term PTCS efficiency in the management of biliary complications following liver transplantation. METHODS: Clinical data of 25 patients who received therapeutic PTCS due to biliary complications after liver transplantation were retrospectively analyzed. RESULTS: Therapeutic PTCS was successfully performed in 25 patients. Biliary complications were anastomotic strictures in seven cases, intrahepatic cholangiolithiasis in four cases, extra-and intrahepatic cholangiolithiasis in three cases, choledocholithiasis complicated with anastomotic strictures in four cases, intrahepatic cholangiolithiasis complicated with non-anastomotic strictures in one case, intrahepatic cholangiolithiasis complicated with anastomotic strictures in five cases, intrahepatic cholangiolithiasis complicated with anastomotic strictures and ischemic cholangitis in one case. The median time between liver transplantation and first PTCS was 24 months, and median times of PTCS was 2.6. Clinical manifestations were significantly improved in most patients after PTCS, and biliary complications were successfully managed through PTCS in 15 cases, which were partially effective in eight cases and ineffective in two cases. PTCS was more effective in tackling anastomotic strictures and cholangiolithiasis. CONCLUSION: PTCS was an effective therapeutic modality for treating refractory biliary complications following liver transplantation.

One-Step Multichannel Percutaneous Transhepatic Cholangioscopic Lithotripsy Applied in Bilateral Hepatolithiasis.

BACKGROUND: The aim of this study was to compare the outcomes of one-step multichannel percutaneous transhepatic cholangioscopic lithotripsy (PTCSL) with traditional PTCSL in the treatment of bilateral hepatolithiasis. METHODS: From February 2011 to June 2015, 156 patients with bilateral hepatolithiasis received surgical treatment in our department. Among these patients, 81 received one-step multichannel PTCSL (group A), and the remaining 75 received traditional PTCSL (group B). RESULTS: Compared with group B, group A was characterized by a significantly shorter operation time (83.7 ± 28.5 min vs 118.1 ± 41.5 min; P = 0.000), hospital stay (11.1 ± 3.4 d vs 17.8 ± 5.6 d; P = 0.034), and postoperative hospital stay (6.9 ± 3.1 d vs 9.6 ± 4.5 d; P = 0.026). In addition, the immediate clearance (62.9% vs 45.3%, P = 0.027) and final clearance (90.1% vs 78.7%, P = 0.048) rates were higher in group A than in group B. During the follow-up period, stone recurrence was significantly less common in group A than in group B (13.6% vs 26.7%, P = 0.041). Multivariate Cox analysis showed that the PTCSL method (HR = 2.32, 95% confidence interval [CI] = 1.09-4.90, P = 0.028), bilateral biliary stricture (HR = 4.17, 95% CI = 1.73-10.03, P = 0.001), and stones located in segments I (HR = 7.75, 95% CI = 3.67-16.38, P = 0.000) were independent predictors of recurrence. CONCLUSIONS: Compared with traditional PTCSL, one-step multichannel PTCSL was more efficient and effective in the treatment of bilateral hepatolithiasis.

Expression and Significance of COX-2 and Ki-67 in Hepatolithiasis with Bile Duct Carcinoma.

BACKGROUND: As an induced enzyme, COX-2 expression is elevated under stimuli from inflammatory mediator or growth factor product. Ki-67, a cell cycle-related proliferative antigen, reflects the tissue proliferative activity. This study analyzed the expressional profile of cyclooxygenase-2 (COX-2) and Ki-67 in hepatolithiasis and bile duct carcinoma tissues, in an attempt to provide evidence for diagnosis and prognosis prediction of disease. MATERIAL AND METHODS: A cohort of tissue samples from hepatolithiasis with bile duct carcinoma (N=47) patients were analyzed using immunohistochemical (IHC) staining method for the expression of COX-2 and Ki-67, in parallel with hepatolithiasis (N=44) and normal bile duct tissues (N=30). The relationship between expression pattern of COX-2 and Ki-67 and pathological conditions was also analyzed, in addition to the correlation with positive expression in hepatolithiasis samples. RESULTS: The positive expression rate of COX-2 and Ki-67 in bile duct carcinoma was 76.6% and 80.9%, respectively, and was significantly higher than those in the hepatolithiasis group, which was also higher than the control group. Expression of both COX-2 and Ki-67 is closely related to TNM staging, lymph node metastasis, and differentiation stage. They were also correlated with the mortality rate of patients. CONCLUSIONS: Both COX-2 and Ki-67 are abundantly expressed in hepatolithiasis and bile duct carcinoma tissues and may play an important role in the disease occurrence, progression, and metastasis.

The intestinal microbiota influences the microenvironment of metastatic colon cancer by targeting miRNAs.

This study aimed to investigate the molecular mechanisms through which the intestinal microbiota and microRNAs (miRNAs) participate in colon cancer metastasis. Intestinal flora data, and the GSE29621 (messenger RNA/long non-coding RNA [mRNA/lncRNA]) and GSE29622 (miRNA) datasets, were downloaded from The Cancer Gene Atlas and Gene Expression Omnibus databases, respectively. Immune-related cells in M1 vs. M0 samples were analyzed using the Wilcoxon test. Furthermore, an lncRNA-miRNA-mRNA (competing endogenous RNA [ceRNA]) network was constructed, and survival analysis of RNAs in the network was performed. A total of 16 miRNA-genus co-expression pairs containing eight microbial genera and 15 miRNAs were screened; notably, Porphyromonas and Bifidobacterium spp. were found to be associated with most miRNAs, and has-miR-3943 was targeted by most microbial genera. Furthermore, five immune cell types, including activated natural killer cells, M1 macrophages, resting mast cells, activated mast cells and neutrophils, were differentially accumulated between the M1 and M0 groups. Enrichment analysis suggested that mRNAs related to colon cancer metastasis were mainly involved in pathways related to bacterial and immune responses. Survival analysis revealed that TMEM176A and PALM3 in the ceRNA network were significantly associated with the prognosis of patients with colon cancer. In conclusion, this study revealed a potential mechanism by which the intestinal microbiota influences the colon cancer microenvironment by targeting miRNAs.

One-step percutaneous transhepatic cholangioscopic lithotripsy in patients with choledocholithiasis.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) may be inappropriate for most patients with choledocholithiasis. This study aimed to evaluate one-step percutaneous transhepatic cholangioscopic lithotripsy (PTCSL) in the treatment of patients with choledocholithiasis who could not undergo ERCP (e.g., failed ERCP, altered anatomy, and/or contra-indications). METHOD: This was a retrospective single-centre series of 67 patients who underwent choledocholithiasis between November 2015 and March 2018: 35 with one-step PTCSL (Group A) and 32 with laparoscopic common bile duct (CBD) exploration (Group B). RESULTS: Compared with Group B, Group A showed shorter duration of operation, length of stay in the hospital, postoperative hospital stay, postoperative drainage time, and time to oral intake (all P<0.05). Intraoperative blood loss, costs, conversion to open surgery (one in group A vs. seven in group B; P=0.023), and bile leakage (none in group A vs. four in group B; P=0.047) were lower in Group A than in Group B. There were no significant differences between the two groups regarding the intraoperative clearance rate, ultimate clearance rate, and several postoperative complications. CONCLUSION: One-step PTCSL could be an alternative for patients with choledocholithiasis, especially when ERCP is not feasible.

Comparison Between Percutaneous Transhepatic Rigid Cholangioscopic Lithotripsy and Conventional Percutaneous Transhepatic Cholangioscopic Surgery for Hepatolithiasis Treatment.

BACKGROUND: Percutaneous transhepatic cholangioscopy (PTCS) is one option for treating hepatolithiasis without surgical resection. This approach can use conventional biliary drainage methods over a long period, but a shorter procedure needs to be evolved. OBJECTIVE: To evaluate the short-term and the long-term therapeutic outcomes of percutaneous transhepatic cholangioscopic lithotripsy (PTCSL) in comparison with conventional PTCS. METHODS: In this retrospective study, 118 patients with hepatolithiasis were enrolled who underwent treatment in our hospital between March 2007 and July 2014. About 67 of them received PTCSL and the remaining 51 patients received conventional PTCS. Preoperative data, surgical operation-related records, the postoperative therapeutic effect, and the long-term hepatolithiasis recurrence rate were collected for comparison between the 2 groups. RESULTS: The age, sex, and surgical history were similar between the 2 groups, but there was a significant difference in the Child-Pugh score, with more grade 3 patients in the PTCS group (P=0.002). However, the operation time, intraoperative blood infusion, and the blood loss were similar between the 2 groups. The final clearance ratio of calculus in the PTCSL group was significantly better than in the PTCS group after multivariate analysis (P=0.021; OR=0.201; 95% CI, 0.051-0.785). Calculus recurrence was 9% (PTCSL) and 22% (PTCS). The postoperative hospital stay was significantly shorter in the PTCSL group (P=0.001; OR=1.337; 95% CI, 1.132-1.58). CONCLUSIONS: PTCSL was a satisfactory therapeutic option for hepatolithiasis treatment, with less operation time and a superior long-term therapeutic effect compared with conventional PTCS.

Histone deacetylase inhibitor valproic acid (VPA) promotes the epithelial mesenchymal transition of colorectal cancer cells via up regulation of Snail.

Histone deacetylase inhibitors (HDACIs) have been shown to have antiproliferative activity through cell-cycle arrest, differentiation, and apoptosis in colorectal cancer (CRC) cells. Our present study revealed that one HDAC inhibitor, valproic acid (VPA), can obviously promote in vitro motility of HCT-116 and SW480 cells. VPA treatment significantly down regulates the expression of epithelial markers E-Cadherin (E-Cad) and Zona occludin-1(ZO-1) while up regulates the mesenchymal markers Vimentin (Vim) and N-cadherin (N-Cad), suggesting that VPA can trigger the epithelial-mesenchymal transition (EMT) of CRC cells. VPA treatment significantly increases the expression and nuclear localization of Snail, the key transcription factors of EMT. Snail knockdown by siRNAs obviously reverses VPA induced EMT of HCT-116 and SW480 cells. Further, VPA can decrease the ubiquitination, increase the acetylation, and then elevate the stabilization of Snail. VPA also increases the phosphorylation of Akt/GSK-3ß. The inhibitor of PI3K/Akt, LY2994002, significantly attenuates VPA induced phosphorylation of Akt and GSK-3ß and up regulation of Snail and Vim. Collectively, our data reveal that VPA can trigger the EMT of CRC cells via up regulation of Snail through AKT/GSK-3ß signals and post-transcriptional modification. It suggests that more attention should be paid when VPA used as a new anticancer drug for CRC patients.

Effect of p38 mitogen-activate protein kinase on MUC5AC protein expression of bile duct epithelial cells in hepatolithiasis patients.

Primary hepatolithiasis is a common bile duct disease with benign nature but complicated mechanisms. Current studies have revealed its correlation with cytokine release by chronic inflammation, which also increased mucin (MUC) synthesis. This study investigated the role of p38 mitogen-activated protein kinase (MAPK) in regulating cytokine release and mucin synthesis, in an attempt to elucidate the role of p38 signaling molecule in the pathogenesis of hepatolithiasis. In human intrahepatic bile duct endothelial cells (HIBECs), lipoprotein (LPS) was used to induce the high expression of MUC. Small interference RNA (siRNA) was then used to silencing p38 gene expression. Cytokines including interleukin (IL)-1ß and tumor necrosis factor (TNF)-α were measured, along with MUC5AC protein and mRNA expression assay. The interference of p38 gene expression inhibited the release of IL-1ß and TNF-α in cultured cells. It also depressed both mRNA and protein levels of MUC5A. P38 MAPK signal pathway may be involved in the formation and progression of hepatolithiasis. This study provides potential new strategy for treating hepatolithiasis using p38 MAPK signal pathway as the drug target.