Endoscopic retrograde cholangiopancreatography (ERCP) remains the gold standard for Common bile duct (CBD) stone management, yet biliary cannulation challenges persist in some cases. There are limited data on primary Insulation-tipped (IT) knife precut for the biliary cannulation. Our aim was to investigate the efficacy and safety of IT nano knife-assisted primary precut in comparison to conventional cannulation for biliary access for the first time. This multicenter randomized controlled trial compared the efficacy and safety of primary IT knife nano-assisted precut sphincterotomy (group A) versus conventional cannulation (group B) in 340 patients with choledocholithiasis. Outcomes included initial/overall biliary cannulation success, procedural time, and adverse events (AEs). Group A demonstrated superior initial cannulation success compared to group B (85.9

BACKGROUND Endoscopic retrograde cholangiopancreatography (ERCP) is a pivotal diagnostic and therapeutic modality for the assessment and management of pancreatic and bile duct disorders. Percutaneous transhepatic biliary drainage (PTBD) is a prevalent and progressively favored primary treatment modality for malignant obstructive jaundice, providing rapid biliary decompression, achieving high technical success rates, and serving as a conduit for subsequent interventions. Rendezvous techniques are poised to play a lasting role, given the rising demand for palliative care interventions following failed conventional ERCP. CASE SUMMARY This report details the case of a 69-year-old male patient who presented with complaints of jaundice, lower abdominal discomfort, and fatigue. The patient underwent two ERCP procedures with biliary stenting, and his PTBD catheter required regular replacement. However, the PTBD catheter failed to provide adequate drainage. The underlying condition was bile duct stenosis caused by malignant tumor compression, which proved refractory to conventional ERCP treatment. A guidewire was advanced through the existing PTBD tract, followed by the successful implantation of a biliary stent, which achieved intrahepatic biliary drainage. The PTBD catheter was intentionally left in place as a precaution against potential re-obstruction. CONCLUSION The PTBD-guided ERCP rendezvous technique is an effective salvage strategy when standard ERCP fails and can be flexibly applied by clinicians.

Background. Distal malignant biliary obstruction (DMBO) can result in obstructive jaundice. Endoscopic ultrasound- (EUS-) guided biliary drainage (EUS-BD) has been an alternative for DMBO after failed ERCP. Aim. To compare the efficacy and safety between antegrade and transluminal approaches in patients with unresectable DMBO when ERCP failed. Methods. Patients with DMBO leading to obstructive jaundice after failed ERCP were enrolled in this study. We retrospectively evaluated the safety and efficacy between EUS-guided transluminal stenting (TLS group) and antegrade stenting (AGS group). Results. 82 patients were enrolled, of which 45 patients were in TLS group and 37 in AGS group. There were no statistical differences in the malignancy type, baseline common bile duct diameter, total bilirubin level, reason for EUS-BD, and history of biliary drainage between TLS and AGS groups. The technical success rate was statistically higher in TLS group than in AGS group (97.8 vs. 81.1%, P=0.031). There were no statistical differences in clinical success rate, procedure-related adverse events, stent migration rate, stent dysfunction rate, reintervention rate, and overall patient survival time between TLS and AGS groups. The median time to stent dysfunction or patient death in TLS and AGS groups was 53 and 81 days, respectively (P=0.017). Conclusions. Although AGS had a lower technical success rate than TLS, it was superior to TLS in stent patency in patients with DMBO.

Background: Our study aims to analyze the association between Lauren's classification and gastric adenocarcinoma prognosis using comprehensive statistical analyses. Methods: According to the selection criteria, patients were included from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate Cox regression, propensity score matching, and a multivariate competing risk model were used to investigate the association between Lauren's classification and prognosis. Subgroup analysis was used to investigate the role of confounding factors on the association between Lauren types and prognosis. Results: After exclusion, a total of 20,218 patients from the SEER database were included, with 14,374 intestinal types and 5,844 diffuse types. The univariate Cox regression analysis revealed that the diffuse type had a poorer cancer-specific survival (CSS) rate [hazard ratio (HR), 1.44; 95% confidence interval (CI), 1.38-1.50]. After adjusting for confounding variables, the diffuse type also showed a higher risk of cancer-specific death (HR, 1.20; 95% CI, 1.15-1.20). Sensitivity analysis showed that after propensity score matching, the diffuse type had a poorer CSS rate (HR, 1.23; 95% CI, 1.10-1.36), and the competing risk model further validated these results [subdistribution HR (SHR), 1.32; 95% CI, 1.23-1.41]. Moreover, subgroup analysis demonstrated stable results in the subgroups, except for patients with T1 stage (HR, 1.06; 95% CI, 0.87-1.28) and a tumor size <2 cm (HR, 1.00; 95% CI, 0.83-1.21). Conclusions: Diffuse-type gastric adenocarcinoma had an overall poorer prognosis compared to the intestinal type. However, in patients with T1 stage and tumor size <2 cm, the diffuse type had a comparable survival rate with the intestinal type.

BACKGROUND:Abdominal pain is often observed after endoscopic retrograde cholangiopancreatography (ERCP). Few studies have focused on the risk factors of post-ERCP abdominal pain without post-ERCP pancreatitis (PEP). This study aimed to identify risk factors of post-ERCP abdominal pain without PEP and investigate characteristics of the abdominal pain in non-PEP patients. METHODS:Data from patients who underwent ERCP from August 2019 to January 2020 were retrospectively collected. Characteristics of the abdominal pain after ERCP were recorded and compared between PEP and non-PEP patients. Multivariate analysis was conducted to identify risk factors of non-PEP abdominal pain. RESULTS:A total of 1295 ERCP procedures were investigated in this study, among which 100 (7.72%) patients presented post-ERCP abdominal pain without PEP and 63 (4.86%) patients with PEP. Multivariate analysis found 9 risk factors of non-PEP abdominal pain: age ≤ 65 years [odds ratio (OR): 1.971], primary ERCP (OR: 2.442), dilated extrahepatic bile duct (OR: 1.803), no papilla opening (OR: 2.095), pancreatic guidewire passages (OR: 2.258), white blood cells (WBC) ≤ 6.0 × 109/L (OR: 1.689), platelet (PLT) ≤ 250 × 109/L (OR: 2.505), serum γ-glutamyl transferase (γ - GT) ≤ 35 U/L (OR: 2.190), and albumin ≥ 40 g/L (OR: 1.762). The PEP group had later pain onset, higher pain frequency and longer hospital stay than those of the non-PEP pain group (P < 0.05). There were no significant differences in the pain duration, visual analogue scale score and mortality between the PEP group and non-PEP pain group (P > 0.05). CONCLUSIONS:This study indicated that age ≤ 65 years, primary ERCP, dilated extrahepatic bile duct, no papilla opening, pancreatic guidewire passages, lower WBC, lower PLT, normal γ - GT and elevated albumin were independent risk factors for post-ERCP abdominal pain without PEP. The pain occurred earlier in non-PEP patients than in PEP patients.

Background: A few models have been proposed for the prediction of the risk of post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP), but many include factors that are not assessed routinely. Herein, we intend to develop and validate a predictive model for the occurrence of PEP. Methods: Data of patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) from January 01, 2016 to May 16, 2019 (training set and internal test set) and from May 17, 2019 to December 25, 2019 (external test set) were retrospectively collected. The performance of the model was validated in the two validation cohorts. Results: A total of 342 patients were included for the external test set, and 47 (13.7%) developed PEP. The variables included in the scoring system were gastrectomy history, high direct bilirubin (DBIL), high albumin (ALB), villous type of papillary orifice, nodular type of papillary orifice, pancreatic guidewire passages, precut sphincterotomy, and high operator experience. A total score >5 indicated high risk. In the external test set, the area under the curve (AUC) was 0.718, the sensitivity was 0.723, and the specificity was 0.676. In the external test set, the probability of PEP was 6.1%, 17.0%, and 37.5% in patients with low (<0), moderate (0-5), and high (>5) risk scores, respectively. Conclusions: This study established a scoring system for predicting the risk of PEP using routinely measured clinical variables. Its application in routine work warrants further investigation.

Laparoscopic cholecystectomy is the routine method to treat gallbladder polyps. Nowadays, endoscopic ultrasound (EUS)-guided cholecystostomy as a bridge for per-oral transmural endoscopic resection of gallbladder polyps is introduced because preservation of gallbladder is increasingly getting attention. The aim of our study was to evaluate the approach in the treatment of patients with gallbladder polyps and symptomatic gallstones. EUS-guided cholecystostomy with the placement of a lumen-apposing metal stent (LAMS) was performed for those patients with accompanying gallbladder polyps and symptomatic gallstones. Several days after the cholecystostomy with LAMS, a gastroscope was introduced into the gallbladder to remove gallbladder polyps. All patients were successfully performed with the procedures of EUS-guided cholecystoduodenostomy (n = 3) or cholecystogastrostomy (n = 1) and endoscopic resection of gallbladder polyps. One patient experienced severe peritonitis. During the follow-up at 3 months, 1 patient was performed with laparoscopic cholecystectomy because ultrasonography examination showed the reappeared gallstones. No stone recurrence was found in other patients. During the follow-up of 3 to 15 months, no polyp recurrence was found in all the patients. The approach is novel for performing EUS-guided gallbladder fistulization, which can subsequently allow procedures of per-oral transmural endoscopic resection of gallbladder polyps to avoid cholecystectomy in the patients with gallbladder polyps and gallstones. However, further studies are needed before clinical recommendation because of the complications and stone recurrence.

Endoscopic transpapillary cannulation of the gallbladder is useful but challenging. This study aimed to investigate cystic duct anatomy patterns, which may guide cystic duct cannulation. A total of 226 patients who underwent endoscopic transpapillary cannulation of the gallbladder were analyzed retrospectively. According to the cystic duct take-off, 226 cystic duct patterns were divided into 3 patterns: Type I (193, 85.4%), located on the right and angled up; Type II (7, 3.1%), located on the right and angled down; and Type III (26, 11.5%), located on the left and angled up. Type I was further divided into three subtypes: Line type, S type (S1, not surrounding the common bile duct; S2, surrounding the common bile duct), and α type (α1, forward α; α2, reverse α). Types I and III cystic ducts were easier to be cannulated with a higher success rate (85.1 and 86.4%, respectively) compared with Type II cystic duct (75%) despite no statistically significant difference. The reasons for the failure of gallbladder cannulation included invisible cyst duct take-off, severe cyst duct stenosis, impacted stones in cyst duct or neck of the gallbladder, sharply angled cyst duct, and markedly dilated cyst duct with the tortuous valves of Heister. Classification of cystic duct patterns was helpful in guiding endoscopic transpapillary gallbladder cannulation.

Colorectal cancer (CRC) is the third most common malignancy and a leading cause of cancer-related death worldwide. GEF-H1 is considered a RhoA-specific guanine nucleotide exchange factor. GEF-H1 upregulation may contribute to cancer cell migration and invasion and tumor progression. However, the expression and role of GEF-H1 in CRC have not yet been elucidated. This study attempted to elucidate how GEF-H1 drives tumor formation, motility, invasion and metastasis in colon cancer (CC). The expression of GEF-H1 in CC tissue microarrays (TMAs) was analyzed by immunohistochemistry (IHC). GEF-H1 was upregulated in CC tissues compared with adjacent non-tumoral tissues. In addition, we found that high GEF-H1 expression correlated with shorter overall survival and distant metastasis. Migration and invasion assays showed that GEF-H1 upregulation increased CC cell motility, invasion and metastasis. In contrast, functional knockdown of GEF-H1 by RNAi rescued the effects caused by GEF-H1 overexpression in CC cells. Overexpression of GEF-H1 re-organized the actin cytoskeleton, with increased punctate paxillin staining and F-actin stress fibers. Furthermore, western blotting showed that RhoA activation triggered by GEF-H1 overexpression caused phosphorylation of its downstream target, MLC2, in CC cells. In summary, the present study revealed that GEF-H1 is upregulated in CC tissues and plays a key role in CC metastasis through the GEF-H1-RhoA-MLC2 signaling pathway.

A 29-year-old woman was admitted to our hospital with jaundice for 1 month. Laboratory findings showed an increased total bilirubin level (4.4 mg/dL) and direct bilirubin level (3.9 mg/dL). Magnetic resonance cholangiopancreatography showed dilated intrahepatics and cystic dilatation of the extrahepatic bile duct (Figure A). Subsequent endoscopic retrograde cholangiopancreatography (ERCP) via the major papilla confirmed a markedly dilated intrahepatic biliary tree with saccular dilation of the common bile duct (Figure B). Also noted was a long common channel (20 mm) with filling of a short Duct of Wirsung branching off into fine regular arborization. After placement of a double-pigtail stent in the bile duct, ERCP via the minor papilla showed a dominant dorsal duct with a normal Duct of Santorini and complete pancreas divisum (Figure C). A single-pigtail pancreatic stent was inserted into the dorsal pancreatic duct (Figure D).The amylase level in the collected bile during ERCP was 1580 U/L, which is higher than the upper limit of serum amylase of 110 U/L. The diagnosis of a type IA choledochal cyst was made, along with an anomalous pancreaticobiliary junction and complete pancreas divisum. The patient ultimately was referred for surgical management of the choledochal cyst.

The risk factors for post-ERCP cholecystitis (PEC) have not been characterized. Hence, this study aimed to identify the potential risk factors for PEC.

Background: To assess the short-term outcomes after endoscopic sphincterotomy (EST) plus endoscopic papillary balloon dilation (EPBD) versus EPBD alone and appropriate balloon dilation time in EPBD alone. Materials and Methods: A total of 413 patients with common bile duct stones (CBDSs) were included in the EST plus EPBD group and 84 were in the EPBD alone group. We retrospectively evaluated the safety and efficacy between EST plus EPBD and EPBD alone group. The patients in EPBD alone group were assigned to dilation time ≥5 minutes group (n=35) and time <5 minutes group (n=49). Further, we preliminarily discussed the influence of balloon dilation time on the procedure-related complications. Results: Compared with EST plus EPBD, the patients in EPBD alone group were younger [56.6 (range: 18 to 95) vs. 65.1 (24 to 92) y; P =0.006], had smaller diameter of the largest stone [10.4 (range: 3 to 20) vs. 12.3 (5 to 30) mm; P <0.001] and were lesser frequently performed with jaundice [22 (26.2%) vs. 189 (45.8%); P =0.001]. The mean duration of postoperative hospital stay in EPBD alone group was significantly shorter than EST plus EPBD group [6.3 (range: 1 to 18) vs. 9.2 (1 to 44) d; P <0.001]. The patients in EPBD alone group had higher risk of post endoscopic retrograde cholangiopancreatography pancreatitis than EST plus EPBD group [11 (13.1%) vs. 22 (5.3%); P =0.009]. Patients in the dilation time <5 minutes group had higher risk to suffer from postoperative pancreatitis than the EST plus EPBD group [9 (18.4%) vs. 22 (5.3%); P =0.002], while patients in the dilation time ≥5 minutes group had less procedure-related hemorrhage than the EST plus EPBD group [0 vs. 36 (8.7%); P =0.047]. Conclusion: Long balloon dilation time in EPBD alone is safe and effective in treating CBDSs.

Objective To assess the safety and efficacy of endoscopic retrograde cholangiopancreatography (ERCP) for children with pancreaticobiliary diseases. Methods Data of children under 14 years old who have underwent ERCP in Nanjing Drum Tower Hospital between September 2007 and August 2016 were reviewed for completion, complications and therapeutic methods. Results A total of 41 children underwent 68 ERCP, including 6(8. 8%) diagnostic and 62(91. 2%) therapeutic procedures. All procedures were performed under deep sedation. Cannulation failed in only 1 child with anomalous junction of pancreaticobiliary duct. The procedure success rate was 98. 5%( 67/68 ) . There were 8 adverse events, including 7 mild post?ERCP pancreatitis and 1 fever. Incidence of adverse event was 11. 8%( 8/68) . There was no such severe adverse event as bleeding, perforation, death, or other anesthesia related adverse event. Thirty?two children ( 78. 0%) had follow?up, ranging from 2 month to 6 years. Children followed lived well with no long?term adverse event. Conclusion ERCP is an effective and safe procedure for the diagnosis and treatment of pancreaticobiliary diseases in children.

Pancreatic duct guidewire placement (PDGP) includes double guidewire technique (DGT) and transpancreatic sphincterotomy (TPS). DGT can be switched to TPS with ease due to the existing guidewire in the pancreatic duct. In this study, we aimed to combine DGT and TPS as a single technique, named sequential PDGP, and to compare its performance with needle knife precut sphincterotomy (NKPS) in treating difficult biliary cannulation (BC). A total of 83 patients with difficult BC were enrolled in this study. Of these, 63 underwent sequential PDGP and 20 underwent NKPS. Cannulation success rate, cannulation time and endoscopic retrograde cholangiopancreatography (ERCP)-related complications were prospectively recorded and compared between the two groups. Successful BC was achieved in 88.9% (56/63) of the patients in the sequential PDGP group compared with 70.0% (14/20) in the NKPS group ( P = 0.095). Cannulation time was 7.49 ± 5.03 min in the sequential PDGP group and 10.60 ± 7.24 min in the NKPS group ( P = 0.086). Post-ERCP pancreatitis occurred in 12.7% of patients in the sequential PDGP group and 10.0% in the NKPS group ( P = 1.000). There was no significant difference in the rates of other complications (bleeding, perforation and cholangitis) between the two groups. Sequential PDGP is a safe and effective alternative method to NKPS in cases of difficult BC. In those with failed standard cannulation, sequential PDGP can be considered when the guidewire is inadvertently inserted into the pancreatic duct or can be placed in the pancreatic duct without difficulty.

OBJECTIVE: Pancreatic duct guidewire placement (PDGP) includes double guidewire technique (DGT) and transpancreatic sphincterotomy (TPS). DGT can be switched to TPS with ease due to the existing guidewire in the pancreatic duct. In this study, we aimed to combine DGT and TPS as a single technique, named sequential PDGP, and to compare its performance with needle knife precut sphincterotomy (NKPS) in treating difficult biliary cannulation (BC).METHODS: A total of 83 patients with difficult BC were enrolled in this study. Of these, 63 underwent sequential PDGP and 20 underwent NKPS. Cannulation success rate, cannulation time and endoscopic retrograde cholangiopancreatography (ERCP)-related complications were prospectively recorded and compared between the two groups.RESULTS: Successful BC was achieved in 88.9% (56/63) of the patients in the sequential PDGP group compared with 70.0% (14/20) in the NKPS group (P = 0.095). Cannulation time was 7.49 +/- 5.03 min in the sequential PDGP group and 10.60 +/- 7.24 min in the NKPS group (P = 0.086). Post-ERCP pancreatitis occurred in 12.7% of patients in the sequential PDGP group and 10.0% in the NKPS group (P = 1.000). There was no significant difference in the rates of other complications (bleeding, perforation and cholangitis) between the two groups.CONCLUSIONS: Sequential PDGP is a safe and effective alternative method to NKPS in cases of difficult BC. In those with failed standard cannulation, sequential PDGP can be consideredwhen the guidewire is inadvertently inserted into the pancreatic duct or can be placed in the pancreatic duct without difficulty.

OBJECTIVE: The aim of this study was to investigate a possible association between hydrogen peroxide and human leukocyte antigen G (HLA-G) in preeclampsia.STUDY DESIGN: We explored the correlation between HLA-G and hydrogen peroxide in preeclamptic (n = 30) and normotensive (n = 30) placentas, which was confirmed by in vitro experiments. Furthermore, RNA interference was used to explore the influence of HLA-G on the proliferation, apoptosis and invasion of HTR-8/SVneo cells when exposed to hydrogen peroxide.RESULTS: We found an inverse correlation between hydrogen peroxide and HLA-G expression in preeclamptic placentas. High levels of hydrogen peroxide could down-regulate HLA-G expression in HTR-8/SVneo. Compared with HLA-G knockdown HTR-8/SVneo, increased proliferation inhibition, higher apoptosis, and decreased cell invasion were found in the cell expressing HLA-G when exposed to hydrogen peroxide.CONCLUSION: Our findings highlight that high levels of hydrogen peroxide can down-regulate HLA-G expression in trophoblasts during preeclampsia and trophoblasts expressing HLA-G are vulnerable to oxidative stress.

Background: hMLH1 is an essential member of DNA mismatch repair (MMR) system, which plays an important role in the recognition and repairment of mismatched bases in DNA replication. hMLH1 gene polymorphism is of significant value in the diagnosis of sporadic colorectal cancer (CRC). Aims: To assess the correlation between hMLH1-93G/A promoter gene polymorphism and CRC. Methods: Three hundred and twelve CRC patients and 300 controls from Jan. 2008 to Oct. 2010 were enrolled in this study. DNA was extracted from the peripheral white blood cells and hMLH1-93G/A promoter gene polymorphism was detected by TaqMan MGB probe fluorescent quantitative PCR. Results: The frequencies of hMLH1-93G/A genotype were not significantly different between CRC patients and controls (P=0.219). Stratified analysis of CRC patients showed that the frequencies of A allele and AA genotype in patients with Dukes C/D stage and lymphatic metastasis were significantly higher than those in patients with Dukes A/B stage (60.5% vs. 48.1%, P=0.004; 39.8% vs. 23.3%, P=0.015) and without lymphatic metastasis (60.5% vs. 49.1%, P=0.010; 39.5% vs. 25.0%, P=0.031). Conclusions: hMLH1-93G/A promoter gene polymorphism has no correlation with the development of CRC, but its A allele and AA genotype are related to the progression of CRC.

OBJECTIVE: To explore the relationship between suppressor genes p16,MGMT,DAPK promoter methylation and clinicopathological parameters of patients with gastric cancer and the sensitivity to chemotherapeutic drugs.METHODS: Fresh tissues from 38 pathologically diagnosed gastric carcinoma patients and normal tissues(n=20) were collected.The methylation-specific PCR was used to detect the promoter methylation of p16,MGMT,DAPK.The chemosensitivity of chemotherapeutic drugs(5-FU,DDP,ADM,GEM,MMC),combined administration or sole-administration,to gastric cancer cell lines from the tissues was tested by MTT assay and the chemosensitivity difference of the methylated group was compared with that of the unmethylated group to the chemotherapy drugs.RESULTS: The rates of methylation of p16,MGMT and DAPK were higher than those in corresponding normal tissues(P0.05).The p16 methylation rates in intestinal type were higher than those in diffuse type gastric cancer,and DAPK methylation was associated with TNM stage(P0.05).p16 methylation was associated with a higher chemosensitivity to 5-FU,5-FU+DDP+ADM and 5-FU+DDP+GEM.DAPK methylation was associated with a lower chemosensitivity to MMC(P0.05).CONCLUSIONS: Promoter hypermethylation of tumor suppressor gene may be major events in the development of gastric carcinoma.Different suppressor genes promoter methylation perhaps has different impact on the chemosensitivity of gastric cancer.