Adjuvant Chemotherapy for Resected Ampulla of Vater Carcinoma: Retrospective Analysis of 646 Patients.

PURPOSE: This study evaluated the efficacy of adjuvant chemotherapy (AC) in patients with resected ampulla of Vater (AoV) carcinoma. MATERIALS AND METHODS: Data from 646 patients who underwent surgical resection at Asan Medical Center between 2000 and 2017 were retrospectively reviewed. RESULTS: The median age of the patients was 62 years, and 54.2% were male. Patients were classified into AC group (n=165, 25.5%) and no AC group (n=481, 74.5%). With a median follow-up duration of 88 months, in patients with stage I, II, III, median recurrence-free survival (RFS) was not reached, 44 months, and 15 months, respectively, and the median overall survival (OS) were not reached, 88 months and 35 months, respectively. Despite no statistical significance, RFS and OS were better in stage II patients with AC than in those without AC (median RFS, 151 months vs. 38 months; p=0.156 and median OS, 153 months vs. 74 months; p=0.299). In multivariate analysis for RFS and OS, TNM stage, R1 resection status, presence of lymphovascular invasion, and perineural invasion remained significant factors, whereas AC (hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.54 to 1.00; p=0.052) was marginally related with RFS. After propensity score matching in only stage II/III patients, RFS and OS with AC were numerically longer than those without AC (HR, 0.80; 95% CI, 0.60 to 1.06; p=0.116 and HR, 0.77; 95% CI, 0.56 to 1.06; p=0.111). CONCLUSION: AC with fluoropyrimidine did not improve survival of patients with resected AoV carcinoma. However, multivariate analysis with prognostic factors showed a marginally significant survival benefit with AC.

Alterations of the Bile Microbiome in Recurrent Common Bile Duct Stone.

OBJECTIVE: Common bile duct stone (CBDS) recurrence is associated with bile microbial structure. This study explored the structure of bile microbiome in patients with recurrent CBDS, and its relationship with the recurrence of CBDS. METHODS: Patients with recurrent CBDS (recurrence group) and controls without CBDS (control group) requiring endoscopic retrograde cholangiopancreatography (ERCP) were prospectively included. The control group was noncholelithiasis patients, mainly including benign and malignant biliary stenosis. Bile samples were collected, and bile microbiome structure was analyzed by the 16S rRNA encoding gene (V3-V4). RESULTS: A total of 27 patients in the recurrence group and 19 patients in the control group were included. The diversity of bile microbiome in the recurrence group was significantly lower than that in the control group (Shannon index: 2.285 vs. 5.612, P = 0.001). In terms of bile microbial distribution, patients with recurrent CBDS had significantly higher Proteobacteria (86.72% vs. 64.92%, P = 0.037), while Bacteroidetes (3.16% vs. 8.53%, P = 0.001) and Actinobacteria (0.29% vs. 6.74%, P = 0.001) are significantly lower compared with the control group at the phylum level. At the genus level, the recurrence group was mainly the Escherichia, and there was a variety of more evenly distributed microbiome in the control group, with significant differences between the two groups. CONCLUSION: The diversity of bile microbiome in patients with recurrent CBDS is lower. Patients with recurrent CBDS may have bile microbial imbalance, which may be related to the repeated formation of CBDS.

Approaches to Biopsy and Resection Specimens from the Ampulla.

The ampulla of Vater gives rise to a versatile group of cancers of mixed/hybrid histologic phenotype. Ampullary carcinomas (ACs) are most frequently intestinal or pancreatobiliary adenocarcinomas but other subtypes, such as medullary, mucinous, or signet ring/poorly cohesive cell carcinoma, may be encountered. Ampullary cancer can also be subclassified based on immunohistochemical features, however these classification systems fail to show robust prognostic reliability. More recently, the molecular landscape of AC has been uncovered, and has been shown to have prognostic and predictive significance. In this article, the site-specific, histologic, and genetic characteristics of ampullary carcinoma and its precursor lesions are discussed.

Does periampullary diverticulum affect ERCP cannulation and post-procedure complications? an up-to-date meta-analysis.

Research conclusions differ on the impact of periampullary diverticulum (PAD) on endoscopic retrograde cholangiopancreatography (ERCP). An up-to-date meta-analysis evaluated the role of PAD in ERCP, especially in terms of cannulation failure and early complications. A comprehensive literature search was performed. All statistical analyses were carried out with the Review Manager 5.3 software. Horizontal lines represented a 95% confidence interval (CI) and the area of each square in forest plots. Twenty-six studies including 23 826 patients with or without PAD who underwent ERCP were evaluated. PAD was associated with an increase in the overall cannulation failure rate (RR=1.46, 95% CI: 1.27-1.67; p<.00001), but in the subgroup of studies performed post-2000, PAD was irrelevant to cannulation failure (RR=1.16, 95% CI: 0.96-1.41; p=0.12). In overall analyses, PAD was also associated with a high risk of ERCP-related pancreatitis (RR=1.32, 95% CI: 1.10-1.59; p=0.003), perforation (RR=1.73, 95% CI: 1.06-2.82; p=0.030), and bleeding (RR=1.48, 95% CI: 1.13-1.93; p=0.005). The presence of PAD increased the overall cannulation failure rate, but not the rate post-2000. PAD also affected the occurrence of early pancreatitis, perforation, and bleeding.

Histopathologic Predictors of Survival and Recurrence in Resected Ampullary Adenocarcinoma: International Multicenter Cohort Study.

OBJECTIVE: The aim of the study was to define histopathologic characteristics that independently predict overall survival (OS) and disease-free survival (DFS), in patients who underwent resection of an ampullary adenocarcinoma with curative intent. SUMMARY BACKGROUND DATA: A broad range of survival rates have been described for adenocarcinoma of the ampulla of Vater, presumably due to morphological heterogeneity which is a result of the different epitheliums ampullary adenocarcinoma can arise from (intestinal or pancreaticobiliary). Large series with homogenous patient selection are scarce. METHODS: A retrospective multicenter cohort analysis of patients who underwent pancreatoduodenectomy for ampullary adenocarcinoma in 9 European tertiary referral centers between February 2006 and December 2017 was performed. Collected data included demographics, histopathologic details, survival, and recurrence. OS and DFS analyses were performed using Kaplan-Meier curves and Cox proportional hazard models. RESULTS: Overall, 887 patients were included, with a mean age of 66 ±â€Š10 years. The median OS was 64 months with 1-, 3-, 5-, and 10-year OS rates of 89%, 63%, 52%, and 37%, respectively. Histopathologic subtype, differentiation grade, lymphovascular invasion, perineural invasion, T-stage, N-stage, resection margin, and adjuvant chemotherapy were correlated with OS and DFS. N-stage (HR = 3.30 [2.09-5.21]), perineural invasion (HR = 1.50 [1.01-2.23]), and adjuvant chemotherapy (HR = 0.69 [0.48-0.97]) were independent predictors of OS in multivariable analysis, whereas DFS was only adversely predicted by N-stage (HR = 2.65 [1.65-4.27]). CONCLUSIONS: Independent predictors of OS in resected ampullary cancer were N-stage, perineural invasion, and adjuvant chemotherapy. N-stage was the only predictor of DFS. These findings improve predicting survival and recurrence after resection of ampullary adenocarcinoma.

Transcholecystic approach for distal common bile duct stricture in a non-dilated biliary system: an alternative route.

A 63-year-old patient was admitted to intensive treatment unit with biliary sepsis due to a small distal common bile duct stone. Endoscopic retrograde cholangiopancreatography was initially attempted for insertion of a biliary stent but failed due to the presence of a periampullary diverticulum. Referral to interventional radiology for percutaneous drainage was considered the next alternative even though there was no dilatation of intrahepatic ducts. Due to complete absence of intrahepatic duct dilatation, the traditional percutaneous transhepatic route was considered rather challenging. An alternative percutaneous approach via the gallbladder and subsequent catheterisation of the duodenum via the distal common bile duct was successfully performed instead without complication. We would like to describe this technique as an alternative option for drainage of the non-dilated biliary system in patients with sepsis.

Pyogenic granuloma of the ampulla of Vater: unexpected cause of gastrointestinal bleeding.

We describe the case of a previously healthy 8-year-old girl presenting with a 1-year history of iron deficiency anemia. There was no report of hematemesis, abdominal pain or melena. Laboratory work-up excluded iron malabsorption as the underlying cause. Therefore, endoscopic evaluation was performed to exclude gastrointestinal blood loss, which revealed the presence of a 7 mm reddish lesion located within the ampulla of Vater. Capsule endoscopy excluded alternative diagnoses and concomitant lesions. Histopathological examination confirmed the diagnosis of pyogenic granuloma. The young age of the child and the benign nature of this lesion along with the absence of complications favored conservative management. Pyogenic granuloma is a benign vascular lesion that presents as a polypoid red mass. In the gastrointestinal tract, it is a rare condition and occurs more commonly in the elderly. The most common sites are the small intestine, esophagus, and colon, but they can occur throughout the entire gastrointestinal tract with a propensity to bleed that may cause iron deficiency anemia. In pediatric age patients, there are few reports of gastrointestinal pyogenic granulomas, most of which occur in the colon and rectum. Its identification and location in the ampulla of Vater is an exceptional finding.

Common bile duct dilation after bariatric surgery.

BACKGROUND: Biliary dilation suggests obstruction and prompts further work up. Our experience with endoscopic ultrasound and endoscopic retrograde cholangiopancreatography in the symptomatic post-bariatric surgery population revealed many patients with radiographically dilated bile ducts, but endoscopically normal studies. It is unclear if this finding is phenomenological or an effect of surgery. Additionally, it is unknown whether the type of bariatric surgery alters biliary pathophysiology. Thus, we studied whether a change occurs in biliary diameter following Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG). METHODS: A single-center retrospective study assessing biliary diameter before and after RYGB or SG based on radiographic imaging. All adult patients undergoing RYGB or SG from January 2010 to December 2013 who had imaging studies before and > 3 months after surgery were included. Those with known obstructive etiologies and those without post-operative imaging were excluded. Common bile duct (CBD) diameter was re-read by a radiologist at the same location in the CBD for pre- and post-operative imaging. Baseline clinical factors and cholecystectomy status were collected. RESULTS: 269 patients met inclusion criteria (193 RYGB;76 SG). Between the groups, there were no significant differences in pre-operative characteristics. Average time from surgery to repeat imaging was 24.1 months. After adjusting for pre-operative factors, subjects who underwent an RYGB had an increase in CBD diameter of 1.4 mm (95% CI 0.096, 0.18), which was greater than the change following SG 0.5 mm(95% CI - 0.007, 0.11). The magnitude of this change did not depend on prior cholecystectomy in the RYGB cohort. Within the SG group, for patients without a prior cholecystectomy, there was a significant increase in post-operative CBD diameter of 0.8 mm(95% CI 0.02, 0.14). CONCLUSION: Bariatric surgery results in CBD dilation, with changes more pronounced after RYGB. Biliary dilation occurs irrespective of cholecystectomy status. Further work is necessary to determine the cause and clinical implications of this phenomenon.

Risk Factors and Nomogram for Common Bile Duct Stricture in Chronic Pancreatitis: A Cohort of 2153 Patients.

GOALS: To identify the risk factors and develop nomograms for common bile duct (CBD) stricture in chronic pancreatitis (CP) patients. BACKGROUND: CBD stricture is a common complication in CP and has a variable clinical presentation ranging from asymptomatic to overt jaundice and cholangitis. STUDY: Patients with CP admitted to Changhai Hospital (Shanghai, China) from January 2000 to December 2013 were enrolled. Cumulative rates of CBD stricture after onset and diagnosis of CP were calculated. Patients were randomly assigned, in a 2:1 ratio, to the training and validation cohort. On the basis of the training cohort, risk factors for CBD stricture and symptomatic CBD stricture were identified through Cox proportional hazards regression model, and nomograms was developed, respectively. Internal and external validations were performed based on the training and validation cohort, respectively. RESULTS: With a total of 2153 patients, the median duration of follow-up was 7.0 years. CBD strictures were detected in 340 (15.8%) patients, whereas 159 of them were symptomatic. Male gender, age at onset of CP, smoking, body mass index, and morphology of main pancreatic duct were identified risk factors for CBD stricture development. Age at onset of CP, body mass index, and type of pain were identified risk factors for symptomatic CBD stricture development. Both nomograms achieved good concordance indexes with well-fitted calibration curves. CONCLUSIONS: The nomogram achieved an individualized prediction of symptomatic CBD stricture development in CP patients. It may help the early diagnosis and intervention of symptomatic CBD stricture and reduce the rates of severe adverse events.

Perioperative outcomes of laparoscopic pancreaticoduodenectomy for benign and borderline malignant periampullary disease compared to open pancreaticoduodenectomy.

PURPOSE: The objective of this study was to compare perioperative outcomes between laparoscopic pancreaticoduodenectomy (LPD) and open pancreaticoduodenectomy (OPD) for benign and borderline malignant periampullary diseases. METHODS: Of 107 pancreaticoduodenectomy cases for non-malignant diseases from March 1993 to July 2017, 76 patients underwent OPD and 31 patients received LPD. To adjust for baseline differences and selection bias, operative outcomes and complications were compared after propensity score matching (PSM). RESULTS: After 1:1 PSM, well-matched 31 patients in each group were evaluated. As a result, significant differences were observed between two groups in some aspects: mean operative time (LPD 426.8 ± 98.58 vs. OPD 355.03 ± 100.0 min, p = 0.031), estimated blood loss (LPD 477.42 ± 374.80 vs. OPD 800.00 ± 531.35 ml, p = 0.008), and postoperative hospital stay (LPD 14.74 ± 5.40 vs. OPD 23.81 ± 11.63 days, p < 0.001). The average visual analogue scores for pain observed from patients in LPD group on postoperative day (POD) 1 (4.23 ± 1.83 vs. 5.55 ± 2.50, p = 0.021) and POD 3 (3.32 ± 1.66 vs. 5.26 ± 2.76, p = 0.002) were significantly less than those from patients in OPD group, as well. There were no significant differences between groups about major complications including the rate of postoperative pancreatic fistula. CONCLUSIONS: LPD is a safe procedure and provides less postoperative pain and the shortening length of hospitalization. LPD may serve the feasible alternative approach for benign and borderline malignant periampullary disease.

Hypothermic oxygenated machine perfusion reduces bile duct reperfusion injury after transplantation of donation after circulatory death livers.

Dual hypothermic oxygenated machine perfusion (DHOPE) of the liver has been advocated as a method to reduce ischemia/reperfusion injury (IRI). This study aimed to determine whether DHOPE reduces IRI of the bile ducts in donation after circulatory death (DCD) liver transplantation. In a recently performed phase 1 trial, 10 DCD livers were preserved with DHOPE after static cold storage (SCS; www.trialregister.nl NTR4493). Bile duct biopsies were obtained at the end of SCS (before DHOPE; baseline) and after graft reperfusion in the recipient. Histological severity of biliary injury was graded according to an established semiquantitative grading system. Twenty liver transplantations using DCD livers not preserved with DHOPE served as controls. Baseline characteristics and the degree of bile duct injury at baseline (end of SCS) were similar between both groups. In controls, the degree of stroma necrosis (P = 0.002) and injury of the deep peribiliary glands (PBG; P = 0.02) increased after reperfusion compared with baseline. In contrast, in DHOPE-preserved livers, the degree of bile duct injury did not increase after reperfusion. Moreover, there was less injury of deep PBG (P = 0.04) after reperfusion in the DHOPE group compared with controls. In conclusion, this study suggests that DHOPE reduces IRI of bile ducts after DCD liver transplantation. Liver Transplantation 24 655-664 2018 AASLD.

Massive Biliary Dilation after Roux-en-Y Gastric Bypass: Is it Ampullary Achalasia?

BACKGROUND: This series of patients with a history of Roux-en-Y gastric bypass (RYGB) and cholecystectomy presented with symptoms consistent with obstructive biliary disease and massive biliary dilation of ≥15 mm, suggesting a structural cause. Findings from laparoscopic-assisted transgastric (TG) ERCP were a normal-appearing ampulla without structural lesions or stones, suggesting a functional cause instead. STUDY DESIGN: Patients who underwent TGERCP from January 2008 to October 2016 and had a surgical history of RYGB and cholecystectomy were identified from an institutional database. Inclusion criteria was biliary dilation ≥15 mm, age 18 years or older, and no explanatory obstructive pathology. RESULTS: Nine female patients met the inclusion criteria. At time of TGERCP, their mean age was 53.9 years, mean BMI was 32.5 kg/m2, mean bile duct diameter was 18.1 mm, and all patients experienced abdominal pain. Six patients (66.7%) presented with abnormal liver enzymes, 5 (55.6%) with nausea and/or vomiting, and 4 (44.4%) with earlier episode(s) of acute pancreatitis. Each patient had a normal-appearing papilla of Vater without stones or strictures at the time of TGERCP, with 8 (88.9%) patients experiencing cessation of abdominal pain after biliary sphincterotomy. CONCLUSIONS: This cohort of patients with a history of RYGB and cholecystectomy presented with massively dilated biliary trees lacking an obstructive disease process and experienced immediate symptom improvement after sphincterotomy. Their surgical history predisposed them to vagal nerve injury, leading to denervation of the sphincter of Oddi, and resulting in tonic contraction of the ampulla, that is, ampullary achalasia.