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.

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.

The presence of periampullary diverticulum increased the complications of endoscopic retrograde cholangiopancreatography.

BACKGROUND: The use of needle-knife fistulotomy technique in patient with periampullary diverticula (PAD) for biliary duct cannulation may lead to risk of complications. The present study aimed to investigate the association between PAD and the complications of endoscopic retrograde cholangiopancreatography (ERCP), unsuccessful cannulation rates and to determine the rates of cannulation complications using sphincterotomy and needle-knife fistulotomy. MATERIALS AND METHODS: The ERCP procedures were held in Gastroenterology Endoscopy Unit between September 2015 and October 2016 and were retrospectively evaluated. The patients were divided into two groups, a PAD group and a non-PAD group. These groups were compared regarding demographic characteristics, ERCP complications and mortality. RESULTS: A total of 827 patients fulfilling the criteria for ERCP were enrolled in the study. Of 827 patients, 164 had PAD and 663 did not have PAD (non-PAD). The success rate of cannulation was 98.8% in patients with PAD and 98.6% in patients without PAD. There was no statistical difference of cannulation types with sphincterotomy and with needle-knife fistulotomy between the two groups. Mean baseline number of guide wire cannulation attempts was 1.96±0.20 in PAD group. No complications were observed in PAD patients treated with needle-knife fistulotomy. ERCP-related complications rates (bleeding, pancreatitis, and perforation) were higher in the PAD group (P=0.007). CONCLUSION: In conclusion, there is a strong association between PAD and higher rates of cannulation complications, independent of cannulation technique. In certain situations, and in the hands of experienced endoscopists, needle-knife fistulotomy might be a feasible option for successful biliary cannulation in certain patients with PAD.

Frey procedure combined with biliary diversion in chronic pancreatitis.

BACKGROUND: The Frey procedure has become the standard operative treatment in chronic painful pancreatitis. Biliary diversion could be combined when associated with common bile duct obstruction. The aim of the present study was to evaluate the impact of the type of biliary diversion combined with the Frey procedure on late morbidity. METHODS: The data from consecutive patients undergoing the Frey procedure and having a minimum follow-up of 2 years were extracted from a maintained prospective database. The mean endpoint was the rate of secondary biliary stricture after the Frey procedure combined with biliary diversion (bilioenteric anastomosis or common bile duct reinsertion in the resection cavity). RESULTS: Between 2006 and 2013, 55 consecutive patients underwent the Frey procedure. Twenty-nine patients had common bile duct obstruction (52.7%). The technique of biliary diversion resulted in bilioenteric anastomosis in 19 patients (65.5%) and common bile duct reinsertion in 10 patients (34.5%). Preoperative characteristics and early surgical outcomes were comparable. Pain control was similar. There was significantly more secondary biliary stricture after common bile duct reinsertion than after bilioenteric anastomosis (60% vs 11%, P = .008). CONCLUSION: Combined bilioenteric anastomosis during the Frey procedure is an efficient technique for treating common bile duct obstruction that complicates chronic painful pancreatitis. Bilioenteric anastomosis was associated with less secondary biliary stricture than common bile duct reinsertion in the pancreatic resection cavity.

Management of ampullary neoplasms: A tailored approach between endoscopy and surgery.

Ampullary neoplasms, although rare, present distinctive clinical and pathological features from other neoplastic lesions of the periampullary region. No specific guidelines about their management are available, and they are often assimilated either to biliary tract or to pancreatic carcinomas. Due to their location, they tend to become symptomatic at an earlier stage compared to pancreatic malignancies. This behaviour results in a higher resectability rate at diagnosis. From a pathological point of view they arise in a zone of transition between two different epithelia, and, according to their origin, may be divided into pancreatobiliary or intestinal type. This classification has a substantial impact on prognosis. In most cases, pancreaticoduodenectomy represents the treatment of choice when there is an overt or highly suspicious malignant behaviour. The rate of potentially curative resection is as high as 90% and in high-volume centres an acceptable rate of complications is reported. In selected situations less invasive approaches, such as ampullectomy, have been advocated, although there are some concerns mainly because of a higher recurrence rate associated with limited resections for invasive carcinomas. Importantly, these methods have the drawback of not including an appropriate lymphadenectomy, while nodal involvement has been shown to be frequently present also in apparently low-risk carcinomas. Endoscopic ampullectomy is now the procedure of choice in case of low up to high-grade dysplasia providing a proper assessment of the T status by endoscopic ultrasound. In the present paper the evidence currently available is reviewed, with the aim of offering an updated framework for diagnosis and management of this specific type of disease.

Periampullary choledochal diverticula are not choledochal cysts.

BACKGROUND: Choledochal cysts (CC) are rare, congenital anomalies of the biliary tree, associated with the development of biliary malignancies. Small periampullary choledochal diverticula (PCD) are a previously unreported type of biliary anomaly found primarily at ERCP. OBJECTIVE: The aim of this study was to assess whether PCD are congenital or acquired lesions by comparing the clinical presentation, management, and risk of malignancy between patients with PCD and CC. DESIGN: Retrospective analysis of a medical center database. SETTING: Academic tertiary referral center. PATIENTS: Over the study period, data regarding 16 patients with PCD were identified and compared with that of 118 patients with CC. INTERVENTION: Retrospective review of ERCP, surgical pathology, billings, and a diagnostic imaging database from our institution from 1985 to 2009 was done. MAIN OUTCOME MEASUREMENTS: Clinical presentation, investigations, management strategies, complication rates, and long-term outcomes were compared in patients with classic CC and PCD over the same time period. RESULTS: Patients with PCD were less likely to be female (50% vs 81%), older aged (mean 68 vs 28 years), to complain of abdominal pain (88% vs 68%), and were less likely to present with jaundice (0% vs 32%) (P<.05 for all pairs). Patients with PCD also were noted to have lower frequency of anomalous pancreatobiliary junction (0% vs 83%) and biliary neoplasia (0% vs 5%) and more likely to have sphincter of Oddi dysfunction (63% vs 1%). Management of PCD was done with ERCP in 87% of cases and with surgery in 0% of cases, whereas management of CC was done with ERCP in 20% of cases and surgery in 80% of cases (P<.001). Long-term complications at a mean follow-up of 3.7 years after therapy were more common in CC (40% vs 6%, P=.02). LIMITATIONS: Retrospective study. Lack of structured follow up. CONCLUSION: Small, periampullary, choledochal diverticula are a newly reported, likely acquired anomaly of the biliary tract that are frequently associated with sphincter of Oddi dysfunction and may be secondary to biliary hypertension. These acquired lesions should not be classified as CC.

Trend towards primary closure following laparoscopic exploration of the common bile duct.

INTRODUCTION: The aim of this study was the assessment of patient outcome, peri-operative complications, length of stay and duration of operation after laparoscopic primary closure of the common bile duct (CBD) compared with choledochotomy with T-tube drainage and trans-cystic exploration. PATIENTS AND METHODS: Analysis of prospectively collected data on 71 explorations of the common bile duct between July 2001 and March 2006. RESULTS: A total of 71 patients had exploration of the CBD. Within this group, 12 were referred after failed endoscopic retro-grade cholangiopancreatography (ERCP). The methods of exploration included trans-cystic (9 cases), choledochotomy with T-tube (12), and choledochotomy with primary closure (50). CBD stones were found in 66 patients. In the remaining cases, we found a stricture in 1, debris in 2, and dilatation of the CBD without a stone in 2. There were 5 conversions to open technique and 3 patients required postoperative ERCP (1 with permanent stenting). Peri-operative complications included T-tube (3), primary closure group (9), and trans-cystic (0). There was no statistical significant difference (Chi-square test, P = 0.296) between the groups. There was a trend towards a shorter length of stay in the primary closure group as compared with the trans-cystic and T-tube groups of 4.16, 4.44, and 6.33 days, respectively. However, it did not reach statistical significance (one-way analysis of variance with Boneferroni correction, mean difference between groups 1.89, 0.28, 2,17, statistical significance at P < 0.05). The shortest operating time was in the primary closure group (95.92 min) which was statistically significant (P < 0.001). We did not use a biliary drain in the last 48 patients. CONCLUSIONS: Primary laparoscopic closure of the CBD is safe and results in a reduction in operating time. Choledochoscopy ensures clearance of the CBD and eliminates the need for T-tube.

Endoscopic sphincterotomy for acute relapsing pancreatitis associated with periampullary diverticula: a long-term follow-up.

BACKGROUND AND STUDY AIMS: Periampullary diverticula (PAD) are extraluminal outpouchings of the duodenum arising within a radius of 2-3 cm from the ampulla of Vater. Data concerning the association of PAD with biliopancreatic disease are inconsistent, but an association between acute pancreatitis and PAD has been reported. The aim of this retrospective study was to evaluate the outcome of endoscopic sphincterotomy (ES) in a Greek cohort of patients with acute relapsing pancreatitis associated with PAD. PATIENTS AND METHODS: A total of 344 patients who had undergone ERCP between 1994 and 2005 for investigation of acute pancreatitis were retrospectively entered into a database. Of these patients, 11 (3.19% ; median age: 69 years; range: 58-78; 3 men, 8 women) were found to have acute relapsing pancreatitis associated with PAD. All patients underwent ES and were followed for new episodes of acute pancreatitis or other complications. RESULTS: No further episodes of acute pancreatitis occurred after ES, during a long-term follow-up (median: 4.3 years, range: 1.9-10.4). Two patients (18.2%) presented post-procedure mild pancreatitis and one patient (9.1%) post-ES stenosis with two small common bile duct stones and was treated with ES and extraction of stones. CONCLUSION: ES is the treatment of choice for patients with acute relapsing pancreatitis associated with PAD.

Biliary stenting versus bypass surgery for the palliation of malignant distal bile duct obstruction: a meta-analysis.

The objective of this analysis is to compare endoscopic stenting with surgical bypass in patients with unresectable, malignant, distal common bile duct obstruction using the technique of meta-analysis. The inclusion criteria for the studies were randomized patient assignment, publication in the English language, 20 or more patients per group, all patients followed up until death, and follow-up and complications reported in an equivalent way for both treatment arms. Data extraction was performed independently by 2 of the authors. The number of treatment failures, serious complications, requirement for additional treatment sessions, and 30-day mortality were extracted. Three existing trials met the inclusion criteria, all of which compared surgery with the use of plastic stents. There were no studies identified that used metallic expandable stents. For the rate of treatment failure and serious complications, the odds ratios (ORs) of the 3 trials were heterogeneous, and no summary ORs were calculated. More treatment sessions were required after stent placement than after surgery, and a common OR was estimated to be 7.23 (95% confidence interval [CI], 3.73 to 13.98). Thirty-day mortality was not significantly different (OR = 0.522; 95% CI, 0.263 to 1.036). Although surgical bypass required fewer additional treatment sessions, existing data do not allow a definitive conclusion on which treatment is preferable. A larger randomized controlled trial using newer metallic stents and proper quality-of-life instruments is required.

Open biliary tract surgery: multivariate analysis of factors affecting mortality.

BACKGROUND/AIM: The overall mortality rate in patients undergoing supraduodenal choledochotomy for benign biliary tract disease is around 3%. The aim of this study is to identify and quantify factors affecting the mortality in a group of patients undergoing open common bile duct exploration for benign biliary disease. METHODS: Patients (n = 158) who underwent common bile duct exploration during a 5-year period in a teaching hospital were retrospectively reviewed. RESULTS: Univariate and multivariate statistical analyses were performed. The former identified four statistically significant variables: age (p < 0.001), acute cholangitis on admission (p < 0. 001), heart disease (p < 0.05), and a dilated common bile duct on preoperative ultrasound scan (p < 0.05). Multivariate analysis identified three variables which independently increased operative mortality: age (p = 0.05), heart disease (p = 0.03), and cholangitis (p = 0.008). The latter was associated with the greatest operative mortality, since it increased almost eight times the risk to die after surgical intervention. CONCLUSION: We conclude that an adequate perioperative cardiovascular management may be important in order to improve surgical outcome. Appropriate antibiotic prophylaxis and subsequent treatment after routine operative bile cultures may reduce septic complications and mortality. Finally, an alternative procedure, such as endoscopic sphincterotomy, may be indicated in high-risk patients in order to drain the common bile duct preoperatively and to decrease the risk of unresponsive biliary sepsis.

Biliary stenting with a prototype expandable Teflon endoprosthesis.

BACKGROUND AND STUDY AIMS: A new balloon-expandable Teflon endoprosthesis was developed for endoscopic placement in the biliary tree. After deployment to its maximum diameter the stent is hardened by exposure to UV light. We present our preliminary results with a prototype 18 Fr prosthesis. PATIENTS AND METHODS: Three patients with a distal common bile duct obstruction due to unresectable pancreatic head carcinoma were treated with this stent. Insertion of the stent was the only palliative procedure. Patients were followed up until stent dysfunction or death. RESULTS: Stent placement was successful in all patients and no procedural complications occurred. Distal migration occurred in one patient, clogging of the stent after 149 days in another. CONCLUSION: In patients with a malignant biliary stricture this newly developed expandable endoprosthesis is effective in relieving obstructive jaundice. The technique has potential advantages over placement of current expandable metal mesh stents.

Predictive factors for survival of patients with inoperable malignant distal biliary strictures: a practical management guideline.

BACKGROUND: Stenting is the treatment of choice for inoperable malignant strictures of the common bile duct. Criteria for the choice of stents (plastic versus metallic) remain controversial because predicting survival is difficult. AIMS: To define prognostic factors in order to improve the cost effectiveness of endoscopic palliation. PATIENTS: One hundred and one patients were included in a prospective trial. Seven prognostic variables for survival were analysed (age, sex, bilirubinaemia, weight loss, presence of liver metastases, and tumour histology and size). All patients were followed until death or at least one year after inclusion. By the end of the study, 81 (80.2%) patients had died. RESULTS: In univariate analysis, the variables associated with survival were weight loss (p < 0.05) and tumour size (p < 0.01). By multivariate analysis, tumour size was the only independent prognostic factor (p < 0.05). A threshold of 30 mm at diagnosis distinguished two survival profiles: the median survival of patients with a tumour greater than 30 mm was 3.2 months, whereas it was 6.6 months for patients with a tumour less than 30 mm (p < 0.001). CONCLUSIONS: A practical strategy could be based on tumour size at diagnosis: a metal stent should be systematically chosen for patients with an inoperable tumour smaller than 30 mm, while larger tumours are efficiently palliated by a plastic stent.

Common bile duct obstruction due to malignancy: treatment with plastic versus metal stents.

PURPOSE: To compare the clinical efficacy and treatment costs of plastic versus metal biliary stents. MATERIALS AND METHODS: In a randomized trial, 101 patients with malignant common bile duct obstruction underwent transhepatic stent implantation and were followed up until death. Patients were stratified into risk and nonrisk groups. Forty-nine patients received 12-F plastic stents, and 52 received expandable metal stents. Plastic endoprostheses were placed in a two-step procedure; metal stent, in a single procedure. Kaplan-Meier analyses were used to compare patient survival and stent patency rates. RESULTS: The 30-day mortality rate was significantly lower for metal stents (five of 52 [10%]) than plastic stents (12 of 49 [24%]; P = .05). The obstruction rate was 19% (10 of 52; median patency, 272 days) for metal stents and 27% for plastic stents (13 of 49; median patency, 96 days; P < .01). Median time until death or obstruction was longer for metal stents (122 vs 81 days; P < .01). Placement of metal stents was associated with shorter hospital stay (10 vs 21 days; P < .01) and lower cost ($7,542 vs $12,129; P < .01). CONCLUSION: Use of self-expanding metal stents appears to show substantial benefits for patients and to be cost-effective.

[The results of duodenopancreatectomy in periampullar pathology]. / Resultados de la duodenopancreatectomía cefálica en patología periampular.

OBJECTIVE: To examine mortality and morbidity rates after pancreaticoduodenectomy in 69 consecutive patients with periampullar disease operated on between 1985 and 1993 at the Reina Sofía Hospital, Córdoba, Spain. PATIENTS: Fifty five patients (79.7%) had malignant neoplasm whereas 14 (20.3%) had benign disease. In 58 patients a Whipple procedure was performed; pancreaticoduodenectomy with preservation of the pylorus (Traverso-Longmire) was performed in the remaining 11 patients. RESULTS: Eighteen patients (26%) had postoperative complications; peritoneal bleeding (1); biliary fistula (3); pancreatic fistula (4); digestive fistula (2); and pancreatitis (2). Two patients with pancreatic and duodenal carcinoma died. Thirteen patients were readmitted: 3 bleeding episodes in anastomotic ulcer; 3 hepaticojejunostomy obstruction; and the remaining 6 patients with tumor recurrence. CONCLUSIONS: In our experience duodenopancreatectomy was a safe procedure in periampullar disease, with an acceptable morbidity and mortality rates.

[Transduodenal papillosphincteroplasty in the treatment of choledocholithiasis and benign stenosis of the terminal choledochus and papilla Vateri]. / Transduodenalnata papilosfinkteroplastika v lechenieto na choledokholitiazata i dobrokachestvenite stesneniia na terminalniia kholedokh i papilla Vateri.

The article contains data form the surgical treatment of 297 patients with choledocholithiasis and benign stenosis of choledochus terminal and papilla Vateri, treated in the Academy of Medicine-General and Operative Surgery within the period 1983-1992. The data relate to 59 patients with biliodigestive anastomosis, 114 patients with choledochotomy and T-drainage (Kehr drainage) and 124 patients with transduodenal papillosphincteroplastica. The postoperative lethality in the general series of patients was 3.03%, for the patients with transduodenal papillosphincteroplastica--0.8%. The serious complications in the postoperative period in the cases of papillosphincteroplastica represent 0%, while the excellent and very good results in the distant period--95.16%. The authors state the precise moments of the surgical techniques in the cases of transduodenal papillosphincteroplastica and their importance for the postoperative results. The authors specify the indications and the contraindications for carrying out the different surgical and endoscopic procedures.

[Transduodenal papillosphincteroplasty in the treatment of benign diseases of the terminal choledochus and papilla Vateri]. / Transduodenalnata papilosfinkteroplastika v lechenieto na dobrokachestvenite zaboliavaniia na terminalniia kholedokh i papilla Vateri.

The modern state of the problem and the indications and contraindications for performing transduodenal papillosphincteroplasty are discussed. Personal experience is recorded with 67 transduodenal papillosphincteroplasties, performed for the period 1983-1989, against the background of 1091 operations on the hepatobiliary system, 171 of them on the extrahepatic bile ducts, performed during the same period. Proceeding from their own experience and from available data in the literature, the authors analyse and evaluate the surgical and nonsurgical methods of treatment of benign diseases of the terminal common bile duct and the duodenal papilla, manifested by stenotic lesions. The most important indications and contraindications for applying the different therapeutic methods are adduced. Remarks are made on the technique, which is of major practical importance and the respective conclusion is substantiated.

[Is hyperbilirubinemia a risk factor in biliary surgery?]. / L'iperbilirubinemia è un fattore di rischio in chirurgia biliare?

The Authors, by means of a retrospective analysis of the patients operated on for biliary tract diseases (obstructive or not), evaluated the role of the serum bilirubin level as risk factor in this type of surgery. They show data about 474 patients divided into two groups on the basis of serum bilirubin level, examine mortality and morbidity rates also as a function of the age and analyze the results with the chi-square test. The Authors conclude that the serum bilirubin level have no statistically significant influence on the mortality and the morbidity rates, while elderly age results to be a risk factor.

Benign disease of the common bile duct.

The incidence of common bile duct (CBD) pathology in a group of patients with benign biliary disease (n = 505) was found to be 23.2 per cent. The spectrum included 111 patients (90.2 per cent) with CBD stones, 37 of whom (33.3 per cent) had no symptoms or findings pre-operatively indicating CBD involvement. Five patients had papillary stenosis, three had postoperative CBD strictures, one had a choledochal cyst and one had an external biliary fistula. Of the 100 CBDs measuring more than 10 mm in diameter, 90 harboured calculi. In the remaining 23 CBDs measuring less than 10 mm, calculi were present in 21. The presence of CBD calculi was demonstrated by intra-operative cholangiography in 49 patients. In the remaining patients (n = 74), the diagnosis of CBD pathology was made either by percutaneous transhepatic cholangiography, endoscopic retrograde cholangio-pancreatography, T-tube cholangiography or peroperative palpation. The surgical procedures performed included choledochotomy and T-tube drainage (n = 74), transduodenal sphincteroplasty (n = 27) and choledochoduodenostomy (n = 18). The overall mortality and morbidity of CBD exploration was 3.3 per cent and 24.4 per cent respectively, which was significantly greater than that for cholecystectomy alone (0.3 per cent and 8.6 per cent respectively). Transduodenal sphincteroplasty carried a much higher mortality (11 per cent) and morbidity (52 per cent) when compared with other procedures.