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.

Tubercular biliary hilar stricture: A rare case report.

Localized hepatic tuberculosis (TB) with or without bile duct involvement is a rare form of hepatobiliary tuberculosis; accounting for less than 1% of all tuberculous infections. We report an uncommon case of cholestatic jaundice with disseminated TB in an immunocompetent male who presented with simultaneous involvement of liver and biliary system.

Vanishing bile duct syndrome in the context of concurrent temozolomide for glioblastoma.

Temozolomide, an oral alkylating agent, is used in the treatment of glioblastoma. We describe a case of a 62-year-old woman developing jaundice with significant derangement of liver function tests on day 17 of focal radiotherapy with concomitant temozolomide. There was no structural abnormality on imaging and liver biopsy was performed. Pathology revealed absence of small terminal bile ducts affecting up to 60% of sampled portal tracts and senescence of many of the remaining small bile ducts, in keeping with a diagnosis of acute vanishing bile duct syndrome. This is a rare syndrome. It has been documented in association with Hodgkin's lymphoma and viral causes. Drugs implicated as precipitating this condition include antiseizure medications, some antibiotics, ibuprofen and antifungals. Temozolomide was stopped. The patient received supportive care, ursodeoxycholic acid 750 mg daily and cholestyramine 4 g twice daily. She was otherwise asymptomatic and her blood results returned to normal by day 129.

Lipoic acid prevents hepatic and intestinal damage induced by obstruction of the common bile duct in rats.

INTRODUCTION: Cholestatic liver diseases are characterized by impaired hepatocellular secretion of bile, resulting in intracellular accumulation of bile acids which result in a shift in the oxidant/prooxidant balance in favor of increased free radical activity and injury of different tissues including liver and intestine. The aim of this research was to study protective effect of lipoic acid (LA) as a potent antioxidant in cholestsis induced hepatic and intestinal injury in rats. MATERIALS AND METHODS: Forty five adult male Wistar rats were randomly assigned to four groups each containing fifteen rats as follows: sham operation (SO) (control), bile duct ligating (BDL), and BDL+LA (25 mg/kg). After fourteen days hepatic and intestinal tissue sampled and blood serum sampled for pathologic and biochemical studies. RESULTS: Levels of SOD and GPx antioxidant enzymes were higher in BDL+LA group comparing to BDL group, levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and γ-glutamyltranspeptidase (GGT), and pathologic scores in liver and intestine were lower in BDL+LA group comparing to BDL group significantly, but there is no significant difference in concentrations of total bilirubin between groups. CONCLUSIONS: Our results showed the protective potential of LA with liver and intestine damage. Despite improvements in operative technique and the development of potent, broad-spectrum antibiotics, biliary tract surgery in patients with obstructive jaundice is still associated with high morbidity and mortality rates In summary, our results show that BDL induced hepatic and intestinal injury were significantly attenuated by LA administration and the administration of LA could effectively diminish this damage.

IgG4-related disease in Singapore: a description of two cases and review of the literature.

We describe a 42-year-old man who presented with painless obstructive jaundice, organomegaly and lymphadenopathy. Biopsy of the ampulla of Vater revealed the presence of increased populations of plasma cells which stained positively for immunoglobulin G4. He was treated with prednisolone and demonstrated significant clinical improvement 1 month later. A further case is described and a review of the literature is also provided.

Effects in the control of edema of the papilla of Vater by epinephrine saline irrigation after endoscopic retrograde cholangiopancreatography in an endoscopy center in Japan, 2003 to 2007: exploratory retrospective analysis to evaluate the characteristics of eligible patients with a focus on serum amylase levels.

OBJECTIVE: To evaluate the effects of localized irrigation with epinephrine saline after endoscopic retrograde cholangiopancreatography (ERCP). PATIENTS AND METHODS: One hundred and fourteen patients who underwent ERCP in our institute were treated with or without irrigation using epinephrine diluted in saline after ERCP to prevent post-ERCP pancreatitis. The serum amylase levels, white blood cell counts, and urine amylase levels were measured at 24 and 48 hours after ERCP. RESULTS: The treatment resulted in improvements in all items. A univariate analysis of the explanatory variables between the treatment and untreated groups revealed the treatment to be effective, but not statistically significant. Gender and cannulation of the pancreatic duct were the only variables with significant partial regression coefficients in the multiple regression model with all explanatory variables (p=0.045). When a stratified analysis was conducted using gender as a moderator variable, the treatment became a significant preventive factor (p=0.038), and cannulation of the pancreatic duct was a significant risk factor (p=0.027) in female patients. CONCLUSION: We suggest that irrigating with epinephrine saline into the papilla may be effective for preventing pancreatitis in female patients who received ERCP with cannulation of their pancreatic duct.

Effects of vardenafil, a phosphodiesterase type-5 inhibitor, on sphincter of Oddi motility in patients with suspected biliary sphincter of Oddi dysfunction.

BACKGROUND: The therapeutic approach in patients with sphincter of Oddi (SO) dysfunction (SOD) aims to reduce the resistance to the flow of bile or pancreatic juice. Vardenafil inhibits the activity of phosphodiesterase type 5 (PDE-5), which degrades cyclic guanossine monophosphate (cGMP) and results in relaxation of smooth muscle. OBJECTIVE: The present study was performed to determine the effects of vardenafil on SO motility in patients with suspected SOD. DESIGN: Prospective study. SETTINGS: Single university center. PATIENTS AND INTERVENTIONS: Twenty consecutive adult patients with suspected SOD were scheduled to undergo ERCP and SO manometry by standard methods. A second recording was performed in the same position 20 minutes after administration of 10 mg vardenafil dissolved in 10 mL saline solution into the duodenum through a conventional catheter. SO pressures and motor function were compared in all patients with suspected SOD before and after administration of vardenafil. RESULTS: After administration of 10 mg of vardenafil, the mean basal sphincter pressure was reduced from 59.5 to 26.9 mm Hg (P < .001), and the mean phasic amplitude was reduced from 132.2 to 66.2 mm Hg (P < .001). The mean phasic wave frequency was not changed after administration of vardenafil (7.2/min vs 6.6/min, respectively, P = .07). These results did not differ between SOD types. No significant difference in manometric data were detected before and after administration of vardenafil between cholecystectomy and gallbladder in situ groups. Transient headache was observed in 1 patient, and the procedure-related complication was post-ERCP pancreatitis (n = 2 [10%]). LIMITATIONS: The small sample size and uncontrolled study. CONCLUSION: Vardenafil inhibits SO motility in patients with suspected SOD and reduces basal SO pressure, without significant adverse effects.

Clinical significance of swollen duodenal papilla in autoimmune pancreatitis.

OBJECTIVES: To evaluate the clinical significance of a swollen main duodenal papilla and the associated immunohistopathologic findings in patients with autoimmune pancreatitis (AIP). METHODS: Seventeen consecutive patients with AIP registered between April 2001 and October 2005 who underwent both endoscopic retrograde cholangiopancreatography and endoscopic biopsy were enrolled in this study. The endoscopic features, stromal inflammatory cell infiltrate (SICI), and results of immunohistochemical examination of the duodenal papilla using IgG4, CD3, and CD79a antibodies were retrospectively reviewed. These findings in the AIP patients were compared with those in 12 patients with chronic alcoholic tumor-forming pancreatitis (CAP). The numbers of cells in the SICI and of IgG4-positive plasma cells per high-power field were counted in all the histopathologic specimens. RESULTS: A swollen main duodenal papilla was observed in 11 (11 [64.7%]/17) patients with AIP and 4 (4 [33.3%]/12) patients with CAP (P < 0.05). Resolution of the swollen main duodenal papilla was observed in all of these 11 patients with AIP (11 [100%]/11) in response to treatment with corticosteroids. On the other hand, the 6 patients without elevated serum IgG4 or a swollen duodenal papilla, but with a swollen pancreas, improved even without corticosteroid treatment. The number of cells in the SICI in the AIP patients was significantly higher than that in the CAP patients. Although in 13 of 17 AIP patients, infiltration by IgG4-positive plasma cells was detected in the duodenal papilla, no such significant infiltration of the duodenal papilla by IgG4-positive plasma cells was observed in the patients with CAP (P < 0.05). More predominant T-cell infiltration of the duodenal papilla was recognized in the AIP patients than in the CAP patients (P < 0.05). CONCLUSIONS: These results suggest that a swollen main duodenal papilla with IgG4-positive plasma cell and T-cell-dominant infiltration and an abundant stromal cell infiltrate are characteristic findings in AIP. We suggest that these findings may be valuable adjuncts to the diagnosis of AIP as well as for selecting suitable candidates for corticosteroid therapy.

Resolution of tuberculous biliary stricture after medical therapy.

Tuberculosis (TB) is a very rare cause of biliary stricture that is difficult to diagnose and usually requires surgical intervention in order to rule out underlying malignant etiology. We report a 56-year-old man presented with jaundice, weight loss and poor appetite. Initial work up showed the dilated biliary system secondary to distal common bile duct stricture. Investigations to define the etiology of this stricture showed inconclusive brush cytology with absent abdominal masses and lymph nodes but enlarged mediastinal lymph nodes. Biopsy from these lymph nodes showed a non-caseating epitheliod granuloma with negative acid fast bacilli (AFB) stain. The patient had a dramatic response to empirical anti-tuberculosis therapy. Six weeks later, culture from lymph nodes was positive for Mycobacterium tuberculosis. Three months later, follow-up cholangiogram showed complete resolution of the stricture with normalization of liver enzymes 6 mo after starting anti-tuberculosis therapy. Treatment was continued for 12 mo and the patient had a normal life with normal liver enzymes and regression of the mediastinal lymph nodes at the time when he was reported in this paper. Although 16 cases of tuberculous biliary stricture are available in the English literature, up to our knowledge, this is the second published report of tuberculous biliary stricture, which resolved completely after medical therapy alone and the second reported case from the Middle East. This report emphasizes the importance of keeping TB as a possibility of biliary stricture in this part of the world.

A study of unfractionated and low molecular weight heparins in a model of cholestatic liver injury in the rat.

Forty-eight rats with biliary obstruction induced by double ligation and section of the common bile duct were randomly and blindly assigned to receive subcutaneous injection of either conventional heparin sodium (1000IU kg(-1)), three already marketed low molecular weight heparin (LMWH) preparations: nadroparin (1000 anti-Xa IU kg(-1)), tinzaparin (1000 anti-Xa IU kg(-1)), enoxaparin (180 anti-Xa IU kg(-1)) or saline. Drugs were administered once a day, starting 7 days after surgery and continued for 3 weeks. At the end of the treatment period, rats were killed and analyzed for blood biochemistry and liver pathology. Liver fibrosis was assessed by image analysis. Data indicated that treatment with nadroparin decreased plasma total bilirubin, serum alkaline phosphatase (ALP) and gamma glutamyltransferase (GGT) levels by 80.3, 70.7 and 42%, compared with bile duct ligated (BDL) control values. The reduction in plasma total protein observed in BDL controls was prevented by nadroparin. Enoxaparin-treated rats showed significant reduction in plasma total bilirubin and alanine aminotransferase levels by 32.5 and 38.4% versus BDL controls. Liver necrosis evaluated histologically was significantly reduced in the nadroparin- and enoxaparin-treated rats. Morphometric analysis showed significant reduction in fibrosis on nadroparin and enoxaparin treatment: area of fibrosis: 1.66 +/- 0.17% and 14.03 +/- 1.1% versus 18.94 +/- 2.4% (P<0.05); nadroparin and enoxaparin versus BDL control. By contrast, neither conventional heparin nor tinzaparin prevented the bile duct ligation-induced liver damage as indicated by increased plasma aminotransferases, ALP and GGT concentrations and the histological evidence of necrosis. Total serum bilirubin was increased by 27.5% in rats treated with conventional heparin, while ALP and GGT levels were 38.6 and 31.4% higher after tinzaparin treatment versus BDL controls. Significant increase in the area of fibrosis was observed after tinzaparin treatment compared to BDL control group. Results suggest a beneficial effect for nadroparin and enoxaparin in the therapy of patients with obstructive jaundice or cholestatic liver disorders. The present data from bile duct ligated rats suggest an antifibrotic effect for nadroparin and enoxaparin.