José Eduardo M. Cunha

Guidewire Cannulation Reduces Risk of Post-ERCP Pancreatitis and Facilitates Bile Duct Cannulation

OBJECTIVE:To evaluate if using a soft-tipped guidewire to cannulate the common bile duct may ameliorate development of post-ERCP pancreatitis and facilitate cannulation of the CBD.DESIGN AND SETTING:A single-center, blinded, randomized trial of conventional cannulation technique using sphinctertome and contrast injection versus guidewire cannulation technique.METHODS:We prospectively randomized 300 patients to conventional cannulation (group I) or guidewire cannulation (group II) technique.OUTCOME MEASURES:Primary outcome measure was incidence of acute pancreatitis and secondary outcome measures were ease of cannulation of common bile duct (assessed by attempts required for common bile duct cannulation & rates of precut sphincterotomy) and overall complication rates.RESULTS:Guidewire cannulation was associated with significantly lower likelihood of post-ERCP pancreatitis (adjusted OR 0.43, 95% CI 0.21–0.89, P = 0.02). Twenty-five patients (16.6%) in group I and thirteen patients (8.6%) in group II developed acute pancreatitis, P = 0.037. All instances of pancreatitis were mild. There were more women in group II; 41 in group I and 59 in group II, P = 0.028. Otherwise the two groups were comparable for age, age under 35 yr, indication for ERCP, diagnosis, and number of patients with SOD. The number of patients requiring 0–3, 4–6, and 7–10 attempts for successful cannulation of the common bile duct were 87, 48, and 15 in group I and 117, 24, and 9 in group II, respectively, P = 0.001. A total of 33 patients in group I and 13 patients in group II required precut sphincterotomy, P = 0.007. Rates of accidental pancreatic duct cannulation were 21 in group I and 27 in group II, P = 0.34. Rates of overall complication were not significantly different in the two groups.CONCLUSIONS:Guidewire technique for bile duct cannulation lowers likelihood of post-ERCP pancreatitis by facilitating cannulation and reducing need for precut sphincterotomy.

Surgery or Endoscopy for Palliation of Biliary Obstruction Due to Metastatic Pancreatic Cancer

BACKGROUND AND AIMS:Both endoscopic and surgical drainage procedures are effective palliative methods for malignant biliary obstruction. Surgical drainage is still preferred in developing countries due to the high cost of procuring metal biliary stents. The aim of this study was to evaluate the quality of life and the cost of care in patients with metastatic pancreatic cancer after endoscopic biliary drainage and surgical drainage.PATIENTS AND METHODS:This is a prospective, randomized controlled trial conducted in a tertiary referral center in Brazil. Patients with biliary obstruction due to metastatic pancreatic cancer and liver metastasis, but without gastric outlet obstruction, were included in the study. Endoscopic biliary drainage with the insertion of a metal stent into the bile duct was compared with the surgical drainage procedure (choledochojejunostomy and gastrojejunostomy). Quality of life was assessed before, and 30 days, 60 days, and 120 days after the drainage procedure. The cost of drainage procedure, cost during the first 30 days and the total cost from drainage procedure to death were calculated.RESULTS:Of the 273 patients with pancreatic malignancy seen at our hospital between July 2001 and October 2004, 35 patients were eligible for the study, and 30 agreed to participate in the study. Both surgical and endoscopic drainage procedures were successful, without any mortality in the first 30 days. The cost of biliary drainage procedure (US

Endoscopic sphincterotomy before deployment of covered metal stent is associated with greater complication rate: a prospective randomized control trial.

2,832 ± 519 vs 3,821 ± 1,181, p = 0.031), the cost of care during the first 30 days after drainage (US

Kras mutation analysis of fine needle aspirate under EUS guidance facilitates risk stratification of patients with pancreatic mass

3,122 ± 877 vs 6,591 ± 711, p = 0.001), and the overall total cost of care that included initial care and subsequent interventions and hospitalizations until death (US

Lymph Node Involvement and Not the Histophatologic Subtype Is Correlated with Outcome After Resection of Adenocarcinoma of the Ampulla of Vater

4,271 ± 2,411 vs 8,321 ± 1,821, p = 0.0013) were lower in the endoscopy group compared with the surgical group. In addition, the quality of life scores were better in the endoscopy group at 30 days (p = 0.042) and 60 days (p = 0.05). There was no difference between the two groups in complication rate, readmissions for complications, and duration of survival.CONCLUSIONS:Endoscopic biliary drainage is cheaper and provides better quality of life in patients with biliary obstruction and metastatic pancreatic cancer.

Clinical and pathologic prognostic factors for curative resection for pancreatic cancer

Objective Endoscopic sphincterotomy (ES) may facilitate insertion of self expandable metal stent (SEMS) and also help avert the development of pancreatitis from stent-related occlusion of the pancreatic duct. On the other hand, ES is also independently associated with pancreatitis, bleeding, and perforation. We evaluated whether ES before SEMS placement was associated with a greater likelihood of stent migration and other complications in patients with malignant obstruction of the distal common bile duct. Methods Seventy-four patients with unresectable distal bile duct obstruction were prospectively randomized to biliary stenting following ES (group 1) and without ES (group 2). Main outcome measures included overall procedure complications rates including stent migration, stent occlusion, oxygen desaturation, bleeding, perforation, and pancreatitis. Results Covered SEMS were successfully deployed in all patients in both groups. Stent migration occurred in 6 patients (16%) in group 1 and 1 patient (3%) in group 2, P=0.075. Overall, complications occurred in 18 patients in group 1 and 4 patients in group 2, P=0.006. There was no pancreatitis in either group. Conclusions Deployment of covered SEMS without prior ES in patients with distal common bile duct obstruction owing to pancreatic cancer is feasible and prevents the development of complications such as stent migration, bleeding, and perforation.

Local and systemic effects of hypertonic solution (NaCl 7.5%) in experimental acute pancreatitis.

Objectives The accuracy of endoscopic ultrasound-fine needle aspiration cytology (EUS-FNAC) for the diagnosis of pancreatic cancer is suboptimal. Mutational activation of the kras oncogene is almost universally present in pancreatic cancer tissue. We, therefore, investigated if analysis for mutant kras gene in the EUS-FNAC aspirates supplements cytopathology for the diagnosis of pancreatic adenocarcinoma (PAC). Methods EUS-FNAC specimens obtained from 74 patients with pancreatic masses were analyzed for the presence of kras mutation on codon 12 using polymerase chain reaction-restriction fragment length polymorphism and MvaI restriction enzyme. Definitive diagnosis was based on surgical pathology or long-term follow-up (median 27.8 mo); 57 patients had PAC, 11 patients chronic pancreatitis, and 9 patients nonfunctioning neuroendocrine tumors. Results Analysis of mutant kras gene in addition to cytopathology allowed the detection of PAC in 4 additional patients as compared with cytopathology alone. Cytopathology and kras mutant analysis were negative for PAC in 17 patients of whom 6 patients (35%) had PAC. The respective sensitivity (90.9% vs. 82.5%), specificity (47.6% vs. 97.9%), positive predictive value (89.5% vs. 83.8%), negative predictive value (98.1% vs. 94.1%), accuracy (89.2% vs. 58.8%) of cytopathology plus kras mutation versus cytopathology were numerically superior but did not reach statistical significance. Conclusions Analysis for the presence of mutant kras gene supplements conventional cytopathology for the diagnosis of PAC even without a cytopathologist in attendance and using only 3 needle passes. Among patients with negative cytopathology, the presence of kras mutation represents pancreatic cancer while the absence of kras mutation increases the possibility of benign lesion.

Effect of platelet-activating factor antagonists (BN-52021, WEB-2170, and BB-882) on bacterial translocation in acute pancreatitis.

BackgroundIntestinal and pancreaticobiliary types of Vater’s ampulla adenocarcinoma have been considered as having different biologic behavior and prognosis. The aim of the present study was to determine the best immunohistochemical panel for tumor classification and to analyze the survival of patients having these histological types of adenocarcinoma.MethodNinety-seven resected ampullary adenocarcinomas were histologically classified, and the prognosis factors were analyzed. The expression of MUC1, MUC2, MUC5AC, MUC6, CK7, CK17, CK20, CD10, and CDX2 was evaluated by using immunohistochemistry.ResultsForty-three Vater’s ampulla carcinomas were histologically classified as intestinal type, 47 as pancreaticobiliary, and seven as other types. The intestinal type had a significantly higher expression of MUC2 (74.4% vs. 23.4%), CK20 (76.7% vs. 29.8%), CDX2 (86% vs. 21.3%), and CD10 (81.4% vs. 51.1%), while MUC1 (53.5% vs. 82.9%) and CK7 (79.1% vs. 95.7%) were higher in pancreatobiliary adenocarcinomas. The most accurate markers for immunohistochemical classification were CDX2, MUC1, and MUC2. Survival was significantly affected by pancreaticobiliary type (p = 0.021), but only lymph node metastasis, lymphatic invasion, and stage were independent risk factors for survival in a multivariate analysis.ConclusionThe immunohistochemical expression of CDX2, MUC1, and MUC2 allows a reproducible classification of ampullary carcinomas. Although carcinomas of the intestinal type showed better survival in the univariate analysis, neither histological classification nor immunohistochemistry were independent predictors of poor prognosis.

MECHANISMS OF THE BENEFICIAL EFFECT OF HYPERTONIC SALINE SOLUTION IN ACUTE PANCREATITIS.

BACKGROUND Pancreatic cancer is the fifth leading cause of cancer-related deaths in the world. Operative resection is the only therapeutic option with curative potential for this disease. OBJECTIVE The aim of the present study was to correlate clinical and pathologic parameters with survival in patients submitted to pancreatic resection for pancreatic adenocarcinoma. METHODS Surgical resection with curative intent (R0 and R1 resections) was performed in 65 pancreatic cancer patients between 1990 and 2006. The overall results of surgical treatment were retrospectively analyzed and compared with the clinicopathologic features of these patients. RESULTS Pylorus-preserving pancreatoduodenectomy was performed in 37 patients (56.9%), classic resection in 35.4%, distal pancreatectomy in 4.6% and total pancreatectomy in 3.6%. The inhospital mortality was 5% (three patients). Postoperative complications occurred in 28 patients (43%). Mean survival and five-year survival rate after curative resection were 27 months and 9.0%, respectively. Sex, TNM stage, tumor differentiation, neural invasion, tumor size and involvement of resection margin were significant prognostic factors on univariate analysis. Multivariate analysis showed tumor differentiation and neural invasion as prognostic factors. CONCLUSION Patients with pancreatic cancer, even those with poor prognostic factors should be given the opportunity of surgical resection with curative intent.

Inhibition of cyclooxygenase-2 in experimental severe acute pancreatitis

Objectives: Severe acute pancreatitis (AP) is characterized by hemodynamic alterations and a systemic inflammatory response, leading to a high mortality rate. Treatment of hemorrhagic shock with hypertonic saline solutions significantly reduces mortality through an improvement in the hemodynamic conditions and possibly by an anti-inflammatory effect. Therefore, hypertonic solutions could be effective in AP. Methods: Wistar rats were divided in 4 groups: group C, control, without AP; group NT, AP, without treatment; group NS, treatment with normal saline solution (NaCl 0.9%) 1 hour after AP; group HTS, treatment with hypertonic saline solution (NaCl 7.5%) 1 hour after AP. AP was induced by injection of 2.5% sodium taurocholate into the pancreatic duct. Mean arterial blood pressure (MAP) and heart rate were recorded at 0 and 2, 4, 24, and 48 hours after AP. After induction of AP, animals were killed at 2, 12, 24, and 48 hours for serum amylase, interleukin (IL)-6, and IL-10 analysis, pancreatic tissue culture and histologic analysis, oxidation and phosphorylation of liver mitochondria, pulmonary myeloperoxidase activity (MPO), and mortality study. Results: In animals of groups NS and NT, a significant decrease of MAP was observed 48 hours after AP (NS: 91 ± 3 mm Hg; NT: 89 ± 3 mm Hg) compared with baseline (C: 105 ± 2 mm Hg) and to HTS group (HTS: 102 ± 2 mm Hg; P < 0.05). In animals of group NT, NS, and HTS, serum IL-6 and IL-10 levels were significantly higher at 2 hours after AP compared with the control group. However, IL-6 levels at 12 hours after AP and IL-10 levels at 2 and 12 hours after AP were significant lower in group HTS compared with NS and NT groups (P < 0.05). In group HTS, a decrease of pulmonary MPO activity and of pancreatic infection was observed 24 hours after AP compared with NT and NS groups (P < 0.05). A significant reduction on pancreatic acinar necrosis and mitochondrial dysfunction was observed after 48 hours of AP in animals of group HTS compared with groups NT and NS (P < 0.05). A significant reduction on mortality was observed in HTS (0/14) compared with NS (6/17; 35%) and NT (7/20; 35%). Conclusions: The administration of hypertonic saline solution in experimental AP attenuated hemodynamic alterations, decreased inflammatory cytokines, diminished systemic lesions and pancreatic acinar necrosis, prevented pancreatic infection, and reduced the mortality rate.