Antioxidants as a treatment for acute pancreatitis: A meta-analysis.

OBJECTIVE: To assess the efficacy of antioxidants in acute (AP) pancreatitis. METHODS: We searched PubMed, Embase and the Cochrane library for all randomized controlled trials (RCT) involving administration of antioxidants in the therapy of AP until February 2012. AP studies were pooled to analyze the effect of antioxidants on hospital stay, mortality, and complications. Subgroup analyses were performed on the use of the antioxidant glutamine. RESULTS: In total, eleven RCTs were included. Among patients with AP, antioxidant therapy resulted in a borderline significant reduction in hospital stay (mean difference -1.74; 95%CI -3.56 to 0.08), a significant decrease in complications (RR 0.66; 95%CI 0.46-0.95) and a non-significant decrease in mortality rate (RR 0.66; 95%CI 0.30-1.46). Subgroup analyses showed that glutamine significantly reduced complications (RR 0.51; 95%CI 0.34-0.78) and mortality rate (RR 0.33; 95%CI 0.13-0.85). CONCLUSION: The present meta-analysis shows a possible benefit of glutamine supplementation in patients with acute pancreatitis. However, large randomized trials are needed to confirm these observations.

Variety in vegetable and fruit consumption and the risk of gastric and esophageal cancer in the European Prospective Investigation into Cancer and Nutrition.

Diets high in vegetables and fruits have been suggested to be inversely associated with risk of gastric cancer. However, the evidence of the effect of variety of consumption is limited. We therefore investigated whether consumption of a variety of vegetables and fruit is associated with gastric and esophageal cancer in the European Prospective Investigation into Cancer and Nutrition study. Data on food consumption and follow-up on cancer incidence were available for 452,269 participants from 10 European countries. After a mean follow-up of 8.4 years, 475 cases of gastric and esophageal adenocarcinomas (180 noncardia, 185 cardia, gastric esophageal junction and esophagus, 110 not specified) and 98 esophageal squamous cell carcinomas were observed. Diet Diversity Scores were used to quantify the variety in vegetable and fruit consumption. We used multivariable Cox proportional hazard models to calculate risk ratios. Independent from quantity of consumption, variety in the consumption of vegetables and fruit combined and of fruit consumption alone were statistically significantly inversely associated with the risk of esophageal squamous cell carcinoma (continuous hazard ratio per 2 products increment 0.88; 95% CI 0.79-0.97 and 0.76; 95% CI 0.62-0.94, respectively) with the latter particularly seen in ever smokers. Variety in vegetable and/or fruit consumption was not associated with risk of gastric and esophageal adenocarcinomas. Independent from quantity of consumption, more variety in vegetable and fruit consumption combined and in fruit consumption alone may decrease the risk of esophageal squamous cell carcinoma. However, residual confounding by lifestyle factors cannot be excluded.

Helicobacter pylori infection assessed by ELISA and by immunoblot and noncardia gastric cancer risk in a prospective study: the Eurgast-EPIC project.

BACKGROUND: In epidemiological studies, Helicobacter pylori infection is usually detected by enzyme-linked immunosorbent assay (ELISA). However, infection can spontaneously clear from the mucosa during the progression of atrophy and could lead to substantial under-detection of infection and underestimation of its effect on gastric cancer (GC) risk. Antibodies detected by western blot are known to persist longer after the loss of the infection. METHODS: In a nested case-control study from the Eurogast-EPIC cohort, including 88 noncardia GC cases and 338 controls, we assessed the association between noncardia GC and H. pylori infection comparing antibodies detected by western blot (HELICOBLOT2.1) to those detected by ELISA (Pyloriset EIA-GIII(®)). RESULTS: By immunoblot, 82 cases (93.2%) were H. pylori positive, 10 of these cases (11.4%) were negative by ELISA and only 6 cases (6.8%) were negative by both ELISA and immunoblot. Multivariable odds ratio (OR) for noncardia GC comparing immunoglobulin G positive versus negative by ELISA was 6.8 [95% confidence interval (CI) 3.0-15.1], and by immunoblot, the OR was 21.4 (95% CI 7.1-64.4). CONCLUSIONS: Using a western blot assay, nearly all noncardia GC were classified as H. pylori positive and the OR was more than threefold higher than the OR assessed by ELISA, supporting the hypothesis that H. pylori infection is a necessary condition for noncardia GC.

The burden of endoscopic retrograde cholangiopancreatography (ERCP) performed with the patient under conscious sedation.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is an invasive procedure that proves burdensome to patients. Nevertheless, very little data are available on patient tolerance of this procedure that may improve practice guidelines and could aid in decreasing the burden of ERCP. This study therefore investigated the burden of ERCP performed with the patient under conscious sedation. METHODS: Consecutive patients receiving ERCP under conscious sedation between November 2007 and December 2008 at the University Medical Center Utrecht and Erasmus MC Rotterdam (The Netherlands) were asked to participate in this study. The patients completed questionnaires on demographics, medical history, burden of ERCP (mental health, discomfort, and pain), symptoms and the EuroQol-5D (EQ-5D), including the EQ-VAS (lower EQ-5D scores and higher EQ-VAS scores represent a better quality of life). The paired t-test, the Kruskal­Wallis test, Pearson correlation, and logistic regression were used to evaluate the results. RESULTS: The questionnaire was returned by 149 (54%) of 276 eligible patients, 139 of whom completed the entire questionnaire (54% males; mean age, 60 ± 14 years). Throat ache (p < 0.001) was the only symptom higher than baseline value 1 day after the ERCP. On day 1, about one-tenth of the patients experienced moderate to severe mental health problems, which were associated with a higher EQ-5D score before ERCP (p = 0.01). Slightly fewer than half of the patients experienced pain and discomfort during and immediately after ERCP. More discomfort was experienced by patients who underwent therapeutic ERCP (p < 0.05) and those with a higher EQ-5D score (p < 0.001) or lower VAS (p < 0.01). Pain was associated with younger age (p < 0.01), higher EQ-5D score (p < 0.001), and lower VAS (p < 0.01). CONCLUSION: One-third to one-half of patients experience pain and discomfort during and immediately after ERCP when it is performed with conscious sedation for the patient. Other sedation strategies, such as the use of general anesthesia or propofol, may well reduce the burden of ERCP, particularly for patients with a higher EQ-5D score, younger age, or therapeutic ERCP treatment. However, randomized trials are warranted.

Diabetes mellitus, glycated haemoglobin and C-peptide levels in relation to pancreatic cancer risk: a study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

AIMS/HYPOTHESIS: There has been long-standing debate about whether diabetes is a causal risk factor for pancreatic cancer or a consequence of tumour development. Prospective epidemiological studies have shown variable relationships between pancreatic cancer risk and blood markers of glucose and insulin metabolism, overall and as a function of lag times between marker measurements (blood donation) and date of tumour diagnosis. METHODS: Pre-diagnostic levels of HbA(1c) and C-peptide were measured for 466 participants with pancreatic cancer and 466 individually matched controls within the European Prospective Investigation into Cancer and Nutrition. Conditional logistic regression models were used to estimate ORs for pancreatic cancer. RESULTS: Pancreatic cancer risk gradually increased with increasing pre-diagnostic HbA(1c) levels up to an OR of 2.42 (95% CI 1.33, 4.39 highest [≥ 6.5%, 48 mmol/mol] vs lowest [≤ 5.4%, 36 mmol/mol] category), even for individuals with HbA(1c) levels within the non-diabetic range. C-peptide levels showed no significant relationship with pancreatic cancer risk, irrespective of fasting status. Analyses showed no clear trends towards increasing hyperglycaemia (as marked by HbA(1c) levels) or reduced pancreatic beta cell responsiveness (as marked by C-peptide levels) with decreasing time intervals from blood donation to cancer diagnosis. CONCLUSIONS/INTERPRETATION: Our data on HbA(1c) show that individuals who develop exocrine pancreatic cancer tend to have moderate increases in HbA(1c) levels, relatively independently of obesity and insulin resistance-the classic and major risk factors for type 2 diabetes. While there is no strong difference by lag time, more data are needed on this in order to reach a firm conclusion.

Safety and efficacy of a new non-foreshortening nitinol stent in malignant gastric outlet obstruction (DUONITI study): a prospective, multicenter study.

BACKGROUND AND STUDY AIMS: Gastric outlet obstruction (GOO) is a late complication of advanced gastric, periampullary, and duodenal malignancies. Palliation of obstruction is the primary aim of treatment in these patients. Self-expandable metal stents have emerged as a promising treatment option. Our aim was to investigate the safety and efficacy of a new non-foreshortening nitinol duodenal stent. PATIENTS AND METHODS: A total of 52 patients with symptomatic malignant GOO were studied in this prospective multicenter cohort study. All patients received a D-Weave Niti-S duodenal stent (Taewoong Medical, Seoul, South Korea). Patients were followed up until withdrawal of informed consent or death. RESULTS: The cause of GOO was pancreatic cancer in the majority of patients (62%). The technical and clinical success rates were 96% and 77%, respectively. The GOO Scoring System score improved significantly (P < 0.0001) when the scores before stenting were compared with the mean scores until death. Median survival was 82 days and stent patency was observed in 75% for up to 190 days, accounting for death as a competing risk. In 13 patients (25%) stent dysfunction occurred (tumor ingrowth in 11, stent migration in two). Over time, the body mass index, the World Health Organization performance score, and the EuroQol visual analog scale revealed a not significant change (P = 0.52, P = 0.43, and P = 0.15, respectively), whereas the global health status improved significantly (P = 0.001). CONCLUSION: Placement of a new non-foreshortening nitinol enteral stent is safe and without major complications. This stent design produces significant relief of obstructive symptoms and improves quality of life in patients with incurable malignant GOO.

Predictors of complications after endoscopic retrograde cholangiopancreatography: a prognostic model for early discharge.

BACKGROUND: Several studies have evaluated predictors for complications of endoscopic retrograde cholangiopancreatography (ERCP), but their relative importance is unknown. In addition, currently used blood tests to detect post-ERCP pancreatitis are inconsistent. The aim of this study was to determine predictors of post-ERCP complications that could discriminate between patients at highest and lowest risk of post-ERCP complications and to develop a model that is able to identify patients that can safely be discharged shortly after ERCP. METHODS: In a single-center, retrospective analysis over the period 2002-2007, predictors of post-ERCP complications were evaluated in a multivariable analysis and compared with those identified from a literature review. A prognostic model was developed based on these risk factors, which was further evaluated in a prospective patient population. RESULTS: From our retrospective analysis and literature review, we selected the eight most important risk factors for post-ERCP pancreatitis and cholangitis. In the prognostic model, the risk factors (precut) sphincterotomy, sphincter of Oddi dysfunction, younger age, female gender, history of pancreatitis, pancreas divisum, and difficult cannulation accounted for a score of 1 each, whereas primary sclerosing cholangitis (PSC) accounted for a score of 2. A sum score of 4 or more in the prognostic model was associated with a high risk of developing pancreatitis and cholangitis (27%; 6/22) in the prospective patient population, whereas a sum score of 3 or less was associated with a low to intermediate risk (8%; 20/252). CONCLUSIONS: We identified specific patient- and procedure-related factors that are associated with post-ERCP complications. The prognostic model based on these factors is able to identify patients who can be safely discharged the same day after ERCP.

[Gastrojejunostomy versus endoscopic stent placement as palliative treatment of malignant stenosis of the duodenum: overview of advantages and disadvantages on the basis of a literature study]. / Gastrojejunostomie versus endoscopische stentplaatsing als palliatieve behandeling bij een maligne vernauwing van het duodenum: overzicht van voor- en nadelen op basis van een literatuurstudie.

OBJECTIVE: To compare the results of stent placement and gastrojejunostomy in patients with malignant gastric outlet obstruction. Design. Systematic review. METHOD: PubMed was searched for relevant articles from January 1996 to January 2006 and further articles were obtained from their reference lists. Using results from these publications, average study scores for improvement of oral intake, complications, survival and costs were calculated. Results from randomized and comparative studies were pooled and odds ratios with 95% confidence intervals for improvement oforal intake and complications were calculated. RESULTS: A total of 44 publications were identified, including 2 randomized trials and 6 comparative studies. Information on study outcomes was not available in all publications. Long-term effectiveness was higher after gastrojejunostomy than after stent placement, with only 1% of patients needing a reintervention after gastrojejunostomy; more patients developed minor complications after gastrojejunostomy (33%) and the post-operative hospital stay was on average 13 days longer. After stent placement obstructive symptoms were relieved in 89% of patients and this effect was observed to occur more quickly after placement (within 0-2 days). More patients (approximately 20%) required a reintervention after stent placement due to stent migration or obstruction. CONCLUSION: Stent placement appeared to have favourable short-term results and gastrojejunostomy was associated with better long-term results. Well-performed clinical trials with an adequate number of patients were not found, which precluded more solid conclusions.

[Gastrojejunostomy versus endoscopic stent placement as palliative treatment for a malignant constriction of the duodenum: the SUSTENT-study]. / Gastrojejunostomie versus endoscopische stentplaatsing als palliatieve behandeling bij een maligne vernauwing van het duodenum: de SUSTENT-studie.

Gastric-outlet obstruction often results from inoperable distal stomach, periampullary (pancreatic or cholangio-), or duodenal carcinoma. Gastrojejunostomy and stent placement are standard palliative treatments. An advantage of gastrojejunostomy is the long-term efficacy; a disadvantage is the prolonged postoperative recovery time. The advantage of stent placement is the rapid ability to consume a soft diet; a disadvantage is that around 20% of the patients require re-intervention because of recurrent symptoms. A randomised multicentre study was started in January 2006 in the Netherlands in which gastrojejunostomy is compared with stent placement in the palliative treatment of malignant gastroduodenal obstruction: 'Surgery versus stent for malignant gastroduodenal obstruction', the SUSTENT-study. The primary-outcome measurement is survival adjusted for the time patients are not able to consume (soft) food. Other outcome measurements are medical effects (complications, re-interventions), quality of life, cost and cost-effectiveness. This study aims to provide individualised recommendations for effective palliative treatment of patients with malignant gastroduodenal obstruction.

Cost comparison of gastrojejunostomy versus duodenal stent placement for malignant gastric outlet obstruction.

BACKGROUND: Gastrojejunostomy (GJJ) and stent placement are the most commonly used palliative treatments for malignant gastric outlet obstruction (GOO). In a recent randomized trial, stent placement was preferred in patients with a relatively short survival and GJJ in patients with a longer survival. As health economic aspects have only been studied in general terms, we estimated the cost of GJJ and that of stent placement in such patients. METHODS: In the SUSTENT study, patients were randomized to GJJ (n = 18) or stent placement (n = 21). Pancreatic cancer was the most common cause of GOO. We compared initial costs and costs during follow-up. For cost-effectiveness, the incremental cost-effectiveness ratio was calculated. RESULTS: Food intake improved more rapidly after stent placement than after GJJ, but long-term relief of obstructive symptoms was better after GJJ. More major complications (P = 0.02) occurred and more reinterventions were performed (P < 0.01) after stent placement than after GJJ. Initial costs were higher for GJJ compared to stent placement (euro8315 vs. euro4820, P < 0.001). We found no difference in follow-up costs. Total costs per patient were higher for GJJ compared to stent placement (euro12433 vs. euro8819, P = 0.049). The incremental cost-effectiveness ratio of GJJ compared to stent placement was euro164 per extra day with a gastric outlet obstruction scoring system (GOOSS) >or=2 adjusted for survival. CONCLUSIONS: Medical effects were better after GJJ, although GJJ had higher total costs. Since the cost difference between the two treatments was only small, cost should not play a predominant role when deciding on the type of treatment assigned to patients with malignant GOO (ISRCTN 06702358).

Overview of the clinical problem: facts and current issues of mucinous cystic neoplasms of the pancreas.

Pancreatic cystic lesions are uncommon and consist of pseudocysts, congenital cysts and cystic neoplasms including mucinous cystic neoplasms, intraductal papillary mucinous neoplasms and serous cystic neoplasms. Mucinous cystic neoplasms are large septated cysts without connection to the ductal system, characterised by the presence of thick-walled ovarian-type stroma and mucin. They occur predominantly in women and often are malignant. Therefore, surgical resection is recommended. Intraductal papillary mucinous neoplasms are neoplasms with tall, columnar, mucin-containing epithelium involving the main pancreatic ducts or major side branches. Intraductal papillary mucinous neoplasms occur in men and women in their 60s and 70s and may differentiate into malignant neoplasms. Therefore, surgical resection is mandatory. Serous cystic neoplasms appear as multiple cysts lined with cubic flat epithelium containing glycogen-rich cells with clear cytoplasm. They mainly occur in women in their 50s and are generally benign. Therefore, a conservative approach is recommended. As both mucinous cystic neoplasm and intraductal papillary mucinous neoplasms have a high malignant potential, it is important to differentiate between the various pancreatic cystic lesions. Several imaging techniques and tumour markers have been evaluated. Nonetheless, definitive guidelines to differentiate between serous cystic neoplasms, mucinous cystic neoplasms and intraductal papillary mucinous neoplasms are still poorly defined. A number of management issues regarding these neoplasms are still under debate, for example which imaging technique to use, differentiation between malignant or benign lesions and the preferred treatment modality for each pancreatic cystic neoplasm. Further research may lead to a definitive guideline for the diagnosis and treatment of mucinous cystic neoplasms, intraductal papillary mucinous neoplasms and serous cystic neoplasms.

Gastrojejunostomy versus stent placement in patients with malignant gastric outlet obstruction: a comparison in 95 patients.

AIM: Gastrojejunostomy (GJJ) and duodenal stent placement are the most commonly used palliative treatment modalities for gastric outlet obstruction (GOO). In this retrospective study, we compared GJJ and stent placement with regard to medical effects. METHODS: Medical records of 95 patients who had undergone palliative treatment between 1994 and 2006 in a Dutch university hospital, were reviewed. Study outcomes were improvement of food intake, complications, persistent and recurrent symptoms, re-interventions, hospital stay, and survival. RESULTS: Fifty-three patients were referred for duodenal stent placement and 42 patients underwent GJJ. There were no differences in technical and clinical success and the incidence of minor and early major complications and survival. Food intake improved more rapidly after stent placement than GJJ (P = 0.01). The time to late major complications, recurrent obstructive symptoms and re-intervention was significantly shorter after stent placement than GJJ (P = 0.004, 0.002, and 0.004, respectively). Hospital stay was also shorter after stent placement than GJJ (P < 0.001). CONCLUSION: These findings suggest that stent placement is associated with better short-term outcomes and GJJ with better long-term outcomes. A large randomized controlled trial is however needed to systematically compare stent placement with GJJ with regard to medical effects, quality of life and costs.