Marianna Signoretti

Role of the gut barrier in acute pancreatitis

The small intestine is one of the distant organs that become damaged during severe acute pancreatitis, due to microcirculation disturbance associated with loss of fluids in the “third space,” hypovolemia, splanchnic vasoconstriction, and finally an ischemia-reperfusion injury. In this scenario, the gut acts as the starter for severe systemic complications, as the failure of the intestinal barrier is associated with translocation of bacteria and inflammatory and toxic products produced in the intestinal wall, which can be responsible for sepsis and infection of the necrotic pancreas and for systemic inflammatory response. Therefore, one of the main goals of treatment in the early phases of severe acute pancreatitis should be to maintain the integrity of the gut barrier in the small intestine. These strategies include appropriate fluid resuscitation to limit the damage due to the relative hypovolemia and early enteral feeding. The role of intravenous antibiotics to prevent infection of the pancreatic necrosis is controversial and the role of probiotics, which seemed a promising tool in vitro and in early clinical trials, needs to be further investigated to better understand the effects of the single specific strains at various doses and timing before designing new clinical trials.

Systematic review and meta-analysis: Small intestinal bacterial overgrowth in chronic pancreatitis

Background Evidence on small intestinal bacterial overgrowth (SIBO) in patients with chronic pancreatitis (CP) is conflicting. Aim The purpose of this study was to perform a systematic review and meta-analysis on the prevalence of SIBO in CP and to examine the relationship of SIBO with symptoms and nutritional status. Methods Case-control and cross-sectional studies investigating SIBO in CP patients were analysed. The prevalence of positive tests was pooled across studies, and the rate of positivity between CP cases and controls was calculated. Results In nine studies containing 336 CP patients, the pooled prevalence of SIBO was 36% (95% confidence interval (CI) 17–60%) with considerable heterogeneity (I2 = 91%). A sensitivity analysis excluding studies employing lactulose breath test gave a pooled prevalence of 21.7% (95% CI 12.7–34.5%) with lower heterogeneity (I2 = 56%). The odds ratio for a positive test in CP vs controls was 4.1 (95% CI 1.6–10.4) (I2 = 59.7%). The relationship between symptoms and SIBO in CP patients varied across studies, and the treatment of SIBO was associated with clinical improvement. Conclusions One-third of CP patients have SIBO, with a significantly increased risk over controls, although results are heterogeneous, and studies carry several limitations. The impact of SIBO and its treatment in CP patients deserve further investigation.

Small intestinal bacterial overgrowth in patients with chronic pancreatitis

Goals: To assess the prevalence of small intestinal bacterial overgrowth (SIBO) in chronic pancreatitis (CP), and analyze factors related with SIBO in CP. Background: SIBO is to be considered a factor that worsens symptoms and nutritional status in patients with CP. However, the few studies evaluating the rate of SIBO in CP patients used nonuniform and nonstandardized procedures, and reported a wide range of positivity (0% to 92%). Those studies often investigated CP patients with previous resection surgery (cause of SIBO per se). Study: CP patients and controls evaluated for SIBO by the H2 glucose breath test with a standard protocol. For CP patients, the relationship between test results, abdominal symptoms, and clinical and biochemical variables was analyzed. Results: A total of 43 CP patients and 43 controls were enrolled. Of the CP patients, 8 had advanced disease (defined by M-ANNHEIM index) and none had undergone previous surgery. The glucose breath test positivity rate was higher in the CP patients than in the controls (21% vs. 14%), albeit without a significant difference (P=0.57). Mean fasting H2 excretion and mean H2 excretion at 120 minutes also had a trend toward higher levels in CP patients. There were no clinical differences between CP patients with or without SIBO, but there were nutritional differences for lower levels of vitamin D and higher levels of folate in these patients with SIBO. Conclusions: Our findings suggest that SIBO is not uncommon in uncomplicated CP patients. The lack of a significant difference compared with controls might be due to the study being underpowered. SIBO in CP patients does not seem to be related to peculiar clinical features, but it might affect nutritional status.

The Neutrophil/Lymphocyte Ratio at Diagnosis Is Significantly Associated with Survival in Metastatic Pancreatic Cancer Patients

Different inflammation-based scores such as the neutrophil/lymphocyte ratio (NLR), the Odonera Prognostic Nutritional Index (PNI), the Glasgow Prognostic Score, the platelet/lymphocyte ratio, and the C-reactive protein/albumin ratio have been found to be significantly associated with pancreatic cancer (PDAC) prognosis. However, most studies have investigated patients undergoing surgery, and few of them have compared these scores. We aimed at evaluating the association between inflammatory-based scores and PDAC prognosis. In a single center cohort study, inflammatory-based scores were assessed at diagnosis and their prognostic relevance as well as that of clinic-pathological variables were evaluated through multiple logistic regression and survival probability analysis. In 206 patients, age, male sex, tumor size, presence of distant metastasis, access to chemotherapy, and an NLR > 5 but not other scores were associated with overall survival (OS) at multivariate analysis. Patients with an NLR < 5 had a median survival of 12 months compared to 4 months in those with an NLR > 5. In the 81 patients with distant metastasis at diagnosis, an NLR > 5 resulted in the only variable significantly associated with survival. Among patients with metastatic disease who received chemotherapy, the median survival was 3 months in patients with an NLR > 5 and 7 months in those with an NLR < 5. The NLR might drive therapeutic options in PDAC patients, especially in the setting of metastatic disease.

Repeated transabdominal ultrasonography is a simple and accurate strategy to diagnose a biliary etiology of acute pancreatitis.

Objectives Transabdominal ultrasonography (US) usually reveals diagnosis of biliary acute pancreatitis (AP). Guidelines suggest repeating US in AP patients without cause at first examination. This approach has been poorly investigated, as well as the accuracy of repeated US as compared with that of magnetic resonance cholangiopancreatography. This study aims at evaluating the diagnostic accuracy of repeated US for biliary AP. Methods The accuracy of each test for diagnosis of biliary AP was evaluated according to the final diagnosis. Comparison between tests was obtained by examining the areas under the receiver operating characteristic curves. Results Among 155 patients, the etiology was biliary in 52% and alcoholic in 20%. The accuracy of the first US alone and of the 2 combined examinations for a biliary etiology were 66% and 83%, respectively. Comparison of receiver operating characteristic curves showed a better performance of repeated US (difference between areas under the curve, 0.135; 95% confidence interval, 0.02–0.24; P = 0.021). Magnetic resonance cholangiopancreatography had high specificity (93%) but low sensitivity (62%), with 76% accuracy. The accuracy of the combination of the 2 US examinations and of elevated alanine transferase was 87%. Conclusions Repeated US is effective for biliary AP diagnosis. The combination of repeated US examinations and biochemical tests seems an effective approach, whereas magnetic resonance cholangiopancreatography might be restricted to selected cases.

Endoscopy-guided ablation of pancreatic lesions: Technical possibilities and clinical outlook

Endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreatography (ERCP)-guided ablation procedures are emerging as a minimally invasive therapeutic alternative to radiological and surgical treatments for locally advanced pancreatic cancer (LAPC), pancreatic neuroendocrine tumours (PNETs), and pancreatic cystic lesions (PCLs). The advantages of treatment under endoscopic control are the real-time imaging guidance and the possibility to reach a deep target like the pancreas. Currently, radiofrequency probes specifically designed for ERCP or EUS ablation are available as well as hybrid cryotherm probe combining radiofrequency with cryotechnology. To date, many reports and case series have confirmed the safety and feasibility of that kind of ablation technique in the pancreatic setting. Moreover, EUS-guided fine-needle injection is emerging as a method to deliver ablative and anti-tumoral agents inside the tumuor. Ethanol injection has been proposed mostly for the treatment of PCLs and for symptomatic functioning PNETs, and the use of gemcitabine and paclitaxel is also interesting in this setting. EUS-guided injection of chemical or biological agents including mixed lymphocyte culture, oncolytic viruses, and immature dendritic cells has been investigated for the treatment of LAPC. Data on the long-term efficacy of these approaches, and large prospective randomized studies are needed to confirm the real clinical benefits of these techniques for the management of pancreatic lesions.

Recurrent biliary acute pancreatitis is frequent in a real-world setting

BACKGROUND Data about recurrent acute pancreatitis (RAP) are limited. AIMS To evaluate the rate of RAP and associated factors. METHODS Single-centre prospective study of consecutive patients at first episode of acute pancreatitis (AP) being followed-up. RESULTS Of 266 consecutive AP patients, (47% biliary, 15.4% alcoholic, 14.3% idiopathic) 66 (24.8%) had RAP in a mean follow-up of 42 months; 17.9% of recurrences occurred within 30 days from discharge. Age, gender, smoking and severity of first AP were not associated with RAP risk. The rate of biliary RAP was 31.3% in patients who did not receive any treatment, 18% in those treated with ERCP only, 16% in those who received cholecystectomy only, and 0% in those treated both with surgery and ERCP. Patients with biliary AP who received cholecystectomy had a significantly longer time of recurrence-free survival and reduced recurrence risk (HR = 0.45). In patients with alcoholic AP, the rate of recurrence was lower in those who quit drinking (5.8% vs 33%; p = 0.05). The alcoholic aetiology was associated with a higher risk of having >2 RAP episodes. CONCLUSION RAP occurs in about 25% of cases, and failure to treat biliary aetiology or quitting drinking is associated with increased recurrence risk.

Surveillance for Pancreatic Cancer in High-Risk Individuals: First-Round Screening Results of a Multicentric Italian Program

I. C. A. W. Konings1 , M. I. Canto3, J. A. Almario3, F. Harinck1, P. Saxena3,10, A. L. Lucas5, F. Kastrinos6, D. C. Whitcomb7, R. E. Brand7, J. Lachter11, G. Malleo12, S. Paiella12, S. Syngal8, J. R. Saltzman8, E. M. Stoffel9, J. E. van Hooft2, R. H. Hruban4, J. W. Poley1, P. Fockens2, M. G. Goggins3 and M. J. Bruno1, on behalf of the International CAncer of the Pancreas Screening (CAPS) Consortium 1Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, and 2Department of Gastroenterology and Hepatology, Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands, 3Department of Gastroenterology and Hepatology, Johns Hopkins Medical Institutions, and 4Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland, 5Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, and 6Division of Digestive and Liver Diseases, Columbia University Medical Center, New York, 7Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, 8Department of Gastroenterology, Brigham and Women’s Hospital and Population Sciences Division, Dana Farber Cancer Institute, Boston, Massachusetts, and 9Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA, 10Department of Gastroenterology and Hepatology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia, 11Department of Gastroenterology, Rambam Healthcare Campus, Haifa, Israel, and 12Department of General Surgery, University Hospital of Verona, Verona, Italy Correspondence to: Dr I. C. A. W. Konings, Erasmus MC, University Medical Centre Rotterdam, PO Box 2040, 3000 CA Rotterdam, the Netherlands (e-mail: i.konings@erasmusmc.nl)

921 Small Intestinal Bacterial Overgrowth in Chronic Pancreatitis: Systematic Review and Meta-Analysis

Background & aim: Small intestinal bacterial overgrowth (SIBO) has been proposed as a factor causing symptoms and potentially impairing the nutritional status of patients with chronic pancreatitis (CP), but evidence is conflicting. A systematic review and meta-analysis were conducted on the prevalence of SIBO in CP. Methods: Medline was searched up to November 2014. Case series and case-control studies investigating SIBO in adult patients with CP were considered eligible. The prevalence of positive tests was pooled for included studies, and the rate of positivity between CP cases and controls, and the relative OR and 95% confidence interval (CI) calculated. Results: Six studies were identified from an initial list of 1579, containing 186 CP patients. The pooled prevalence of positive tests (either glucose or lactulose H2 Breath Test) was 30% (95% CI 15%-51%), with significant heterogeneity (I2=77%). A sensitivity analysis excluding the only study employing lactulose BT gave a pooled prevalence of 23% (95% CI 14%-36%), with reduced heterogeneity (I2=58%). The pooled odds ratio for positive tests in CP cases compared with controls was 5.7 (95% CI 1.6-20.7; p=0.007; I2=67%), being reduced to 2.8 (95% CI 1.2-6.8; p=0.017; I2=32%) when the study employing lactulose was excluded. Conclusions: One of four patients with CP is affected by SIBO, with a significantly increased risk over controls, although results are heterogeneous, and studies carry several limitations. The use of lactulose H2 BT seem to overestimate SIBO. The impact of SIBO and its treatment on the nutritional status of CP patients deserve further investigation.

Celiac disease and CFTR mutations in patients with chronic asymptomatic pancreatic hyperenzymemia.

Celiac Disease and CFTR Mutations in Patients With Chronic Asymptomatic Pancreatic Hyperenzymemia