Giulia Zerboni

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.

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.

Exclusive and Combined Use of Statins and Aspirin and the Risk of Pancreatic Cancer: a Case-Control Study

Data on the association between aspirin and statin use and Pancreatic Ductal AdenoCarcinoma (PDAC) risk are conflicting. These drugs are often co-prescribed, but no studies evaluated the potential combined or confounding effect of the two at the same time. We aimed to investigate the association between aspirin and statin exclusive and combined use and PDAC occurrence. Data on environmental factors, family and medical history were screened in a case-control study. PDAC cases were matched to controls for age and gender. Power calculation performed ahead. Odds ratios (OR) and 95% confidence intervals(CI) were obtained from multivariable logistic regression analysis. In 408 PDAC patients and 816 matched controls, overall statin (OR 0.61; 95%CI,0.43–0.88), but not aspirin use was associated to reduced PDAC risk. Compared to non-users, exclusive statin (OR 0.51; 95%CI,0.32–0.80) and exclusive aspirin users (OR 0.64; 95%CI,0.40–1.01) had reduced PDAC risk. Concomitant statin and aspirin use did not further reduce the risk compared with statin use alone and no interaction was evident. Statin protective association was dose-dependent, and consistent in most subgroups, being stronger in smokers, elderly, obese and non-diabetic patients. The present study suggests that statin use is associated to reduced PDAC risk, supporting a chemopreventive action of statins on PDAC.

The Use of Complementary and Alternative Medicine is Frequent in Patients With Pancreatic Disorders.

Background: Herbal remedies and other complementary and alternative medicine (CAM) are used by 30% of the patients with liver and inflammatory bowel diseases. However, there are no data regarding CAM use in patients with pancreatic disorders, including potential pancreatotoxicity. Aim of the Study: The aim of the study was to assess the prevalence of CAM use in patients with pancreatic disorders and screen for pancreatotoxicity. Materials and Methods: This was a cross-sectional survey of consecutive outpatients seen at a Pancreas Center. Data were collected in a specific questionnaire. Descriptive statistics were used to analyze the prevalence and the patterns of CAM use. Characteristics associated with CAM use were analyzed by appropriate statistics. Results: Of 108 patients (52% male; mean age, 65±13 years), 47 (43.5%) used CAM. The use of CAM was more frequent among patients with previous acute pancreatitis (47%). Reported reasons for the use of CAM were to help standard therapies and for an overall better feeling. About 61% of the patients reported advantages with treatment. As compared with nonusers, CAM users were more often female (55% vs. 42%), with a higher school degree (43% vs. 36%), more frequently performing physical activity (51% vs. 41%), and reporting anxiety (45% vs. 31%). However, none of these differences were statistically significant. Three patients with previous acute pancreatitis reported the use of Serenoa repens that is potentially pancreatotoxic. Discussion: The rate of CAM use in patients with pancreatic disorders is similar to those reported for other digestive diseases. CAM use seems to be more frequent in women with a higher education level and a “healthier lifestyle.” Patients might not be aware of the potential pancreatotoxicity of CAM, which should be carefully considered by physicians.

Colonic small cell neuroendocrine carcinoma in a patient with long-standing ulcerative colitis treated with azathioprine

We report the case of a patient with long-standing ulcerative olitis (UC) treated with Azathioprine (AZA) who developed a neuoendocrine small cell carcinoma arising from the sigmoid colon. A 61-year old man was diagnosed with extensive UC in 2002. fter initial response to oral and topical mesalazine, azathioprine AZA) 2.5 mg/kg/day was added five years after diagnosis because f steroid-dependency. After AZA introduction the patient achieved ustained steroid-free remission but, 3 years later, he was diagosed with idiopathic autoimmune hemolytic anemia requiring epeated steroid courses despite concomitant immunosuppresion. Eight years after diagnosis the patient was in remission ff-steroids and endoscopic surveillance for long-standing disease as started. At index colonoscopy (2010) erythema and decreased ascular pattern were observed in the whole colon except for the

A safety evaluation of budesonide MMX for the treatment of ulcerative colitis

ABSTRACT Introduction: Budesonide belongs to low-bioavailability steroids class. A novel oral formulation of budesonide, which uses the Multi-Matrix System (MMX) for delivering drugs to the colon, is now available as a possible treatment of ulcerative colitis patients intolerant or not-responding to first-line therapy with 5-ASA. Areas covered: in this review we present information about the development and the use of budesonide MMX and we provide data about its mechanism of action as well as, pharmacodynamics and pharmacokynetics. Moreover, we present the available literature data about the efficacy and, mainly, the safety of budesonide-MMX. Expert opinion: budesonide-MMX is a new therapeutic option in mild-to-moderate UC patients. Its good safety profile in clinical trials undoubtedly represents a strength for a possible wide use in clinical practice, mainly if it will be confirmed by post-marketing data. Other indications, such as treatment of colonic Crohn’s disease, could theoretically be considered, if sustained by reliable scientific data.

The prevalence of pancreatic cystic lesions in patients with liver cirrhosis is double that in controls

Background and aims Pancreatic cystic lesions (PCLs) are commonly diagnosed incidentally and are often preneoplastic. Their presence may influence the management of patients with chronic diseases such as liver cirrhosis (LC). This study evaluated the prevalence and nature of PCLs in LC patients. Methods The images of 192 LC patients and 192 controls who underwent either computed tomography scan or nuclear magnetic resonance were reviewed for the presence and nature of PCLs. The prevalence of PCLs in both groups and differences between LC patients with and without PCLs were analysed. Multiple logistic regression analysis was used to investigate factors associated with PCLs. Results Thirty-five of 192 LC patients (18%) and 19/192 controls (10%) had PCLs (p = .027). The prevalence of presumptive intraductal pancreatic mucinous neoplasm (IPMN) was double in LC patients compared with controls (14% vs 7%; p = .065). In multivariate analysis, age, LC and having undergone a magnetic resonance cholangiopancreatography were factors associated with PCLs and IPMNs. LC patients with PCLs were older at the time of imaging and had a longer history of liver disease (67 vs. 43 months; p = 0.039) compared with LC patients without PCLs. Conclusions PCLs are more common in LC patients than in controls, and most are IPMNs. The occurrence of PCLs in LC patients seems to be related to age and disease duration.

Lack of Association for Reported Endocrine Pancreatic Cancer Risk Loci in the PANDoRA Consortium

Background: Pancreatic neuroendocrine tumors (PNETs) are rare neoplasms for which very little is known about either environmental or genetic risk factors. Only a handful of association studies have been performed so far, suggesting a small number of risk loci. Methods: To replicate the best findings, we have selected 16 SNPs suggested in previous studies to be relevant in PNET etiogenesis. We genotyped the selected SNPs (rs16944, rs1052536, rs1059293, rs1136410, rs1143634, rs2069762, rs2236302, rs2387632, rs3212961, rs3734299, rs3803258, rs4962081, rs7234941, rs7243091, rs12957119, and rs1800629) in 344 PNET sporadic cases and 2,721 controls in the context of the PANcreatic Disease ReseArch (PANDoRA) consortium. Results: After correction for multiple testing, we did not observe any statistically significant association between the SNPs and PNET risk. We also used three online bioinformatic tools (HaploReg, RegulomeDB, and GTEx) to predict a possible functional role of the SNPs, but we did not observe any clear indication. Conclusions: None of the selected SNPs were convincingly associated with PNET risk in the PANDoRA consortium. Impact: We can exclude a major role of the selected polymorphisms in PNET etiology, and this highlights the need for replication of epidemiologic findings in independent populations, especially in rare diseases such as PNETs. Cancer Epidemiol Biomarkers Prev; 26(8); 1349–51. ©2017 AACR.

Cachexia is an Insidious Symptom of Pancreatic Ductal Adenocarcinoma Associated with Delayed Diagnosis and Advanced Stage of Disease

Context Pancreatic ductal adenocarcinoma (PDAC) is an aggressive neoplasm, frequently presenting with cachexia that seems to retard the diagnosis and leading to worse prognosis. Molecular mechanism of cachexia are increasing explained, but its clinical features and its impacts on prognosis are still unclear. Objective To evaluate prevalence and features of a cachexia as presenting symptom of PDAC, clinical factors associated to its occurrence and its associated survival in PDAC patients. Methods Database retrospective analysis of prospective enrolled PDAC (Jan 2006 to Jan 2012): symptoms, tumor’s features and outcome of patients with cachexia (defined as weight loss >5 kg in the year before diagnosis) compared to those without it. Results Two-hundred and 91 PDAC patients enrolled: 144 (49.4%) presented cachexia (C+). C+ patients had similar medical history (chronic pancreatitis, diabetes, insulin and statin usage) than C-, but they were more frequently male (61.0% C+ vs . 46.5% C-; P=0.04) and overweight subjects (mean BMI: 28.6 kg/m 2 C+ vs . 25.9 kg/m 2 C-; P=0.0001). The onset symptoms other than cachexia were similarly frequent in C- and C+ patients, but for unspecific abdominal pain which was more frequent in C+ (56.4 %) than C- (40.8%; P=0.004). Patients with cachexia had a longer diagnostic delay than C- (4.81 months vs . 2.23 P=0001). C+ and C- patients had similar site and size of primary tumor, as well as histological grading, but C+ had more frequently distant metastasis at diagnosis (44.4% C+ vs . 32.6% C-; P=0.04) and a shorter, although non significantly, overall survival (7 vs . 11 months; P=0.19) compared to C-. Conclusion In our cohort of incident PDAC, about half of patients presented with cachexia. Cachexia was frequently associated with abdominal pain and with a diagnostic delay, and with a metastatic stage at diagnosis. The results suggest that unexplained weight loss and recurrent abdominal pain are under-evaluated symptoms of PDAC, and their investigation might lead to an earlier diagnosis of this aggressive disease.