Expanding endoscopic treatment strategies for pancreatic leaks following pancreato-duodenectomy: a single centre experience.

BACKGROUND AND AIM: Clinically relevant pancreatic leaks of jejunal-pancreatic anastomosis after pancreato-duodenectomy (PD) occur in 9-15% of cases. Endoscopic strategies for management of pancreatic fistula, may allow to avoid reoperation and shorten times for fistula closure, but are still understudied and not widely performed. Aim of the present paper is to describe different endoscopic techniques used to treat such conditions. METHODS: It was a retrospective, single centre, study. All patients who underwent endoscopic treatment for pancreatic leaks following PD between 1st January 2013 and 31th May 2019 at our Centre were reviewed. Depending on the morphology and severity of the leak, four main endoscopic techniques were performed: (1) trans-anastomotic intraductal pancreatic stent insertion; (2) lumen-apposing metal stent between the jejunal loop and the retroperitoneum toward the pancreatic stump insertion ("yoyo-stent"); (3) large calibre nose-to-retroperitoneum drain insertion; (4) when a wide damage of the jejunal wall or a coexistent biliary-jejunal leak were observed, triple metal stent insertion was performed as follow in order to close the defect: enteral fully-covered SEMS in the jejunal stump, a pancreatic metal stent into the Wirsung duct and a fully-covered SEMS across the bilio-digestive anastomosis, through the meshes of the enteral stent. In all cases, surgical drain was simultaneously retracted. RESULTS: We identified 13 patients who underwent endoscopic treatment for POPF after PD. In total, 5 patients underwent "Yoyo stent insertion", 3 with nose-to-collection drain placement and four patients were treated with triple-stent insertion; in only one patient intrapancreatic SEMS insertion was performed. Technical success was 100% and clinical success was 83.3%. Mean time for leak closure was 4.8 days (range 2-10). During the follow-up interval, no leak recurrences were observed. CONCLUSIONS: Our experience confirms efficacy and safety of endoscopic management of POPF following pancreatoduodenectomy management. Endoscopy should play a central role in this clinical scenario.

Endoscopic entero-enteral bypass: an effective new approach to the treatment of postsurgical complications of hepaticojejunostomy.

BACKGROUND: Management of biliary adverse events (BAEs) after biliodigestive anastomosis is challenging. We propose a new endoscopic approach to improve BAEs in this clinical setting. METHODS: Patients who had BAEs after a hepaticojejunostomy with Roux-en-Y loop or a Whipple procedure underwent creation of an entero-enteral endoscopic bypass (EEEB) between the duodenal/gastric wall and the biliary jejunal loop under endoscopic ultrasound (EUS) and fluoroscopic guidance using specifically designed fully covered self-expandable metal stents. RESULTS: 32 consecutive patients underwent EEEB, which was successful in all but one patient. One procedural and five long-term mild adverse events occurred. Endoscopic retrograde cholangiography (ERC) through the EEEB successfully treated all types of BAEs in these patients. Disease recurred in two patients who were successfully re-treated through the EEEB. CONCLUSIONS: Our retrospective study showed that in patients with BAEs after biliodigestive anastomosis, EEEB is safe, feasible, and allows a successful long-term treatment of different BAEs in a tertiary referral center with high-level experience in both endoscopic retrograde cholangiopancreatography and EUS.

Beneficial effect of refined red palm oil on lipid peroxidation and monocyte tissue factor in HCV-related liver disease: a randomized controlled study.

BACKGROUND: A large amount of endotoxin can be detected in the peripheral venous blood of patients with liver cirrhosis, contributing to the pathogenesis of hepatotoxicity because of its role in oxidative stress. The present study aimed to test the effect of the supplementation with red palm oil (RPO), which is a natural oil obtained from oil palm fruit (Elaeis guineensis) rich in natural fat-soluble tocopherols, tocotrienols and carotenoids, on lipid peroxidation and endotoxemia with plasma endotoxin-inactivating capacity, proinflammatory cytokines profile, and monocyte tissue factor in patients with chronic liver disease. METHODS: The study group consisted of sixty patients (34 males and 26 females; mean age 62 years, range 54-75) with Child A/B, genotype 1 HCV-related cirrhosis without a history of ethanol consumption, randomly enrolled into an 8-week oral daily treatment with either vitamin E or RPO. All patients had undergone an upper gastrointestinal endoscopy 8 months before, and 13 out of them showed esophageal varices. RESULTS: Both treatments significantly decreased erythrocyte malondialdehyde and urinary isoprostane output, only RPO significantly affected macrophage-colony stimulating factor and monocyte tissue factor. Liver ultrasound imaging did not show any change. CONCLUSIONS: RPO beneficially modulates oxidative stress and, not least, downregulates macrophage/monocyte inflammatory parameters. RPO can be safely advised as a valuable nutritional implementation tool in the management of chronic liver diseases.

Nonalcoholic fatty liver disease increases risk for gastroesophageal reflux symptoms.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is now recognized as a leading cause of liver dysfunction. Gastroesophageal reflux disease (GERD) is a common disorder causing symptoms that often impair patients' quality of life. In recent years, the prevalence of both these diseases has increased, partially overlapping the rise of metabolic disorders. AIMS: We investigated whether a relation does exist between NAFLD and GERD symptoms. METHODS: Cross-sectional study among 206 outpatients diagnosed with NAFLD and 183 controls. We collected clinical and laboratory data, assessed severity and frequency of GERD symptoms and the esophageal endoscopic pattern. RESULTS: The prevalence of GERD symptoms was higher in NAFLD patients than controls (61.2 vs. 27.9%, p < 0.001). We found a positive association between NAFLD and the experiencing of heartburn, regurgitation and belching. GERD symptoms were related to body mass index (BMI) and metabolic syndrome (MetS); a strong association persisted after adjustment for all the covariates (adjusted OR 3.49, 95 CI% 2.24-5.44, p < 0.001). CONCLUSIONS: Our data show that the prevalence of GERD typical symptoms is higher in patients with NAFLD. GERD was associated with higher BMI and MetS, but not with age and diabetes type 2. NAFLD remained strongly associated with GERD, independently of a coexisting MetS status. Consistent with these findings, MetS can be considered a shared background, but cannot completely explain this correlation. We suggest NAFLD as an independent risk factor for GERD symptoms.

Testing a novel bioactive marine nutraceutical on osteoarthritis patients.

Osteoarthritis (OA) is a slow, chronic joint disease characterized by focal degeneration of articular cartilage and alterations of the chemical and mechanical articular function and also major cause of pain and physical disability. There is clinical evidence that increasing dietary n-3 relative to n-6 may be beneficial in terms of symptom management in humans but not all studies conclude that dietary n-3 PUFA supplementation is of benefit, in the treatment of OA. Our recent studies highlight the effect of a biomarine compound (LD-1227) on MMPs, collagen metabolism and on chondrocyte inflammatory markers. Thus, the aim of the present work was to test such bioactive compound versus a common nutraceutical intervention (glucosamine/chrondroitin sulfate) in knee osteoarthritis patients. The patients population consisted of 60 subjects with a recent diagnosis of knee osteoarthririts of mild-moderate severity. Patients were randomized in a double-blind study comparing LD-1227 (group A) versus a mixture of glucosamine (500 mg), chondroitin sulfate (400 mg) (group B). Patients were allowed their established painkillers on demand. At 4, 9 and 18 weeks patients were evaluated as for: VAS score assessing pain at rest, and during physical exercise, Lequesne index, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scale and KOOS scale. Moreover, serum concentrations of IL-6, IL-ß, CRP, TNF-sR1 and TNF-sR2 were assessed. As compared to GC treatment, LD-1227 yielded a quicker and higher degree of improvement of the whole clinical indexes and a lower NSAIDs use at the end of the study. LD-1227 brought about also a more significant downregulation of the tested cytokines cascade. Taken overall, these data suggest that LD-1227 has the potential to be included in the nutraceutical armamentarium in the management of OA.

A sturgeon-derived bioactive compound beneficially modulates nuclear receptors controlling metabolic functions in patients with metabolic syndrome.

The aim of the present study was to test the possible effects of a novel sturgeon-derived compound  (LD-1227) on inflammatory markers related to metabolic nuclear receptors in patients with metabolic syndrome. The study population consisted of 76 patients with metabolic syndrome and 30 healthy subjects who were maintained to their current treatments and randomly supplemented: A) LD-1227 (n=38) or B) placebo (n=38) as compared to C) healthy controls (n=30). LD-1227 or placebo (water-soluble starch) were given daily at breakfast and dinner for three months. Levels of hs-CRP, IL-6, TNF-α, leptin and adiponectin/ resistin index were assayed at the entry, 1 month and 3 months afterwards. At the end of the study period, as compared to B group, LD-1227-treated patients showed a significant improvement of all parameters tested, irrespective of the presence of diabetes. In particular, levels of adiponectin and adiponectin/ resistin index significantly increased following LD-1227 administration. Although the metabolic syndrome remains a multifaceted condition requiring a complex approach, LD-1227 could be a potential safe therapeutic tool to be integrated into a wider treatment and preventive medicine schedule strategy.

Peroral Endoscopic Diverticulotomy (POED) for Zenker Diverticulum Using Submucosal Injection to Perform a Complete Myotomy.

Endoscopic diverticulotomy associated with cricopharyngeal myotomy is a well-known and safe treatment for Zenker diverticulum. We describe our first 5 consecutive cases treated by a new variant of the technique that allows a deeper and longer myotomy than the standard one. Technical success was achieved in all the cases. All patients showed a significant improvement and relevant disappearance of preoperative dysphagia. Tips for the technique are described in the paper. This variant of peroral endoscopic diverticulotomy for Zenker diverticulum is feasible, effective, and guarantees a complete myotomy in selected patients.

Switching from infliximab originator to a first biosimilar is safe and effective. Results of a case-control study with drug levels and antibodies evaluation.

BACKGROUND: Inflammatory bowel disease is treated with anti-TNF agents such as infliximab and its biosimilars, but use of biosimilars is limited due to perceived risks of adverse events. AIM: To explore safety and effectiveness of switching from the infliximab originator to a first biosimilar. PATIENTS AND METHODS: Clinical and biological outcomes were compared between 53 patients who switched from the infliximab originator to the biosimilar CT-P13 (Switched group) and 13 patients treated with CT-P13 from the beginning (Naïve group). Infliximab trough levels and antidrug antibodies were measured. RESULTS: At enrolment, patients in the Switched group had a longer median duration of infliximab treatment than Naïve (4.0 vs. 0.6 years, p < 0.0001) but similar proportions of patients were in remission (77% and 62%, respectively). Infliximab discontinuation due to adverse events or loss of efficacy was less common in the Switched (26%) than Naïve group (62%, p = 0.017). Variables independently associated with time to discontinuation were disease activity (p < 0.0001) and immunomodulating treatment (p = 0.019) at enrolment. Trough levels and antidrug antibodies were similar between groups during observation. CONCLUSION: This study confirms that switching from infliximab originator to a first biosimilar is safe and effective. Patients at highest risk of losing treatment efficacy are those with active disease, irrespective of the therapeutic switch.

JAK inhibitors: Novel developments in management of ulcerative colitis.

Janus kinase inhibitors are small molecules, orally administered, under development for the treatment of ulcerative colitis. These molecules reduce the immune response, blocking the signal transduction of multiple cytokines implicated in the activation of inflammation. Currently multiple JAK inhibitors are being evaluated in clinical trials. The aim of this review is to examine the efficacy and the safety of the JAK inhibitors being tested and to discuss the available data on the use of these drugs in moderate-to-severe ulcerative colitis, in order to understand how these new molecules can fit into the therapeutic algorithm of patients with ulcerative colitis.

Exploring the metabolic syndrome: Nonalcoholic fatty pancreas disease.

After the first description of fatty pancreas in 1933, the effects of pancreatic steatosis have been poorly investigated, compared with that of the liver. However, the interest of research is increasing. Fat accumulation, associated with obesity and the metabolic syndrome (MetS), has been defined as "fatty infiltration" or "nonalcoholic fatty pancreas disease" (NAFPD). The term "fatty replacement" describes a distinct phenomenon characterized by death of acinar cells and replacement by adipose tissue. Risk factors for developing NAFPD include obesity, increasing age, male sex, hypertension, dyslipidemia, alcohol and hyperferritinemia. Increasing evidence support the role of pancreatic fat in the development of type 2 diabetes mellitus, MetS, atherosclerosis, severe acute pancreatitis and even pancreatic cancer. Evidence exists that fatty pancreas could be used as the initial indicator of "ectopic fat deposition", which is a key element of nonalcoholic fatty liver disease and/or MetS. Moreover, in patients with fatty pancreas, pancreaticoduodenectomy is associated with an increased risk of intraoperative blood loss and post-operative pancreatic fistula.