Endoscopic management of malignant biliary obstructions.

Malignant biliary obstruction (MBO), both distal and hilar, represents an ensemble of different clinical conditions frequently encountered in everyday practice. Given the frequent unresectability of the disease at presentation and the increasing indications for neoadjuvant chemotherapy, endoscopic biliary drainage is generally required during the course of the disease. With the widespread use of interventional endoscopic ultrasound (EUS) and the introduction of dedicated devices, EUS-guided biliary drainage has rapidly gained acceptance, together with transpapillary endoscopic biliary drainage and the percutaneous approach. This comprehensive review describes the current role of endoscopy for distal and hilar MBO supported by evidence, with a focus on the current hot topics in this field.

Early Rectal Cancer and Local Excision: A Narrative Review.

A rise in the incidence of early rectal cancer consequent to bowel-screening programs around the world and an increase in the incidence in young adults has led to a growing interest in organ-sparing treatment options. The rectum, being the most distal portion of the large intestine, is a fertile ground for local excision techniques performed with endoscopic or surgical techniques. Moreover, the advancement in endoscopic optical evaluation and the better definition of imaging techniques allow for a more precise local staging of early rectal cancer. Although the local treatment of early rectal cancer seems promising, in clinical practice, a significant number of patients who could benefit from local excision techniques undergo total mesorectal excision (TME) as the first approach. All relevant prospective clinical trials were identified through a computer-assisted search of the PubMed, EMBASE, and Medline databases until January 2024. This review is dedicated to endoscopic and surgical local excision in the treatment of early rectal cancer and highlights its possible role in current and future clinical practice, taking into account surgical completion techniques and chemoradiotherapy.

Endoscopic Management of Bleeding in Altered Anatomy after Upper Gastrointestinal Surgery.

Postoperative non variceal upper gastrointestinal haemorrhage may occur early or late and affect a variable percentage of patients-up to about 2%. Most cases of intraluminal bleeding are an indication for urgent Esophagogastroduodenoscopy (EGD) and require endoscopic haemostatic treatment. In addition to the approach usually adopted in non-variceal upper haemorrhages, these cases may be burdened with difficulties in terms of anastomotic tissue, angled positions, and the risk of further complications. There is also extreme variability related to the type of surgery performed, in the context of oncological disease or bariatric surgery. At the same time, the world of haemostatic devices available in digestive endoscopy is increasing, meeting high efficacy rates and attempting to treat even the most complex cases. Our narrative review summarises the current evidence in terms of different approaches to endoscopic haemostasis in upper bleeding in altered anatomy after surgery, proposing an up-to-date guidance for endoscopic clinicians and at the same time, highlighting areas of future scientific research.

Chronic non-allergic rhinitis with neutrophils is associated with higher acid exposure time: A pH-impedance monitoring study.

BACKGROUND & AIM: Chronic rhinitis, a diffuse disease with a prevalence of 40%, can be classified in allergic (AR) and non-allergic rhinitis (NAR). Nasal cytology allows for the identification of different NAR sub-types according to the inflammatory cell infiltrate. NAR etiopathogenesis is not well clarified and, for NARNE (non-allergic rhinitis with neutrophils) subtype, gastroesophageal reflux disease (GERD) has been suggested as one of the etiopathogenetic factors. Aim of this study is to evaluate the role of GERD in patients with NARNE. METHODS: Fifty-one consecutive patients referred to our Ear, Nose and Throat (ENT) unit with nasal symptoms and cytology suggestive for NAR, were enrolled in the study. All the patients performed a gastroenterological evaluation, high resolution esophageal manometry and a 24-h pH-Impedance monitoring. RESULTS: Twenty-five (49%) patients tested positive at nasal cytology for NARNE. A pathologic pH-impedance was identified in seven patients (28%) with NARNE, as opposed to only one (4%) with different NAR subtypes. Statistical analysis showed that higher acid exposure time (AET) and weaker post nasal drainage were more common in NARNE vs. other NAR patients. CONCLUSIONS: NARNE strongly correlates with higher AET and refluxes number; thus, NARNE patients should be tested with pH-impedance monitoring in addition to nasal cytology.

Simkania negevensis in Crohn's Disease.

BACKGROUND: Simkania negevensis is an obligate intracellular Gram-negative bacterium (family Simkaniaceae, order Chlamydiales) that has been isolated from domestic and mains water supplies, is able to infect human macrophages, and can induce an inflammatory response in the host. METHODS: From June to December 2016, in a single-center observational study, colonic Crohn's disease patients and controls (subjects undergoing screening for colorectal cancer) underwent blood tests to identify serum-specific immunoglobulin G (IgG) and immunoglobulin A (IgA) to S. negevensis and a colonoscopy with biopsies for detection of S. negevensis DNA by polymerase chain reaction (PCR). RESULTS: Forty-three Crohn's disease patients and 18 controls were enrolled. Crohn's disease patients had higher prevalence of IgA antibodies to S. negevensis compared with controls (20.9% versus 0%, p = 0.04). Simkaniaceae negevensis DNA was detected in 34.9% and 5.6% of intestinal biopsies in Crohn's disease patients and controls, respectively (p = 0.02). All Crohn's disease patients with PCR-positive biopsies for S. negevensis were IgG seropositive, with specific IgA in 60% of them (p < 0.001). Immunosuppressive therapies, extraintestinal manifestations, or disease activity did not influence the presence of S. negevensis in the Crohn's disease population. CONCLUSIONS: We identified S. negevensis in Crohn's disease patients by demonstrating the presence of S. negevensis mucosal DNA and seropositivity to the bacterium. These results could support the presence of an acute or persistent S. negevensis infection and suggest a possible role in the pathogenesis of Crohn's disease.

Retention Rate, Persistence and Safety of Adalimumab in Inflammatory Bowel Disease: A Real-Life, 9-Year, Single-Center Experience in Italy.

BACKGROUND: "Real-life" data of retention rate and persistence of adalimumab in inflammatory bowel disease are still limited. AIMS: To analyze retention rate, persistence, and safety of adalimumab in a 9-year real-life cohort of inflammatory bowel disease patients. METHODS: In this observational, retrospective single-center study, all adult patients treated with adalimumab as the first- and second-line biological treatment for steroid-dependent or refractory inflammatory bowel disease between March 2008 and March 2017 were included. Primary outcomes were persistence, retention rate, and adverse events; the secondary outcome was the identification of predictors of withdrawal. RESULTS: Ninety-six out of 181 patients (53%) withdrew their first course of adalimumab. The retention rate was 47% and 46.9% in Crohn's disease and ulcerative colitis patients, respectively; median persistence was 26 and 24 months in CD and UC patients, respectively. The cumulative probability of treatment persistence was 80.2%, 54.5%, and 29.6% and 69.6%, 40.4%, and 21.5% in CD and UC patients, respectively. The incidence rate of any adverse event was 12.5/100 patients-year; severe adverse events were 1.7/100 patients-year. The Cox regression revealed that CD patients with baseline disease duration > 72 months have a higher likelihood for withdrawal due to failure and/or adverse events (HR 1.62, 95% CI 1-2.62, p = 0.04); no predictors of discontinuation were found in UC. CONCLUSIONS: Adalimumab showed a great persistence in the first 12 months of therapy and excellent safety profile. Early treatment of CD patients could increase efficacy and reduce the adverse event rate.

Periendoscopic management of direct oral anticoagulants: a prospective cohort study.

OBJECTIVE: To assess the frequency of adverse events associated with periendoscopic management of direct oral anticoagulants (DOACs) in patients undergoing elective GI endoscopy and the efficacy and safety of the British Society of Gastroenterology (BSG) and European Society of Gastrointestinal Endoscopy (ESGE) recommendations (NCT02734316). DESIGN: Consecutive patients on DOACs scheduled for elective GI endoscopy were prospectively included. The timing of DOAC interruption and resumption before and after the procedures were recorded, along with clinical and procedural data. Procedures were stratified into low-risk and high-risk for GI-related bleeding, and patients into low-risk and high-risk for thromboembolic events. Patients were followed-up for 30 days for major and clinically relevant non-major bleeding events (CRNMB), arterial and venous thromboembolism and death. RESULTS: Of 529 patients, 38% and 62% underwent high-risk and low-risk procedures, respectively. There were 45 (8.5%; 95% CI 6.3% to 11.2%) major or CRNMB events and 2 (0.4%; 95% CI 0% to 1.4%) thromboembolic events (transient ischaemic attacks). Overall, the incidence of bleeding events was 1.8% (95% CI 0.7% to 4%) and 19.3% (95% CI 14.1% to 25.4%) in low-risk and high-risk procedures, respectively. For high-risk procedures, the incidence of intraprocedural bleeding was similar in patients who interrupted anticoagulation according to BSG/ESGE guidelines or earlier (10.3%vs10.8%, p=0.99), with a trend for a lower risk as compared with those who stopped anticoagulation later (10.3%vs25%, p=0.07). The incidence of delayed bleeding appeared similar in patients who resumed anticoagulation according to BSG/ESGE guidelines or later (6.6%vs7.7%, p=0.76), but it tended to increase when DOAC was resumed earlier (14.4%vs6.6%, p=0.27). The risk of delayed major bleeding was significantly higher in patients receiving heparin bridging than in non-bridged ones (26.6%vs5.9%, p=0.017). CONCLUSION: High-risk procedures in patients on DOACs are associated with a substantial risk of bleeding, further increased by heparin bridging. Adoption of the BSG/ESGE guidelines in periendoscopic management of DOACs seems to result in a favourable benefit/risk ratio. TRIAL REGISTRATION NUMBER: NCT02734316; Pre-results.

The Imbalance between n-6/n-3 Polyunsaturated Fatty Acids and Inflammatory Bowel Disease: A Comprehensive Review and Future Therapeutic Perspectives.

Eating habits have changed dramatically over the years, leading to an imbalance in the ratio of n-6/n-3 polyunsaturated fatty acids (PUFAs) in favour of n-6 PUFAs, particularly in the Western diet. Meanwhile, the incidence of inflammatory bowel disease (IBD) is increasing worldwide. Recent epidemiological data indicate the potential beneficial effect of n-3 PUFAs in ulcerative colitis (UC) prevention, whereas consumption of a higher ratio of n-6 PUFAs versus n-3 PUFAs has been associated with an increased UC incidence. The long-chain dietary n-3 PUFAs are the major components of n-3 fish oil and have been shown to have anti-inflammatory properties in several chronic inflammatory disorders, being involved in the regulation of immunological and inflammatory responses. Despite experimental evidence implying biological plausibility, clinical data are still controversial, especially in Crohn's disease. Clinical trials of fish-oil derivatives in IBD have produced mixed results, showing beneficial effects, but failing to demonstrate a clear protective effect in preventing clinical relapse. Such data are insufficient to make a recommendation for the use of n-3 PUFAs in clinical practice. Here, we present the findings of a comprehensive literature search on the role of n-3 PUFAs in IBD development and treatment, and highlight new therapeutic perspectives.

Sulfasalazine in Prevention of Pouchitis After Proctocolectomy with Ileal Pouch-Anal Anastomosis for Ulcerative Colitis.

BACKGROUND: Pouchitis is the most frequent complication after ileal pouch-anal anastomosis for refractory ulcerative colitis. A non-standardized preventative treatment exists. Sulfasalazine has proved effective in acute pouchitis therapy. AIMS: The aim of this study was to retrospectively evaluate the effect of sulfasalazine in primary prophylaxis of pouchitis after proctocolectomy with ileal pouch-anal anastomosis. METHODS: Data files of patients who underwent total proctocolectomy with ileal pouch-anal anastomosis for refractory ulcerative colitis and/or dysplasia from January 2007 to December 2014, with a follow-up until August 2015, were analyzed. After closure of loop ileostomy, on a voluntary basis, patients received a primary prophylaxis of pouchitis with sulfasalazine (2000 mg per day) continually until acute pouchitis flare and/or drop out due to side effects. RESULTS: Follow-up data were available for 51 of the 55 surgical patients. Median follow-up time was 68 months (range 10-104). Thirty postoperative complications occurred in 25 patients. 45% of patients developed pouchitis. Sulfasalazine prophylaxis was administered in 39.2% of patients; 15% of the these developed pouchitis versus 64.5% (20/31) of the non-sulfasalazine patients (p < 0.001). Pouchitis-free survival curves were 90.55 months in sulfasalazine patients and 44.46 in non-sulfasalazine patients (log-rank test p = 0.001, Breslow p = 0.001). CONCLUSION: Sulfasalazine may be potentially administered in pouchitis prophylaxis after proctocolectomy with ileal pouch-anal anastomosis, but large prospectively controlled trials are needed.

How to predict clinical relapse in inflammatory bowel disease patients.

Inflammatory bowel diseases have a natural course characterized by alternating periods of remission and relapse. Disease flares occur in a random way and are currently unpredictable for the most part. Predictors of benign or unfavourable clinical course are required to facilitate treatment decisions and to avoid overtreatment. The present article provides a literature review of the current evidence on the main clinical, genetic, endoscopic, histologic, serologic and fecal markers to predict aggressiveness of inflammatory bowel disease and discuss their prognostic role, both in Crohn's disease and ulcerative colitis. No single marker seems to be reliable alone as a flare predictor, even in light of promising evidence regarding the role of fecal markers, in particular fecal calprotectin, which has reported good results recently. In order to improve our daily clinical practice, validated prognostic scores should be elaborated, integrating clinical and biological markers of prognosis. Finally, we propose an algorithm considering clinical history and biological markers to intercept patients with high risk of clinical relapse.

The Pharmacokinetic Profile of a New Gastroresistant Capsule Preparation of Eicosapentaenoic Acid as the Free Fatty Acid.

Supplementation with n-3 polyunsaturated fatty acids (n-3 PUFAs) may be beneficial for patients with inflammatory bowel diseases (IBD). In this study we analyzed the pharmacokinetic profile of eicosapentaenoic acid (EPA), as the free fatty acid (FFA), in an enteric-coated preparation, in 10 ulcerative colitis (UC) and 10 Crohn's disease (CD) patients and 15 healthy volunteers (HV). Subjects received 2 g daily of EPA-FFA for 8 weeks. Plasma phospholipid and red blood cell (RBC) membrane fatty acid content were measured by gas chromatography-mass spectrometry. There was a rapid incorporation of EPA into plasma phospholipids by 2 weeks and a slower, but highly consistent, incorporation into RBC membranes (4% total fatty acid content; coefficient of variation 10-16%). There was a concomitant reduction in relative n-6 PUFA content. Elongation and desaturation of EPA into docosahexaenoic acid (DHA) via docosapentaenoic acid (DPA) were apparent and DHA content also increased in membranes. EPA-FFA is well tolerated and no difference in the pharmacokinetic profile of n-3 PUFA incorporation was detected between IBD patients and HV. Our data support the concept that EPA can be considered the "universal donor" with respect to key n-3 PUFAs and that this enteric-coated formulation allows long term treatment with a high level of compliance.

Clinical application of faecal calprotectin in ulcerative colitis patients.

OBJECTIVE: Faecal calprotectin (FC) is the most relevant noninvasive biomarker for monitoring inflammatory status, response to treatment and for predicting clinical relapse in ulcerative colitis (UC). The aim of this study was to evaluate the role of FC in predicting both clinical/endoscopic activity and clinical relapse in a large UC patient cohort. PATIENTS AND METHODS: A two-phase prospective study was carried out. In the first phase, the relationship between FC and clinical/endoscopic activity was evaluated. In the second phase, a cohort of asymptomatic patients with endoscopic mucosal healing was followed up using clinical and FC level determinations. RESULTS: One hundred and twenty-one UC patients were enrolled. The FC concentrations were directly correlated with both clinical and endoscopic activity (r=0.76 and 0.87, respectively, P<0.05) and were capable of differentiating between different degrees of endoscopic severity (P<0.01). An FC cut-off value of 110 µg/g was highly predictive (95%) of endoscopic activity. Seventy-four patients in clinical remission with mucosal healing were followed up for a year or until relapse and 27% developed a clinical relapse. The FC concentration of nonrelapsed patients (48 µg/g) versus relapsed patients (218 µg/g) was significantly different (P<0.01). An FC cut-off value of 193 µg/g had an accuracy of 89% in predicting clinical relapse. High FC levels were associated with clinical relapse using survival analysis and multivariate analysis. CONCLUSION: Our data strongly support the use of FC for staging the activity of disease, predicting relapse and leading decision-making in a UC setting.

Mycobacterium avium subspecies paratuberculosis in the etiology of Crohn's disease, cause or epiphenomenon?

The origin of inflammatory bowel disease is unknown. Attempts have been made to isolate a microorganism that could explain the onset of inflammation, but no pathological agent has ever been identified. Johne's disease is a granulomatous chronic enteritis of cattle and sheep caused by Mycobacterium avium subspecies paratuberculosis (MAP) and shows some analogies with Crohn's disease (CD). Several studies have tried to clarify if MAP has a role in the etiology of CD. The present article provides an overview of the evidence in favor and against the "MAP-hypothesis", analyzing the methods commonly adopted to detect MAP and the role of antimycobacterial therapy in patients with inflammatory bowel disease. Studies were identified through the electronic database, MEDLINE, and were selected based on their relevance to the objective of the review. The presence of MAP was investigated using multiple diagnostic methods for MAP detection and in different tissue samples from patients affected by CD or ulcerative colitis and in healthy controls. On the basis of their studies, several authors support a close relationship between MAP and CD. Although increasing evidence of MAP detection in CD patients is unquestionable, a clear etiological link still needs to be proven.

A rare case of giant pseudopolyp and colitis cystica profunda coexistence in an ulcerative colitis patient / Un caso raro de coexistencia de un pseudopólipo gigante y colitis cística profunda en un paciente con colitis ulcerosa

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Asymptomatic and persistent elevation of pancreatic enzymes in an ulcerative colitis patient.

Azathioprine has been extensively used in the management of inflammatory bowel diseases. It might cause pancreatic damage in the form of either asymptomatic elevation in serum amylase/lipase or overt acute pancreatitis. Here we report the case of a 61-year-old patient with ulcerative colitis who had been treated with azathioprine for three years, achieving clinical remission. During treatment he presented an asymptomatic elevation of serum pancreatic enzymes, without any signs of pancreatitis at imaging. This evidence brought us to reassess the drug dosage, without achieving a normalization of biochemical analysis. Autoimmune pancreatitis was excluded. One year after the suspension of azathioprine, we still face persistent high levels of amylase/lipase. Normalization of enzymatic values in patients who develop intolerance to azathioprine, in the form of either asymptomatic elevation in serum amylase/lipase or overt acute pancreatitis, is usually achieved in about two months after stopping drug intake. Asymptomatic elevation in serum pancreatic enzymes in the absence of pancreatic disease is reported in the literature and defined as "Gullo's syndrome," but nobody of the subjects studied had been treated in the past with pancreatotoxic drugs. Might this case be defined as "benign pancreatic hyperenzymemia"?