Clinical management and patient outcomes of acute lower gastrointestinal bleeding. A multicenter, prospective, cohort study.

BACKGROUND & AIM: Although acute lower GI bleeding (LGIB) represents a significant healthcare burden, prospective real-life data on management and outcomes are scanty. Present multicentre, prospective cohort study was aimed at evaluating mortality and associated risk factors and at describing patient management. METHODS: Adult outpatients acutely admitted for or developing LGIB during hospitalization were consecutively enrolled in 15 high-volume referral centers. Demographics, comorbidities, medications, interventions and outcomes were recorded. RESULTS: Overall 1,198 patients (1060 new admissions;138 inpatients) were included. Most patients were elderly (mean-age 74±15 years), 31% had a Charlson-Comorbidity-Index ≥3, 58% were on antithrombotic therapy. In-hospital mortality (primary outcome) was 3.4% (95%CI 2.5-4.6). At logistic regression analysis, independent predictors of mortality were increasing age, comorbidity, inpatient status, hemodynamic instability at presentation, and ICU-admission. Colonoscopy had a 78.8% diagnostic yield, with significantly higher hemostasis rate when performed within 24-hours than later (21.3% vs.10.8%, p = 0.027). Endoscopic hemostasis was associated with neither in-hospital mortality nor rebleeding. A definite or presumptive source of bleeding was disclosed in 90.4% of investigated patients. CONCLUSION: Mortality in LGIB patients is mainly related to age and comorbidities. Although early colonoscopy has a relevant diagnostic yield and is associated with higher therapeutic intervention rate, endoscopic hemostasis is not associated with improved clinical outcomes [ClinicalTrial.gov number: NCT04364412].

[Diverticular disease: towards 2020. An evidence-based approach]. / La malattia diverticolare verso il 2020. Un approccio evidence-based.

Diverticular disease (DD) of the colon has an increasing burden on health service resources, in terms of hospital admissions, mortality and surgery rate. We present an overview of the clinical history of DD, and of the ways that gastroenterologists have to modify it. Prevalence of the disease increases with aging. Most of diverticulosis are occasionally identified on colonscopy, and most of them remain asymptomatic for all life. Only 4% of these subjects develop diverticulitis. However, 4-25% of these patients are expected to present a second episode of diverticulitis, and 15% of them develop complications. Hospitalizations for diverticulitis and relapses of diverticulitis show strong growth (+21% 2013 vs 2003 in USA). The total annual costs for hospitalization for DD in USA are over 2,2 billion of dollars, and in Italy exceed 63 million of euros. In-hospital mortality can reach 0,5%. Diagnosis of diverticulitis is based on clinical history, lab tests and imaging (ultrasonography, CAT). Clinical diagnosis has a sensitivity of 68% and specificity around 98%. According to a meta-analysis, the performance of ultrasonograhy and CAT results very high ("pooled" sensitivity 92-94%, and specificity 90-99%; "pooled" Likelihood Ratio positive 9.6 for ultrasonography and 78.4 for CAT. Likelihood Rato negative 0.09 and 0.06 respectively). Evidences for preventing relapse are poor. Anyway, a very recent meta-analysis on 6 RCTs suggests no role for mesalazine (GRADE SCALE for evidence 3). Non absorbable antibiotics (rifaximin) have been used in two studies (one RCT, one retrospective observational). Data from the two studies suggest some evidence in favour of its use (GRADE SCALE 1). The number of admitted patients is 291. Considering a base-line risk of 19 relapses every 100 patients (5-year observation period), the absolute risk difference is minus 9 patients with relapse (CI 95% -14 a + 3) in the RCT and minus 14 patients (CI 95% -17 a -5) in the observational study. A 2020 preview suggests an exploding interest in assessing the risk factors for relapse (including aspirin and NSAIDs) and identifying the better strategy to reduce it. Further trials are requested, including the use of probiotics alone.

Neoadjuvant chemo-radiotherapy for patients with borderline resectable pancreatic cancer: a meta-analytical evaluation of prospective studies.

CONTEXT: For patients with borderline resectable pancreatic cancer, the benefit of neoadjuvant therapy remains to be defined. OBJECTIVE: We did a systematic search of the literature on this topic. METHODS: Prospective studies where chemotherapy with or without radiotherapy was given before surgery to patients with borderline resectable cancer, were analyzed by a meta-analytical approach. MAIN OUTCOME MEASURES: Primary outcome was surgical exploration and resection rates; tumor response, therapy-induced toxicity, and survival were secondary outcomes. Data were expressed as weighted pooled proportions with 95% confidence intervals (95% CI). RESULTS: Ten studies with 182 participants were included. Following treatment, 69% of patients (95% CI: 56-80%) were brought to surgery and 80% (95% CI: 66-90%) of surgically-explored patients were resected. Eighty-three percent (95% CI: 74-90%) of resected specimens were deemed R0 resections. The weighted fractions of resected patients alive at 1 and 2 years were 61% (95% CI: 48-100%) and 44% (95% CI: 32-59%), respectively. At restaging following neoadjuvant therapy, weighted frequencies for complete/partial response were 16% (95% CI: 9-28%), 69% (95% CI: 60-76%) for stable disease, and 19% (95% CI: 13-25%) for progressive cancer. Treatment-related grade 3-4 toxicity was 32% (95% CI: 21-45%). CONCLUSION: This meta-analysis shows that downstaging of the lesion following neoadjuvant therapies is uncommon for patients with borderline resectable pancreatic cancer. A clear benefit of this regimen could be to spare surgery to patients with progressive disease during the frame-time chemo-radiotherapy is being delivered.

Neoadjuvant/preoperative gemcitabine for patients with localized pancreatic cancer: a meta-analysis of prospective studies.

BACKGROUND: Long-term prognosis for localized pancreatic cancer remains poor. We sought to assess the benefit of neoadjuvant/preoperative chemotherapy with or without radiotherapy. METHODS: Prospective studies where gemcitabine with or without radiotherapy was provided before surgery in patients with initially resectable or unresectable disease were reviewed by meta-analysis. Primary outcome was survival, and secondary outcomes were tumor response after therapy, toxicity, surgical exploration, and resection rates. RESULTS: Twenty independent studies with 707 participants were included, 366 with resectable lesions and 341 with unresectable lesions. Seven studies were phase I/II trials, 10 phase II, and 3 prospective cohort studies. Estimated 1- and 2-year survival probabilities after resection were 91.7% (95% confidence interval [CI] 75-100) and 67.2% (95% CI 38-87) for initially resectable patients, and 86.3% (95% CI 78-100) and 54.2% (95% CI 25-100) for initially unresectable patients. The complete/partial response rate was 12% (95% CI 4-23) and 27% (95% CI 18-38) in resectable and unresectable lesions, respectively. The rate of treatment-related grade 3-4 toxicity was 31% (95% CI 21-42). Of resectable patients evaluable after restaging, 91% (95% CI 83-97) underwent surgery, and 82% (95% CI 65-95) of explored patients underwent resection. R0 resections amounted to 89% (95% CI 83-94). Of unresectable patients evaluable after restaging, 39% (95% CI 28-50) underwent surgery, and 68% (95% CI 53-82) of explored patients were resected, with 60% (95% CI 50-71) R0 resections. CONCLUSIONS: Current analysis provides marginal support to the assumed benefits of neoadjuvant therapies for patients with resectable cancer, and indicates a potential advantage only for a minority of those with unresectable lesions.

Artificial neural networks can classify uninvestigated patients with dyspepsia.

There is consensus on investigating older patients presenting with or without alarm symptoms and/or risk factors, and irrespective of their Helicobacter pylori status. Remaining patients with uninvestigated dyspepsia, however, represents a 'grey' population for whom no clearly defined guidelines have been delineated. Physicians often struggle with the decision of whether or not to undertake noninvasive testing, treat dyspeptic patients empirically or perform an invasive endoscopy of the upper gastrointestinal tract. We have explored the contribution of artificial neural networks (ANNs) to provide appropriate interpretation of presenting complaints and clinical characteristics for these patients. By taking into account all the 86 recorded features of 101 dyspeptic patients, the overall predictive capability of ANNs in sorting out organic from functional disease amounted to 74.2% and increased to a figure of 85.0% when only the 55 best performing input variables were analyzed. The ANNs performed much better in extracting those patients with a functional dyspepsia (90% accuracy rate), but even in patients with organic disease the 80% accuracy value was remarkable. In patients with an uninvestigated dyspepsia, ANNs found a unique combination of socioenvironmental data, past medical history, risk factors for organic disease, and presenting abdominal complaints that each patient brings to the clinical encounter. With this ability, ANNs can be used to assist in the classification and treatment of patients with uninvestigated dyspepsia, and to bring a greater level of confidence to this process.

Long-term outcome of Crohn's disease following corticosteroid-induced remission.

INTRODUCTION: Corticosteroids are the gold standard in the treatment of moderate to severe Crohn's disease but are often associated with severe and potentially dangerous side effects. Despite an initial clinical response many patients become steroid dependent or require further steroid courses in the long term. The aim of the present study was to assess the probability of the need for further steroid treatment in Crohn's disease patients following steroid-induced remission and to establish if clinical variables can predict further steroid needs. PATIENTS AND All METHODS: patients at their first steroid course and with corticosteroid-induced remission, defined as a Crohn's Disease Activity Index (CDAI) <150, 4 wk after steroid weaning, were studied and observed at follow-up for 12 months. The main outcome was clinical relapse requiring further steroid treatment. Statistical analysis was performed using the Kaplan-Meier method and multivariable Cox proportional hazard regression model taking into consideration gender, age at diagnosis, disease location and behavior, smoking habits, CDAI score before steroid treatment, and C reactive protein values at steroid weaning, as covariates. RESULTS: A total of 77 patients with steroid-induced remission were included. One-year follow-up was available in 75 of the 77 patients (97.4%). During follow-up 49 of 75 patients (65.3%) maintained remission or presented mild relapse not requiring steroids while 26 of 75 patients (34.6%) had moderate to severe relapse requiring further steroid treatment. The cumulative probability of a course free from steroids was 93.3%, 82.6%, 78.6%, and 66.6% at 3, 6, 9, and 12 months, respectively. At multivariate analysis, increased C reactive protein at steroid weaning and penetrating complications were independent risk factors for further steroid requirement (OR 5.57, 95% CI 1.20-25.91, P= 0.001 and OR 4.20, 95% CI 1.76-10.04, P= 0.005, respectively). CONCLUSION: Despite an initial clinical response and successful steroid tapering, 35% of patients required further steroid treatment within 1 yr. An increased C reactive protein value, at steroid weaning, despite clinical remission, and penetrating complications may predict further steroid requirement in already steroid responsive patients.

Survival of cirrhotic patients with early hepatocellular carcinoma treated by percutaneous ethanol injection or liver transplantation.

For "early" hepatocellular carcinoma (HCC), surgery, orthotopic liver transplantation (OLT) and percutaneous ethanol injection (PEI) improve the natural history of the disease. We performed a retrospective study to evaluate the outcome of patients with cirrhosis and early HCC treated by PEI (n = 417) or OLT (n = 172). Overall, 589 patients with cirrhosis were studied. The proportion of patients in Child-Turcotte-Pugh (CTP) classes A, B, and C was 52.5%, 33.6%, and 13.9%, respectively. Most patients (78.9%) had solitary HCC. Overall 5-year and 10-year cumulative survival rates were 36.1% and 15.5% after PEI, and 66.3% and 49.1% after OLT, respectively (P < .0001). Overall 5-year and 10-year cumulative tumor-free survival rates were 25.3% and 18.0% after PEI, and 84.6% and 82.2% after OLT, respectively (P < .0001). When patients were sorted according to the severity of cirrhosis, mean survival times in PEI and OLT patients were 67 and 80 months in CTP class A (P = .05), 38 and 90 months in class B (P < .0001), and 31 and 95 months in class C (P = .0004). Similarly, mean tumor-free survival times in the 2 series of patients were 49 and 98 months in CTP class A (P < .0001), 39 and 121 months in class B (P < .0001), and 35 and 139 months in class C (P < .0001). In conclusion, this study challenges the therapeutic efficacy of PEI for patients with cirrhosis and early HCC, when compared to OLT: the proportion of both long-term survivors and tumor-free survivors was increased by OLT over PEI. The benefit of OLT extends to all patients, regardless of the degree of liver impairment.

Prophylaxis of ERCP-related pancreatitis: a randomized, controlled trial of somatostatin and gabexate mesylate.

BACKGROUND & AIMS: It still is debated whether post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis can be prevented by administering either somatostatin or gabexate mesylate. The aim of the study is to assess the efficacy of a 6.5-hour infusion of somatostatin or gabexate mesylate in preventing ERCP-related complications. METHODS: In a double-blind multicenter trial, 1127 patients undergoing ERCP were randomly assigned to intravenous administration of somatostatin (750 microg; n = 351), gabexate mesylate (500 mg; n = 381), or placebo (saline; n = 395). The drug infusion started 30 minutes before and continued for 6 hours after endoscopy. Patients were evaluated clinically, and serum amylase levels were determined at 4, 24, and 48 hours after endoscopy. RESULTS: No significant differences in incidences of pancreatitis, hyperamylasemia, or abdominal pain were observed among the placebo (4.8%, 32.6%, and 5.3%, respectively), somatostatin (6.3%, 26.8%, and 5.1%, respectively), and gabexate mesylate groups (5.8%, 31.5%, and 6.3%, respectively). Univariate analysis of patient characteristics and endoscopic maneuvers showed that a Freeman score >1 (P < 0.0001), >/=3 pancreatic injections (P < 0.00001), and precut sphincterotomy (P = 0.01) were significantly associated with post-ERCP pancreatitis. At multiple logistic regression analysis, >/=3 pancreatic injections (odds ratio [OR], 1.95; 95% confidence interval [CI], 1.45-2.63) and a Freeman score >1 (OR, 1.47; 95% CI, 1.11-1.94) retained their predictive power. CONCLUSIONS: Long-term (6.5-hr) administration of either somatostatin or gabexate mesylate is ineffective for the prevention of post-ERCP pancreatitis. Pancreatic injury seems to be related to difficulty in common bile duct access.

Amoxicillin/tetracycline combinations are inadequate as alternative therapies for Helicobacter pylori infection.

BACKGROUND: Triple therapy with proton pump inhibitors or ranitidine bismuth citrate, clarithromycin and either amoxicillin or nitroimidazole derivatives are the present gold standards for cure of Helicobacter pylori infection. However, primary resistance to either clarithromycin or nitroimidazole derivatives is increasing and alternative therapies are needed. AIM: To determine the efficacy and safety of three regimens consisting of amoxicillin and tetracycline or doxycycline combined with either lansoprazole or ranitidine bismuth citrate. METHODS: Two hundred and seventy H. pylori infected patients were randomly given one of the following treatments: amoxicillin 1 g twice a day (b.i.d.) plus tetracycline 500 mg four times a day (q.i.d.) with either lansoprazole 30 mg b.i.d. (group LAT) or ranitidine bismuth citrate 400 mg b.i.d. (group RBCAT) for 7 days and amoxicillin 1 g b.i.d. plus doxycycline 100 mg b.i.d. and lansoprazole 30 mg b.i.d. for 14 days (group LAD). Eradication rate was assessed by UBT at 4-6 weeks after therapy. RESULTS: The three groups (LAT, RBCAT, and LAD) of patients achieved eradication rates of 35% (25-45), 20% (12-29) and 36% (25-46), respectively, on intention-to-treat analysis. Patient compliance was optimal and side-effects minimal in all three groups. CONCLUSIONS: Although the amoxicillin/tetracycline combination is attractive (inexpensive, safe, and with low primary resistance rate), it can not be recommended for H. pylori eradication.