Standard of Care Versus Octreotide in Angiodysplasia-Related Bleeding (the OCEAN Study): A Multicenter Randomized Controlled Trial.

BACKGROUND & AIMS: Gastrointestinal angiodysplasias are vascular anomalies that may result in transfusion-dependent anemia despite endoscopic therapy. An individual patient data meta-analysis of cohort studies suggests that octreotide decreases rebleeding rates, but component studies possessed a high risk of bias. We investigated the efficacy of octreotide in reducing the transfusion requirements of patients with angiodysplasia-related anemia in a clinical trial setting. METHODS: The study was designed as a multicenter, open-label, randomized controlled trial. Patients with angiodysplasia bleeding were required to have had at least 4 red blood cell (RBC) units or parental iron infusions, or both, in the year preceding randomization. Patients were allocated (1:1) to 40-mg octreotide long-acting release intramuscular every 28 days or standard of care, including endoscopic therapy. The treatment duration was 1 year. The primary outcome was the mean difference in the number of transfusion units (RBC + parental iron) between the octreotide and standard of care groups. Patients who received at least 1 octreotide injection or followed standard of care for at least 1 month were included in the intention-to-treat analyses. Analyses of covariance were used to adjust for baseline transfusion requirements and incomplete follow-up. RESULTS: We enrolled 62 patients (mean age, 72 years; 32 men) from 17 Dutch hospitals in the octreotide (n = 31) and standard of care (n = 31) groups. Patients required a mean number of 20.3 (standard deviation, 15.6) transfusion units and 2.4 (standard deviation, 2.0) endoscopic procedures in the year before enrollment. The total number of transfusions was lower with octreotide (11.0; 95% confidence interval [CI], 5.5-16.5) compared with standard of care (21.2; 95% CI, 15.7-26.7). Octreotide reduced the mean number of transfusion units by 10.2 (95% CI, 2.4-18.1; P = .012). Octreotide reduced the annual volume of endoscopic procedures by 0.9 (95% CI, 0.3-1.5). CONCLUSIONS: Octreotide effectively reduces transfusion requirements and the need for endoscopic therapy in patients with angiodysplasia-related anemia. CLINICALTRIALS: gov, NCT02384122.

Non-adherence to the rule of 3 does not increase the risk of adverse events in esophageal dilation.

BACKGROUND AND AIMS: Although the rule of 3 is recommended to minimize the risk of perforation when esophageal dilation is performed using bougie dilators, there are no data to validate its use. Our aim was to investigate the association between the rule of 3 and adverse events (AEs) in esophageal dilation. METHODS: A retrospective chart review in patients who underwent esophageal bougie or balloon dilation between December 1991 and February 2013 at a tertiary hospital was performed. Data collection included patient demographics, stricture and procedural characteristics, AEs, and follow-up. Univariate logistic regression models were used to assess the risk of AEs and perforations. RESULTS: A total of 297 patients (median age, 63 years; 60% men) underwent 2216 esophageal bougie or balloon dilations. Major AEs occurred in 22 (1%) dilation sessions, including 11 (0.5%) perforations, 4 (0.2%) fistulas, 3 (0.1%) hospitalizations for pain management, 2 (0.09%) clinically significant hemorrhages, 1 (0.04%) fever, and 1 (0.04%) tracheoesophageal voice prosthesis leak. Mean duration of treatment was 43.2 months (standard deviation, 47.7 months). Most strictures were benign (n = 275; 93%) and complex in nature (n = 198; 67%). Non-adherence to the rule of 3 occurred in 190 (13%) dilations with bougie dilators. Non-adherence was not associated with a higher rate of major AEs (1/190, 0.5% vs 15/953, 1.6%; P = .18) and perforations (0/190, 0% vs 7/952, 0.7%; P = .18). Gender, complex strictures, location of the stricture, type of dilator, and additional interventions were also not associated with major AEs or perforations. However, malignant strictures were associated with an increased risk of major AEs (odds ratio, 3.5; 95% confidence interval, 1.1-12.0) and perforations (odds ratio, 8.3; 95% confidence interval, 2.2-31.9). CONCLUSIONS: Non-adherence to the rule of 3 does not appear to increase the risk of AEs, particularly perforation, after esophageal dilation using bougie dilators. Caution is needed with the dilation of malignant strictures, as there is an increased risk of perforations and AEs. However, large prospective studies are needed to verify the results of this study.

Stent-in-stent technique for removal of embedded partially covered self-expanding metal stents.

BACKGROUND: Removal of embedded partially covered self-expanding metal stents (PCSEMS) is associated with an increased risk of adverse events compared with removal of fully covered self-expanding stents (FCSES) due to tissue ingrowth. Successful removal of embedded PCSEMS has been described by the stent-in-stent (SIS) technique. AIMS: To report the first US experience from three high-volume quaternary care centers on the safety and efficacy of the SIS technique for removal of embedded PCSEMS. METHODS: Retrospective study of outcomes for consecutive patients who underwent the SIS for removal of embedded PCSEMS over a 5-year period. RESULTS: Twenty-seven embedded PCSEMS were successfully removed using the SIS technique (100 %) from 25 patients (11 males), median age 65 (range 37-80). All stents were successfully removed in one endoscopic session (no repeat SIS procedures were required for persistently embedded stents). The embedded PCSEMS had been in situ for a median of 76 days (range 26-501). Median SIS dwell time (FCSES in situ of PCSEMS) was 13 days (interquartile range 8-16 days; range 4-212 days). One adverse event (self-limited bleeding) occurred during a median follow-up period of 3 months (range 1-32). No patients died, required surgery, or had long-term disability due to adverse events attributed to the SIS technique. Twelve patients required additional interventions following SIS procedure for persistence or recurrence of the underlying pathology. CONCLUSION: When performed by experienced endoscopists, safe and effective removal of embedded PCSEMS can be achieved via the SIS technique.

[A harmless form of pneumomediastinum: avoid unnecessary diagnostics and treatment]. / Een onschuldige vorm van pneumomediastinum.

BACKGROUND: Pneumomediastinum is a potentially life-threatening condition. Patients can present with a variety of symptoms at the emergency department. Pneumomediastinum can be spontaneous or secondary due to perforation of the esophagus or tracheobronchial tree. CASE DESCRIPTION: A 20-year old man was seen at the emergency department with the suspicion of esophageal perforation. He noticed subcutaneous 'crackles' arising after an episode of severe vomiting. In the emergency room a non-acute ill patient was seen with subcutaneous emphysema of the neck and chest. A CT-scan with oral contrast did not show esophageal contrast leakage or other pathology that could be the cause of his pneumomediastinum. Therefore, we diagnosed the patient with a spontaneous pneumomediastinum. He was discharged after an observation period of 24 hours. CONCLUSION: Spontaneous pneumomediastinum is a rare, self-limiting disease with an excellent prognosis. Differentiating spontaneous pneumomediastinum from more severe secondary causes will avoid unnecessary therapy and prolonged hospitalization.

Effectiveness and predictors of response to somatostatin analogues in patients with gastrointestinal angiodysplasias: a systematic review and individual patient data meta-analysis.

BACKGROUND: Gastrointestinal angiodysplasias are vascular malformations that often cause red blood cell transfusion-dependent anaemia. Several studies suggest that somatostatin analogues might decrease rebleeding rates, but the true effect size is unknown. We therefore aimed to investigate the efficacy of somatostatin analogues on red blood cell transfusion requirements of patients with gastrointestinal angiodysplasias and to identify subgroups that might benefit the most from somatostatin analogue therapy. METHODS: We did a systematic review and individual patient data meta-analysis. We searched MEDLINE, Embase, and Cochrane on Jan 15, 2016, with an updated search on April 25, 2021. All published randomised controlled trials and cohort studies that reported on somatostatin analogue therapy in patients with gastrointestinal angiodysplasias were eligible for screening. We excluded studies without original patient data, single case reports, small case series (ie, <10 participants), studies in which patients had a specific aetiology of gastrointestinal angiodysplasias, and studies in which somatostatin analogue therapy was initiated simultaneously with other treatment modalities. Authors of eligible studies were invited to share individual patient data. Aggregated data was used if individual patient data were not provided. The primary outcome was the mean reduction in the number of red blood cell transfusions during somatostatin analogue therapy, compared with baseline, expressed as the incidence rate ratio (IRR) and absolute mean decrease. We defined patients as either good responders (≥50% reduction in the number of red blood cell transfusions) or poor responders (<50% reduction). A mixed-effects negative binomial regression was used to account for clustering of patients and skewness in data. This study was registered in the International Prospective Register of Systematic Reviews (PROSPERO), number CRD42020213985. FINDINGS: We identified 11 eligible studies (one randomised controlled trial and ten cohort studies) of moderate-to-high quality and obtained individual patient data from the authors of nine (82%) studies. The remaining two (18%) studies provided sufficient information in the published manuscript to extract individual patient data. In total, we analysed data from 212 patients. Somatostatin analogues reduced the number of red blood cell transfusions with an IRR of 0·18 (95% CI 0·14-0·24; p<0·0001) during a median treatment duration of 12 months (IQR 6·0-12·0) and follow-up period of 12 months (12·0-12·0), correlating with a mean absolute decrease in the number of red blood cell transfusions from 12·8 (95% CI 10·4-15·8) during baseline to 2·3 (1·9-2·9) during follow-up-ie, a reduction of 10·5 red blood cell transfusions (p<0·0001). 177 (83%) of 212 patients had a good response to somatostatin analogue therapy (defined as at least a 50% reduction in the number of red blood cell transfusions). Heterogeneity across studies was moderate (I2=53%; p=0·02). Location of gastrointestinal angiodysplasias in the stomach compared with angiodysplasias in the small bowel and colon (IRR interaction 1·92 [95% CI 1·13-3·26]; p=0·02) was associated with worse treatment response. Octreotide was associated with a better treatment response than lanreotide therapy (IRR interaction 2·13 [95% CI 1·12-4·04]; p=0·02). The certainty of evidence was high for the randomised controlled trial and low for the ten cohort studies. Adverse events occurred in 38 (18%) of 212 patients receiving somatostatin analogue therapy, with ten (5%) discontinuing this therapy because of adverse events. The most common adverse events were loose stools (seven [3%] of 212), cholelithiasis (five [2%]), flatulence (four [2%]), and administration site reactions (erythema, five [2%]). INTERPRETATION: Somatostatin analogue therapy is safe and effective in most patients with red blood cell transfusion-dependent bleeding due to gastrointestinal angiodysplasias. Somatostatin analogue therapy is more effective in patients with angiodysplasias located in the small bowel and colon, and octreotide therapy seems to be more effective than lanreotide therapy. FUNDING: The Netherlands Organisation for Health Research and Development and the Radboud University Medical Center.

The association between obesity and outcomes in acute pancreatitis: an individual patient data meta-analysis.

OBJECTIVES: There are data to suggest that obesity is associated with local and systemic complications as well as mortality in acute pancreatitis (AP). Cohort studies to date, however, have shown conflicting results from mostly unadjusted analyses. Therefore, we performed an individual patient data meta-analysis with the primary aim to investigate the association between obesity and mortality in AP. Our secondary aim was to investigate the association between obesity and necrosis, organ failure, multiple organ failure, and invasive intervention. PATIENTS AND METHODS: We systematically searched four electronic databases for prospective studies on obesity and outcomes in AP. Researchers of eligible studies were invited to share individual patient data using a standardized data collection form. All end points were investigated with a one-stage mixed effects Poisson model with random intercepts and forced entry of relevant confounders. RESULTS: We included five databases with 1302 patients, of whom 418 (32%) were obese. In total, 466 (36%) patients had necrosis, 328 (25%) had organ failure, 188 (14%) had multiple organ failure, 210 (16%) had an intervention, and 84 (7%) patients died. We found no significant association between obesity and mortality [relative risk (RR) 1.40, 95% confidence interval (CI): 0.89-2.20], necrosis (RR: 1.08, 95% CI: 0.90-1.31) or invasive intervention (RR: 1.10, 95% CI: 0.83-1.47) after adjustment for confounders. However, obesity was independently associated with the development of organ failure (RR: 1.38, 95% CI: 1.11-1.73) and multiple organ failure (RR: 1.81, 95% CI: 1.35-2.42). CONCLUSION: Obesity is independently associated with the development of organ failure and multiple organ failure in AP. However, there is no association between obesity and mortality, necrosis, and an intervention.

Tranexamic acid in treatment-resistant chronic transfusion-dependent gastrointestinal angiodysplasia bleeding.

A small proportion of gastrointestinal angiodysplasia bleeding leads to chronic blood cell transfusion dependency. There are no guidelines supporting decision-making among various treatments in patients with gastrointestinal angiodysplasia bleeding. When endoscopic argon plasma coagulation is ineffective, the angiogenesis inhibitors thalidomide and octreotide can be considered. We describe a 77-year-old woman who had side effects of these angiogenesis inhibitors, which caused her to have continued bleeding. She was successfully treated with tranexamic acid with a substantial decrease in need for red blood cell transfusions.

Decreased health-related quality of life in angiodysplasia patients: A cross-sectional cohort.

Gastrointestinal angiodysplasias may cause anemia. Quality of life (QoL) is a valid patient reported outcome and improvement of QoL represents an important treatment goal. There is a paucity of data on the effect of angiodysplasias on QoL. Therefore, we aim to evaluate QoL and fatigue in angiodysplasia patients. We performed a cross-sectional patient-reported outcome study. We included patients with endoscopy proven angiodysplasias and measured QoL with Short Form-36 and level of fatigue using Multi Fatigue Inventory-20. We distinguished three subgroups of patients according to disease severity: 1) with treatment for angiodysplasias, 2) without treatment for angiodysplasias and 3) without recent hospital visits. The primary outcome was the physical component summary (PCS) score on the SF-36. Multivariate regression analysis were performed to correct for differences at baseline. A total of 144 patients completed the questionnaires (response rate = 62%; mean age 68 years; 65% men). Angiodysplasia patients have a significant lower PCS compared to the age-matched general population (respectively 41.0 vs. 43.3, p = 0.01). Disease severity is independently associated with a negative outcome on QoL (ß -4.6, 95% CI -7.8--1.3). Similarly patients score lower on multiple QoL subdomains, i.e. role limitations due to physical health problems (40.8 vs. 44.0, p<0.01), general health (39.7 vs. 47.3, p<0.01). Angiodysplasia patients are more fatigued compared to the general population (male 56.1 vs. 48.5, p<0.01, female 59.2 vs. 51.5, p = 0.01). In conclusion, angiodysplasias are independently associated with clinically significant impairments in multiple domains of health-related QoL, especially in measures of functional limitation.

High variation in treatment strategies for gastrointestinal angiodysplasias.

OBJECTIVE: Angiodysplasias (ADs) are the second leading cause of gastrointestinal bleeding in the elderly. The impact extends from no symptoms to chronic anaemia. Treatment guidelines are lacking. The aim of this study was to assess the current practice of gastrointestinal ADs and explore possible new research areas. On the basis of existing evidence, we would like to propose a treatment algorithm. METHODS: We administered a 19-item web-based survey to gastroenterologists in the Netherlands between February and April of 2015. RESULTS: A total of 111 (response rate 28%) gastroenterologists completed the survey (mean age=47 years; 24% women). The respondents identified Von Willebrand disease (17%), chronic kidney disease (21%) and aortic stenosis (77%) as risk factors for the development of ADs. Colonoscopy (54%) and esophagogastroduodenoscopy (43%) were the preferred first tools to screen for ADs. The favoured (77%) first treatment option is endoscopic argon plasma coagulation, whereas 20% start iron supplementation or blood transfusions. Treatment strategy is mostly (65%) based on the location of the ADs. Small bowel ADs are considered the most difficult to treat, because of the need for balloon enteroscopy. Of the gastroenterologists, 13% would treat ADs as a coincident finding during endoscopy. Medical therapy is mostly started in refractory ADs, and thalidomide (40%) is preferred over octreotide (19%). Thalidomide is more preferred by gastroenterologists working in a teaching hospital. CONCLUSION: Identification of risk factors and treatment of ADs vary widely between gastroenterologists in the Netherlands. Further research is needed to create an evidence-based guideline and thereby optimize the management of symptomatic ADs.

Inconclusive evidence that age predicts a prolonged or chronic course of acute rhinosinusitis in adults: a systematic review of the evidence base.

OBJECTIVE: To review the evidence whether the risk for a prolonged or chronic course increases with age in adult patients with acute rhinosinusitis. DATA SOURCES: PubMed, EMBASE, and the Cochrane Library. REVIEW METHODS: A comprehensive literature search was performed on March 24, 2013, and articles were screened and selected using predefined inclusion and exclusion criteria. Articles reporting studies on age as a predictor for the course in patients with acute rhinosinusitis were included. For included articles, the design of reported studies was assessed for directness of evidence and risk of bias. We aimed to extract hazard ratios for age as a continuous variable. RESULTS: Out of 13,382 unique publications, 3 articles with moderate risk of bias were included, with a maximum follow-up period of 30 days. The reported hazard ratios for recovery at 10, 15, and 30 days are 1.0 (95% confidence interval, 0.9-1.1) for age as a continuous variable, 0.86 (0.66-1.11) for age dichotomized at 38 years, and 0.58 (0.40-0.84) for age dichotomized for an increase with 20 years, respectively. CONCLUSION AND RECOMMENDATION: There is no evidence that age increases the risk for chronic rhinosinusitis in adult patients with acute rhinosinusitis. The literature is inconclusive that age increases the risk for a prolonged course of acute rhinosinusitis and, therefore, does not provide grounds for different management according to age of patients. As such, patients can be managed according to clinical practice guidelines with expectant observation and symptomatic treatment.