The Answer to "When to Clip" After Colorectal Endoscopic Mucosal Resection Based on a Cost-Effectiveness Analysis.

INTRODUCTION: Delayed bleeding (DB) is the most common major complication of endoscopic mucosal resection (EMR). Two randomized clinical trials recently demonstrated that clip closure after EMR of large nonpedunculated colorectal polyps (LNPCPs) reduces the risk of DB. We analyzed the cost-effectiveness of this prophylactic measure. METHODS: EMRs of LNCPCPs were consecutively registered in the ongoing prospective multicenter database of the Spanish EMR Group from May 2013 until July 2017. Patients were classified according to the Spanish Endoscopy Society EMR group (GSEED-RE2) DB risk score. Cost-effectiveness analysis was performed for both Spanish and US economic contexts. The average incremental cost-effectiveness ratio (ICER) thresholds were set at 54,000 € or $100,000 per quality-adjusted life year, respectively. RESULTS: We registered 2,263 EMRs in 2,130 patients. Applying their respective DB relative risk reductions after clip closure (51% and 59%), the DB rate decreased from 4.5% to 2.2% in the total cohort and from 13.7% to 5.7% in the high risk of the DB GSEED-RE2 subgroup. The ICERs for the universal clipping strategy in Spain and the United States, 469,706 € and $1,258,641, respectively, were not cost effective. By contrast, selective clipping in the high-risk of DB GSEED-RE2 subgroup was cost saving, with a negative ICER of -2,194 € in the Spanish context and cost effective with an ICER of $87,796 in the United States. DISCUSSION: Clip closure after EMR of large colorectal lesions is cost effective in patients with a high risk of bleeding. The GSEED-RE2 DB risk score may be a useful tool to identify that high-risk population.

Clip Closure After Resection of Large Colorectal Lesions With Substantial Risk of Bleeding.

BACKGROUND & AIMS: It is not clear whether closure of mucosal defects with clips after colonic endoscopic mucosal resection (EMR) prevents delayed bleeding, although it seems to have no protective effects when risk is low. We performed a randomized trial to evaluate the efficacy of complete clip closure of large (≥2 cm) nonpedunculated colorectal lesions after EMR in patients with an estimated average or high risk of delayed bleeding. METHODS: We performed a single-blind trial at 11 hospitals in Spain from May 2016 through June 2018, including 235 consecutive patients who underwent EMR for large nonpedunculated colorectal lesions with an average or high risk of delayed bleeding (based on Spanish Endoscopy Society Endoscopic Resection Group score). Participants were randomly assigned to groups that received closure of the scar with 11-mm through-the-scope clips (treated, n = 119) or no clip (control, n = 116). The primary outcome was proportion of patients in each group with delayed bleeding, defined as evident hematochezia that required medical intervention within 15 days after colonoscopy. RESULTS: In the clip group, complete closure was achieved in 68 (57%) cases, with partial closure in 33 (28%) cases and failure to close in 18 (15%) cases. Delayed bleeding occurred in 14 (12.1%) patients in the control group and in 6 (5%) patients in the clip group (absolute risk difference, reduction of 7% in the clip group; 95% confidence interval, -14.7% to 0.3%). After completion of the clip closure, there was only 1 (1.5%) case of delayed bleeding (absolute risk difference, reduction of 10.6%; 95% confidence interval, -4.3% to 17.9%). CONCLUSIONS: In a randomized trial of patients with large nonpedunculated colorectal lesions undergoing EMR, we found that clip closure of mucosal defects in patients with a risk of bleeding can be a challenge, but also reduces delayed bleeding. Prevention of delayed bleeding required complete clip closure. ClinicalTrials.gov ID: NCT02765022.

[Inappropriateness rate for colonoscopy indications in an open access unit]. / Grado de adecuación de las indicaciones de la colonoscopia en una unidad de acceso abierto.

INTRODUCTION AND OBJECTIVE: The suitability of indications for colonoscopy is important to optimize the available resources. The aim of this study was to assess the appropriateness of colonoscopy indications in an open access endoscopy unit using the EPAGE II criteria. METHODS: Colonoscopies performed between October 1 and November 30, 2011 were retrospectively included. The appropriateness of the colonoscopy was established according to the EPAGE II criteria. Demographics, medical applicants, indications and relevant findings from these examinations were recorded. RESULTS: We included 440 colonoscopies (60.8 ± 016.3 years, 54% women). The indication was appropriate in 75.4% (CI, 71-79.3%), uncertain in 13.1% (CI, 10.2-16.6%) and inappropriate in 11.4% (CI, 8.7-14.8%). In the univariate analysis, the relevant findings in the colonoscopy were associated with age, sex, colonoscopy indications and EPAGE II. In the logistic regression analysis, factors independently associated with the presence of relevant findings were age (≥ 50 years) (OR, 1.84), male sex (OR, 2.7) and two indications, inflammatory bowel disease and post-polypectomy surveillance (P < .03). The diagnostic yield of EPAGE II criteria was 37.3% for appropriate colonoscopies and 28.3% for inappropriate colonoscopies (P = .09). CONCLUSIONS: The rate of unnecessary colonoscopy is high, especially in young patients (<50 years) and some colonoscopy indications. Age (≥ 50 years) and male sex are independently associated with the presence of relevant findings in colonoscopy. The diagnostic yield of EPAGE II criteria does not differ between appropriate and inappropriate examinations.

Sugar malabsorption in functional abdominal bloating: a pilot study on the long-term effect of dietary treatment.

BACKGROUND: Functional abdominal bloating is a functional bowel disorder dominated by a feeling of abdominal fullness without sufficient criteria for another functional gastrointestinal disorder. Gas-related complaints (i.e., passage of flatus), which are present in a subgroup of these patients, might be associated with carbohydrate malabsorption. AIM: To evaluate the presence of lactose and/or fructose plus sorbitol malabsorption, and the long-term efficacy of malabsorbed sugar-free diets, in patients with Rome II criteria of functional abdominal bloating and gas-related symptoms. METHODS: Thirty-six consecutive patients (age, 51+/-3.1 years; sex, 12 M, 24 W) with Rome II criteria of functional abdominal bloating and gas-related symptoms were included in a pilot study. In all cases, the presence of malabsorption of both lactose (20 g) and fructose plus sorbitol (20+3.5 g) was assessed by means of hydrogen breath test. Patients with sugar malabsorption were put on a malabsorbed sugar-free diet. Follow-up visits were scheduled at both 1 and 12 months after starting the diet. Global rating scales of change as compared to the beginning of the study were used to assess symptom changes. RESULTS: Twenty-six of 36 patients (72.2%) presented sugar malabsorption (six lactose, 12 fructose plus sorbitol, and eight both). Seventeen of the 26 (65%) patients with malabsorption had symptoms of sugar intolerance during the 3-h breath testing period. All 26 were put on malabsorbed sugar-free diets. Eighty-one per cent of patients referred clinical improvement at 1-month visit, which was maintained at 12 months in 67% of them (complete improvement in 50% and partial improvement in 16.7%). CONCLUSIONS: Sugar malabsorption and intolerance seem to be frequent in patients with functional abdominal bloating and gas-related complaints. A malabsorbed sugar-free diet might be a long-term effective therapy in a high percentage of patients. Further controlled clinical trials are warranted.

Helicobacter pylori infection as a cause of iron deficiency anaemia of unknown origin.

AIM: To assess the aetiological role of Helicobacter pylori (H. pylori) infection in adult patients with iron-refractory or iron-dependent anaemia of previously unknown origin. METHODS: Consecutive patients with chronic iron-deficient anaemia (IDA) with H. pylori infection and a negative standard work-up were prospectively evaluated. All of them had either iron refractoriness or iron dependency. Response to H. pylori eradication was assessed at 6 and 12 mo from follow-up. H. pylori infection was considered to be the cause of the anaemia when a complete anaemia resolution without iron supplements was observed after eradication. RESULTS: H. pylori was eradicated in 88 of the 89 patients. In the non-eradicated patient the four eradicating regimens failed. There were violations of protocol in 4 patients, for whom it was not possible to ascertain the cause of the anaemia. Thus, 84 H. pylori eradicated patients (10 men; 74 women) were available to assess the effect of eradication on IDA. H. pylori infection was considered to be the aetiology of IDA in 32 patients (38.1%; 95%CI: 28.4%-48.8%). This was more frequent in men/postmenopausal women than in premenopausal women (75% vs 23.3%; P < 0.0001) with an OR of 9.8 (95%CI: 3.3-29.6). In these patients, anaemia resolution occurred in the first follow-up visit at 6 mo, and no anaemia or iron deficiency relapse was observed after a mean follow-up of 21 ± 2 mo. CONCLUSION: Gastric H. pylori infection is a frequent cause of iron-refractory or iron-dependent anaemia of previously unknown origin in adult patients.

Lymphocytic duodenosis: aetiology and long-term response to specific treatment.

BACKGROUND: The clinical significance of lymphocytic duodenosis remains unclear. AIM: To prospectively assess the aetiology of lymphocytic duodenosis and the patterns of clinical presentation. METHODS: Ninety consecutive patients with lymphocytic duodenosis and clinical symptoms of the coeliac disease spectrum were prospectively included. All subjects underwent serological testing and HLA genotyping for coeliac disease, assessment of Helicobacter pylori infection, and parasite stool examination. Intake of non-steroidal anti-inflammatory drugs was also recorded. The final aetiology of lymphocytic duodenosis was evaluated on the basis of the long-term response to specific therapy. RESULTS: More than one initial potential aetiology was observed in 44% of patients. The final diagnosis was gluten-sensitive enteropathy alone or associated with Helicobacter pylori infection in 43.3%, Helicobacter pylori infection (without gluten-sensitive enteropathy) in 24.4%, non-steroidal anti-inflammatory drugs intake in 5.5%, autoimmune disease in 3.3%, and parasitic infection in 2.2%. Among first degree relatives and patients with chronic diarrhoea, the most common final diagnosis was gluten-sensitive enteropathy. In contrast, in the group presenting with chronic dyspepsia the most common diagnosis was Helicobacter pylori infection ('Diarrhoea' vs 'Dyspepsia' groups, p=0.008). CONCLUSIONS: Lymphocytic duodenosis is often associated with more than one potential initial aetiology. Clinical presentation may be useful to decide the initial therapeutic approach with these patients.

Evolution of the incidence of collagenous colitis and lymphocytic colitis in Terrassa, Spain: a population-based study.

BACKGROUND: Previous studies suggest an increase in the incidence rate of microscopic colitis in recent decades. The aim was to evaluate changes in the population-based incidence rate of microscopic colitis and its subtypes over time in Terrassa, Spain. METHODS: This was a prospective study during the period 2004-2008, with a comparison of data from the period 1993-1997. The catchment area was a mixed rural-urban type, with nearly 290,000 inhabitants. All patients with nonbloody chronic diarrhea referred for a diagnostic colonoscopy were included. Multiple biopsy specimen samples were obtained when the macroscopic appearance of the colonic mucosa was normal to rule out microscopic colitis. Crude and adjusted incidence rates based on either the year of diagnosis or the date of onset of symptoms were calculated. RESULTS: Forty patients with collagenous colitis (CC) and 32 with lymphocytic colitis (LC) were identified. The mean annual incidence of CC and LC based on the year of onset of symptoms was 2.6/10(5) inhabitants (95% confidence interval [CI], 1.9-3.3), and 2.2/10(5) inhabitants (95% CI, 1.5-3.0), respectively. Incidence rates for CC based on the year of onset of symptoms were significantly higher in the period 2004-2008 than in 1993-1997 (2.6 versus 1.1/10(5) ; P = 0.012). The increase in CC incidence was more marked in women (P = 0.047) than in men (P = 0.19). CONCLUSIONS: The annual incidence of CC in Terrassa increased over time, mainly in women. Nevertheless, the rates were much lower than those observed in northern Europe, suggesting that there is a north-south difference in the incidence of microscopic colitis.

Mild enteropathy as a cause of iron-deficiency anaemia of previously unknown origin.

BACKGROUND AND AIMS: We assessed whether mild enteropathy with negative coeliac serology may be gluten-dependent, and a cause of iron-deficiency anaemia. In cases not responding to gluten-free diet, the role of Helicobacter pylori infection was evaluated. METHODS: 55 consecutive unexplained iron-deficiency anaemia patients were included. In all of them we performed: HLA-DQ2/DQ8 coeliac genetic study, distal duodenum biopsies, and tests to assess H. pylori infection. A gluten-free diet or H. pylori eradication was used as indicated. Final diagnosis was established based on response to specific therapy after a 12-month follow-up period. RESULTS: Histological findings were: (1) group A (positive genetics): 21 Marsh I, 2 Marsh IIIA, 12 normal; (2) group B (negative genetics): 16 Marsh I, 4 normal. Final diagnosis of anaemia in patients with enteropathy were: group A, gluten-sensitive enteropathy, 45%; H. pylori infection, 20%; gluten-sensitive enteropathy plus H. pylori, 10%; other, 10%; unknown, 15%; group B, gluten-sensitive enteropathy, 10%; H. pylori infection, 0% (1 non-eradicated case, 10%); non-steroidal anti-inflammatory drug intake, 20%; other, 20%; unknown, 40% (p=0.033). CONCLUSIONS: Mild enteropathy is frequent in patients with unexplained iron-deficiency anaemia and negative coeliac serology. Most cases are secondary to either gluten-sensitive enteropathy or H. pylori infection, or both; however, there is also a substantial number of patients without a definitive diagnosis.

Apoptosis resistance of mucosal lymphocytes and IL-10 deficiency in patients with steroid-refractory Crohn's disease.

BACKGROUND: Apoptosis resistance of T-cells is considered an abnormality of immune pathways in Crohn's disease (CD). It has been previously shown that corticosteroids induce apoptosis of cells involved in inflammation. Thus, our aim was to assess the apoptosis of mononuclear cells and pro/antiinflammatory cytokines in the intestinal mucosa of patients with active CD, related to steroid response, and identify cellular and molecular factors that may predict this response to therapy. METHODS: Patients with CD (n = 26), ulcerative colitis (UC) (n = 32), and controls (n = 10) were prospectively studied with mucosal biopsies before and 7-10 days after corticosteroid treatment. Immunophenotype and apoptosis of T and B lymphocytes, plasma cells, and macrophages were assessed by flow cytometry, immunohistochemistry, and immunofluorescence. The cytokine expression pattern was evaluated by quantitative polymerase chain reaction (PCR). RESULTS: Apoptosis resistance of T and B lymphocytes was observed only in steroid-refractory and -dependent CD patients as compared to responsive patients (P = 0.032; P = 0.004, respectively), being evident after steroid treatment. Interleukin (IL)-10 was markedly increased at baseline in steroid-responsive patients compared to the nonresponders (P = 0.006; sensitivity: 88.8%; specificity: 66.6% to predict steroid response). CONCLUSIONS: Apoptosis resistance of mucosal T and B cells in steroid-refractory and -dependent CD patients appears during the evolution of the acute phase, limiting its clinical application as a predictor marker. In contrast, increased expression of IL-10 at an early stage of active steroid-sensitive CD patients supports its usefulness at predicting a good steroid response. Steroid-dependent and -refractory CD patients share similar molecular and cellular pathophysiological mechanisms.

Drug consumption and the risk of microscopic colitis.

BACKGROUND: Microscopic colitis is a rare disease of unknown etiology. It has been described that some drugs could cause or worsen the disease; however, the scientific evidence is limited. AIM: To investigate the possible association of chronic drug consumption with microscopic colitis. METHODS: This was a case-control study in which groups of cases were: Group 1-39 patients with collagenous colitis; Group 2-39 patients with lymphocytic colitis; and Group 3-52 patients with chronic watery diarrhea of functional characteristics. 103 subjects formed the control group. At diagnosis, a drug consumption history of at least 2-wk duration was registered. An age- and sex-adjusted logistic regression analysis was used, and the odds ratio (OR, 95% CI) was calculated. RESULTS: Drug consumption was more frequent in lymphocytic colitis than in the control group (92.3%vs 76.3%, P < 0.05). The mean daily number of drugs by person was also higher in lymphocytic colitis (3.79 +/- 0.44 vs 2.13 +/- 0.22, P= 0.04). The following associations as compared with the control group were observed: Group 1-Consumption of NSAIDs (46.2%vs 23%, OR 2.9, 1.3-6.4), selective serotonin reuptake inhibitors (SSRIs) (18%vs 1%, OR 21, 2.5-177), specifically, sertraline (15.4%vs 0%, P < 0.0005); Group 2-SSRIs (28%vs 1%, OR 37.7, 4.7-304), beta-blockers (13 vs 3%, OR 4.79, 1.04-20), statins (13%vs 3%, OR 4.6, 1.04-20), biphosphonates (8%vs 0%, P= 0.022); Group 3-SSRIs (15%vs 1%, OR 16.2, 2-135), statins (11.5%vs 3%, OR 5.4, 1.2-24). As compared with the chronic diarrhea group, a significant association with the usage of sertraline in LC (P= 0.005) and a trend for NSAIDs in CC (P= 0.057) were found. CONCLUSIONS: Drug consumption increases the risk of microscopic colitis. Some drugs might be trigger factors of colonic inflammation in predisposed hosts, and others might only worsen self-evolving microscopic colitis.

Systematic evaluation of the causes of chronic watery diarrhea with functional characteristics.

UNLABELLED: BACKGROUND Causes of chronic watery diarrhea are multiple. There is not definite scientific evidence about AND AIMS: which are the recommended explorations to be performed in the diagnostic workup of patients with functional diarrhea. The aim was to assess prospectively the presence of gluten-sensitive enteropathy, bile acid malabsorption, and sugar malabsorption in consecutive patients with chronic watery diarrhea of obscure origin fulfilling Rome II criteria of functional disease. METHODS: A total of 62 patients with chronic watery diarrhea, defined as more than 3 loose or liquid bowel movements a day for at least 4 wk and a stool weight >200 g/day were included. The following tests were performed: (a) HLA-DQ2/DQ8 genotyping, and if positive, endoscopic biopsies from distal duodenum were obtained, and intestinal damage assessed; (b) SeHCAT (Se-homotaurocholate) abdominal retention test; (c) small bowel follow-through; and (d) hydrogen breath test (lactose, fructose + sorbitol). Gluten- or sugar-free diet, or cholestyramine was administered according to results. Functional disease was diagnosed if all tests performed were normal or if either there was no response to specific therapy or diarrhea relapsed during a 12-month follow-up. RESULTS: Bile acid malabsorption was considered to be the cause of diarrhea in 28 (45.2%) patients, sugar malabsorption in 10 (16.1%), gluten-sensitive enteropathy in 10 (16.1%), and both bile acid and sugar malabsorption in 2 patients. Twelve (19.4%) patients remained without a specific diagnosis and were considered as functional bowel disease. Diarrhea stopped in the 50 patients after specific treatment, decreasing the daily stool number from 5.4 +/- 0.3 to 1.5 +/- 0.1 (P < 0.0005), without relapse after the 12-months follow-up. CONCLUSIONS: The diagnosis of functional disease in patients with chronic watery diarrhea should be performed with caution since in most cases there is an organic cause that justifies diarrhea.