Endoscopic treatment (endoscopic balloon dilation/self-expandable metal stent) vs surgical resection for the treatment of de novo stenosis in Crohn's disease (ENDOCIR study): an open-label, multicentre, randomized trial.

BACKGROUND: Stenosis is one of the most common complications in patients with Crohn's disease (CD). Endoscopic balloon dilation (EBD) is the treatment of choice for a short stenosis adjacent to the anastomosis from previous surgery. Self-expandable metal stents (SEMS) may be a suitable treatment option for longer stenoses. To date, however, there is no scientific evidence as to whether endoscopic (EBD/SEMS) or surgical treatment is the best approach for de novo or primary stenoses that are less than 10 cm in length. METHODS/DESIGN: Exploratory study as "proof-of-concept", multicentre, open-label, randomized trial of the treatment of de novo stenosis in the CD; endoscopic treatment (EBD/SEMS) vs surgical resection (SR). The type of endoscopic treatment will initially be with EDB; if a therapeutic failure occurs, then a SEMS will be placed. We estimate 2 years of recruitment and 1 year of follow-up for the assessment of quality of life, costs, complications, and clinical recurrence. After the end of the study, patients will be followed up for 3 years to re-evaluate the variables over the long term. Forty patients with de novo stenosis in CD will be recruited from 15 hospitals in Spain and will be randomly assigned to the endoscopic or surgical treatment groups. The primary aim will be the evaluation of the patient quality of life at 1 year follow-up (% of patients with an increase of 30 points in the 32-item Inflammatory Bowel Disease Questionnaire (IBDQ-32). The secondary aim will be evaluation of the clinical recurrence rate, complications, and costs of both treatments at 1-year follow-up. DISCUSSION: The ENDOCIR trial has been designed to determine whether an endoscopic or surgical approach is therapeutically superior in the treatment of de novo stenosis in CD. TRIAL REGISTRATION: ClinicalTrials.gov NCT04330846. Registered on 1 April 1 2020. https://clinicaltrials.gov/ct2/home.

Self-expandable metal stents versus endoscopic balloon dilation for the treatment of strictures in Crohn's disease (ProtDilat study): an open-label, multicentre, randomised trial.

BACKGROUND: Endoscopic balloon dilation (EBD) is the established endoscopic treatment for short strictures in Crohn's disease. Fully covered self-expandable metal stents (FCSEMS) have been used for endoscopic treatment of patients for whom EBD was unsuccessful. We aimed to determine the efficacy and safety of the two endoscopic treatments in patients with Crohn's disease with stenosis and compare the mean cost of both treatments. METHODS: This multicentre, open-label, randomised trial was done in 19 tertiary and secondary hospitals in Spain. Patients with Crohn's disease with obstructive symptoms and predominantly fibrotic strictures of less than 10 cm in length were eligible for inclusion. We excluded patients with stenosis treated with SEMS or EBD in the previous year and stenosis not accessible to a colonoscope. Patients were randomly assigned (1:1) to receive either EBD (EBD group) or FCSEMS (FCSEMS group) using a digital en-block randomisation system (block size of four). In the EBD group, dilation was done with a CRE Boston Scientific (Marlborough, MA, USA) pneumatic balloon with the diameter set at the discretion of the endoscopist; a maximum of two sessions of dilation were allowed with a minimum interval of 15-30 days between them. In the FCSEMS group, a 20 mm diameter Taewoong (Gimpo-si, South Korea) fully covered metal stent was placed; stent length was set at the discretion of the endoscopist. The primary outcome was to assess the efficacy of the endoscopic treatment, defined by the proportion of patients free of a new therapeutic intervention (EBD, FCSEMS, or surgery) due to symptomatic recurrence at 1 year of follow-up. Patients were analysed according to the intention-to-treat principle. Adverse events were recorded for all the patients; events were considered associated to be with the procedure when a causal association was possible, probable, or definite. This trial is registered with ClinicalTrials.gov, NCT02395354. FINDINGS: From Aug 28, 2013, to Oct 9, 2017, we assessed the eligibility of 99 patients, of whom 19 (19%) patients were excluded. Thus, 80 (81%) patients were randomly assigned to treatment: 39 (49%) patients to the FCSEMS group and 41 (51%) patients to the EBD group. 33 (80%) of 41 patients in the EBD group and 20 (51%) of 39 patients in the FCSEMS group were free of a new therapeutic intervention at 1 year (odds ratio [OR] 3·9 [95% CI 1·4-10·6]; p=0·0061). Two (3%) of 80 patients had severe adverse events (one [2%] patient in the EBD group and one [3%] patient in the FCSEMS group); both patients had perforations. INTERPRETATION: EBD is more effective than FCSEMS for Crohn's disease strictures, with a good safety profile for both treatments. FUNDING: Spanish National Institute of Health, Foundation of Spanish Society of Digestive Endoscopy, Catalan Society of Gastroenterology, and Taweoong.

Location, morphology and invasiveness of lateral spreading tumors in the colorectum differ between two large cohorts from an eastern and western country.

BACKGROUND AND STUDY AIMS: Data from Japanese series show that surface morphology of laterally spreading tumors (LST) in the colon identifies lesions with different incidence and pattern of submucosal invasion. Such data from western countries are scarce. We compared clinical and histological features of LST in a western country and an eastern country, with special interest on mucosal invasiveness of LST, and investigated the effect of clinical factors on invasiveness in both countries. PATIENTS AND METHODS: Patients with LST lesions ≥20mm were included from a multicenter prospective registry in Spain and from a retrospective registry from the National Cancer Center Hospital East, Japan. The primary outcome was the presence of submucosal invasion in LST. The secondary outcome was the presence of high-risk histology, defined as high-grade dysplasia or submucosal invasion. RESULTS: We evaluated 1102 patients in Spain and 663 in Japan. Morphological and histological characteristics differed. The prevalence of submucosal invasion in Japan was six-fold the prevalence in Spain (Prevalence Ratio PR=5.66; 95%CI: 3.96, 8.08), and the prevalence of high-risk histology was 1.5 higher (PR=1.44; 95%CI: 1.31, 1.58). Compared to the granular homogeneous type and adjusted by clinical features, granular mixed, flat elevated, and pseudo-depressed types were associated with higher odds of submucosal invasion in Japan, whereas only the pseudo-depressed type showed higher risk in Spain. Regarding high-risk histology, both granular mixed and pseudo-depressed were associated with higher odds in Japan, compared with only the granular mixed type in Spain. CONCLUSION: This study reveals differences in location, morphology and invasiveness of LST in an eastern and a western cohort.

Cardiorespiratory complications directly related to endoscopy: associated or not with sedation?

With the advent of routine sedation in digestive endoscopy, specifically the use of propofol, multiple reports have focused on the complications that may potentially emerge because of sedation, and whether administration is safer by anesthetists or trained gastroenterologists. Complications associated with endoscopy itself, whether diagnostic or therapeutic, have also been described. However, the fact that both upper and lower endoscopy per se may be accompanied by complications, both during the procedure or thereafter, is usually overlooked.

Gastric ulcers with upper gastrointestinal bleeding in patients with severe SARS-CoV-2.

A new coronavirus, SARS-CoV-2, was identified earlier this year and spread rapidly globally. The clinical manifestations that it produces have gradually become known and the typical clinical picture is respiratory. Although gastrointestinal symptoms have been described in several communications, information on endoscopic findings in these patients is practically zero. We describe two cases of upper gastrointestinal bleeding in patients with COVID-19. In both cases, the presence of gastric ulcers was identified in an unusual location, the gastric fundus. After ruling out malignancy, our suspicion was an ischemic etiology that is consistent with terminal gastric vascularization at the gastric fundus level and increased thrombotic phenomena in patients with COVID-19.

Safety in digestive endoscopy during the ongoing COVID-19 pandemic.

We read with interest the study by Hernández-Camba et al. about the low value of antibody testing for COVID-19 before endoscopic procedures and we would like to make some comments. Nine months after the first state of alarm was declared in Spain due to the SARS-CoV-2 pandemic, we knew that infections in endoscopy staff were scarce if adequate protection was worn and non-urgent procedures were postponed in patients with an active infection. Therefore, the conclusions of the study currently appear to be self-evident. However, things were different at the time it was performed.

Clinical validation of risk scoring systems to predict risk of delayed bleeding after EMR of large colorectal lesions.

BACKGROUND AND AIMS: The Endoscopic Resection Group of the Spanish Society of Endoscopy (GSEED-RE) model and the Australian Colonic Endoscopic Resection (ACER) model were proposed to predict delayed bleeding (DB) after EMR of large superficial colorectal lesions, but neither has been validated. We validated and updated these models. METHODS: A multicenter cohort study was performed in patients with nonpedunculated lesions ≥20 mm removed by EMR. We assessed the discrimination and calibration of the GSEED-RE and ACER models. Difficulty performing EMR was subjectively categorized as low, medium, or high. We created a new model, including factors associated with DB in 3 cohort studies. RESULTS: DB occurred in 45 of 1034 EMRs (4.5%); it was associated with proximal location (odds ratio [OR], 2.84; 95% confidence interval [CI], 1.31-6.16), antiplatelet agents (OR, 2.51; 95% CI, .99-6.34) or anticoagulants (OR, 4.54; 95% CI, 2.14-9.63), difficulty of EMR (OR, 3.23; 95% CI, 1.41-7.40), and comorbidity (OR, 2.11; 95% CI, .99-4.47). The GSEED-RE and ACER models did not accurately predict DB. Re-estimation and recalibration yielded acceptable results (GSEED-RE area under the curve [AUC], .64 [95% CI, .54-.74]; ACER AUC, .65 [95% CI, .57-.73]). We used lesion size, proximal location, comorbidity, and antiplatelet or anticoagulant therapy to generate a new model, the GSEED-RE2, which achieved higher AUC values (.69-.73; 95% CI, .59-.80) and exhibited lower susceptibility to changes among datasets. CONCLUSIONS: The updated GSEED-RE and ACER models achieved acceptable prediction levels of DB. The GSEED-RE2 model may achieve better prediction results and could be used to guide the management of patients after validation by other external groups. (Clinical trial registration number: NCT03050333.).

Gastrointestinal lesions in chronic kidney disease patients with anaemia. / Lesiones gastrointestinales en pacientes con enfermedad renal crónica y anemia.

INTRODUCTION: Despite the frequency with which anaemia is present in patients with chronic kidney disease (CKD), its relationship with gastrointestinal lesions has not been studied. METHOD: A cross-sectional, analytical, observational study involving one year of recruitment was carried out to determine the prevalence of endoscopic gastrointestinal lesions and associated risk factors in asymptomatic patients with chronic kidney disease stages 1-5 and anaemia who had a positive qualitative immunochemical faecal occult blood test. RESULTS: A total of 9,658 patients with CKD were analysed, of which 286 (2.9%) had anaemia; 198 had a positive faecal occult blood test (47% male, 71.1±11.8 years). The endoscopic study revealed 255 lesions, with at least one lesion in 68.2% of patients, with the most prevalent being: adenomatous colorectal polyps (39.6%), acute lesions of the gastric mucosa (22.6%), neoplastic lesions 15.1%), angiodysplasia (14.4%), oesophagitis (8.4%), inflammatory bowel disease (4.8%) and ischaemic colitis (3.1%). Uraemia and acetylsalicylic acid were identified as risk factors for acute gastric mucosal lesions. Angiodysplasia was associated with alcoholism, a more advanced stage of chronic kidney disease, anaemia, and lack of response to erythropoiesis-stimulating agents. Age and refractory anaemia were risk factors for adenomatous polyps and colorectal cancer. CONCLUSION: Renal patients with anaemia could benefit from an endoscopic study due to their high prevalence of gastrointestinal lesions, particularly adenomatous polyps and colorectal cancer, which are more common in those over 50 years of age with CKD stages 3-5.

Is the education available to anesthetists adequate to provide sedation in endoscopy units?

It is a letter that aims to emphasize the type of sedation that is sometimes used by anesthetists to perform a standard endoscopy and the excessive use of the operating room, which increases the cost of endoscopy and reduces the resources of surgical time.

A Scoring System to Determine Risk of Delayed Bleeding After Endoscopic Mucosal Resection of Large Colorectal Lesions.

BACKGROUND & AIMS: After endoscopic mucosal resection (EMR) of colorectal lesions, delayed bleeding is the most common serious complication, but there are no guidelines for its prevention. We aimed to identify risk factors associated with delayed bleeding that required medical attention after discharge until day 15 and develop a scoring system to identify patients at risk. METHODS: We performed a prospective study of 1214 consecutive patients with nonpedunculated colorectal lesions 20 mm or larger treated by EMR (n = 1255) at 23 hospitals in Spain, from February 2013 through February 2015. Patients were examined 15 days after the procedure, and medical data were collected. We used the data to create a delayed bleeding scoring system, and assigned a weight to each risk factor based on the ß parameter from multivariate logistic regression analysis. Patients were classified as being at low, average, or high risk for delayed bleeding. RESULTS: Delayed bleeding occurred in 46 cases (3.7%, 95% confidence interval, 2.7%-4.9%). In multivariate analysis, factors associated with delayed bleeding included age ≥75 years (odds ratio [OR], 2.36; P < .01), American Society of Anesthesiologist classification scores of III or IV (OR, 1.90; P ≤ .05), aspirin use during EMR (OR, 3.16; P < .05), right-sided lesions (OR, 4.86; P < .01), lesion size ≥40 mm (OR, 1.91; P ≤ .05), and a mucosal gap not closed by hemoclips (OR, 3.63; P ≤ .01). We developed a risk scoring system based on these 6 variables that assigned patients to the low-risk (score, 0-3), average-risk (score, 4-7), or high-risk (score, 8-10) categories with a receiver operating characteristic curve of 0.77 (95% confidence interval, 0.70-0.83). In these groups, the probabilities of delayed bleeding were 0.6%, 5.5%, and 40%, respectively. CONCLUSIONS: The risk of delayed bleeding after EMR of large colorectal lesions is 3.7%. We developed a risk scoring system based on 6 factors that determined the risk for delayed bleeding (receiver operating characteristic curve, 0.77). The factors most strongly associated with delayed bleeding were right-sided lesions, aspirin use, and mucosal defects not closed by hemoclips. Patients considered to be high risk (score, 8-10) had a 40% probability of delayed bleeding.

Radiofrequency ablation for the treatment of radiation proctitis.

BACKGROUND AND STUDY AIMS: The main endoscopic therapy for radiation proctitis is argon plasma coagulation (APC); however treatment is not always successful. Radiofrequency ablation (RFA) is a possible treatment for radiation proctitis but data are scarce. The aim of this study was to report on the safety and efficacy of RFA in the treatment of radiation proctitis. PATIENTS AND METHODS: This study was an open-label, retrospective, multicenter study of patients with chronic hemorrhagic radiation proctitis who were treated with RFA. Data included a three-item symptom score, the number of packed red blood cell transfusions, the lowest hemoglobin concentration, and complications, during the 6 months prior to and after RFA. Clinical success was defined as a decrease in the symptom score. Biological success was defined as an increase in the hemoglobin rate with equal or decreased number of transfusions required. RESULTS: A total of 17 patients underwent a median of 2 RFA sessions (range 1 - 4), without perioperative complications. Symptom scores decreased in 16 patients (clinical success 94 %), from a mean score of 3.6 (median 4) to 1.4 (median 1) (P < 0.01). Two patients developed rectal ulceration, with no local symptoms. During the 6 months after RFA, hemoglobin concentration increased in all 17 patients (from mean 8.3 ± 2.8 g/dL [median 7.5] to 11.3 ± 2.2 g/dL [median 11.0]; P < 0.01). Among 13 patients who were transfusion dependent prior to RFA (mean 7.2 ± 7.7 transfusions [median 4]), 9 patients (69 %) were weaned off transfusions after RFA. A significant increase in the hemoglobin level was observed in this subgroup of patients (from mean 7.2 ± 1.4 g/dL [median 7.3] to 10.7 ± 1.5 g/dL [median 10.5]; P < 0.001). Biological success was 100 %. CONCLUSIONS: RFA seems to significantly decrease clinical symptoms and increase the hemoglobin concentration, thus reducing the need for transfusions.

Radiofrequency ablation for the treatment of gastric antral vascular ectasia.

BACKGROUND AND STUDY AIMS: The traditional endoscopic treatment for gastric antral vascular ectasia (GAVE) is argon plasma coagulation, but results are not always positive. Radiofrequency ablation (RFA) is a new endoscopic therapy that may be an attractive option for the treatment of GAVE. The aim of this study was to assess the efficacy and safety of RFA for the treatment of GAVE. PATIENTS AND METHODS: This was an open-label, retrospective, case series study. The main outcome measures were number of red blood cell (RBC) packs transfused (transfusion requirement) and hemoglobin concentrations (g/dL) in the 6 months prior to and after RFA. Success was defined as a decrease in transfusion requirement in the 6 months after RFA compared with before treatment. RESULTS: A total of 24 patients underwent a mean of 1.8 ± 0.8 RFA sessions. No complications were reported. One patient was referred for additional argon plasma coagulation during follow-up. The mean number of RBC packs decreased in all 23 transfusion-dependent patients, from a mean of 10.6 ± 12.1 during the 6 months prior to RFA, to a mean of 2.5 ± 5.9 during the 6 months after RFA treatment (P < 0.001), and 15 patients (65.2 %) were weaned off transfusions completely. An increase in the hemoglobin concentration was reported in all patients after RFA (from 6.8 ± 1.4 g/dL to 9.8 ± 1.8 g/dL; P < 0.001). CONCLUSION: RFA for the treatment of GAVE seems feasible and safe, and significantly reduced the need for RBC transfusion and increased the hemoglobin level in this retrospective case series.

Predominio del gen de la hemocromatosis en pacientes con hepatitis tóxicas / HFE genotype prevalence in patients with drug-induced hepatotoxicity

La toxicidad hepática por fármacos y su mecanismo han sido durante mucho tiempo desconocidos. Se ha observado que los pacientes con hepatitis aguda elevan los niveles séricos de ferritina. El objetivo de este estudio es determinar si existe una asociación de hepatotoxicidad por medicamentos y las mutaciones en el gen HFE asociadas con la hemocromatosis hereditaria. Material y métodos: Se analizaron10 pacientes ingresados en nuestro hospital con el diagnóstico de hepatitis aguda inducida por fármacos. A todos se les hicieron pruebas de laboratorio para el estudio de enfermedades hepáticas, la mutación del gen HFE y las características histopatológicas. Resultados: Un paciente con hepatitis secundaria a fármacos era heterocigoto para la mutación C282Y y uno heterocigoto para las mutaciones C282Y y H63D. Hubo un paciente homocigoto para la mutación H63D y seis fueron heterocigotos para la mutación H63D. La prevalencia general de las mutaciones del gen HFE en pacientes con enfermedad hepática inducida por fármacos fue del 90%. Conclusiones: La prevalencia de las mutaciones del gen HFE asociadas con hemocromatosis hereditaria está muy aumentada entre los pacientes que presentan hepatotoxicidad por medicamentos. Las mutaciones del gen HFE podrían estar involucradas en la hepatotoxicidad por fármacos...

[Current management of nonvariceal upper gastrointestinal bleeding in Spain]. / Situación actual del manejo de la hemorragia digestiva alta no varicosa en España.

BACKGROUND: Mortality related to nonvariceal upper gastrointestinal bleeding (NVUGIB) has not changed. More information is needed to improve the management of this entity. The aims of this study were: a) to determine the characteristics of bleeding episodes, b) to describe the clinical approaches routinely used in NVUGIB, and c) to identify adverse outcomes related to endoscopic or medical treatments in Spain. METHODS: The European survey of nonvariceal upper GI bleeding (ENERGiB) was an observational, retrospective cohort study on NVUGIB with endoscopic evaluation carried out across Europe. The present study focused on Spanish patients in the ENERGiB study. The patients were managed according to routine care. The mean and standard deviation were calculated for quantitative variables and absolute and relative frequencies were calculated for categorical variables. RESULTS: Patients (n=403) were mostly men (71%), with a mean age of 65 years, and co-morbidities (62.5%). Most of the patients were managed by gastroenterologists (57.1%) or internal medicine teams (25.1%). A proton pump inhibitor was used empirically in 80% before endoscopy. Bleeding persistence occurred in 6.4% and recurrence in 6.7%. The mortality rate at 30 days was 3.5%. CONCLUSIONS: This study contributes to the characterization of Spanish patients and NVUGIB episodes in a real clinical setting and identifies the routine management of this entity, which is in line with the standards proposed by recent clinical practice guidelines. A notable finding was that age and the number of comorbidities in NVUGIB patients were increasing. These factors could explain the persistent mortality rate, despite the evident advances in the management of this entity.

ERCP during pregnancy.

BACKGROUND AND AIMS: ERCP during pregnancy is always challenging for the entire team performing the endoscopic intervention. In this study techniques and different interventional aspects used at several centres about the clinical experience on ERCP in pregnant women are analyzed. PATIENTS AND METHODS: the practice on ERCP in pregnant women in six centres during a period of ten years is reported. RESULTS: eleven patients were included in the study. Mean age was 30.6 years. Indication for ERCP was always symptomatic common bile duct stone (CBDS) disease. Before the procedure abdominal ultrasound was performed at all times and magnetic resonance cholangiopancreatography in four occasions. Conscious sedation by means of midazolam and fentanyl or meperidine was applied. Sphincterotomes and guidewires were used for bilary cannulation. Sometimes, rapid exchange platforms with short-length guidewires controlled by the same endoscopist were employed. Biliary cannulation was confirmed in 9 occasions by bile aspiration. In five procedures, a mean of 30 seconds of fluoroscopy was used, both to verify cannulation and to corroborate complete CBDS clearance. These patients had the pelvic zone protected with a lead shield and radiation dose was measured. Ten biliary sphincterotomies were performed followed by CBDS extraction. Two plastic stents were inserted. Relief of biliary obstruction was attained in all circumstances. Only one patient had hyperamylasemia after ERCP. All pregnant women had healthy foetuses with normal deliveries. CONCLUSIONS: with experience, ERCP appears to be a safe technique during pregnancy. With simple measures fluoroscopic time can be diminished or even abolished. It seems that ERCP during pregnancy is underused in our working areas, although it has shown to be a useful technique for relieving biliary obstruction.

Antral localization worsens the efficacy of enteral stents in malignant digestive tumors.

BACKGROUND AND AIMS: Malignant gastric outlet obstruction can be treated by means of enteral stenting or surgical gastrojejunalanatomosis. We evaluated in a prospective and multicentre study the efficacy of the enteral stent on food intake, the quality of life impact, and the relationship between efficacy and determined clinical and technical parameters. PATIENTS AND METHODS: Seventy one patients affected by symptoms arising from gastroduodenal obstruction due to malignant tumors, with criteria of irresecability, metastatic disease or very high surgical risk, were treated by means of self expanding metal stents. We used the GOOSS index to evaluate efficacy, and the Euro Qol-5D index to evaluate quality of life. RESULTS: Before stenting patients with GOOSS 0 and 1 were 68 (98.5%). After stenting patients with GOOSS 2 and 3 (semisolid and solid food) were 58 (84,1%) (P<.0001). The Euro Qol-5D index measured before and a month after stenting were 10.17 and 10.04 respectively (P=.6). The median survival was 91 days (9-552). The enteral stents for localised tumors in the duodenum and the gastrojejunalanastomosis were effective in 26 patients (70.2%) and 13 patients respectively (86.6%), while the enteral stents of tumors in the antrum were effective in only 5 patients (29.4%). CONCLUSIONS: The palliative treatment of malignant gastric outlet obstruction with a uncovered metal stent produces a significant improvement of oral food intake and maintains the overall quality of life index. The antral localization is associated with a lower efficacy of the procedure.

[Reversibility of hepatitis B virus-induced liver cirrhosis after prolonged antiviral therapy]. / Desaparición de cirrosis hepática por VHB tras tratamiento prolongado con antivirales.

Reversibility of liver fibrosis or cirrhosis involves complete restoration of normal liver architecture. This phenomenon has been well documented in chronic liver diseases such as autoimmune hepatitis, biliary obstruction, hemochromatosis, nonalcoholic steatohepatitis, and viral hepatitis. There are very few reports of reversal of cirrhosis after antiviral therapy in patients with chronic hepatitis B virus (HBV) infection. We report a case of disappearance of HBV-induced liver cirrhosis after years of treatment with distinct antiviral drugs, documented by successive biopsy results. This disappearance was accompanied by normalization of platelet count, gammaglobulin titers, and radiologic findings.