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.

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.).

Clinical guidelines for endoscopic mucosal resection of non-pedunculated colorectal lesions.

This document summarizes the contents of the Clinical Guidelines for the Endoscopic Mucosal Resection of Non-Pedunculated Colorectal Lesions that was developed by the working group of the Spanish Society of Digestive Endoscopy (GSEED of Endoscopic Resection). This document presents recommendations for the endoscopic management of superficial colorectal neoplastic lesions.

Clinical guidelines for endoscopic mucosal resection of non-pedunculated colorectal lesions. / Guía clínica para la resección mucosa endoscópica de lesiones colorrectales no pediculadas.

This document summarizes the contents of the Clinical Guidelines for the Endoscopic Mucosal Resection of Non-Pedunculated Colorectal Lesions that was developed by the working group of the Spanish Society of Digestive Endoscopy (GSEED of Endoscopic Resection). This document presents recommendations for the endoscopic management of superficial colorectal neoplastic lesions.

Stratifying risk in the prevention of recurrent variceal hemorrhage: Results of an individual patient meta-analysis.

Endoscopic variceal ligation plus beta-blockers (EVL+BB) is currently recommended for variceal rebleeding prophylaxis, a recommendation that extends to all patients with cirrhosis with previous variceal bleeding irrespective of prognostic stage. Individualizing patient care is relevant, and in published studies on variceal rebleeding prophylaxis, there is a lack of information regarding response to therapy by prognostic stage. This study aimed at comparing EVL plus BB with monotherapy (EVL or BB) on all-source rebleeding and mortality in patients with cirrhosis and previous variceal bleeding stratified by cirrhosis severity (Child A versus B/C) by means of individual time-to-event patient data meta-analysis from randomized controlled trials. The study used individual data on 389 patients from three trials comparing EVL plus BB versus BB and 416 patients from four trials comparing EVL plus BB versus EVL. Compared with BB alone, EVL plus BB reduced overall rebleeding in Child A (incidence rate ratio 0.40; 95% confidence interval, 0.18-0.89; P = 0.025) but not in Child B/C, without differences in mortality. The effect of EVL on rebleeding was different according to Child (P for interaction <0.001). Conversely, compared with EVL, EVL plus BB reduced rebleeding in both Child A and B/C, with a significant reduction in mortality in Child B/C (incidence rate ratio 0.46; 95% confidence interval, 0.25-0.85; P = 0.013). CONCLUSION: Outcomes of therapies to prevent variceal rebleeding differ depending on cirrhosis severity: in patients with preserved liver function (Child A), combination therapy is recommended because it is more effective in preventing rebleeding, without modifying survival, while in patients with advanced liver failure (Child B/C), EVL alone carries an increased risk of rebleeding and death compared with combination therapy, underlining that BB is the key element of combination therapy. (Hepatology 2017;66:1219-1231).

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.

Impact of anticoagulation on upper-gastrointestinal bleeding in cirrhosis. A retrospective multicenter study.

UNLABELLED: Recent studies have shown that liver cirrhosis (LC) behaves as an acquired hypercoagulable state with increased thrombotic risk. This is why anticoagulation therapy (AT) is now frequently used in these patients. Variceal bleeding is a severe complication of LC. It is unknown whether AT may impact the outcome of bleeding in these patients. Fifty-two patients on AT with upper gastrointestinal bleeding (UGIB) were evaluated. Portal vein thrombosis (PVT) and different cardiovascular disorders (CVDs) were the indication for AT in 14 and 38 patients, respectively. Overall, 104 patients with LC and UGIB not under AT matched for severity of LC, age, sex, source of bleeding, and Sequential Organ Failure Assessment (SOFA) score served as controls. UGIB was attributed to portal hypertension (PH) in 99 (63%) patients and peptic/vascular lesions in 57 (37%). Twenty-six (17%) patients experienced 5-day failure; SOFA, source of UGIB, and PVT, but not AT, were independent predictors of 5-day failure. In addition, independent predictors of 6-week mortality, which was observed in 26 (11%) patients, were SOFA, Charlson Comorbidity index, and use of AT for a CVD. There were no differences between patients with/without AT in needs for rescue therapies, intensive care unit admission, transfusions, and hospital stay. CONCLUSIONS: Factors that impact the outcome of UGIB in patients under AT are degree of multiorgan failure and comorbidity, but not AT itself.

Experimental study of hybrid-knife endoscopic submucosal dissection (ESD) versus standard ESD in a Western country.

BACKGROUND: Endoscopic submucosal dissection (ESD) is an effective but time-consuming treatment for early neoplasia that requires a high level of expertise. OBJECTIVE: The objective of this study was to assess the efficacy and learning curve of gastric ESD with a hybrid knife with high pressure water jet and to compare with standard ESD. MATERIAL AND METHODS: We performed a prospective non survival animal study comparing hybrid-knife and standard gastric ESD. Variables recorded were: Number of en-bloc ESD, number of ESD with all marks included (R0), size of specimens, time and speed of dissection and adverse events. Ten endoscopists performed a total of 50 gastric ESD (30 hybrid-knife and 20 standard). RESULTS: Forty-six (92 %) ESD were en-bloc and 25 (50 %) R0 (hybrid-knife: n = 13, 44 %; standard: n = 16, 80 %; p = 0.04). Hybrid-knife ESD was faster than standard (time: 44.6 +/- 21.4 minutes vs. 68.7 +/- 33.5 minutes; p = 0.009 and velocity: 20.8 +/- 9.2 mm(2)/min vs. 14.3 +/- 9.3 mm(2)/min (p = 0.079). Adverse events were not different. There was no change in speed with any of two techniques (hybrid-knife: From 20.33 +/- 15.68 to 28.18 +/- 20.07 mm(2)/min; p = 0.615 and standard: From 6.4 +/- 0.3 to 19.48 +/- 19.21 mm(2)/min; p = 0.607). The learning curve showed a significant improvement in R0 rate in the hybrid-knife group (from 30 % to 100 %). CONCLUSION: despite the initial performance of hybrid-knife ESD is worse than standard ESD, the learning curve with hybrid knife ESD is short and is associated with a rapid improvement. The introduction of new tools to facilitate ESD should be implemented with caution in order to avoid a negative impact on the results.

Efficacy and safety of anticoagulation on patients with cirrhosis and portal vein thrombosis.

BACKGROUND & AIMS: Portal vein thrombosis (PVT) is a frequent event in patients with cirrhosis; it can be treated with anticoagulants, but there are limited data regarding safety and efficacy of this approach. We evaluated this therapy in a large series of patients with cirrhosis and non-neoplastic PVT. METHODS: We analyzed data from 55 patients with cirrhosis and PVT, diagnosed from June 2003 to September 2010, who received anticoagulant therapy for acute or subacute thrombosis (n = 31) or progression of previously known PVT (n = 24). Patients with cavernomatous transformation were excluded. Thrombosis was diagnosed, and recanalization was evaluated by using Doppler ultrasound, angio-computed tomography, and/or angio-magnetic resonance imaging analyses. RESULTS: Partial or complete recanalization was achieved in 33 patients (60%; complete in 25). Early initiation of anticoagulation was the only factor significantly associated with recanalization. Rethrombosis after complete recanalization occurred in 38.5% of patients after anticoagulation therapy was stopped. Despite similar baseline characteristics, patients who achieved recanalization developed less frequent liver-related events (portal hypertension-related bleeding, ascites, or hepatic encephalopathy) during the follow-up period, but this difference was not statistically significant (P = .1). Five patients developed bleeding complications that were probably related to anticoagulation. A platelet count <50 × 109/L was the only factor significantly associated with higher risk for experiencing a bleeding complication. There were no deaths related to anticoagulation therapy. CONCLUSIONS: Anticoagulation is a relatively safe treatment that leads to partial or complete recanalization of the portal venous axis in 60% of patients with cirrhosis and PVT; it should be maintained indefinitely to prevent rethrombosis.

Increased bactericidal/permeability increasing protein in patients with cirrhosis.

BACKGROUND: High levels of endotoxin in patients with cirrhosis are thought to be responsible for the activation of tumour necrosis factor-alpha (TNF)-alpha-mediated pro-inflammatory pathways involved in haemodynamic alterations. Bactericidal/permeability increasing protein (BPI) is a protein found in neutrophils with endotoxin-binding and neutralization capacity. It is not known whether defective BPI production or release is present in cirrhosis. AIMS: We investigated the levels of BPI in cirrhotic patients and its relation to other endotoxin-binding proteins and inflammatory markers. METHODS: Plasmatic levels of BPI, lipopolysaccharide-binding protein, soluble CD14, TNF-alpha and BPI mRNA expression in neutrophils were determined in 130 patients and 30 healthy controls. The capacity of patients' plasma to inhibit lipopolysaccharide (LPS)-mediated TNF-alpha production by monocytes from healthy donors was assessed in vitro. RESULTS: Patients with cirrhosis exhibited an increase in BPI mRNA and plasma level of BPI when compared with healthy controls (P<0.05). Child C group displayed the highest frequency of patients with a high concentration of BPI. A positive correlation was found between TNF-alpha and plasma levels of BPI (P<0.01). High levels of BPI in plasma were able to significantly reduce in vitro TNF-alpha release by monocytes after a challenge with LPS (8.54 +/- 1.04 vs. 10.44 +/- 0.85 pg/ml, P=0.028). CONCLUSION: BPI is increased in cirrhotic patients, especially in those with more severe liver disease. The amount of BPI in the plasma correlated with the TNF-alpha level and was able to reduce LPS-mediated TNF production by monocytes. BPI possibly plays a regulatory role by antagonizing the pro-inflammatory mechanisms mediated by TNF-alpha.

[Comparison of esophageal stenoses produced by endoscopic sclerotherapy versus variceal ligation]. / Comparación de las estenosis esofágicas producidas por escleroterapia o ligadura de varices.

INTRODUCTION: Variceal ligation (VL) eradicates esophageal varices faster than endoscopic sclerotherapy (ES) with a lower rebleeding rate and fewer secondary effects. However, most studies have evaluated the short-term effects of these treatments and some late complications may be overlooked. PATIENTS AND METHODS: To determine the incidence and the characteristics of stenosis, we included 253 cirrhotic patients treated endoscopically for variceal bleeding from 1988 to 2004 in our hospital. ES was carried out with ethanolamine 5% and polidocanol 1.5%. ES and VL were carried out every 15 days until varices were eradicated and then at 3-, 6- and 12-month intervals; if varices reappeared, the initial treatment was repeated. Stenosis was considered mild when esophageal size was more than 10 mm and severe when the endoscope could not be passed through the stricture. RESULTS: We found stenosis in seven out of 105 (6.7%) ES-treated patients and in 10 out of 148 (6.7%) VL-treated patients. The clinical characteristics of the patients and the previous number of endoscopic sessions were similar in both groups. Four out of seven ES patients developed stenosis during the first eradication process (mean: 11 months, 1-60), but this early stenosis was observed in one out of 10 VL patients (mean: 20 months, 1-72). Stenosis was severe in three out of seven ES patients (43%) but in only two out of ten VL patients (20%) (NS). CONCLUSIONS: The incidence of esophageal stenosis was similar after treatment of esophageal varices with ES and VL, although VL had a tendency to produce later stenosis.

Variceal ligation plus nadolol compared with ligation for prophylaxis of variceal rebleeding: a multicenter trial.

beta-Blockers and endoscopic variceal ligation (EVL) have proven to be valuable methods in the prevention of variceal rebleeding. The aim of this study was to compare the efficacy of EVL combined with nadolol versus EVL alone as secondary prophylaxis for variceal bleeding. Patients admitted for acute variceal bleeding were treated during emergency endoscopy with EVL or sclerotherapy and received somatostatin for 5 days. At that point, patients were randomized to receive EVL plus nadolol or EVL alone. EVL sessions were repeated every 10 to 12 days until the varices were eradicated. Eighty patients with cirrhosis (alcoholic origin in 66%) were included (Child-Turcotte-Pugh A, 15%; B, 56%; C, 29%). The median follow-up period was 16 months (range, 1-24 months). The variceal bleeding recurrence rate was 14% in the EVL plus nadolol group and 38% in the EVL group (P = .006). Mortality was similar in both groups: five patients (11.6%) died in the combined therapy group and four patients (10.8%) died in the EVL group. There were no significant differences in the number of EVL sessions to eradicate varices: 3.2 +/- 1.3 in the combined therapy group versus 3.5 +/- 1.3 in the EVL alone group. The actuarial probability of variceal recurrence at 1 year was lower in the EVL plus nadolol group (54%) than in the EVL group (77%; P = .06). Adverse effects resulting from nadolol were observed in 11% of the patients. In conclusion, nadolol plus EVL reduces the incidence of variceal rebleeding compared with EVL alone. A combined treatment could lower the probability of variceal recurrence after eradication.