Implementation of esophageal endoscopic submucosal dissection in Spain: Results from the nationwide registry. / Implementación de la disección endoscópica submucosa esofágica en España: resultados del registro nacional.

INTRODUCTION AND AIMS: The outcomes of endoscopic submucosal dissection (ESD) in the esophagus have not been assessed in our country. Our primary aim was to analyze the effectiveness and safety of the technique. MATERIAL AND METHODS: Analysis of the prospectively maintained national registry of ESD. We included all superficial esophageal lesions removed by ESD in 17 hospitals (20 endoscopists) between January 2016 and December 2021. Subepithelial lesions were excluded. The primary outcome was curative resection. We conducted a survival analysis and used logistic regression analysis to assess predictors of non-curative resection. RESULTS: A total of 102 ESD were performed on 96 patients. The technical success rate was 100% and the percentage of en-bloc resection was 98%. The percentage of R0 and curative resection was 77.5% (n=79; 95%CI: 68%-84%) and 63.7% (n=65; 95%CI: 54%-72%), respectively. The most frequent histology was Barrett-related neoplasia (n=55 [53.9%]). The main reason for non-curative resection was deep submucosal invasion (n=25). The centers with a lower volume of ESD obtained worse results in terms of curative resection. The rate of perforation, delayed bleeding and post-procedural stenosis were 5%, 5% and 15.7%, respectively. No patient died or required surgery due to an adverse effect. After a median follow-up of 14months, 20patients (20.8%) underwent surgery and/or chemoradiotherapy, and 9 patients died (mortality 9.4%). CONCLUSIONS: In Spain, esophageal ESD is curative in approximately two out of three patients, with an acceptable risk of adverse events.

Fecal occult blood and calprotectin testing to prioritize primary care patients for colonoscopy referral: The advantage study.

BACKGROUND: Colonoscopy is the gold standard for colorectal cancer (CRC) diagnosis and screening, but endoscopy services are usually overburdened. This study aims to investigate the usefulness of fecal hemoglobin (fHb) and calprotectin (FC) for the identification of patients with high probability of CRC who need urgent referral. METHODS: In a multicenter prospective study, we enrolled symptomatic patients referred from primary care for colonoscopy. Prior to bowel preparation, fHb and FC quantitative tests were performed. The diagnostic performance was estimated for each biomarker/combination. We built a multivariable predictive model based on logistic regression, translated to a nomogram and a risk calculator to assist clinicians in the decision-making process. RESULTS: The study included 1224 patients, of whom 69 (5.6%) had CRC. At the fHb cut-offs of >0 and 10 µg/g, the negative predictive values for CRC were 98.8% (95% confidence interval 97.8%-99.3%) and 98.6% (95%CI 97.7%-99.1%), and the sensitivities were 85.5% (95%CI 75.0%-92.8%) and 79.7% (95%CI 68.3%-88.4%), respectively. When we added the cut-off of 150 µg/g of FC to both fHb thresholds, the sensitivity of fecal tests improved. In the multivariate logistic regression model, the concentration of fHb was an independent predictor for CRC; age and gender were also independently associated with CRC. CONCLUSIONS: fHb and FC are useful as part of a triage tool to identify those symptomatic patients with high probability of CRC. This can be easily applied by physicians to prioritize high-risk patients for urgent colonoscopy.

Gastric calcinosis ulcer in a renal transplanted patient.

A 53-year-old lady with dysfunctional renal transplant and post-surgical hypoparathyroidism with phosphocalcic metabolism impairment was admitted to hospital because of long-lasting epigastric pain and nausea. An esophagogastroduodenoscopy was performed, visualising a nodular lesion of 1 cm diameter with a depressed and ulcerated base. Microscopically the lesion was in relation with a metastatic calcinosis ulcer. Pantoprazole was initiated and serum phosphocalcic levels adjusted, achieving symptom remission. In the follow-up esophagogastroduodenoscopy, the lesion was healing with a fibrinous base and the histopathological report diagnosed superficial gastritis.

Hepatic subcapsular hematoma post-endoscopic retrograde cholangiopancreatography requiring embolization.

Endoscopic retrograde cholangiopancreatography (ERCP) placement of biliary stents is the procedure of choice for bile duct strictures. Complications of endoscopic retrograde cholangiopancreatography have a low incidence. Hepatic subcapsular hematoma is uncommon but potentially serious. It is caused by laceration of the bile duct with guidewire or biliary traction during the procedure. Initial management is conservative with supportive measures. In case of hemodynamic instability or superinfection, embolization of the affected branch or even surgery could be performed.

Colonoscopy - When quality matters.

Colonoscopy technical quality is a primary determinant of clinical outcome. Unfortunately, there is enough evidence available for significant variability in endoscopists' performance. An assessment of the factors determining these differences will be crucial for designing measures to ensure effectiveness and safety in these procedures.

Germline CDH1 G212E Missense Variant: Combining Clinical, In Vitro and In Vivo Strategies to Unravel Disease Burden.

E-cadherin, encoded by CDH1, is an essential molecule for epithelial homeostasis, whose loss or aberrant expression results in disturbed cell-cell adhesion, increased cell invasion and metastasis. Carriers of CDH1 germline mutations have a high risk of developing diffuse gastric cancer and lobular breast cancer, associated with the cancer syndrome Hereditary Diffuse Gastric Cancer (HDGC). The ubiquitous availability of cancer panels has led to the identification of an increasing amount of "incidental" CDH1 genetic variants that pose a serious clinical challenge. This has sparked intensive research aiming at an accurate classification of the variants and consequent validation of their clinical relevance. The present study addressed the significance of a novel CDH1 variant, G212E, identified in an unusually large pedigree displaying strong aggregation of diffuse gastric cancer. We undertook a comprehensive pipeline encompassing family data, in silico predictions, in vitro assays and in vivo strategies, which validated the deleterious phenotype induced by this genetic alteration. In particular, we demonstrated that the G212E variant affects the stability and localization, as well as the adhesive and anti-invasive functions of E-cadherin, triggering epithelial disruption and disorganization. Our findings illustrate the clinical implication of a complementary approach for effective variant categorization and patient management.

Long-term follow-up after endoscopic submucosal dissection of colorectal lesions in a Spanish cohort.

INTRODUCTION: ESD in the colon is an increasingly important technique in Western countries. There are few studies that include long term follow-up. AIM: to analyze the long term recurrence free survival rate after ESD and to compare recurrence rates according to different variables. METHODS: this was a prospective observational study of patients with a planned ESD from September 2008 to December 2015. When it was not possible to achieve an ESD, hybrid ESD was performed, either en bloc or piecemeal. Kaplan-Meier survival curves were used to assess the five year local recurrence free survival rate and the recurrence rate. The results were compared according to different factors. RESULTS: of the 89 patients scheduled for ESD who were initially enrolled in the study, 69 were finally included for follow-up. ESD was performed in 31 (45%) patients, KAR in eleven (16%) and pKAR in 27 (39%). The median follow-up was 27 months (range 6-60). The five year disease free survival rate was 81%. The average number of endoscopies needed to eliminate recurrence was two (range 2-7) and no patient required surgery for this reason. The recurrence rate was significantly higher in piecemeal resections vs en bloc resections (27% vs 15%, p = 0.036) and R1 resections vs R0 resections (26% vs 0%, p = 0.034). The presence of affected or unknown lateral margins in en bloc resections without other poor prognosis factors had higher recurrence rates but the difference was not statistically significant (28% vs 0%, p = 0.09). CONCLUSIONS: in our study, the five year disease free survival rate was 81% and no patient required surgery during follow-up. Piecemeal and R1 resections had significantly higher recurrence rates, as well as LM involvement, although this was not statistically significant.

Endoscopic submucosal dissection for gastric epithelial lesions: long-term results in a Spanish cohort.

INTRODUCTION: endoscopic submucosal dissection for gastric lesions (ESD-G) is a technique that allows en-bloc resection of early gastric tumors, with a cure rate similar to that of surgery but lower morbidity and mortality rates. OBJECTIVE: to assess total survival, disease-free survival and relapse rate during the course of disease in a Spanish cohort of patients undergoing ESD-G. MATERIAL AND METHODS: this was a prospective observational study of patients undergoing ESD-G from 2008 to 2015, with a follow-up ranging from six to 60 months. Recurrence at five years was analyzed using Kaplan-Meier curves and the results were compared according to several factors using the log-rank test. These included en-bloc versus piecemeal resection and R0 curative resection versus resection with affected lateral margins (LM+). RESULTS: a total of 35 patients undergoing ESD-G were assessed, with a median follow-up of 33.62 months. Four relapses were identified (11.4%) during this period, of which three were managed with repeat ESD-G. A histological specimen with LM+ was associated with a higher local relapse rate during follow-up (p = 0.06). Piecemeal resections had a higher relapse risk, although no statistically significant differences were identified (p = 0.49). No deaths from gastric cancer occurred and no gastrectomies due to persistent disease were performed during this period. The overall survival rate in our series was 94.3%. CONCLUSIONS: ESD-G in our setting provides high long-term cure rates, while avoiding surgery. These results are similar to those reported by the European series and remain far removed from the cure and relapse rates obtained in Asian cohorts. Local relapse cases may be monitored with endoscopy.

Endoscopic surveillance after colonic polyps and colorrectal cancer resection. 2018 update. / Vigilancia tras resección de pólipos de colon y de cáncer colorrectal. Actualización 2018.

There is limited scientific evidence available to stratify the risk of developing metachronous colorectal cancer after resection of colonic polyps and to determine surveillance intervals and is mostly based on observational studies. However, while awaiting further evidence, the criteria of endoscopic follow-up needs to be unified in our setting. Therefore, the Spanish Association of Gastroenterology, the Spanish Society of Family and Community Medicine, the Spanish Society of Digestive Endoscopy, and the Colorectal Cancer Screening Group of the Spanish Society of Epidemiology, have written this consensus document, which is included in chapter 10 of the "Clinical Practice Guideline for Diagnosis and Prevention of Colorectal Cancer. 2018 Update". Important developments will also be presented as regards the previous edition published in 2009. First of all, situations that require and do not require endoscopic surveillance are established, and the need of endoscopic surveillance of individuals who do not present a special risk of metachronous colon cancer is eliminated. Secondly, endoscopic surveillance recommendations are established in individuals with serrated polyps. Finally, unlike the previous edition, endoscopic surveillance recommendations are given in patients operated on for colorectal cancer. At the same time, it represents an advance on the European guideline for quality assurance in colorectal cancer screening, since it eliminates the division between intermediate risk group and high risk group, which means the elimination of a considerable proportion of colonoscopies of early surveillance. Finally, clear recommendations are given on the absence of need for follow-up in the low risk group, for which the European guidelines maintained some ambiguity.

Colorectal cancer screening and survival.

It is difficult to resist the undeniable allure of screening as a means to diagnose common, potentially serious diseases before their natural history reaches an incurable stage. Colorectal cancer (CRC) is a classical example where the benefits seem to be within reach: we have technologies available that allow its diagnosis before symptoms or signs develop, at a reasonable cost, and using methods acceptable by a significant percentage of the population.

Switching from endoscopic submucosal dissection to salvage piecemeal knife-assisted snare resection to remove a lesion: A preoperative risk score from the beginning.

BACKGROUND AND AIMS: endoscopic submucosal dissection (ESD) in the Western setting remains a challenge. Therefore, other simplified techniques such as knife-assisted snare resection (KAR) have been reported to overcome this issue. METHODS: patients who underwent an ESD for the treatment of gastrointestinal neoplasms were included in a retrospective cross-sectional observational study. Factors associated with the end of ESD as a salvage p-KAR were identified and a logistic regression model was developed. RESULTS: a total of 136 lesions in 133 patients were analyzed. Operator experience of under 50 cases and the combination of lesion size > 30 mm and colorectal location were independent predictive factors for switching to a salvage p-KAR according to the multivariate logistic regression analysis. We developed a risk scoring system based on these four variables (experience, size, location and the combination of size and location) with a receiver operating characteristic curve of 0.81 (95% CI: 0.74-0.89). The diagnostic accuracy of the score for a cut-off point ≥ 5 had a sensitivity of 0.79 (95% CI: 0.66-0.93) and a specificity of 0.71 (95% CI: 0.61-0.80). CONCLUSION: a simple predictive score system that includes four preoperative factors accurately predicts ESD to finish as a p-KAR. A careful selection of cases considering these variables could be useful to achieve better outcomes in the Western setting.

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.

Real-life chromoendoscopy for neoplasia detection and characterisation in long-standing IBD.

OBJECTIVE: Outside clinical trials, the effectiveness of chromoendoscopy (CE) for long-standing IBD surveillance is controversial. We aimed to assess the effectiveness of CE for neoplasia detection and characterisation, in real-life. DESIGN: From June 2012 to 2014, patients with IBD were prospectively included in a multicentre cohort study. Each colonic segment was evaluated with white light followed by 0.4% indigo carmine CE. Specific lesions' features were recorded. Optical diagnosis was assessed. Dysplasia detection rate between expert and non-expert endoscopists and learning curve were ascertained. RESULTS: Ninety-four (15.7%) dysplastic (1 cancer, 5 high-grade dysplasia, 88 low-grade dysplasia) and 503 (84.3%) non-dysplastic lesions were detected in 350 patients (47% female; mean disease duration: 17 years). Colonoscopies were performed with standard definition (41.5%) or high definition (58.5%). Dysplasia miss rate with white light was 40/94 (57.4% incremental yield for CE). CE-incremental detection yield for dysplasia was comparable between standard definition and high definition (51.5% vs 52.3%, p=0.30). Dysplasia detection rate was comparable between expert and non-expert (18.5% vs 13.1%, p=0.20). No significant learning curve was observed (8.2% vs 14.2%, p=0.46). Sensitivity, specificity, and positive and negative predictive values for dysplasia optical diagnosis were 70%, 90%, 58% and 94%, respectively. Endoscopic characteristics predictive of dysplasia were: proximal location, loss of innominate lines, polypoid morphology and Kudo pit pattern III-V. CONCLUSIONS: CE presents a high diagnostic yield for neoplasia detection, irrespectively of the technology and experience available in any centre. In vivo, CE optical diagnosis is highly accurate for ruling out dysplasia, especially in expert hands. Lesion characteristics can aid the endoscopist for in situ therapeutic decisions. TRIAL REGISTRATION NUMBER: NCT02543762.

Extrinsic esophageal compression by the vertebral body.

A 78-year-old woman with hypertension, diabetes, dyslipidemia, and revascularized ischemic heart disease was diagnosed with gastric adenocarcinoma in 2011, with suspected bilateral adrenal metastatic disease, and was treated with subtotal gastrectomy and palliative chemotherapy. A follow-up gastroscopy in 2015 identified a protruding, erosive mid-esophageal lesion suggestive of extrinsic compression or ulcerated submucosal lesion, which had not been described previously. Follow-up was advised, and the lesion persisted after three months. The patient had no esophageal symptoms, and subsequent thoracoabdominal CT scans found no bony abnormalities in the cervicothoracic spine or mediastinal changes. Endoscopic ultrasound was recommended given the patient's cancer history.

Colonic endoscopic full-thickness resection (EFTR) with the over-the-scope device (FTRD): a short case series.

The endoscopic treatment of early gastrointestinal neoplasms usually involves the resection of the superficial layers, mucosa and submucosa, of the wall. However, in some circumstances, a full-thickness resection may be necessary. Endoscopic full-thickness resection (EFTR) may be an adequate approach in challenging lesions such as adenomas or early cancers with severe submucosal fibrosis or small sub-epithelial lesions in the lower GI tract. Furthermore, this novel technique has the potential to spare surgical therapy in a subset of cases. In this paper, we describe our results with the full-thickness resection device (FTRD) in three different situations.

Evaluation of the short- and long-term effectiveness and safety of fully covered self-expandable metal stents for drainage of pancreatic fluid collections: results of a Spanish nationwide registry.

BACKGROUND AND AIMS: Initial reports suggest that fully covered self-expandable metal stents (FCSEMSs) may be better suited for drainage of dense pancreatic fluid collections (PFCs), such as walled-off pancreatic necrosis. The primary aim was to analyze the effectiveness and safety of FCSEMSs for drainage of different types of PFCs in a large cohort. The secondary aim was to investigate which type of FCSEMS is superior. METHODS: This was a retrospective, noncomparative review of a nationwide database involving all hospitals in Spain performing EUS-guided PFC drainage. From April 2008 to August 2013, all patients undergoing PFC drainage with an FCSEMS were included in a database. The main outcome measurements were technical success, short-term (2 weeks) and long-term (6 months) effectiveness, adverse events, and need for surgery. RESULTS: The study included 211 patients (pseudocyst/walled-off pancreatic necrosis, 53%/47%). The FCSEMSs used were straight biliary (66%) or lumen-apposing (34%). Technical success was achieved in 97% of patients (95% confidence interval [CI], 93%-99%). Short-term- and long-term clinical success was obtained in 94% (95% CI, 89%-97%) and 85% (95% CI, 79%-89%) of patients, respectively. Adverse events occurred in 21% of patients (95% CI, 16%-27%): infection (11%), bleeding (7%), and stent migration and/or perforation (3%). By multivariate analysis, patient age (>58 years) and previous failed drainage were the most important factors associated with negative outcome. CONCLUSIONS: An FCSEMS is effective and safe for PFC drainage. Older patients with a history of unsuccessful drainage are more likely to fail EUS-guided drainage. The type of FCSEMS does not seem to influence patient outcome.

Colorectal endoscopic submucosal dissection from a Western perspective: Today's promises and future challenges.

Over the last few years, endoscopic submucosal dissection (ESD) has shown to be effective in the management of early colorectal neoplasms, particularly in Asian countries where the technique was born. In the Western world, its implementation has been slow and laborious. In this paper, the indications for ESD, its learning model, the available methods to predict the presence of deep submucosal invasion before the procedure and the published outcomes from Asia and Europe will be reviewed. Since ESD has several limitations in terms of learning achievement in the West, and completion of the procedure for the first cases is difficult in our part of the world, a short review on colorectal assisted ESD has been included. Finally, other endoscopic and surgical treatment modalities that are in competition with colorectal ESD will be summarized.

Endoscopic surveillance in patients with multiple (10-100) colorectal polyps.

BACKGROUND AND STUDY AIMS: Endoscopic surveillance in patients with multiple colorectal polyps aims to reduce colorectal cancer (CRC) incidence and mortality, as well as the need for colorectal surgery. The aim of this study was to determine the risk of developing CRC or the need for surgery during endoscopic surveillance in a cohort of patients with multiple (10 - 100) colorectal polyps. PATIENTS AND METHODS: This was a multicentrer, longitudinal, observational study in 15 CRC high risk clinics in Spain, carried out between January 2009 and December 2010. Patients who were included in the EPIPOLIP trial and had at least 1 year of follow-up were included in the study. The primary outcome of interest was the incidence of CRC at least 1 year following the initial colonoscopy. The secondary outcome was the need for colorectal surgery. RESULTS: A total of 265 patients were followed for a median of 3.8 years. Patients underwent a median of 5 colonoscopies, and 17 patients (6.4 %) were diagnosed with CRC. A total of 32 patients (12.1 %) underwent surgery, including 15 (5.7 %) for prophylaxis without a diagnosis of CRC. The corresponding incidence density rates for CRC and colorectal surgery were 1.4 (95 % confidence interval [CI] 0.7 to 2.1) and 2.7 (95 %CI 1.7 to 3.6) per 100 patient-years, respectively. Only the presence of symptoms at first colonoscopy was independently associated with CRC diagnosis (hazard ratio [HR] 7.7, 95 %CI 1.1 to 59.3) and colorectal surgery (HR 4.6, 95 %CI 1.02 to 20.6). CONCLUSIONS: Patients with more than 10 neoplastic polyps required frequent colonoscopies within a short follow-up period. More than 10 % of patients required colorectal surgery within 4 years, more than half for incident CRC.

Endoscopic submucosal dissection (ESD) of antral subepithelial lesion suspected of malignancy.

Subepithelial gastric tumours comprise a heterogeneous group of lesions. Endoscopic ultrasonography with fine-needle aspiration (EUS-FNA) is a useful approach but cannot always offer a definitive diagnosis to guide future therapeutic decisions. In the case we describe, biopsy samples of an antral subepithelial lesion and cytological analysis obtained with an EUS-FNA suggested the diagnosis of an adenocarcinoma. Endoscopic submucosal dissection (ESD) allowed en bloc resection of the tumour ensuring diagnosis and providing a definitive treatment.