Epithelial-specific ERBB3 deletion results in a genetic background-dependent increase in intestinal and colon polyps that is mediated by EGFR.

ERBB3 has gained attention as a potential therapeutic target to treat colorectal and other types of cancers. To confirm a previous study showing intestinal polyps are dependent upon ERBB3, we generated an intestinal epithelia-specific ERBB3 deletion in C57BL/6-ApcMin/+ mice. Contrary to the previous report showing a significant reduction in intestinal polyps with ablation of ERBB3 on a B6;129 mixed genetic background, we observed a significant increase in polyp number with ablation of ERBB3 on C57BL/6J compared to control littermates. We confirmed the genetic background dependency of ERBB3 by also analyzing polyp development on B6129 hybrid and B6;129 advanced intercross mixed genetic backgrounds, which showed that ERBB3 deficiency only reduced polyp number on the mixed background as previously reported. Increased polyp number with ablation of ERBB3 was also observed in C57BL/6J mice treated with azoxymethane showing the effect is model independent. Polyps forming in absence of ERBB3 were generally smaller than those forming in control mice, albeit the effect was greatest in genetic backgrounds with reduced polyp numbers. The mechanism for differential polyp number in the absence of ERBB3 was through altered proliferation. Backgrounds with increased polyp number with loss of ERBB3 showed an increase in cell proliferation even in non-tumor epithelia, while backgrounds showing reduced polyp number with loss of ERBB3 showed reduced cellular proliferation. Increase polyp number caused by loss of ERBB3 was mediated by increased epidermal growth factor receptor (EGFR) expression, which was confirmed by deletion of Egfr. Taken together, this study raises substantial implications on the use of ERBB3 inhibitors against colorectal cancer. The prediction is that some patients may have increased progression with ERBB3 inhibitor therapy, which is consistent with observations reported for ERBB3 inhibitor clinical trials.

The Role of Self-Determination in Changing Physical Activity Behavior in People Diagnosed With Bowel Polyps: A Pilot Randomized Controlled Trial.

This nonblinded randomized controlled trial investigated the efficacy of a physical activity (PA) intervention underpinned by self-determination theory. Participants (N = 31, mean age 69 years [SD = 4.9]) diagnosed with bowel polyps were randomized to an active lifestyle program (ALP; n = 17) or standard care (n = 14). ALP received supervised exercise and counseling for 6 months. Both groups were followed up at 12 months. Outcomes were change in PA and behavioral regulation. Data were analyzed with intention to treat. At 6 months, differences were observed for behavioral regulation in favor of ALP (p < .05). PA differences were significant for leisure, walking, and vigorous in favor of ALP (p < .05). The self-determination theory can be an effective strategy for promoting PA behavior change in this population, but a larger trial is needed to further explore the utility of the self-determination theory in this context.

[Tumor neuroendocrino ano-rectal: desde un pólipo con buen pronóstico hasta un carcinoma letal]. / Ano-rectal neuroendocrine tumour: from a polyp with a good prognosis to a lethal carcinoma.

INTRODUCCIÓN: Aunque los tumores neuroendocrinos rectales son neoplasias poco frecuentes, su incidencia está aumentando en las tres últimas décadas. El objetivo de este trabajo es el estudio del comportamiento de dichos tumores basándonos en sus variables clínicas, diagnósticas, terapéuticas y anatomopatológicas en un hospital terciario. MÉTODO: Estudio retrospectivo de los tumores neuroendocrinos rectales desde el año 2000 hasta el año 2017 en nuestro hospital. Se realizó una búsqueda informatizada en el programa SNOMED del servicio de anatomía patológica, empleando los criterios «tumor neuroendocrino¼ y «tumor carcinoide¼. RESULTADOS: Se hallaron 16 pacientes con tumor neuroendocrino ano-rectal. El 75% eran varones. La mediana de edad fue de 53 años (rango: 34-83). El diagnóstico fue incidental en el 62,5%. El tratamiento fue endoscópico en 13 (81%) pacientes y quirúrgico en 3 (19%). El 75% de las lesiones fueron T1. El 68,7% de los tumores presentaban un grado de agresividad G1. La media de seguimiento fue de 29 meses; no hubo recidivas. Durante el seguimiento fallecieron 3 (18,5%) pacientes, todos ellos con tumor G3 metastásico, y la supervivencia media fue de 8 meses. CONCLUSIONES: Los tumores neuroendocrinos rectales son cada vez más frecuentes y presentan unos patrones variables, cuyo pronóstico dependerá de su agresividad histológica. El aumento de su incidencia puede deberse a una mayor concienciación de la existencia de estos tumores, a las campañas de cribado del cáncer colorrectal, al aumento del número de colonoscopias realizadas y a la generalización de los estudios histológicos con marcadores neuroendocrinos. BACKGROUND: Although rectal neuroendocrine tumours are rare neoplasms, their incidence is increasing in the last three decades. The objective of this work is to study the behaviour of these tumours based on their clinical, diagnostic, therapeutic, and pathological variables in a tertiary hospital. METHOD: Retrospective study of rectal neuroendocrine tumours from 2000 to 2017 in our hospital. A computerized search was performed in the SNOMED program of the pathological anatomy service, using the criteria "neuroendocrine tumour" and "carcinoid tumour". RESULTS: We found 16 patients with ano-rectal neuroendocrine tumour; 75% were male. The median age was 53 years (range: 34-83). The diagnosis was incidental in 62.5%, with endoscopic treatment in 13 patients (81%) and surgical treatment in 3 (19%). 75% of the lesions were T1. 68.7% of the tumours showed a degree of G1 aggression. The mean follow-up was 29 months; no recurrences. During follow-up, three patients died (18.5%), all of them with metastatic G3 tumour and the mean survival was 8 months. CONCLUSIONS: The rectal neuroendocrine tumours are increasingly frequent and present variable patterns, whose prognosis will depend on their histological aggressiveness. The increase incidence may be due to a greater awareness of the existence of these tumours, to colorectal cancer screening, to the increase in the number of colonoscopies performed and to the generalization of histological studies with neuroendocrine markers.

Evaluation and management of gastric epithelial polyps.

Gastric polyps include a wide spectrum of lesions with different histology and neoplastic potential. They are found in up to 6% of upper gastrointestinal endoscopy and are usually asymptomatic and incidentally diagnosed, being in the vast majority epithelial gastric polyps. Hyperplastic, fundic gland and adenomas are the most common types of gastric polyps and, although each type may have typical endoscopic appearances, they all must be sampled at the initial endoscopy for histological assessment. Also, the normal appearing gastric mucosa should be sampled to stage atrophic changes, rule out endoscopically non-visible dysplasia and to diagnose Helicobacter pylori. Polyposis syndromes that affect the stomach are rare but should be taken into account. Hamartomatous polyps can be found in Juvenile polyposis, Cowden syndrome and Peutz-Jeghers syndrome. On the other hand, multiple fundic gland polyps are present in the majority of patients with familial adenomatous polyposis. In this study we provide a comprehensive review on the evaluation and management of gastric epithelial polyps, in this way helping physicians to properly handle this type of lesions.

Management of duodenal polyps.

Duodenal adenomas are the most common type of polyp arising from the duodenum. These adenomas can occur within and outside of genetic syndromes, and are broadly classified as non-ampullary or ampullary depending on their location. All adenomas have malignant potential and are therefore appropriately treated by endoscopic resection. However, the unique anatomical properties of the duodenum, namely its relatively thin and vascular walls, narrow luminal diameter and relationship to the ampulla and its associated pancreatic and biliary drainage, pose an increased degree of complexity for any endoscopic interventions in this area. This review will discuss the epidemiology of duodenal adenomas, their endoscopic detection and diagnosis, and techniques for safe and effective endoscopic resection of ampullary and non-ampullary lesions.

Management of small bowel polyps: A literature review.

Despite the small bowel comprising 90% of the mucosal surface area of the gastrointestinal tract, it is a rare site for neoplasia and only accounts for a little over 3% of the tumors that arise in the digestive tract. Benign small bowel lesions include lipomas, lymphangiomas, leiomyomas, neurofibromas, nodular lymphoid hyperplasia and adenomas, many of which are precursors to malignant lesions. Several polyposis syndromes are associated with small bowel polyps as well, including familial adenomatous polyposis syndrome, lynch syndrome, Peutz-Jeghers syndrome, Cowden syndrome and juvenile polyposis syndrome. Our aim was to review non-malignant small bowel polyps and discuss the prevalence, typical location, clinical presentation, diagnosis, endoscopic and histologic description and lastly management of each of these lesions.

Management of Non-neoplastic Gastric Lesions.

Benign gastric lesions represent various pathologic entities and management considerations. Upper endoscopy serves as the primary diagnostic modality for gastric lesions. Persistent or giant gastric ulcers represent unique subtypes of ulcers, requiring investigation of the underlying cause. Medical management remains the mainstay of treatment; however, indications for surgical intervention remain. Gastric polyps also represent diverse etiologies, and accurate diagnosis requires pertinent information and tissue samples. Neoplastic lesions often present as polypoid lesions; a high index of suspicion is required when discovered endoscopically. Malignant transformation potential varies widely between the various lesions; therefore an accurate diagnosis is imperative to determine management.

TeleCondutas: pólipos colorretais / TeleGuides: colorectal polyps

Pólipos colorretais são pequenas protrusões da mucosa colônica e do reto, sendo a sua grande maioria de potencial maligno baixo (como os adenomas tubulares com displasia de baixo grau) ou nulo (como os pólipos hiperplásicos). Os pólipos que contêm potencial maligno ­ os adenomas ­ são a parte inicial da cascata de carcinogênese de 95% das neoplasias malignas colorretais e podem ser diagnosticados e removidos através da colonoscopia. Esta guia apresenta informação que orienta a conduta para casos de pólipos colorretais no contexto da Atenção Primária à Saúde, incluindo: classificação dos pólipos colorretais, avaliação dos pólipos colorretais, seguimento das lesões pré-malignas, manejo dos pólipos colorretais, colonoscopia - procedimento e cuidados, rastreamento e vigilância de câncer colorretal, encaminhamento para serviço especializado.

Small Bowel Neoplasms and Polyps.

The small intestine is a relatively privileged organ that only rarely develops malignant or even benign tumors. Given this rarity, the relative inaccessibility of the organ during routine endoscopic procedures, and the typical absence or nonspecific nature of clinical manifestations, these tumors often go undiagnosed. Treatment and prognosis are tailored to each histological subtype of tumor. This chapter will discuss the epidemiology, presentation, diagnostics, and management for the most common small bowel tumors, and will highlight the importance of recognizing patients at higher risk of small bowel neoplasia.

Nonampullary duodenal adenoma: Current understanding of its diagnosis, pathogenesis, and clinical management.

Nonampullary duodenal adenomas are relatively common in familial adenomatous polyposis (FAP), but nonampullary sporadic duodenal adenomas (SDAs) are rare. Emerging evidence shows that duodenal adenomas, regardless of their anatomic location and whether they are sporadic or FAP-related, share morphologic and molecular features with colorectal adenomas. The available data suggest that duodenal adenomas develop to duodenal adenocarcinomas via similar mechanisms. The optimal approach for management of duodenal adenomas remains to be determined. The techniques for endoscopic resection of duodenal adenoma include snare polypectomy, endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD), and argon plasma coagulation ablation. EMR may facilitate removal of large duodenal polyps. Although several studies have reported cases of successful ESD for duodenal adenomas, the procedure is technically difficult to perform safely because of the anatomical properties of the duodenum. Although current clinical practice recommends endoscopic resection of all large duodenal adenomas in patients with FAP, endoscopic treatment is usually insufficient to guarantee a polyp-free duodenum. Surgery is indicated for FAP patients with severe polyposis or nonampullary SDAs or FAP-related polyps not amenable to endoscopic resection. Further studies are needed to develop newer endoscopic techniques to guide diagnostic and therapeutic decisions for future management of nonampullary duodenal adenomas.

Endoscopic and surgical treatment of malignant colorectal polyps: a population-based comparative study.

BACKGROUND: Long-term population-based data comparing endoscopic therapy (ET) and surgery for management of malignant colorectal polyps (MCPs) are limited. OBJECTIVE: To compare colorectal cancer (CRC)-specific survival with ET and surgery. DESIGN AND SETTING: Population-based study. PATIENTS: Patients with stage 0 and stage 1 MCPs were identified from the Surveillance Epidemiology and End Results (SEER) database (1998-2009). Demographic characteristics, tumor size, location, treatment modality, and survival were compared. Propensity-score matching and Cox proportional hazards regression models were used to evaluate the association between treatment and CRC-specific survival. INTERVENTIONS: ET and surgery. MAIN OUTCOME MEASUREMENTS: Mid-term (2.5 years) and long-term (5 years) CRC-free survival rates and independent predictors of CRC-specific mortality. RESULTS: Of 10,403 patients with MCPs, 2688 (26%) underwent ET and 7715 (74%) underwent surgery. Patients undergoing ET were more likely to be older white men with stage 0 disease. Surgical patients had more right-sided lesions, larger MCPs, and stage 1 disease. There was no difference in the 2.5-year and 5-year CRC-free survival rates between the 2 groups in stage 0 disease. Surgical resection led to higher 2.5-year (97.8% vs 93.2%; P < .001) and 5-year (96.6% vs 89.8%; P < .001) CRC-free survival in stage 1 disease. These results were confirmed by propensity-score matching. ET was a significant predictor for CRC-specific mortality in stage 1 disease (hazard ratio 2.40; 95% confidence interval, 1.75-3.29; P < .001). LIMITATIONS: Comorbidity index not available, selection bias. CONCLUSIONS: ET and surgery had comparable mid- and long-term CRC-free survival rates in stage 0 disease. Surgical resection is the recommended treatment modality for MCPs with submucosal invasion.

Meeting the challenges of recruitment to multicentre, community-based, lifestyle-change trials: a case study of the BeWEL trial.

BACKGROUND: Recruiting participants to multicentre, community-based trials is a challenge. This case study describes how this challenge was met for the BeWEL trial, which evaluated the impact of a diet and physical activity intervention on body weight in people who had had pre-cancerous bowel polyps. METHODS: The BeWEL trial was a community-based trial, involving centres linked to the Scottish National Health Service (NHS) colorectal cancer screening programme. BeWEL had a recruitment target of 316 and its primary recruitment route was the colonoscopy clinics of the Scottish Bowel Screening Programme. RESULTS: BeWEL exceeded its recruitment target but needed a 6-month no-cost extension from the funder to achieve this. The major causes of delay were lower consent rates (49% as opposed to 70% estimated from earlier work), the time taken for NHS research and development department approvals and the inclusion of two additional sites to increase recruitment, for which there were substantial bureaucratic delays. A range of specific interventions to increase recruitment, for example, telephone reminders and a shorter participant information leaflet, helped to increase the proportion of eligible individuals consenting and being randomized. CONCLUSIONS: Recruitment to multicentre trials is a challenge but can be successfully achieved with a committed team. In a UK context, NHS research and development approval can be a substantial source of delay. Investigators should be cautious when estimating consent rates. If consent rates are less than expected, qualitative analysis might be beneficial, to try and identify the reason. Finally, investigators should select trial sites on the basis of a formal assessment of a site's past performance and the likelihood of success in the trial being planned. TRIAL REGISTRATION: Current Controlled Trials ISRCTN53033856.

Ileal polypoid lymphangiectasia bleeding diagnosed and treated by double balloon enteroscopy.

Intestinal lymphangiectasia is a rare disease characterized by focal or diffuse dilated enteric lymphatics with impaired lymph drainage. It causes protein-losing enteropathy and may lead to gastrointestinal bleeding. Commonly, lymphangiectasia presents as whitish spots or specks. To our knowledge, small bowel bleeding resulting from polypoid intestinal lymphangiectasia has not been reported. Here, we report a rare case of active bleeding from the small bowel caused by polypoid lymphangiectasia with a review of the relevant literature. An 80-year-old woman was hospitalized for melena. Esophagogastroduodenoscopy could not identify the source of bleeding. Subsequent colonoscopy showed fresh bloody material gushing from the small bowel. An abdominal-pelvic contrast-enhanced computed tomography scan did not reveal any abnormal findings. Video capsule endoscopy showed evidence of active and recent bleeding in the ileum. To localize the bleeding site, we performed double balloon enteroscopy by the anal approach. A small, bleeding, polypoid lesion was found in the distal ileum and was successfully removed using endoscopic snare electrocautery.

Tumor de Vanek o pólipo fibroide inflamatorio: reporte de un caso / Vanek's tumor or inflammatory fibroid polyp: Report of a case

El tumor de Vanek o pólipo fibroide inflamatorio, se conoce como una lesión benigna, rara, de localización submucosa, no encapsulada, cuya ubicación puede darse a lo largo del tracto digestivo, siendo más común en el antro gástrico (80 por ciento), aunque también se ha descrito en la unión gastroesofágica, duodeno, yeyuno, íleon y colon. Representa el tumor gástrico benigno menos frecuente (1-4 por ciento), con ligero predominio en el sexo masculino y un pico de incidencia a partir de la sexta década de la vida, siendo la malignización un evento excepcional. En este reporte de caso se presentó un paciente masculino de 47 años de edad, con tumor de Vanek de localización antra, diagnosticado en el Hospital Provincial Universitario Arnaldo Milián Castro, de la ciudad de Santa Clara(AU)

The Vanek's tumor or inflammatory fibroid polyp (IFP) is a rare benign lesion of submucosal location, not encapsulated, that may be located throughout the digestive tract, being more common in the gastric antrum (80 percent), although it has also been described in the gastroesophageal junction, duodenum, jejunum, ileum and colon. It is the less frequent benign gastric tumor (1-4 percent) with slight predominance in males and a peak incidence after the sixth decade of life, being its process of getting malignant an exceptional event. This case report presents a 47-year-old male patient with a Vanek's tumor of antral localization that was diagnosed at the Teaching Provincial Hospital Arnaldo Milian Castro, of Santa Clara(AU)

Serrated polyps of the large intestine: current understanding of diagnosis, pathogenesis, and clinical management.

Approximately 30% of colorectal carcinomas develop via the serrated neoplasia pathway characterized by widespread DNA methylation and frequent BRAF mutation. Serrated polyps represent a heterogeneous group of polyps which are the precursor lesions to serrated pathway colorectal carcinomas. The histological classification of serrated polyps has evolved over the last two decades to distinguish three separate entities: hyperplastic polyp, sessile serrated adenoma (SSA), and traditional serrated adenoma (TSA). The malignant potential of SSAs and TSAs has been clearly demonstrated. SSAs are more challenging to detect by colonoscopy and are likely to account for some interval carcinomas of the proximal colon. Serrated polyposis syndrome is now widely recognized as conferring a high risk of colorectal carcinoma although its cause remains elusive. The current understanding of the actual malignant potential of each serrated polyp subtype is still limited due to the lack of large-scale prospective studies. Patient management guidelines have been recently updated although high-level evidence to support them is still required.

Advances in modern enteroscopy therapeutics.

Advances in modern enteroscopy have been largely due to endoscope development but also through the improved availability of endoscopic accessories along with improved understanding in their application. Device assisted enteroscopy began with the double balloon system in 2001 and was quickly followed by single balloon enteroscopy and spiral enteroscopy. These tools revolutionised deep small bowel endoscopy and allowed for the delivery of virtually all known therapeutic endoscopy intervention to almost all segments of the small bowel. This review covers the types of interventions in regards to indications, methods and their safety profiles as well as reviewing the various device assisted endoscopes available and their attributes.

Nonsurgical management of small-bowel polyps in Peutz-Jeghers syndrome with extensive polypectomy by using double-balloon endoscopy.

BACKGROUND: The major problem in the management of Peutz-Jeghers syndrome (PJS) is small-bowel polyps, which can cause intussusception and bleeding. Double-balloon endoscopy (DBE) enables endoscopic resection of small-bowel polyps. OBJECTIVE: The aim of this study was to determine the efficacy and safety of endoscopic management of small-bowel polyps in PJS patients by using DBE. DESIGN: Retrospective chart review. SETTING: Single university hospital. PATIENTS: Consecutive patients with PJS who underwent multiple sessions of DBE for evaluation or treatment of small-bowel polyps between September 2000 and April 2009. INTERVENTIONS: Endoscopic resection of small-bowel polyps in PJS patients was performed by using DBE. MAIN OUTCOME MEASUREMENTS: Efficacy, safety, and long-term laparotomy rate after the procedures were evaluated. RESULTS: Fifteen patients (10 men, mean age 34.0 ± 15.8 years) underwent DBE for a mean 3.0 ± 1.0 sessions. The mean numbers of resected polyps larger than 20 mm significantly decreased as sessions advanced (first, 3.6; second, 1.3; third, 0.7; fourth, 0.4; and fifth, 1.0; P = .02). The mean maximum sizes of resected polyps also significantly decreased at each session: 33, 19, 12, 17, and 30 mm (P = .01). One patient had a perforation, but was managed conservatively. Other complications were pancreatitis (n = 2) and bleeding (n = 2). Only 1 patient underwent surgery for intussusception during the study period. LIMITATIONS: This was a small single-center retrospective study of short duration. CONCLUSIONS: Endoscopic management of small-bowel polyps in PJS patients by using DBE is safe and effective and avoids urgent laparotomy.