Solobacterium moorei promotes the progression of adenomatous polyps by causing inflammation and disrupting the intestinal barrier.

BACKGROUND: Adenomatous polyps (APs) with inflammation are risk factors for colorectal cancer. However, the role of inflammation-related gut microbiota in promoting the progression of APs is unknown. METHODS: Sequencing of the 16S rRNA gene was conducted to identify characteristic bacteria in AP tissues and normal mucosa. Then, the roles of inflammation-related bacteria were clarified by Spearman correlation analysis. Furthermore, colorectal HT-29 cells, normal colon NCM460 cells, and azoxymethane-treated mice were used to investigate the effects of the characteristic bacteria on progression of APs. RESULTS: The expression levels of inflammation-related markers (diamine oxidase, D-lactate, C-reactive protein, tumor necrosis factor-α, interleukin-6 and interleukin-1ß) were increased, whereas the expression levels of anti-inflammatory factors (interleukin-4 and interleukin-10) were significantly decreased in AP patients as compared to healthy controls. Solobacterium moorei (S. moorei) was enriched in AP tissues and fecal samples, and significantly positively correlated with serum inflammation-related markers. In vitro, S. moorei preferentially attached to HT-29 cells and stimulated cell proliferation and production of pro-inflammatory factors. In vivo, the incidence of intestinal dysplasia was significantly increased in the S. moorei group. Gavage of mice with S. moorei upregulated production of pro-inflammatory factors, suppressed proliferation of CD4+ and CD8+cells, and disrupted the integrity of the intestinal barrier, thereby accelerating progression of APs. CONCLUSIONS: S. moorei accelerated the progression of AP in mice via activation of the NF-κB signaling pathway, chronic low-grade inflammation, and intestinal barrier disruption. Targeted reduction of S. moorei presents a potential strategy to prevent the progression of APs.

Increased Risk of Advanced Colonic Adenomas and Timing of Surveillance Colonoscopy Following Solid Organ Transplantation.

BACKGROUND: Detection and removal of colonic adenomatous polyps (CAP) decreases colorectal cancer (CRC) development, particularly with more or larger polyps or polyps with advanced villous/dysplastic histology. Immunosuppression following solid organ transplantation (SOT) may accelerate CAP development and progression compared to average-risk population but the benefit of earlier colonoscopic surveillance is unclear. AIMS: Study the impact of maintenance immunosuppression post-SOT on developmental timing, multiplicity and pathological features of CAP, by measuring incidence of advanced CAP (villous histology, size ≥ 10 mm, ≥ 3 polyps, presence of dysplasia) post-SOT and the incidence of newly diagnosed CRC compared to average-risk age-matched population. METHODS: Single-center retrospective cohort study of SOT recipients. RESULTS: 295 SOT recipients were included and were compared with 291 age-matched average-risk controls. The mean interval between screening and surveillance colonoscopies between SOT and control groups was 6.3 years vs 5.9 years (p = 0.13). Post-SOT maintenance immunosuppression mean duration averaged 59.9 months at surveillance colonoscopy. On surveillance examinations, SOT recipients exhibited more advanced (≥ 10 mm) adenomas compared to matched controls (9.2% vs. 3.8%, p = 0.034; adjusted OR 2.38; 95% CI 1.07-5.30). CONCLUSION: SOT recipients appear at higher risk for developing advanced CAP, suggesting that earlier surveillance should be considered.

Non-conventional types of dysplastic changes in gastrointestinal tract mucosa - review of morphological features of individual subtypes.

Evaluation of the dysplastic changes evolving in mucosa of various segments of gastrointestinal tract is a part of routine practice. Morphologically different or non-conventional types of dysplastic changes are described in the mucosa of gastrointestinal tract besides the most common conventional type of dysplasia. Non-conventional dysplasias can arise de-novo or they can be found in association with chronic gastrointestinal conditions, such as Barretts esophagus, chronic atrophic gastritis, and inflammatory bowel disease. Non-conventional types of dysplasia include serrated, crypt base of foveolar dysplasia and lesions as pyloric or oxyntic gland adenoma. Non-conventional types of dysplasia arising in inflammatory bowel disease represent specific category with broad morphological spectrum of changes. The aim of this work is to present a comprehensive review of morphological characteristics of individual subtypes of non-conventional dysplastic changes with focus on differences and specificity in particular parts of gastrointestinal tract and provide a functional handout for daily diagnostic practice.

Endoscopic diode laser therapy for gastric hyperplastic polyps in cirrhotic patients.

Purpose Endoscopic polypectomy to remove gastric hyperplastic polyps in cirrhotic patients is associated to a high risk of postprocedural bleeding. The current study set out to examine the effect of diode laser therapy used to treat this type of polyps in cirrhotic patients. Methods This single-center study retrospectively examined the data of cirrhotic patients with macroscopic bleeding or anemia who underwent diode laser therapy (940 nm wave length, 30-W power setting in continuous mode) to remove histology-confirmed hyperplastic gastric polyps. Results A total of 222 polyps (mean diameter 10 ± 8 mm) were treated in 55 patients who were included in the study. No complications such as bleeding or perforations were reported. After a mean of 5 ± 4 sessions, 31 patients (56%) were completely healed. In 16 patients (29%), there was only a partial response (mean polyp reduction diameter of 64 ± 15%), while 8 (15%) patients did not respond to treatment. Statistically significant better results were noted in the patients who underwent ≥ 2 laser sessions. Hemoglobin levels and number of blood transfusions required were not statistically different after treatment. After a mean study period of 21 ± 17 months, polyp recurrences were noted in 11 patients (20%), but none of the polyps had degenerated. Conclusion Diode laser therapy was found to be a safe treatment for hyperplastic polyps in cirrhotic patients. Due to the presence of others bleeding lesions in cirrhotic patients, this treatment did not have an impact on anemia and transfusion requirements.

Integrated Analysis of the Endoscopic, Pathological and Molecular Characteristics of Colorectal Tumorigenesis.

BACKGROUND: Colorectal cancers (CRCs) develop through the accumulation of genetic and epigenetic alterations of oncogenes and tumor suppressor genes. In addition to the well-characterized adenoma-carcinoma sequence, the serrated neoplasia pathway is now recognized as an alternative pathway for CRC development. SUMMARY: Through analysis of the colonoscopic, pathological, and molecular features of colorectal tumors, we identified a novel microsurface structure characteristic of serrated lesions. The Type II-Open (Type II-O) pit pattern is highly specific to sessile serrated adenoma/polyps (SSA/Ps), and Type-II-O-positive tumors frequently exhibit v-raf murine sarcoma viral oncogene homolog B1 (BRAF) mutation and 5'-C-phosphate-G-3' (CpG) island hypermethylation. By screening DNA methylation associated with the development of serrated lesions, we detected methylation of secreted protein acidic and rich in cysteine (SPARC)-related modular calcium binding 1 (SMOC1) in traditional serrated adenomas (TSAs). Epigenetic silencing of SMOC1 is prevalent among TSAs but it is rarely observed in SSA/Ps, which suggests SMOC1 could be a useful diagnostic marker of serrated lesions. We also searched for epigenetic alterations associated with the growth pattern of colorectal tumors and found that methylation of neurotensin receptor 1 is associated with lateral and non-invasive tumor growth. Key Message: Through the summarized studies, we have been able to identify novel morphological and molecular features that could contribute to a better understanding of colorectal tumors and to improved clinical diagnosis.

Patients with Non-Hodgkin's Lymphoma Are at Risk of Adenomatous Colon Polyps.

BACKGROUND: Patients with non-Hodgkin's lymphoma (NHL) are frequently referred for colonoscopy to evaluate gastrointestinal symptoms during their treatment course. Here, we described the rate of colonic adenomas in patients with NHL. METHODS: This was a retrospective study of patients with NHL who underwent colonoscopy after being diagnosed with NHL between January 2000 and December 2017. RESULTS: Of the 17,938 patients who had been diagnosed with NHL in the study period, 2176 met the inclusion criteria. The mean age at the time of colonoscopy was 61 years. Most patients were male (61%). Overall, 1273 polyps were detected in 811 patients (37%). Sessile serrated adenomas were detected in 102 (5%) patients. The overall ADR was 12% in patients younger than 40 years of age (n = 103), 26% in patients aged 40-50 (n = 251), 34% in patients aged 51-60 (n = 630), and 43% in patients older than 60 (n = 1212). Most polyps were located in the right colon (63%), and 101 (8%) were larger than 1 cm. Villous adenomatous features were present in 1% of polyps, while high-grade dysplasia was detected in 22%. Invasive adenocarcinoma was identified in 4%. The median interval from lymphoma diagnosis to adenoma detection was 1.4 years (interquartile range 0.5-3.8 years). A repeat colonoscopy was performed in 343 patients. The overall ADR on repeat colonoscopy was 30%. Cox regression analysis revealed that age (hazards ratio 1.04; 95% confidence interval 1.03-1.05; P < 0.001) and male sex (hazards ratio 1.35; 95% confidence interval 1.13-1.60; P = 0.001) were independent factors associated with worse overall survival. By contrast, screening colonoscopy was associated with longer survival duration (hazards ratio 0.48; 95% confidence interval 0.36-0.63; P < 0.001). CONCLUSION: The ADR in NHL patients aged 40-50 years was equivalent to that reported in the literature in non-cancer patients aged 50-70 years. Early screening colonoscopy may be warranted in NHL patients younger than 50 years. Screening colonoscopy significantly improved the overall survival of patients with NHL.

The first European family with gastric adenocarcinoma and proximal polyposis of the stomach: case report and review of the literature.

BACKGROUND AND AIMS: Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) has to date been recognized in only 8 families worldwide. Recently, different point mutations within the Ying Yang 1 (YY1) binding motif in promoter 1B of the APC gene were assigned as causal in 6 families with GAPPS. METHODS: We diagnosed GAPPS across 3 generations in a Czech white family. RESULTS: The proband's mother died of gastric cancer at 49 years of age. The proband died of gastric cancer at 56 years of age. All 3 of the proband's daughters inherited polyposis, involving exclusively the gastric fundus and body, with relative sparing of the lesser curve. The daughters have all been regularly surveyed endoscopically. Polyposis progressed rapidly with intestinal differentiated low-grade and high-grade dysplasia present on polypectomy specimens 5 years after the original diagnosis. On this basis, all 3 of the proband's daughters were scheduled for prophylactic total gastrectomy. Unfortunately, the middle daughter presented with generalized gastric adenocarcinoma and died at the age of 26 years. The other 2 daughters (aged 30 and 23 years) underwent total gastrectomy within 6 weeks of their sister's death; histology of surgical specimens showed gastric adenocarcinoma stage IA (pT1a, N0, M0) in both cases. Bi-directional Sanger sequencing of promoter 1B revealed a point mutation (c.-191 T>C) in all 3 daughters of the proband. CONCLUSIONS: Atypical endoscopic progression of the fundic gland polyposis, with the presence of dysplasia on polypectomy specimens and genetic testing with recently discovered mutations in promoter 1B of the APC gene might help clinicians to decide whether prophylactic gastrectomy should be performed.

Malignant transformation of a gastric hyperplastic polyp in a context of Helicobacter pylori-negative autoimmune gastritis: a case report.

BACKGROUND: Gastric foveolar hyperplastic polyps (GFHPs) are common findings in clinical practice. GFHPs commonly arise in a background of chronic atrophic gastritis, including autoimmune gastritis (type A gastritis), and have a potential risk of malignant transformation. CASE PRESENTATION: In 2005, a 55-year-old Japanese woman underwent upper endoscopy at another hospital and was found to have a pedunculated polyp (10 mm in diameter) on the greater curvature of the lower gastric body. On biopsy, the polyp was diagnosed as a GFHP. Nine years later, the polyp had grown to 20 mm in diameter, and the biopsy specimen taken at this time showed tubular adenocarcinoma. On admission to our hospital, the serum Helicobacter Pylori (H. pylori) immunoglobulin G antibody and stool H. pylori antigen were both negative. Anti-gastric parietal cell antibody was positive, as was the anti-intrinsic factor antibody, and the fasting serum gastrin level was markedly increased. In 2014, en bloc resection of the pedunculated polyp was performed by endoscopic submucosal dissection. The final histological diagnosis was adenocarcinoma of the stomach with submucosal and lymphatic invasion. Subsequently, additional radical distal gastrectomy was performed. At the latest follow-up (12 months postoperatively), no recurrence was noted. CONCLUSIONS: We here reported a rare case of malignant transformation of GFHP arising in a context of type A gastritis. To our knowledge, there are no previous reports on malignant transformation of GFHP with submucosal and lymphatic invasion arising in a background of type A gastritis in the English literature. Further, there is currently no effective treatment other than endoscopic or surgical treatment for such cases. Given the potential risk of malignant transformation due to hypergastrinemia, we consider that endoscopic treatment should be considered as a first-line therapy when a malignant growth is suspected.

Endoscopic evaluation of gastrointestinal tract in patients with hereditary hemorrhagic telangiectasia and correlation with their genotypes.

PURPOSE: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal-dominant vascular dysplasia characterized by telangiectases and arteriovenous malformations. Three causative genes are known: ENG (HHT-1), ACVRL1 (HHT-2), and SMAD4 (mutated in HHT in association with juvenile polyposis). Gastrointestinal bleeding is the most common symptom after epistaxis. The stomach and the duodenum are the main gastrointestinal sites of telangiectases. Our aim was to explore gastrointestinal tract of consecutive HHT patients to assess distribution, number, size, and type of telangiectases in relation to genotype. METHODS: HHT patients underwent gastroduodenoscopy, video capsule endoscopy, and colonoscopy. Molecular analysis of ENG and ACVRL1 was performed to identify the disease-causing mutation. RESULTS: Twenty-two patients (13 men; mean age: 59 ± 9 years) were analyzed: 7 with HHT-1, 13 with HHT-2, and 2 undefined. Gastrointestinal telangiectases were identified as follows: at gastroduodenoscopy in 86% of HHT-1 patients and in 77% of HHT-2 patients, at video capsule endoscopy in all HHT-1 patients and in 84% of HHT-2 patients, and at colonoscopy in 1 patient for each group. HHT-1 showed multiple telangiectases with a higher prevalence, more relevant in the duodenum. CONCLUSION: Our data demonstrate extensive involvement of the gastrointestinal tract with a more severe association in HHT-1. Gastroduodenoscopy provides significant information on gastrointestinal involvement, and video capsule endoscopy may be added in selected patients. Colonic polyps/adenomas were identified as occasional findings.

[Gastrointestinal lesions and characteristics of acute gastrointestinal bleeding in acenocoumarol-treated patients]. / Lesiones gastrointestinales y características de las hemorragias digestivas agudas en los pacientes anticoagulados con acenocumarol.

UNLABELLED: In the last few years, the number of anticoagulated patients has significantly increased and, as a consequence, so have hemorrhagic complications due to this therapy. We analyzed gastrointestinal (GI) bleeding because it is the most frequent type of major bleeding in these patients, and we hypothesized that they would have lesions responsible for GI bleeding regardless of the intensity of anticoagulation, although excessively anticoagulated patients would have more serious hemorrhages. OBJECTIVES: To study the characteristics of anticoagulated patients with GI bleeding and the relationship between the degree of anticoagulation and a finding of causative lesions and bleeding severity. PATIENTS AND METHODS: We prospectively studied 96 patients, all anticoagulated with acenocoumarol and consecutively admitted to hospital between 01/01/2003 and 09/30/2005 because of acute GI bleeding. We excluded patients with severe liver disease, as well as nine patients with incomplete details. RESULTS: The incidence of GI bleeding requiring hospitalization was 19.6 cases/100,000 inhabitants-year. In 90% of patients, we found a causative (85% of upper GI bleeding and 50% of lower GI bleeding) or potentially causative lesion, and 30% of them required endoscopic treatment, without differences depending on the intensity of anticoagulation. No relationship was found between the type of lesions observed and the degree of anticoagulation in these patients. Patients who received more intense anticoagulation therapy had more severe hemorrhages (23% of patients with an INR ≥4 had a life-threatening bleed versus only 4% of patients with INR <4). CONCLUSIONS: We found an incidence of 20 severe GI bleeding episodes in anticoagulated patients per 100,000 inhabitants-year, with no difference in localization or in the frequency of causative lesions depending on the intensity of anticoagulation. Patients receiving more intense anticoagulation had more severe GI bleeding episodes.

[Brunner's gland adenoma: a rare tumor as cause of pyloric syndrome in an AIDS patient]. / Adenoma de glándulas de Brunner: un tumor raro como causa de sindrome pilórico en un paciente con SIDA.

Brunner's gland adenoma is a rare neoplasm that accounts for only the 0.008% of all benign duodenal tumors. Here we describe the case ofan HIV-seropositive man who developed a severe pyloric stenosis due to a Brunner's adenoma of the bulb and the first duodenal portion. Gastroduodenoscopy showed a large polypoid tumor that obstructed the pyloric region. The lesion was resected by surgery and a gastroduodenal anastomosis was made. The histopathologic examination of the surgical specimen showed a large proliferation of Brunner's glands into a large pedunculated polyp that confirmed the diagnosis of this hamartoma.

[Gastric cancer arising from gastric polyps in gardner syndrome - a case report].

The patient was a 48-year-old woman who was diagnosed with early gastric cancer during a long-term follow-up period for Gardner syndrome. Subtotal colectomy for colon leiomyoma was performed when the patient was 22 years old. Partial resection of the ileum was performed for ileum leiomyoma at the age of 27. Total resection of the remaining colon with ileostomy was performed for a pelvic desmoid tumor at the age of 40. In addition, resection of a desmoid tumor of the abdominal wall was performed 8 times in the 25 years since the first operation. During the follow-up for gastric polyps associated with Gardner syndrome, gastric cancer was detected from biopsy specimens of a wide range of the fundus polyps. Endoscopic resection was considered not to be applicable because of the extensive nature of the lesion. Total gastrectomy was also considered not to be applicable because of concerns about short bowel syndrome due to intestinal reconstruction. Therefore, proximal gastrectomy with esophagogastric anastomosis was performed. The pathological diagnosis was 0-IIa, 70 × 44 mm, tub1, m, ly0, v0, n0, PM (-), DM (-), stageIA. The postoperative course was uneventful, and the patient was discharged on postoperative day (POD) 16. We speculate that long-term survival of patients with Gardner syndrome without severe short bowel syndrome might result in carcinogenesis of gastric polyps.

Colonic adenomatous polyp with florid presence of monoclonal lambda Russell bodies: Case report and etiopathogenic hypothesis.

Russell bodies (RBs) are round eosinophilic intracytoplasmic inclusions formed by condensed immunoglobulins in mature plasma cells, which are called Mott cells. These cells are rarely found in the gastric tract, with even less cases reported in the colorectal region. There are still many questions about this event, as it is still unknown the relationship between the agents reported of increasing the probability of appearance of these cells and the generation of RBs. In this case report we describe the fifth patient presenting an infiltration of Mott cells in a colorectal polyp, being the second case with a monoclonal origin without a neoplastic cause, and the first one monoclonal for lambda. A comparison with previously similar reported cases is also done, and a possible etiopathogenic hypothesis proposed.

Fibre-rich Foods to Treat Obesity and Prevent Colon Cancer trial study protocol: a randomised clinical trial of fibre-rich legumes targeting the gut microbiome, metabolome and gut transit time of overweight and obese patients with a history of noncancerous adenomatous polyps.

INTRODUCTION: Recently published studies support the beneficial effects of consuming fibre-rich legumes, such as cooked dry beans, to improve metabolic health and reduce cancer risk. In participants with overweight/obesity and a history of colorectal polyps, the Fibre-rich Foods to Treat Obesity and Prevent Colon Cancer randomised clinical trial will test whether a high-fibre diet featuring legumes will simultaneously facilitate weight reduction and suppress colonic mucosal biomarkers of colorectal cancer (CRC). METHODS/DESIGN: This study is designed to characterise changes in (1) body weight; (2) biomarkers of insulin resistance and systemic inflammation; (3) compositional and functional profiles of the faecal microbiome and metabolome; (4) mucosal biomarkers of CRC risk and (5) gut transit. Approximately 60 overweight or obese adults with a history of noncancerous adenomatous polyps within the previous 3 years will be recruited and randomised to one of two weight-loss diets. Following a 1-week run-in, participants in the intervention arm will receive preportioned high-fibre legume-rich entrées for two meals/day in months 1-3 and one meal/day in months 4-6. In the control arm, entrées will replace legumes with lean protein sources (eg, chicken). Both groups will receive in-person and written guidance to include nutritionally balanced sides with energy intake to lose 1-2 pounds per week. ETHICS AND DISSEMINATION: The National Institutes of Health fund this ongoing 5-year study through a National Cancer Institute grant (5R01CA245063) awarded to Emory University with a subaward to the University of Pittsburgh. The study protocol was approved by the Emory Institutional Review Board (IRB approval number: 00000563). TRIAL REGISTRATION NUMBER: NCT04780477.

Outcome of screening endoscopy in common variable immunodeficiency disorder and X-linked agammaglobulinemia.

Gastrointestinal symptoms are common in patients with common variable immunodeficiency disorders (CVID) and less frequent in X-linked agammaglobulinemia (XLA) although the exact prevalence is not well established. In this study, endoscopic screening was performed in 30 patients with CVID and four patients with XLA. Endoscopic and/or histological abnormalities were detected in 25 of 30 patients with CVID (83 %), regardless of symptoms, and in nine of these patients the results prompted medical treatment. Helicobacter pylori-associated gastritis, adenomatous polyps, and lymphoid hyperplasia were most frequently encountered; no malignancies were detected. Adenomatous polyps were found in two of the four patients with XLA at a relative young age. In conclusion, gastrointestinal pathology is frequent in patients with CVID regardless of symptoms. Patients with XLA seem to be at risk for colorectal adenomas at a young age.

Intestinal bleeding from arteriovenous malformations of the small bowel in a patient with Cowden syndrome: report of a case.

This report presents the case of a patient with Cowden syndrome who had arteriovenous malformations (AVMs) at the jejunum and the ileum and experienced intestinal bleeding. A 54-year-old Japanese male presented with general fatigue and melena. Endoscopic examinations showed gastrointestinal polyposis from the esophagus to the rectum. However, the site of bleeding was not identified. There were some papules on his face and neck. He also had macrocephaly and had multiple papillomas along the gum-line. These findings indicated a clinical diagnosis of Cowden syndrome. Enhanced computed tomography (CT) and angiography analyses indicated the presence of AVMs at the jejunum and the ileum. He was treated with partial resection of the jejunum and ileum including these two AVMs. This was a rare case of two AVMs involving the small bowel in a patient with Cowden syndrome. Enhanced CT was very useful and convenient for the detection of gastrointestinal AVMs in this case.

[Juvenile gastric polyposis in a patient with antiphospholipid syndrome].

We report a case of juvenile gastric polyposis associated with antiphospholipid syndrome. A 42-year-old woman was admitted with a chief complain of fatigue. Six years earlier, antiphospholipid syndrome was diagnosed and treated with aspirin. Two years earlier, gastric polyps were endoscopically observed, the number and size of which subsequently increased. Juvenile gastric polyposis was diagnosed on the basis of the pathological features of the biopsy specimens. Bleeding was repeatedly identified from the polyposis. Total gastrectomy was performed because of worsening anemia and hypoalbuminemia.