A study on the genomic alterations of transformation from colorectal adenoma to colorectal cancer.

e15607 Background: Colorectal cancer is one of the most common malignancies worldwide. Approximately 85% of colorectal cancers are thought to result from adenoma. However, the molecular mechanism of adenoma transformation into colorectal cancer is still unclear. Methods: Ninety-nine adenoma patients aged from 25 to 78 years old were enrolled in this study. We collected tissue sample from each patient and 77 matched blood samples. Pathological subtypes included tubular villous adenomas, villous adenomas, tubular adenomas, high-grade intraepithelial neoplasia, and polyps. Eighty-one stage I colorectal cancer patients (CRC I) were also enrolled in this study. All samples underwent Next-generation sequencing with a panel of 405 cancer related genes. Results: Mutational profiles of adenoma and CRC I patients were compared. The top 5 most frequently mutated genes in adenoma were APC (71%), KRAS (41%), ATM (33%), RIF1 (31%), SYNE1 (28%). While in CRC I patients, top 5 mutated genes were APC (78%), TP53 (57%), TTN (35%), KRAS (33%) and TCF7L2 (22%). There were significant differences between TP53 and TTN by chi-square test. The frequency, number and TMB of mutations in stage I colorectal cancer patients were significantly higher than those in various adenoma subtypes. Stage I colorectal cancer patients have more mutated genes enriched in the Wnt and Notch pathways than adenoma patients. We analyzed mutation signatures in CRC I and adenoma patients, and CRC I were more focused on mutation signatures of mismatch repair such as signature 1, signature 6, signature 10, and signature 15. A total of 391 mutations were identified in tissue samples, while 130 mutations were found in plasma cell-free DNA, with 116 mutations shared between them. The two genes with the highest consistency between tissue and blood were PAX7 and KMT2D. Conclusions: TP53 and TTN are associated with the transition from CRC I to adenoma, and Wnt and Notch pathways may also be involved. PAX7 and KMT2D mutations frequently found in adenoma tissue and blood cfDNA demonstrate the diagnostic potential of these two genes in clinic.

Resección de adenoma velloso gigante causante del síndrome de Mckittrick-Wheelock

Large colorectal villous adenomas are unusual. They can cause a rectal bleeding, a chronic diarrhea and less frequently a rectal obstruction and a prolapse. In addition, they can secrete a mucinous material rich in electrolytes, causing hydroelectrolyte disturbances, dehydration and acute kidney injury. In most cases, the management of these adenomas due to their size has been surgical, but endoscopic treatment has been reported with promising results, reducing the morbidity. We report and discuss the case of a 73-year-old man, who presented with syncope, with chronic diarrhea and a hydroelectrolytic alteration. Colonoscopy revealed a granular lateral spreading tumor of the rectum, and pathology confirmed a villous adenoma with a low-grade dysplasia. An initial symptomatic management of diarrhea and electrolyte disorders was performed with a subsequent surgical treatment using pull through technique with coloanal anastomosis.

Impact of antithrombotics on the fecal immunochemical test for colorectal cancer screening : a multi-center Belgian experience

Background : Impact of antithrombotics on the fecal immunochemical test (FIT) for colorectal cancer (CRC) screening remains unclear. Methods : Patients undergoing colonoscopy for positive FIT in 2015 were assessed at 3 Belgian centers. Significant findings were advanced polyps (AP) (sessile serrated, tubular or villous adenomas >1cm or high-grade dysplasia) and CRC. False positive FIT and detection of AP/CRC with antithrombotics were calculated. Results : 510 patients (64% male, median (IQR) age 63.2 (60.2-66.4) years) were included. Colorectal pathology in 371/510 (73%) was associated with male gender (70% vs. 48% ; p= .0001) and family history (16% vs. 8% ; p= .02). Antithrombotics in 125/510 (25%) were associated with male gender (78% vs. 59% ; p= .0001), older age (65.2 (62.2-70.3) vs. 62.3 (58.7-66.3) years ; p= .0001) and GI-symptoms (18% vs. 11% ; p= .04). False positive FIT (25% vs. 28% ; p= .52) and detection of AP (42% vs. 36% ; p= .27) or CRC (6% vs. 5% ; p= .69) were similar in patients with vs. no antithrombotics. Use of antithrombotics did not predict a higher chance of colorectal pathology after adjusting for confounders. Conclusion : Although antithrombotics were prescribed more frequently in male and older patients, detection of AP/CRC was similar. Despite increased GI symptoms, false positive FIT was similar with antithrombotics.

Tubulovillous Adenoma of Duodenum: A Case Report

Tumors arising from the upper GIT are usually of epithelial origin and are mostly benign. Even when they do occur, they are usually considered as premalignant lesions with a risk of transformation to malignant ones.Tubulo-villous adenomas represent lesions that are histologically intermediate between tubular and villous polyps. These account for the majority of colonic polyps.We present a case of benign adenomas arising from the duodenum, an extremely rare diagnosis with an average annual incidence rate of 9.9 per million people.Among these uncommon tumors,Duodenal tumors are even rarer with average incidence rate of 0.4% only. Histopathological examination mostly shows villous type.Tubulovillous histology is extremely rare with an incidence of less than 1% of all duodenal tumors. However, these tumors are being diagnosed with increasing frequency due to more widespread use of endoscopy. J Shaheed Suhrawardy Med Coll, December 2020, Vol.12(1); 58-60

Giant villous adenoma of the sigmoid colon: an unusual cause of homogeneous, segmental bowel wall thickening

Colonic adenomas are commonly encountered lesions that are a precursor of colorectal cancer. Of these, villous adenomas are a rarer, more advanced subtype that are larger in size than tubular adenomas and have a higher risk of malignant transformation. We present a patient with a giant villous adenoma of the sigmoid colon identified on CT as homogeneous segmental bowel wall thickening.

Findings on Colonoscopy after Diverticulitis: A Multicenter Review

Diverticular disease is a common problem where patients with diverticulosis have a 1–4 per cent risk of acute diverticulitis. Current guidelines recommend a colonoscopy after.the resolution of acute diverticulitis. The aim of this study was to evaluate the yield of significant findings on colonoscopy after an episode of diverticulitis. This is a retrospective analysis of patients who underwent colonoscopy after an episode of diverticulitis between November 2005 and August 2017 at three major teaching hospitals. Advanced adenomas were defined as adenomas ≥1 cm, serrated adenomas, and tubulovillous or villous adenomas. A total of 584 patients (298 males; 51%) underwent colonoscopy for a history of diverticulitis after resolution of acute symptoms. Colonoscopy was complete in 488 patients (84%). Among these 488 patients, 446 had diverticular disease, 31 had advanced adenomas, and four had adenocarcinomas. Colonoscopies were incomplete in 96 patients (16%). Forty-six of those patients underwent surgery. The overall incidence of advanced adenomas and adenocarcinomas was 32 (5.4%) and nine (1.5%), respectively. In our study, the prevalence of advanced adenomas and adenocarcinomas was relatively high compared with the average risk individuals. Our findings support that patients after an episode of diverticulitis should continue to get a colonoscopy.

Prolapso rectal incarcerado secundario a adenoma velloso gigante

Villous adenomas may present with bleeding, diarrhea, electrolyte imbalance (Mackittrick-Weelock syndrome), obstruction, being a very rare cause of rectal prolapse. Rectal prolapse is a full thickness protrusion of the rectum through the anal canal and its presentation as an incarcerated rectal prolapse is very infrequent. If manual reduction is deemed impossible, perineal recto-sigmoidectomy, or Altemeier’s procedure, is one of the best surgical options, as an alternative transanal excision of the polyp could be performed with subsequent manual reduction of the rectal prolapse. We report the case of a female patient, admitted to the emergency room presenting an incarcerated rectal prolapse with a friable ulcerated mass of 10 × 8 × 5 cm, compatible with a villous polyp in the back side of the rectum. Since manual reduction was considered not feasible, surgery was decided and a transanal excision of the polyp was performed, following a successful manual reduction of the rectal prolapse. This case is of particular interest for its unusual association of incarcerated rectal prolapse due to a giant villous adenoma, having only 4 cases been reported in the literature.

Villous Adenoma Arising in the Native Bladder Mucosa and the Upper Urinary Tract With Coexisting Neuroendocrine Carcinoma Following Augmentation Cystoplasty

Villous adenomas arising in the bladder following augmentation cystoplasty procedures are exceedingly rare. Even rarer is their occurrence in the native bladder mucosa and the upper urinary tract. In this article, we present a unique case of multifocal recurrent villous adenoma involving native bladder mucosa of an augmented bladder, bilateral ureters, and renal pelvis, with coexistent foci of adenocarcinoma and neuroendocrine carcinoma, in a patient with history of augmentation colocystoplasty. We additionally discuss the pathogenesis of development of carcinoma in the setting of augmentation cystoplasty.

Immunohistochemical expression of heparanase isoforms and syndecan-1 proteins in colorectal adenomas

<p>The proteoglycan syndecan-1 and the endoglucuronidases heparanase-1 and heparanase-2 are involved in molecular pathways that deregulate cell adhesion during carcinogenesis. Few studies have examined the expression of syndecan-1, heparanase-1 and mainly heparanase-2 proteins in non-neoplastic and neoplastic human colorectal adenoma tissues. The aim of this study was to analyze the correlation among the heparanase isoforms and the syndecan-1 proteins through immunohistochemical expression in the tissue of colorectal adenomas. Primary anti-human polyclonal anti-HPSE and anti-HPSE2 antibodies and primary anti-human monoclonal anti-SDC1 antibody were used in the immunohistochemical study. The expressions of heparanase-1 and heparanase-2 proteins were determined in tissue samples from 65 colorectal adenomas; the expression of syndecan-1 protein was obtained from 39 (60%) patients. The histological type of adenoma was tubular in 44 (67.7%) patients and tubular-villous in 21 (32.3%); there were no villous adenomas. The polyps were &lt;1.0 cm in size in 54 (83.1%) patients and ≥1.0 cm in 11 (16.9%). The images were quantified by digital counter with a computer program for this purpose. The expression index represented the relationship between the intensity expression and the percentage of positively stained cells. The results showed that the average of heparanase-1, heparanase-2 and syndecan-1 expression index was 73.29 o.u./µm², 93.34 o.u./µm², and 55.29 o.u./µm², respectively. The correlation between the heparanase-1 and syndecan-1 expression index was positive (R=0.034) and significant (P=0.035). There was a negative (R= -0.384) and significant (P=0.016) correlation between the expression index of heparanase-1 and heparanase-2. A negative (R= -0.421) and significant (P=0.008) correlation between the expression index of heparanase-2 and syndecan-1 was found. We concluded that in colorectal adenomas, the heparanase-1 does not participate in syndecan-1 degradation; the heparanase-2 does not stimulate syndecan-1 degradation by the action of heparanase-1, and the heparanase-2 may be involved in the modulation of the heparanase-1 activity.</p>

Absence of GNAS Mutation in Colorectal Carcinogenesis

Aims and background The incidence rate of colorectal cancer (CRC) increases every year in Korean populations. However, association between the GNAS mutation and colorectal precancerous lesions has not been studied in in Korean populations. To contribute to better understanding of colorectal carcinogenesis, we analyzed GNAS mutation in 100 cancerous and 96 precancerous colorectal lesions. Methods The records of colonoscopic polypectomy performed at Dongsan Medical Center between 1999 and 2003 were reviewed retrospectively. Precancerous lesions included 7 villous adenomas, 59 tubular adenomas, and 18 sessile serrated adenomas, and 12 hyperplastic polyps. Keimyung Human Bio-Resource Bank at Dongsan Medical Center provided 100 CRC samples. Results GNAS mutation was not found in any colorectal cancer or any precancerous colorectal lesions, including villous adenoma, which is thought to harbor the mutation. Conclusions The role of GNAS mutation might be limited in colorectal neoplasms of the Korean population.