Bean's syndrome (blue rubber bleb nevus syndrome - BRBNS) as a gastrointestinal bleeding - case report and review of the literature.

BRBNS is a rare syndrome of vascular malformations caused by the TEK mutation associated with numerous lesions of the skin and gastrointestinal tract. We present a case report of 41 year old man with severe anemia with recurrent bleedings. The detailed clinical, endoscopical and histopathological description is given as a wide range of differential diagnosis of vascular lesions based on pathophysiology and updated classification of vascular lesions. Clinicopathological diagnosis and treatment options of BRBNS are discussed.

Increased Rate of Adenoma Detection Associates With Reduced Risk of Colorectal Cancer and Death.

BACKGROUND & AIMS: The quality of endoscopists' colonoscopy performance is measured by adenoma detection rate (ADR). Although ADR is associated inversely with interval colorectal cancer and colorectal cancer death, the effects of an increasing ADR have not been shown. We investigated whether increasing ADRs from individual endoscopists is associated with reduced risks of interval colorectal cancer and subsequent death. METHODS: We performed a prospective cohort study of individuals who underwent a screening colonoscopy within the National Colorectal Cancer Screening Program in Poland, from January 1, 2004, through December 31, 2008. We collected data from 146,860 colonoscopies performed by 294 endoscopists, with each endoscopist having participated at least twice in annual editions of primary colonoscopy screening. We used annual feedback and quality benchmark indicators to improve colonoscopy performance. We used ADR quintiles in the whole data set to categorize the annual ADRs for each endoscopist. An increased ADR was defined as an increase by at least 1 quintile category, or the maintenance of the highest category in subsequent screening years. Multivariate frailty models were used to evaluate the effects of increased ADR on the risk of interval colorectal cancer and death. RESULTS: Throughout the enrollment period, 219 endoscopists (74.5%) increased their annual ADR category. During 895,916 person-years of follow-up evaluation through the National Cancer Registry, we identified 168 interval colorectal cancers and 44 interval cancer deaths. An increased ADR was associated with an adjusted hazard ratio for interval colorectal cancer of 0.63 (95% confidence interval [CI], 0.45-0.88; P = .006), and for cancer death of 0.50 (95% CI, 0.27-0.95; P = .035). Compared with no increase in ADR, reaching or maintaining the highest quintile ADR category (such as an ADR > 24.56%) decreased the adjusted hazard ratios for interval colorectal cancer to 0.27 (95% CI, 0.12-0.63; P = .003), and 0.18 (95% CI, 0.06-0.56; P = .003), respectively. CONCLUSIONS: In a prospective study of individuals who underwent screening colonoscopy within a National Colorectal Cancer Screening Program, we associated increased ADR with a reduced risk of interval colorectal cancer and death.

Leadership training to improve adenoma detection rate in screening colonoscopy: a randomised trial.

OBJECTIVE: Suboptimal adenoma detection rate (ADR) at colonoscopy is associated with increased risk of interval colorectal cancer. It is uncertain how ADR might be improved. We compared the effect of leadership training versus feedback only on colonoscopy quality in a countrywide randomised trial. DESIGN: 40 colonoscopy screening centres with suboptimal performance in the Polish screening programme (centre leader ADR ≤ 25% during preintervention phase January to December 2011) were randomised to either a Train-Colonoscopy-Leaders (TCLs) programme (assessment, hands-on training, post-training feedback) or feedback only (individual quality measures). Colonoscopies performed June to December 2012 (early postintervention) and January to December 2013 (late postintervention) were used to calculate changes in quality measures. Primary outcome was change in leaders' ADR. Mixed effect models using ORs and 95% CIs were computed. RESULTS: The study included 24,582 colonoscopies performed by 38 leaders and 56,617 colonoscopies performed by 138 endoscopists at the participating centres. The absolute difference between the TCL and feedback groups in mean ADR improvement of leaders was 7.1% and 4.2% in early and late postintervention phases, respectively. The TCL group had larger improvement in ADR in early (OR 1.61; 95% CI 1.29 to 2.01; p<0.001) and late (OR 1.35; 95% CI 1.10 to 1.66; p=0.004) postintervention phases. In the late postintervention phase, the absolute difference between the TCL and feedback groups in mean ADR improvement of entire centres was 3.9% (OR 1.25; 95% CI 1.04 to 1.50; p=0.017). CONCLUSIONS: Teaching centre leaders in colonoscopy training improved important quality measures in screening colonoscopy. TRIAL REGISTRATION NUMBER: NCT01667198.

Suspicious macroscopic features of small malignant colorectal polyps.

OBJECTIVE: The aim of this analysis was to retrospectively review video recordings of malignant polyps <10 mm in search for suspicious macroscopic features in white light endoscopy. METHODS: Database entries and recordings of screening colonoscopies from a single tertiary referral center between June 2009 and December 2012 were reviewed. Malignant polyps <10 mm were analyzed. The recordings were reviewed by two expert endoscopists in search for suspicious morphological features: irregular contours, central depression, contact bleeding, shape deformity, central depression, chicken skin sign, circumscribed area with abnormal vascular and/or surface pattern. Then, six experienced endoscopists watched the recordings in search of listed features. Next, video recordings of these malignant polyps were mixed with randomly drawn video recordings of 20 non-malignant polyps matched by size and reviewed by 14 blinded endoscopists to assess the sensitivity and specificity for the diagnosis of malignant polyps. RESULTS: Five of the 8651 (0.06%) subjects who underwent screening colonoscopy during the study period were diagnosed with a malignant polyp <10 mm. Only one of them was ad hoc identified by performing endoscopist as suspicious. On recordings review performed by the experts, each of the four remaining polyps presented at least one suspicious macroscopic feature. Presence of these features was confirmed by experienced endoscopists. The sensitivity and specificity for the diagnosis of malignant polyp were 73.21% and 85.35%, respectively, if at least two suspicious macroscopic features defined malignant polyp. CONCLUSIONS: On careful white light endoscopy examination small malignant colorectal polyps show suspicious macroscopic features, which were frequently unrecognized by examining endoscopists.

Colonoscopy in colorectal-cancer screening for detection of advanced neoplasia.

BACKGROUND: Recommendations for colorectal-cancer screening are based solely on age and family history of cancer, not sex. METHODS: We performed a cross-sectional analysis of the data from a large colonoscopy-based screening program that included 50,148 participants who were 40 to 66 years of age. People 40 to 49 years of age were eligible only if they had a family history of cancer of any type. Of the 43,042 participants 50 to 66 years of age, 13.3% reported a family history of colorectal cancer, as did 66.3% of the 7106 participants who were 40 to 49 years of age. We defined advanced neoplasia as cancer or adenoma that was at least 10 mm in diameter, had high-grade dysplasia, or had villous or tubulovillous histologic characteristics, or any combination thereof. We used multivariate logistic regression to identify associations between participants' characteristics and advanced neoplasia in a primary (or derivation) data set, and we confirmed the associations in a secondary (or validation) data set. RESULTS: Advanced neoplasia was detected in 2553 (5.9%) participants 50 to 66 years of age and in 243 (3.4%) participants 40 to 49 years of age. The rate of complications during colonoscopy was 0.1%, and no participants died. In the validation set, a logistic-regression model showed that male sex was independently associated with advanced neoplasia (adjusted odds ratio, 1.73; 95% confidence interval, 1.52 to 1.98; P<0.001). In each age group (40 to 49 years, 50 to 54 years, 55 to 59 years, and 60 to 66 years), the number of persons who would have to undergo colorectal-cancer screening in order to detect one advanced neoplasia was significantly lower in men than in women (23 vs. 36, 17 vs. 28, 12 vs. 22, and 10 vs. 18, respectively). CONCLUSIONS: We detected advanced neoplasia at a significantly higher rate in men than in women, which may warrant refinement of the screening recommendations for colorectal cancer.

Mutation Profiling of Premalignant Colorectal Neoplasia.

Accumulation of allelic variants in genes that regulate cellular proliferation, differentiation, and apoptosis may result in expansion of the aberrant intestinal epithelium, generating adenomas. Herein, we compared the mutation profiles of conventional colorectal adenomas (CNADs) across stages of progression towards early carcinoma. DNA was isolated from 17 invasive adenocarcinomas (ACs) and 58 large CNADs, including 19 with low-grade dysplasia (LGD), 21 with LGD adjacent to areas of high-grade dysplasia and/or carcinoma (LGD-H), and 28 with high-grade dysplasia (HGD). Ion AmpliSeq Comprehensive Cancer Panel libraries were prepared and sequenced on the Ion Proton. We identified 956 unique allelic variants; of these, 499 were considered nonsynonymous variants. Eleven genes (APC, KRAS, SYNE1, NOTCH4, BLNK, FBXW7, GNAS, KMT2D, TAF1L, TCF7L2, and TP53) were mutated in at least 15% of all samples. Out of frequently mutated genes, TP53 and BCL2 had a consistent trend in mutation prevalence towards malignancy, while two other genes (HNF1A and FBXW7) exhibited the opposite trend. HGD adenomas had significantly higher mutation rates than LGD adenomas, while LGD-H adenomas exhibited mutation frequencies similar to those of LGD adenomas. A significant increase in copy number variant frequency was observed from LGD through HGD to malignant samples. The profiling of advanced CNADs demonstrated variations in mutation patterns among colorectal premalignancies. Only limited numbers of genes were repeatedly mutated while the majority were altered in single cases. Most genetic alterations in adenomas can be considered early contributors to colorectal carcinogenesis.

Vascular lesions of the gastrointestinal tract.

Classification of vascular abnormalities of the gastrointestinal tract on the basis of anatomy and pathophysiology has recently been suggested. Angiodysplasia, an example of an arteriovenous lesion, may cause either acute or chronic bleeding. Diagnosis may be difficult. High-quality standard endoscopy, capsule endoscopy, and double-balloon enteroscopy are most efficacious. Therapy using argon plasma coagulation is currently preferred. Pharmacological therapy has been employed, but a final conclusion about its efficacy cannot yet be drawn. Dieulafoy lesion, an arterial type of vascular abnormality, is rare but serious. It can be responsible for severe haemorrhage. Mechanical endoscopic methods are the most efficacious. Gastric antral vascular ectasia (GAVE), a capillary lesion, can be safely biopsied; it coincides with several diseases (including liver cirrhosis), may cause chronic iron-deficiency anaemia, and is best treated by argon plasma coagulation. Haemangiomas, benign neoplastic lesions, usually occur as part of other specific syndromes; they are difficult to manage due to the multiplicity and size of the lesions.

Outcomes of colonoscopic polypectomy for malignant adenomas: a prospective 30­year cohort study from a single center (STROBE 1a).

INTRODUCTION: Surgery is recommended following endoscopic polypectomy for malignant adenoma (MA) in the large bowel in patients with risk factors for tumor recurrence or distant metastasis are present. OBJECTIVES: We present long­term outcomes of a prospective study in patients with endoscopically removed MAs. PATIENTS AND METHODS: A total of 128 patients who underwent endoscopic polypectomy were followed up for a median of 70.4 months. The criteria for adequate polypectomy included endoscopically and histologically (margin ≥2 mm) complete excision, lack of angioinvasion, and good tumor differentiation (G1 or G2). Sixty­seven patients did not meet 1 or more of the criteria (high­risk group) and 61 met all of the criteria (low­risk group). Unfavorable outcomes were residual disease, lymph node metastasis, recurrent disease, distant metastasis, or death due to colorectal cancer. Histological samples from 85 patients were reassessed to determine the effect of a margin width of 1 mm or more and tumor budding on the outcomes. RESULTS: Surgery was performed in 36 patients (28.1%), of whom 32 (47.7%) were high­risk and 4 (6.5%) were low­risk. Unfavorable outcome was observed in 10 patients (7.8%; all high­risk; 10 of 67 patients, 14.9%). Favorable outcome was observed in 61 of 128 patients who had a 2­mm free margin, and in 44 of 85 patients who fulfilled the modified criterion of 1­mm free margin. Tumor budding was detected in 17 of 85 patients (20.9%). Unfavorable outcome was observed in 2 of these patients (11.7%) and in 5 patients (7.3%) without tumor budding (P >0.05). DISCUSSION: Long­term outcomes of an endoscopic resection of MAs are good. Bowel resection does not prevent unfavorable outcomes, while a reduction of the tumor­free margin would not deteriorate the results (STROBE 1B).

Small bowel tumors detected and missed during capsule endoscopy: single center experience.

AIM: To characterize small bowel (SB) tumors detected by capsule endoscopy (CE), and identify missed tumors. METHODS: The study included 145 consecutive patients in whom 150 CEs were performed. Following CE, the medical records of the study population were reviewed. Results of double- or single-balloon enteroscopy performed after CE and the results of surgery in all patients operated on were retrieved. The patients were contacted through telephone interviews or postal mail. In addition, the national cancer registry and the polish clinical gastrointestinal stromal tumor (GIST) Registry were searched to identify missed neoplasms. RESULTS: Indications for CE included overt and occult obscure gastrointestinal bleeding (n = 81, 53.7%), anemia (n = 19, 12.7%), malabsorption (n = 18, 12%), abnormal CB follow through (n = 9, 6%), abdominal pain (n = 7, 5%), celiac disease (n = 5, 3%), neuroendocrine tumor (n = 3, 2%), Crohn's disease (n = 2, < 2%), Peutz-Jeghers syndrome (n = 2, < 2%), other polyposes (n = 2, < 2%), and diarrhea (n = 2, < 2%). The capsule reached the colon in 115 (76.6%) examinations. In 150 investigations, CE identified 15 SB tumors (10%), 14 of which were operated on or treated endoscopically. Malignancies included metastatic melanoma (n = 1), adenocarcinoma (n = 2), and GIST (n = 3). Benign neoplasms included dysplastic Peutz-Jeghers polyps (n = 4). Non-neoplastic masses included venous malformation (n = 1), inflammatory tumors (n = 2), and a mass of unknown histology (n = 1). During the follow-up period, three additional SB tumors were found (2 GISTs and one mesenteric tumor of undefined nature). The National Cancer Registry and Polish Clinical GIST Registry revealed no additional SB neoplasms in the post-examination period (follow-up: range 4.2-102.5 mo, median 39 mo). The sensitivity of CE for tumor detection was 83.3%, and the negative predictive value was 97.6%. The specificity and positive predictive value were both 100%. CONCLUSION: Neoplasms may be missed by CE, especially in the proximal SB. In overt obscure gastrointestinal bleeding, complementary endoscopic and/or radiologic diagnostic tests are indicated.

Modeling oncogenic signaling in colon tumors by multidirectional analyses of microarray data directed for maximization of analytical reliability.

BACKGROUND: Clinical progression of colorectal cancers (CRC) may occur in parallel with distinctive signaling alterations. We designed multidirectional analyses integrating microarray-based data with biostatistics and bioinformatics to elucidate the signaling and metabolic alterations underlying CRC development in the adenoma-carcinoma sequence. METHODOLOGY/PRINCIPAL FINDINGS: Studies were performed on normal mucosa, adenoma, and carcinoma samples obtained during surgery or colonoscopy. Collections of cryostat sections prepared from the tissue samples were evaluated by a pathologist to control the relative cell type content. The measurements were done using Affymetrix GeneChip HG-U133plus2, and probe set data was generated using two normalization algorithms: MAS5.0 and GCRMA with least-variant set (LVS). The data was evaluated using pair-wise comparisons and data decomposition into singular value decomposition (SVD) modes. The method selected for the functional analysis used the Kolmogorov-Smirnov test. Expressional profiles obtained in 105 samples of whole tissue sections were used to establish oncogenic signaling alterations in progression of CRC, while those representing 40 microdissected specimens were used to select differences in KEGG pathways between epithelium and mucosa. Based on a consensus of the results obtained by two normalization algorithms, and two probe set sorting criteria, we identified 14 and 17 KEGG signaling and metabolic pathways that are significantly altered between normal and tumor samples and between benign and malignant tumors, respectively. Several of them were also selected from the raw microarray data of 2 recently published studies (GSE4183 and GSE8671). CONCLUSION/SIGNIFICANCE: Although the proposed strategy is computationally complex and labor-intensive, it may reduce the number of false results.