Andrzej Mroz

Detection rate of serrated polyps and serrated polyposis syndrome in colorectal cancer screening cohorts: a European overview

Objective The role of serrated polyps (SPs) as colorectal cancer precursor is increasingly recognised. However, the true prevalence SPs is largely unknown. We aimed to evaluate the detection rate of SPs subtypes as well as serrated polyposis syndrome (SPS) among European screening cohorts. Methods Prospectively collected screening cohorts of ≥1000 individuals were eligible for inclusion. Colonoscopies performed before 2009 and/or in individuals aged below 50 were excluded. Rate of SPs was assessed, categorised for histology, location and size. Age–sex–standardised number needed to screen (NNS) to detect SPs were calculated. Rate of SPS was assessed in cohorts with known colonoscopy follow-up data. Clinically relevant SPs (regarded as a separate entity) were defined as SPs ≥10 mm and/or SPs >5 mm in the proximal colon. Results Three faecal occult blood test (FOBT) screening cohorts and two primary colonoscopy screening cohorts (range 1.426–205.949 individuals) were included. Rate of SPs ranged between 15.1% and 27.2% (median 19.5%), of sessile serrated polyps between 2.2% and 4.8% (median 3.3%) and of clinically relevant SPs between 2.1% and 7.8% (median 4.6%). Rate of SPs was similar in FOBT-based cohorts as in colonoscopy screening cohorts. No apparent association between the rate of SP and gender or age was shown. Rate of SPS ranged from 0% to 0.5%, which increased to 0.4% to 0.8% after follow-up colonoscopy. Conclusions The detection rate of SPs is variable among screening cohorts, and standards for reporting, detection and histopathological assessment should be established. The median rate, as found in this study, may contribute to define uniform minimum standards for males and females between 50 and 75 years of age.

Cytomegalovirus infection in ulcerative colitis is related to severe inflammation and a high count of cytomegalovirus-positive cells in biopsy is a risk factor for colectomy

BACKGROUND AND AIMS Cytomegalovirus [CMV] infection often reactivates in the course of inflammatory bowel disease, but the significance of this remains disputable. Our aim was to evaluate whether severity of CMV colitis is associated with colectomy risk in ulcerative colitis [UC] patients. The secondary aim was to evaluate agreement between immunohistochemistry [IHC] and blood CMV polymerase chain reaction [PCR]. METHODS UC patients with CMV assessment of the colon, hospitalised in a referral unit between 2005 and 2012 were retrospectively identified. The course and severity of the disease were analysed, with inflammation graded histologically across the range 0-3. The numbers of CMV IHC-positive cells per biopsy section were counted, and results for blood CMV PCR were also retrieved. Data on colectomies were also collected. RESULTS Of 141 patients, 95 were analysed, with 33 found to be CMV IHC-positive and 62 negative. The colectomy risk was significantly higher in patients with ≥ 5 IHC-positive cells, as opposed to those with none or less than 5 [p = 0.014] with median follow-up of 1.9 and 3.2 years, respectively. The CMV IHC-positive patients had lower haemoglobin [median 11.0g/dl vs 12.0; p = 0.028] and albumin [median 29.5g/l vs 33.1; p = 0.038] levels and more intense histological inflammation [p = 0.020] compared with CMV IHC-negative patients. There was substantial agreement between IHC and blood PCR [Cohens kappa coefficient 0.72]. CONCLUSIONS Five or more CMV IHC-positive cells per biopsy section were indicative of a greater colectomy risk. CMV infection was related to more severe inflammation. Blood CMV PCR is a useful tool in UC.

Predictive factors of proximal advanced neoplasia in the large bowel.

Introduction The aim of the study was to evaluate the impact of sex, age, family history and distal findings on the risk of proximal advanced neoplasia (cancer or advanced adenoma) in the large bowel. Material and methods Records for 10 111 asymptomatic participants of the Colonoscopy Screening Program (CSP), recruited from the Warsaw region between 2000 and 2004, were analyzed. A multivariate logistic regression model was used to estimate the impact of sex, age, family history and most advanced distal lesions on the occurrence of proximal advanced neoplasia. To enhance comparability of the study two definitions of the proximal colon were applied – either the splenic flexure (1st) or the bend between the descending and sigmoid colon (2nd definition) represented the boundary. Results One hundred and thirty-three (1st) and 167 patients (2nd definition) were found to have at least one advanced neoplastic lesion in the proximal part, respectively. Eleven and 14 patients were found to have carcinoma, while in 130 and 163 patients at least one proximal advanced adenoma appeared. Men were at twice as high risk of having advanced neoplasia in the proximal colon than women (OR = 1.94, 95% CI: 1.31–2.87, p = 0.001 or OR = 1.69, 95% CI: 1.20–2.40, p = 0.003, respectively). The presence of distal advanced neoplastic lesions was associated with 3.5 times higher risk of proximal advanced neoplasia (OR = 3.58, 95% CI: 2.00–6.43, p < 0.0001 or OR = 3.41, 95% CI: 1.95–5.96, p < 0.0001), respectively. Conclusions The results may confirm some limitation of flexible sigmoidoscopy in the screening settings in comparison with colonoscopy, at least in men and people with distal advanced neoplasia.

α-Methylacyl-CoA racemase (AMACR) in gastric cancer: correlation with clinicopathologic data and disease-free survival.

Diagnostic and prognostic significance of &agr;-methylacyl-CoA racemase (AMACR) has been established in many human cancers. Its correlation with clinical and pathologic data in gastric cancer has not been fully elucidated and its impact on surveillance has not been studied thus far. We analyzed consecutive gastric cancer cases in terms of AMACR expression and clinical/pathologic characteristics and followed patients’ postoperative history. AMACR was expressed in 94/164 gastric cancers (57.3%). We did not find correlation between AMACR expression and sex, age, location, histologic type, pTN staging, vascular and nerve sheaths invasion. Overall disease-free survival tended to be worse in AMACR-positive patients (P=0.062), and in adenocarcinoma subgroup, it was significantly shorter (P=0.021). AMACR expression might represent promising adverse prognostic factor in gastric cancer, particularly in adenocarcinoma histologic type.

The effects of selected drugs and dietary compounds on proliferation and apoptosis in colorectal carcinoma

Like many malignancies, the development of colorectal carcinoma (CRC) can be considered as an imbalance between the compromised process of programmed cell death (apoptosis) and excessive, uncontrolled proliferation. Several mutations and epigenetic alterations are acquired during colorectal carcinogenesis. These are responsible for the cell cycle regulation, cellular sensitivity to pro- and antiapoptotic factors, cell proliferation, angiogenesis, invasiveness, as well as metastatic potential. The molecular alterations, along with their morphological expressions, have been recognised in detail, and most of the CRC cases can be attributed to either adenoma-carcinoma or serrated neoplasia pathways: in the first, the antiapoptotic features prevail; while in the second, the proliferative activity is of the utmost importance. The aim of the work is to discuss the influence of selected drugs and dietary compounds on the proliferation and apoptosis in CRC.

Suspicious macroscopic features of small malignant colorectal polyps

Abstract 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.

Cyclooxygenase-2 immunohistochemical expression in serrated polyps of the colon

Aim of the study Cyclooxygenase-2 (COX-2) expression has been observed in a substantial percentage of classical adenomas of the large bowel. The aim of the study was to assess and compare the expression of COX-2 in serrated polyps of the colon. Material and methods One hundred and nineteen serrated polyps were analyzed. There were 83 hyperplastic polyps (HP), 19 sessile serrated polyps (SSP) and 17 traditional serrated adenomas (TSA). COX-2 expression was assessed semi-quantitatively (0–2) and each lesion was fully characterized in terms of anatomical location, size, histology, age and sex of the patient. The general estimating equation (GEE) model with logit link was used in the statistical analysis. Results Epithelial expression of COX-2 was found in 85/119 serrated polyps (71.43%): 57/83 (68.67%) HP, 16/19 (84.21%) SSP, and 12/17 (70.59%) TSA. In HP and SSP it was predominantly of weak (49/83 HP, 12/19 SSP), whereas in TSA it was mainly of medium/strong intensity (8/17). The TSA category was associated with more frequent COX-2 expression (OR = 7.00, 95% CI: 1.49–32.88, p = 0.014) than HP, but such relation was not found for SSP vs. HP (p > 0.1). No associations between COX-2 expression and clinical parameters were found. Conclusions Immunohistochemical COX-2 expression cannot serve as a diagnostic adjunct to differentiate HP and SSP.

Chronic low-dose aspirin use does not alter colonic mucosa in asymptomatic individuals: a prospective cross-sectional study (STROBE 1a).

Objectives Aspirin may be involved in microscopic colitis (MC) development, but there are no data on colon histology in asymptomatic aspirin users. We prospectively assessed colonic and rectal mucosa from aspirin users, searching for MC features. Methods From colonoscopy screenees, two biopsy samples were taken from each of three locations: ascending colon, transverse colon and rectum. A pathologist measured chronicity of inflammation and activity indicators, epithelial cell height and subepithelial collagen layer width. Intraepithelial lymphocytes (IELs), intralaminal eosinophils and apoptotic cells/100 crypts were counted. Panel data models were used to analyse associations between aspirin use, biopsy location and microscopic parameters. Results Of 100 screenees (age: 40–65 years), 42 were current aspirin users. Median duration of aspirin usage was 48 months (range: 36–60) with dosage ranging from 75–325 mg/day. We observed reduced epithelium polymorphs in subjects who used aspirin for <48 months versus non-users (p=0.008). Paneth cell metaplasia was significantly less frequent in aspirin users versus non-users (p=0.006). Inflammatory cells in lamina propria (eosinophils) and epithelium (IELs) were most abundant in the ascending colon and decreased distally (ascending colon vs transverse colon and transverse colon vs rectum). Cryptitis was more frequent in the ascending colon vs the rectum. Conclusions We observed no specific MC features in asymptomatic chronic low-dose aspirin users. We found subtle physiological and histopathological differences between the bowel segments.

Detection of cytomegalovirus by immunohistochemistry of colonic biopsies and quantitative blood polymerase chain reaction: evaluation of agreement in ulcerative colitis

Abstract Objectives: Cytomegalovirus (CMV) often reactivates in ulcerative colitis (UC). In diagnostics, along with immunohistochemistry (IHC) of colonic biopsies, blood CMV polymerase chain reaction (PCR) is gaining increasing application. We aimed to assess agreement between the density of infected colonic cells by IHC and the viral load in the blood by PCR. Material and methods: We retrospectively identified patients with active UC or indeterminate colitis in whom blood CMV PCR had been performed while biopsies had been taken simultaneously. The latter were re-evaluated and the numbers of IHC–positive cells per square millimetre counted. Results: The analyses extended to 234 sample pairs, among which there were 184 cases (78.6% of the total) in which IHC was equal to 0. The median among the remaining 50 non-zero values for IHC was 1.7 cells/mm2. PCR was equal to 0 in 192 cases (82.1%), while the median among the remaining 42 non-zero values was 4995.3 IU/ml. The Spearman correlation coefficient was 0.43 (p < .001). The area under the curve (AUC) values did not differ significantly between different IHC cut-offs. The highest AUC of 0.753 was obtained while predicting if IHC would be above the 3rd quartile (>5.6 cells/mm2), where PCR > 0 had a sensitivity of 0.615 and a specificity of 0.846. Conclusions: In active CMV colitis, the specificity and negative predictive value of blood PCR are high, while the sensitivity grows with the intensity of colon infection. A highly positive result could justify the administration of antiviral treatment being brought forward in selected patients.

Exome scale map of genetic alterations promoting metastasis in colorectal cancer

BackgroundApproximately 90% of colorectal cancer (CRC) deaths are caused by tumors ability to migrate into the adjacent tissues and metastase into distant organs. More than 40 genes have been causally linked to the development of CRC but no mutations have been associated with metastasis yet. To identify molecular basis of CRC metastasis we performed whole-exome and genome-scale transcriptome sequencing of 7 liver metastases along with their matched primary tumours and normal tissue. Multiple, spatially separated fragments of primary tumours were analyzed in each case. Uniformly malignant tissue specimen were selected with macrodissection, for three samples followed with laser microdissection.Results> 100 sequencing coverage allowed for detection of genetic alterations in subpopulation of tumour cells. Mutations in KRAS, APC, POLE, and PTPRT, previously associated with CRC development, were detected in most patients. Several new associations were identified, including PLXND1, CELSR3, BAHD1 and PNPLA6.ConclusionsWe confirm the essential role of inflammation in CRC progression but question the mechanism of matrix metalloproteinases activation described in other work. Comprehensive sequencing data made it possible to associate genome-scale mutation distribution with gene expression patterns. To our knowledge, this is the first work to report such link in CRC metastasis context.