Liver Cirrhosis Increases the Risk of Developing Advanced Colon Polyps.

GOALS: To analyze our experience with adenoma detection rates in patients with liver cirrhosis in a community setting. BACKGROUND: Colorectal cancer (CRC) is the third most common cancer and leading cause of cancer death in men and women in the USA. The majority of CRCs arise from premalignant polyps (adenomas), which are typically detected and removed during colonoscopy. Data are limited on the risk of CRC in patients with various chronic liver diseases and the association between CRC and demographics, liver disease etiology and colonoscopy findings. STUDY RESULTS: A total of 351 colonoscopies were performed (2006 to 2019) in patients with liver cirrhosis. Mean age was 62.3 ± 9.4 years, there were 158 females and 193 males. Adenomas were found in 159 procedures (49.07%) and were more likely found in the right colon (76.73%) vs the left colon (18.87%). Left-sided adenoma occurrence was significantly lower in women (61% lower than men, p = 0.05). Neither indication for the procedure (p = 0.08) nor advancing age (p = 0.94) affected adenoma detection rates. No significant differences were observed in the findings of adenomas between different chronic liver diseases. CONCLUSIONS: Adenoma detection rates in patients with cirrhosis (49%) undergoing elective colonoscopy were higher than rates reported in the literature for LT candidates (22-42%) undergoing standardized screenings. Colonoscopy screenings should be expanded to all patients with cirrhosis, regardless of etiology.

Altered mucosal immunity in HIV-positive colon adenoma: decreased CD4+ T cell infiltration is correlated with nadir but not current CD4+ T cell blood counts.

BACKGROUND: People living with HIV (PLWH) face greater risks of developing non-AIDS-defining cancers (NADCs) than the general population; however, the underlying mechanisms remain elusive. The tumor microenvironment plays a significant role in the carcinogenesis of colorectal cancer (CRC), an NADC. We studied this carcinogenesis in PLWH by determining inflammatory phenotypes and assessing PD-1/PD-L1 expression in premalignant CRC stages of colon adenomas in HIV-positive and HIV-negative patients. METHODS: We obtained polyp specimens from 22 HIV-positive and 61 HIV-negative participants treated with colonoscopy and polyp excision. We analyzed adenomas from 33 HIV-positive and 99 HIV-negative patients by immunohistochemistry using anti-CD4, anti-CD8, anti-FoxP3, and anti-CD163 antibodies. Additionally, we analyzed the expression levels of immune checkpoint proteins. We also evaluated the correlation between cell infiltration and blood cell counts. RESULTS: HIV-positive participants had fewer infiltrating CD4+ T cells than HIV-negative participants (p = 0.0016). However, no statistical differences were observed in infiltrating CD8+ and FoxP3+ T cells and CD163+ macrophages. Moreover, epithelial cells did not express PD-1 or PD-L1. Notably, CD4+ T cell infiltration correlated with nadir blood CD4+ T cell counts (p <  0.05) but not with current blood CD4+ T cell counts. CONCLUSION: Immune surveillance dysfunction owing to decreased CD4+ T cell infiltration in colon adenomas might be involved in colon carcinogenesis in HIV-positive individuals. Collectively, since the nadir blood CD4+ T cell count is strongly correlated with CD4+ T cell infiltration, it could facilitate efficient follow-up and enable treatment strategies for HIV-positive patients with colon adenomas.

The impact of body weight on dysplasia of colonic adenomas: a case-control study.

OBJECTIVE: Colorectal cancer (CRC) is common across countries in males and females. Most cases originate from adenomas harboring high grade dysplasia. Among risk factors, weight excess has been suggested to positively influence dysplasia progression. In this study, the relationship between dysplasia grade of adenomas and body mass index (BMI) categories was analyzed. METHODS: This was a retrospective case-control study. A total of 4745 charts (59.8% females) from patients undergoing colonoscopy were collected. Data regarding age, sex, smoking habits, occupation, residence, personal history of CRC, personal history of polyps and BMI were retrieved. Adenomas with high-grade dysplasia were labeled as advanced. RESULTS: They were 970 (20.4%) subjects with adenomas (cases: mean age 64.67 ± 11.35 years) and 3775 without (controls: mean age 56.43 ± 16.56 years). As expected, adenomas were significantly associated with overweight or obesity. After adjusting for all covariates the presence of advanced adenoma was significantly associated with age, male sex, smoking habits, personal history of CRC, overweight (OR = 1.298, IC 95% 1.092-1.697) and obesity (OR = 1.780, IC 95% 1.260-2.515). CONCLUSIONS: Our findings support the protective effect a normal weight against advanced adenomas. Reduction of BMI value should be pursued in healthy programs.

Pre-cancerous colon polyps in the young - incidental adenoma detection in average-risk persons forty and younger.

Of 166 consecutive diagnostic colonoscopies performed on persons aged forty and under (excluding those at an increased risk of colon neoplasms) by a single gastroenterologist in community practice with an Adenoma Detection Rate (ADR) approaching 70% in average-risk screening colons in persons over fifty, 34 had incidentally detected colon adenomas and 38 had serrated polyps. We suggest routine tabulation of incidentally detected polyps in young people to better understand colon neoplasm biology and plan prevention strategies.

Inflammation of colon adenoma in the setting of type 1 autoimmune pancreatitis.

Although immunoglobulin G4-related diseases (IgG4-RD) have been found to affect many organs, little is known about their effects on the colonic mucosae. Pathological examination of colon adenomas has shown inflammatory cell infiltration into the stroma. We therefore assessed the clinicopathological characteristics of colon adenomas in patients with type 1 autoimmune pancreatitis (AIP-1), a representative IgG4-RD. Both colon adenomas from patients with (IgG4 adenomas) and without (Non-IgG4 adenomas) IgG4-RD were characterized by moderate to severe lymphoplasmacytic and eosinophilic inflammation without fibrosis or phlebitis. The ratio of IgG4-positive to IgG-positive plasma cells (IgG4/IgG ratio) and the numbers of IgG4-positive plasma cells were significantly higher in IgG4 adenomas than in Non-IgG4 adenomas. IgG4-positive plasma cells tended to be distributed diffusely in lower areas of the mucosae in IgG4 adenomas. We were unable to confirm whether IgG4 adenomas constituted an IgG4-RD. However, IgG4 adenomas in the setting of IgG4-RD may provide useful pathological information, supplementing a diagnosis of IgG4-RD outside the colon, or may facilitate examination for IgG4-RD, especially AIP-1. IgG4 adenomas warrant further investigation.

Disparate cell proliferation and p53 overexpression in colonic crypts with normal epithelial lining found below the neoplastic canopy of conventional adenomas.

We previously found colonic crypts with normal epithelial lining but with corrupted shapes (NECS) beneath the adenomatous tissue of conventional adenomas (CoAs). Here we assessed the distribution of proliferating cells (PCs) and explored the possible occurrence of p53-upregulated cells in the NECS in a cohort of CoAs. Sections from 70 CoAs and from 12 normal colon segments were immunostained with the proliferation marker Ki67. In 60 of the 70 CoAs, additional sections were immunostained for the tumor suppressor p53 protein. NECS with asymmetric, haphazardly distributed single PC or PC clusters were recorded in 80% of the CoAs, with a continuous PC domain in one or both slopes of the crypts in 17%, and with haphazardly distributed single PCs in the remaining 3% of the CoAs. In the 12 normal segments (controls), the colon crypts demonstrated normal shapes with symmetric PC domains limited to the lower third portion of the crypts. In 30% of the 60 CoAs immunostained with p53 the NECS revealed haphazardly distributed p53-upregulated cells, singly or in clusters. In sum, the apparently normal epithelium of the NECS beneath the adenomatous tissue of CoAs revealed an unprecedented relocation of the normal PC domains. This unexpected event and the occurrence of p53-upregulated cells strongly suggest that the crypts beneath the neoplastic tissue of CoAs harbor somatic mutations. The accretion of putative mutated NECS beneath the neoplastic canopy of CoA emerges as a previously unaddressed major event, an event that might play an important role in the histogenesis of CoA in the human colon.

Phytoestrogens: Dietary Intake, Bioavailability, and Protective Mechanisms against Colorectal Neoproliferative Lesions.

Phytoestrogens are natural substances that have been extensively studied for their beneficial effect on human health. Herein, we analyzed the data of the literature on the role of phytoestrogens in the prevention of colorectal neoproliferative lesions (CNL). Both in vitro and in vivo studies suggest that the beneficial effects of phytoestrogens on CNL mainly depend on their ability to bind estrogen receptor beta (ERß) in the intestinal mucosa and counter ER-alpha (ERα) activity. Epidemiological data demonstrate a correlation between the low prevalence of CNL in Eastern populations and the consumption of soy products (phytoestrogen-enriched diet). However, both observational and interventional studies have produced inconclusive results. In our opinion, these discrepancies depend on an inadequate evaluation of phytoestrogen intake (dietary questionnaires were not aimed at establishing phytoestrogen intake) and absorption (depending mainly on the intestinal microbiota of the analyzed subjects). For this reason, in the present review, we performed an overview of phytoestrogen dietary intake and metabolism to offer the reader the opportunity for a better interpretation of the literature. Future prospective trials focusing on the protective effect of phytoestrogens against CNL should take into account both their dietary intake and absorption, considering the effective role of the intestinal microbiota.

GNAS gene mutation may be present only transiently during colorectal tumorigenesis.

Mutations of the gene GNAS have been shown to activate the adenylate cyclase gene and lead to constitutive cAMP signaling. Several preliminary reports have suggested a role for GNAS gene mutations during colorectal carcinogenesis, particularly mucinous carcinomas. The aim of this study was to clarify the incidence of GNAS mutations in adenomas (tubular, tubulovillous, and villous), carcinomas with residual adenoma, and carcinomas, and to relate these findings to mutations of the KRAS gene and to the mucinous status of the tumors. We used standard PCR techniques and direct gene sequencing to evaluate tumors for gene mutations. No GNAS mutations were identified in 25 tubular adenomas, but were present in 6.4% of tubulovillous adenomas and 11.2% of villous adenomas. A GNAS mutation was found in 9.7% of the benign portion of carcinoma with residual adenoma, but in none of 86 carcinomas. A similar trend was seen for KRAS mutation across the five groups of tumors. GNAS mutations may function as an important driver mutation during certain phases of colorectal carcinogenesis, but may then be lost once the biological advantage gained by the mutated gene is no longer necessary to sustain or advance tumor development.

Invasive carcinomas may arise in colorectal adenomas with high-grade dysplasia and with carcinoma in situ.

Colorectal carcinomas (CRC) usually arise in colorectal adenomas (CRA) displaying high-grade dysplasia (HGD) or carcinoma in situ (CIS). The aim was to assess the frequency of adenomas displaying HGD or CIS in a cohort of consecutive CRA with submucosal invasive carcinoma. Ninety-two consecutive adenomas were investigated. Sub-mucosal invasion was present in the 39 adenomas with HGD (42%) and in 58% (53/92) of the adenomas with CIS (p<0.05). Sections from 49 adenomas were stained with the DNA-specific Feulgen reaction and for the proliferation marker Ki-67. Five consecutive high power fields (HPFs) were evaluated using a x40 objective. Marked Feulgen reaction was recorded in 91.8% or in 101 of the 110 HPFs studied in adenomas with HGD, but in none of the 135 HPFs studied in adenomas with CIS (p<0.05). Intense Ki-67 expression (>/=75%) was present in 98.2% or in 108 of the 110 HPFs studied in adenomas with HGD, but only in 1.4% or in 2 of the 135 HPFs in adenomas with CIS (p<0.05). Hence, HGD cells and CIS cells can be differentiated not only morphologically but also chemically by the semi-quantitative appreciation of their DNA content and immunohistochemically by the apparent difference in cell proliferation. Although submucosal invasion occurred significantly more frequently in adenomas with CIS than in those with HGD, as many as 42% of the adenomas with submucosal invasion displayed HGD at histology. Despite morphological, chemical and immunohistochemical dissimilarities, these 2 non-invasive neoplasias might have similar biological behaviour in terms of progression towards submucosal invasion.