Risk Of Colorectal Carcinoma Research Articles

Risk of Incident colorectal carcinoma in patients with type 2 diabetes on SGLT-2 inhibitor users: a population-based cohort study

Abstract Background Patients with type 2 diabetes (T2D) are at substantially higher risk for developing colorectal carcinoma (CC) than the general population. Clinical studies have investigated the effects of sodium-glucose co-transporter-2 inhibitor (SGLT-2i) use on the development of incident CC in patients with T2D, but the findings are inconsistent. Purpose This study aimed to examine the association between SGLT-2i use and incident CC risk in patients with T2D. Methods We conducted a nationwide retrospective cohort study using the National Health Insurance Research Database (2015–2021). The primary outcome was the risk of incident CC by estimating hazard ratios (HRs) and 95% confidence intervals (CIs). Therefore, multiple Cox regression modeling was conducted to analyze the association between SGLT-2i use and incident CC risk in patients with T2D. Results 268,495 propensity score-matched pairs of patients with T2D using SGLT-2i and non-using SGLT-2i, 1557 and 1264 incident CCs were recorded, respectively. There was a decreased risk of incident CC for SGLT-2i users after adjusting for the index year, sex, age, comorbidities, and concurrent medication (adjusted HR 0.79, 95% CI 0.74–0.84) compared with non-SGLT-2i users. The sensitivity test for the propensity score 1:2-matched analyses showed similar result (adjusted HR 0.79, 95% CI 0.74–0.85). Conclusions This population-based cohort study found that SLGT2i user was associated with a lower risk of CC by 21% compared to non-SGLT-2i users in T2D patients. More studies are needed to credibly evaluate the effects of SGLT-2i therapy on CC prevention in patients with T2D.

Helicobacter pylori infection is associated with the development of sporadic colorectal carcinoma and colorectal adenomatous polyps

Helicobacter pylori (H. pylori) infection is a well-established carcinogen that has been extensively studied in the context of gastric diseases. Recent studies suggested a potential association between H. pylori and the risk of colorectal carcinoma (CRC). However, available data remains insufficient to definitively establish a causal relationship between H. pylori infection and the development of CRC and its precursor lesions. In our study, we reviewed all patients diagnosed with CRC in 2020 at our institution. H. pylori assessment was performed in all 92 CRC specimens by immunohistochemistry. Notably, two of the three patients detected with H. pylori infection are under the age of 50. Subsequently, we reviewed a total of 52 patients under the age of 50 diagnosed with CRC at our institution from 2015 to 2022. Among these patients, H. pylori infection was detected in 7 CRC specimens (13.46 %). All seven patients had adenocarcinoma on the left side of the colon. In exploring the link between H. pylori infection and the risk of developing CRC precursor lesions, we analyzed 242 patients who underwent colonoscopy guided polypectomy and also had stomach biopsies from 2015 to 2022. Of these patients, 21 were proved to be positive for H. pylori infection in the stomach, while the remaining 221 were negative. Among the H. pylori-positive group, 76.19 % (16 patients) exhibited adenomatous polyps, compared to 33.48 % (74 patients) in the H. pylori-negative patients (p=0.0001). However, no H. pylori was detected in any colonic adenomatous polyps. Our findings contribute additional evidence supporting the association between H. pylori infection and the development of sporadic CRC, probably a particular association with early-onset ones. Furthermore, gastric H. pylori infection appears to be linked to the higher prevalence of colonic adenomatous polyps, suggesting that individuals with gastric H. pylori infection may benefit from closer and earlier monitoring through colonoscopy.

Incidence Rates of Risk Factors for Colorectal Cancer's Early Symptoms in the Community in Gondanglegi District, Malang, East Java, Indonesia: An Epidemiological Study

Background: Colorectal cancer (CRC) is one of the most common types of cancer worldwide. CRC is most typical symptom is hematochezia while the risk factors encompass sex, age, genetic predispositions, history of colorectal polyps or cancer, chronic inflammatory bowel diseases, physical exercise, and specific dietary choices, including high red meat intake, fried food, and low fiber consumption. This study aims to screen the risk factors of colorectal cancer.Subjects and Method: This research was conducted on residents in the Sepanjang village, Malang Regency, involved in community service by the Internist Association of Malang. Community service was carried out in July 2023 and 148 residents were involved in collecting data on risk factors for colorectal carcinoma. Data collection was carried out using a questionnaire with a cross-sectional approach. The questionnaire assesses the presence of symptoms of bloody stools and several habits related to colorectal carcinoma risk factors, including age, gender, exercise routine, and dietary history. Data presentation and analysis were carried out as in the table.Results: Among the risk factors listed assessed using the questionnaire, Men (p=0.021), lack of exercise (p= 0.008), consumption of fried food (p= 0.021), and consumption of instant noodles (p= 0.013) significantly affect the prevalence of hematochezia.Conclusion: Men, lack of exercise, consumption of fried food, and consumption of instant noodles significantly affect the hematochezia indicating CRC.

Higher mortality risk from gynaecological neoplasms and non-Hodgkin’s lymphoma in patients with systemic lupus erythematosus: an observational study from the Spanish National Registry

ObjectiveTo evaluate the impact of the different types of neoplasms and lineages on mortality of patients with SLE.MethodsRetrospective and observational comparison of the neoplasm-related deaths in patients with SLE and...

Relationship Between Adverse Childhood Experiences, Childhood Obesity And Risk of Colorectal Cancer in Adulthood: A Systematic Review

Background: Adverse childhood experiences are traumatic incidents occurring before the age of 18 years that increases the risk ofadult health problems. Such experiences include various types of abuse; physical and emotional neglect; separation betweenparents; serious household dysfunction; peer violence and community violence.Objective: To determine the risk of colorectal cancer in persons in adult life with exposure to early life trauma. To find relationbetween adverse experiences in childhood and early life obesity.Methods: This systematic review was conducted according to PRISMA guidelines 2020. In this review, 5 independent reviewersextracted the data based on the articles published between 2018 and 2023 with the help of Databases such as PubMed/ Medline andGoogle Scholar. In each database, keywords used were: Adverse Childhood Experiences And Childhood Obesity, Adverse ChildhoodExperiences OR Childhood Obesity AND Colorectal Cancer, Childhood Obesity AND Colorectal Cancer. Studies reported anyrelationship between adverse childhood experiences or childhood obesity and adulthood colorectal cancer were selected..Results: A total of 22 articles were identified. Out of these 13 (59.1%) explained the positive relationship between adverse childhoodexperiences and the development of childhood obesity (increased BMI). The most common childhood adversities related toincreased childhood BMI are Household dysfunction, crime proximity, neglect, bereavement, and abuse. There were 9 (40.9%) ofthe 22 identified articles proved a direct relation between childhood obesity and the development of colorectal carcinoma.Conclusion: Necessary steps must be taken to raise awareness about adverse childhood experiences such as abuse andcommunity-related issues children face and prevent such risk factors from increasing the overall risk of Colorectal Carcinoma, thusalleviating the burden on the health system and provide wellness to the society as a whole.

A238 BEST APPROACH TO SURVEILLANCE COLONOSCOPY FOR COLORECTAL CANCER IN PATIENTS WITH PRIMARY SCLEROSING CHOLANGITIS AND INFLAMMATORY BOWEL DISEASE

Abstract Background Primary sclerosing cholangitis (PSC) is a chronic, cholestatic liver disease and it has been recognized as a risk factor for hepatobiliary and colorectal carcinoma (CRC). Inflammatory bowel disease (IBD) is associated with a 6-fold increased risk of CRC as compared to the general population but with co-existing PSC, this risk rises to 30-fold and hence CRC surveillance is critical in these patients. Aims We performed a systematic review of the literature on surveillance colonoscopy for CRC in patients with PSC-IBD, with the aim of identifying the most effective approach. Methods The protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) under ID 472215. The search was executed in the databases Medline, EMBASE, Cochrane, Web of science, Scopus and Google Scholar databases from 1947 to May 2023. Observational or randomized controlled studies were included if patients had PSC-IBD (paediatric or adult) undergoing surveillance colonoscopy. There was no restriction for language. We used a modified version of the Newcastle–Ottawa Quality Assessment Scale to assess the risk of bias. Neoplasia was defined as the presence of low-grade dysplasia, high grade dysplasia or colorectal carcinoma. Results Amongst 2900 studies identified, 7 studies met the inclusion criteria with a total number of 379 PSC-IBD patients and 1884 IBD patients (all adult). The median frequency of surveillance colonoscopy was every 0-2 years. The most common endoscopic presentation of dysplasia in PSC-IBD was a normal appearing mucosa or subtle abnormalities such as mild inflammation. Three studies performed random and targeted biopsies and only one study did quadruple random biopsy (every 10 cm of the colon). Two studies used chromoendoscopy and high-definition endoscopy whereas another two studies used white light colonoscopy. Studies varied in terms of the number of biopsies taken and timing for the frequency and initiation of surveillance. Outcomes included intensive surveillance, resection, and colectomy. Our meta-analysis of 2 studies that reported the prevalence of colorectal dysplasia in PSC-IBD patients revealed a pooled prevalence of 21% (95% CI 1.4%-28%, I2 = 0%, Pampersand:003C0.597, shown in Figure 1) Conclusions Colorectal dysplasia is prevalent in patients with PSC-IBD and is associated with worse disease outcomes. As a result, PSC-IBD patients should be screened annually from the diagnosis of PSC. However, there is variation in practice, and no clear consensus on the best approach to perform screening colonoscopy in this population. Literature comparing various approaches is very sparse. Additional high-quality studies on this subject are needed to guide practice, particularly in paediatrics where data are non-existent. Figure 1: Forest plot for meta-analysis of CRC dysplasia prevalence in PSC-IBD Funding Agencies None

P431 Assessing intestinal barrier healing by fusing ultra-high magnification endoscope and automated spatial multispectral imaging analysis in PSC-colitis patients

Abstract Background PSC colitis is associated with an increased risk of colorectal carcinoma. Endoscopic monitoring is crucial since endoscopic and histological activity can persist in PSC even during clinical remission. Recent evidence suggests that the presence of barrier dysfunction may predict relapse in quiescent patients. This study aims to assess mucosal and barrier healing in quiescent PSC colitis and evaluate the potential to predict outcomes by combining an ultra-high magnification endocytoscope (ECS) with intestinal barrier protein markers. Methods 23 PSC-colitis patients in clinical remission requiring surveillance colonoscopy were prospectively enrolled. Ileal and colonic mucosa were assessed with high definition, virtual chromoendoscopy and ultra-high magnification ECS. Endoscopic remission was defined as MES ≤1, UCEIS≤1, PICaSSO≤3, while histological remission was defined as RHI≤3 without lamina propria or epithelial neutrophils, NHI ≤1 and PHRI=0. A novel ECS score was developed to assess ileal and colonic intestinal barrier (Table 1). The expression of tight junction proteins (Claudin-2, Occludin, and JAM-A) was evaluated through immunohistochemistry and multiplex immunofluorescence, and it was quantified as cell density and mean expression using the automated inForm® Akoya Biosciences digital multiplex platform. The occurrence of significant adverse outcomes (steroid use, flare-ups, hospitalization, colectomy) was evaluated over a 12-month follow-up period. Results Of 18 patients in endoscopic remission, 12 and 13 were in histological remission according to RHI and NHI, respectively. The ECS score correlated moderately with endoscopic score (r=0.57 for MES, r=0.44 for UCEIS and r=0.54 for PICaSSO) and strongly with histological scores (r=0.56 for RHI, r=0.61 for NHI and r=0.62 for PHRI), especially in the right colon. Only 5 patients experienced adverse outcomes. Notably, barrier healing, as indicated by an ECS score<3 in the ileum and <5 in the colon, was significantly associated with better outcomes. The three barrier proteins showed a distinct mucosal localisation in both ileum and colon, with higher cell density of Occludin and Claudin-2 in the epithelium, while higher JAM-A cell density in the lamina propria. The combined assessment of the intestinal barrier by ECS and Claudin-2 cell density significantly predicted outcomes in both colon and ileum (p=0.02 and p=0.04, respectively). Conclusion ECS combined with automated multispectral imaging analysis of intestinal barrier integrity is an innovative tool to assess barrier healing precisely and predicts significant adverse outcomes in PSC colitis patients in clinical, endoscopic, and histological remission.

A case report of appendiceal adenoma - a rare entity

Appendiceal neoplasms are quite uncommon. They are detected in fewer than 0.5 percent of appendectomies and less than 0.5 percent of all gastrointestinal neoplasms. Similar to a colonic adenoma, an appendiceal adenoma is neoplasm with precancerous nature. A rare case of appendiceal adenoma is presented here in a 65-year-old female patient, incidentally discovered at the orifice of the appendix, during the screening analysis. The patient felt well. Abdominal examination and laboratory analysis were regular. Due to the inaccessibility of the lesion by colonoscopy, surgical treatment was recommended. A laparoscopic appendectomy was performed. On pathological examination, diagnosis of tubulovillous adenoma was performed. Endoscopic screening analysis of precancerous appendiceal neoplasm is very important. The method of choice for any appendiceal neoplasm is surgical removal i.e. appendectomy, preferably with a clean caecal margin, which requires stapling of the cecum. Early detection can prevent complications and decrease the risk of consequential appendiceal or colorectal carcinoma.

Causal Relationships of Chronic Constipation and Irritable Bowel Syndrome with Digestive Tract Cancers: A Mendelian Randomization Study.

Chronic constipation and irritable bowel syndrome (IBS) manifest as prevalent gastrointestinal disorders, while digestive tract cancers (DTCs) present formidable challenges to global well-being. However, extant observational studies proffer uncertain insights into potential causal relationships of constipation and IBS with susceptibility to DTCs. We executed Mendelian randomization (MR) analysis to establish causal connections between these conditions and seven distinct categories of DTCs, including colorectal carcinoma (CRC), hepatocellular cancer (HCC), esophageal malignancy (ESCA), pancreatic adenocarcinoma (PAAD), biliary tract carcinoma (BTCs), gastric carcinoma (GC), and small intestine neoplasm (SIC). Leveraging instrumental variables (IVs) obtained from GWAS data of the FinnGen database, we employed a range of analytical methodologies, including inverse-variance weighting multiplicative random effects (IVW_MRE), inverse-variance weighting fixed effects (IVW_FE), maximum likelihood (ML), weighted median (WM), MR‒Egger regression, and the MR-PRESSO test. We observed a substantial linkage between genetically predicted constipation and increased vulnerability to PAAD (OR = 2.29, 95% CI: 1.422-3.69, P = 0.001) via the IVW method. Following the removal of outlier SNPs through MR-PRESSO, genetically predicted IBS was affiliated with an increased risk of CRC (OR = 1.17, 95% CI: 1-1.37, P = 0.05). Nonetheless, decisive causal correlations of constipation or IBS with other DTCs remain elusive. In summary, genetically predicted constipation was associated with an augmented PAAD risk, and IBS was associated with an increased CRC susceptibility within European cohorts, in agreement with some observational studies. Nevertheless, the causal associations of constipation and IBS with other DTCs remain inconclusive.

Role of microRNA in colorectal carcinoma (CRC): a narrative review.

MicroRNAs (miRNAs) are short non-coding RNAs that play a critical role in regulating gene expression by binding to target messenger RNAs (mRNAs). They were first discovered around 8 years after the identification of the first miRNA in 1993, and since then, there has been a significant increase in miRNA-related research and discoveries. MiRNAs have been implicated in various biological processes, including cancer, particularly in colorectal cancer (CRC). In CRC, miRNAs act as either oncogenes or tumor suppressors, influencing essential cellular functions such as cell proliferation, apoptosis, angiogenesis, and metastasis. The dysregulation of miRNAs in CRC can arise from different factors, leading to abnormal expression levels of their target mRNAs and subsequently affecting protein production. Consequently, miRNAs may directly target oncogenes or tumor suppressor genes, thereby contributing to cancer initiation and progression. Notably, tumors often exhibit reduced expression of mature miRNAs. In CRC research, miRNAs offer potential as diagnostic biomarkers and therapeutic targets. Specific miRNA profiles could serve as non-invasive tools for early CRC detection and risk assessment. Additionally, miRNA-based therapies present a promising approach for targeted cancer treatment by modulating miRNA expression. However, challenges related to delivery systems and long-term safety must be addressed to fully harness their therapeutic potential.

Rare germline variants in POLE and POLD1 encoding the catalytic subunits of DNA polymerases ε and δ in glioma families

Pathogenic germline variants in the DNA polymerase genes POLE and POLD1 cause polymerase proofreading-associated polyposis, a dominantly inherited disorder with increased risk of colorectal carcinomas and other tumors. POLE/POLD1 variants may result in high somatic mutation and neoantigen loads that confer susceptibility to immune checkpoint inhibitors (ICIs). To explore the role of POLE/POLD1 germline variants in glioma predisposition, whole-exome sequencing was applied to leukocyte DNA of glioma patients from 61 tumor families with at least one glioma case each. Rare heterozygous POLE/POLD1 missense variants predicted to be deleterious were identified in glioma patients from 10 (16%) families, co-segregating with the tumor phenotype in families with available DNA from several tumor patients. Glioblastoma patients carrying rare POLE variants had a mean overall survival of 21 months. Additionally, germline variants in POLD1, located at 19q13.33, were detected in 2/34 (6%) patients with 1p/19q-codeleted oligodendrogliomas, while POLE variants were identified in 2/4 (50%) glioblastoma patients with a spinal metastasis. In 13/15 (87%) gliomas from patients carrying POLE/POLD1 variants, features of defective polymerase proofreading, e.g. hypermutation, POLE/POLD1-associated mutational signatures, multinucleated cells, and increased intratumoral T cell response, were observed. In a CRISPR/Cas9-derived POLE-deficient LN-229 glioblastoma cell clone, a mutator phenotype and delayed S phase progression were detected compared to wildtype POLE cells. Our data provide evidence that rare POLE/POLD1 germline variants predispose to gliomas that may be susceptible to ICIs. Data compiled here suggest that glioma patients carrying POLE/POLD1 variants may be recognized by cutaneous manifestations, e.g. café-au-lait macules, and benefit from surveillance colonoscopy.

Morphological subtypes of colorectal low-grade intraepithelial neoplasia: diagnostic reproducibility, frequency and clinical impact

AimsSpecial histomorphological subtypes of colorectal low-grade intraepithelial neoplasia (LGIN) with variable prognostic impact were recently described in patients with inflammatory bowel disease (IBD) referred to as non-conventional dysplasia. However, they...

Association of serum superoxide dismutase activity and the incidence of colorectal cancer in a nested case-control study

BackgroundSuperoxide dismutase (SOD) is an antioxidant enzyme that degrades superoxide, a major causative factor in carcinogenesis. We assessed associations between serum SOD activities and incidence of colorectal carcinoma (CRC) in a case-control study nested in the Japan Collaborative Cohort (JACC) study. MethodsAt baseline, 39,242 subjects donated serum samples. Participants diagnosed with CRC during follow-up were regarded as cases. Odds ratios (ORs) for CRC incidence associated with SOD were evaluated with conditional logistic regression models. In the current study, 176 cases and 524 controls were analyzed. ResultsFor the overall cohort, a decreasing trend in risk of CRC with increasing SOD was observed (P for trend=0.054) and the fourth quartile of SOD level showed the lowest risk compared to the first (OR=0.52, 95% confidence interval [CI]=0.29–0.93). This was significant in men (P for trend=0.001), with the fourth quartile of SOD level showing the lowest risk compared to the first (OR, 0.23; 95%CI, 0.09–0.60). It was also exclusively observed for rectal cancer and left-sided CRC (P for trend, 0.037 and 0.020, respectively), with the fourth quartile again showing the lowest risk compared to the first (OR, 0.28 and 0.38; 95%CI, 0.09–0.84 and 0.16–0.91, respectively). Limiting subjects to those followed-up over 2 years, all trends remained unchanged. ConclusionsOur findings suggest that serum SOD activity correlates inversely with risk of CRC, particularly in men and individuals with rectal cancer/left-sided CRC.

Clinical outcomes of endoscopic submucosal dissection for large pedunculated colorectal carcinoma: A retrospective multicenter study.

Complete en-bloc resection of pedunculated colorectal carcinoma is necessary for a proper pathological diagnosis. However, due to poor visibility, large pedunculated colorectal carcinomas are difficult to snare and resect en-bloc using endoscopic resection or polypectomy. Additionally, the bleeding risk of large pedunculated colorectal carcinomas is relatively high. We aimed to assess the feasibility and safety of endoscopic submucosal dissection for large pedunculated colorectal carcinomas. We conducted a retrospective multicenter cohort study to assess 36 consecutive patients with 36 large pedunculated colorectal carcinomas who underwent endoscopic submucosal dissection and evaluated the outcomes of endoscopic submucosal dissection. Furthermore, patients were divided into two groups according to the procedure time, and the factors related to the procedure time were assessed. The mean tumor size was 34.1 ± 9.9 mm. The en-bloc, complete en-bloc, and curative resection rates were 97% (35/36), 97% (35/36), and 81% (29/36), respectively. The rate of severe bleeding during the procedure was 11% (4/36); however, it could be controlled endoscopically in all patients. The rate of intraoperative perforation and delayed bleeding was 0% (0/36). Delayed perforations occurred in one patient that required surgery. A long procedure time was correlated with the location of the flexure and poor endoscope operability. No recurrence was observed in any patient. None of the patients died of colorectal carcinoma. Our results showed the feasibility and safety of endoscopic submucosal dissection for large pedunculated colorectal carcinomas.

Assessment of essential and toxic elemental concentrations in tumor and non-tumor tissues with risk of colorectal carcinoma in Pakistan

BackgroundColorectal tumor is a major cause of cancer morbidity and mortality both in USA and around the globe. Exposure to environmental toxicants such as toxic trace elements has been implicated in colorectal malignancy. However, data linking them to this cancer are generally lacking. MethodsAccordingly, the current study was to investigate the distribution, correlation and chemometric evaluation of 20 elements (Ca, Na, Mg, K, Zn, Fe, Ag, Co, Pb, Sn, Ni, Cr, Sr, Mn, Li, Se, Cd, Cu, Hg and As) in the tumor tissues (n = 147) and adjacent non tumor tissues (n = 147) of same colorectal patients which were analyzed by flame atomic absorption spectrophometry employing nitric acid-perchloric acid based wet digestion method. ResultsOn the average, Zn (p < 0.05), Ag (p < 0.001), Pb (p < 0.001), Ni (p < 0.01), Cr (p < 0.005) and Cd (p < 0.001) showed significantly higher levels in the tumor tissues compared with the non tumor tissues of patients, whereas mean levels of Ca (p < 0.01), Na (p < 0.05), Mg (p < 0.001), Fe (p < 0.001), Sn (p < 0.05) and Se (p < 0.01), were significantly elevated in the non tumor tissues than the tissues of tumor patients. Most of the elements revealed markedly disparities in their elemental levels based on food (vegetarian/nonvegetarian) habits and smoking (smoker/nonsmoker) habits of donor groups. The correlation study and multivariate statistical analyses demonstrated some significantly divergent associations and apportionment of the elements in the tumor tissues and non tumor tissues of donors. Noticeably, variations in the elemental levels were also noted for colorectal tumor types (lymphoma, carcinoids tumor and adenocarcinoma) and stages (I, II, III, & IV) in patients. ConclusionOverall, the study revealed that disproportions in essential and toxic elemental concentrations in the tissues are involved in pathogenesis of the malignancy. These findings provide the data base that helps to oncologist for diagnosis and prognosis of colorectal malignant patients.

Microsatellite instability in noncolorectal and nonendometrial malignancies in patients with Lynch syndrome.

Individuals with Lynch syndrome are at increased hereditary risk of colorectal and endometrial carcinomas with microsatellite instability (MSI-H) and mismatch repair-deficiency (dMMR), which make these tumors vulnerable to therapy with immune checkpoint inhibitors. Our aim is to assess how often other tumor types in these individuals share these characteristics. We retrieved the full tumor history of a historical clinic-based cohort of 1745 individuals with Lynch syndrome and calculated the standardized incidence ratio for all tumor types. MSI status, somatic second hit alterations, and immunohistochemistry-based MMR status were analyzed in 236 noncolorectal and nonendometrial malignant tumors. In individuals with Lynch syndrome MSI-H/dMMR occurred both in Lynch-spectrum and in non-Lynch-spectrum malignancies (85% vs 37%, P < .01). MSI-H/dMMR malignancies were found in nearly all non-Lynch-spectrum tumor types. Almost all breast carcinomas had medullary features, and most of them were MSI-H/dMMR. Breast carcinoma with medullary features were shown to be associated with Lynch syndrome (standardized incidence ratio = 38.8, 95% confidence interval = 16.7 to 76.5). In individuals with Lynch syndrome, MSI-H/dMMR occurs in more than one-half of the malignancies other than colorectal and endometrial carcinomas, including tumor types without increased incidence. The Lynch-spectrum tumors should be expanded to breast carcinomas with medullary features. All malignancies in patients with Lynch syndrome, independent of subtype, should be tested for MSI-H/dMMR in case therapy with immune checkpoint inhibitors is considered. Moreover, Lynch syndrome should be considered an underlying cause of all MSI-H/dMMR malignancies other than colorectal and endometrial carcinomas.

EBV and HPV Infections in Colorectal Cancer and Their Effect on P53 and P16 Protein Expression.

Viral infections contribute to 15-20% of newly diagnosed cancers worldwide. There is evidence of a possible etiological role of Epstein-Barr virus (EBV) and high-risk human papillomaviruses (HR-HPVs) in colorectal carcinoma (CRC). Loss of p53 and p16 function has been found in many cancers and this may occur in many different ways, including gene mutation or interaction with viral oncoproteins. This study aimed to evaluate the presence of EBV and HPV in CRC patients in northern Iran and to assess p53 and p16 protein expression related to these viral infections. Real-time PCR was used to amplify the DNA sequences of these viruses in 55 colorectal tumoral tissues, along with their corresponding non-tumoral adjacent tissues. Additionally, immunohistochemistry (IHC) was utilized to determine p53 and p16 protein expression. EBV DNA was detected in 49.1% of CRC tissues. Furthermore, HPV DNA was present in 7.3% of CRC tissues. Notably, the prevalence of EBV infection in tumoral tissues was significantly higher than in non-tumoral tissues (P=0.001). The EBV DNA polymerase catalytic subunit (BALF5) copy number in tumoral tissues was higher than in non-tumoral tissues and this difference was statistically significant (P=0.008). P53 was positive in 21/26 (80.8%) EBV-positive and in 11/25 (44%) EBV-negative samples and this difference was significant (P=0.007). P16 was positive in 13/26 (50%) EBV-positive and in 14/25 (58.3%) EBV-negative samples (P= 0.668). Our findings suggest that EBV infection can increase the risk of CRC. In addition, EBV seems to stabilize p53 in EBV-positive CRC which needs further research. No significant correlation was detected between EBV infection and p16 expression. Also, we could not find a causal relationship between HPV infection and CRC in the study population.

Oxidative imbalance increases the risk for colonic polyp and colorectal cancer development.

The role of oxidative stress in the pathogenesis of colorectal carcinoma (CRC) has garnered considerable interest recently. Specific oxidative factors have been implicated in the pathogenesis of adenomatous polyps and ultimately adenocarcinoma. To evaluate the effect of oxidative imbalance as quantified by specific serological markers in the development of sporadic colon adenocarcinoma. A total of 170 patients that underwent endoscopy of the lower gastrointestinal tract in a tertiary center within 3 years were included in the study. They were allocated in three groups; those with sporadic colon adenocarcinoma (n = 56, 32.9%), those with colonic polyps (n = 33, 19.4%) and healthy controls (n = 81, 47.7%). All patients were evaluated for oxidant activity and antioxidant capacity with serum measurements of specific markers such as vitamins A, 25(OH) D3, E, C, B12, folic acid, glutathione, selenium (Se), zinc (Zn), free iron (Fe2+), and malondialdehyde and results were compared between groups. Serum levels of vitamins C, E, D, Se, Zn, vitamin B12 and total antioxidant capacity were significantly lower in the combined neoplasia/polyp group than in the control group (P = 0.002, P = 0.009, P < 0.001, P < 0.001, P < 0.001, P = 0.020 and P < 0.001, correspondingly). Increased levels of vitamin E (P = 0.004), vitamin D (P < 0.001), Se (P < 0.001) and Zn (P < 0.001) seem to bestow a protective effect on the development of CRC. For vitamin D (P < 0.001) and Zn (P = 0.036), this effect seems to extend to the development of colon polyps as well. On the other hand, elevated serum levels of malondialdehyde are associated with a higher risk of CRC (OR = 2.09 compared to controls, P = 0.004). Regarding colonic polyp development, increased concentrations of vitamin Α and Fe2+ are associated with a higher risk, whereas lower levels of malondialdehyde with a lower risk. Increased oxidative stress may play an important role in the pathogenesis and progression of CRC. Antioxidants' presence may exert a protective effect in the very early stages of colon carcinogenesis.

The association of age, gender, tumor site, and smoking habit with histopathologic types of colorectal carcinoma patients in Wahidin Sudirohusodo Hospital, Makassar, Indonesia

Background: Colorectal carcinoma is the world's third most common type of cancer. The incidence in India is around 7/100,000. From GLOBOCAN data, the incidence of colorectal cancer in Indonesia is 17.2 per 100,000 adult population, with a mortality of 8.4% of all cancer cases. Several parameters were related to the risk of colorectal carcinoma. This study aims to evaluate the association of age, gender, tumor site, and smoking habit with histopathologic types of colorectal carcinoma patients in Wahidin Sudirohusodo Hospital, Makassar, Indonesia. Methods: The retrospective cross-sectional study was conducted among 158 cases of colorectal carcinoma using a descriptive categorical sampling technique at Wahidin Sudirohusodo Hospital, Makassar, Indonesia, from January-March 2022. The variables assessed in this study were age, gender, tumor site, smoking habit, and histopathologic types of colorectal carcinoma. Data were analyzed using SPSS version 22 for Windows. Results: There were 158 cases of colorectal carcinoma. According to age, most patients were 45-60 years old (41.1%), while 18-44 years and over 60 years had almost the same proportion. In this study, most of the tumors were found in the distal part, namely the rectum (30.4%), rectosigmoid (18.4%) and sigmoid (17.1%). Most of the subjects were smokers (78.5%). Meanwhile, according to the histological type, 85.4% were adenocarcinomas, followed by mucinous adenocarcinomas (13.3%) and signet ring cell types (1.3%). There is no significant relationship between age, gender, tumor location, and smoking habits with the histopathological type of colorectal carcinoma (p&gt;0.05). Conclusion: There is no significant relationship between age, gender, tumor location, and smoking habits with the histopathological type of colorectal carcinoma.

Crypts in Asymmetric Branching in Patients With Ulcerative Colitis in Remission

Background/Aim: To report the frequency of crypts in asymmetric branching (CAB) in biopsies from all colorectal segments in patients with ulcerative colitis in remission (UCR). Patients and Methods: Biopsies in 100 UC patients were investigated: 50 with UCR and 50 with ongoing long-lasting UC (LLU; i.e., controls). Results: The frequency of CAB was significantly lower in UCR than in LLUC, both in the right colon and left colorectum. CAB frequency was not influenced by two important confounders: the age and sex of patients. Conclusion: CAB is a pathologic aberration of colorectal cryptogenesis evoked by chronic mucosal inflammation. When chronic inflammation waned in UCR, the production of CAB plummeted or ceased. Chronic inflammation and protracted disease-duration in LLUC increase the risk for colorectal dysplasia or carcinoma. Importantly, dysplastic CAB were recently detected in LLUC-associated dysplasia. Whether the abrogation of CAB is instrumental in reducing the neoplastic risk in UCR patients, deserves further investigation.