Proximal Rectum Research Articles

Impaired Epithelial CD200L Tolerance Signaling in Irritable Bowel Syndrome Cases With Diarrhea May Be Associated With Recurrent Miscarriages.

There is a higher incidence of irritable bowel syndrome with miscarriages, and recurrent miscarriages of otherwise normal embryos have been linked to subnormal expression of the immune checkpoint inhibitor CD200L. We sought to determine if alterations in the expression of the CD200 immune checkpoint inhibitor occur in colonic tissue in IBS-D patients. Quantitative immunohistochemical staining of biopsies from proximal and distal colon or rectum for the inhibitory CD200L and CD200S molecules was done. CD56 cells were also enumerated as they play a role in recurrent miscarriages and may express CD200S. CD200L was decreased and CD200S was unchanged in epithelium but not stroma of 3 IBS-D cases. One case had an increase in both CD200L and CD200S. CD56 cells were also stained for CD200S. Degranulation was assessed by the percentage of extracellular CD200S that was increased as epithelial CD200L decreased. This pilot study was promising and warrants a larger sample to determine if a correlation between uterine implantation site CD200L and CD200S expression in normal and failing implantation sites is needed. Colonic epithelial CD200L may then provide useful information about the pathogenesis of the spontaneous miscarriage in individual cases.

Small Cell Carcinoma of Rectum - An Infrequent Aggressive Tumor

We report the case of a 63 year old man with small cell carcinoma of rectum. He presented with occasional rectal bleed, anal verge pain and generalized weakness. Colonoscopy revealed an ulcerated growth in proximal rectum. Endoscopic biopsy revealed poorly differentiated carcinoma. Laparoscopic anterior resection was done and histopathogical examination along with IHC confirmed small cell carcinoma(SCC). Colorectal SCC is a rare and aggressive tumor.

The incidence of early onset colorectal cancer in Aotearoa New Zealand: 2000–2020

BackgroundThe incidence of early-onset colorectal cancer (EOCRC), diagnosed before age 50, has been rising in many countries in the past few decades. This study aims to evaluate this trend in Aotearoa New Zealand and assess its impact on Māori.MethodsCrude incidence and age-standardized incidence of colorectal cancer (CRC) was analyzed from all new cases from the Aotearoa New Zealand national cancer registry for the period 2000–2020. Trends were estimated by sex, ethnicity, age group and location of cancer and projections made to 2040.ResultsBetween 2000 and 2020, there were a total of 56,761 cases of CRC diagnosed in Aotearoa New Zealand, 3,702 of these being EOCRC, with age-standardized incidence decreasing significantly (P = 8.2 × 10− 80) from 61.0 to 47.3 cases per 100,000. EOCRC incidence increased on average by 26% per decade (incidence rate ratio (IRR) 1.26, p = < 0.0001) at all sites (proximal colon, distal colon and rectum), while the incidence in those aged 50–79 years decreased on average by 18% per decade (IRR 0.82, p = < 0.0005), again across all sites. There was no significant average change in CRC incidence in those over 80 years. In Māori, there was no significant change in age-standardized incidence. There was however a significant increase in crude incidence rates (IRR 1.28, p = < 0.0005) driven by significant increases in EOCRC (IRR1.36, p = < 0.0005). By 2040, we predict the incidence of EOCRC will have risen from 8.00 to 14.9 per 100,000 (6.33 to 10.00 per 100,000 in Māori). However, due to the aging population an estimated 43.0% of all CRC cases will be diagnosed in those over 80 years of age (45.9% over 70 years of age in Māori).ConclusionThe age-standardized incidence of CRC from 2000 to 2020 decreased in Aotearoa New Zealand, but not for Māori. The incidence of EOCRC over the same period continues to rise, and at a faster rate in Māori. However, with the ageing of the population in Aotearoa New Zealand, and for Māori, CRC in the elderly will continue to dominate case numbers.

Complete separation of the urinary tract from proximal rectum during PSARP surgery: our experience with the noveltechnique

Complete separation of the urinary tract from proximal rectum during PSARP surgery: our experience with the noveltechnique

Predicting Complete Response after Chemoradiation in Patients with Localized Rectal Cancer.

Current strategies for localized rectal cancer include multimodal approach with neoadjuvant treatments followed by surgery. Some patients may present complete response after chemoradiation (CRT) and possible candidates to nonoperative management. We aim to detect complete-responders only based on the pretreatment radiological information using radiomics. We retrospectively studied 44 randomly selected rectal cancer patients who underwent an MR study for rectal cancer staging and, subsequently, were treated with CRT. Median age was 66 y and 59% were females. Tumors were located in the proximal rectum in 11p, 25p in the middle and 8p in the distal. The initial TNM classification, 38p had T3 stage, 19p N1 and 17p N2. Two patients did not receive chemotherapy. Median dose: 50.4Gy (48-54Gy). One radiologist and one radiation oncologist with expertise in MR manually contoured the primary tumor using Phillips IntelliSpace Portal software. We computed a total of 1688 radiomic features from the T2w images using the pyRadiomics package. We compared several machine learning (ML) classification algorithms (linear regression (LR), gaussian processes (GP), multi-layer perceptron (MLP), support vector machines (SVM), and random forest (RF)), as well as several combinations of classifiers using the scikit-learn python module. We used a stratified 5-fold cross validation approach to assess them. The performance was assessed by calculating the average of the area under the curve (AUC) from receiver operating characteristic (ROC) curve analysis for each one of the k splits generated during cross-validation. Mean accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and F1-score were also computed. Pathological TNM (ypTNM): 22p had ypT0N0, 9p ypT3-4, 10p ypT2 and 9p ypN1. Tumor volume between responders and non-responders were: 26.10±16.24cc vs. 22.78±34.49cc (p = 0.68). Predictions from the classifiers showed good classification capabilities identifying ypT0N0 (i.e., AUC≥0.73±0.17) for all classifiers; however, combined classifiers demonstrated superior capabilities compared to stand-alone classifiers. Specifically, the RF-MLP, RF-GP-SVM, RF-GP-MLP and RF-GP-LR combinations showed the best results with a mean accuracy, sensitivity, specificity, PPV, NPV, and F1-score of 0.80±0.13, 0.90±0.20, 0.72±0.10, 0.71±0.12, 0.92±0.16, 0.79±0.15, with slight differences for AUC CONCLUSION: We trained a series of ML algorithms based on T2w MR imaging radiomic features and evaluated their ability to distinguish responders from non-responders. MR data have a richness of information that allows identifying the response to CRT treatment in a predictive context, especially when using combined classifiers. A validation prospective set to detect ypT0N0 is warranted. Clinical utility should be evaluated.

Common Diagnostic Challenges and Pitfalls in Segmental Colitis Associated with Diverticulosis (SCAD).

Segmental colitis associated with diverticulosis (SCAD) is characterized by inflammation involving the sigmoid inter-diverticular mucosa, sparing the proximal colon and rectum. Due to the heterogeneity of clinical manifestations and endoscopic and histological findings, SCAD diagnosis might be challenging in clinical practice. This narrative review aimed to report the SCAD diagnostic criteria adopted in different studies, highlighting the current challenges and main pitfalls in its diagnosis. We analysed fourteen studies, mainly prospective observational studies. Haematochezia and rectal bleeding were the main complaints leading to diagnosis, followed by diarrhoea. An accurate endoscopic description was performed in 86% of studies, while a standardised biopsy sampling protocol (sigma, proximal colon and rectum) was scarcely adopted, being complete only in 28.5% of studies. The evaluation of concomitant drugs potentially inducing colitis was carried out in only 57% of studies. Great heterogeneity in sigmoid endoscopic (edema, erythema, erosions, ulcers, mucosal friability) and histological findings (chronic and/or acute inflammatory infiltrate) was observed. We showed that SCAD diagnosis is often based on not fully adequate macroscopic colonic description and scant biopsy protocol sampling. An accurate clinical and endoscopic evaluation, with an adequate sampling biopsy protocol, with attention to differential diagnosis, seemed to be crucial for a prompt SCAD diagnosis.

Association of gallstone disease with risk of colorectal cancer: a systematic review and meta-analysis of observational studies.

Numerous studies have assessed the association of gallstones or cholecystectomy (CE) with risk of colorectal cancer (CRC). However, the findings are mixed. To systematically review and meta-analyse the association between the presence of gallstone disease (GD), or CE and the incidence of CRC. Secondary endpoints were the risk based on type of exposure, study design, tumour subsites and sex. PubMed and EMBASE were searched from September 2020 to May 2021. The protocol was registered on the Open Science Foundation Platform. We identified and classified studies according to their design into prospective cohort, population-based case-control, hospital-based case-control and necropsy studies reporting CRC incidence among individuals with diagnosed GD or after CE (or both). Among 2157 retrieved studies, 65 (3%) met the inclusion criteria. We followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines. Data were extracted by two independent reviewers. We evaluated the quality of the study according to the Newcastle-Ottawa Scale and only studies with a score of 6 and above were included in the final analyses. We pooled log-transformed odds ratios/risk ratios from the available adjusted models to estimate a summary relative risk (RR) and 95% confidence interval (CI) in a random-effects model. The primary outcome was overall CRC incidence. We also conducted secondary analyses according to sex and CRC subsites (proximal colon, distal colon and rectum). The outcome was measured by RRs with 95% CIs. The overall association of GD and/or CE with CRC was RR = 1.15 (1.08; 1.24), primarily driven by hospital-based case-control studies [RR = 1.61 (1.29; 2.01)], whereas a more modest association was found in population-based case-control and cohort studies [RR = 1.10 (1.02; 1.19)]. Most hospital-based case-control and necropsy studies reported estimates that were adjusted for age and sex only, leaving room for residual confounding; therefore we restricted to population-based case-control and cohort studies for our subsequent analyses. Similar associations were found for women [RR = 1.21 (1.05; 1.4) and men (RR = 1.24 (1.06; 1.44)]. When assessed by CRC subsites, GD and CE were primarily associated with higher risk of proximal colon cancer [RR = 1.16 (1.07; 1.26)] but not distal colon cancer [RR = 0.99 (0.96; 1.03)] or rectal cancer [RR = 0.94 (0.89; 1.00)]. Gallstones are associated with a modestly increased risk of colon cancer, primarily in the proximal colon.

Abstract 5217: Genome-wide interactions of processed and red meat intake on colorectal cancer risk

Abstract Introduction: Colorectal cancer (CRC) is the third most common cancer, and second cause of cancer death worldwide. High red meat and/or processed meat consumption are established risk factors for CRC. Genome-wide association studies have identified over 200 genetic variants that explain ~20% of the variability in CRC risk. However, few large studies have evaluated genome-wide gene by environment (GxE) interactions with meat in CRC. Using the largest CRC pooled dataset available to date we conducted a genome-wide GxE analysis to identify possible interactions between common variants and red meat and/or processed meat intake and CRC risk. Methods: A pooled sample of 29,912 CRC cases and 39,704 unaffected controls of European (EUR) ancestry from 27 studies was analyzed. Sex- and study-specific quartiles for red meat and processed meat intake were constructed from harmonized questionnaire data on meat consumption. Genotyping arrays were imputated to the Haplotype Reference Consortium. To identify novel CRC interaction loci we used the two-step EDGE method, standard GxE analyses and a 1-3 degrees of freedom (DF) test. We removed previously known GWAS hits and SNPs in high linkage disequilibrium with them. Results: Our Meta-analyses confirmed a positive association between quartile consumption increase of red meat and processed meat with CRC risk (Red meat OR = 1.30; 95%CI = 1.21-1.41; Processed meat OR = 1.40; 95% CI = 1.20 -1.63). Greater magnitude in point estimates were observed for case-control studies compared to cohort studies, for processed meat consumption among men compared to women, and for red meat consumption and distal colon localization compared to proximal colon or rectum. Two DF GxE tests of red meat consumption revealed two SNPs in chromosome (Chr) 8 (rs4871179 &amp; rs75212442) and a SNP in Chr10 (rs117674361) that map downstream HAS2, COLEC10 and downstream CCSER2. In addition, the two-step EDGE GxE method identified the rs35352860 SNP that maps to the SMAD7 gene in Chr18. Genotype-stratified analyses showed that the red meat and CRC risk association was restricted to homozygous carriers of major alleles for rs4871179, rs75212442 &amp; rs117674361. Moreover, we observed dose-response increase in the red meat and CRC risk association with additional copies of the T allele of the SNP in Chr18, with homozygous carriers of the T allele having 46% higher chance of developing CRC associated with high red meat intake; this in contrast to homozygous carriers of the reference C allele, that had an 18% higher risk of developing CRC. No statistically significant GXE interactions with processed meat intake were found. Conclusion: In this large-scale genome-wide GxE analysis we identified interactions between 4 SNPs and red meat consumption affecting CRC risk. The interaction with the SMAD7 rs35352860 SNP provides supportive evidence for a role of heme iron in the carcinogenic pathway of red meat intake in CRC development. Citation Format: Joel Sanchez Mendez, Mariana C. Stern, Andre Kim, John Morrison, Juan P. Lewinger, Li Hsu, Eric Kawaguchi, Ulrike Peters, William J. Gauderman, on behalf of GECCO, CCFR and CORECT. Genome-wide interactions of processed and red meat intake on colorectal cancer risk. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5217.

Abstract 5223: Circulating lipoprotein lipids and colorectal cancer risk: A Mendelian randomization analysis from the GECCO consortium

Abstract Background Conventional observational studies have reported conflicting results regarding the association between low density lipoprotein cholesterol (LDL-C) and risk of colorectal cancer (CRC). We conducted a Mendelian randomization analysis to address this association. Methods Single-nucleotide polymorphisms (SNPs) associated with five blood lipids (total cholesterol, HDL-C, high-density lipoprotein cholesterol [HDL-C], non-HDL-C, and triglyceride) were obtained from a genome-wide association study (GWAS) meta-analysis of European ancestry in the Global Lipids Genetics Consortium (GLGC, N ≤ 1 319 982), and two lipids (apolipoprotein A1 and apolipoprotein B) from a GWAS in the UK Biobank (UKB, N ≤ 441 016). Summary statistics were obtained for these SNPs from a GWAS of CRC in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO) including 34,869 cases and 29,051 controls. Associations with CRC risk per one standard deviation increase in the genetically predicted lipids level were generated using inverse-variance weighted random-effects models. Results No overall association was observed between genetically predicted levels of blood lipids and CRC risk. However, increased risks were observed for all LDL-C related traits among women, including total cholesterol (OR = 1.10; 95%CI = 1.02, 1.18), LDL-C (1.07; 1.00, 1.14), non-HDL-C (1.09; 1.02, 1.16), and apolipoprotein B (1.11; 1.02, 1.21); whereas no significant association was found among men. Similar but ostensibly stronger associations of these traits were seen with distal colon cancer cases, with no significant association showing on proximal colon or rectum cancer cases. We also observed similar positive associations of LDL-C related traits among those having CRC before their 50 years. Of note, risk reduction was found for apolipoprotein A1, a major component of HDL-C, in these early-onset cases (0.87; 0.78, 0.98). Conclusion Results from this study suggest that high circulating LDL-C levels may increase the risk of CRC, particularly cancer of the distal colon, and the association may differ by sex and age at CRC onset. Key words: Blood lipids; colorectal cancer; Mendelian randomization. Citation Format: Lili Liu, Wanqing Wen, Jirong Long, Themistocles L Assimes, Luis Bujanda, Stephen B Gruber, Sébastien Küry, Brigid Lynch, Conghui Qu, Minta Thomas, Emily White, Michael O. Woods, Ulrike Peters, Wei Zheng. Circulating lipoprotein lipids and colorectal cancer risk: A Mendelian randomization analysis from the GECCO consortium. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5223.

Epidemiological and molecular evaluation of BRAF, KRAS, NRAS genes and MSI in the development of colorectal cancer

Background and ObjectivesKRAS, NRAS, BRAF mutations and microsatellite instability (MSI) can be associated with Colorectal Cancer (CRC) development. Material and MethodsWe evaluated 828 medical records of CRC patients from a school hospital from January/2016 to December/2020. Variables such as age, gender, ethnicity, literacy level, smoking, alcoholism, primary anatomical site, tumor staging, presence of BRAFV600E, KRAS, NRAS mutations and MSI , survival and metastasis were identified. The statistical analyses were performed (p < 0.05 was considered significant). ResultsThere was a predominance of males (51.93%), whites (90.70%), low education (72.34%), smokers (73.79%), and non–alcoholics (79.10%). Rectum was the most affected site (42.14%), advanced tumor stage was most prevalent (62.07%), and metastasis occurred in (64.61%). Of the enrolled patients; 204 were investigated for BRAF mutation and detected in (2.94%); 216 for KRAS gene and detected in (26.08%); 210 for NRAS gene, and detected in (25.36%); 370 for MSI and detected in (44.68%). A significant association of CRC with NRAS mutation and alcohol habit (p = 0.043) was observed. The presence of MSI was associated with primary site proximal colon (p < 0.000), distal colon (p = 0.001) and rectum (p = 0.010). ConclusionPatients with CRC are male, over 64 years old, white, with low education, smokers and non-alcoholics. The most affected primary site is rectum in advanced stage with metastasis. CRC is associated with NRAS mutation and alcohol habit, there is increased risk for primary site of proximal colon and MSI; decreased risk for distal colon and rectum in the presence of MSI.

The comparison of risk factors for colorectal neoplasms at different anatomical sites

AimBoth the clinical manifestation and molecular characteristics of colorectal cancer (CRC) vary according to the anatomical site. We explored the risk factors for four groups of colorectal neoplasms (CRN) at different anatomical sites.MethodsWe extracted data from the database of Tianjin Colorectal Cancer Screening Program from 2010 to 2020. According to the CRN anatomical sites, patients were divided into four groups: the proximal colon group, the distal colon group, the rectum group, and the multiple colorectal sites. Binary logistic regression analysis was used to explore the differences in risk factors of CRN at different anatomical sites.ResultsThe numbers of patients with CRN in the proximal colon, distal colon, rectum, and multiple colorectal sites were 4023, 6920, 3657, and 7938, respectively. Male sex was associated with a higher risk from the proximal colon to the rectum. Advanced age and obesity were also significantly associated with overall colorectal CRN risk, but there were some differences between men and women. Smoking was associated with CRN risk only in the distal colon and rectum in both men and women. Frequent alcohol consumption and family history of CRC in first-degree relatives (FDRs) were associated with the risk of multisite colorectal CRN only in males.ConclusionsWe observed differences in advanced age, obesity, smoking, alcohol consumption, and family history of colorectal cancer at different anatomical sites of colorectal neoplasms. These factors vary by gender.

Predictors of Lymph Node Involvement in Rectal Cancer Patients Treated with Neoadjuvant Chemoradiotherapy

<h3>Purpose/Objective(s)</h3> Following neoadjuvant chemoradiotherapy (NART), some rectal cancer patients may have pathologic lymph node involvement (ypN+) despite complete response in the primary tumor, and should not be candidates for non-operative management. The aim of this study was to determine risk factors for ypN+ in rectal cancer patients treated with NART. <h3>Materials/Methods</h3> Data of rectal cancer patients treated with NART followed by surgery were evaluated. Patients with synchronous colon cancer, radiotherapy to surgery interval longer than 13 weeks, and those without lymph node (LN) dissection were excluded from the analysis. 92 patients were included. Median age was 59 (30-83). Female/male ratio was 35/57. Tumor location was proximal, mid- and distal rectum in 3, 45 and 44 patients, respectively. Tumor histology was adenocarcinoma in 79 patients, signet ring cell in 6 and mucinous carcinoma in 7. Clinical T stage was T2, T3 and T4 in 3, 81 and 8 patients, respectively. 90 patients had clinical LNs larger than 4 mm (10-34 mm: n=46). Median tumor and LNs SUV_max were 15 (3.9-46) and 2 (0.5-17.6), respectively. Median tumor GTV was 73 (28.9-370) ml. Median tumor length and thickness were 6 (3-14) cm and 16.5 (7-30) mm, respectively. All patients received 56 Gy to the primary tumor and 50.4 Gy to the lymph node regions, simultaneously in 28 fractions, and concurrent capecitabine. 27 patients had ypN+. Clinical and radiological features at initial presentation were analyzed to predict ypN+ using Chi-square or Mann-Whitney U tests. Logistic regression analysis was performed to determine the factors affecting ypN+. ROC analysis was performed to determine the cutoff values. <h3>Results</h3> Age (p=0.027), tumor SUV_max (p=0.001), largest clinical LN size (p=0.007) and number of LNs ≥10 mm in diameter (p=0.033) were significantly different between ypN0 and ypN+ patients in univariate analysis (Table). Only tumor SUV_max (HR (%95 CI): 0.828 (0.731-0.937), p=0.003) and largest clinical LN size (HR (%95 CI): 1.338 (1.023-1.750), p=0.033) were significant in multivariate analysis. Area under the ROC analysis curve (AUC) to determine ypN+ was 68.8% for LN size and 79.3% for tumor SUV_max. Cutoff values of LN size and tumor SUV_max for ypN+ were 10.5 mm (p=0.005) and 12.57 (p<0.001), respectively. Although ypN+ rates were higher in patients with signet ring cell (83%) and mucinous (43%) histology compared to adeno carcinoma (24%), it was not statistically significant. <h3>Conclusion</h3> Rectal cancer patients with lower tumor SUV_max and larger clinical lymph nodes at initial presentation are more likely to have pathologic lymph node involvement following neoadjuvant chemoradiotherapy.

Prospective Analysis of a Deep Learning Auto-Contouring Model for Definitive Radiation of Localized Prostate Cancer

<h3>Purpose/Objective(s)</h3> To analyze the prospective use of a deep learning auto contouring model for patients with localized prostate cancer with or without insertion of a radiopaque hydrogel spacer. <h3>Materials/Methods</h3> The model was initially trained with patients from an academic center. It was implemented for prospective clinical use at a satellite center by three experienced radiation oncologists. The model auto contours prostate, proximal seminal vesicles (SVs), bladder, rectum, femurs, penile bulb and spacer (when existing). The auto contours (ACs) were reviewed and edited by treating physician. The ACs were compared to the approved planning contours (PCs) for the initial 23 patients to evaluate the extent of physician editing required. Each AC was compared to the final PC by one physician using a qualitative 4-point system: 1 (minor discrepancy with significant efficiency gain), 2 (moderate discrepancy with substantial gain), 3 (significant discrepancy with meaningful gain), and 4 (rejected for gross error or no efficiency gain). A composite score was calculated by averaging the score of each structure. A Turing test was performed to see if the physician can differentiate AC vs. PC. Quantitatively, the geometric differences between each AC and PC were analyzed using Dice similarity coefficient (DSC) and mean distance to agreement (MDA). <h3>Results</h3> As shown in Table 1, the mean score was ≤1.4 for all structures except for SVs, and 1.26 for the composite, indicating overall significant efficiency gain. In 97.8% of cases, the ACs led to an efficiency gain. While the passing rate of the Turing test was not high, the failure was frequently due to very minor differences. The DSC was close to 1 for femurs, bladder and spacer, and >0.9 for prostate and rectum. The MDA was <2 mm for all structures except SVs. All quantitative measures except for the SVs were within the tolerance recommended by AAPM TG 132 (DSC ≥ 0.8, MDA ≤ 3 mm). On average, treating physicians estimated 17 minutes were saved for each patient. <h3>Conclusion</h3> Overall, the model can accurately auto contour targets, organs, and spacer with significant efficiency gain. A majority of ACs qualitatively evaluated by a physician had only mild discrepancies. Quantitative analysis demonstrated ACs for most organs had only minor geometric differences, unlikely to result in any significant dose-volume impact.

V-002 MASSIVE INGUINAL HERNIA REPAIR WITH CHEMICAL COMPONENT RELAXATION AND PREOPERATIVE PROGRESSIVE PNEUMOPERITONEUM

Abstract Inguinal hernias are one of the most common procedures performed worldwide. Conversely, massive or giant inguinal hernias; defined as extending below the midpoint of the inner thigh are very uncommon. They are often associated with loss of domain, posing a different set of challenges for the surgeon, specially creating intra-abdominal space for the displaced organs. Preoperative progressive pneumoperitoneum (PPP) coupled with chemical denervation with botulinum toxin A (BTA) is one way to increase the size of the intrabdominal cavity to aid in reduction of the hernia contents and closure of the defect. We present a case of a 51-year-old male with a massive right inguinal hernia with complete loss of domain. The hernia sac contained the entirety of his small bowel and colon except for his proximal duodenum and distal rectum which remained intrabdominal. We preformed preoperative BTA chemical denervation and progressive pneumoperitoneum prior to staged open Inguinal hernia repair. 1 month preoperatively BTA injections were performed under ultrasound guidance into the external and internal obliques at 3 locations bilaterally and an intraabdominal catheter was placed under laparoscopic guidance. The patient was insufflated with filter air 3 times a week for 3 weeks. He then underwent open repair with preperitoneal mesh placed and orchiectomy.

S2050 Inferior Mesenteric Arteriovenous Fistula Treated with Embolization

Introduction: Inferior mesenteric arteriovenous fistulous malformations are a rare yet reversible cause of ischemic colitis. They can cause increased outflow of blood in the venous circulation and predispose to colon ischemia. We report a case of inferior mesenteric arteriovenous fistula causing ischemic colitis in an atypical distribution in the IMA territory. Case Description/Methods: A 50-year-old gentleman presented to the emergency room with a 3-week history of abdominal pain and bloody diarrhea. His symptoms started with a dull pain, 8/10 in intensity, with radiation to his lower back. He had also been having a low appetite for the duration of his abdominal pain. He described having around 10 bowel movements daily with blood mixed with mucus. CT abdomen showed diffuse circumferential thickening involving the entire sigmoid colon, extending to the upper rectum suggesting non-specific colitis. He came to the hospital 2 weeks prior to his presentation and underwent a colonoscopy which grossly showed diffuse severe inflammation in the distal descending colon, sigmoid colon and proximal rectum, till 30 cm from the anal verge suggesting left-sided colitis. Biopsied from the region showed evidence of ischemic colitis. His CT-angiography showed engorgement of the IMA and IMV, with an early contrast in IMV which suggested IMA to IMV AV fistula within the left hemipelvis. That suggested vascular malformation as the cause of the colorectal findings. Patient subsequently underwent embolization of 2 branches of IMA with stent placement in IMA, causing closure of the AV fistula. Patient tolerated the procedure without any complication (Figure). Discussion: Ischemic colitis is most commonly seen in the watershed areas of the colon such as splenic flexure and rectosigmoid junction due to arterial anastomosis between the mesenteric arteries supplying the colon. In these situations, the colonic involvement is focal involves these specific segments. In this case, patient had diffuse gross ischemic findings from the distal rectum extending to descending colon involving the whole part of ischemic artery supply which is atypical for the distribution of colonic ischemia. In such situations, CT angiography comes as a diagnostic tool for identifying the pathology and in this situation it showed AV fistula between IMA and IMV which hampered the colonic blood supply to the extent to cause ischemic colitis with symptoms.Figure 1.: a. Early filling of dilated mesenteric veins (bottom arrow) with adjacent bowel wall edema due to venous congestion (top arrow) b & c. inferior mesenteric artery (arrows) adjacent to ill-defined area of contrast (dashed arrow) thought to represent arterio-venous fistula d. view from sigmoidoscopy showing ischemic colitis in the sigmoid colon.

S2227 A Rare Case of Primary Diffuse Large B Cell Lymphoma of the Colon

Introduction: Primary colorectal lymphomas are rare and account for 0.3% of all large intestinal malignancies, with Diffuse Large B-Cell Lymphoma (DLBCL) representing the most common subtype. We present a case of primary colonic DLBCL that was diagnosed after surgical resection of the sigmoid colon. Case Description/Methods: An 86-year-old White female with a past medical history of diverticulosis and atrial fibrillation presented to the emergency department complaining of abdominal cramping and rectal bleeding. Physical examination was significant for mild abdominal tenderness and vital signs revealed blood pressure of 151/83 mmHg. Laboratory investigations were significant for white blood cell count of 10.56 x 10^3 cells/uL and potassium 2.8 mmol/L. Abdominal and pelvic computed tomography with contrast revealed sigmoid colonic diverticulosis with interposition of colon between liver and right hemidiaphragm. The patient underwent colonoscopy that showed a stricture of benign intrinsic appearance in the sigmoid colon measuring 10 cm in diameter and 3 cm in length. Histological analysis of tissue biopsies taken at that time were only significant for mild to moderate colitis. After colonoscopy, she was taken for laparoscopic low anterior resection of the sigmoid colonic mass that was later converted to an open approach due to the size of the mass. After the incision was extended, the sigmoid colon was further mobilized and the uninvolved portions of the proximal rectum and descending colon were transected. After the sigmoid colon was removed and sent to pathology, the proximal rectum and descending colon were anastomosed with no air leaks identified. Pathology report of the surgical specimen later showed malignant lymphoma with transmural invasion and involvement of numerous adjacent pericolonic nodes with negative tumor margins. Immunostains revealed the tumor to be positive for BCL-2, BCL-6, CD10, and CD20 but negative for CD3 and BCL-1. High proliferative activity was discerned for KI-67 staining in 90% of tumor cells; all evidence supporting the diagnosis of DLBCL. After an uneventful postoperative period and clinical improvement, the patient was discharged to home for close follow-up. Discussion: Primary colonic lymphomas are rare and usually present with nonspecific symptoms. Although in the case discussed, the patient did not present with any obvious predisposing conditions for DLBCL, further data is necessary to determine other possible associations and develop a standardized treatment regimen.

S1961 Isolated Cardiac Metastasis as an Initial Presentation of Colorectal Cancer in a Young Male Due to Lymphatic Spread

Introduction: Malignant pericardial effusion is common, reported in 5–15% of cancer patients. It most commonly arises from metastasis of lymphomas and tumors of the lung, breast, and, infrequently, the gastrointestinal tract. We report a rare case of metastatic colon cancer without the direct involvement of other solid organs suggesting a lymphatic spread. Case Description/Methods: A 28-year-old man presented with one day of sudden onset of shortness of breath at rest. Vitals were significant for tachycardia. On examination, the lungs were clear to auscultation with distant heart sounds; the abdomen was soft without tenderness. The clinical presentation was suggestive of pericardial effusion. Laboratory studies revealed microcytic anemia with hemoglobin of 11.7 g/dl. CT angiography chest with contrast revealed moderate to large PEff and subsegmental pulmonary embolism. An ECHO showed large PEff, without any signs of tamponade. He underwent video-assisted thoracoscopic surgery for PEff with a pericardial window. The mediastinal lymph node biopsy and pericardial fluid cytology showed metastatic adenocarcinoma cells. A CT scan of the chest/abdomen/pelvis was performed to find the primary malignancy, which revealed a segmental thickening of the proximal ascending colon and ileum with proximal cecal distension, lymphadenopathy, without liver metastasis. A CF showed a large polypoidal mass in the ascending colon, and biopsy revealed poorly differentiated adenocarcinoma in ascending colon. He was started on palliative chemotherapy with capecitabine, oxaliplatin, and bevacizumab and was discharged with outpatient oncology follow-up (Figure). Discussion: Colorectal cancer (CRC) is the third most common cancer in the United States. It primarily spreads hematogenous via the portal venous system that drains the colon and proximal rectum to the liver and the lungs to the heart. However, cardiac metastasis is rare. In our patient, we assume lymphatic spread of colon cancer due to isolated pericardial involvement in the absence of solid organ involvement. To our knowledge, this is the second reported case of lymphatic spread of colon cancer. Therefore, we emphasize considering pericardial effusions as a marker of occult malignancy to facilitate rapid diagnosis and prompt treatment. However, the prognosis for carcinomatous pericarditis is poor, with a 2-5 months median survival.Figure 1.: A-Echocardiogram: Parasternal short axis view showing large pericardial effusion, no signs of cardiac tamponade. B-Colonoscopy showing a lobulated mass in cecum. C-Computed Tomography (C.T.) scan with PO/IV contrast showing mass vs segmental inflammation in proximal ascending colon (pink arrow). Mild thickening of terminal ileum (white arrow).

Rectosigmoid perforations in anorectal malformations with perineal fistulae: The case of contrasting outcomes

Anorectal malformation (ARM) constitutes a wide range of developmental anomalies affecting the distal part of the colon and the urogenital tracts. Rectosigmoid perforation complicating ARM with a perineal fistula discharging meconium and air is extremely uncommon and rarely reported. Here, we report two cases of rectosigmoid perforations in ARM with rectoperineal fistulae who had contrasting outcomes. Two full term male neonates, both with birth weight 3.2kg, Case 1 and case 2, were diagnosed with ARM with rectoperineal fistulae following clinical evaluation on day 2 and 4 of life respectively. There was no clinical suspicion of colonic perforation. Intraoperatively , however, a 5 × 2cm perforation was found extending from the distal colon to the proximal rectum for Case 1 whiles Case 2 had a 7 × 2.5cm rectosigmoid perforation. Both perforations were repaired primarily in single layer and a proximal divided sigmoid colostomy was mounted. Case 1 had an uneventful postoperative recovery and was discharged whereas Case 2 unfortunately died on post-operative day 2. Rectosigmoid perforation complicating ARM with rectoperineal fistula is rare, may be occult and carries significant threat to life. Early presentation, high index of suspicion and prompt surgical intervention are key to a good outcome.

Adherence to the Western, Prudent and Mediterranean Dietary Patterns and Colorectal Cancer Risk: Findings from the Spanish Cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Spain).

The aim of this study was to explore the association between three previously identified dietary patterns (Western, Prudent, and Mediterranean) and colorectal cancer (CRC) risk by sex and cancer subtype. The Spanish cohort of the European Prospective Investigation into Cancer and Nutrition study provided dietary and epidemiological information from 15,629 men and 25,808 women recruited between 1992 and 1996. Among them, 568 CRC cases and 3289 deaths were identified during a median follow-up of 16.98 years. The associations between adherence to the three dietary patterns and CRC risk (overall, by sex, and by tumour location: proximal and distal colon and rectum) were investigated by fitting multivariate Cox proportional hazards regression models stratified by study centre and age. Possible heterogeneity of the effects by sex and follow-up time (1–10 vs. ≥10 years) was also explored. While no clear effect of the Prudent dietary pattern on CRC risk was found, a suggestive detrimental effect of the Western dietary pattern was observed, especially during the first 10 years of follow-up (HR1SD-increase (95% CI): 1.17 (0.99–1.37)), among females (HR1SD-increase (95% CI): 1.31 (1.06–1.61)), and for rectal cancer (HR1SD-increase (95% CI): 1.38 (1.03–1.84)). In addition, high adherence to the Mediterranean pattern seemed to protect against CRC, especially when restricting the analyses to the first 10 years of follow-up (HR1SD-increase (95% CI): 0.84 (0.73–0.98)), among males (HR1SD-increase (95% CI): 0.80 (0.65–0.98)), and specifically against distal colon cancer (HR1SD-increase (95% CI): 0.81 (0.63–1.03)). In conclusion, low adherence to the Western diet and high adherence to the Mediterranean dietary pattern could prevent CRC, especially distal colon and rectal cancer.

Abstract 2316: Malignant potential of colorectal adenoma based on the telomere length

Abstract Telomere attrition is a well-known hallmark of malignancy in cancer tissue. Our study analyzed the relative telomere length in adenomas, precursor lesions of colorectal adenocarcinoma. We investigated if the accelerated telomere length shortening occurs before potential malignant transformation to adenocarcinoma and corresponds with clinicopathological characteristics. Relative telomere length was measured in 145 patients using multiplex qPCR. We have recorded significant shortening of telomeres in the adenoma tissue compared to adjacent mucosa (Wilcoxon Signed Rank test, p &amp;lt; 0.0001). Further, we have observed a weak inverse relationship between both adenoma and mucosa telomere length and age (Spearman's and Pearson's correlation, p = 0.021 and p = 0.027, respectively), contrary to our previous study of colorectal cancer patients (n = 696), where the inverse correlation of telomere length was detected only in the non-malignant mucosa (Pearson's correlation, p = 0.029). However, the telomere length ratio of adenoma to adjacent mucosa did not correspond with the degree of dysplasia according to the Vienna classification (Kruskal-Wallis test, p = 0.572). Also, there was no difference in the telomere length ratio among histological types of adenomas and no association with the adenoma localization in proximal and distal colon or rectum (Kruskal-Wallis test, p = 0.648 and p = 0.459, respectively). Preliminary results indicate that telomere shortening occurs indeed as early as in a stage of adenomatous polyps, and it is less pronounced in adenomas compared to cancerous cells. However, the relative telomere length does not seem to correspond with adenoma progression towards malignancy. In planned experiments, we intend to assess mitochondrial DNA damage caused by 8-oxoguanine DNA adducts. These major oxidative base lesions can arise from endogenous reactive oxygen species and impact, among other things, the integrity of telomeres through double-strand breaks to DNA. Mitochondrial DNA is more prone to accumulation of oxidative damage than nuclear DNA and thus might be useful as an early, additional indicator of the precancerous character of adenoma. The study will reveal whether increased mitochondrial DNA damage and telomere loss are commonly present and linked together in adenomas. This study was supported by the Charles University (project GA UK No. 120, UNCE/MED/006) and the Grant Agency of the Czech Republic (21-04607X, 21-27902S). Citation Format: Kristyna Tomasova, Michal Kroupa, Anna Siskova, Josef Horak, Ondrej Vycital, Vaclav Liska, Ludmila Vodickova, Pavel Vodicka. Malignant potential of colorectal adenoma based on the telomere length [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2316.