Siddharth Mathur

Prescreening with FOBT Improves Yield and Is Cost-Effective in Colorectal Screening in the Elderly

Background. Utilization of colonoscopy for routine colorectal cancer (CRC) screening in the elderly (patients over 75) is controversial. This study was designed to evaluate if using fecal occult blood test (FOBT) to select patients for colonoscopy can improve yield and be a cost- effective approach for the elderly. Methods. Records of 10,908 subjects who had colonoscopy during the study period were reviewed. 1496 (13.7%) were ≥75 years. In 118 of these subjects, a colonoscopy was performed to evaluate a positive FOBT. Outcomes were compared between +FOBT group (F-Group) and the asymptomatic screening group (AS-Group). The cost-effectiveness was also calculated using a median estimated standardized worldwide colonoscopy and FOBT cost (rounded to closest whole numbers) of 1000 US

To twist or not to twist: a case of ERCP in situs inversus totalis.

and 10 US

Colorectal cancer screening in elderly African-American patients

, respectively. Results. 118/1496 (7.9%) colonoscopies were performed for evaluation of +FOBT. 464/1496 (31%) colonoscopies were performed in AS-Group. In F-Group, high risk adenoma detection rate (HR-ADR) was 15.2%, and 11.9% had 1-2 tubular adenomas. In comparison, the control AS-Group had HR-ADR of 19.2% and 17.7% had 1-2 tubular adenomas. In the FOBT+ group, CRC was detected in 5.1% which was significantly higher than the AS-Group in which CRC was detected in 1.7% (P = 0.03). On cost-effectiveness analysis, cost per CRC detected was significantly lower, that is, 19,666 US

S1967 Mass Spectrometry MALDI Imaging and LCMS Identification of Colon Cancer Proteins in Benign Polyps

in F-Group in comparison to AS-Group 58,000 US

894 Outcome Analysis of Colonoscopy in Elderly African American, Hispanic and Asian Americans Above Age 85

(P < 0.05). There were no significant differences in other parameters among groups. Conclusion. Prescreening with FOBT to select elderly for colonoscopy seems to improve the yield and can be a cost-effective CRC screening approach in this subset. The benefit in the risk benefit analysis of screening the elderly appears improved by prescreening with an inexpensive tool.

Tu1410 Does Obesity Have an Impact on Bowel Preparation for Screening Colonoscopy? A Prospective Study Using the Boston Bowel Preparation Score

Family history was signifi cant for prostate cancer. His physical examination was signifi cant for mild epigastric tenderness. Initial laboratory data was signifi cant for hemoglobin of 9.1g/dL and hematocrit of 28.6%. A complete metabolic panel was normal. CT scan revealed metastases in the right cardiac ventricle, bilateral adrenal, left gluteal mass and pancreatic tail. Diff use mesenteric, celiac, external iliac and portal venous adenopathy was seen. Echocardiogram showed a mobile echodensity in the right ventricle. MRI of brain showed no masses. A repeat endoscopy revealed a large non-circumferential, non-pigmented, ulcerated gastric mass with stigmata of recent bleeding. Th e stomach biopsy showed sheets of loosely cohesive malignant polygonal cells consistent with malignant melanoma. HMB-45 and vimentin were positive. Th e patient denied any history of cancerous lesions of the skin. A complete examination of his skin, including oral and anal mucosa, showed no suspicious lesions, and fundoscopic examination of the eye was normal. He was diagnosed with metastatic gastric melanoma with an unknown primary. Unfortunately, patient refused further workup and returned to the correctional facility. Although more than 90% of melanomas have a cutaneous origin, occasionally it is discovered as a metastasis without evidence of a primary site. Th e incidence of metastatic malignant melanoma with an unknown primary (MUP) is 3.2 %. Th e frequently asymptomatic character of MUP explains why it oft en eludes detection. However, symptoms may include gastrointestinal bleeding, abdominal pain, nausea, and anorexia. Diagnosis requires careful inspection of the mucosa for metastatic lesions and biopsy with special immunohistochemical stains (HMB-45 and S100). Th is case is presented in view of its rare occurrence and the diffi culties in its diagnostic course. Early detection and surgical intervention is critical for long term cure, though overall prognosis is poor.

W1465: Colonoscopy for CRC Screening in Asymptomatic Elderly African Americans, Hispanics and Asian Americans

The study by Smoot DT et al. [1] is an interesting study highlighting the outcome of colonoscopy in elderly African-American patients. The study included 922 elderly patients who underwent colonoscopy; the predominance of females in the study, i.e. 67.7% female vs. 32.4% male, is not discussed. Females are known to have lower incidence of colorectal cancer (CRC) [2] irrespective of race, but the study has shown a higher incidence of CRC 29/623 (4.6%) as compared to males 13/299 (4.4%). Further, the patients are classified into average and high risk groups based on indication of colonoscopy. In the high risk group, inclusion of the subjects with a personal history of CRC is likely to affect the results as the recurrence rates of colon cancer are high and variable depending on the stage and treatment of colon cancer. The United States Preventive Services Task Force (USPSTF) recommends against routine screening for CRC in adults 76–85 years of age [3]. The considerations that support CRC screening in an individual patient are not clear. Thus, decision to recommend CRC in this subgroup depends on multiple factors. The study has highlighted certain factors such as blood in stools to have a high predictive value for CRC. There are multiple other factors which have a potential impact on colonoscopy outcomes in elderly. The results of previous colonoscopies definitely affect rescreening decisions [4], but the interval from previous colonoscopy should be considered when making the decision to repeat the examination. Similarly, advance age and co-morbidities have shown to adversely affect bowel preparation. The study by Smoot et al. [1] fails to provide information about the previous colonoscopy results/interval/bowel preparation/completion rates. It has been reported that risk of adverse events increases with age and with specific co-morbid conditions [5]; thus, this factor needs to be taken into account when making a decision. Another approach can be screening of selected individuals with non-invasive tests, such as the immunochemical occult-blood test, which has a fair sensitivity of 60–85% for colon cancer, followed by colonoscopy wherever indicated. As in countries like the United Kingdom, Italy and Norway offering flexible sigmoidoscopy as a screening tool can be considered in this subgroup [6]. The benefits of detecting CRC early is the mainstay of our efforts to offer screening. The outcome of CRC depends on the stage of diagnosis. Co-existing chronic illness is associated with a substantial reduction in life expectancy after diagnosis of early-stage CRC, and also affects the tolerance to various therapies [7]. Thus, elderly patients with multiple co-morbidities and limited life expectancy are unlikely to be treatment candidates and thus have questionable benefit from screening colonoscopy. The information about the co-morbidities and stage of CRC is not included in this study; hence, it is difficult to comment on the impact of diagnosing cancers in the study. S. Singhal (&) Gastroenterology, Department of Internal Medicine, Chicago Medical School at Rosalind Franklin University, North Chicago, IL, USA e-mail: sdsinghal@gmail.com

M1557: Predictors of Positive Outcomes in Repeat Colonoscopy Before Recommended Surveillance Interval

Introduction: Recently soma-wide monoallelic germline epigenetic inactivation of MLH1 has been proposed as a potential mechanism for DNA mismatch repair (MMR) gene inactivation in some individuals with colorectal cancer (CRC). The present study aimed to investigate whether this methylation defect would be limited to the MLH1 promoter, or represents a broader epigenetic defect involving multiple genes. Methods: A 20 year old woman presented with a sigmoid colon cancer, and a negative family history for any cancer. Her tumor was evaluated for DNA mismatch repair (MMR) gene defects, and she was tested for germline mutations in MMR genes. Quantitative pyrosequencing and bisulfite sequencing of cloned PCR products was used to ascertain MLH1 methylation status in all three germ-layers (blood, hair and buccal tissues), as well as in her Epstein-Barr virus (EBV)-transformed lymphoblastoid cells. Genome wide/global methylation status for ~1500 genes/methylation loci was determined in the patients blood and controls (which included both parents, her sibling, and 3 unrelated controls) using Illumina GoldenGate methylation microarrays. Results: The patients tumor showed MSI and loss of expression of MLH1, PMS2 and MSH6 proteins. However, no germline mutations were detected in MLH1, MSH2 or MSH6. A single nucleotide polymorphism (SNP) permitted allele identification; 14%monoallelicMLH1 methylation was found in the tumor, but there was no allelic imbalance at MLH1 in the tumor. MLH1 methylation was observed in the patients blood (10%), EBV transformed lymphocytes (10%), buccal mucosa (22%) and hair follicles (48%). No evidence for MLH1 methylation was present in patients family members or any healthy control (all <1%). Interestingly, MLH1 methylation increased to 24% in the patients blood after 5-FU based chemotherapy treatment. Genome wide methylation analyses showed that aberrant methylation in the blood was not limited to MLH1, but included 43 additional hypermethylated genes (including RUNX3, IGF1, PPARγ and NOTCH4) and another 34 genes which were hypomethylated (including CDK2, STAT5 and IL10). Conclusions: This study reports the youngest patient with soma-wide MLH1 hypermethylation and CRC. The increase in MLH1 methylation following chemotherapy suggests that cells with methylated MLH1 promoters are relatively resistant to the toxic effects of this drug. More importantly, our observation that the epigenetic defects were not restricted to the MLH1 promoter suggests the possibility of a broader epigenetic defect in those individuals with soma-wide methylation of MLH1.