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Oral Contraceptive Use, Hormone Replacement Therapy and Rectal Cancer: APopulation Based Case-Control StudyMillie Long, Christopher Martin, Robert Sandler

Background: Lower incidence rates of rectal cancer in women compared to men supportthe possible protective role of female hormones. It is unknown whether exogenous hormoneshave a differential effect by race. Objectives: To determine the associations between oralcontraceptive (OCP) use, hormone replacement therapy (HRT) and rectal cancer. To deter-mine if the relationship of OCP or HRT use to rectal cancer differs by duration of use. Todetermine if there are differences in these associations by race. Methods: The North CarolinaColon Cancer Study-II is a population-based case-control study of incident rectal [sigmoid,recto-sigmoid or rectal] cancer in African Americans and Caucasians in North Carolinaconducted between 2001-2006. Data on OCP use, HRT use, duration of use, patient demo-graphics and risk factors for rectal cancer were obtained via in-person interviews. Oddsratios and 95% confidence intervals for the association between OCP use and HRT useand rectal cancer were estimated via unconditional logistic regression models. The modelscontained indicator variables for strata of age and race, potential covariates and an offsetterm to adjust for sampling probability. Covariates were eliminated from the model basedon change in beta coefficients. The analyses were repeated comparing quartiles for durationof OCP or HRT use, within strata of race and by site-specific location of the cancer. Results:A total of 443 female cases of rectal cancer and 405 female controls were identified. Everuse of HRT was strongly associated with a reduced incidence of rectal cancer (OR 0.52,95% CI 0.38-0.72). There was significant further reduction of rectal cancer with increasedduration of use [<4 years (OR 0.77 95% CI 0.44-1.35), 4-8 years (OR 0.64 95% CI 0.37-1.10), 9-14 years (OR 0.47 95% CI 0.27-0.81), ≥15 years (OR 0.34 95% CI 0.20-0.58)].Ever use of OCP's was not associated with reduced incidence of rectal cancer (OR 0.95,95% CI 0.67-1.34). Duration of use was not significantly associated with rectal cancer [0-2 years (OR 0.63 95% CI 0.38-1.03), 3-4 years (OR 1.11 95% CI 0.61-2.00), 5-9 years(OR 1.18 95% CI 0.70-2.00), ≥10 years (OR 1.32 95% CI 0.79-2.21)]. There were nodifferences in the effects of OCP's or HRT by race or site specific location of the cancer.Conclusions: HRT is strongly protective for rectal cancer, and this protection significantlyincreases with duration of use. OCP use is not protective for rectal cancer. There are nodifferences in these associations by race. HRT use may be partially responsible for thereduced incidence of rectal cancer in women compared to men.

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Don't Judge a Polyp By Its Appearance: Clinical and Endoscopic Features of aLarge Series of Sessile Serrated AdenomasNnenna Okpara, Harlan G. Rich, Edmond Sabo, Baishali Bhattacharya

Introduction: Sessile serrated adenomas (SSAs) are a newly-recognized group of colonicpolyps which superficially resemble hyperplastic polyps (HPs), but differ in terms of histologicfeatures such as dilated crypts, and serrations extending to the base. SSAs are believed tobe precursors of colorectal carcinomas (CRC) showing microsatellite instability. Thus clinicalrecognition of these polyps is essential. Current knowledge about SSAs has focused onhistopathological and molecular characteristics. Our study is the largest series to date lookingat clinical, demographic, and endoscopic features of SSAs. Methods: Pathology databasesfrom 2 major Rhode Island hospitals were searched between the years 2004 and 2007, and191 SSAs in 163 patients were identified. Clinical and endoscopic parameters were extractedby retrospective review of charts. White light images were available for 88 of the 191 polyps.A subset was analyzed for gross morphologic characteristics. Findings: The most commonindications for colonoscopy were average risk screening (36%), and polyp surveillance (20%).12.2% of patients had a family history of CRC, whereas 3.6 % had a personal history ofprior CRC. There was a slight female predominance - 58% female vs. 42% male. The meanage was 63.2 (SD 12.7, range 24-89). The mean polyp size was 8.9 mm (SD 4.97, range5-34 mm). Majority of the SSAs were right-sided (88%), with 51% in the ascending colon,20% in the cecum, and 17% in the transverse colon. 51 patients (31%) had a SSA as theonly finding. 15 patients (9.2%) had synchronous lesions with advanced features. All polypswere sessile; other descriptive terms included “pale”, “flat”, and “thickened fold”. SSAs weremore likely to be poorly demarcated than both HPs and tubular adenomas (TAs) (OR 2.49,p=0.015), however polyp demarcation did not significantly distinguish SSAs from eitherHPs alone or TAs alone. Color change did not significantly distinguish between the polyps.3.1% of SSAs had foci of high-grade dysplasia or CRC. 9 patients (5.5%) were triaged tosurgery. 2 SSAs could not be endoscopically resected, 3 SSAs had high-grade dysplasia orCRC within them, and 4 patients with SSAs had a synchronous advanced lesion. Conclusion:Sessile serrated adenomas are usually large, right-sided, and associated with a significantrisk of synchronous neoplasia. Endoscopic appearance can not reliably differentiate SSAsfrom other polyp subtypes. Because of the importance of these polyps as potential CRCprecursors, more objective techniques, such as image analysis of surface characteristics,would assist the endoscopist in targeting these lesions for appropriate clinical management.

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Computer-Aided Texture Analysis of the Colonic Polyp Surface Visualized ByEndoscopy As a Novel Method for Distinguishing Sessile Serrated Adenomasfrom Other Histologic TypesEdmond Sabo, Nnenna Okpara, Harlan G. Rich, Baishali Bhattacharya, Murray B. Resnick

Introduction: Sessile serrated adenomas (SSAs) are a newly-recognized group of colonicneoplasms, which superficially resemble hyperplastic polyps (HPs), but histologically differfrom those in respect to the shape and size of the crypts. These polyps are considered tobe precursors of colorectal carcinomas with microsatellite instability as part of the serratedneoplasia pathway. Clinical recognition of these polyps is essential for choosing appropriatetreatment approach. So far, endoscopic features have not been able to clearly distinguishbetween SSAs and other polyps. We used a novel method of computer-aided texture analysisof endoscopic images of these polyps to compare between SSAs, HPs and Tubular Adenomas

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(TAs) of the colon. For this purpose, a variety of textural parameters were extracted fromthe images using a combination multiresolution (wavelets based), multifractal, 2D-Fouriertransformation and pixel co-occurrence based analytic algorithms. Methods: We searchedpathology databases from 2 major Rhode Island hospitals, between 2004 and 2007, andidentified a total of 191 SSAs in 163 patients. White light reflected images were availablefor 88 of the 191 polyps. Of these, image analysis was performed on 62 SSAs, 22 HPs, 32TAs. Results: There was a slight female predominance, 58% female vs 42% male, with amean age of 63.2 (SD 12.7, range 24-89). The mean polyp size was 8.9 mm (SD 4.97,range 5-34 mm). All polyps were grossly sessile. SSAs significantly differed from HPs inrespect to a variety of surface textural parameters such as: wavelets (multiresolution): p=0.02, Hurst parameter (multifractals): p<0.001, Fourier Transform: p<0.0001 and Entropy(pixel co-occurrence): p=0.03. When comparing SSAs with TAs, significant differences werealso found for textural heterogeneity (p=0.013), Clumpiness (p=0.0001) and 2D-Fouriertransform (p=0.014). Hyperplastic polyps mainly differed from TAs in respect to the multif-ractal textural characteristics (Hurst parameter: p<0.0001). Generally, SSAs displayed a moreheterogenous texture than other polyp types. Conclusion: A novel method of computer-aided texture analysis of the polyp surface is presented. Various textural parameters extractedfrom the polyp surfaces were able to accurately distinguish between SSAs and other polyptypes. We believe that this method may help clinicians predict polyp type based on itsendoscopic textural features when screening for diagnosis, and may thus help guide appropri-ate initial management.

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The Characteristics of Small and Diminutive Colorectal Polyps As Seen OnConventional ColonoscopySheetal Sharma, Ashar Ata, Seth Richter

Background: With the rising availability of CT colonography, the clinical significance ofsmall and diminutive polyps will become increasingly important. Previous studies havenoted a significant potential for advanced pathology in small and diminutive polyps. Wesought to evaluate the characteristics of small and diminutive polyps that were removed atthe time of colonoscopy. Methods: A retrospective review of all colonoscopies from September2001 through June 2006 was preformed. Polyp size, pathology, gender, age at time ofcolonoscopy, and location was recorded for each case. Advanced pathology was defined ashigh-grade dysplasia, carcinoma, and polyps with >25% villous component. Proximal colonwas defined as that colon from the cecum to the splenic flexure. Results: A total of 5,788polyps were recorded. Of these 69.1% were diminutive (1-5mm, n=3407), 17.6% weresmall (6-9mm, n=868), and 13.3% were large (>10mm, n=653). The mean age of those inthe study was 58.5+/- 12.3yrs for females, and 57.9+/- 11.1years for males. Of the polypsstudied, 63.8% were noted in males. The distribution of polyps in each size category wassimilar between genders. Advanced Pathology: Of all diminutive and small polyps, 1.89%and 5.89% had advanced pathology. Of those polyps with advanced pathology, 20.3% and17.1% were diminutive and small in size, respectively. There was a similar distribution ofadvanced pathology noted between females and males, 6.33% and 6.93% respectively.Location of distribution: Polyps in the proximal colon comprised of 37.3% diminutive and44.4% of small polyps, the remainder of the polyps were located in the distal colon andrectum. Age and pathology: Polyps in those less than 50 years of age comprised 18% of allpolyps studied. Of the polyps with advanced pathology, 13.8% were in those less than 50years of age. Conclusions: Recent studies have demonstrated a significant rate of advancedpathology in small and diminutive polyps based on conventional colonoscopy. Our resultsshow a significant number of small and diminutive polyps are noted on colonoscopy anda similar distribution of polyps with advanced pathology exists between males and females.In all polyps of small and diminutive size, a significant number contained advanced pathology.We also demonstrate that of those polyps with advanced pathology, 37% are in those polyps<10mm in size. Therefore, small and diminutive polyps contain significant rates of advancedpathology, and their clinical significance must be addressed in the light of recent advances,availability, and detection rates of CT colonography.

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Predictors of Flat Adenomas: Results of Screening Using a High ResolutionColonoscope in a Diverse PopulationJoseph C. Anderson, Benjamin Stein, Charles J. Kahi, Ramona Rajapakse, Zvi A. Alpern

Background: Flat adenomas may account for 1/2 of all adenomas in a Western population(Rex,Gastro 2007). Our goal was to determine the risk factors for flat adenomas in a diversecohort of patients undergoing screening colonoscopy. Methods: We used data from anotherstudy powered to determine risk of obesity for advanced lesions. Using a standard form,weprospectively collected age, gender, height, weight, education, family history of CRC, smokinghistory, meds(NSAID,HRT,insulin, Ca,statin), medical history, alcohol use, exercise/physactivity and a detailed 5 yr dietary history from asymptomatic patients >40 yrs presentingfor screening colonoscopy who consented to our study. One endoscopist using an Olympushigh resolution scope performed all screenings with at least 8 min withdrawal time. Allpolyps were photo-documented next to snare catheter for In-Vivo measurement and retrievedfor histology. Polyp morphology was assessed using the Japanese Research Society Classifica-tion (JRSC). Flat adenoma: exophytic lesion whose height was < 1/2 its diameter. Patientswere divided into 3 smoking categories: 1)Never smoked 2) Heavy exposure: smoking >10 pack yrs and still smoking or quit in past 10 yrs 3) Low exposure: those who smoked< 10 pack yrs or those who quit > 10 yrs ago. Advanced adenoma : large (>1cm) adenoma,villous adenoma, high-grade dysplasia or cancer. Results: 600 patients were screened (351female and 249 male). 51% of the female patients were not Caucasian (30% Hispanic, 12%African descent). Tables 1 show the predictors of flat adenoma detection in males andfemales. Advanced flat adenonas were detected in only 10 women and 5 men(p=0.8). Table2 shows the predictors for advanced lesions in the female patients. Conclusions: Smokingwas a strong predictor of flat adenomas in our population. Since high resolution endoscopymay be the most effective method for detecting flat lesions, these data may have implicationsfor screening smokers. Our data may explain the high prevalence of flat adenomas incountries with high rates of smoking.