ORIGINAL ARTICLE Gastroenterology & Hepatology http://dx.doi.org/10.3346/jkms.2015.30.9.1288 • J Korean Med Sci 2015; 30: 1288-1294 The Risk of Colorectal Neoplasia in Patients with Gallbladder Diseases Sung Noh Hong,1 Tae Yoon Lee,2 Cholecystectomy is associated with an increased risk of colorectal cancer, but little is and Sung-Cheol Yun3 known about the relationship between gallbladder disease and colorectal adenoma. Gallbladder polyps and colorectal neoplasia (CRN) share several risk factors such as obesity, 1Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of diabetes and metabolic syndrome, which might account for their association. In this study, Medicine, Seoul; 2Department of Internal Medicine, we investigated whether asymptomatic patients with gallbladder disease are at increased Konkuk University Medical Center, Konkuk University risk of CRN and identified the factors to their association. The study population consisted School of Medicine, Seoul; 3Department of Clinical of 4,626 consecutive, asymptomatic individuals drawn from a prospective health check-up Epidemiology and Biostatistics, Asan Medical Center, University of Ulsan College of Medicine, cohort who underwent both ultrasonography and colonoscopy screening. The prevalence Seoul, Korea of CRNs in patients with gallbladder polyps or gallstones was significantly higher than that in the control group (32.1% vs. 26.8%; P = 0.032, 35.8% vs. 26.9%; P = 0.020). A Received: 16 January 2015 multivariate regression analysis showed that gallbladder polyps were an independent risk Accepted: 3 June 2015 factor for CRN [adjusted odds ratio (OR): 1.29; 95% confidence interval (CI); 1.03-1.62] Address for Correspondence: whereas gallstones were not (adjusted OR: 1.14; 95% CI: 0.79-1.63). The adjusted OR for Tae Yoon Lee, MD the risk of CRN was 1.12 for gallbladder polyps < 5 mm (95% CI, 0.85-1.46) and 1.79 for Department of Internal Medicine, Konkuk University School of Medicine, 120-1 Neungdong-ro, Gwangjin-gu, Seoul 143-729, gallbladder polyps ≥ 5 mm (95% CI, 1.15-2.77). The prevalence of CRN increased with Korea increasing polyp size (P trend = 0.022). Our results suggest that colorectal neoplasia is Tel: +82.2-2030-7497, Fax: +82.2-2030-7748 E-mail: [email protected] significantly related to gallbladder polyps, especially those ≥ 5 mm. Funding: This paper was written as part of Konkuk University’s research support program for its faculty on sabbatical leave in Keywords: Gallbladder; Colorectal Neoplasms; Risk Factors; Korea 2013. INTRODUCTION similarities between the epithelium of the gallbladder and that of the colonic mucosa (18). Thus, the aim of our hospital-based Colorectal cancer is potentially preventable if premalignant ad- case-control study was to investigate the prevalence of CRN in enomas are detected and removed during colonoscopy before patients with gallbladder diseases, including gallstone and gall- they become malignant (1, 2). Consequently, the etiologies and bladder polyps, and to identify the predisposing factors for their risk factors of colorectal adenomas have become the focus of association. attention with regard to strategies for the prevention and screen- ing of colorectal cancer. MATERIALS AND METHODS The relationship between cholecystectomy and colorectal cancer has been investigated extensively and their association Study population has been demonstrated (3-7). By contrast, little is known about This cross-sectional study was based on a consecutive series of the relationship between colorectal neoplasia (CRN) including participants in a colonoscopy and ultrasonography-screening adenoma and cancer and gallbladder diseases, such as gallstone program between January 2011 and December 2011 as part of a and gallbladder polyps, in patients with an intact gallbladder health check-up at the Healthcare Center of Konkuk University (8-12). Several studies investigating the association of gallblad- Medical Center in Seoul, Korea. The details of the examination der disease with CRN have suggested a relationship between were described previously (15). Various examination procedures, gallbladder polyps and colorectal adenoma (9), whereas evi- including ultrasonography and colonoscopy, are available at dence of a relationship between gallstones and CRN is conflict- our center. Most of the study participants were examined as ing (8, 10-12). part of an employee health check-up paid for by their compa- The co-occurrence of CRN and gallbladder disease is sug- nies. Others paid for their health screening examinations them- gested by the similar risk factors for gallstones, gallbladder pol- selves. Individuals screened in the health check-up program re- yps, and CRN, including older age, obesity, metabolic syndrome, ceived written information about the screening program, in- glucose intolerance, and hyperlipidemia (13-17), and by the cluding a toll-free telephone number to call to obtain more in- © 2015 The Korean Academy of Medical Sciences. pISSN 1011-8934 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. eISSN 1598-6357 Hong SN, et al. • Colorectal Neoplasia and Gallbladder Disease formation about the program and/or to schedule an appoint- gallbladder wall into the lumen (19). Gallbladder adenomyo- ment for screening. Telephone interviews were conducted by matosis was diagnosed as diffuse or segmental thickening of experienced nurses to establish that the examinees who called the gallbladder wall and by the appearance of anechoic intra- to make an appointment for screening were asymptomatic. In- mural diverticula on ultrasonography (19). Ultrasonography dividuals with symptoms were urged to seek medical care from was conducted as a screening test, not corresponding to any their usual healthcare providers. One week before the check- symptoms or abnormal blood chemistry. up, screening participants received a standard questionnaire that included questions regarding their personal medical histo- Definitions ry (including history of CRNs), present medications, family his- Glucose intolerance was defined as a fasting glucose level of tory (including colorectal cancer in first-degree relatives), and ≥ 100 mg/dL. Diabetes mellitus was defined as a fasting glucose lifestyle habits (including smoking and alcohol consumption). level of ≥ 126 mg/dL. Abdominal obesity was defined as a waist On the day of the health check-up, physical examinations, circumference ≥ 90 cm in males and ≥ 85 cm in females (20). anthropometry, laboratory assays (including serum glucose Hypertriglyceridemia was defined as a fasting triglyceride level and triglyceride levels), imaging studies (including abdominal of ≥ 150 md/dL. ultrasonography), and endoscopies (including colonoscopy) were performed after the patients had fasted for at least 12 hr. Statistical analysis Ultrasound technicians and colonoscopists were not given the Continuous variables are expressed as means ± standard devi- results of each other’s examinations. The examination data were ations, and categorical variables as absolute values and percen- recorded electronically in a centralized digital medical record tages. Differences between continuous variables were analyzed system. At our center, a prospective registry of health check-up using an unpaired Student’s t-test, and those between categori- participants was constructed in January 2010 by data retrieval cal variables using chi-square tests and Fisher’s exact tests, as from the centralized digital medical record system. appropriate. Logistic regression analysis was used to obtain the The exclusion criteria were as follows: (i) incomplete question- odds ratios (OR) and 95% confidence intervals (CIs) of CRN in naire or refusal to answer the questionnaire, (ii) possible symp- screening participants with gallbladder diseases. To examine toms associated with gallbladder disease or CRN (abdominal the potential confounders for CRN, multivariate models were pain, recent changes in bowel habits, or visible rectal bleeding), adjusted for age, sex, smoking, alcohol consumption, family (iii) a history of colorectal polyp or cancers, (iv) a history of color- history of CRC, abdominal obesity, glucose intolerance or type ectal resections, (v) a history of cholecystectomy, (vi) inflamma- II diabetes, and hypertriglyceridemia. A P value less than 0.05 tory bowel disease. was considered to indicate statistical significance. The analyses were performed with SPSS version 18.0 for Windows (SPSS, Chi- Colonoscopy cago, IL, USA). All colonoscopies conducted for screening purposes were high- definition colonoscopies (CF-H260AI, Olympus, Tokyo, Japan; Ethics statement or an EC-3490Fi, Pentax, Tokyo, Japan) performed by eight ex- This study was approved by the institutional review board of perienced endoscopists. Withdrawal times were adjusted to a Konkuk University Medical Center (Protocol No. 1010339). In- minimum of 6 min per colonoscopy to allow for adequate in- formed consent was waived by the board. spection. During colonoscopy, the location, number, and size of any CRNs were recorded. Histologically confirmed adeno- RESULTS carcinomas or adenomas were considered as CRNs. An advanc- ed CRN was defined as an invasive cancer or adenoma that was Characteristics of the study population ≥ 10 mm in