Obesity and Adenomatous Polyps of the Sigmoid Colon

The relation between obesity and adenomatous polyps of the sigmoid colon was investigated in male self-defense officials who received a retirement health examination at three hospitals of the Self-Defense Forces in Japan between January 1991 and December 1992. Body mass index (BMI) and waist-hip circumference ratio (WHR) were used as indices of obesity. A total of 228 adenoma cases and 1484 controls with normal sigmoidoscopy were identified in 2228 men: cases having small adenomas (<5 mm in diameter) and those with large adenomas (5 mm or greater) numbered 115 and 102, respectively. Smoking, alcohol use, physical activity, rank, and hospital were controlled for by multiple logistic regression analysis. BMI and WHR were classified into four levels using the 30th, 60th, and 90th percentiles of each distribution in the control as cut-off points. There was a significant two-fold elevation in the overall adenoma risk among men at the highest BMI level (≥26.95) compared with those at the lowest level (<22.48), but the risk did not linearly increase: a similar increase was also noted for large adenomas. While WHR was only weakly related to the overall adenoma risk, the risk of large adenomas progressively increased with increasing levels of WHR: odds ratio (OR) 2.9 (95% confidence interval (CI) 1.4–5.9) for the highest (≥0.958) versus lowest (<0.878) levels. BMI was not materially associated with adenoma risk after additional adjustment for WHR, but a positive association between WHR and large adenomas was independent of BMI: OR 3.4 (95%CI 1.5–7.6) for the highest versus lowest levels. These findings suggest that obesity is associated with an increased risk of colon adenomas, probably with adenoma growth.     

Cigarette Smoking, Alcohol Use and Adenomatous Polyps of the Sigmoid Colon

The relationship of adenomatous polyps of the sigmoid colon with cigarette smoking and alcohol use was investigated in male self-defense officials in Japan. In the comparison between 116 cases and 930 controls, total ethanol intake was not at all associated with the risk of adenomatous polyps, but cigarette smoking was strongly related to adenomatous polyps. After adjustment for total ethanol intake, body mass index and rank, odds ratios (and 95% confidence interval) for the categories of 0, 1–399, 400–799, and 800 or more cigarette-years were 1.0 (referent), 2.3 (1.1–4.6), 2.9 (1.5–5.4) and 3.2 (1.6–6.5), respectively. Among five alcoholic beverages (sake, shochu, beer, whiskey including brandy, and wine), only whiskey consumption was weakly related to the risk of adenomatous polyps. Because the present findings disagree with an earlier observation on self-defense officials, we examined the association with smoking and alcohol use separately for small (<5 mm) and large (≥5 mm) adenomas, combining data from these two studies. Cigarette smoking was more strongly associated with small adenomas while the positive association with certain alcoholic beverages were largely confined to large adenomas. These findings suggest that cigarette smoking and alcohol use may be linked with the development of adenoma at different stages of colon tumorigenesis.     

The Relation of Smoking, Alcohol Use and Obesity to Risk of Sigmoid Colon and Rectal Adenomas

We conducted a case-control study, using 429 cases with histologically confirmed sigmoid adenoma, 75 cases with rectal adenoma, and 3101 controls showing normal colonoscopy at least up to 60 cm from the anus. The subjects were male Self-Defense Forces personnel aged 48–56 who received a retirement health examination including a routine sigmoid- or colonoscopy. Lifestyle characteristics were ascertained by a self-administered questionnaire. Smoking in the recent past (ġ 10 years preceding the colonoscopy) and smoking in the remote past (>10 years before the colonoscopy) were both significantly associated with risk of sigmoid adenoma but not with rectal adenoma as a whole. After reciprocal adjustment for smoking in the two periods, only smoking in the recent past was associated with both sigmoid colon and rectal adenomas. Odds ratios (OR) of sigmoid adenoma (and 95% confidence interval) for the categories of 0, 1-150, 151-250 and ġ251 cigarette-years were 1.0 (reference), 1.9 (1.3-2,8), 2.1 (1.4-3.0) and 3.0 (1.9-4.7), respectively ( P for trend < 0.01), and those for rectal adenoma were 1.0 (reference), 1.2 (0.4-3.2), 3.5 (1.4-8.5) and 2.0 (0.6-6.7), respectively ( P for trend = 0.03). Alcohol use was significantly positively associated with sigmoid adenoma, and insignificantly associated with rectal adenoma. Body mass index was significantly positively associated with sigmoid adenoma, especially large ones. No such association was found for rectal adenoma. These findings suggest that smoking, especially in the recent past, and alcohol use are common risk factors for sigmoid colon and rectal adenomas while obesity may be exclusively related to the growth of sigmoid adenoma.     

Flat Serrated Adenomas of the Colorectal Mucosa

A total of 47 flat serrated neoplasias of the colorectal mucosa are presented: 44 were flat serrated adenomas and the remaining 3 flat serrated adenocarcinomas arising in flat serrated adenomas. These lesions were found among 600 flat mucosal lesions removed at colonoscopy during a 3-year period (1992 and 1994) at the Karolinska Hospital. Thirty-five of the 47 patients (74%) were males and the remaining 12 (26%), females. Depending upon the degree of cellular dysplasia within the epithelium, serrated adenomas were divided into those with low-grade dysplasia (LGD), when the dysplastic nuclei were present in the deeper half of the epithelium, and those with high-grade dysplasia (HGD), when the dysplastic nuclei were found even in the upper half of the epithelium. LGD was present in 37 (84.1%) of the 44 serrated adenomas and HGD in the remaining 7 (15.9%). Depending upon the topographic distribution of the dysplastic epithelium within the crypts, flat serrated adenomas were divided into type I, when the dysplastic epithelium was limited to the lower half of the serrated crypts, and type II, when the dysplastic epithelium was even present in the superficial half of the serrated crypts. Of the 44 serrated adenomas, 38 (86.1%) were type I and the remaining 6 (13.9%) type II. The dysplastic epithelium seemed to originate at the base of the crypts and to progress upwards, replacing the scalloped, serrated epithelium of the sides of the crypts. Invasive adenocarcinomas (i.e., with submucosal extension) were seen to arise from flat serrated adenomas with LGD type I (n=2) or with HGD type II ( n = 1). This preliminary survey suggests that flat serrated adenomas of the colorectal mucosa may be lesions with a propensity to evolve into invasive adenocarcinoma, irrespective of the degree of the epithelial dysplasia or of their extension along the crypts.     

Obesity, Weight Gain and Risk of Colon Adenomas in Japanese Men

Obesity has been related to increased risk of colon cancer or adenomas, but the epidemiologic findings are not entirely consistent. We examined the relation of not only body mass index (BMI) but also waist-to-hip ratio (WHR) and weight gain to colon adenoma risk in men who received a preretirement health examination at the Japan Self Defense Forces (SDF) Fukuoka and Kumamoto Hospitals during the period from 995 to 1996. In the series of 803 men at age 47–55 years, 189 cases of colon adenomas and 226 controls with normal total colonoscopy were identified. Weight at 10 years before was ascertained by referring to the recorded data. After allowance for hospital, rank in the SDF, smoking and alcohol use, weight gain over the past 10 years was significantly associated with increased risk of colon adenomas (odds ratio for ≥ 6 kg versus ≤−2 kg = 2.2; 95% confidence interval 1.0–4.8). High BMI and high WHR were each associated with increased risk, but only WHR was related to the risk independently of weight gain. In particular, weight gain accompanied with a high WHR was associated with a significant increase in the risk. Men with high physical activity tended to have lower risk. Associations with obesity-related variables and physical activity were not materially differential as regards the location and size of adenoma. The findings indicate that weight gain in middle age leading to abdominal obesity increases the risk of colon adenomas, and consequently of colon cancer.     

CEA,rasP21和PCNA在大肠腺瘤癌变中的表达

应用ＣＥＡ、ｒａｓＰ２１和ＰＣＮＡ，通过ＡＢＣ法对２５例大肠腺瘤癌变组织进行了检测。结果显示：ＣＥＡ和Ｐ２１在癌变组织中表达类似，但后者更敏感，对乳头型腺瘤癌变组织表达更强。ＰＣＮＡ在癌变组织中阳性表达很敏感。在管状型和乳头型腺瘤癌变组织中表达类似，并与癌变组织的异型性成正相关。     

Relationship of Ornithine Decarboxylase Activity and Human Colon Tumorigenesis

Ornithine decarboxylase (ODC) activity was determined in tumorouslesions of the human colon, and the possibility of ODC actingas a marker of colon tumorigenesis investigated. In adenoma,ODC activity, in pmoles/h/mg protein, was 164± 82 intumorous tissue, which was higher than the 19.6 ± 10.5in macroscopically normal mucosa (control tissue) around thetumorous tissue, while 8.7 ±4.1 in normal colon mucosa.In carcinoma-in-adenoma and carcinoma, ODC activities in thecontrol tissue were 15.3 ±11.9 and 27.5 ±15.0,respectively. The levels were respectively higher than in normaltissue. These results suggest ODC to be a potential indicatorof colon tumorigenesis.     

Glucose Intolerance, Plasma Insulin Levels, and Colon Adenomas in Japanese Men

Hyperinsulinemia may be related to colon carcinogenesis. Several studies have suggested that diabetes mellitus is related to increased risk of colon cancer. We examined cross-sectionally the relation of fasting plasma insulin levels and glucose tolerance status to colon adenomas. In a consecutive series of 951 men undergoing total colonoscopy for a health examination at the Japan Self Defense Forces Fukuoka Hospital from April 1998 to August 1999, we identified 233 cases of colon adenomas and 497 controls with normal colonoscopy. Glucose tolerance status was determined by a 75-g oral glucose tolerance test, and subjects were classified as normal, unpaired glucose tolerance (IGT) or non-insulin dependent diabetes mellitus (NIDDM). Plasma insulin levels were measured after subjects had fasted overnight. Logistic regression analysis and analysis of covariance was used to control for age and obesity. While plasma insulin levels were unrelated to colon adenomas, NIDDM was associated with a significantly increased risk of colon adenomas. There was no association between IGT and colon adenomas. NIDDM was more strongly associated with proximal colon adenomas. The findings suggest that long-term hyperinsulinemic status associated with NIDDM may increase the risk of colon adenomas, and subsequently of colon cancer.     

Relation of Cigarette Smoking,Alcohol Use,and Dietary Habits to Colon Adenomas: a Case-Control Study in Saitama,Japan

A case-control study of colon adenoma in relation to dietary habits was undertaken in Saitama, Japan. The ‍population included 105 patients with newly diagnosed colon adenoma, 843 general population controls, and 84 ‍hospital controls who had no pathologic lesions at colonoscopy. The adenoma patients and the hospital controls ‍underwent total colonoscopy between November 1992 and March 1994. Information about diet, cigarette smoking ‍and alcohol use were obtained with a self-administered questionnaire. Unconditional logistic regression analysis ‍was used to compare adenoma patients with general population controls and with hospital controls. We found that ‍current cigarette smokers had a higher risk (OR = 2.86, CI = 1.20-6.80) than did nonsmoking hospital controls. ‍Current alcohol use did not affect the risk of colon adenoma. Ex-drinkers had a higher risk (OR = 2.36, CI = 1.02- ‍5.45) than did nondrinking general population controls. The same tendency was observed in comparison with ‍hospital controls. The consumption of raw vegetables was inversely related to the risk of colon adenoma when ‍adenoma patients were compared with general population controls (P for trend = 0.02) or hospital controls (trend ‍P=0.17). Having one bowel movement per day was associated with a lower risk than having less or more frequently ‍bowel movements when adenoma patients were compared with either general population or hospital controls. The ‍present study suggests that the high consumption of raw vegetables is important in the primary prevention of colon ‍adenoma.     

自身配对的锯齿状腺瘤与传统腺瘤临床病理特征的比较

目的探讨锯齿状腺瘤与传统腺瘤的癌变潜能的差异。方法 2007年4月～2009年9月经肠镜检出、并经病理检查证实、同时具有锯齿状腺瘤、管状腺瘤的病例。从腺瘤的临床特征（生长部位、直径大小、蒂部情况及异型增生程度）及免疫组化（β-连环蛋白、P53、Ki67）两个方面,比较两者差异。结果同时具有SA及TA的16例,男性13例,女性3例,年龄43～81岁,平均年龄62.9岁;2种腺瘤的部位分布、异型增生程度及直径大小无显著性差异,无蒂的SA明显多于TA,差异有统计学意义（P〈0.05）;β-连环蛋白、P53、Ki67在2种腺瘤中表达水平无显著差异。结论同1个体的锯齿状腺瘤与传统腺瘤的临床病理特征无显著性差异。     

Diet and Lifestyle Intervention among Patients with Colorectal Adenomas: Rationale and Design of a Malaysian Study

Comprehensive evaluation of the large body of consistent evidence from laboratory, epidemiologic and clinical ‍studies has led to the conclusion that modification of the dietary and lifestyle patterns of populations has considerable ‍potential for reducing cancer risk. This paper describes a randomized-controlled trial involving a diet and lifestyle ‍intervention for patients with history of colorectal adenomas. The primary aim of this trial is to evaluate the ‍effectiveness of the intervention with reference to recurrence of adenomatous polyps over a two year period - the ‍first year being the intervention period and the second year of the study allowing for post-intervention follow-up. ‍Subjects found to fit the inclusion criteria are recruited and randomized to two groups: the intervention group and ‍the control group. The intervention group subjects will attend a monthly lecture-discussion session for 10 months ‍and small group counseling on modification of lifestyle behavior and diet as well as receive educational materials ‍which were adapted from the WCRF Diet and Health Recommendations for Cancer Prevention. Control subjects ‍will be provided with the usual care given to such patients. One hundred and sixteen patients who were diagnosed ‍with colorectal adenomatous polyps in the previous twelve months at the Hospital Kuala Lumpur have already ‍been enrolled in this trial. Baseline data collection is on-going.     

Genetic Alterations of Mixed Hyperplastic Adenomatous Polyps in the Colon and Rectum

Some mixed hyperplastic adenomatous polyps (MHAPs) contain dysplastic lesions or even carcinomas. These polyps are considered to be different from ordinary hyperplastic polyps and may have a preneoplastic potential. We investigated APC and K- ras mutations in MHAPs of the colon and rectum, and also in colorectal adenomas and hyperplastic polyps to identify molecular differences between MHAPs, adenomas and hyperplastic polyps, using direct sequencing of mutation cluster regions (MCR) in APC and K- ras . No APC mutations were identified in 12 MHAPs and 8 hyperplastic polyps, whereas 10 of 27 (37.0%) adenomas showed somatic mutations. K- ras mutations were identified in one of 12 (8.3%) MHAPs, one of 8 (12.5%) hyperplastic polyps, and 10 of 27 (37.0%) adenomas. p53 mutation was found in a carcinoma arising in an MHAP. Mutations other than APC mutations may play a role in the development of MHAPs.     

A Solitary Peutz-Jeghers-type Hamartomatous Polyp of the Rectum: Report of a Case and Review of the Literature

A solitary Peutz-Jeghers-type polyp of the rectum in a 64-year-oldJapanese man is reported. Barium enema and endoscopic examinationrevealed a solitary polypoid lesion in the rectum. The polypwas pedunculated, and measured 2 x 1.5 x 1.5 cm. The patienthad neither mucocutaneous pigmentation nor a family historyof gastrointestinal polyposis. Histopathologically, this polyphad an arborizing muscular network originating from the muscularismucosa, and was covered by well organized mucosa with epithelialhyperplasia. The smooth muscle bundles in the polyp were thickerthan those seen in Peutz-Jeghers syndrome, but their networkwas not as complex.     

结肠癌淋巴转移与病理因素关系探讨

通过对进展期结肠癌１００例淋巴清扫的研究，找出了淋巴转移与病理学因素的关系，并提出了扩大根治手术。本组结果表明：进展期结肠癌各站淋巴转移分别为Ｎ＿１４２％；Ｎ＿２１４％；Ｎ＿３８％；Ｎ＿４１０％。因此，进展期结肠癌应行扩大淋巴清除术，同时应考虑其生物学特性。     

Flat Serrated Adenomas and Flat Tubular Adenomas of the Colorectal Mucosa: Differences in the Pattern of Cell Proliferation

In the present work we have investigated the cell proliferation pattern of flat serrated adenomas and flat tubular adenomas. For this purpose tissue sections from 23 consecutive flat serrated adenomas and 22 consecutive flat tubular adenomas of the colorcctal mucosa were challenged with MID1, a monoclonal antibody directed against a proliferation-related antigen. The results (including semi-quantitative studies) demonstrated that, whereas flat serrated adenomas had a high cell proliferation at the lower part of the crypts, flat tubular adenomas had a high cell proliferation in the upper part of the crypts. In serrated adenomas with invasive adenocarcinoma, high cell proliferation was demonstrated both at the lower portion of the crypts and in the subjacent submucosa. This suggests that the cells of the lower portion of the crypts in serrated adenomas are truely neoplastic, with the capacity to evolve into invasive growth. The difference in cell proliferation betweeen the two types of flat lesions reported here is a new argument in favor of the classification of flat serrated adenomas as a novel and independent type of neoplastic change of the colorectal mucosa.     

Serial Section Study of Colonic Adenomas with Special Reference to Minute Carcinoma

A total of 73 colonic adenomas, 20 with mild atypia, 26 with moderate atypia and 27 with focal carcinoma (severe atypia), were examined by complete serial section in order to find the distribution of various degrees of atypia in adenomas. In serial sections minute carcinomatous foci were found in 3 (15%) and 12 (46.2%) of the adenomas with mild and moderate atypia, respectively. Fourteen adenomas (51.9%) with focal carcinoma had multiple foci of minute carcinoma elsewhere. Adenomas less than 1 cm in diameter showed 27% malignancy rate in serial sections. From this observation it is postulated that the malignant potential of colonic adenomas is much higher than previously believed.     

结肠癌术前血浆纤维蛋白原水平与临床病理特征的关系

目的 探讨结肠癌术前血浆纤维蛋白原与临床病理特征的关系。方法 收集新疆医科大学附属肿瘤医院2005年6月至2008年6月收治的接受根治术治疗的255例结肠癌患者临床病理资料,对其术前纤维蛋白原水平与临床病理特征间的关系进行单因素分析,Logistic回归进行多因素分析。结果 255例结肠癌患者的术前纤维蛋白原为（3.17±0.88）g/L,单因素分析显示年龄、吸烟、肿瘤大小、肿瘤位置、TNM分期、mGPS（modify glasgow prognostic）评分、白细胞计数、NLR（neutrophil/lymphocyte ratio）、PLR（platelet/lymphocyte ratio）及CEA均与纤维蛋白原有相关性,差异具有统计学意义（P<0.05）;而民族、BMI、分级、大体类型、神经/淋巴管浸润、AFP均与纤维蛋白原无相关性（P>0.05）。多因素分析显示白细胞计数（RR=4.08, 95.0%CI:2.07~8.04, P=0.00）和PLR（RR=1.79,95.0%CI:1.02~3.14, P=0.04）与纤维蛋白原具有相关性,差异具有统计学意义（P<0.05）。结论 年龄、吸烟、肿瘤大小、肿瘤位置、TNM分期、mGPS评分、白细胞计数、NLR、PLR及CEA与纤维蛋白原均具有相关性,白细胞计数与PLR可能成为影响纤维蛋白原的独立危险因素;这一发现为降低血清纤维蛋白原以纠正高凝状态、降低炎性微环境提供理论基础。     

Colorectal ornithine decarboxylase activity in human mucosa and tumors: elevation of enzymatic activity in distal mucosa

To examine the value of ornithine decarboxylase (ODC) assay as a biological marker of potential malignancy in large bowel, we harvested 43 colorectal carcinoma, 7 adenoma, 6 polyps, and 77 normal-appearing mucosa at surgery from patients with colorectal carcinoma. In addition, 13 normal rectal mucosa were obtained at biopsy from patients with benign diseases or diseases unrelated to colorectal carcinoma as normal control. ODC activity was significantly higher in polyps and adenocarcinomas than in normal-appearing mucosa from patients with colorectal carcinoma. ODC activity in normal-appearing mucosa varied throughout the large intestine, with significantly higher activities in the distal segment of the large bowel. The higher ODC activity detected in the sigmoid colon and rectum correlates with the larger incidence of tumor development in this region of the large bowel. This observation needs to be taken into consideration when ODC activities of the colorectal mucosa are measured as biological markers of potential malignancies.     

基因异常表达在判断垂体腺瘤侵袭性中的作用

有关垂体腺瘤侵袭性的研究很多,肿瘤相关基因的异常表达揭示垂体腺瘤侵袭性的一个重要方面。癌基因、抑癌基因的表达与垂体腺瘤侵袭性相关。通过对肿瘤相关基因的研究,有助于我们进一步了解垂体腺瘤侵袭性的产生机制,为临床治疗垂体腺瘤提供帮助。