Risk factors for colorectal adenomas among immediate family members of patients with colorectal cancer in Taiwan: a case-control study

OBJECTIVES: The incidence of colorectal cancer or adenoma among first-degree relatives of patients with colorectal cancer is significantly high. However, a well defined screening and surveillance consensus has not been developed for these families in Taiwan. We conducted this study to evaluate the colorectal adenoma prevalence pattern in screened immediate family members in Taiwan, and to derive implications for future screening programs. METHODS: A total of 234 immediate family members (aged 51.6 +/- 21.5 yr) of 186 patients with colorectal cancer were offered a colonoscopy. Each relative examined was then paired with two control subjects for age, sex, and symptoms. The prevalence of colorectal adenomas was then compared using multiple logistic regression analysis. RESULTS: The estimated risk of developing adenomas among immediate family members of patients with colorectal cancer was significantly increased (OR = 2.33; 95% CI, 1.43-3.78; p < 0.001). This trend was more striking for men (OR = 2.46; 95% CI, 1.40-4.31; p = 0.001). Immediate family members were at an increased risk for high-risk adenomas (> or = 1.0 cm, with a villous component, and/or with severe dysplasia) (OR = 4.5; 95% CI, 1.91-10.60; p = 0.002), and developed adenomas at an earlier age than did controls. Individuals with index cancer relatives diagnosed at < 50 yr of age or male relatives posed a higher risk of developing colorectal adenomas. CONCLUSIONS: The prevalence of colorectal adenoma in persons with a colorectal cancer family history in Taiwan is similar to that reported in Western countries. This high-risk population should be offered a screening colonoscopy beginning at 40 yr of age.     

Cancer characteristics in Swedish families fulfilling criteria for hereditary nonpolyposis colorectal cancer

BACKGROUND & AIMS: The present study quantified the prevalence of families that fulfill the Amsterdam or Bethesda criteria for hereditary nonpolyposis colorectal cancer (HNPCC) in the whole Swedish population and investigated the extent to which tumors in the classified families are HNPCC-related. METHODS: The families of the Swedish Family-Cancer Database with at least 4 generations (N = 566,877) were classified according to the Amsterdam and the Bethesda criteria. Survival methods were used to assess the risk of cancer in the classified families, the prognosis of cancer patients, and the risk of subsequent malignancies after colorectal adenomas and after colorectal/endometrial adenocarcinomas. RESULTS: The Bethesda criteria identified 0.9% of all Swedish families and 11.2% of patients with colorectal cancer. Families that fulfilled the Bethesda criteria showed increased risks of cancer in the colorectum, endometrium, small bowel, ovary, stomach, bile ducts, renal pelvis, and ureter; members of Bethesda criteria families were at decreased risks of lung and cervical cancers. The prognosis of cancer in the ureter, renal pelvis, stomach, ovary, and colorectum, but not in the endometrium, was better in Bethesda criteria than in nonclassified families. CONCLUSIONS: Most malignancies in the classified families reflect typical features of HNPCC (association with subsequent malignancies, accelerated adenoma-carcinoma sequence, and better survival). The data presented in this study should help to define surveillance strategies for members of families that fulfill the criteria for HNPCC testing.     

The role of high-magnification-chromoscopic colonoscopy in hereditary nonpolyposis colorectal cancer screening: a prospective "back-to-back" endoscopic study

BACKGROUND: In hereditary nonpolyposis colorectal cancer flat and diminutive adenomas occur, particularly in the right colon. Such lesions may assume a high risk of malignant transformation. Interval cancers are known to occur in this group. Chromoscopic colonoscopy enhances detection in patients assuming a moderate to high lifetime risk of colorectal cancer. AIM: To prospectively assess the efficacy of high-magnification-chromoscopic colonoscopy for the detection of neoplastic lesions in patients undergoing hereditary nonpolyposis colorectal cancer screening. METHODS: Twenty-five asymptomatic patients fulfilling modified Amsterdam criteria underwent "back-to-back" colonoscopy. Conventional colonoscopy with targeted chromoscopy was performed initially followed by pan-colonic chromoscopic colonoscopy. Diagnostic extubation times and volumes of normal saline and indigo carmine (IC) were controlled. RESULTS: Using conventional colonoscopy and targeted chromoscopy 24 lesions were detected in 13 patients (20 exophytic/4 flat). Pan-colonic chromoscopy identified a further 52 lesions in 16 patients (17 exophytic/35 flat). Pan-chromoscopy identified significantly more adenomas than conventional colonoscopy (p= 0.001) and a significantly high number of flat adenomas (p= 0.004). CONCLUSIONS: Pan-colonic chromoscopic colonoscopy improves detection of significant neoplastic lesions in hereditary nonpolyposis colorectal cancer screening. Pan-chromoscopy may help better stratify colorectal cancer "risk" in this cohort and aid planning of surveillance colonoscopic follow-up.     

Hereditary non-polyposis colorectal cancer: clinical and molecular evidence for a new entity of hereditary colorectal cancer

BACKGROUND: Hereditary non-polyposis colorectal cancer (HNPCC) is clinically defined by familial clustering of colorectal cancer and other associated tumours. METHODS: By thorough molecular and clinical evaluation of 41 families, two different groups were characterised: group 1, 25 families with truncating mutations in MLH1 or MSH2 (12 novel mutations); and group 2, 16 Amsterdam positive families without mutations in these genes and without microsatellite instability in their corresponding tumours. RESULTS: Significant clinical differences between these two groups were found. Firstly, earlier age of onset for all colorectal cancers (median 41 v 55 years; p < 0.001) and all tumours (median 43 v 56 years; p = 0.022) was observed, comparing groups 1 and 2. Secondly, 68% of the index colorectal cancers were localised proximally of the splenic flexure in group 1 compared with 14% in group 2 (p < 0.010). Thirdly, more synchronous and metachronous colorectal (p = 0.017) and extracolorectal tumours (p < 0.001) were found in group 1. Fourthly, a higher colorectal adenoma/carcinoma ratio (p = 0.030) and a tendency towards more synchronous or metachronous adenomas in group 2 (p = 0.084) was observed, indicating a slower progression of adenomas to carcinomas. As three mutation negative tumours revealed chromosomal instability after comparative genomic hybridisation, these tumours may be caused by one or more highly penetrant disease alleles from the chromosomal instability pathway. CONCLUSION: These data show that HNPCC includes at least two entities with clinical and molecular differences. This will have implications for surveillance programmes and for cancer research.     

Controlled 15-year trial on screening for colorectal cancer in families with hereditary nonpolyposis colorectal cancer

BACKGROUND & AIMS: Identification of the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome enables prevention of colorectal cancer (CRC) by means of colonoscopy and polypectomies. We evaluated the efficacy of screening in a controlled trial over 15 years. METHODS: Incidence of CRC and survival were compared in 2 cohorts of at-risk members of 22 families with HNPCC. Colonic screening at 3-year intervals was arranged for 133 subjects; 119 control subjects had no screening. Genetic testing was offered to subjects in whose families the causative mutation was known. RESULTS: CRC developed in 8 screened subjects (6%) compared with 19 control subjects (16 %; P = 0.014). The CRC rate was reduced by 62%. In mutation-positive subjects alone, the CRC rates were 18% in screened subjects and 41% in controls (P = 0.02). The decrease resulted from the removal of adenomas in 13 mutation-positive individuals (30%) and in 6 subjects with unknown mutation status (40%). All CRCs in the study group were local, causing no deaths, compared with 9 deaths caused by CRC in the controls. The overall death rates were 10 vs. 26 subjects in the study and control groups (P = 0.003), 4 vs. 12 in mutation-positive subjects (P = 0.05). CONCLUSIONS: Colonoscopic screening at 3-year intervals more than halves the risk of CRC, prevents CRC deaths, and decreases overall mortality by about 65% in HNPCC families.     

Risk of colorectal adenomas in patients with a family history of colorectal cancer: some implications for screening programmes.

BACKGROUND AND AIMS: Most colorectal cancers (CRC) arise in colorectal adenomas. A case-control study was conducted to see whether a family history of CRC is associated with a higher prevalence of colorectal adenomas. SUBJECTS: Subjects were drawn from all patients who underwent colonoscopy at the Royal Brisbane Hospital between 1980-1982 and 1985, and included 141 cases with colorectal adenomas diagnosed at colonoscopy and 882 controls who were free of polyps at colonoscopy. METHODS: The prevalence of family history of CRC was compared between patients with adenomas and negative colonoscopy controls. RESULTS: Overall, patients with one first degree relative with CRC were at no greater risk for adenomas at colonoscopy than patients with no family history (odds ratio (OR) = 0.8, 95% confidence intervals (CI) = 0.4, 1.5). Patients with two or more affected first degree relatives had a more than doubled risk for adenomas (OR = 2.3, 95% CI = 0.5, 8.2), and were also more likely to carry moderately or severely dysplastic adenomas (OR = 14.1, 95% CI = 2.0, 62.9). CONCLUSIONS: These findings are consistent with the hypothesis that some families, in addition to those with familial adenomatous polyposis, have an increased susceptibility to develop colorectal adenomas, and that adenomas in such families may have a greater tendency to undergo malignant transformation.     

Increased prevalence of colorectal adenomas in women with breast cancer

BACKGROUND: The frequency of colorectal adenomas and carcinomas was investigated in a large cohort of women with breast cancer in comparison with matched controls, since data on the occurrence of second tumors in women with breast cancer is controversial. DESIGN: In a cohort study, 188 consecutive women (median age 57 years) with primary breast cancer and 376 age-matched women who served as controls were examined by total colonoscopy. Breast cancer patients and controls were compared for the frequency of colorectal adenomas and carcinomas. RESULTS: Women with breast cancer showed a higher risk of colorectal adenomas than controls (14.9 vs. 9.3%, p=0.047, OR 1.7, 95% CI 1.0-2.9). This increased prevalence resulted primarily from an increased prevalence in the age group 65-85 (31 vs. 10%, p=0.004, OR 3.8, 95% CI 1.6-9.3). Colorectal carcinomas were found infrequently in both groups (2 in each group). Women with breast cancer receiving anti-estrogen therapy showed a trend towards a lower risk of adenomas compared to women without anti-estrogen therapy (3.7 vs. 17.2%, p=0.053, OR 0.16, 95% CI 0.0-1.1). CONCLUSIONS: Women with breast cancer above the age of 65 years have an increased risk of colorectal adenomas compared to women without breast cancer. Women with a diagnosis of breast cancer should especially be encouraged to participate in colorectal cancer-screening programs which, in most countries, call for screening of all average-risk individuals over the age of 50 years.     

Incidence and recurrence rates of colorectal adenomas in first-degree asymptomatic relatives of patients with colon cancer

OBJECTIVES: Subjects with one first-degree relative affected with colorectal cancer are considered to be at increased risk of colorectal adenomas. We compared the recurrence and incidence rates of colorectal adenomas among subjects with one first-degree relative with colorectal cancer and those without family history. METHODS: A series of consecutive asymptomatic subjects successfully underwent a colonoscopy, were found to have either normal results or at least one adenoma, provided a detailed family history, and were offered a second colonoscopy 3 yr later; 190 out of 436 subjects accepted, 134/172 with one or more adenomas and 56/264 with no abnormalities at the initial examination. A first-degree family history was reported by 43/134 and 26/56, respectively. RESULTS: By multivariate analysis, the presence of adenomas at follow-up examination was significantly associated with a positive family history of colorectal cancer in both subgroups, those with a previously resected adenoma (odds ratio = 2.23, 95% CI = 1.04-4.79) and those without (odds ratio = 8.95, CI = 1.29-62.22). CONCLUSION: A history of one first-degree relative with colorectal cancer is associated with a significant increase in 3-yr cumulative incidence and recurrence rates of adenomas.     

Colonoscopy surveillance of individuals at risk of familial colorectal cancer

BACKGROUND: Individuals with first degree relatives affected with colorectal cancer (CRC) at a young age, or more than one relative affected but who do not fulfil the Amsterdam criteria for a diagnosis of hereditary non-polyposis colon cancer (HNPCC), are believed to be at an increased risk of CRC. However, there is a paucity of prospective data on the potential benefit of colonoscopic surveillance in such groups categorised by empiric family history criteria. We report a prospective study of 448 individuals seeking counselling about their perceived family history of CRC. PATIENTS AND METHODS: Following pedigree tracing, verification, and risk assignment by genetic counsellors, colonoscopy was undertaken for those at a moderate or high risk (HNPCC). Those classified as low risk were reassured and discharged without surveillance. Here we report our findings at the prevalence screen in the 176 patients of the 448 assessed who underwent colonoscopy. RESULTS: Fifty three individuals had a family history that met Amsterdam criteria (median age 43 years) and 123 individuals were classed as moderate risk (median age 43 years). No cancers were detected at colonoscopy in any group. Four individuals (8% (95% confidence limits (CL) 0.4-15%)) in the high risk group had an adenoma detected at a median age of 46 years and all four were less than 50 years of age. Five (4% (95% CL 0.6- 8%)) of the moderate risk individuals had an adenoma at a median age of 54 years, two of whom were less than 50 years of age. CONCLUSIONS: These findings indicate that the prevalence of significant neoplasia in groups defined by family history is low, particularly in younger age groups. These prospective data call into question the value of colonoscopy before the age of 50 years in moderate risk individuals.     

A screening clinic for relatives of patients with colorectal cancer in a district general hospital.

A family cancer screening clinic was set up to screen and counsel subjects at above average risk of developing colorectal cancer. Criteria for referral were one first degree relative under 50 years or two of any age with colorectal cancer. Pedigree information was used to estimate lifetime risks of developing colorectal cancer and offer appropriate screening: colonoscopy for high risks (greater than 1 in 10), faecal occult blood testing for lower risks. One hundred and eleven subjects from 76 families were seen over four years. Forty two families gave a pedigree consistent with dominantly inherited non-polyposis colorectal cancer syndrome (HNPCC). Three subjects from one family were found to have familial adenomatous polyposis. Ninety two colonoscopies yielded 21 patients with polyps (12 had tubular adenomas, including one with early malignant invasion). Thirty three per cent (four of 12) of the tubular adenomas were beyond the reach of a flexible sigmoidoscope. Three hundred and forty two further high risk relatives were identified from the family history.     

Prevention of colorectal cancer by colonoscopic surveillance in families with hereditary colorectal cancer

OBJECTIVE: In recent years persons at risk for colorectal cancers (CRC) have been subjected to follow-up with colonoscopy in many centres. There is, however, limited knowledge about the effect of such interventions. The objective of this study was to report the results of our observations during the past 15 years. MATERIAL AND METHODS: Healthy persons were included in the study according to their family history of CRCs, and prospectively followed with colonoscopies. RESULTS: Altogether, 1133 individuals were included and observed for a total of 3474 follow-up years from the first to the last colonoscopy initiated by our activity. Mismatch repair (MMR) mutations were detected in 6.5% of cases. A total of 1383 polyps were removed, 72% were less than 5 mm in diameter. Findings were scored as hyperplastic polyps (n=887), adenomas with mild to moderate dysplasia (n=460), adenomas with high-grade dysplasia (n=30) and cancers (n=6). Two cancers were observed after the first colonoscopy, compared with 2.6 expected by chance and more than 20 expected under the hypothesis of predominant inherited diseases in the families. Observed annual incidence rates for adenomas were similar in all groups, while in the mutation carriers there was a higher frequency of progression to severe dysplasia or infiltrating cancer. CONCLUSIONS: A simple explanation for the combined findings may be that all selected families had a similar tendency to produce adenomas, while mutation carriers more frequently demonstrated dysplasia/cancer in the adenomas. The low annual incidence rates for CRC indicated that the removal of adenomas may have prevented cancers.     

Prevalence of adenomas among young individuals at average risk for colorectal cancer

OBJECTIVES: We evaluated the prevalence and characteristics of adenomas in a young population not genetically predisposed for the development of colorectal cancer (CRC). METHODS: The databases of the Dutch Hereditary Colorectal Cancer Registry were used. The study population included patients (n = 444) who had regular endoscopy until mutation analysis revealed they did not carry the (Adenomatous Polyposis Coli (APC)/Mismatch Repair) gene defect identified in their family. RESULTS: At first colonoscopy (n = 342; 50% males, mean age 37 yr) a total of 19 adenomas (10 males, mean age 50 yr, range 24-91 yr) and two CRCs (2 males, age 49 and 72 yr) were identified, and at first sigmoidoscopy (n = 102; 53% males, mean age 29 yr) three adenomas (2 males, age 8, 40, and 41 yr) were found. A second colonoscopy was performed in 14 patients with, and in 162 patients without an adenoma. Three of 14 patients (21%) developed a new adenoma (all >50 yr) and 8 of 162 (5%) patients developed their first adenoma during follow-up. In the colonoscopy group, the cumulative proportion of patients free of adenomas at age 50 yr was 86%. Of all adenomas diagnosed during colonoscopy (n = 49), 65% were located distal from the flexura lienalis. Of the adenomas detected during all endoscopies (n = 53), 9.8% were > or =7 mm, 7.5% showed high-grade dysplasia, and 7.5% showed tubulovillous features. CONCLUSIONS: On the basis of our findings during colonoscopy we conclude that the risk of developing adenomas/CRC in young individuals without genetic risk factors is low. Adenoma surveillance programs should focus on young individuals with a positive family (or personal) history for adenomas/CRC, or on individuals >50 yr.     

Prospective results of surveillance colonoscopy in dominant familial colorectal cancer with and without Lynch syndrome

BACKGROUND & AIMS: Lynch syndrome is an autosomal dominant predisposition to colorectal cancer caused by mutations in DNA mismatch repair genes; colorectal cancer risk is high. Few studies have addressed colorectal cancer risk in individuals from dominant families without mismatch repair deficiency. We sought to establish whether these individuals are also at increased risk by examining the incidence of advanced neoplasia during surveillance. METHODS: In this prospective cohort study, BAT26 testing of tumors was carried out at 2 tertiary centers on 125 individuals from 97 families (with a dominant colorectal cancer history) to classify families as Lynch syndrome (microsatellite unstable) or non-Lynch syndrome (microsatellite stable). Colonoscopy results in 288 at-risk family members were compared. RESULTS: Twenty-nine families were classified as Lynch syndrome and 68 as non-Lynch syndrome. Seven hundred seventy-six colonoscopies were undertaken. High-risk adenomas occurred in 7 of 91 (7.7%) Lynch syndrome individuals and 15 of 197 (7.6%) non-Lynch syndrome individuals, adjusted relative risk 1.15 (95% CI: 0.6-2.3). Cancer was observed only in Lynch syndrome individuals (4/91; 4.4%), Fisher exact test, P = .010. Multiple adenomas were only seen in non-Lynch syndrome individuals (13/197; 6.6%), Fisher exact text, P = .06. CONCLUSIONS: Individuals with an autosomal dominant family history of colorectal cancer with and without evidence of Lynch syndrome are at equal risk of high-risk adenomas during surveillance, but colorectal cancer was only seen in Lynch syndrome. Therefore non-Lynch syndrome individuals do require colonoscopic surveillance, but the interval could be lengthened because risk of (interval) cancer is low. Lynch syndrome individuals require short surveillance intervals as is the recommended practice.     

符合Amsterdam标准的结肠肿瘤患者异时结直肠肿瘤发病风险研究

目的探讨符合Amsterdam标准的结肠肿瘤患者术后异时结直肠癌及高危腺瘤的发病风险及对生存的影响。 方法回顾分析南京医科大学附属江苏省肿瘤医院收治的34例符合Amsterdam标准的结肠肿瘤患者术后生存与异时结直肠肿瘤发病的随访资料。 结果6例患者接受了结肠全切除治疗,中位随访122个月,无异时结直肠肿瘤发生。28例患者接受了结肠部分切除治疗,中位随访82个月,10例发生了异时结直肠癌,1例发生了需要手术切除的异时结肠腺瘤。结肠部分切除组5年和10年累计异时结直肠肿瘤发病风险分别为24.1%和48.2%,与结肠全切除组相比差异具有统计学意义（P=0.047）。全组总体5年和10年生存率分别为100%和85.6%。结肠部分切除组与结肠全切除组总体生存率差异无统计学意义（P=0.306）。发生异时结直肠肿瘤的患者与没有发生异时结直肠肿瘤的患者相比,总体生存率差异无统计学意义（P=0.901）。结肠部分切除后患者性别、年龄、既往结直肠癌手术史、肿瘤部位、分化程度和分期与异时结直肠肿瘤的发病风险均无显著相关关系。 结论符合Amsterdam标准的结肠肿瘤患者术后发生异时结直肠肿瘤的风险相当高,与结肠部分切除相比,结肠全切除治疗有助于预防异时结直肠肿瘤,但不能显著改善总体生存率。     

Immunological fecal occult blood test vs. serum ferritin for detection of colorectal neoplasia in high risk asymptomatic population

Introduction: Fecal occult blood tests (FOBT) (biochemical or immunological) are based on the fact that most of the polyps or cancers bleed. Anemia due to iron deficiency is a wellknown sign for colorectal cancer (CRC). Ferritin is frequently used to select candidates for colonoscopy. Objective: To determine and compare the diagnostic value of immunological fecal occult blood test vs. ferritin for the detection of colorectal neoplasia (cancer or polyps) in high-risk patients. Methods: A transversal prospective study at National Cancer Institute, Mexico City, in consecutive asymptomatic subjects at high risk for CRC was performed, comparing two tests (immunological against serum ferritin) with colonoscopy plus histopathology. Both tests were performed in a blindly fashion previous to colonoscopy. Results: Fifty patients were included in the study; twenty-eight patients had colorectal neoplasia (21 CRC, 7 adenomas). All immunologic tests for fecaloccult blood were positive in patients with colorectal lesions (sensitivity, 98%). There was no difference between the mean ferritin levels in patients with CRC or adenomas vs. those with negative colonoscopy (p = 0.58). The cutoff point where significant relationship between serum ferritin levels and colon lesions was established was ?46 ng/mL. In anemic patients with serum ferritin levels <46 ng/mL, the test had a sensitivity 53%, specificity 86%, positive predictive value 83%, and negative predictive value of 59% (p = 0.003). Conclusions: The immunological FOBT is a better diagnostic tool than serum ferritin for screening of colonic neoplasms.     

Clinical identification and long-term surveillance of 22 hereditary non-polyposis colon cancer Italian families

OBJECTIVE: To assess the efficacy of a hereditary non-polyposis colon cancer (HNPCC) identification and surveillance policy. METHODS: Familial clustering of colorectal cancer (CRC) and extracolonic cancers (ECs) was investigated in 1520 consecutive CRC patients and relatives. HNPCC was identified by Amsterdam criteria, and individuals at risk were offered biennial colonoscopy and other examinations, starting from age 25 years. RESULTS: Twenty-two HNPCC families were identified. The CRC prevalence was 27.8% (121/435), decreasing from 59.4% in the first generation to 24.4% and 8% in the second and third generation, respectively. Twenty-nine patients had multiple CRC and 34 patients (in 12 families) had ECs.A total of 199/331 at-risk individuals accepted surveillance. The mean follow-up was 48+/-32 months. CRCs were detected at first surveillance in four out of 199 surveilled individuals (2%); in two surveilled individuals (1%), three CRCs developed during follow-up. The overall CRC incidence was 7/199 (3.5%) in surveilled individuals and 5/132 (3.7%) in unsurveilled individuals. CRCs were less advanced in surveilled than in unsurveilled patients. Eleven individuals had 22 adenomas (one with high-grade dysplasia). Three individuals had adenomas at first surveillance; two of them and eight more individuals during surveillance. Seven surveilled individuals and six unsurveilled individuals, all belonging to families with a history of EC, had EC during the study period.All patients with CRC detected by surveillance are alive. One of the unsurveilled patients who had CRC died 18 months after the diagnosis. CONCLUSIONS: Data confirm the importance of the family history collected in each patient with CRC for identification of HNPCC and support the efficacy of repeated colonoscopies for early diagnosis and prevention of CRC in at-risk members. Reasons for surveillance failure could be an accelerated progression of small adenomas and a lesion missing at colonoscopy. Longer follow-up is required to assess the efficacy of surveillance for EC.     

Use of flexible sigmoidoscopy to screen for colorectal cancer in HIV-infected patients 50 years of age and older

BACKGROUND: Although many patients with human immunodeficiency virus (HIV) infection are now living well beyond 50 years of age, there are no data available on colorectal cancer screening in this population. The aim of this study was to determine the utility of screening flexible sigmoidoscopy in patients with HIV. METHODS: Consecutive patients at average risk for colorectal cancer who were referred for screening flexible sigmoidoscopy were prospectively identified. A detailed medical history was obtained from all patients before flexible sigmoidoscopy, and colonoscopy was recommended for all subjects with positive sigmoidoscopic findings. RESULTS: A total of 2382 patients were enrolled in the study; 165 were HIV positive. The prevalence of neoplastic lesions (adenomas or adenocarcinomas) in the distal colon was significantly higher in HIV-infected patients than in control subjects (25.5% vs 13.1%, P<.001), and the odds of HIV-infected patients having a neoplastic lesion was significantly higher even after adjustment for potential confounding variables (odds ratio, 2.34; 95% confidence interval, 1.60-3.44). The prevalence of adenomas of any size (25.5% vs 12.9%, P<.001) and advanced neoplasia (7.3% vs 3.8%, P = .03) in the distal colon was significantly higher in HIV-infected patients. Among individuals with positive results on flexible sigmoidoscopy, proximal colonic neoplastic lesions on follow-up colonoscopy were more common in HIV-infected patients after adjustment for age, sex, and race/ethnicity (odds ratio, 1.88; 95% confidence interval, 1.02-3.46). CONCLUSIONS: Patients infected with HIV are more likely to have colonic neoplasms on screening flexible sigmoidoscopy than those without HIV, and these individuals should be offered colorectal cancer screening.     

First-degree relatives of patients with advanced colorectal adenomas have an increased prevalence of colorectal cancer.

BACKGROUND & AIMS: The risk of colorectal cancer in relatives of patients with adenomatous colonic polyps is not well defined. This study assessed whether finding colonic neoplasia during screening colonoscopy was related to the family history of colorectal cancer among the participants' parents and siblings. METHODS: Self-reported family history of colorectal cancer was recorded for all participants in a screening colonoscopy study. The size and location of all polyps were recorded before their removal and histologic examination. Participants were grouped according to the most advanced lesion detected. RESULTS: Three thousand one hundred twenty-one patients underwent complete colonoscopic examination. Subjects with adenomas were more likely to have a family history of colorectal cancer than were subjects without polyps (odds ratio [OR], 1.36; 95% confidence interval [CI], 1.09-1.70). The finding of a small (<1 cm) tubular adenoma as the most advanced lesion was associated with only a modest increase in the OR of colorectal cancer in family members (OR, 1.26; 95% CI, 0.99-1.61), but the presence of an advanced adenoma was associated with a higher OR (OR, 1.62;5% CI, 1.16-2.26). Younger age of adenoma diagnosis was not related to a higher prevalence of a family history of colorectal cancer. CONCLUSIONS: Relatives patients with advanced colorectal adenomas have an increased risk of colorectal cancer. Individuals with advanced colorectal adenomas should be counseled about the increased risk of colorectal cancer among their relatives.     

Suspected hereditary nonpolyposis colorectal cancer

PURPOSE: The aim of this study was to determine the frequency of mutations in the mismatch repair genes in families suspected of having hereditary nonpolyposis colorectal cancer. METHODS: We devised two criteria for families suspected of having hereditary nonpolyposis colorectal cancer (Criteria I and II). Criteria I consist of at least two first-degree relatives affected with colorectal cancer with at least one of the following: development of multiple colorectal tumors including adenomatous polyp, at least one colorectal cancer case diagnosed before the age of 50, and occurrence of a hereditary nonpolyposis colorectal cancer extracolonic cancer (endometrium, urinary tract, small intestine, stomach, hepatobiliary system, or ovary) in family members. Criteria II consist of one colorectal cancer patient with at least one of the following: early age of onset (<40 years); endometrial, urinary tract, or small intestine cancer in the index patient or a sibling (one aged <50 years); and two siblings with other integral hereditary nonpolyposis colorectal cancer extracolonic cancers (one aged <50 years). A questionnaire was mailed to members of the International Collaborative Group on Hereditary Non-Polyposis Colorectal Cancer to determine the mutation detection rate in mismatch repair genes from the families fulfilling these criteria. For comparison the mutation detection rate for families fulfilling the Amsterdam hereditary nonpolyposis colorectal cancer criteria in each institution was also obtained. RESULTS: Data were obtained from eight different institutions (in 7 different countries). In a total of 123 patients from 123 families (67 families fulfilling Criteria I and 56 families fulfilling Criteria II), genetic testing for germline mismatch repair gene variants was performed. Germline mutations of the hMLH1 or hMSH2 genes were identified in 24 families (20 percent). Of these, the mutation detection rate for families fulfilling Criteria I was 28 percent (19/67). The mutation detection rate for families fulfilling Criteria II was 9 percent (5/56). In these eight institutions, the overall mutation detection rate for families fulfilling the Amsterdam hereditary nonpolyposis colorectal cancer criteria was 50 percent (77/154). CONCLUSION: The Criteria I for suspected hereditary nonpolyposis colorectal cancer have the advantages that they can be applied to nuclear families and they can include extracolonic cancers. The results of this study suggest that families fulfilling Criteria I should be offered genetic testing. The relatively low mutation detection rate in those families fulfilling Criteria II suggests that, using current techniques, genetic testing in these families is not practical.     

Patterns of metachronous adenoma after colorectal cancer surgery]

BACKGROUND/AIMS: After colorectal cancer surgery, colonoscopic surveillance should be done for prevention and early detection of secondary cancer. This study aimed to identify the group with high risk of developing colorectal adenoma after curative surgery of colorectal cancer. METHODS: We retrospectively investigated the medical records of the subjects of 130 patients who had been examined using colonoscopy before and after the curative surgery. RESULTS: The average age was 59.4 years. Synchronous adenomas were in 42 patients (32.3%). The occurrence rate was significantly high in men (38.8%) than women (22.0%). After the operation, the mean interval of examining colonoscopy was 11.6 months (3-24 months) and metachronous adenomas were detected in 26 patients (20.0%). The patients who have both metachronous and synchronous adenomas were observed in 13/42 (30.9%) and the patients of metachronous adenomas without synchronous adenomas were observed in 13/88 (14.8%). The occurrence rate of metachronous adenomas with synchronous adenomas was significantly high. The frequency of synchronous adenomas didn't increase with age. However, the frequency of metachronous adenomas increased with age: 0/9 (0%) under 40 years, 7/49 (14.3%) in 41-61 years and 19/72 (26.4%) over 61 years. The occurrence rate was higher in men (26.3%) than women (10.0%). CONCLUSIONS: The occurrence rate of metachronous adenomas after colorectal cancer surgery was higher in the patients with synchronous adenomas, male gender and old aged patients.