Clinical implications of recognition of the hereditary non-polyposis colon cancer syndrome (HNPCC) for the early detection of colorectal cancer.

UNLABELLED: Hereditary non-polyposis colon cancer (HNPCC), also known as the Lynch syndrome or, previously, as the cancer family syndrome (CFS) is a recently defined autosomal cancer syndrome which is different from familial adenomatous polyposis and accounts for a considerable proportion of colorectal cancer (CRC). The main features of HNPCC include familial aggregation of CRC (either solely or combined with other, particularly gynaecological cancer sites- Lynch I or II, resp.), very frequent localization of the cancer in the right colon, a considerably lower age at the time of occurrence and a high risk of synchronous and metachronous tumours. Recognition of the syndrome through family history offers an important chance to detect CRC at a presymptomatic stage with a positive effect on the prognosis. In 1981/82 we started a prospective follow-up of symptom-free subjects conforming with the criteria of HNPCC. Up to 1994 we found 364 subjects of this type coming from 38 families. After initial colonoscopy these subjects entered a system of colonoscopic surveillance built up according to the individual degree of risk. Initial colonoscopy revealed cancer in 61 and adenomas in 122 subjects, both in more than 70% in the right colon. The mean age at this time was 47.5 in cancer and 45.3 in adenomas. More cancers and adenomas were found on repeated colonoscopies during surveillance. All the cancers were well resectable, a 5 year survival in all. During this course in a group of 239 non-screened symptomatic cases of the HNPCC syndrome, detected only at the time of colonoscopy, cancer was found in 146 and adenomas in 71 patients. Five year survival was 65% in this group. The cancers in the screened group were Dukes A and B (mostly A) in 82% and C in 18%, in the symptomatic group Dukes A or B (mostly B) in 67%, C in 18 and D in 15%. - CONCLUSIONS: The results show more favourable colonoscopic findings and better prognosis in symptom-free, colonoscopally screened cases of HNPCC than in symptomatic ones and fully justify an active approach based on colonoscopic surveillance of HNPCC subjects prior to diagnosis.

[Early diagnosis of colorectal carcinoma in the familial carcinoma syndrome (Lynch I and II)]. / Casná diagnóza kolorektálního karcinomu v syndromu karcinomové rodiny (Lynch I a II).

The hereditary form of colorectal cancer (Lynch syndrome, cancer family syndrome "nonpolyposis hereditary colorectal cancer"), which is different from familial adenomatous polyposis, represents probably 5-8% of the development of this malignancy. The main characteristics of the syndrome include an autosomal dominant hereditary type, frequent familial occurrence of colorectal cancer (either solely at this site--Lynch variant I--or in combination with other, particularly gynecological sites of cancer-Lynch variant II), younger age at the time of diagnosis, more frequent localization in the right colon and more frequent occurrence of synchronic and metachronic cancer. During the years 1982-1992, we found 339 asymptomatic members of families meeting the criteria of the syndrome. After initial colonoscopy these individuals entered a long-term surveillance system with repeated colonoscopies; intervals between them where organized according to the individual degree of risk and to at the initial finding. Results of initial colonoscopy showed colorectal cancer in 16.2% and adenomas in 32.1% of the whole group. The right colon was affected in 74.5% of the cancers and in 64% of the adenomas; the mean age of the probands with these findings was 46.4% years. The Lynch variant I was found in 34%, the variant II in 66%. Cancer in relatives of the variant II was mostly in the colorectal, followed by the gynecological region. The highest number of cancers detected on initial colonoscopy was found in probands with the highest degree of genetic risk-with 3 or more than 3 direct relatives. On repeated colonoscopies a new cancer was found in 7 further probands. All the cancers were well resectable, mostly DUKES A and B.(ABSTRACT TRUNCATED AT 250 WORDS)

[Significance of the detection of the familial carcinoma syndrome (Lynch I and II) in the early diagnosis of colorectal carcinoma]. / Význam detekce syndromu karcinomové rodiny (Lynch I a II) pro casnou diagnózu kolorektální rakoviny.

In 1982-1991 at the Fourth Medical Clinic 309 asymptomatic family members meeting the criteria of the hereditary form of colorectal carcinoma (Lynch syndrome--syndrome of familial cancer, also "non-polypous" hereditary colorectal carcinoma) which differs from familial polyposis (adenomatosis) of the colon. The syndrome is characterized by autosomal dominant heredity and by familial incidence of colorectal carcinoma (Lynch I) or colorectal carcinoma and carcinoma of other, in particular gynaecological areas (Lynch II) and a younger age of the affected subjects, a more frequent localization in the right colon, synchronous and metachronous neoplasia. In the authors group 34% were type I, the remainder type II. Initial total coloscopy revealed carcinoma in 51 subjects (78% in the right colon), adenomatous polyps in 99 (73% in the right colon). The mean age of the patients with carcinoma was 47.5 years, of those with adenoma 46.5 years. The majority of cases were recorded in subjects with three or more than three direct relatives with carcinoma (highest risk grade). During subsequent coloscopic check-up examinations at intervals depending on individual risk, colorectal carcinoma was detected in another six subjects. In 30 patients it was carcinoma Dukes A, in 12 B and in 3 Dukes C. These results indicate that identification of asymptomatic cases of Lynch syndromes via the family-history and coloscopic follow-up contributes to the early diagnosis of colorectal carcinoma.