Jarvinen HJ, Aarnio M, Mustonen H, Aktan-Collan K, Aaltonen LA, Peltomaki P, de la Chapelle A, Mecklin JPControlled 15-year trial on screening for colorectal cancer in families with hereditary nonpolyposis colorectal cancer. Gastroenterology 118: 829-834

Second Department of Surgery, Helsinki University Central Hospital, Helsinki, Finland.
Gastroenterology (Impact Factor: 16.72). 06/2000; 118(5):829-34. DOI: 10.1016/S0016-5085(00)70168-5
Source: PubMed


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.
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.
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).
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.

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    • "Currently, prospective data support the benefit of colorectal cancer screening and consensus guidelines recommend colonoscopy every 1–2 years beginning at age 20–25 years until age 40 and then annually thereafter, although age initiation can be increased in patients with MSH6 and PMS2 mutations [1] [11] [12]. Data on the efficacy of endometrial cancer screening are limited; however, annual endometrial biopsy beginning between the ages of 30 and 35 years is an option, especially for MLH1 and MSH2 carriers [1] [13]. "
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    ABSTRACT: Objective To determine comfort and knowledge among obstetrician/gynecologists and general surgeons regarding recommendations for cancer screening for women with Lynch syndrome. Methods A questionnaire on Lynch syndrome was administered to all obstetrician/gynecologists and general surgeons at a hospital in New York, USA. Results Fifty obstetrician/gynecologists and 62 general surgeons completed the survey (67% response rate). Physicians were more comfortable counseling on colon cancer than endometrial cancer screening (51% vs 28%; P < 0.001). Obstetrician/gynecologists were more comfortable than general surgeons counseling patients on endometrial cancer screening (36% vs 21%; P = 0.090) but less comfortable counseling patients on colon cancer screening (36% vs 63%; P = 0.008). There was no significant difference between the specialties in the number of knowledge-based questions answered correctly. Furthermore, there was no correlation between a physician’s perceived knowledge and number of correct answers. Conclusion Most physicians did not report being comfortable counseling about recommendations for endometrial cancer screening. While obstetrician/gynecologists reported greater comfort than general surgeons, we found no significant difference in disease knowledge between the groups. Because appropriate cancer screening can improve the outcomes of patients with Lynch syndrome, physicians must be knowledgeable and comfortable with screening recommendations for both endometrial and colon cancer, regardless of clinical specialty.
    Full-text · Article · Aug 2014 · International Journal of Gynecology & Obstetrics
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    • "Since the 1980s, conventional surveillance by colonoscopy has been recommended for Lynch syndrome families. Some studies have shown that periodic examination by colonoscopy can detect CRC at an early stage, leading to a 62 % reduction in the risk of malignancy and a significant reduction in mortality associated with CRC [4–8]. While screening may be effective for the early detection of endometrial cancer in these patients [9–11], the efficacy of surveillance for other forms of co-occurring tumors has not yet been established. "
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    ABSTRACT: Lynch syndrome is an autosomal dominant disease associated with a high incidence of colorectal, endometrial, stomach, ovarian, pancreatic, ureter and renal pelvis, bile duct and brain tumors. The syndrome can also include sebaceous gland adenomas and keratoacanthomas, and carcinoma of the small bowel. The lifetime risk for bile duct cancer in patients with Lynch syndrome is approximately 2 %. The present report describes a case of Lynch syndrome with metachronous bile duct cancer diagnosed at an early stage. The patient was a 73-year-old Japanese male who underwent a successful left lobectomy of the liver, and there was no sign of recurrence for 2 years postoperative. However, this patient harbored a germline mutation in MLH1, which prompted diagnostic examinations for noncolorectal tumors when a periodic surveillance blood examination showed abnormal values of hepatobiliary enzymes. Although most patients with bile duct cancer are diagnosed at an advanced stage, the bile duct cancer was diagnosed at an early stage in the present patient due to the observation of the gene mutation and the preceding liver tumor. This case illustrates the importance of continuous surveillance for extracolonic tumors, including bile duct cancer, in patients with Lynch syndrome.
    Full-text · Article · Jul 2013 · Surgery Today
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    • "A significantly increased SMR was found for cancer of the small bowel (SMR = 18.3), brain (SMR = 9.1), kidney/ureter (SMR = 5.9), ovary (SMR = 2.3), pancreas (SMR = 2.2), and stomach (SMR = 2.1). Colorectal cancer surveillance reduces the risk of cancer and improves survival in LS.53 Life expectancy may also be improved by more extensive colectomy at diagnosis, with 2.3 years of extra life predicted for a 27-year-old undergoing subtotal colectomy over hemicolectomy.54 We could not identify any study that assessed overall life expectancy in LS. "
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    ABSTRACT: There are several hereditary diseases that are a predisposition to early-onset tumors. These include syndromic conditions like neurofibromatosis 1 and 2, von Hippel-Lindau syndrome, Gorlin syndrome, multiple endocrine neoplasia, and familial adenomatous polyposis; and conditions which are usually not possible to diagnose clinically in a single individual, such as Lynch syndrome and BRCA1/2. Understanding of the mortality in hereditary cancer predisposing diseases is important for developing effective disease treatment programs. A number of studies have been undertaken to investigate the genetic predictors, prevalence and incidence, and treatment outcomes of these diseases; however, the majority examine only the most common of these diseases (eg, neurofibromatosis or BRCA), or look into postoperative survival. The mortality of individuals who are diagnosed with one of these hereditary diseases remains an area for investigation. This review is the first to attempt identification of studies investigating life expectancy in hereditary diseases which predispose to early-onset tumors.
    Full-text · Article · Jul 2013 · The Application of Clinical Genetics
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