Optimising the antibiotic treatment of uncomplicated acute appendicitis: a protocol for a multicentre randomised clinical trial (APPAC II trial).

BACKGROUND: Based on epidemiological and clinical data acute appendicitis can present either as uncomplicated (70-80%) or complicated (20-30%) disease. Recent studies have shown that antibiotic therapy is both safe and cost-effective for a CT-scan confirmed uncomplicated acute appendicitis. However, based on the study protocols to ensure patient safety, these randomised studies used mainly broad-spectrum intravenous antibiotics requiring additional hospital resources and prolonged hospital stay. As we now know that antibiotic therapy for uncomplicated acute appendicitis is feasible and safe, further studies evaluating optimisation of the antibiotic treatment regarding both antibiotic spectrum and shorter hospital stay are needed to evaluate antibiotics as the first-line treatment for uncomplicated acute appendicitis. METHODS: APPAC II trial is a multicentre, open-label, non-inferiority randomised controlled trial comparing per oral (p.o.) antibiotic monotherapy with intravenous (i.v.) antibiotic therapy followed by p.o. antibiotics in the treatment of CT-scan confirmed uncomplicated acute appendicitis. Adult patients with CT-scan diagnosed uncomplicated acute appendicitis will be enrolled in nine Finnish hospitals. The intended sample size is 552 patients. Primary endpoint is the success of the randomised treatment, defined as resolution of acute appendicitis resulting in discharge from the hospital without the need for surgical intervention and no recurrent appendicitis during one-year follow-up. Secondary endpoints include post-intervention complications, late recurrence of acute appendicitis after one year, duration of hospital stay, pain, quality of life, sick leave and treatment costs. Primary endpoint will be evaluated in two stages: point estimates with 95% confidence interval (CI) will be calculated for both groups and proportion difference between groups with 95% CI will be calculated and evaluated based on 6 percentage point non-inferiority margin. DISCUSSION: To our knowledge, APPAC II trial is the first randomised controlled trial comparing per oral antibiotic monotherapy with intravenous antibiotic therapy continued by per oral antibiotics in the treatment of uncomplicated acute appendicitis. The APPAC II trial aims to add clinical evidence on the debated role of antibiotics as the first-line treatment for a CT-confirmed uncomplicated acute appendicitis as well as to optimise the non-operative treatment for uncomplicated acute appendicitis. TRIAL REGISTRATION: Clinicaltrials.gov , NCT03236961, retrospectively registered on the 2nd of August 2017.

Economic evaluation of antibiotic therapy versus appendicectomy for the treatment of uncomplicated acute appendicitis from the APPAC randomized clinical trial.

BACKGROUND: An increasing amount of evidence supports antibiotic therapy for treating uncomplicated acute appendicitis. The objective of this study was to compare the costs of antibiotics alone versus appendicectomy in treating uncomplicated acute appendicitis within the randomized controlled APPAC (APPendicitis ACuta) trial. METHODS: The APPAC multicentre, non-inferiority RCT was conducted on patients with CT-confirmed uncomplicated acute appendicitis. Patients were assigned randomly to appendicectomy or antibiotic treatment. All costs were recorded, whether generated by the initial visit and subsequent treatment or possible recurrent appendicitis during the 1-year follow-up. The cost estimates were based on cost levels for the year 2012. RESULTS: Some 273 patients were assigned to the appendicectomy group and 257 to antibiotic treatment. Most patients randomized to antibiotic treatment did not require appendicectomy during the 1-year follow-up. In the operative group, overall societal costs (€5989·2, 95 per cent c.i. 5787·3 to 6191·1) were 1·6 times higher (€2244·8, 1940·5 to 2549·1) than those in the antibiotic group (€3744·4, 3514·6 to 3974·2). In both groups, productivity losses represented a slightly higher proportion of overall societal costs than all treatment costs together, with diagnostics and medicines having a minor role. Those in the operative group were prescribed significantly more sick leave than those in the antibiotic group (mean(s.d.) 17·0(8·3) (95 per cent c.i. 16·0 to 18·0) versus 9·2(6·9) (8·3 to 10·0) days respectively; P < 0·001). When the age and sex of the patient as well as the hospital were controlled for simultaneously, the operative treatment generated significantly more costs in all models. CONCLUSION: Patients receiving antibiotic therapy for uncomplicated appendicitis incurred lower costs than those who had surgery.

The role of surgery in Crohn's disease: a retrospective analysis from a single hospital.

BACKGROUND: Traditionally, in Crohn's disease (CD), surgery has played an essential role in the treatment of complications. TNF-α-blockers have significantly improved results of conservative treatment but they do not definitely cure Crohn's disease. AIM: Our aim was to examine the prevalence of and indications for surgical procedures in CD in our hospital. MATERIAL AND METHODS: A retrospective survey included all CD patients diagnosed in our hospital referral area during a 10-year period in 1996-2005. RESULTS: Altogether 114 new patients with CD were diagnosed, 56 (49%) males, 58 (51%) fe-males. The median follow-up time was 5.0 years. In all, 31 (27%) patients underwent some sur-gical procedure, and of these, 12 (39%) underwent an emergency operation. The most common indication for surgery was bowel obstruction. The most frequent procedures were ileocolic re-section in 12 (39%) patients and small bowel resection in 10 (32%). CONCLUSIONS: Almost one-third of CD patients needed surgical therapy in an early phase of their disease, and more than one-third of these underwent an emergency procedure. Obstructive symptoms were the most common indication for surgery in the early phase of CD.

Effect of directorial intervention on web-based student feedback.

UNLABELLED: The Medical Faculty of the University of Helsinki decided to employ a web-based evaluation system as an integral and essential part of all courses beginning in the autumn term of 2006. OBJECTIVES: To analyse the effects of the intervention on dental students' web-based responses at the University of Helsinki, Finland. SUBJECTS AND METHODS: A previously developed web-based tool was used for all preclinical and clinical courses from the beginning of the 2006-2007 academic year. We analysed data sets of student feedback for all courses before (2005-2006) and after (2006-2007) the intervention. We then compared the quantity and quality of the students' feedback for the six standardised questions used in the evaluation, and calculated the means and standard deviations of values obtained with a Likert scale. The students' assessments in the open questions were categorised according to key issues. RESULTS: Implementation of the system resulted in a considerable increase in student feedback: the mean response rate for the preclinical phase rose from 59% (SD 15.0; range 25-80) before the intervention to 90% (SD 9.6; range 72-100) after it. In the clinical phase, the response rates more than doubled from 34% (SD 15.9; range 9-69) to 73% (SD 12.9; range 45-100). The students' assessments showed no significant change despite the marked rise in response rates. The educators' positive attitude towards the students was appreciated (4.2-4.3) whereas the general goals for the courses in the clinical phase seemed unclear to the students (3.4) (P < 0.05). CONCLUSIONS: Web-based evaluation as an integral part of all courses in the dental curriculum proved successful: shortly after the intervention, we observed a considerable increase in student feedback with no significant change in quality.

Recurrent groin hernia surgery after primary open inguinal procedures: a reappraisal of the open preperitoneal (Ugahary) technique.

PURPOSE: There are several methods for repairing recurrent inguinal hernia, depending on the type of initial repair. Our aim was to analyze our long follow-up results on the open preperitoneal repair for patients with recurrent inguinal hernia. METHODS: Our retrospective survey included 135 consecutive recurrent inguinal hernia patients, operated on during 1999-2010, with a mean follow-up time of 8.7 years. RESULTS: During the mean follow-up time of 8.7 years, only four (3%) patients developed a re-recurrence. Two of these patients were asymptomatic, and the two other were operated on. Early postoperative complications occurred in four (3%) patients. The complications comprised one hematoma, one seroma, and two infections. Chronic pain was diagnosed in five (3.7%) patients, but their symptoms disappeared spontaneously within a few years. CONCLUSIONS: We conclude that in competent hands, the open preperitoneal repair (Ugahary) is a good surgical option in operating recurrent inguinal hernias.

Differential cancer predisposition in Lynch syndrome: insights from molecular analysis of brain and urinary tract tumors.

Hereditary non-polyposis colorectal carcinoma (Lynch syndrome) is among the most common hereditary cancers in man and a model of cancers arising through deficient DNA mismatch repair (MMR). Lynch syndrome patients are predisposed to different cancers in a non-random fashion, the basis of which is poorly understood. We addressed this issue by determining the molecular profiles for different tumors from a nationwide cohort of Lynch syndrome families (approximately 150 tumors in total). We focused on some less prevalent cancers, affecting the brain (n = 7) and urinary tract (five bladder and five ureter uroepithelial cancers and four kidney adenocarcinomas), and compared their molecular characteristics to those of the most common cancers, colorectal, gastric and endometrial adenocarcinomas, from the same families. Despite origin from verified MMR gene mutation carriers, the frequency of high-level microsatellite instability in tumors varied between high (100-96% for ureter, stomach and colon), intermediate (63-60% for endometrium and bladder) and low (25-0% for kidney and brain). In contrast to gastrointestinal and endometrial carcinomas, active (nuclear) beta-catenin was rare and KRAS mutations were absent in brain and urological tumors. Compared with other tumors, frequent stabilization of p53 protein characterized urinary tract cancers. Promoter methylation of tumor suppressor genes discriminated the tumors in an organ-specific manner. Our findings suggest that different Lynch syndrome tumors develop along different routes. Uroepithelial cancers of the ureter (and bladder to lesser extent) share many characteristics of MMR deficiency-driven tumorigenesis, whereas brain tumors and kidney adenocarcinomas follow separate pathways.

The Accuracy of the Computed Tomography Diagnosis of Acute Appendicitis: Does the Experience of the Radiologist Matter?

BACKGROUND AND AIMS: To assess the accuracy of computed tomography in diagnosing acute appendicitis with a special reference to radiologist experience. MATERIAL AND METHODS: Data were collected prospectively in our randomized controlled trial comparing surgery and antibiotic treatment for uncomplicated acute appendicitis (APPAC trial, NCT01022567). We evaluated 1065 patients who underwent computed tomography for suspected appendicitis. The on-call radiologist preoperatively analyzed these computed tomography images. In this study, the radiologists were divided into experienced (consultants) and inexperienced (residents) ones, and the comparison of interpretations was made between these two radiologist groups. RESULTS: Out of the 1065 patients, 714 had acute appendicitis and 351 had other or no diagnosis on computed tomography. There were 700 true-positive, 327 true-negative, 14 false-positive, and 24 false-negative cases. The sensitivity and the specificity of computed tomography were 96.7% (95% confidence interval, 95.1-97.8) and 95.9% (95% confidence interval, 93.2-97.5), respectively. The rate of false computed tomography diagnosis was 4.2% for experienced consultant radiologists and 2.2% for inexperienced resident radiologists (p = 0.071). Thus, the experience of the radiologist had no effect on the accuracy of computed tomography diagnosis. CONCLUSION: The accuracy of computed tomography in diagnosing acute appendicitis was high. The experience of the radiologist did not improve the diagnostic accuracy. The results emphasize the role of computed tomography as an accurate modality in daily routine diagnostics for acute appendicitis in all clinical emergency settings.

Comparative genomic hybridization reveals differences in DNA copy number changes between sporadic gastric carcinomas and gastric carcinomas from patients with hereditary nonpolyposis colorectal cancer.

Comparative genomic hybridization was used to search for DNA copy number changes in samples of gastric cancer from 12 hereditary nonpolyposis colon cancer (HNPCC) patients and in samples of sporadic gastric carcinoma from 13 patients. The gastric cancer samples from HNPCC patients showed gains affecting 19q, Xp, and whole chromosome 22, each in a single patient. Neither high-level amplifications nor losses of DNA copy number were detected. On the other hand, 10 of the 13 (77%) sporadic gastric carcinoma samples had multiple DNA copy number changes. The most frequent gains occurred with minimal common overlapping regions at 1q22-q31, 8q23-qter, 17p11.2-q22, and 20q, all at a frequency of 31%. High-level amplifications were also seen at 17q21 in three cases (23%). Losses were rare, and the most frequent loss was with a minimal common overlapping region at 4q32 (23%). This suggests that multiple DNA copy number changes are needed for the development of sporadic gastric carcinoma but not for gastric carcinoma in HNPCC patients.

The role of biofeedback therapy in functional proctologic disorders.

BACKGROUND AND AIMS: The question which patients with functional proctologic disorders truly benefit from the biofeedback has not been equivocally resolved. The aim of this study was to assess our results of biofeedback therapy in patients with anal incontinence or constipation. MATERIAL AND METHODS: Fifty-two consecutive patients who were treated with biofeedback therapy between January 1998 and March 2002 were studied. Data was collected from our proctologic database. RESULTS: Of the twenty-two patients with anal incontinence who underwent biofeedback therapy during the study period, twenty patients had incontinence affecting quality of life. Twelve patients (60 percent) benefited from biofeedback as judged by improvement of incontinence symptoms affecting quality of life; all four patients with partial sphincter defects, three out of four patients after secondary repair, three out of five patients with persistent incontinence after rectal prolapse surgery and two out of seven patients having idiopathic incontinence. Of the thirty patients who underwent biofeedback therapy for constipation, twenty-five had intractable symptoms of constipation. Constipation resolved in sixteen patients (64 percent); in thirteen out of nineteen (68 percent) of those with pelvic floor dysfunction (PFD) and in three out of six (50 percent) having combined PFD and slow transit constipation. In patients with PFD constipation was resolved in ten out of thirteen patients (77 percent) with anismus but in only three out of six (50 percent) having other causes. CONCLUSIONS: Biofeedback therapy improves incontinence after sphincter repairs and in patients with partial external sphincter defects, but does not improve idiopathic incontinence. Biofeedback is also effective in patients with constipation, especially when anismus is the only cause for symptoms of constipation and difficult evacuation.

Blood chemistry and endoparasites of the mountain hare (Lepus timidus L.) in high and low density populations.

In order to study the effect of high population density on the condition, blood characteristics and helminth parasitism of mountain hares (Lepus timidus), 12 specimens were shot in December 1982 and 12 more in February 1983 on the west coast of central Finland (group 1, dense population). In addition 14 hares were shot in December 1982 about 100 km from group 1 (group 2, dense population). Group 3 consists of 15 hares from stable, rather low density populations shot in southern Finland during three previous winters. The hares in group 1 were the lightest, had the least fat and were the most seriously infected with Protostrongylus pulmonalis and Trichostrongylus retortaeformis, while those in group 2 were the heaviest and had the highest Ca, Mg, alkaline phosphatase and creatinine values. The group 3 hares had the most fat. The group 1 animals shot in February 1983 had higher Ca, Mg, triglyceride and cholesterol values than those shot in December 1982. It seems that high population density combined with a lack of suitable food leads to poor condition and high endoparasite abundances. The differences in Ca and Mg are probably due to diet. The higher creatinine values in group 2 and in the hares with little or no T. retortaeformis infection may be due to the greater muscle mass.

Sharing electronic medical record on the WWW using InterCare architecture and smart cards.

Southern-Finland is a partner of the European Commission funded telematics project, InterCare, which is developing and demonstrating the WWW--based regional architecture and application integrated with smart cards. The InterCare project will combine the results from the most important EC funded healthcare telematics projects in their respective areas--Cardlink 2, Hector, Star, Synapses and TrustHealth. The primary objective is to achieve a convergence of results and to demonstrate & promote the synergy between projects from different areas of the healthcare telematics programme.

Is gastric cancer part of the tumour spectrum of hereditary non-polyposis colorectal cancer? A molecular genetic study.

BACKGROUND: Gastric cancer is the second most common extracolonic malignancy in individuals with hereditary non-polyposis colorectal cancer (HNPCC)/Lynch syndrome. As gastric cancer is relatively common in the general population as well, it is not clear whether or not gastric cancer is a true HNPCC spectrum malignancy. AIM: To determine whether or not gastric cancer is a true HNPCC spectrum malignancy. SUBJECTS AND METHODS: The molecular and clinicopathological profiles of gastric cancers (n = 13) from HNPCC mutation carriers were evaluated and compared with the profiles of sporadic gastric cancers (n = 46) stratified by histology and microsatellite instability (MSI) status. RESULTS: This study on sporadic and HNPCC gastric cancers revealed several important universal associations. Loss of heterozygosity in the adenomatous polyposis coli (APC) region was associated with intestinal histology regardless of the MSI (p = 0.007). KRAS-mutations (p = 0.019) and frameshift mutations in repeat tracts of growth-regulatory genes (p<0.001) were associated with MSI tumours being absent in microsatellite stable (MSS) tumours. The average number of methylated tumour suppressor gene loci among the 24 genes studied (methylation index) was higher in MSI than in MSS tumours regardless of histology (p<0.001). Gastric cancers from HNPCC mutation carriers resembled sporadic intestinal MSI gastric cancers, except that MLH1 promoter methylation was absent (p<0.001) and the general methylation index was lower (p = 0.038), suggesting similar, but not identical, developmental pathways. All these lacked the mismatch repair protein corresponding to the germline mutation and displayed high MSI. CONCLUSION: The present molecular evidence, combined with the previous demonstration of an increased incidence relative to the general population, justify considering gastric cancers as true HNPCC spectrum malignancies.

Surveillance on mutation carriers of DNA mismatch repair genes.

Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant inherited cancer susceptibility syndrome signifying a very high risk of colorectal and endometrial cancer at young age. It also entails an increased risk of a variety of other tumours, such as ovarian, gastric, uroepithelial and biliary tract cancer. The underlying pathogenic mutation lies in one of the five known DNA mismatch repair genes (MSH2, MLH1, PMS1, PMS2, and MSH2). The majority of HNPCC patients and families can at present be identified and the underlying mutation detected by genetic diagnostics. This provides the opportunity for predictive genetic testing to exclude or identify the mutation carrier status of the family members at risk. Mutation-negative individuals can then be relieved from any extra cancer threat. For mutation-positive individuals a preventive surveillance programme offers substantial benefits in reducing the cancer incidence, almost precluding death of colorectal cancer and reducing overall mortality.

Associations of health-related behaviors, school type and health status to physical activity patterns in 16 year old boys and girls.

Sedentary behavior often begins in childhood and is associated with the development of risk factors for many chronic diseases in adulthood. Physical activity is considered important in the prevention of unfavorable changes in the risk factors. We investigated whether health-related behaviors, school type and health status are associated to physical activity among adolescents. A questionnaire was sent to all Finnish 16-year-old twins in 1991-93. A total of 3,254 twins responded. The response rate was 88%. Physical activity was classified into five categories (very active, active, moderately active, hardly active, inactive) based on self-reported frequency and intensity of physical activity. The analysis considered all subjects as individuals. Smoking was strongly associated with physical activity among girls and boys. Those who smoked regularly were less active. The type of school was also associated with physical activity. In general, those who attended comprehensive school or high school were physically more active, while those in vocational schools, particularly boys, were less active. Girls in lower physical activity groups reported more psychosomatic symptoms. Associations of self-reported health-related behaviors, school type and health status to physical activity seem to be the same among boys and girls. However, as the more active students are in comprehensive school or high school and the less active in vocational school, and physical inactivity is related to smoking and use of alcohol, health education should be tailored by school type.

Associations of health related behaviour, social relationships, and health status with persistent physical activity and inactivity: a study of Finnish adolescent twins.

OBJECTIVE: To examine the association between leisure time physical activity over a three year period and health related behaviour, social relationships, and health status in late adolescence as part of a nationwide longitudinal study. METHODS: Five birth cohorts of adolescent twins aged 16 at baseline (n = 5028; 2311 boys and 2717 girls) participated in the study. Questionnaires on leisure time physical activity, other health related behaviour, social relationships, and health status were sent to the twins on their 16th and 17th birthdays and six months after their 18th birthday. The combined response rate to the three questionnaires was 75.8% for boys and 81.7% for girls. Those who answered in all three questionnaires that their frequency of physical activity was 4-5 times a week or more were defined as persistent exercisers, and those who exercised at most twice a month in all three were defined as persistently inactive. Logistic regression analyses were used to identify baseline variables associated with outcome measures. RESULTS: Overall, 20.4% of boys and 13.0% of girls were persistent exercisers and 6.5% of boys and 5.3% of girls were persistently inactive. In both sexes, smoking, irregular breakfast eating, attending vocational school, and poor self perceived current health were significantly associated with persistent inactivity. CONCLUSIONS: Persistent physical inactivity in adolescents is associated with a less healthy lifestyle, worse educational progression, and poor self perceived health. Tailoring methods to promote physical activity may prove useful for influencing other health habits. Such programmes are indicated for vocational schools in particular.

Familial aggregation of leisure-time physical activity -- a three generation study.

Studies of parental influence on children's physical activity have had different results. Parental effect on physical activity during adolescence is less studied, and three generation studies have not been carried out. The purpose of our study was to examine intra- and intergenerational associations of leisure time physical activity among family members in three generations. Due to the major changes in society during this time, we also took into consideration the socioeconomic status of the adult subjects. The material consisted of 3254 twins at the age of 16, their parents and grandparents. Twins and their parents received a questionnaire in 1991-1993, which included questions about the health and lifestyle, socioeconomic status and leisure time physical activity. The parents' questionnaire also included questions about their own parents' leisure time physical activity and socioeconomic status. Based on these questions adolescents, parents and grandparents were classified into physical activity classes. The socioeconomic classification of parents and grandparents was based on their occupation. Intragenerational physical activity patterns were significantly associated with each other. Among adolescents the strongest correlation were between monozygotic boys (0.720) and monozygotic girls (0.638). Physical activity patterns were not associated between generations, but there was a significant difference between very active and inactive mothers concerning their daughters' physical activity. Farmers had the lowest proportion of very active subjects only among the parental generation. Because physical activity patterns do not appear to be transmitted from one generation to the next, it is probable that by constant training and education we can obtain the benefits of physical activity.

Surveillance improves survival of colorectal cancer in patients with hereditary nonpolyposis colorectal cancer.

Some patients with the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome develop carcinoma despite surveillance. The aim of this study was to determine whether survival was greater in colorectal cancer (CRC) cases detected by surveillance than in patients who had disease diagnosed on the basis of symptoms. All 150 CRC cases detected in 57 HNPCC families over the last 15 years were divided into two groups depending on whether they had been included in the surveillance program (n = 35) or not (n = 115). The stage distribution of the tumors in the group that underwent surveillance (Dukes' A, 50%; B, 35%; C, 15%; D, 0%) was significantly more favorable (P < .001) than in the group without surveillance (Dukes' A, 17%; B, 50%; C, 16%; D, 17%). CRC-specific 10-year survival was 93% in the surveillance group, significantly better than the 68% in the nonsurveillance group (P < .02). The overall survival did not differ significantly between the two groups despite a tendency in favor of the surveillance group. Colonoscopic surveillance enables early detection of CRC in HNPCC and reduces CRC mortality.

Are smokers a risk group for delayed healing of tibial shaft fractures?

A total of 135 patients with a fresh tibial shaft fracture and with no other significant injuries underwent primary conservative treatment. Data on their smoking habits were obtained from hospital records and by questionnaire. Although the smokers had better prospects for healing of the fracture at the outset than non-smokers (lower mean age and less fractures caused by high-energy injuries), the smokers were found to have a significantly longer mean time to clinical union and a higher incidence of delayed union. According to a crude calculation, smokers had a 4.1-fold risk of tibial shaft fracture caused by low-energy injury, compared with non-smokers. An accelerated failure time model showed that the more comminuted or open the fracture, the higher the number of cigarettes smoked and the older the patient, the longer was the time to clinical union of the tibial shaft fracture. Female sex appeared to be a further risk factor for delayed healing. A logit model indicated that comminution of the fracture, smoking and female sex were associated with delayed union and non-union. If a patient has a markedly raised probability of delayed union of tibial shaft fracture because of many risk factors as reported in the previous literature or in this study, operative treatment should be considered as the primary alternative instead of conservative treatment. Stopping smoking during healing of tibial shaft fracture could also promote the union of the fracture.

Life-time risk of different cancers in hereditary non-polyposis colorectal cancer (HNPCC) syndrome.

Identification of hereditary non-polyposis colorectal cancer (HNPCC) indicates theoretical life-time risks of 50% for the descendants of an affected family member and of 100% for the true gene carriers. However, besides colorectal cancer (CRC), many other cancer types and sites are also involved, which gives reason to evaluate the magnitude of risk for various other cancer types. A detailed pedigree analysis of 40 families with HNPCC identified 414 patients affected with cancer. A Kaplan-Meier life-table analysis for the cumulative risk of various cancers was performed on the basis of the 293 putative gene carriers who had adequate clinical and histological documentation of their tumors. Cumulative risks were highest for colorectal (78%) and endometrial cancers (43%, women only), followed by gastric, biliary tract, urinary tract and ovarian cancers (19-9%). For the other probably HNPCC-related cancer types, such as small bowel carcinoma and brain tumors, the life-time risk was only 1%. The risk of any metachronous cancer reached 90% after treatment of CRC and 75% after endometrial cancer; the second tumor was most often a new CRC or endometrial cancer. CRC remains the most important cancer type in the HNPCC syndrome but does not develop in all gene carriers. This makes the decision of possible prophylactic colectomy for test-detected gene carriers difficult. Of the many other cancer types involved, at least endometrial cancer is common enough to necessitate a specific surveillance program.