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.

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.

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.

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.

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.

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.

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.

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.

Stability of leisure-time physical activity during adolescence--a longitudinal study among 16-, 17- and 18-year-old Finnish youth.

Participation in physical activity during childhood and adolescence is frequently mentioned as one factor likely to promote a more active lifestyle in adulthood with its health benefits. We studied the changes in leisure-time physical activity pattern and self-reported fitness during a three-year period in adolescence and investigated whether the type of sports has an effect on stability of physical activity at leisure. A questionnaire with identical physical activity items was sent to Finnish twins on their 16th and 17th birthdays and 6 months after the 18th birthday. A total of 1338 boys and 1596 girls responded to all three questionnaires, with response rates of 73.6% and 86.5%. The proportions of very active adolescents and adolescents with very good self-reported fitness seem to be alike at each age. Among girls, 23.7% to 27.7% reported being very active (4-5 times a week) and 13.7% to 15.1% considered their physical fitness to be very good at the ages of 16, 17 and 18. Among boys, the comparable percentages were 31.5% to 35.5% and 30.6% to 34.4%. However, the longitudinal three-year follow up showed substantial changes over time among individuals from one physical activity group to another. Only 19.1% of boys and 11.2% of girls were persistent exercisers (i.e., very active on all three years) and 15.6% of boys and 5.1% of girls were persistently fit (i.e., very good self-reported fitness on all three years). Stability of leisure-time physical activity was highest among those who participated in several different types of sports. Among boys the proportion of persistent exercisers was highest for those who participated in cross-country skiing, jogging and body-building (22.0-41.5%) and among girls for those who participated in ball games (11.9-28.6%). Those who participated in organised sports were more often persistent exercisers than those who did not (odds ratio = 13.2 for boys (CI 9.4-18.7) and 8.9 for girls (CI 6.4-12.5)). Also, those who participated in organised sports were more often persistently fit (odds ratio = 7.3 for boys (CI 5.2-10.2) and 10.4 for girls (CI 6.4-16.9). Adolescents are recommended to participate in and try different types of sports, and especially for girls ball games would appear to favour long-term maintenance of leisure-time physical activity.

No support for endoscopic surveillance for gastric cancer in hereditary non-polyposis colorectal cancer.

BACKGROUND: The DNA mismatch repair gene mutations underlying hereditary non-polyposis colorectal cancer syndrome (HNPCC) also predispose, besides colorectal and endometrial cancer, to gastric cancer. usually of the intestinal type. The carcinogenetic pathway behind the elevated gastric cancer risk is largely unknown. METHODS: The aim of this study was to determine whether there are any premalignant lesions to search for in gastric surveillance in HNPCC by comparing gastric histopathology between mutation-positive and mutation-negative family members. We searched for differences in occurrence of Helicobacter pylori, inflammation, atrophy, intestinal metaplasia and dysplastic changes. Upper gastrointestinal endoscopy was performed for 73 mutation-positive and 32 mutation-negative family members. RESULTS: One case of duodenal cancer was detected in the mutation-positive group, but no gastric neoplastic lesions were seen in either group. There were no differences in the occurrence of polyps, H. pylori, inflammation, activity, atrophy nor intestinal metaplasia tested with binaric, logistic, regression analysis. CONCLUSIONS: We conclude that surveillance gastroscopy may not be beneficial in HNPCC, since neither cases of early cancer nor premalignant lesions could be detected in our series of 73 mutation-positive subjects.

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.

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.

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.

Cancer risk in mutation carriers of DNA-mismatch-repair genes.

Excessive incidence of various cancers is a challenging feature of the hereditary-non-polyposis-colorectal-cancer (HNPCC) syndrome. This study estimated the cancer incidences in HNPCC compared with the general population. Individuals in a cohort of 1763 members of 50 genetically diagnosed families were categorized according to their genetic status as mutation carriers, non-carriers, or individuals at 50 or 25% risk of being a carrier. Incidences of cancers in these groups were compared with those in the Finnish population overall. In 360 mutation carriers, standardized incidence ratios (SIR) were significantly increased for colorectal [68; 95% confidence intervals (CI), 56 to 81], endometrial (62; 95% CI, 44 to 86), ovarian (13; 95% CI, 5.3 to 25), gastric (6.9; 95% CI, 3.6 to 12), biliary tract (9.1; 95% CI, 1.1 to 33), uro-epithelial (7.6; 95% CI, 2.5 to 18) and kidney (4.7; 95% CI, 1 to 14) cancers and for central-nervous-system tumours (4.5; 95% CI, 1.2 to 12). The SIR increased with increasing likelihood of being a mutation carrier. The cumulative cancer incidences were 82, 60, 13 and 12% for colorectal, endometrial, gastric and ovarian cancers respectively. For other tumours associated with increased risk, corresponding incidences were below 4%. Interestingly, the incidence of endometrial cancer (60%) exceeded that for colorectal cancer in women (54%). The tumour spectrum associated with germline mutations of DNA-mismatch-repair genes involves 8 or more organ sites, suggesting a need to develop methods to screen for extra-colonic cancer also.

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.

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.

Prognosis of colorectal cancer varies in different high-risk conditions.

Variation in prognosis between different colorectal cancer (CRC) patient groups was studied by comparing the survival rates of patients belonging to three cancer predisposition groups with those with sporadic CRC. The high-risk groups included 43 members of hereditary nonpolyposis colorectal cancer (HNPCC) families, 25 patients with familial adenomatous polyposis (FAP) and 33 patients with underlying ulcerative colitis (UC). The control group included 122 consecutive sporadic CRC patients. Cumulative 5-year survival was highest in HNPCC (86%), which is significantly better than in sporadic colorectal cancer (59%, hazard ratio 0.41, P = 0.02). Cancer associated with UC had a 5-year survival rate of 39%, which is significantly less than in sporadic cancer (hazard ratio 1.83, P = 0.03). There was no significant difference in the survival between patients with FAP and patients with sporadic CRC (hazard ratio 1.27, P = 0.5). Exclusion of cases detected by screening examinations slightly reduced the survival rates; 85% for HNPCC, 53% for FAP and 28% for UC. However, the differences between the groups remained significant. The survival of patients with HNPCC was found to be better than that among other groups in this study, which probably relates to the specific tumourigenesis involving DNA mismatch repair dysfunction.