PJS patients are markedly at risk for several malignancies, in particular gastrointestinal cancers and breast cancer. On the basis of these elevated risks, a surveillance recommendation is developed to detect malignancies in an early phase and to remove polyps that may be premalignant and may cause complications, so as to improve the outcome.

PJS patients carry a high cumulative intussusception risk at young age. Intussusceptions are generally caused by polyps >15 mm and treatment is mostly surgical. These results support the approach of enteroscopic surveillance, with removal of small-intestinal polyps >10-15 mm to prevent intussusceptions. The effect of such an approach on the incidence of intussusception remains to be established in prospective trials.

A small fraction of families with familial adenomatous polyposis (FAP) display an attenuated form of FAP (AFAP). We aimed to assess the presence of germline mutations in the MUTYH and adenomatous polyposis coli (APC) genes in AFAP families and to compare the clinical features between the two causative genes. Families with clinical AFAP were selected from the Dutch Polyposis Registry according to the following criteria: (a) at least two patients with 10-99 adenomas diagnosed at age >30 years or (b) one patient with 10-99 adenomas at age >30 years and a first-degree relative with colorectal cancer (CRC) with a few adenomas, and, applying for both criteria, no family members with more than 100 polyps before the age of 30 years. All probands were screened for germline mutations in the APC and MUTYH genes. Twenty-five of 315 Dutch families with FAP (8%) met our criteria for AFAP. These families included 146 patients with adenomas and/or CRC. Germline APC mutations were identified in nine families and biallelic MUTYH mutations in another nine families. CRC was identified at a mean age of 54 years (range 24-83 years) in families with APC and at 50 years (range 39-70 years) in families with MUTYH (p = 0.29). APC and biallelic MUTYH mutations are responsible for the majority of AFAP families. Based on our results and those reported in the literature, we recommend colonoscopy once every 2 years in AFAP families, starting surveillance from the late teens in APC mutation carriers and from age 20-25 years in biallelic MUTYH mutation carriers.

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Objective: Very-low-calorie diets (VLCDs) are used to promote short-term weight loss in obese patients. However, long-term maintenance of weight loss is generally poor. We assessed the efficacy and safety of sibutramine in maintaining weight loss achieved in obese patients by means of a 3-month VLCD. Design: A multicenter double-blind, parallel-group trial conducted over 18 months, following a 3-month open label VLCD runin. Setting: Eight hospital centers in The Netherlands, with subsequent follow-up in general practice. Subjects: A total of 221 obese subjects, of whom 189 were randomized (mean screening BMI 36.6 kg/m 2 ; mean age 42.6 y). Measurements: Patients were given a 3-month VLCD and were required to lose 10% or more of their initial weight. A total of 189 patients completed this phase (mean percentage weight loss 14.573.2%) and were randomized to sibutramine 10 mg/day (n ¼ 94) or matching placebo (n ¼ 95). All patients received a recommended diet and exercise program. The primary analysis was outcome in terms of achieving 80% weight maintenance of the VLCD period at month 18. Secondary analysis was percentage of initial weight loss maintained at months 6, 12, 18 and end point. Results: At month 18, the odds ratio for achieving successful weight maintenance was 1.76 (95% CI 1.06, 2.93) in favor of sibutramine (P ¼ 0.03). In intention-to-treat analysis, more than 80% of the weight loss achieved during the VLCD phase was maintained by 70, 51 and 30% of sibutramine-treated patients at months 6, 12 and 18, respectively, compared to 48, 31 and 20% of placebo-treated patients. The differences between the treatment groups were significant (Pr0.03) at all time points. Conclusion: Weight loss achieved with a VLCD is more effectively maintained with sibutramine in combination with a recommended diet and exercise program than with placebo over a follow-up period of 18 months. Sibutramine is well tolerated, with a safety profile consistent with that seen in other previous trials.