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Obesity is a significant risk factor for the development of endometrial hyperplasia and cancer. More conservative prevention and management strategies are attractive due to the increased surgical risk and complication rates associated with obesity. The Levonorgestrel-releasing intrauterine system (LNG-IUS, Mirena) has been shown to reduce the risk of developing endometrial cancer. The recent joint Green Top Guideline on the Management of Endometrial Hyperplasia published by the Royal College of Obstetricians and Gynaecologists (RCOG) with the British Society for Gynaecological Endoscopy (BSGE) recommends the LNG-IUS for the medical management of endometrial hyperplasia without atypia. This case study reports on the development of endometrioid adenocarcinoma despite the presence of an LNG-IUS following a negative hysteroscopy in a 56-year-old woman with morbid obesity. This report highlights the need for patients and clinicians to remain vigilant to the early warning signs of developing endometrial cancer, especially in those at an increased risk secondary to obesity.

Background Neoadjuvant chemotherapy (NAC) is increasingly used in the framework of breast-conserving therapy (BCT). Localization of the initial tumor is essential to guide surgical resection after NAC. This study describes the results obtained with I-125 seed localization in BCT including NAC. Patients and methods Between January 2009 and December 2010, 85 patients treated with NAC and BCT after I-125 seed localization were included. Radiological and pathological response and resection margins were retrospectively evaluated. Results BCT was carried out in 85 patients without secondary local excisions. Nineteen patients with unifocal tumors and seven patients with multifocal tumors showed a complete pathological response (P = 0.18). Tumor-free resection margins were obtained in 78 patients (50 patients with unifocal and 28 patients with multifocal tumors, P = 0.27). Focally involved margins were found in four patients (two patients with a unifocal and two patients with a multifocal tumor, P = 0.27). A subsequent mastectomy was carried out in three patients (two patients with multifocal tumors, P = 0.29). Conclusions BCT after NAC can be carried out successfully after initial localization with I-125 seeds in both unifocal and multifocal breast tumors with complete resection rates of >90%.

About 5% of colorectal cancers are associated with the autosomal dominantly inherited cancer susceptibility syndrome hereditary non-polyposis colorectal cancer (HNPCC).1,2 HNPCC is characterised by a high risk of developing colorectal cancer and endometrial cancer at a young age (cumulative lifetime risk 80-90% and 30-40%, respectively), and by an increased risk of developing various other tumour types, such as ovarian, uroepithelial, small intestine, biliary tract, stomach, brain, and skin cancers.2–5 Germline mutations in one of three mismatch repair genes ( MSH2 , MLH1 , and MSH6 ) were found to be responsible for a majority of HNPCC families.6–9 Knowledge of the causative mutation in a particular HNPCC family enables the identification of at risk family members by genetic testing. Clearly, the absence or presence of a mutation is of considerable medical and psychological significance. Subjects not carrying the mutation are relieved from a continuous anxiety and can be dismissed from medical surveillance, saving them trouble and reducing health care costs.10 Importantly, subjects with the mutation can benefit from a medical surveillance programme. For HNPCC, colonoscopy has been shown to be a potent tool for the detection and treatment of premalignant adenomas or early colorectal carcinomas in at risk subjects, reducing the risk of developing colorectal cancer and decreasing the overall mortality by about 65%.11,12 The possibility of early detection of colorectal cancer by stool analysis using the genetic markers TP53, BAT26, and K-RAS raises expectations for the development of less invasive surveillance procedures.13 Furthermore, intervention trials with non-steroidal anti-inflammatory drugs (NSAID) in subjects at risk for developing colorectal cancer are in progress.14,15 So far, studies on the use of genetic testing in HNPCC families have used families or subjects who had been registered for research purposes.10,16,17 It is …

Males with a BRCA1/BRCA2 mutation are not at greatly increased risk for cancer, whereas their (grand)daughters, and other female relatives who carry the mutation, are. Males from BRCA1/BRCA2 families may opt for genetic testing to confirm whether or not they may have transmitted the mutation to their children and, if so, to inform them at an appropriate age about the genetic risk and its implications. The psychological implications of genetic testing for men at risk of being a BRCA1/BRCA2 mutation carrier have received little attention. We report on 28 men requesting BRCA1 or BRCA2 testing, and their partners. Men were at 25% (n =4) or 50% risk (n =24) of being a mutation carrier, the majority with daughters and half of them with daughters aged over 20 years. Levels of psychological distress were assessed several weeks before and after disclosure of the test result. In addition, we investigated the level of intrusive thoughts and feelings about breast and ovarian cancer and the tendency to avoid these. By means of interviews and questionnaires, participants could report on (expected) emotional implications of genetic testing for themselves and their children, on experiences with cancer in the family and on personality trait optimism. Distress levels prior to the result in tested men and their partners were low. Many men and partners expected the test result to affect their children's, but not their own level of problems. Men without daughters and those with an optimistic personality had especially low distress prior to disclosure. Most men reported that they did not actively avoid the issue. Only four of the 28 men were identified as mutation carriers. High distress after disclosure of the result was reported by one mutation carrier and by three non-mutation carriers. Verbatim transcripts from interviews showed a large variation of psychological reactions in male mutation carriers (eg regarding guilt feelings). Low pre-test distress in males does not necessarily indicate avoidance of the issue. Future studies may indicate which psychological reactions occur in male mutation carriers when the problem becomes more acute, eg when a daughter is found to carry the mutation and/or is diagnosed with breast or ovarian cancer.

Twenty-six patients under treatment with the calcium channel blockers flunarizine (Fz) or cinnarizine (Cz) were examined with single-photon emission computed tomography using [123I]iodobenzamide as a ligand. The striatal dopamine D2 receptor-binding potential was determined and found to be reduced by 14 to 63% (39.5 ± 15.0%; p < 0.0001) in patients compared with age-matched control values. This reduction was larger in 12 patients with extrapyramidal symptoms and was only slowly reversible after discontinuation of treatment. Patients treated for >6 months had significantly larger reductions than patients treated for a shorter period. Parkinsonian symptoms were only seen in patients older than 50 years. Our findings prove a neuroleptic-like action of Fz and Cz, which seems to be the major reason for their extrapyramidal side effects. Older age and long-term treatment are predisposing factors for these effects.