Nipple-sparing mastectomy in patients with BRCA1/2 mutations and variants of uncertain significance.

BACKGROUND: Nipple-sparing mastectomy (NSM) is associated with improved cosmesis and is being performed increasingly. Its role in BRCA mutation carriers has not been well described. This was a study of the indications for, and outcomes of, NSM in BRCA mutation carriers. METHODS: BRCA mutation carriers who underwent NSM were identified. Details of patient demographics, surgical procedures, complications, and relevant disease stage and follow-up were recorded. RESULTS: A total of 177 NSMs were performed in 89 BRCA mutation carriers between September 2005 and December 2013. Twenty-six patients of median age 41 years had NSM for early-stage breast cancer and a contralateral prophylactic mastectomy. Mean tumour size was 1·4 (range 0·1-3·5) cm. Sixty-three patients of median age 39 years had prophylactic NSM, eight of whom had an incidental diagnosis of ductal carcinoma in situ. There were no local or regional recurrences in the 26 patients with breast cancer at a median follow-up of 28 (i.q.r. 15-43) months. There were no newly diagnosed breast cancers in the 63 patients undergoing prophylactic NSM at a median follow-up of 26 (11-42) months. All patients had immediate breast reconstruction. Five patients (6 per cent) required subsequent excision of the nipple-areola complex for oncological or other reasons. Skin desquamation occurred in 68 (38·4 per cent) of the 177 breasts, and most resolved without intervention. Debridement was required in 13 (7·3 per cent) of the 177 breasts, and tissue-expander or implant removal was necessary in six instances (3·4 per cent). CONCLUSION: NSM is an acceptable choice for patients with BRCA mutations, with no evidence of compromise to oncological safety at short-term follow-up. Complication rates were acceptable, and subsequent excision of the nipple-areola complex was rarely required.

What does general paediatric surgery involve? An audit of paediatric cases in 1 year.

BACKGROUND: As all tertiary paediatric hospitals are based in the capital of Dublin, it is therefore necessary for general surgeons in centres outside of Dublin to undertake routine elective and emergency paediatric surgery to provide children with care close to home. The aim of this study is to assess the volume and type of procedures this entails. METHODS: Prospective analysis of the elective and emergency paediatric surgical services provided by a single surgeon in a regional university hospital to determine the volume and nature of general paediatric operative procedures performed. RESULTS: There were 126 operative procedures performed on patients less than 16 years of age during a 12-month period, accounting for 22.8 % of all operations. There were 56 emergency (44.4 %) and 70 elective procedures (55.5 %). The median age was 4.7 years (median age for emergencies 5.4 years, median age for elective surgery 3.8 years). Paediatric operations accounted for 23.4 % of all emergency and 26.2 % of all elective operations. The most commonly performed emergency operations were appendicectomies and pyloromyotomies, representing 73 % of all emergency cases. Inguinal hernia repair, excision of ingrown toenail and percutaneous endoscopic gastrostomy (PEG) tube insertion represented 61 % of elective procedures. CONCLUSIONS: The range of procedures in general paediatric surgery is small with only five procedures representing the majority of all elective and emergency procedures performed. This suggests that a period of specialist paediatric surgery training would enable more general surgeons to provide this vital service.

Molecular profiling techniques and bioinformatics in cancer research.

AIMS: Our aim was to describe the commonly used molecular profiling techniques in cancer research, to examine their limitations and to discuss the challenges of bioinformatics. METHODS: A literature search was performed using the PubMed database to identify publications relevant to this review. Citations from these articles were also examined to yield further relevant publications. RESULTS: We describe the use of DNA microarrays, comparative genomic hybridisation, tissue microarrays and digital differential display. The limitations of these technologies, their contribution to cancer research and the challenges of bioinformatics are also discussed. CONCLUSIONS: Although these high throughput technologies each have their own limitations they are rapidly developing and contributing significantly to our understanding of cancer genetics. They have also led to the emergence of bioinformatics as a rapidly developing and vital field.

Roles for the calcium sensing receptor in primary and metastatic cancer.

AIM: To review the role of the calcium sensing receptor (CASR) in colorectal, breast and parathyroid cancers and related cell lines, and to discuss the effects of CASR in the setting of bone metastases from breast cancer. METHODS: We performed a literature search of the PubMed database of the National Library of Medicine (NLM) to identify articles concerning the CASR's involvement in different cancers. Further relevant papers were obtained from the references of those identified in the original search. RESULTS: Loss of CASR expression is understood to be associated with abnormal differentiation and progression of colorectal carcinoma. It is expressed in both normal and malignant breast tissues and has been implicated in the vicious cycle of bone metastases through its interactions with the parathyroid hormone related peptide (PTHrP). In parathyroid tissue, CASR expression has been linked to proliferation of both parathyroid adenomas and carcinomas. CONCLUSION: Apart from its role in calcium homeostasis, the CASR has many diverse functions in a variety of tissue types throughout the body, and is involved in various signalling pathways relating to cell proliferation and differentiation. CASR has been shown to be involved in the progression and spread of a variety of cancers such as colorectal, breast and parathyroid, and is likely to be the focus of much research to further elucidate its precise role.

Poor awareness of colorectal cancer symptoms; a preventable cause of emergency and late stage presentation.

AIMS: To assess knowledge of colorectal cancer (CRC) symptoms among outpatient attendees, and to review disease stage, presentation and duration of symptoms in patients diagnosed with CRC. METHODS: A questionnaire survey was used to evaluate knowledge of symptoms of CRC and other malignancies. A review of patients diagnosed with CRC during a two-year period was performed. RESULTS: Of 350 survey participants 26.6% could name a CRC symptom, compared to 53.4% for lung cancer and 71.5% for breast cancer. Of 102 patients diagnosed with CRC 3.9% had Dukes A disease, 32.4% had Dukes B, 39.2% had Dukes C and 24.5% had distant metastases. Forty per cent of patients presented acutely. The mean duration of symptoms was 24 weeks. CONCLUSIONS: Knowledge of CRC symptoms is poor and is reflected in the percentage of late stage and emergency presentations. Increasing public awareness of CRC may lead to earlier presentation and improved survival.