Risk Profile of the RET A883F Germline Mutation: An International Collaborative Study.

Context: The A883F germline mutation of the rearranged during transfection (RET) proto-oncogene causes multiple endocrine neoplasia 2B. In the revised American Thyroid Association (ATA) guidelines for the management of medullary thyroid carcinoma (MTC), the A883F mutation has been reclassified from the highest to the high-risk level, although no well-defined risk profile for this mutation exists. Objective: To create a risk profile for the A883F mutation for appropriate classification among the ATA risk levels. Design: Retrospective analysis. Setting: International collaboration. Patients: Included were 13 A883F carriers. Intervention: The intervention was thyroidectomy. Main Outcome Measures: Earliest age of MTC, regional lymph node metastases, distant metastases, age-related penetrance of MTC and pheochromocytoma (PHEO), overall and disease-specific survival, and biochemical cure rate. Results: One and three carriers were diagnosed at age 7 to 9 years (median, 7.5 years) with a normal thyroid and C-cell hyperplasia, respectively. Nine carriers were diagnosed with MTC at age 10 to 39 years (median, 19 years). The earliest age of MTC, regional lymph node metastasis, and distant metastasis was 10, 20, and 20 years, respectively. Fifty percent penetrance of MTC and PHEO was achieved by age 19 and 34 years, respectively. Five- and 10-year survival rates (both overall and disease specific) were 88% and 88%, respectively. Biochemical cure for MTC at latest follow-up was achieved in 63% (five of eight carriers) with pertinent data. Conclusions: MTC of A883F carriers seems to have a more indolent natural course compared with that of M918T carriers. Our results support the classification of the A883F mutation in the ATA high-risk level.

Incidence, prevalence and risk factors for post-surgical hypocalcaemia and hypoparathyroidism.

Hypocalcaemia following thyroid surgery is common and is associated with significant short and long term morbidity. Damage to or devascularisation of parathyroid glands is the predominant underlying mechanism; although other factors such as hungry bone syndrome may occasionally contribute to it in the immediate post-operative period. The reported incidence of post-surgical hypocalcaemia and/or hypoparathyroidism (PoSH) varies significantly in the literature; the variation thought to be at least partly due to differences in the definitions used. Figures on the prevalence of chronic or long term post-surgical hypocalcaemia in the population are unclear. Risk factors for PoSH have been extensively studied in recent years and may be classified into patient, disease and surgery related factors. Some risk factors are modifiable; but both modifiable and non-modifiable factors help in generating a risk profile that may be used to select patients for preventative measures and/or changes in surgical strategy. This narrative review discusses recent literature on the incidence, prevalence and risk factors for PoSH.

Thyroid incidentalomas on PET imaging--evaluation of management and clinical outcomes.

OBJECTIVES: 1. To determine the incidence of 'thyroid incidentaloma' in patients undergoing PET/CT in Sheffield. 2. To assess the distribution of cancer type, stage and short term outcomes of incidentally detected thyroid cancer in this cohort. METHODOLOGY: Patients with an unexpected thyroid radio-isotope uptake on reports of whole body nuclear imaging performed in Sheffield Teaching Hospitals NHS Foundation Trust for 'non-thyroid' indications from April 2008 to March 2011 were identified. Patients who have undergone PET imaging were then selected. The management, clinical and pathology details and short term 'thyroid-related' outcomes of patients with thyroid incidentaloma on PET scans were analysed. RESULTS: 1730 PET nuclear imaging studies were performed in this period. Thyroid incidentalomas were detected in 65 (3.8%)of these scans. Two thyroid cancers were detected in this cohort, both demonstrated focal uptake on the PET scan. Histology showed papillary thyroid cancer (TNM classification; pT1N1Mx and pT1bNxMx). CONCLUSION: The risk of cancer in PET detected thyroid incidentaloma in this series (3%) is low compared to published literature (5-50%). Potential reasons are discussed. The low rate of thyroid cancer in our incidentaloma cohort will influence decision making regarding management of these lesions. Only two thyroid cancers were detected in our cohort, limiting the narrative on type, stage of PET detected thyroid cancer and outcomes. Further observational research is required to study the natural history of these lesions in settings where there is a clear protocol for imaging, biopsy and treatment.

A breast cancer risk haplotype in the caspase-8 gene.

Recent large-scale studies have been successful in identifying common, low-penetrance variants associated with common cancers. One such variant in the caspase-8 (CASP8) gene, D302H (rs1045485), has been confirmed to be associated with breast cancer risk, although the functional effect of this polymorphism (if any) is not yet clear. In order to further map the CASP8 gene with respect to breast cancer susceptibility, we performed extensive haplotype analyses using single nucleotide polymorphisms (SNP) chosen to tag all common variations in the gene (tSNP). We used a staged study design based on 3,200 breast cancer and 3,324 control subjects from the United Kingdom, Utah, and Germany. Using a haplotype-mining algorithm in the UK cohort, we identified a four-SNP haplotype that was significantly associated with breast cancer and that was superior to any other single or multi-locus combination (P=8.0 x 10(-5)), with a per allele odds ratio and 95% confidence interval of 1.30 (1.12-1.49). The result remained significant after adjustment for the multiple testing inherent in mining techniques (false discovery rate, q=0.044). As expected, this haplotype includes the D302H locus. Multicenter analyses on a subset of the tSNPs yielded consistent results. This risk haplotype is likely to carry one or more underlying breast cancer susceptibility alleles, making it an excellent candidate for resequencing in homozygous individuals. An understanding of the mode of action of these alleles will aid risk assessment and may lead to the identification of novel treatment targets in breast cancer.

Ruptured staphylococcal splenic abscess resulting in peritonitis: report of a case.

A 50-year-old man presented with features of peritonitis of 2 days duration. The signs were more marked in the left upper abdomen. Investigations followed by a laparotomy showed a ruptured splenic abscess, the cause of which was not apparent. We herein present the case report of this unusual cause of peritonitis along with a relevant review of the literature.