1112 Consecutive Bilateral Neck Explorations for Primary Hyperparathyroidism

Background Bilateral neck exploration has been the standard approach for patients with primary hyperparathyroidism. Improved localization studies and the availability of intraoperative parathyroid hormone monitoring have challenged the necessity of four-gland exploration. In this series we report a single surgeon’s experience with bilateral neck exploration for primary hyperparathyroidism in an effort to establish benchmark outcomes from which to evaluate minimally invasive protocols. Methods The charts of 1112 consecutive patients who underwent neck exploration for primary hyperparathyroidism by a single surgeon over a 17-year period were reviewed. All patients underwent bilateral neck exploration under either general (n = 264) or local (n = 848) anesthesia. Results The overall cure rate was 97.4% with a complication rate of 3.4%. Morbidity included recurrent laryngeal nerve injury (0.2%), postoperative bleeding (0.8%), and transient hypocalcemia (1.8%). There was no mortality. Overall mean operating time was 52.5 ± 30.2 minutes. A single gland was removed in 78.4% of patients, and 22.3% of patients underwent concomitant thyroidectomy. The cure rate was lower for patients undergoing reexploration (89.2% vs. 97.9%, p < 0.05). Choice of anesthetic approach did not affect the cure or complication rate. The overall conversion rate from local to general anesthesia was 1.5%. Patients undergoing general anesthesia were operated on earlier in the series and were less likely to be managed on an ambulatory basis (local 87.5% vs. general 38.4%, p < 0.05). During the last 5 years of the series, more than 90% of patients underwent exploration under local anesthesia. Conclusion This large modern series of neck explorations for primary hyperparathyroidism confirms the safety, feasibility, and efficacy of the bilateral approach. It further demonstrates that individual surgeons can achieve outcomes equivalent to those with four-gland explorations under local anesthesia.     

BRAF and KRAS gene mutations in intraductal papillary mucinous neoplasm/carcinoma (IPMN/IPMC) of the pancreas

The Raf/MEK/ERK (MAPK) signal transduction is an important mediator of a number of cellular fates including growth, proliferation, and survival. The BRAF gene is activated by oncogenic RAS, leading to cooperative effects in cells responding to growth factor signals. Our study was performed to elucidate a possible role of BRAF in the development of IPMN (Intraductal Papillary Mucinous Neoplasm) and IPMC (Intraductal Papillary Mucinous Carcinoma) of the pancreas. Mutations of BRAF and KRAS were evaluated in 36 IPMN/IPMC samples and two mucinous cystadenomas by direct genomic sequencing. Exons 1 for KRAS, and 5, 11, and 15 for BRAF were examined. Totally we identified 17 (47%) KRAS mutations in exon 1, codon 12 and one missense mutation (2.7%) within exon 15 of BRAF. The mutations appear to be somatic since the same alterations were not detected in the corresponding normal tissues. Our data provide evidence that oncogenic properties of BRAF contribute to the tumorigenesis of IPMN/IPMC, but at a lower frequency than KRAS.     

Characterization of 11 microsatellite loci for the brown smooth-hound shark, Mustelus henlei (Triakidae), discovered with next-generation sequencing

The brown smooth-hound shark, Mustelus henlei (Triakidae), is an endemic member of the eastern Pacific shark assemblage considered both commercially and recreationally important. Here, microsatellite loci for M. henlei discovered by next-generation sequencing (Roche 454 pyrosequencing) are described. All loci were polymorphic (3?C10 alleles) with observed heterozygosities between 0.24 and 0.89 and expected heterozygosities between 0.23 and 0.86. These loci are the first to be characterized explicitly for M. henlei and should be useful for the investigation of population structure and gene flow in this species and for other members of the Triakidae.     

Characterization of 13 microsatellite loci for the tope shark, Galeorhinus galeus, discovered with next-generation sequencing and their utility for eastern Pacific smooth-hound sharks (Mustelus)

The tope shark, Galeorhinus galeus, is a commercially important member of the Triakidae that has been exploited globally for the past 80 years. Here we describe 13 microsatellite loci for G. galeus discovered by next-generation sequencing (Roche 454 pyrosequencing) and their utility for eastern Pacific smooth-hound sharks (Mustelus). These loci were polymorphic (3–12 alleles) with observed heterozygosity between 0.11 and 0.86 and expected heterozygosity between 0.24 and 0.87. Several loci (7 of 13) amplified consistently for Mustelus californicus and M. henlei. These loci are the first to be characterized explicitly for G. galeus and should be useful in the investigation of population structure of this vulnerable elasmobranch.     

Intravenous immunoglobulin modulates the expansion and cytotoxicity of CD8+ T cells

Intravenous immunoglobulin (IVIg) is successfully used in the treatment of autoimmune diseases involving self‐reactive CD8⁺ T cells. However, its direct influence on the cytotoxic response remains unknown. Using an antigen cross‐presentation assay and a mouse model of ovalbumin (OVA) immunization, we showed that IVIg decreases the in vitro activation, proliferation and cytokine secretion of OVA‐specific CD8⁺ T cells (OT‐I), as well as the in vivo generation of OVA‐specific CD8⁺ T cells. In addition, IVIg significantly decreases the proportion of perforin‐ and CD107a‐expressing CD8⁺ T cells, and inhibits the cytotoxic activity of OVA‐activated OT‐I cells. The interference of IVIg with the CD8⁺ T‐cell response is associated with T‐cell receptor blockade, therefore reducing the interaction between effector and target cells. A similar blockade is observed on human CD8⁺ T cells, suggesting that the observations reported here could apply to the IVIg‐mediated improvement of CD8⁺ T‐cell‐mediated autoimmune conditions in human patients.     

Pancreaticoduodenectomy can be Performed Safely in Patients Aged 80 years and Older

Background  

Surgery offers the only chance for cure in patients with pancreatic cancer, and a growing number of elderly patients are being offered resection. We examined outcomes after pancreaticoduodenectomy in patients 80 years and older.