Change in Predicted 10-Year Cardiovascular Risk Following Laparoscopic Roux-en-Y Gastric Bypass Surgery

Background  Bariatric surgery is being conducted more often for morbid obesity, but little evidence exists about how it affects the risk of future cardiovascular events. The goal of this study was to quantify the change in predicted 10-year cardiovascular risk following laparoscopic Roux-en-Y gastric bypass (LRYGBP). Methods  We conducted a prospective clinical study of morbidly obese adults undergoing LRYGBP at a university hospital in the USA. Our primary outcome measure was mean change in 10-year cardiovascular risk at 12 months. We estimated cardiovascular risk by using the Framingham risk equation, which calculates the absolute risk of cardiovascular events for patients with no known history of heart disease, stroke, or peripheral vascular disease by using information on age, sex, blood pressure, total and high-density lipoprotein cholesterol levels, smoking status, and history of diabetes. Results  Ninety-two participants underwent LRYGBP between December 2004 and October 2005. Their predicted baseline 10-year cardiovascular risk was 6.7%. At 6 and 12 months, their predicted risk had decreased to 5.2% and 5.4%, respectively. Assuming no change in risk among untreated patients, this represents an absolute risk reduction of 1.3%; which suggests that 77 morbidly obese patients would have to undergo LRYGBP to avert one new case of cardiovascular disease over the ensuing 10 years (number needed to treat = 77). Conclusion  Our findings indicate that LRYGBP is associated with improvements in cardiovascular risk factors and a corresponding decrease in predicted 10-year risk of cardiovascular disease.     

Fractionated proton beam radiotherapy for acoustic neuroma

OBJECTIVE: This study evaluated proton beam irradiation in patients with acoustic neuroma. The aim was to provide maximal local tumor control while minimizing complications such as cranial nerve injuries. METHODS: Thirty-one acoustic neuromas in 30 patients were treated with proton beam therapy from March 1991 to June 1999. The mean tumor volume was 4.3 cm(3). All patients underwent pretreatment neurological evaluation, contrast enhanced magnetic resonance imaging, and audiometric evaluation. Standard fractionated proton radiotherapy was used at daily doses of 1.8 to 2.0 cobalt Gray equivalent: patients with useful hearing before treatment (Gardner-Robertson Grade I or II) received 54.0 cobalt Gray equivalent in 30 fractions; patients without useful hearing received 60.0 cobalt Gray equivalent in 30 to 33 fractions. RESULTS: Twenty-nine of 30 patients were assessable for tumor control and cranial nerve injury. Follow-up ranged from 7 to 98 months (mean, 34 mo), during which no patients demonstrated disease progression on magnetic resonance imaging scans. Eleven patients demonstrated radiographic regression. Of the 13 patients with pretreatment Gardner-Robertson Grade I or II hearing, 4 (31%) maintained useful hearing. No transient or permanent treatment-related trigeminal or facial nerve dysfunction was observed. CONCLUSION: Fractionated proton beam therapy provided excellent local control of acoustic neuromas when treatment was administered in moderate doses. No injuries to the Vth or VIIth cranial nerves were observed. A reduction in the tumor dose is being evaluated to increase the hearing preservation rate.     

Emergency Presenting Colon Cancer Is an Independent Predictor of Adverse Disease-Free Survival

Twenty percent of colon cancers present as an emergency. However, the association between emergency presentation and disease-free survival (DFS) remains uncertain. Consecutive patients who underwent elective (CC) and emergent (eCC) resection for colon cancer were included in the analysis. Survival outcomes were compared between the 2 groups in univariate/multivariate analyses. A total of 439 patients underwent colonic resection for colon cancer during the interval 2000−2010; 97 (22.1%) presented as an emergency. eCC tumors were more often located at the splenic flexure (P = 0.017) and descending colon (P = 0.004). The eCC group displayed features of more advanced disease with a higher proportion of T4 (P = 0.009), N2 tumors (P < 0.01) and lymphovascular invasion (P< 0.01). eCC was associated with adverse locoregional recurrence (P = 0.02) and adverse DFS (P < 0.01 ) on univariate analysis. eCC remained an independent predictor of adverse locoregional recurrence (HR 1.86, 95% CI 1.50–3.30, P = 0.03) and DFS (HR 1.30, 95% CI 0.88–1.92, P = 0.05) on multivariate analysis. eCC was not associated with adverse overall survival and systemic recurrence. eCC is an independent predictor of adverse locoregional recurrence and DFS.Key words: Emergency presentation, Colon cancer, Disease free survival, Locoregional recurrenceColorectal cancer (CRC) is a significant cause of mortality, with over 40,000 new cases diagnosed annually in the UK contributing to over 16,000 deaths (Bowel Cancer UK).^1,2 Up to 20% of colon cancers (CC) present as an emergency (eCC) necessitating emergent surgery.^3,4 Although eCC has been shown to be associated with poorer overall survival (OS), much discrepancy exists in the literature regarding its association with disease-free survival (DFS).⁵⁻⁷Studies reporting the oncologic outcomes of CRC presenting as an emergency consist of heterogeneous populations of patients with colon and rectal cancers.^3,5 Colon and rectal cancers are 2 distinct entities with different molecular, clinical, pathologic, and biologic characteristics and treatment modalities.^8,4,9−11 Since the incorporation of combined multimodal treatment and total mesorectal excision the disparity in OS and DFS between colon and rectal cancer has increased.¹²⁻¹⁷ Rectal cancer patients may alter the impression of outcomes in emergency presenting colon cancer. Consequently, previous studies assessing outcomes in eCC may be flawed. Furthermore, the negative impact of eCC has previously been attributed to immediate postoperative complications with an inpatient hospital mortality of approximately 15%. Inclusion of such cases in studies assessing long-term outcomes may have overestimated the negative impact of eCC.¹⁸The aim of the current study was to determine the association between eCC and disease-free/overall survival.     

The targeting of phosphoinositide-3 kinase attenuates pulmonary metastatic tumor growth following laparotomy

OBJECTIVE: We aimed to characterize a potential role for phosphatidylinositol 3-kinase (PI3k) in leading to accelerated postoperative metastatic tumor growth. BACKGROUND: PI3k enhances tumor cell survival in part by phosphorylating Akt and reducing apoptosis. Postoperatively, apoptosis is reduced within local recurrences and distant metastases. This reduction is associated with the phenomenon of accelerated postoperative tumor growth. METHODS: Balb/c mice underwent a tail vein injection of 1x10 metastatic murine mammary adenocarcinoma 4T1 cells. Animals were divided into the following treatment groups (n=10/group): group A, controls; group B, DMSO intraperitoneally (IP) daily from days 14 to 21; group C, IP LY294002 daily from days 14 to 21; group D, laparotomy only; group E, laparotomy followed by IP DMSO for 7 days; and group F, laparotomy followed by LY294002 IP for 7 days. All laparotomies were performed on day 14. Animals were killed at day 28. Metastatic tumor burden was assessed using the lung/body weight ratio and a histologic metastatic index. Mitotic counts and apoptotic indices were established using a combination of hematoxylin and eosin histology and TUNEL immunohistochemistry. A parallel survival study was performed, and PI3k activity was assessed using western blots for phospho-Akt. RESULTS: Laparotomy was associated with increased systemic tumor burden (P=0.001). Postoperatively, LY294002 significantly attenuated metastatic tumor growth (P<0.001). Effective PI3k inhibition was confirmed by demonstrating a reduced Akt phosphorylation. Moreover, PI3k inhibition led to reduced proliferation, increased apoptosis (P<0.001), and enhanced postoperative survival (P<0.001). CONCLUSIONS: Targeting PI3k with postoperative LY294002 significantly attenuates the acceleration in postoperative metastatic tumor growth seen following laparotomy.     

Impaired survival of peripheral T cells, disrupted NK/NKT cell development, and liver failure in mice lacking Gimap5

The loss of Gimap5 (GTPase of the immune-associated protein 5) gene function is the underlying cause of lymphopenia and autoimmune diabetes in the BioBreeding (BB) rat. The in vivo function of murine gimap5 is largely unknown. We show that selective gene ablation of the mouse gimap5 gene impairs the final intrathymic maturation of CD8 and CD4 T cells and compromises the survival of postthymic CD4 and CD8 cells, replicating findings in the BB rat model. In addition, gimap5 deficiency imposes a block of natural killer (NK)- and NKT-cell differentiation. Development of NK/NKT cells is restored on transfer of gimap5(-/-) bone marrow into a wild-type environment. Mice lacking gimap5 have a median survival of 15 weeks, exhibit chronic hepatic hematopoiesis, and in later stages show pronounced hepatocyte apoptosis, leading to liver failure. This pathology persists in a Rag2-deficient background in the absence of mature B, T, or NK cells and cannot be adoptively transferred by transplanting gimap5(-/-) bone marrow into wild-type recipients. We conclude that mouse gimap5 is necessary for the survival of peripheral T cells, NK/NKT-cell development, and the maintenance of normal liver function. These functions involve cell-intrinsic as well as cell-extrinsic mechanisms.     

Epitopes of the Highly Immunogenic Trichomonas vaginalis α-Actinin Are Serodiagnostic Targets for Both Women and Men

There is a need for a point-of-care serodiagnostic test for women and men for sexually transmitted infections (STIs) caused by Trichomonas vaginalis. Sera from women with this STI and sera from men that were analyzed in studies showing a relationship between serostatus and prostate cancer are highly seropositive in response to trichomonad α-actinin and its truncated protein (ACT-P2) (positive control sera). Epitope mapping experiments showed that positive control sera from women had antibodies to 13 distinct epitopes, 5 of which were detected by positive control sera from men. Sera from women and men that were unreactive with α-actinin (negative control sera) failed to detect any of the epitopes or other α-actinin amino acid sequences. The T. vaginalis α-actinin amino acid sequence and the sequences of the epitopes showed little or no identity with those of other proteins of microbial pathogens or the human α-actinin 1 (HuACTN1) homolog. Immunoassays such as dot blot, immunoblot, and enzyme-linked immunosorbent assays were used. Positive control sera did not detect HuACTN1 in immunoassays, and the range of levels of identity of α-actinin epitopes with HuACTN1 was 0% to 50%. Comparison of the T. vaginalis α-actinin epitopes with proteins in data banks, such as Tritrichomonas suis, Candida albicans, and Saccharomyces cerevisiae proteins, gave a range of identity levels of 0% to 22%. Specific 15-mer peptide epitopes of α-actinin with low to no identity with other proteins were synthesized and were reactive with positive control sera only. These findings identify epitopes of α-actinin as candidate serodiagnostic targets and suggest strongly that a highly seropositive reaction to α-actinin suggests exposure to T. vaginalis.     

Consensus Recommendations for the Diagnosis and Management of Pancreatic Neuroendocrine Tumors: Guidelines from a Canadian National Expert Group

Annals of Surgical Oncology - Pancreatic neuroendocrine tumors (pNETs) are rare heterogeneous tumors that have been steadily increasing in both incidence and prevalence during the past few decades....