Small Pancreatic and Periampullary Neuroendocrine Tumors: Resect or Enucleate?

Objective  The aim of this study was to compare the outcomes of enucleation versus resection in patients with small pancreatic, ampullary, and duodenal neuroendocrine tumors (NETs). Methods  Multi-institutional retrospective review identified all patients with pancreatic and peri-pancreatic NETs who underwent surgery from January 1990 to October 2008. Patients with tumors ≤3 cm and without nodal or metastatic disease were included. Results  Of the 271 patients identified, 122 (45%) met the inclusion criteria and had either an enucleation (n = 37) and/or a resection (n = 87). Enucleated tumors were more likely to be in the pancreatic head (P = 0.003) or functioning (P < 0.0001) and, when applicable, less likely to result in splenectomy (P = 0.0003). The rate of pancreatic fistula formation was higher after enucleation (P < 0.01), but the fistula severity tended to be worse following resection (P = 0.07). The enucleation and resection patients had similar operative times, blood loss, overall morbidity, mortality, hospital stay, and 5-year survival. However, for pancreatic head tumors, enucleation resulted in decreased blood loss, operative time, and length of stay compared to pancreaticoduodenectomy (P < 0.05). Conclusion  These data suggest that most outcomes of enucleation and resection for small pancreatic and peri-pancreatic NETs are comparable. However, enucleation has better outcomes than pancreaticoduodenectomy for head lesions and the advantage of preserving splenic function for tail lesions. Presented at the 2009 American Hepatopancreaticobiliary Association, March 14, 2009, Miami, FL American College of Surgeons Resident Research Scholarship, NIH Grant T32 CA009614 Physician Scientist Training in Cancer Medicine.     

Liver transplantation for hepatocellular cancer: should the current indication criteria be changed?

Liver transplantation (LTx) is the best treatment for hepatocellular carcinoma (HCC), but should be offered only to selected patients. The usual procedure is to transplant only for small and unilobular tumors. The aim of this paper is to verify whether the actual indication criteria are still justified. The details of 121 patients with HCC who were submitted to LTx from 1985 to 2000 were analyzed. Age, gender, liver disease, Child class, alpha-fetoprotein (AFP) level, presence of tumor capsule, vascular invasion, size and number of nodules, histological grade, and pTNM were considered. The 5- and 10-year actuarial survival rates were 61.7% and 53.1%. Freedom from recurrence was 85.9% and 85.9%, respectively. At univariate analysis, size, presence of capsule, AFP levels, vascular invasion, grade, pTNM, transarterial chemoembolization (TACE), Child class, and age were all significantly related to survival and/or cancer recurrence. Presence of capsule, AFP levels, and viral cirrhosis were independent variables in Cox's analysis for survival, whereas histological grade, AFP levels, and vascular invasion were significant independent variables for recurrence. In conclusion, a strict selection should be made to optimize graft allocation while size and multifocality should probably no longer be considered a contraindication for LTx. Histological grade, AFP levels, and vascular invasion, as indicator of tumor behavior, more likely reflect the risk of recurrence.     

Cardiac resynchronization therapy: variations in echo-guided optimized atrioventricular and interventricular delays during follow-up

BACKGROUND: Relatively few data are available on long-term echocardiographic optimization of atrioventricular (AV) and interventricular (VV) delay programming in cardiac resynchronization therapy (CRT). We assessed variations in optimized AV and VV delays during long-term follow-up. METHODS: Thirty-seven consecutive heart failure patients received Doppler echocardiographic optimization of AV and VV delay within 48 hours from CRT device implantation, at 6 months and at 12 months (the last for the first enrolled 14 patients). RESULTS: After implantation, median optimized AV delay was 100 ms (range, 45 ms); VV optimization led to simultaneous biventricular activation in 4 patients, left ventricular preactivation in 17 patients and right ventricular preactivation in 16 patients. At 12 months median AV delay decreased to 85 ms (23 ms) (P < 0.05 vs. baseline). With respect to previous assessment, VV delay variations > or =40 ms were observed in 41% of the patients at 6 months and in 57% of the tested patients at 12 months. A nonconcordance (by Kappa test) of optimized VV delays was found between each new assessment and the previous one. VV delay optimization was associated with significant (P < 0.001) increases in aortic velocity time integral both at baseline and during follow-up. CONCLUSIONS: Echocardiographic optimization of AV and VV delay is associated with broad intraindividual variability during follow-up. A new assessment of optimized VV delays during long-term follow-up reveals a nonconcordance with previous values and provides increases in forward stroke volume.     

HIV-1 matrix protein p17 binds to the IL-8 receptor CXCR1 and shows IL-8-like chemokine activity on monocytes through Rho/ROCK activation

Exogenous HIV-1 matrix protein p17 was found to deregulate biologic activities of many different immune cells that are directly or indirectly involved in AIDS pathogenesis after binding to unknown cellular receptor(s). In particular, p17 was found to induce a functional program in monocytes related to activation and inflammation. In the present study, we demonstrate that CXCR1 is the receptor molecule responsible for p17 chemokine-like activity on monocytes. After CXCR1 binding, p17 was capable of triggering rapid adhesion and chemotaxis of monocytes through a pathway that involved Rho/ROCK. Moreover, CXCR1-silenced primary monocytes lost responsiveness to p17 chemoattraction, whereas CXCR1-transfected Jurkat cells acquired responsiveness. Surface plasmon resonance studies confirmed the capacity of p17 to bind CXCR1 and showed that the p17/CXCR1 interaction occurred with a low affinity compared with that measured for IL-8, the physiologic CXCR1 ligand. In all of its activities, p17 mimicked IL-8, the natural high-affinity ligand of CXCR1. Recent studies have highlighted the role of IL-8 and CXCR1 in HIV-1 replication and AIDS pathogenesis. Our findings herein call for an exploration of the therapeutic potential of blocking the p17/IL-8/CXCR1 axis in HIV-1 infection.     

High prevalence of polymorphisms of angiotensin-converting enzyme (I/D) and endothelial nitric oxide synthase (Glu298Asp) in patients with systemic sclerosis

PURPOSE: Systemic sclerosis is characterized by progressive microvascular occlusion and fibrosis and by an imbalance in the fibrinolytic system. In vivo and in vitro studies suggest that the renin-angiotensin system partly regulates vascular fibrinolytic balance. Angiotensin II increases the production and secretion of plasminogen activator inhibitor-1, while angiotensin-converting enzyme (ACE) contributes to reduced production of tissue plasminogen activator and endothelial nitric oxide synthesis by bradykinin degradation. The aim of our study was to investigate the effects of ACE insertion/deletion (I/D) and endothelial nitric oxide synthase (eNOS) Glu298Asp (G894-->T) and T-786-->C polymorphisms in patients with systemic sclerosis. SUBJECTS AND METHODS: We studied 73 consecutive patients (47 with limited and 26 with diffuse cutaneous systemic sclerosis) and 112 control subjects. ACE I/D and eNOS polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis. RESULTS: The ACE I/D and the eNOS G894-->T polymorphisms were more common in patients than in controls (for the ACE D allele: odds ratio [OR] = 3.4; 95% confidence interval [CI]: 1.5 to 7.9; P = 0.003; for the eNOS T allele: OR = 1.9; 95% CI: 1.0 to 3.4; P = 0.04). There was no association between the eNOS T-786-->C polymorphism and systemic sclerosis. CONCLUSIONS: Our findings of an increased risk of systemic sclerosis in ACE D and eNOS 894T allele carriers suggest that these polymorphisms may contribute to the pathogenesis of the disease.