Faculty Bibliography

Background: A pancreaticoduodenectomy (PD) offers the only chance of a cure for pancreatic cancer and can be performed with low mortality and morbidity. However, little is known about outcomes of a PD in octogenarians. Methods: Differences in two groups of patients (Group Y, <80 and Group O, >/=80 year-old) who underwent a PD for pancreatic adenocarcinoma were analysed. Study end-points were length of post-operative stay, overall morbidity, 30-day mortality and overall survival. Results: There were 175 patients in Group Y (mean age 64 years) and 25 patients in Group O (mean age 83 years). Octogenarians had worse Eastern Cooperative Oncology Group (ECOG) Performance Status (PS >/=1: 90% vs. 51%) and American Society of Anesthesiology (ASA) score (>2: 71% vs. 47%). The two groups were similar in underlying co-morbidities, operative time, rates of portal vein resection, intra-operative complications, blood loss, pathological stage and status of resection margins. Octogenarians had a longer post-operative stay (20 vs. 14 days) and higher overall morbidity (68% vs. 44%). There was a single death in each group. At a median follow-up of 13 months median survival appeared similar in the two groups (17 vs. 13 months). Conclusions: As 30-day mortality and survival are similar to those observed in younger patients, a PD can be offered to carefully selected octogenarians.

BACKGROUND: Simulation-based training provides a low-stress learning environment where real-life emergencies can be practiced. Simulation can improve surgical education and patient care in crisis situations through a team approach emphasizing interpersonal and communication skills. OBJECTIVE: This study assessed the effects of simulation-based training in the context of trauma resuscitation in teams of trainees. METHODS: In a New York State-certified level I trauma center, trauma alerts were assessed by a standardized video review process. Simulation training was provided in various trauma situations followed by a debriefing period. The outcomes measured included the number of healthcare workers involved in the resuscitation, the percentage of healthcare workers in role position, time to intubation, time to intubation from paralysis, time to obtain first imaging study, time to leave trauma bay for computed tomography scan or the operating room, presence of team leader, and presence of spinal stabilization. Thirty cases were video analyzed presimulation and postsimulation training. The two data sets were compared via a 1-sided t test for significance (p < 0.05). Nominal data were analyzed using the Fischer exact test. RESULTS: The data were compared presimulation and postsimulation. The number of healthcare workers involved in the resuscitation decreased from 8.5 to 5.7 postsimulation (p < 0.001). The percentage of people in role positions increased from 57.8% to 83.6% (p = 0.46). The time to intubation from paralysis decreased from 3.9 to 2.8 minutes (p < 0.05). The presence of a definitive team leader increased from 64% to 90% (p < 0.05). The rate of spine stabilization increased from 82% to 100% (p < 0.08). After simulation, training adherence to the advanced trauma life support algorithm improved from 56% to 83%. CONCLUSIONS: High-stress situations simulated in a low-stress environment can improve team interaction and educational competencies. Providing simulation training as a tool for surgical education may enhance patient care

BACKGROUND & AIMS: The cellular mediators of acute pancreatitis are incompletely understood. Dendritic cells (DCs) can promote or suppress inflammation, depending on their subtype and context. We investigated the roles of DC in development of acute pancreatitis. METHODS: Acute pancreatitis was induced in CD11c.DTR mice using caerulein or L-arginine; DCs were depleted by administration of diphtheria toxin. Survival was analyzed using Kaplan-Meier method. RESULTS: Numbers of major histocompatibility complex II(+)CD11c(+) DCs increased 100-fold in pancreata of mice with acute pancreatitis to account for nearly 15% of intrapancreatic leukocytes. Intrapancreatic DCs acquired a distinct immune phenotype in mice with acute pancreatitis; they expressed higher levels of major histocompatibility complex II and CD86 and increased production of interleukin-6, membrane cofactor protein-1, and tumor necrosis factor-alpha. However, rather than inducing an organ-destructive inflammatory process, DCs were required for pancreatic viability; the exocrine pancreas died in mice that were depleted of DCs and challenged with caerulein or L-arginine. All mice with pancreatitis that were depleted of DCs died from acinar cell death within 4 days. Depletion of DCs from mice with pancreatitis resulted in neutrophil infiltration and increased levels of systemic markers of inflammation. However, the organ necrosis associated with depletion of DCs did not require infiltrating neutrophils, activation of nuclear factor-kappaB, or signaling by mitogen-activated protein kinase or tumor necrosis factor-alpha. CONCLUSIONS: DCs are required for pancreatic viability in mice with acute pancreatitis and might protect organs against cell stress

Background: The AJCC staging for pancreatic cancer is relatively non-discriminatory for prediction of survival after resection. At the Moffitt Cancer Center a prognostic score for patients with localized pancreatic cancer (AJCC <= IIb) has been developed. In the Moffitt Prognostic Index (MPI) patients are grouped in 5 risk categories on the basis of extra-pancreatic tumor extension, degree of differentiation and lymphatic invasion. The aim of this study is to assess the MPI's predictive value in an independent cohort of patients who underwent pancreaticoduodenectomy (PD) at the New York University. Methods From our retrospective pancreatic adenocarcinoma database of 248 patients, we identified and grouped by MPI category patients with AJCC stage <= IIb who underwent PD (1990-2009). Differences between groups were evaluated using ANOVA and chi-squared test. Overall survival (OS) for each group was estimated using the Kaplan-Meier method and compared using the log-rank statistic. Results Among 131 patients with stage Ia-IIb cancer, MPI could be calculated for 126 (96%). Only few patients fell in MPI lower-risk groups 1- 4 (respectively 1, 4, 3, 22), while the majority (96, 76.1%) fell in MPI group 5 (poor prognosis). The 5 groups were similar in demographics, underlying comorbidities, laboratory data, ASA score and ECOG performance status. There were no differences in operative time, blood loss, intra- and post-operative complications, length of stay, 30-day mortality. Pathology revealed more advanced stage in groups 3 to 5 (p=0.001). At mean follow-up of 18 months, there was no difference in median OS across MPI groups (respectively 19, 6, 16, 17, 12 months, p=0.91). Of note, AJCC staging did correlate with median OS (respectively 43, 12, 16, 11 months in stages Ia to IIb, p = 0.004). Conclusions In our experience the MPI performed worse than AJCC staging as a prognostic tool. The clustering of patients in the worst-prognosis group defied the very purpose of prognosis discrimination. Furthermore, in our experience MPI did not correlate with overall survival in patients undergoing DP for earlystage (<= IIb) pancreatic cancer

Introduction: Surgery offers the only chance for cure in patients with pancreatic cancer. Currently, pancreaticoduodenectomy can be performed with a mortality of under 5% and a morbidity of 40-50%. Little, however, is known about outcomes of pancreaticoduodenectomy (PD) in octogenarians. This manuscript details outcomes after PD for adenocarcinoma in patients 80 years and older. Methods: From our comprehensive pancreatic adenocarcinoma database of 248 patients, we identified 200 patients who underwent PD (1990-2009). We categorized patients into two groups, according to age at time of surgery: Group I (>= 80 year-old) and Group II (< 80 year-old). The study end-points were length of post-operative stay (LOS), overall morbidity, 30-day mortality, overall survival (OS). Differences between groups were evaluated using t-test or chi-squared test. Survival was compared using Kaplan-Meier analysis and log-rank test. Results: There were 25 patients in group I (mean age 83.1) and 175 patients in Group II (mean age 64.4). Octogenarians had worse ECOG performance status (PS >= 1 in 90% vs. 50.8%, p < 0.01) and ASA score (ASA 3- 4 in 70.8% vs. 47.4%, p < 0.01). The two groups were similar in regard to underlying co-morbidities (including coronary artery disease, COPD, diabetes, chronic renal failure), operative time, rates of portal vein resection, intraoperative complications, blood loss, pathologic AJCC stage, status of resection margins. Octogenarians had longer LOS (20 vs. 13.7 days, p=0.01) and higher overall morbidity (68% vs. 44%, p=0.03). There was a single death in each group (p=0.23). At median follow-up of 13 months older patients had a median OS of 17.3 months compared to 13.1 months in younger patients (p=0.06). Conclusions: Surgical morbidity and LOS are significantly increased in octogenarians. However 30-day mortality was not significantly increased and OS was superior (but not statistically significant) when compared to younger patients. The decision for PD should be individualized and offered to carefully selected octogenarians

The normal liver is characterized by immunologic tolerance. Primary mediators of hepatic immune tolerance are liver sinusoidal endothelial cells (LSECs). LSECs block adaptive immunogenic responses to Ag and induce the generation of T regulatory cells. Hepatic fibrosis is characterized by both intense intrahepatic inflammation and altered hepatic immunity. We postulated that, in liver fibrosis, a reversal of LSEC function from tolerogenic to proinflammatory and immunogenic may contribute to both the heightened inflammatory milieu and altered intrahepatic immunity. We found that, after fibrotic liver injury from hepatotoxins, LSECs become highly proinflammatory and secrete an array of cytokines and chemokines. In addition, LSECs gain enhanced capacity to capture Ag and induce T cell proliferation. Similarly, unlike LSECs in normal livers, in fibrosis, LSECs do not veto dendritic cell priming of T cells. Furthermore, whereas in normal livers, LSECs are active in the generation of T regulatory cells, in hepatic fibrosis LSECs induce an immunogenic T cell phenotype capable of enhancing endogenous CTLs and generating potent de novo CTL responses. Moreover, depletion of LSECs from fibrotic liver cultures mitigates the proinflammatory milieu characteristic of hepatic fibrosis. Our findings offer a critical understanding of the role of LSECs in modulating intrahepatic immunity and inflammation in fibro-inflammatory liver disease

Coomb's positive autoimmune hemolytic anemia with giant cell hepatitis (GCH) is a rare cause of liver failure and is usually associated with poor prognosis. A child with liver kidney microsomal (LKM) antibody positivity underwent successful liver transplantation for liver failure secondary to GCH with Coomb's positive hemolytic anemia. Autoimmune neutropenia developed ten months after transplant. Four months later, pemphigoid skin lesions developed. The diagnosis of bullous pemphigoid (BP) was made on the basis of skin biopsy, direct and indirect immunofluorescence test results. Treatment was with immunosuppressants - prednisone and azathioprine/rapamycin, with addition of dapsone when lesions persisted. This child is unique in that his liver function and hemolytic anemia appeared to normalize after liver transplant, but neutropenia and BP both thought to be autoimmune in etiology, developed more than a year post-transplant

This publication is the ninth in a series of safety evaluations performed by the Expert Panel of the Flavor and Extract Manufacturers Association (FEMA). In 1993, the Panel initiated a comprehensive program to re-evaluate the safety of more than 1700 GRAS flavoring substances under conditions of intended use. Elements that are fundamental to the safety evaluation of flavor ingredients include exposure, structural analogy, metabolism, pharmacokinetics and toxicology. Flavor ingredients are evaluated individually and in the context of the available scientific information on the group of structurally related substances. Scientific data relevant to the safety evaluation of the use of phenethyl alcohol, aldehyde, acid, and related acetals and esters as flavoring ingredients is evaluated. The group of phenethylalcohol, aldehyde, acid, and related acetals and esters was reaffirmed as GRAS (GRASr) based, in part, on their self-limiting properties as flavoring substances in food, their rapid absorption, metabolic detoxication, and excretion in humans and other animals, their low level of flavor use, the wide margins of safety between the conservative estimates of intake and the no-observed-adverse effect levels determined from subchronic and chronic studies and the lack of significant genotoxic and mutagenic potential. This evidence of safety is supported by the fact that the intake of phenethyl alcohol, aldehyde, acid, and related acetals and esters as natural components of traditional foods is greater than their intake as intentionally added flavoring substances