Early analysis of laparoscopic common bile duct exploration simulation.

BACKGROUND: We developed a laparoscopic common bile duct exploration (LCBDE) simulation course for resident surgeons (RS) and practicing surgeons (PS). We hypothesized that course completion would provide LCBDE procedural skills and increase procedure utilization. METHODS: RS and PS were prospectively enrolled. Pre- and post-course ability were assessed with written examinations and LCBDE simulations. PS completed pre-course, post-course, and 1-year follow-up surveys (5-point Likert-type scale). RESULTS: 17 RS and 8 PS were enrolled. Median written test scores improved (70.0%-80.0%, p < 0.001) and median LCBDE simulation times (seconds) improved (585-314, p = 0.001) among all participants. Comparing RS and PS, median written assessment scores pre-course (70% vs 72.5%, p = 0.953) and post-course (77.5% vs 80.0%, p = 0.198) were not significantly different. Simulation completion times (seconds) improved similarly from pre-course (608.0 vs 521.5, p = 0.885) to post-course (314.0 vs 373.0, p = 0.287) between groups. PS comfort with LCBDE improved (2-4, p = 0.03). All PS reported LCBDE utilization 1 year post-course. CONCLUSIONS: The LCBDE course is appropriate for RS and PS. PS also reported increased comfort with LCBDE and procedure utilization.

Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios can Predict Treatment Response to Neoadjuvant Therapy in Esophageal Cancer.

INTRODUCTION: We hypothesized that serum neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios may predict pathologic complete response to neoadjuvant chemoradiotherapy in esophageal cancer patients. The ability to predict favorable treatment response to therapy may aid in determining optimal treatment regimens. MATERIALS AND METHODS: A retrospective review of a prospective esophageal disease registry was conducted. Neutrophil-to-lymphocyte ratio was defined as the pre-chemoradiotherapy serum neutrophil count divided by lymphocyte count. Platelet-to-lymphocyte ratio was similarly defined. Logistic regression was applied to analyze these ratios and their effect on pathologic complete response. A Cox proportional-hazards model was used to analyze survival. RESULTS: Sixty patients were included. Elevated neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio were both negative predictors of pathologic complete response (odds ratio: 0.62; 95% confidence interval: 0.37-0.89, P = 0.037 and odds ratio: 0.91; 95% confidence interval: 0.82-0.98, P = 0.028, respectively). Only platelet-to-lymphocyte ratio was predictive of decreased overall survival (hazard ratio: 1.05, 95% confidence interval: 0.94-1.16, P = 0.40). CONCLUSION: Elevated neutrophil and platelet-to-lymphocyte ratios were significant predictors of a poor treatment response to neoadjuvant therapy. Only elevated platelet-to-lymphocyte ratio was predictive of worse overall survival. Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios may offer a simple serum test to assess the likelihood of a pathologic complete response after neoadjuvant therapy in esophageal cancer.

The Global Burden of Esophageal Cancer: A Disability-Adjusted Life-Year Approach.

INTRODUCTION: Esophageal cancer is the eighth most common cancer worldwide and the sixth leading cause of cancer-related deaths. As a significant cause of morbidity and mortality, its burden on society has yet to be fully characterized. The aim of this study is to examine its global burden through estimation of the disability-adjusted life years (DALYs) attributable to it. METHODS: Global incidence and mortality estimates for esophageal cancer were obtained from the International Agency for Research on Cancer GLOBOCAN 2008 database. DALYs were calculated, using methodology established by the World Health Organization. RESULTS: In 2008, 3,955,919 DALYs were attributed to esophageal cancer, at a global rate of 0.58 DALYs per 1000 people annually. Years of life lost (YLL) accounted for 96.8 % of DALYs, while years lived with disability (YLD) accounted for 3.2 %. 83.8 % of the global DALYs occurred in less-developed countries, with most accrued in Eastern Asia, comprising 50.9 % of the total. The highest rate of DALY accrual was in Southern Africa, at 1.62 DALYs per 1000 people annually. CONCLUSIONS: A substantial number of years of life were lost or affected by esophageal cancer worldwide in 2008, with the burden resting disproportionately on less-developed countries. Geographically, the greatest burden is in Eastern Asia. The vast majority of DALYs were due to YLL, rather than YLD, indicating the need to focus resources on disease prevention and early detection. Our findings provide an additional basis upon which to formulate global priorities for interventions that affect DALY reduction in esophageal cancer.

Molecular Marker Expression Is Highly Heterogeneous in Esophageal Adenocarcinoma and Does Not Predict a Response to Neoadjuvant Therapy.

A reliable method to identify pathologic complete responders (pCR) or non-responders (NR) to neoadjuvant chemoradiation therapy (NAT) would dramatically improve therapy for esophageal cancer. The purpose of this study is to investigate if a distinct profile of prognostic molecular markers can predict pCR after neoadjuvant therapy. Expression of p53, Her-2/neu, Cox-2, Beta-catenin, E-cadherin, MMP-1, NFkB, and TGF-B was measured by immunohistochemistry in pre-treatment biopsy tissue and graded by an experienced pathologist. A pCR was defined as no evidence of malignancy on final pathology. Molecular profiles comparing responders to non-responders were analyzed using classification and regression tree analysis to investigate response to NAT and overall survival. Nineteen patients were pCRs and 34 were NRs. pCRs were more likely to be alive at follow-up than NRs (p < 0.01). Thirty-seven distinct profiles were identified. Expression of molecular markers was highly heterogeneous between patients and did not correlate with a response to NAT, survival (p = 0.47) or clinical stage (p = 0.39) when evaluated either as individual markers or in combination with other expression patterns. NAT dramatically impacts survival through a mechanism independent of known molecular markers of esophageal cancer, which are expressed in a highly heterogeneous fashion and do not predict response to NAT or survival.

Lymph Node Harvest During Esophagectomy Is Not Influenced by Use of Neoadjuvant Therapy or Clinical Disease Stage.

INTRODUCTION: The purpose of this study was to evaluate the effects of neoadjuvant therapy on lymph node harvest (LNH), lymph node ratio (LNR), and overall survival rates after esophagectomy. METHODS: A retrospective analysis of 111 patients who underwent esophagectomy for esophageal adenocarcinoma from 2001 to 2010 was performed. Patients were divided into two groups: neoadjuvant chemoradiotherapy prior to surgery (NEOSURG) versus surgery alone (SURG). RESULTS: There were 83 patients (75%) in the NEOSURG group and 28 (25%) in the SURG group with a mean age of 66 and 67 years, respectively. The median LNH in the NEOSURG group and SURG group was 16.0 and 15.5, respectively (p = 0.57). Within the NEOSURG group, the median LNH was 16 for complete responders, 14 for partial responders, 16 for nonresponders, and 18 in those who were pathologically upstaged (p = 0.434). The median LNR was 0, 0, 0.1, and 0.2, respectively (p < 0.001). Complete response after neoadjuvant therapy demonstrated a trend toward improved survival (p = 0.056). CONCLUSION: The LNH was not significantly influenced by neoadjuvant treatment or pathologic response. The LNR was inversely related to pathologic response after neoadjuvant therapy. Complete pathologic response to neoadjuvant therapy trends to improve survival rates.

The incidence of hiatal hernia after minimally invasive esophagectomy.

INTRODUCTION: Minimally invasive esophagectomy (MIE) has evolved as a means to minimize the morbidity of an operation which is traditionally associated with a significant risk. However, this approach may have its own unique postoperative complications. In this study, we describe the incidence and outcomes of hiatal hernia in a cohort of MIE patients. METHODS: Clinical follow-up data on 114 patients who had undergone minimally invasive esophagectomy between 2003 and 2011 were retrospectively reviewed. Clinical presentation and computed tomography (CT) scans of the chest and abdomen were used to establish the diagnosis of hiatal herniation after minimally invasive esophagectomy. Age, gender, presenting complaint, comorbid conditions, clinical tumor stage, surgical specimen size, length and cost of hospital admissions, operation performed for hiatal herniation, and mortality were all recorded for analysis. RESULTS: Nine (8%) of the 114 patients who underwent MIE had postoperative hiatal herniation. Five of these patients were asymptomatic. All patients except two who presented emergently were repaired laparoscopically on an elective basis. The average length of stay after hiatal hernia repair was 5.5 days (range 2-12) at an average charge of $40,785 (range $25,264-$83,953). At follow-up, one patient complained of symptoms associated with reflux. CONCLUSION: Hiatal herniation is not a rare event after MIE. It is also associated with significant health-care cost and may be lethal. Most occurrences appear to be asymptomatic and, if detected, can be repaired with good resolution of symptoms, minimal associated morbidity, and no mortality.

The general surgery job market: analysis of current demand for general surgeons and their specialized skills.

BACKGROUND: The majority of general surgery residents pursue fellowships. However, the relative demand for general surgical skills vs more specialization is not understood. Our objective was to describe the current job market for general surgeons and compare the skills required by the market with those of graduating trainees. STUDY DESIGN: Positions for board eligible/certified general surgeons in Oregon and Wisconsin from 2011 to 2012 were identified by review of job postings and telephone calls to hospitals, private practice groups, and physician recruiters. Data were gathered on each job to determine if fellowship training or specialized skills were required, preferred, or not requested. Information on resident pursuit of fellowship training was obtained from all residency programs within the represented states. RESULTS: Of 71 general surgery positions available, 34% of positions required fellowship training. Rural positions made up 46% of available jobs. Thirty-five percent of positions were in nonacademic metropolitan settings and 17% were in academic metropolitan settings. Fellowship training was required or preferred for 18%, 28%, and 92% of rural, nonacademic, and academic metropolitan positions, respectively. From 2008 to 2012, 67% of general surgery residents pursued fellowship training. CONCLUSIONS: Most general surgery residents pursue fellowship despite the fact that the majority of available jobs do not require fellowship training. The motivation for fellowship training is unclear, but residency programs should tailor training to the skills needed by the market with the goal of improving access to general surgical services.

Tailoring esophageal cancer surgery.

Esophageal cancer is a significant source of major mortality worldwide and is increasing dramatically in incidence. Without treatment this disease leads rapidly to death, but intervention also carries significant risk, so a carefully tailored approach must be used to maximize oncological efficacy while minimizing the negative consequences of intervention. Careful patient selection based on histologic and anatomic staging, consideration of each patient's clinical variables, appropriately timing chemo- and radiation therapy, and minimizing the morbidity of surgical intervention may significantly improve a patient's chances of surviving this disease, but each must be carefully orchestrated with a tailored approach to treatment. This review will serve as a guide to tailoring surgery for esophageal cancer.

Temperature modifies potentiation but not depotentiation in bidirectional hippocampal plasticity of Syrian hamsters (Mesocricetus auratus).

Previous studies have shown that one form of neuroplasticity, population spike (PS) potentiation, can be established in the hamster hippocampus at temperatures above 20 degrees C. Here, we tested three related hypotheses; namely, that in Syrian hamsters: (1) PS potentiation can be elicited below 20 degrees C and that at any constant temperature, potentiation can be described by a pair of sigmoidal functions matched to input/output curves; (2) potentiation can be partially reversed by depotentiation (a second and distinctive form of neuroplasticity); and (3) tetanus evokes long-term potentiation in slices from animals housed under conditions corresponding to various stages of the annual hibernation cycle. To test these hypotheses, we measured PS amplitudes and fEPSP slopes in CA1 pyramidal cells in hippocampal slices. We found that sigmoidal functions before and after tetanus showed PS enhancement at 18 degrees C and a larger enhancement at 28 degrees C, thereby supporting hypothesis 1. We also found that low-frequency stimulation reduced the amplitude of the potentiated PS by approximately 29% at both 18 degrees C and 28 degrees C, consistent with hypothesis 2; and that slices from nonhibernating hamsters on long and short photoperiods and from hamsters in hibernation all showed at least 40% increases in fEPSP slope following tetanus at a slice temperature of 23 degrees C, supporting hypothesis 3. Thus, bidirectional plasticity is present in hamsters. That is, both potentiation and depotentiation were readily evoked at 28 degrees C; potentiation was muted, while depotentiation (the reversal of the potentiation) remained robust at 18 degrees C. Moreover, potentiated responses could be elicited in slices from animals housed under diverse conditions.

LOXL null mice demonstrate selective dentate structural changes but maintain dentate granule cell and CA1 pyramidal cell potentiation in the hippocampus.

Lysyl oxidase-like protein (LOXL), part of the lysyl oxidase copper-dependent amine oxidase family, is expressed in the extracellular matrix and in the nucleus. It likely plays a role in cross-linking collagen and elastin, possibly modulating cellular functions. Immunohistochemical studies show the presence of LOXL in the pyramidal cell layer of the hippocampus; and in this study, we report that cells in the granule cell layer have significantly smaller somas in LOXL -/- compared to LOXL +/+ mice. In addition we tested the hypothesis that these structural alterations in the dentate granule layer were associated with synaptic efficacy and thus muted long-term potentiation in mice lacking the protein. Electrical recordings were obtained in 300-mum hippocampal slices in dentate and CA1 pyramidal cell layers in age-matched wild type and LOXL null mice. Potentiation in the CA1 cell layer of 10 LOXL -/- and 8 LOXL +/+ mice was 191.0+/-9.3% and 181.6+/-9.1%, respectively (mean+/-S.E.M.). Dentate potentiation was 120.8+/-7.0% and 121.0+/-3.4% in 11 LOXL -/- and 11 LOXL +/+ mice, respectively. No phenotypic difference in potentiation of population spike amplitude (or in EPSP slope) in either layer was observed. Thus, contrary to expectation, structural changes in the hippocampus of LOXL -/- mice did not affect synaptic remodeling in a manner that impaired the establishment of LTP.