55.08 Impact of Body Mass Index on Liver Regeneration After Major Liver Hepatectomy

Posted on January 18, 2016

N. Amini1, G. A. Margonis1, S. Buttner1, S. Besharati2, Y. Kim1, F. Gani1, F. Sobhani2, I. R. Kamel2, T. M. Pawlik1 1Johns Hopkins University School Of Medicine,Surgery,Baltimore, MD, USA 2Johns Hopkins University School Of Medicine,Radiology,Baltimore, MD, USA

Introduction: Obese patients may present with several metabolic abnormalities including hyperglycemia, hyper-insulinemia, and hyperlipidemia. These metabolic perturbations, as well as increased production of cytokines from visceral adipose tissue, negatively affect hepatocyte proliferation. Data on the impact of obesity on liver regeneration after major liver hepatectomy are lacking. As such, we sought to compare the liver volume regeneration index (RI) among patients by body mass indexes (BMI).

Methods: : Patients undergoing a major hepatectomy (≥3 segments) between July 2004 and April 2015 with available pre- and postoperative computed tomographic (CT) scans were identified. Patients were stratified by preoperative BMI; normal BMI (<25), overweight (25-29), and obese (≥30). Patients were matched on the number of segments resected, as well as the remnant liver volume (RLV) to total liver volume (TLV) ratio. TLV was assessed preoperatively, while RLV was measured at 2-3 and 6-7 months after surgery. The resected volume at surgery was subtracted from TLV to define postoperative RLV (RLVp). The liver volume RI was defined as the relative increase within 2-3 months [(RLV2-3m-RLVp)/RLVp] and 6-7 months [(RLV6-7m-RLVp)/RLVp] after surgery.

Results:Among a matched cohort of 80 patients, median age was 58 years (IQR, 49.7-68.6) and most were male (53.8%). Of note, while clinicopathological characteristics were similar across the three groups, obese patients presented with a higher incidence of diabetes (normal, 10% vs. overweight, 33.3% vs. obese, 46.2%; P=0.01). 48.7% of patients underwent a right hepatectomy while 25.0% and 26.3% underwent a left or extended hepatectomy, respectively. Obese patients had a higher median blood loss (normal, 300cc vs. overweight, 500cc vs. obese, 800 cc; P<0.001) and were more likely to be transfused (normal; 3.9% vs. overweight; 13.6% vs. obese; 30.4%, P=0.04). Initial postoperative RLVp/TLV was comparable across BMI categories (normal, 55.3% vs. overweight, 69.4% vs. obese, 67.8%, P=0.43). While BMI did not impact the RI within the first 2-3 months (normal weight, 32.5% vs. overweight, 24.7% vs. obese, 31.9% cc; P=0.60), the RI at 6-7 months was lower among overweight and obese patients (normal weight, 66.0% vs. overweight, 25.2% vs. obese, 47.9%, P=0.04, Figure).

Conclusion:Following major hepatic resection, BMI did not impact short-term liver regeneration over the initial 2-3 months. In contrast, liver regeneration assessed at 6-7 months was lower among overweight and obese patients compared with normal weight patients. Further research is necessary to investigate the metabolic factors and cytokine pathways that may influence long-term liver regeneration.

55.09 Outcomes of Minimally Invasive Esophagectomy: Is There a Benefit with Transthoracic Approaches?

Posted on January 18, 2016

A. Salem1, R. Shridhar2, K. Almhanna2, S. Hoffe2, K. Meredith3 3Florida State University College Of Medicine,Department Of Surgery,Tallahassee, FL, USA 1University Of Wisconsin,Department Of Surgery,Madison, WI, USA 2Moffitt Cancer Center And Research Institute,Department Of Surgery,Tampa, FL, USA

Introduction:
Surgery is pivotal in the management of patients with esophageal cancer. Recent prospective data demonstrates advantages of minimally invasive techniques compared to historical open cohorts. However, varying surgical techniques precludes the recommendation of a standard approach. We sought to examine our outcomes with differing approaches to minimally invasive esophagectomy.

Methods:
We queried a prospectively maintained esophageal database to identify patients who underwent minimally invasive esophagectomy (MIE) from 1994 to 2014. Surgical approaches included trans-hiatal (TH), Ivor Lewis (IVL), and robotic assisted Ivor Lewis (RAIL). Demographics, operative variables and post-operative complications were all compared and considered significant at p<=0.05.

Results:
We identified 280 patients who underwent MIE with a mean age of 65.65 ± 10.5 and a median follow-up of 48 months. Fifty-seven patients underwent IVL, 78 underwent TH, and 145 underwent RAIL. The length of operation was significantly longer in IVL and RAIL approaches compared to TH (TH=242 min, IVL=320 min, RAIL=415 min, p=0.001). Mean estimated blood loss did not differ between cohorts (TH=150 mL, IVL=125 mL, RAIL=158 mL, p=0.8). Rates of anastomotic leak, stricture, pneumonia, and wound infections were all higher in the TH compared to the trans-thoracic approaches p=0.04, p=0.02, p=0.01, and p<0.001 respectively (Table 1.). Operative mortality was low for each cohort and did not differ between approaches (TH=2.6%, IVL=0%, RAIL=2%, p=0.2). The median length of hospitalization also did not differ between groups (TH=10 days, IVL=8.5 days, RAIL=9 days, p=0.15). Oncologic outcomes were measured by completeness of resection and nodal harvest. There was decreased R1 resections in both the IVL and RAIL compared to TH (TH=8%, IVL=0%, and RAIL=0% p=0.04). Additionally, the mean number of lymph nodes harvested was lower in patients undergoing TH compared to IVL and RAIL groups (TH=9.2, IVL=12.8, and RAIL=20.6, p=0.05).

Conclusion:
In our large series comparing minimally invasive approaches to esophageal resection we have demonstrated improved operative outcomes in trans-thoracic approaches compared to trans-hiatal approach. Additionally, improved nodal harvest and increased R0 resection rates were improved with the trans-thoracic approaches. We recommend that patients undergoing minimally invasive esophagectomy be strongly considered for a trans-thoracic approach.

55.10 Effect of Standardizing Post-Operative Clinical Care Following Total Gastrectomy at a Cancer Center

Posted on January 18, 2016

L. V. Selby1, M. B. Rifkin1, M. F. Brennan1, C. E. Ariyan1, V. E. Strong1 1Memorial Sloan-Kettering Cancer Center,Surgery,New York, NY, USA

Introduction: Standardization of post-operative care has been shown to decrease length of stay following colectomy, but has not been evaluated in other complex intra-abdominal operations such as total gastrectomy.

Methods: In June 2009 we instituted a standardized post-operative care pathway emphasizing early oral feeding, early administration of oral pain medication, and early cessation of IV fluids in an attempt to decrease length of stay following total gastrectomy. Patients on pathway receive: clear liquid diet on post-operative day 1, diet progression as tolerated, early oral pain control, and discontinuation of IV fluids when tolerating a post-gastrectomy diet and oral pain medications. Variations of these principles had been employed previously, but not uniformly, among gastric surgeons at our center. We do not routinely place naso-jejeunal tubes or enteral feeding tubes, and only image the esophago-jejeunal anastomosis when clinically indicated. All curative intent gastrectomies performed within two years of standardization were reviewed to determine the effect standardization had on time to oral feeding, oral pain medication, length of stay, complications, and readmissions. Differences between groups were examined using a ranksum test for continuous variables and chi2 test for categorical variables; significance was defined as p <0.05.

Results: Between June 2007 and July 2011, 111 patients underwent curative intent total gastrectomy, 53 patients prior to standardization (pre) and 58 patients afterwards (post). Patients were predominantly male (70%), median age was 63, median BMI was 27 (pre vs post p = NS). Standardization of post-operative care resulted in a decrease in median time to beginning both a clear liquid diet (pre vs post: 3 days [IQR 2-4] vs 2 days [IQR 1-2]; p < 0.01) and a post-gastrectomy diet (pre vs post: 6 days [IQR 5-7] vs 4 days [IQR 4-5]; p < 0.01), earlier removal of epidural catheters (pre vs post: 6 days [IQR 5-7] vs 5 days[IQR 4-5]; p = 0.03), earlier use of oral pain medication (pre vs post: 7 days [IQR 5-8] vs 4 days [IQR 4-6]; p < 0.01), less time receiving IV fluids (pre vs post: 7 days [IQR 6-9] vs 5 days [IQR 4-8]; p < 0.01), and decreased length of stay (pre vs post: 9 days [IQR 7-12] vs 7 days [IQR 6-9]; p < 0.01). There was no difference between groups in complication rates, complication severity, or the percentage of patients who did not tolerate their diet, returned to our ER, or were readmitted.

Conclusion: Institution of a standardized post-operative clinical care pathway for total gastrectomy was associated with a significantly shorter length of stay with earlier oral feeding without increasing post-operative complication, ER visits, or readmissions.

55.05 Predictors of Improved Survival for Patients with Retroperitoneal Sarcoma

Posted on January 18, 2016

N. Nagarajan1, K. Giuliano1, J. K. Canner1, C. Wolfgang1, T. M. Pawlik1, S. Terezakis2, J. Herman2, E. B. Schneider1, N. Ahuja1 1Johns Hopkins University School Of Medicine,Surgery,Baltimore, MD, USA 2Johns Hopkins University School Of Medicine,Radiation Oncology,Baltimore, MD, USA

Introduction:
Retroperitoneal sarcomas (RPS) are rare tumors that can be locally aggressive with high rates of recurrence. Given that data on survival of patients with RPS are conflicting, we sought to use a nationwide cancer database to define factors associated with survival in patients with RPS.

Methods:
The Surveillance, Epidemiology and End-Results (SEER) database was utilized to identify patients with RPS from 2002 to 2012. Univariable and multivariable survival analysis was performed using Cox proportional hazard models. Since the underlying hazard function was not proportional, a relative time (Time Ratio) to event (cause-specific mortality) was modeled using a generalized gamma parametric survival function. Exposures of interest included age, sex, race, anatomical region, histological type (using ICD-O-3 codes), grade, size, local extension, lymph node and distant metastases, surgery, and radiation. Choice of appropriate modeling technique was based on Akaike Information Criteria (AIC) values.

Results:
A total of 2,920 patients were included; median age was 63 (IQR: 52-73) years, and 51.6% were female. The most common histological subtypes were liposarcoma (46.9%) and leiomyosarcoma (25.0%). The majority of tumors (84.5%) were <5 cm in size, 42.3% were high grade, and 39.5% had extension to adjacent organs/structures. About three quarters (75.6%) of patients underwent surgical resection, 25.9% had radiation therapy, and 21.6% received both. Overall 5- and 10-year survival were 57.1% and 38.9%, respectively. On multivariable survival analysis, increasing age, histological type (leiomyosarcoma, sarcoma not otherwise specified and others, as compared to liposarcoma), higher grade, increasing size, local extension, and presence of lymph node and distant metastasis were associated with increased risk of death (all p<0.05). After controlling for other factors, patients undergoing surgical resection survived 2.5 times longer than patients who did not undergo surgery (95% CI: 2.1-3.0, p<0.001). Patients who received radiation therapy survived 1.4 times longer than patients who did not receive radiation (95% CI: 1.2-1.7, p<0.001). A similar additive benefit of radiation was seen in the sub-cohort of patients who underwent surgery [Time Ratio: 1.4 (95% CI: 1.1-1.7), p=0.002] (Figure).

Conclusion:
Over the last decade RPS patients treated with radiation demonstrate longer survival compared with patients who did not receive radiation. This relationship was observed both among patients undergoing surgical resection, as well as among patients who did not undergo surgery. Further study is needed to fully elucidate the mechanisms that underlie the radiation-related survival benefit observed in this study.

55.06 Neoadjuvant Chemotherapy Provides a Survival Advantage in Clinical Stage II Pancreatic Head Cancer

Posted on January 18, 2016

W. Lutfi1, O. Kantor2, C. H. Wang3, E. Liederbach1, D. J. Winchester1, R. A. Prinz1, M. S. Talamonti1, M. S. Baker1 1Northshore University Health System,Department Of Surgery,Evanston, IL, USA 2University Of Chicago,Department Of Surgery,Chicago, IL, USA 3Northshore University Health System,Center For Biomedical Research Informatics,Evanston, IL, USA

Introduction:
There continues to be substantial international debate regarding the efficacy of neoadjuvant chemotherapy (NCT) prior to resection in early stage pancreatic cancer.

Methods:
We queried the National Cancer Data Base to identify patients that underwent pancreaticoduodenectomy (PD) for clinical stage (cStage) I-II pancreatic adenocarcinoma (PDAC) between 2000 and 2011. Multivariate logistic regression was used to analyze treatment trends and outcomes. Cox-modeling was used for survival analysis.

Results:
For the period studied, 8,099 patients underwent PD for cStage I-II PDAC. 3,237 (40.0%) were cStage I and 4,562 (60.0%) were cStage II. A total of 926 of the total recevied NCT; 271 (8.4%) with cStage I disease and 655 (13.5%) patients with cStage II disease received NCT. Use of NCT more than doubled over the period evaluated (6.5% of total patients in 2000 to 15.8% in 2011, p<0.01). Patients were more likely to receive NCT if they had vascular abutment (30.1% vs. 6.9%, p<0.01), were treated at an academic center (13.6% vs. 8.5%, p<0.01), or at a high volume hospital (17.8% vs. 10.2%, p<0.01). On univariate analysis, patients receiving NCT were more likely to have margin negative resection (81.8% vs. 75.3%, p<0.01) and be lymph node negative on final pathology (57.4% vs. 32.0% p<0.01) than those that did not. Multivariate regression adjusting for age, sex, race, comorbidities, insurance, socio-economic status, hospital type, location and volume, tumor grade, and vascular abutment identified patient age <56 years (OR 2.62, CI: 1.88-3.63), African-American race (OR 1.41, CI: 1.08-1.85), tumors that had vascular abutment (OR 5.18, CI: 4.27-6.28), cStage II disease (OR 1.33, CI: 1.13-1.57), and treatment at a facility with high surgical volume (OR 2.28, CI: 1.73-2.99) to be factors independently associated with use of NCT. Cox survival analysis adjusted for age, sex, race, comorbidities, insurance, socio-economic status, hospital type, location and volume, tumor grade, margins, and vascular abutment demonstrated a significant survival benefit for NCT in patients determined to have cStage II disease with median overall survival 21.6 months for those treated with NCT vs. 16.5 months receiving no treatment prior to surgery (p<0.01). Patients with cStage I treated with NCT demonstrated no difference in overall survival compared to those having surgery prior to systemic therapy (median overall survival 19.4 months vs. 19.7 months, p>0.90).

Conclusion:
Patients with cStage I and II disease treated with NCT prior to resection demonstrate higher rates of margin negative and node negative resection than stage-matched patients receiving no chemotherapy prior to resection. NCT appears to provide a statistically relevant survival benefit to patients presenting with clinical stage II but not stage I disease at time of diagnosis.

55.07 Utility of Lymph Node Yield as a Quality Metric for Node-negative Pancreatic Head Adenocarcinoma

Posted on January 18, 2016

P. R. Varley1, A. L. Gleisner1, S. T. Tohme1, A. P. Chidi1, D. A. Geller1, A. Tsung1 1University Of Pittsburg,Department Of Surgery,Pittsburgh, PA, USA

Introduction: Previous studies have suggested that survival is associated with the number of lymph nodes examined in patients with node-negative adenocarcinoma of the pancreatic head. For this reason current National Comprehensive Cancer Network guidelines recommend examination of at least 11 lymph nodes for accurate staging. In this study we are the first to investigate whether adherence to this guideline by treatment centers is associated with improved patient survival in a large, multi-institutional dataset.

Methods: The National Cancer Data Base from 1998-2012 was queried for patients undergoing pancreatic resection for adenocarcinoma of the pancreatic head. Adherence to NCCN guidelines was measured by calculating the proportion of patients who had at least 11 lymph nodes (LN) examined at a given treatment center. This proportion was subsequently used in a Cox proportional hazards model with shared frailty was used to evaluate its association with patient survival while controlling for random effects at the level of treatment center. Hierarchical linear regression was used to evaluate the influence of treatment center on LN yield following pancreatic resection.

Results: There were 9,247 patients available for analysis. Mean age for the cohort was 66.4±10.8 years. The majority of patients were T3 (54.8%), while 24.3% were T2 and 14.5% were T1. Median yearly treatment center volume ranged from 1 to 86 cases (median 2, IQR 2-4.25). The median proportion of patients having 11 LNs examined at a specific center was 40% (IQR 22.6%-56.7%). Center volume and adherence to the 11 LN guideline were significantly correlated (ρ=0.21, p < 0.001). Centers were divided into tertiles based on adherence, and unadjusted median survival for patients treated at the least adherent tertile was 20.6 months (95% CI 19.5-22.2) and 31.2 months (95% CI 30.0-33.0) at the most adherent. However after adjusting for other covariates and center-specific variation (Table 1), a 10 percent increase in adherence to the 11 LN guideline only revealed a modest association with improved survival (HR 0.97, p = 0.002). Finally in a hierarchical regression analysis clustering within treatment centers accounted for only 15.3% of the variance in the number of nodes examined.

Conclusion: While our results confirm that nodal yield after resection for pancreatic head adnenocarcinoma is associated with survival in node-negative patients, they also show that its utility as a quality metric is limited. Our results confirm the well-described volume-outcome relationship in pancreatic adenocarcinoma and suggest that the survival advantage conferred by treatment at these centers is related to factors unrelated to lymph node yield.

55.01 Lymphovascular Invasion is Associated with Compromised Survival for Papillary Thyroid Cancer

Posted on January 18, 2016

L. N. Pontius1, L. M. Youngwirth1, S. M. Thomas1, R. P. Scheri1, S. A. Roman1, J. A. Sosa1 1Duke University Medical Center,Durham, NC, USA

Introduction: Data regarding the association between lymphovascular invasion for survival for papillary thyroid cancer (PTC) are limited. This study sought to examine lymphovascular invasion as an independent prognostic factor for patients with PTC undergoing total thyroidectomy.

Methods: The National Cancer Data Base (2010-2011) was queried for all patients with a diagnosis of PTC undergoing total thyroidectomy. Patients were classified into two groups based on the presence/absence of lymphovascular invasion. Demographic, clinical, and pathologic features at the time of diagnosis were evaluated for all patients. A Cox proportional hazards model was developed to identify factors associated with survival.

Results: In total, 40,324 patients met inclusion criteria; 12.5% had lymphovascular invasion. Patients with lymphovascular invasion were more likely to have larger tumors (2.8 cm vs 1.6 cm, p<0.01), metastatic lymph nodes (75.1% vs 34.1%, p<0.01), and distant metastases (3.1% vs 0.5%, p<0.01). They also were more likely to receive radioactive iodine when compared to patients without lymphovascular invasion (70.2% vs 48.7%, p<0.01). Unadjusted overall survival was reduced for patients with lymphovascular invasion compared to patients without it (log-rank p<0.01), with 5-year survival rates of 86.1% and 94.2%, respectively. After adjustment, increasing patient age (HR=1.06, p<0.01), male gender (HR=1.63, p<0.01), presence of metastatic lymph nodes (HR=1.73, p<0.01), presence of distant metastases (HR=4.90, p<0.01), and presence of lymphovascular invasion (HR=1.99, p<0.01) all were associated with compromised survival. Treatment with radioactive iodine was protective in both patients with lymphovascular invasion (HR=0.42, p<0.01) and patients without lymphovascular invasion (HR=0.48, p<0.01).

Conclusion: The presence of lymphovascular invasion among patients undergoing total thyroidectomy for PTC is independently associated with compromised survival. Patients with PTC and lymphovascular invasion should be considered higher risk, and providers should consider aggressive surgical and adjuvant treatment measures to maximize patient outcomes.

55.02 National Evaluation of Performance on the New Commission on Cancer Melanoma Quality Measures

Posted on January 18, 2016

C. A. Minami3,4, J. A. Wayne1, A. Yang1,3, M. Martini2, P. Gerami2, S. Chandra5, T. Kuzel2,5, K. Y. Bilimoria1,3,4 1Northwestern University,Department Of Surgery,Chicago, IL, USA 2Northwestern University,Department Of Dermatology,Chicago, IL, USA 3Northwestern University,Surgical Outcomes And Quality Improvement Center,Chicago, IL, USA 4Northwestern University,Center For Healthcare Studies,Chicago, IL, USA 5Northwestern University,Division Of Hematology/Oncology,Chicago, IL, USA 6Northwestern University,Department Of Pathology,Chicago, IL, USA

Introduction: To increase adherence to cancer management guidelines, the Commission on Cancer (CoC) approved 5 melanoma quality measures (Figure 1) in 2015, and performance on these measures may soon be used in accrediting hospitals. Our objectives were to formally evaluate national performance on these melanoma quality indicators and to examine patient, tumor, and hospital characteristics associated with adherence.

Methods: This retrospective observational study used the 2012 National Cancer Data Base to identify patients with invasive, non-metastatic melanoma. Inclusion and exclusion criteria were based on theCoC definition of each measure. Patient-level and hospital-level-adherence rates were calculated for the 5 measures. A hospital was deemed ‘adherent’ if it met the CoC standard, which requires 90% of patients to receive the measure-specific recommended care. Patient, tumor, and hospital characteristics potentially associated with higher likelihood of adherence at the patient-level were estimated using hierarchical random effects logistic regression models to account for hospital-level clustering.

Results: A total of 31,598 patients from 1343 hospitals were examined. Patient-level adherence rates varied from 31.6% (Measure #5: ≥10 lymph nodes removed/examined in axillary dissections) to 72.6% (Measure #1: sentinel lymph node biopsy (SLNB) overuse measure). Hospital-level adherence rates ranged from 19.3% for Measure #5 (n=538 hospitals) to 56.2% for Measure #1 (n=1090 hospitals). To improve Measure #1’s specifications, patients with high-risk features (ulceration, mitoses, age<40 years) were excluded from the measure’s denominator as SLNB in these patients remains controversial, with a resultant improvement in the patient-level adherence rate (original measure: 72.6%; modified measure: 83.8%, p<0.001); with these adjustments, 277 (20.6%) more hospitals would achieve the 90% threshold and pass Measure #1. Only 319 (24%) hospitals would pass all 5 measures, and most hospitals would pass 3 measures or fewer (53%). No hospital-level factors (e.g., teaching status, case volume) were consistently associated with better adherence.

Conclusion: National adherence rates to the 5 new CoC melanoma quality metrics is low and most hospitals would not meet the CoC requirement of 90% adherence. Feedback of these measures to hospitals may be an impetus for improving guideline adherence, but the measures need refinement to adequately capture the nuances of melanoma care before being used for accreditation purposes.

55.03 Heterogeneity of CD8 Tumor Infiltrating Lymphocytes (TIL) in Melanoma

Posted on January 18, 2016

J. M. Obeid1, G. Erdag3, T. Bullock4, N. Wages2, C. L. Slingluff1 1University Of Virginia,Surgery,Charlottesville, VA, USA 2University Of Virginia,Public Health Sciences,Charlottesville, VA, USA 3Johns Hopkins University School Of Medicine,Dermatology,Baltimore, MD, USA 4University Of Virginia,Pathology, Research,Charlottesville, VA, USA

Introduction: Infiltration of melanoma metastases by CD8+ T cells predicts improved survival and is believed to reflect immune-mediated tumor rejection. Thus, CD8 count is used as a marker of prognosis and response to immune therapy in clinical trials. Increases in CD8 T cells between pre- and post-treatment biopsies may reflect response to immune therapy, which is increasingly important for assessing effects of combination immunotherapies. Tumor heterogeneity may complicate these measures, but there are insufficient data to address heterogeneity when tracking changes in CD8 infiltrates. Furthermore, there is a need to assess differences in immune infiltration between synchronous and subsequent tumors. We hypothesized that variation of CD8 T cell counts among different samples of the same or synchronous metastases would be limited to a coefficient of variation (CV) of less than 50% of the mean. We also hypothesized that CD8 counts would decrease over time between metachronous tumors.

Methods: Tissue microarrays (TMAs) were constructed from 197 melanoma formalin-fixed paraffin-embedded tumors from 154 patients, of which 27 had 2 or more tumors resected at different times, and six patients had 2 tumors resected simultaneously. For each tumor, up to four 1 mm diameter tissue cores were included in the TMA. The number of CD8 T cells per core was determined by immunohistochemistry. Mean, standard deviation (SD), and coefficient of variation (CV = SD/mean) were calculated for tumors with 3-4 evaluable cores (N=175). In patients with metachronous tumors, CD8 counts of the first and second tumors were compared with a paired T-test. For simultaneous metastases, CD8 counts were studied for differences in decile ranks among all 197 tumors.

Results:CD8 counts varied widely among different cores of the same tumors (average CV 0.77, 95% CI: 0.70 to 0.84). The CV was greater for lower means (CV>0.7 for mean <134 CD8/mm2, CV<0.5 for >294 CD8/mm2). The inverse association of CV with the mean was significant (r = -0.38, p<0.0001). Among the 6 patients with simultaneous excision of two tumors, 4 pairs of tumors had counts in the same decile, 1 differed by 1 decile and 1 by 2 deciles. Among the 27 patients with metachronous tumors, if the first tumor had CD8 counts higher than the median (84 cells/mm2), CD8 counts decreased by 47% in the second tumor (p=0.005). For those with CD8 counts lower than the median, CD8 counts trended higher in the second tumor (p=0.058, +140%).

Conclusion:Heterogeneity among tumor samples was greater than hypothesized, but means across 3-4 cores were similar between synchronous metastases. In patients, differences in CD8 T cell counts after treatment may be explained by heterogeneity if tumor samples are small and especially if differences are less than 2-fold. The impact of tumor heterogeneity on CD8 T cell counts may be minimized by taking multiple samples of each tumor and powering clinical trials to allow for heterogeneity.

55.04 734 Patients with Primary Malignant Sarcoma of the Liver: A Population-Based Analysis

Posted on January 18, 2016

T. B. Tran1, J. N. Leal1, M. M. Dua1, G. A. Poultsides1, J. A. Norton1, B. C. Visser1 1Stanford University,Surgery,Stanford, CA, USA

Introduction: Primary liver sarcomas are extremely rare malignancies. Clinical outcomes after operative intervention and prognostic factors associated with long-term survival remain poorly understood.

Methods: We queried the Surveillance, Epidemiology, and End Results database (SEER) to identify patients with malignant sarcoma of the liver from 1988 to 2012. Demographic factors, tumor characteristics, resection status, and long-term survival were evaluated. Multivariate Cox regression analysis was performed to determine predictors of survival.

Results: A total of 734 patients with primary malignant sarcoma of the liver were identified. The median age of diagnosis was 58 years and the majority of patients were men (54.8%). The median tumor size was 10cm. Based on SEER clinical stage, the patients were evenly distributed by extent of disease (localized disease 29%, regional disease 25%, and distant disease 34%, unstaged 11.6%).). Only 30% of patients in the cohort underwent surgery. The overall 5-year survival rates based on the SEER clinical stage were 40.2% for localized disease, 23.3% for regional disease, and 12.7% for distant disease; p<0.001. Among patients who underwent surgical resection, patients with embryonal sarcoma had better 5-year survival compared with angiosarcoma and other miscellaneous histologic subtypes (70% vs 23.3% vs. 40.6%, respectively; p<0.001, Figure 1). Survival was modestly better for low grade vs. high grade tumors, but did not reach statistical significance (5 year: 68.2% vs 47.9%; p=0.244). Tumor size did not influence prognosis (e.g., <10 cm vs >10 cm: 54.2% vs. 57.1%; p=0.973). While transplantation was uncommon (20 cases in entire cohort) survival seemed to be poorer than after resection (even for tumors less than 5 cm, 5 year survival 42.9%, vs 63.9%, respectively, p=0.317). On multivariate analysis, surgery and female sex were associated with improved survival, while older age, advanced stage, and angiosarcoma histology were the strongest independent predictors of poor survival.

Conclusion:

This is the largest US series of primary malignant sarcoma of the liver analyzed to date. Histologic subtype, more so than tumor size or differentiation, is the dominant factor determining outcomes.. Complete resection is associated with the longest survival.

54.08 Quality of Life of Adults Born with Cleft Lip and Palate With No Access to Basic Surgical Services

Posted on January 18, 2016

A. J. Rios Diaz6, M. S. Ramos6,7, P. T. Vaughn7, A. V. Moscoso10, J. Lam9, E. J. Caterson10 7Harvard Medical School. Brigham And Women’s Hospital,Department Of Surgery,Boston, MA, USA 8Harvard University,School Of Dental Medicine,Boston, MA, USA 9Boston University,School Of Medicine,Boston, MA, USA 10Brigham And Women’s Hospital, Harvard Medical School,Division Of Plastic And Reconstructive Surgery, Department Of Surgery,Boston, MA, USA 6Both Authors Contributed Equally. Harvard Medical School. Brigham And Women’s Hospital,Center for Surgery and Public Health, Department Of Surgery,Boston, MA, USA

Introduction: Cleft lip and palate (CLP) are common congenital craniofacial anomalies. It has been shown that children with this condition are susceptible to discrimination, emotional problems, lower self-esteem and increased anxiety, affecting their lifestyle even after surgical repair. Globally, there is no data on the impact of this condition on Health-Related Quality of Life (HRQoL) in older populations (≥ 25 years). The objective of this study was to assess the HRQoL of unrepaired cases of CLP in a rural population of a lower-middle-income country, where deficiencies in access to care have contributed to an important backlog of adult cases.

Methods: A prospective study conducted in the State of Assam, India from Feb 2013 to May 2014. A total of 147 adult (≥ 18 years) subjects were surveyed, 89 with CLP compared to 58 without CLP. Subjects living throughout the state were recruited at a CLP dedicated hospital in the city of Guwahati (CLP group), and in their home towns (normal group). All subjects completed the World Health Organization HRQoL questionnaire (WHOQOL-BREF) and comparisons between groups were made for each of the four domains (Physical Health, Psychological, Social Relationships and Environment) of the instrument (scoring range 21-100). Descriptive statistics, independent sample t-tests, Pearson's chi-square test, and general lineal models controlling for age, gender, education level, literacy and occupation were used to analyze the data with a significance threshold set at p<0.05.

Results: CLP and normal groups were similar in age (median age 30 vs. 30.5; p=0.754), gender (females 49.4% vs. 43.1%; p=0.452), marital status (married/living as married 53.4% vs. 60.3%; p=0.476) religion (Hindu 76.2% vs. 87.8%; p=0.619), annual income (60,000 vs. 72,000 Indian Rupees; p=0.82) and number of people per household (median 5 vs. 5; p= 0.654). Conversely, the cleft group had significantly higher proportion of illiteracy (55.1% vs. 14.3%; p<0.001), no education (51.1% vs. 10.3%; p<0.001) and hand-laborer occupation (74.7% vs. 38.6% farmer/labor industry; p<0.001). Adjusted models revealed a significantly lower mean difference for the Environment domain [5.24 (95% Confidence Interval 0.97-9.51; p=0.016)], and no significant difference for the other domains.

Conclusions: Environmental consequences of unrepaired CLP on HRQoL are present even after childhood. Some of these include financial resources, access/quality to health and social care, participation in recreational/leisure activities, opportunities for acquiring information and skills, physical and home environment, physical safety and security. Given the life long deleterious consequences of living with an unrepaired CLP, more financial resources need to be allocated to understand and treat the backlog of adult CLP cases. Using CLP-tailored instruments instead of generic ones may increase the sensitivity of capturing additional impact of unrepaired CLP on HRQoL.

54.09 Referral Patterns and Predictors of Referral Delays for Patients with Injuries in Rural Rwanda

Posted on January 18, 2016

T. Nkurunziza1, G. Toma1,2, J. Odhiambo1, R. Maine2,3, R. Riviello2,4,6, N. Gupta1,4, A. Bonane5,6, C. Habiyakare7, T. Mpunga7, B. Hedt-Gauthier1,2,5 1Partners In Health/Inshuti Mu Buzima,Clinical,Kigali, , Rwanda 2Harvard School Of Medicine,Department Of Global Health And Social Medicine,Brookline, MA, USA 3University Of California – San Francisco,Surgery,San Francisco, CA, USA 4Brigham And Women’s Hospital,Boston, MA, USA 5University Of Rwanda,College Of Medicine And Health Sciences,Kigali, , Rwanda 6Kigali University Teaching Hospital,Surgery,Kigali, , Rwanda 7Ministry Of Health,Kigali, , Rwanda

Introduction:
In low-and middle-income countries, nine out of ten patients lack access to timely, safe and affordable surgical care. Most patients seek care at district hospitals with limited surgical capacity, creating a need for referral. Weaknesses in referral systems lead to delays that contribute to substantial disability and death. This study assesses the predictors of delayed referrals for injured patients.

Methods:
This retrospective cohort study included all injured patients between January 1 and December 31, 2013 from three rural district hospitals in Rwanda, with a focused analysis on those recommended for referral. We defined delayed referral as non-execution of referral or execution of referral more than two days after referral recommendation. We performed a multivariate logistic regression using stepwise backward selection to identify the risk factors for delayed referral.

Results:

Of the 1,227 patients with injuries evaluated, 23% (n=282) were recommended for referral. Of these patients, 36.5% were injured through road traffic accidents and 53.6% were diagnosed with closed fractures. Overall, 46.5% (n=107) of the patients recommended for referral had a delay in referral execution. Reasons for delay that were documented in 57 patients’ files included awaiting appointment (45.6%, n=26), lack of space at referral hospitals (40.4%, n=23) and financial (14%, n=8).

In the multivariate model, the major risk factors for delayed referral included district hospital (OR:3.77, 95% CI: 1.5- 9.18), age >35 years (OR=2.45, 95%CI: 1.09-5.50), closed fractures/dislocation (OR=16.37, 95%CI: 3.13-85.78), admission to surgical wards (OR=10.25, 95%CI: 2.70-38.82) and admission for at least seven days prior to referral recommendation (OR=4.80, 95%CI:1.38-16.63).

Conclusion:
Although it is promising that over fifty percent of referrals were completed in a timely fashion, services at district hospitals should be improved to minimize the need for referral. Specifically, improved availability of surgical infrastructure, equipment, supplies, and trained staff at district hospitals may improve the execution of timely and appropriate referrals. Further, patient-centered programs to facilitate referral and support patient expenses may contribute to timely referral and should be further studied.

54.10 The Role of Endoscopy After Upper Gastrointestinal Bleed in Sub-Saharan Africa: A Prospective Study

Posted on January 18, 2016

J. Gallaher1, G. Mulima2, J. Qureshi1, C. Shores1, B. Cairns1, A. Charles1,2 1University Of North Carolina At Chapel Hill,Surgery,Chapel Hill, NC, USA 2Kamuzu Central Hospital,Surgery,Lilongwe, , Malawi

Introduction: Upper gastrointestinal (UGI) bleed is a significant public health problem in sub-Saharan Africa especially in resource-poor environments, where there is a lack of diagnostic adjuncts such as endoscopy. This study sought to characterize UGI bleeding at a tertiary care hospital in sub-Saharan Africa and the role of endoscopy in management.

Methods: A prospective analysis of adult patients (age ≥ 18 years) presenting with a clinical diagnosis of UGI bleed to Kamuzu Central Hospital (KCH) in Lilongwe, Malawi over two years was performed (October 2011 – September 2013). Patient characteristics and both short and long-term outcomes were recorded. Long-term outcomes were recorded in an outpatient clinic or via communication with family. Bivariate and logistic regression analyses were used to compare endoscopy and non-endoscopy patient cohorts.

Results: 293 patients were included in the study. Mean age was 41.8 years (SD ± 15.8) with an overall male preponderance (62.9%). 38.9% (n=114) received endoscopy. There were no differences between the endoscopy and non-endoscopy cohorts in clinical history, physical exam, vital signs, laboratory studies, or imaging findings. However, patients who received endoscopy received more blood transfusions (mean 1.9 vs. 1.5 units, p=0.0108) and were more often medicated with beta-blockers (71.1 vs. 55.3%, p=0.007). In the endoscopy cohort, 64.9% (n=74) had findings of esophageal or gastric varices and 43.0% (n=49) of these had endoscopic banding. Length of stay was longer for patients who received endoscopy (14.9 vs. 8.7 days, p<0.001) but mortality was substantially lower in the endoscopy cohort (4.4 vs. 12.9%, p=0.016). The adjusted odds ratio for mortality for patients not receiving endoscopy was 3.53 (CI 1.25-9.99, p=0.017). Outpatient follow-up rates were similar between the two cohorts (31.3 vs. 29.0%, p=0.671). At follow-up, there were similar rates of repeat upper gastrointestinal bleed (5.6 vs. 6.1%, p=0.843) and post-hospitalization mortality (5.0 vs. 6.1%, p=0.683) between the endoscopy and the non-endoscopy cohorts.

Conclusion: Diagnostic endoscopy with or without therapeutic intervention had a significant in-hospital mortality benefit for patients presenting with upper gastrointestinal bleed even with a relatively low utilization rate. Varices were the most common cause and these patients responded well to banding. Prioritizing the improvement of endoscopy capacity in resource-poor environments would likely have a significant impact on mortality.

54.04 Multi-institutional study of prehospital care curriculum in fast developing economies

Posted on January 18, 2016

R. Abraham1, M. Hollis1,2, A. Malhotra3, D. Vyas1 1Michigan State University,Department Of Surgery,Lansing, MI, USA 2Harvard Medical School,Department Of Urology,Boston, MA, USA 3Virginia Commonwealth University,Department Of Surgery,Richmond, VA, USA

Introduction: The trauma pandemic is one of the leading causes of death worldwide, but especially in fast developing economies. Perhaps a common cause of trauma-related mortality in these settings comes from the rapid expansion of motor vehicle ownership without the corresponding national pre-hospital training in developed countries. The resulting road traffic injuries often never make it to the hospital in time for effective treatment, resulting in preventable disability and death. The current paper examines the program evaluation of medical first responder training that has the potential to reduce this unnecessary morbidity and mortality.

Methods: An intensive training workshop has been differentiated into two progressive tiers: Acute Trauma Training (ATT) and Broad Trauma Training (BTT) protocols. These four-hour and two-day protocols, respectively, allow for the mass education of laypersons—such as police officials, fire brigade, and taxi/ambulance drivers—who are most likely to interact first with pre-hospital victims. Over 750 ATT participants and 168 BTT participants were trained across three Indian educational institutions at Jodhpur and Jaipur. Trainees were given didactic and hands-on education in a series of critical trauma topics, in addition to pre- and post-survey self-assessments to rate clinical confidence across curricular topics.

Results: A variety of career backgrounds enrolled both in our ATT and BTT workshops, run by local physicians with a spectrum of medical specialties as well as ATT-trained police officials. Statistical analysis revealed significant improvements in clinical confidence across all curricular topics for both ATT and BTT protocols. In addition, the pre- and post-survey confidence levels were generally similar across the multi-institutional settings.

Conclusion: These results suggest a promising level of reliability and reproducibility across different geographic areas in fast developing settings. Program expansion can offer an exponential growth in the training rate of medical first responders, which can help curb the trauma-related mortality in fast developing economies. Future directions will include clinical competency assessments and further progressive differentiation into higher tiers of trauma expertise.

54.05 The Association Between Trauma Admission And Financial Economic Indicators

Posted on January 18, 2016

B. Zangbar1, P. Rhee1, S. Mirghasemi1, N. Kulvatunyou1, A. Tang1, T. O’Keeffe1, D. Green1, R. Latifi1, R. S. Friese1, B. Joseph1 1University Of Arizona,Trauma Surgery,Tucson, AZ, USA

Introduction: Several factors have been suggested to explain the variation in intentional trauma admissions. However, the impact of changing economic conditions on trauma admissions remains unknown. The aim of this study was to determine the association between economic indicators and intentional trauma admission rate.

Methods: We performed a 5-year (2008-2012) retrospective analysis of state trauma database. Intentional injury was defined as self-inflicted injury or assault. Rate of admission of trauma patients with intentional injury was calculated per day. After smoothing the admission rates using centered moving average, data was adjusted for seasonal variation, state unemployment rate, state crime rate, and estimated state population. Dow Jones Industrial Average (DJI) was used as an indicator for economic changes in United States. Correlation and multivariate linear regression analysis was performed.

Results: A total of 142,738 trauma admissions were identified of which 21,540 were due to intentional trauma. DJI significantly correlated with intentional trauma admissions (p=0.004). After adjusting for unemployment rate, crime rate, state population, and time trend DJI was independently associated with intentional trauma admissions (β= -0.224, 95% CI= -0.448 – -0.02, p=0.04). For every 1000 unit decrease in DJI, intentional trauma admissions increased by 0.22 per month.

Conclusion: Variation in economic conditions independently impacts intentional trauma admissions independently. A nation wide evaluation may help in identifying additional social factors and the true nature of this association.

54.06 The Volume and Outcomes of Surgical Procedures in Mexico in 2014.

Posted on January 18, 2016

T. Uribe-Leitz1, S. R. Rosas Osuna2, M. M. Esquivel1, A. Cervantes Trejo3,4, N. Y. Garland1, J. Cervantes5,6, K. L. Staudenmayer1, D. A. Spain1, T. G. Weiser1 1Stanford University School Of Medicine,Department Of Surgery,PALO ALTO, CA, USA 2Mexican Ministry Of Health,National Council Of Injury Prevention,MEXICO, DF, Mexico 3National Institute For Educational Evaluation,MEXICO, DF, Mexico 4Anahuac University,Institute Of Public Health,Huxquilucan, MEXICO, Mexico 5Universidad Nacional Autónoma De México (UNAM),Facultad De Medicina,MEXICO, DF, Mexico 6American British Cowdray Medical Center,Department Of Surgery,MEXICO, DF, Mexico

Introduction: Mexico has a robust epidemiologic public hospital reporting system, yet little has been published about the volume and outcomes of surgical procedures. In light of the recent Lancet Commission on Global Surgery recommendations on indicators of capacity and outcomes, we sought to understand the volume of surgery and outcomes for public hospitals in Mexico in 2014. We also assessed four common procedures – cesarean delivery, appendectomy, cholecystectomy, and groin hernia repair – to better understand access to basic surgical care. Finally, we evaluated the number of clinicians available to provide care.

Methods: We queried the online public database of the Ministry of Health in Mexico to obtain information on the volume of operations occurring in public hospitals. We used ICD10 Current Procedural Terminology (CPT) codes reported per hospital discharge by state in 2014, filtered by procedure type, to ascertain the number of reported surgical procedures. We also identified deaths during hospitalizations that included a surgical procedure. We evaluated four commonly performed operations –cesarean delivery, appendectomy, cholecystectomy, and groin hernia repair– to assess both specific volume and proportion of total surgical volume. We also obtained in-hospital deaths, population data, and number of general and specialized surgeons and obstetricians/gynecologists (Ob/Gyns) in each state.

Results: A total of 1,655,468 operations were performed in public hospitals in 2014. Of this total, 22.6% were cesarean deliveries, 4.1% cholecystectomies, 3.6% appendectomies, and 1.8% groin hernia repairs. From these operations 13,277 patients died, yielding a mean case fatality rate (deaths per 1000 procedures) of 8.02. The mean case fatality rate ranged substantially by state (2.59-14.28). Mortality also varied by procedure. The national mean case fatality rate was 0.28 for cesarean deliveries (range 0-0.95 by state), 4.64 for cholecystectomy (range 0.73-12.42 by state), 3.03 for appendectomy (range 0-9.55 by state), and 3.78 for groin hernia repair (range 0-12.64 by per state). We identified 3,910 individual general and specialized surgeons and 4,802 Ob/Gyns. The mean number of providers per 100,000 people was 3.27 (range 0.92 -7.02 by state) for surgeons and 4.01 (range 2.19 –7.43 by state) for Ob/Gyn.

Conclusion:The national mean case fatality rate for the selected surgical procedures in Mexican public hospitals is low and is comparable to highly developed countries. However, closer examination reveals a large degree of variation by state, by procedure, and by provider density suggesting an opportunity for improvement. National standardized data collection systems are essential for analyzing access and provision of surgical care, and understanding patient outcomes. However, the private sector is not included in this reporting system.

54.07 Uptake and performance of clinical breast exam screening program by trained laywomen in Malawi

Posted on January 18, 2016

L. Gutnik1,3, V. Msosa4, A. Moses3,4, C. Stanley3, S. Mzumara4, B. Dhungel4, G. Liomba4, C. Lee2, S. Gopal2,3 1Montefiore Medical Center/Albert Einstien College Of Medicine,Surgery,Bronx, NY, USA 2University Of North Carolina At Chapel Hill,Chapel Hill, NC, USA 3UNC Project Malawi,Lilongwe, , Malawi 4Kamuzu Central Hospital,Surgery,Lilongwe, , Malawi

Introduction: Breast cancer mortality is high in sub-Saharan Africa (SSA) partly due to limited breast cancer awareness and early detection. We trained laywomen to promote breast cancer awareness and perform screening clinical breast exam (CBE) in urban clinics. This is the first breast cancer screening study in Malawi, and the first study in SSA to assess CBE by laywomen delivered with other health services.

Methods: Four laywomen were trained to deliver breast cancer educational talks and conduct CBE. After training, screening was implemented in diverse urban health clinics. Eligible women to undergo CBE were ≥30 years, with no prior breast cancer or breast surgery, and clinic attendance for reasons other than a breast concern. Women with abnormal CBE were referred to a study surgeon. All palpable masses confirmed by surgeon exam were pathologically sampled. Patients with abnormal screening CBE but normal surgeon exam underwent breast ultrasound confirmation. Additionally, 50 randomly selected women with normal screening CBE underwent breast ultrasound, and 45 different women with normal CBE were randomly assigned to surgeon exam.

Results:175 educational talks were delivered to 4295 people across 5 clinics. Among 1220 eligible women, 1000 (82%) agreed to CBE. Lack of time (68%) was the most common reason for refusal. CBE agreement varied across clinics from 71% to 86% (p=0.001). Women who attended the talk were more likely to accept CBE than women who did not (83% vs 77%, p=0.012). Among 1000 women screened, 7% had abnormal CBE. All 50 women with normal CBE randomized to ultrasound had normal findings. Of 45 women with normal CBE randomized to surgeon exam, 43 had normal surgeon exams and 2 had axillary lymphadenopathy not detected by screening CBE. Sixty of 67 women (90%) with abnormal CBE attended the referral visit. Of these, 29 (48%) had concordant abnormal surgeon exam, and 15 were recommended to have pathologic sampling. Fourteen women had nipple discharge or breast pain identified by both CBE and surgeon exam, which did not require further work-up after surgeon review. Thirty-one women (52%) had discordant normal surgeon exam, all of whom had normal breast ultrasounds. Compared to surgeon exam, sensitivity for CBE by laywomen was 94% (CI 79-99%), specificity 58% (CI 46-70%), positive predictive value 48% (CI 35-62%), and negative predictive value 96% (CI 85-100%). Of 15 women who underwent pathologic sampling, 2 had cytologic dysplasia and are awaiting surgical excision, 7 had fibroadenomas, 2 normal tissue, 1 galactocele, 1 abscess, 1 lymph node with Kaposi sarcoma, and 1 tumoral calcinosis.

Conclusion:Uptake of CBE screening in Lilongwe clinics was high. CBE by laywomen compared favorably with surgeon exam, and follow-up was good. Our intervention can serve as a model for wider implementation. Performance in rural areas, effects on breast cancer stage distribution and mortality, and cost-effectiveness require further evaluation.

54.01 Hepatocellular Carcinoma in Latin America, which are our dates?

Posted on January 18, 2016

S. Hoyos1,2,3 1Hepatobiliary and Pancreatic Unit Hospital Pablo Tobón Uribe (HPTU) 2Liver Transplant Program HPTU – Universidad de Antioquia (UdeA) 3Gastrohepatology group UdeA – Epidemiology group Universidad CES

Introduction:

Hepatocellular carcinoma (HCC) is a malignant tumor that usually emerges in cirrhotic patients, mostly associated with chronic alcohol intake, hepatitis C and hepatitis B. The incidence of HCC is highly variable across the world, depending on the relative presence of the underlying liver diseases at each región. (1,2). Is highly prevalent in the east, especially in China, but in Latin America (LA) there is a lack of information about it that is worrisome.

The problem of poor data is attributable to the limited resources that are available to treat costly cancer-related detection and treatment. If the detection of HCC is problematic in more affluent countries (3), what is the possibility of even higher levels of under-estimation in poorer countries because of a combination of data problems, as well as a lack of screening facilities.

The underestimation of HCC is indicated as an underestimation factor that is applied to the current Globocan 2012 country level incidence rates. It is suggests that at least 120,722 cases of HCC may have been missed in 2012 which translates into a revised global incidence of 12.0 versus an observed 10.1 per 100,000. In total, 78 countries appeared to have a significantly underestimated HCC incidence. The underestimation factor (see Fig. 1) for the top 15 countries ranged between a maximum of 9.2 (Cameroon) and 3.5 (Peru). The adjusted country level incidence highlights the widespread increase in HCC in Asia, Africa and South America (4).

Fig. 1. Countries with a significant underestimation of HCC based on the model prediction, 2012

A search in pubmed, medline, scielo, and google academic was done to find articles about HCC in different regions of LA, the terms: “liver cáncer”, “hepatocellular carcinoma”, “liver tumors” and the name of the LA countries were used with the boolean connector AND. Finally, the results from a large multicenter Latin American study of Liver transplant in HCC are presented
In Latin America, some retrospective studies have been performed, basically looking for the different etiologies of HCC, not the prevalence.

In a prospective, multicenter, international study, the etiology of hepatocellular carcinoma in Latin America was presented, 240 patients with HCC were uploaded in a database from different Latin American countries (5). 174 were male (72.5%), 66 were female (27.5%). Median age was 64 years old, interquartile range 57-72, minimal 19, maximal 92 years old. In 205 out of 240 (85.4%) cases, patients had underlying cirrhosis. The main etiology of liver disease were: HCV (30.8%), Alcohol (20.4%), Cryptogenic (14.6%) and HBV (10.8%).

A multicenter Latin American cohort study was done to find the rates of recurrence of hepatocellular carcinoma after liver transplantation (6). A total of 2018 adult patients were consecutively transplanted during the study period in the 15 LT centers in Latin America. From this cohort, 327 of 422 patients with HCC were included in the final analysis, mean age was 57 ± 8 years, 81.7% were men, the most frequent etiology of liver disease was chronic hepatitis B virus infection in 27.8% followed by hepatitis C in 27.2% and alcohol in 17.7%.

In conclusion, although HCC is not still a big problem in Latin America, the inappropriate cancer registries in this countries, makes that the current data are not accurate enough to make an ideal health policies for cancer registry, control and treatment that the patients deserve

References:
1. Sherman M. Hepatocellular carcinoma: epidemiology, risk factors, and screening. Semin Liv Dis 2005; 25: 143-54.

2. Bosch FX, Ribes J, Díaz M, Cléries R. Primary liver cancer: worldwide incidence and trends. Gastroenterology 2004; 127: S5-S16.

3. di Bisceglie AM. Issues in screening and surveillance for hepatocellular carci- noma. Gastroenterology 2004;127:S104–7.

4. K. Sartorius, B. Sartorius, C. Aldous, P.S. Govender T.E. Madiba. Global and country underestimation of hepatocellular carcinoma (HCC) in 2012 and its implications. Cancer Epidemiology 39 (2015) 284–290.

5. Fassio E, Díaz S, Santa C, Reig ME, Martínez Y, Alves de Mattos A, et al. Etiology Of Hepatocellular Carcinoma In Latin America: A Prospective, Multicenter, International Study Ann Hepatol 2010;9:63-69

6. Piñero F, Tisi M, de Ataide EC, Hoyos S, Marciano S, Varón A, et al. Liver Transplantation for Hepatocellular carcinoma: Validation of the French model in a multicenter Latin American cohort. In Press.

54.02 Genetic epidemiology of hereditary deafness: Data from a Cross National Survey of Deafness in Nigeria

Posted on January 18, 2016

A. O. Lasisi1, B. O. Yusuf2, B. O. Adedokun2, K. Omokanye3, A. O. Afolabi3, T. J. Lasisi4, F. Olatoke6, O. A. Sulaiman7, S. A. Ogunkeyede8, A. A. Salman8, A. O. Oluokun8, A. M. Oriyomi7, W. A. Adedeji5, H. O. Lawal9, M. O. Kelani9, T. Yusuf10, G. Bademci11, J. Foster II11, S. Blanton11, M. Tekin11 1Dept. of Otorhinolaryngology, University of Ibadan and Ladoke Akintola University Teaching Hospital, Osogbo, Nigeria 2Dept. of Epidemiology and Statistics, University of Ibadan, Nigeria 3Dept. of Otolaryngology, University of Ilorin, Ilorin Nigeria 4Dept of Physiology, University of Ibadan 5Dept. of Clinical Pharmacology, University College Hospital, Ibadan, Nigeria 6Dept. of Otolaryngology, Federal Medical Center, Lokoja 7Dept. of Otolaryngology, Federal Medical Center, Katsina 8Dept of Otorhinolaryngology, Ladoke Akintola University, Ogbomoso 9Dept of Otorhinolaryngology, General Hospital, Maitama, Abuja, Nigeria 10Department of Otorhinolaryngology, University College Hospital, Ibadan 11Dr. John T. Macdonald Foundation Department of Human Genetics and John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL 33136, USA

Introduction:
The prevalence of deafness is high in sub Saharan Africa. The WHO reported the prevalence of hearing loss affecting communication in children in sub Saharan Africa (SSA) to be 1.8%, second only to the south Asia region (2.3%) [2] However, there is need for a recent survey to document an up to date figure in Nigeria among other SSA. Importantly too, the role of genetics have only been sparsely documented despite the fact that in Europe, America and Asia, genetics contributed about 50% of deafness and the main mutations include GJB2, GJB6, SLC26A4 and mitochondrial DNA 1555A>G among others. This Cross National Survey of Deafness started as collaboration between the University of Miami Florida, USA and my institution and it was sponsored by the grants from the National Institute of Health and Tertiary Education Trust Fund of Nigeria. This survey is aimed at determining critical epidemiological determinants of hereditary deafness and documenting the genetic mutations responsible for deafness among Nigerians

Method:
This survey was carried out in 6 states spread in 5geopolitical zones of Nigeria including all the major tribes – Hausa, Yoruba and Ibo. The participants were selected from various vocational and professional groups, schools and religious groups and using questionnaire, deafness was identified as hereditary and acquired. Blood samples were collected from those identified with hereditary deafness and DNA was extracted using a salting-out method with Qiagen, followed by genotyping using Sanger and Next Generation sequencing for the identification of the gene mutation. This study had ethical approval from the Ethics Committee of the Joint UI/University College Hospital Ibadan and the University of Miami.

Result:

There were 2600 deaf subjects, made up of 63% males and 37% females. The age at detection of deafness ranged between 0 and 8years, (mean=2.37±2.035). Molecular analysis identified a novel POU3f4 mutation involving c.987T>C; p.(Ile308Thr) in 5year old Nigeria from Yoruba ethnic group. However, the analyses did not identify a pathogenic or polymorphic variant in GJB2, GJB6, SLC26A4 and mitochondrial DNA 1555A>G genes. The important epidemiologic variables which significantly mitigated interest in genetic testing include male respondents and low level of education.

Conclusion:

Mutations in POU3f4 is the first documented gene mutation responsible for deafness among Nigerians, in addition, GJB2, GJB6, SLC26A4 and mitochondrial DNA 1555A>G gene mutations are not common causes of deafness in Nigeria. This suggests that this region may harbour uniquely infrequent genetic causes (compared to the rest of the world) of hearing loss and provides the impetus for conducting further genetic studies in the SSA. The use of the epidemiologic data in underpinning deafness control policy in SSA is discussed.

54.03 Worldwide volume of procedures needed to address basic, essential surgical disease burden

Posted on January 18, 2016

J. W. Scott1,2, J. A. Rose1, M. Esquivel3, T. G. Weiser3, S. W. Bickler4 1Brigham And Women’s Hospital,Center For Surgery And Public Health, Department Of Surgery,Boston, MA, USA 2Program For Global Surgery And Social Change,Harvard Medical School,Boston, MA, USA 3Stanford University,Department Of Surgery,Palo Alto, CA, USA 4University Of California – San Diego, School Of Medicine,Department Of Surgery,San Diego, CA, USA

Introduction:
The 2015 Disease Control and Priorities 3 (DCP3) outlined a basic surgical package (BSP) capable of averting 3.2% of all deaths in LMICs by providing a focused package of basic yet essential procedures to care for conditions with significant health burden and available, feasible, and cost-effective treatments. Specifically, the BSP focuses on treatment of four common digestive diseases (appendicitis, paralytic ileus and intestinal obstruction, inguinal and femoral hernia, and gallbladder and bile duct disease), four maternal-neonatal conditions (maternal hemorrhage, obstructed labor, abortion, and neonatal encephalopathy), and injuries that could be treated with basic interventions. The aim of this study is to determine the volume of procedures needed to provide the BSP on a global scale.

Methods:
Prevalence of diseases and conditions from the Global Burden of Disease Study (GBD) 2010 was organized into 119 categories corresponding to the WHO’s Global Health Estimate and then apportioned to the 21 GBD epidemiological regions and seven GBD super-regions. Using data from the Lancet Commission on Global Surgery (LCoGS) on the incident need for surgery based on each category, we calculated the number of procedures needed to provide the BSP. Using the LCoGS estimates of minimum surgical needs for each GBD region, we also calculated the proportion of procedures accounted for by the BSP, as well as rates of procedures per 100,000 population necessary to provide the BSP for each super-region.

Results:

We estimate that the BSP represents 96.6 million needed procedures annually. The worldwide per population rate of procedures needed is 1402/100K population and ranges from 955/100K in the Latin America and Caribbean super-region to 1,779/100K in Sub-Saharan Africa (Figure). Based on prior estimates of surgical need, the BSP accounts for 30.0% of all needed procedures worldwide, with a range of 25.9% to 33.5% by GBD super-region.

Conclusion:
Providing the DCP3 recommended Basic Surgical Package to cover a focused set of diseases accounts for almost one-third of the minimum estimated need for surgery worldwide. In order to provide these basic but essential services, surgical infrastructure must be sufficient to provide at least 1,400 procedures/100K population. Health systems could use these data for targeting national-scale up of essential surgical services.

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