20.10 Can Medicaid Expansion Decrease Disparity in Surgical Cancer Care at High Quality Hospitals?

Posted on January 25, 2017

D. Xiao1,2,3, C. Zheng1,2,3, M. Jindal1,2,3, C. Ihemelandu1,2,3, L. Johnson1,2,3, T. DeLeire2,3, N. Shara1,2,3, W. Al-Refaie1,2,3  1MedStar Georgetown University Hospital,Washington, DC, USA 2MedStar Georgetown Surgical Outcomes Research Center,Washington, DC, USA 3Georgetown University Medical Center,Washington, DC, USA

Introduction:  Skepticism on Medicaid program’s ability to provide quality care has contributed to the debate on Affordable Care Act’s (ACA) Medicaid expansion. It is unknown whether Medicaid expansion can improve access to high-quality surgical cancer care for poor Americans. To address this gap, we examined the effects of the largest pre-ACA expansion in Medicaid eligibility, which occurred in New York in 2001. We hypothesized that this policy decreased disparity in access to surgical cancer care at high-quality hospitals (HQH) by insurance type and by race.

Methods:  We identified 67,685 non-elderly adults 18-64 years old from the 1997-2006 New York State Inpatient Database who underwent one of nine major cancer resections. HQHs were defined as either high-volume hospitals (HVH, assigned yearly as hospitals of highest procedure volumes that treated 1/3 of all patients) or low-mortality hospitals (LMHs), whose observed-to-expected mortality ratio were < 0.7. Analysis examining access to HVH was restricted only to patients of procedures with strong volume-outcome relationship (esophagus, liver, stomach, pancreas, and urinary bladder; N=10,737).   

Disparity was defined as the model-adjusted difference in percentage of patients operated at HQH by insurance type (Medicaid/uninsured vs privately insured) or by race (blacks vs whites). Consistent with published literature, we combined Medicaid and uninsured patients to capture changes in access to care due to newly gained Medicaid coverage by an otherwise uninsured patient. Covariates included age, sex, procedure type and emergency admission. Levels of disparity were calculated quarterly for each pair of comparison, then regressed using interrupted time series to evaluate the impact of Medicaid expansion.

Results: Overall, 15.0% of our study cohort were Medicaid/self-pay and 12.1% were blacks. The disparity in access to HVH by insurance type was reduced by 0.61 percentage points per quarter following the expansion (p=0.003) (Figure). Meanwhile, the Medicaid/uninsured beneficiaries had similar access to LMH as the privately insured; no significant change was detected around the expansion. Conversely, racial disparity has increased by 0.86 percentage points per quarter (p<0.001) in access to HVH (Figure) and by 0.48 percentage points per quarter (p=0.005) in access to LMH after the expansion.

Conclusions: The pre-ACA Medicaid expansion reduced the disparity in access to surgical cancer care at HQH by insurance type. However, it was associated with an increased racial gap in access to HQH for surgical cancer care. Further investigations are needed to explore whether Medicaid expansion may aggravate racial disparity in surgical cancer care.

20.07 Failure to Rescue Following Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy

Posted on January 25, 2017

K. Li1, A. A Mokdad1, M. Augustine1, S. Wang1, M. Porembka1, A. Yopp1, R. Minter1, J. Mansour1, M. Choti1, P. Polanco1  1University Of Texas Southwestern Medical Center,Division Of Surgical Oncology,Dallas, TX, USA

Introduction: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) has been shown to significantly improve the survival of selected patients with peritoneal carcinomatosis (PC). However, this invasive procedure can result in significant morbidity and mortality. Using a national cohort of patients, this study aims to identify perioperative patient characteristics predictive of failure to rescue (FTR)–mortality following postoperative complications from CRS/HIPEC.

Methods: Patients who underwent CRS/HIPEC between 2005 and 2013 were identified in the American College of Surgeons National Surgical Quality Improvement Program dataset (NSQIP). Patients who suffered any post-operative complication were identified. Major complications were defined as those corresponding to Clavien-Dindo grade III or IV. Failure to rescue (FTR) was defined as 30-day mortality in the setting of a treatable complication. Patients who suffered FTR were compared against those who survived a complication (non-FTR) using patient characteristics, pre-operative clinical information, types of resections, and severity of complication. Univariable comparisons were conducted using the Wilcoxon rank-sum test for continuous variables and the Fischer’s exact test for categorical variables. Predictors of FTR were identified using a multi-variable logistic regression model.

Results: From the NSQIP database, 915 eligible CRS/HIPEC cases were identified in the study period. Overall, 382 patients (42%) developed postoperative complications and constituted our study population. A total of 88 (10%) patients suffered one or more major complications. Seventeen patients died following a complication, amounting to an FTR rate of 4%. Patients’ age, gender, and race were similar between FTR and non-FTR groups. Colorectal cancer was the most common diagnosis in the FTR and non-FTR groups (35% vs 25%, respectively). The rates of multi-visceral resections were also similar (88% vs 86%, p=1.00). FTR patients were more likely than non-FTR patients to have dependent functional status (18% vs 2%, p=0.01), have ASA class 4 status (29% vs 8%, p=0.01), develop three or more complications (65% vs 24%, p<0.01), and suffer a major complication (94% vs 20%, p<0.01). Independent predictors of FTR were as follows: having a major complication (odds ratio [OR] 66.0, 95% confidence interval [CI] 8.4-516.6), dependent functional status (OR 5.9, 95%CI 0.8-41.9), and ASA class 4 (OR 13.4, 95%CI 1.2-146.8). Procedure type and diagnosis were not predictive of FTR.

Conclusion: Morbidity associated with CRS/HIPEC is comparable to other complex surgical procedures and has an acceptable low rate of death in this national cohort of patients. Dependent functional status and ASA class 4 are patient factors predictive of FTR. These patients have a prohibitively high risk of 30-day mortality following postoperative complications and should be considered ineligible for CRS/HIPEC.

20.04 Preoperative Enteral Access is not Requite Prior to Multimodality Treatment of Esophageal Cancer

Posted on January 25, 2017

T. K. Jenkins4, A. N. Lopez4, G. A. Sarosi1,2, K. Ben-David3, R. M. Thomas1,2  1University Of Florida,Department Of Surgery,Gainesville, FL, USA 2North Florida/South Georgia Veterans Health System,Department Of Surgery,Gainesville, FL, USA 3Mount Sinai Medical Center,Department Of Surgery,Miami Beach, FL, USA 4University Of Florida,College Of Medicine,Gainesville, FL, USA

Introduction:  While prior research has shown that preoperative (preop) enteral access is feasible and safe in patients to support their nutrition prior to esophagectomy, controversy exists regarding its necessity, as subjective dysphagia is a poor indicator of need for enteral access. We hypothesized that patients who underwent preop enteral access prior to esophagectomy for cancer fared no better than those who had surgical enteral access performed at the time of esophagectomy.

Methods: An IRB approved retrospective database of patients undergoing esophagectomy for esophageal malignancy from 2007-2014 was established. Clinicopathologic factors were recorded including preop enteral access, weight change, nutritional labs, preop cancer stage, operative details, and perioperative complications.

Results: One hundred fifty-six patients were identified, of which 99 (63.5%) received preop chemoradiation (cXRT) prior to esophagectomy. Since preop cXRT can influence perioperative nutrition, this group comprised the study cohort. Fifty (50.5%) underwent preop enteral access [esophageal stent (1), gastrostomy (14), jejunostomy (32), nasoenteric (1), combination (2); “access group”] prior to cXRT followed by esophagectomy and feeding jejunostomy unless it was pre-existing. There was no difference in demographics, preop tumor staging, or operative details between the access and non-access groups. No difference was noted between access and non-access groups in subjective dysphagia [n=43 (86%) vs 37 (75.5%), respectively; p=0.2)] or mean preop serum albumin (gm/dl) [3.9 (range 3.1-4.5) vs 4 (range 3.3-6.4), respectively; p=0.2]. To account for potential cXRT delays, there was no difference in median time from diagnosis to surgery in the access vs non-access groups (126d vs 126d, p=0.5). Comparing weight loss 6mo preop to surgery, the access group had a mean 5.2% weight loss (range -29.4 – +6.6%) vs 4.5% reduction (range -19.4% – +68.2%) in the non-access group (p=0.8). Additionally, mean weight loss 6mo preop to 6mo postop was similar in the access vs non-access groups [-11.2% (range -44% – +5.3%) vs -15.4% (range -34.1% – -1.4%), respectively p=0.1].  Complication rates between access and non-access groups (64% vs 51%, respectively; p=0.2) were likewise similar.  In patients with reported dysphagia, there was no difference in weight change 6mo preop to 6mo postop in the access vs non-access group (-11% vs -15.2%, p=0.1; respectively).

Conclusions: Despite the bias of establishing enteral access prior to preop cXRT for esophageal malignancy in candidates for esophagectomy, there was no difference in weight change, preop albumin, or complication rates in patients who had preop enteral access versus those who did not. Patients with esophageal malignancy should therefore proceed directly to appropriate neoadjuvant and surgical therapy with enteral access performed at the time of definitive resection or reserved for those with obstruction confirmed on endoscopy.

19.05 Protease Tailored Flourogenic Substrates Outperform CEA in Identifying Mucinous Pancreatic Cysts

Posted on January 25, 2017

D. A. Dominguez1, S. Ivry3, S. Hatcher3, E. Gilbert2, S. Kumar2, W. Park6, M. Schmidt7, R. Brand4, A. O’Donoghue5, K. Kirkwood2, C. Craik3  1UCSF East Bay,Department Of General Surgery,Oakland, CA, USA 2UCSF,Department Of General Surgery,San Francisco, CA, USA 3UCSF,Department Of Pharmaceutical Chemistry,San Francisco, CA, USA 4University Of Pittsburgh,Department Of Gastroenterology,Pittsburgh, PA, USA 5UCSD,Department Of Pharmacy And Pharmaceutical Sciences,San Diego, CA, USA 6Stanford University,Department Of Gastroenterology,Palo Alto, CA, USA 7Indiana University,Department Of Surgery,Indianapolis, IN, USA

Introduction:  Risk stratification of pancreatic cystic lesions remains an area of great clinical uncertainty.  Measurement of cyst fluid CEA is used to predict which cysts are mucinous, and therefore may have malignant potential, but its accuracy limits its usefulness.  Due to this lack of definitive pre-operative characterization, some patients will die from undiagnosed cancers, while others undergo unnecessary pancreatic resections with significant morbidity.  Dysregulation of protease expression and activity has been previously reported in mucinous pancreatic cyst fluid.  We tested the hypothesis that differences in proteolytic activity between mucinous (MUC) and non-mucinous (NON-MUC) cysts could be used to improve our ability to identify pre-malignant pancreatic tumors.

Methods:  We first analyzed cyst fluid from a cohort of human pancreatic neoplasms (MUC, n=16; NON-MUC, n=7) using multiplex substrate-profiling by mass spectrometry (MSP-MS), which is an unbiased, comprehensive technology for analyzing patterns of proteolytic activity. We found that aspartyl protease activity was unique to MUC pancreatic cysts. Next, using shotgun proteomic analysis, we identified 2 proteases (Prot1, Prot2), that were selectively expressed in MUC cyst fluid.  Specific cleavage profiles were used to design a selective fluorescent substrate for each protease. Substrates were then used to assess the activity of each protease in a larger patient cohort (MUC, n=71; NON-MUC, n=39); ROC curves were generated for each substrate.  Performance was compared with CEA values (CLIA lab) using >= 192 ng/mL as a cut off for MUC cysts. 

Results:  Receiver operator characteristic (ROC) curves for Prot1 and Prot2 exhibited an area under the curve (AUC) of 0.98 and 0.82, respectively. Prot1 demonstrated a sensitivity of 93% and specificity of 100%.  Prot2 had a sensitivity of 70% and a specificity of 92%.  Testing required < 0.2 mL cyst fluid.  CEA had an AUC of 0.86, and a sensitivity and specificity of 65% and 94%, respectively.

Conclusion:  MSP-MS is a powerful technology to examine dysregulated proteolysis in complex biological fluids.  The resultant fluorogenic substrates outperformed CEA, the highest of which had a sensitivity of 93% and a specificity of 100%, for the detection of MUC pancreatic cysts.  Our fluorescent assay has the potential to be a rapid, inexpensive, and highly accurate predictor of MUC pancreatic cysts. 

 

19.04 DNA released from PAD4-mediated NETosis enhances tumor growth in murine pancreatic cancer

Posted on January 25, 2017

J. Miller-Ocuin1, W. R. Doerfler1, X. Liang1, B. Boone1, A. Singhi1, M. Lotze1, H. Zeh1  1University Of Pittsburgh,Surgical Oncology/Surgery/Medicine,Pittsburgh, PA, USA

Introduction: Activated neutrophils release intracellular material in a process known as neutrophil extracellular trap (NET) formation. NETs result from histone citrullination, chromatin decondensation, and ultimately DNA release from the cell. Peptidyl arginine deiminase 4 (PAD4) is an enzyme required for NET formation. Increased NET formation is associated with cancer progression in preclinical models of murine pancreatic cancer. We hypothesized mice deficient in PAD4 would demonstrate decreased tumorigenesis.

Methods: Luciferase-transfected Panc02 cells were injected into the pancreas of WT controls or PAD4-/- mice. Tumorigenesis continued for 5 weeks in untreated experiments. DNAse (5mg/kg IP) or vehicle was injected daily for 3 weeks in treated experiments. Mice were imaged weekly using an in vivo imaging system (IVIS) for tumor growth; area of interest (ROI) is represented as photon/sec/cm2/Sr. At conclusion of experiments, mice were sacrificed for tumor weights, immunohistochemistry (IHC) and serum DNA quantification. Bone marrow chimeras using Pdx-Cre KrasG12D (KC) transgenic mice, which develop spontaneous pancreatic cancer, were generated with lethal irradiation followed by reconstitution with PAD4-/- or WT bone marrow. 21 days after treatment with cerulein, which induces pancreatitis to accelerate tumor growth, animals were sacrificed and organs harvested. Hematoxylin and eosin stained tumor sections were evaluated by a pancreatic pathologist.

Results: PAD4-/-tumor bearing mice showed decreased NETs on IHC and decreased serum DNA (406ng/ml vs 858ng/ml, p=0.03), a surrogate NET marker. Tumorigenesis was significantly decreased in PAD4-/- vs. WT mice (921mg vs. 326mg, p=0.001; ROI: 2.4×107 vs. 1.6×106, p=0.05). DNAse treatment of WT mice lead to significantly decreased tumor growth vs. sham treated controls (336mg vs. 206mg, p=0.05; ROI: 9.9×105 vs. 3.8×105, p=0.05) while there was no significant change in tumor growth in PAD4-/- animals treated with DNAse (195mg vs. 217mg, p=0.29; ROI: 8.5×105 vs. 6.9×105, p=0.43). There was a trend toward decreased high-grade precursors and invasive cancers in PAD4-/- bone marrow recipients as compared to WT recipients (p=0.29) with significantly diminished NET formation by isolated bone marrow supernatant DNA levels (197ng/mL vs. 796ng/mL, p=0.001).

Conclusion: Murine pancreatic tumors in PAD4-/-mice show decreased tumorigenesis and decreased NET formation. DNA released during NET formation leads to increased tumor growth, which is suppressed by DNAse administration. Future studies will focus on the mechanism through which NET DNA promotes tumor growth.

 

19.03 Gut Microbiome Promotes Pancreatic Oncogenesis by Inducing Innate and Adaptive Immune Suppression

Posted on January 25, 2017

M. Hundeyin1, S. Pushalkar1, D. Daley1, G. Werba1, N. Mohan1, S. Lall1, B. Wadowski1, B. Aykut1, E. Kurz1, U. Soni1, E. Morales-Vicente1, D. Saxena1, G. Miller1  1New York University School Of Medicine,Surgery,New York, NY, USA

Introduction:
Pancreatic ductal adenocarcinoma (PDA) is the 3rd most lethal cancer in the United States and accounts for 85% of all pancreatic malignancies. The gut microbiome has emerged as an important regulator in the balance between health and disease, including oncogenesis. However, the microbiome has not been directly linked to pancreatic oncogenesis. We postulated that hosts with PDA harbor an altered pancreatic and gut microbiome and that dysbiosis influences PDA progression. 

Methods:
To determine whether endoluminal gut bacteria can access the pancreas, we administered fluorescently-labeled Enterococcus faecalis to WT mice via oral gavage. To determine whether bacteria promote the progression of pancreatic oncogenesis, we employed the slowly progressive p48Cre;LSL-KrasG12D (KC) mouse model of PDA and rederived KC mice in a germ-free environment. To identify possible perturbations in the gut microbiome associated with the progressive pancreatic oncogenesis, we evaluated the composition of the gut microbial community of KC mice compared with age-matched WT littermate controls by performing 16S gene sequencing. Lastly to determine the mechanism of immunosuppression; we injected F21242 pancreatic tumor cell line orthotopically into the pancreas of WT mice after bacterial ablation and vehicle, isolated the pancreatic leukocytes and analyzed them by flow cytometry. 

Results:
In the pre-morbid state the intestinal microbiome is similar in mice bearing pancreas-specific oncogenic mutations and in controls; however, as mice age, PDA-bearing hosts develop a unique gut microbiome including expansion of Actinobacteria and Deferribacteres. We found that gut bacteria access the pancreas and the cancerous pancreas harbors a distinct microbiome in mice. Further, genotypically identical PDA-bearing mice that exhibit divergent disease phenotypes harbor stage-specific microbiomes suggesting that microbial structure is associated with disease aggressiveness. Germ-free or ablative antibiotic treated mice were protected against PDA whereas transfer of gut bacteria from PDA-bearing mice, but not from control mice, reversed the tumor-protection. Bacterial ablation was associated with innate and adaptive immunogenic reprogramming of the PDA tumor microenvironment including a marked reduction in myeloid-derived suppressor cells and immune-suppressive macrophages, increased Th1 differentiation of CD4+ T cells, and expansion and activation of cytotoxic CD8+ T cells. In addition, we show that gut bacterial ablation and PD-1 blockade offer synergistic efficacy.

Conclusion:
These data suggest that endogenous microbiota promote the crippling immune-suppression characteristic of PDA and that the microbiome has marked potential as a biomarker and therapeutic target in PDA.
 

19.01 Arid1a Has Context-Dependent Oncogenic and Tumor Suppressive Roles in Liver Cancer

Posted on January 25, 2017

S. C. Wang1,2, X. Sun2, I. Nassour1,2, X. Luo2, J. Chuang2, L. Li2, T. Maples2, C. Celen2, L. H. Nguyen2,3, S. Zhang2, H. Zhu2  1University Of Texas Southwestern Medical Center,Division Of Surgical Oncology,Dallas, TX, USA 2University Of Texas Southwestern Medical Center,Children’s Research Institute,Dallas, TX, USA 3Howard Hughes Medical Institute,Chevy Chase, MD, USA

Introduction:

ARID1A, a component in the SWI/SNF chromatin-remodeling complex, is one of the most commonly mutated genes in cancer. Because a majority of the mutations are loss-of-function, ARID1A is widely assumed to be a tumor suppressor. However, the functional effect of ARID1A loss is unclear. Here, we used a genetically engineered mouse model to dissect the effects of Arid1a loss in liver cancer.

 

Methods:

A liver-specific Tet-Off MYC overexpression liver cancer model was used. The tetracycline transactivator was driven by the liver activator protein promoter and MYC expression was under the control of the tetracycline response element (LAP-tTA; TRE-MYC, referred heretofore as LAP-MYC mice). MYC was induced at birth by removal of doxycycline. Liver specific Arid1a knockout (LKO) was achieved by crossing in Albumin-Cre; Arid1af/f . A lentiviral system was used to stably express shArid1a in the mouse hepatoma Hepa1c1c7 cell line. The Arid1a overexpression construct was delivered with adenovirus.

 

Results:

LAP-MYC LKO mice had significantly improved survival as compared to LAP-MYC mice (Figure A; HR: 0.45; 95% CI: 0.28 to 0.80, P < 0.01) suggesting that Arid1a had oncogenic properties. When we overexpressed Arid1a in LAP-MYC mice, we found increased tumor burden, confirming that Arid1a could be oncogenic (Figure B; P < 0.01). Next, we transplanted Hepa1c1c7 cell lines that stably expressed shArid1a in the subcutaneous tissue of immunocompromised mice. The tumors grew at the same rate as cells that had normal Arid1a expression. These data suggest that Arid1a was required for normal initiation of liver cancer but did not constrain the growth of established cancer cells.

 

RNA-seq of LAP-MYC and LAP-MYC LKO tumors demonstrated pro-invasion and metastasis gene programs were upregulated in the LAP-MYC LKO tumors, signifying that in this context, Arid1a had tumor suppressive effects. To test the functional metastatic effects of Arid1a loss, we delivered the shArid1a expressing Hepa1c1c7 cells systemically via tail vein injections and found that the Arid1a knockdown cells resulted in more lung metastases than control cells (Figure C; P < 0.001). This showed that in established cancers Arid1a was tumor suppressive and its loss conferred increased metastatic potential.

 

Conclusions:

Arid1a in liver cancer has both oncogenic and tumor suppressive properties dependent on temporal context. It potentiates tumor initiation and constrains metastases. Other contexts, such as tissue type and dosage, should also be explored to fully characterize the role that Arid1a plays in cancer.

17.20 Chemotherapy versus Chemoradiotherapy for Resected Pancreatic Cancer: Defining the Optimal Regimen

Posted on January 25, 2017

C. Mosquera1, L. M. Hunter1, T. L. Fitzgerald1  1East Carolina University Brody School Of Medicine,Surgical Oncology,Greenville, NC, USA

Introduction:  Postoperative adjuvant therapy for pancreatic adenocarcinoma has engendered significant controversy and is the subject of yet to be completed clinical trials. Pending these trials, data to guide optimal patient management is needed.

Methods:  Patients with resected adenocarcinomas of the pancreas undergoing surgery only, postoperative chemotherapy (CT), and chemoradiotherapy (CRT) from 2004-2013 were identified using the NCDB.

Results: A total of 26,821 patients were included. A majority were male (50.6%), white (86.3%), stage of II (82.4%), and with a Charlson comorbidity score of 0 (67.7%). On univariate analysis, adjuvant therapy was most strongly associated with younger age, race, insurance status, lymphatic invasion, high grade, and size > 2cm., p<.0001. On multivariate analysis, the associations continued for age <50 years (OR 5.24), lymphatic invasion (OR 1.60), high-grade (OR 1.37) and size > 2cm (OR 1.35), but not race or insurance status. On univariate survival analysis, patients that received adjuvant therapy had a greater median survival compared to surgery alone (22.0 vs 18.2 months, p<.0001). On multivariate survival analysis adjuvant therapy continued to be associated with survival (1.39, p<.0001). A total of 16,549 patients received postoperative CT or CRT. On univariate analysis patients who were older, had negative margins, and with Medicare were most likely to receive CT, p<.0001. On multivariate analysis age and negative margins were significant (OR 1.73, p<.0001), lymphatic invasion, tumor size, and insurance status were not. When survival analysis was restricted to those receiving CT or CRT, the highest median survival was seen in low grade (31.2 months, p<.0001) and size < 2cm. (33.1 months, p<.0001). Patients who received CRT had longer median survival than those who received CT (22.9 vs 21.8 months, p=.0001). On multivariate analysis of CT vs CRT (HR 1.14), high grade (HR 1.64), positive margins (HR 1.53), and lymphatic invasion (HR 1.50) continue to be associated with diminished survive, p <0.0001.

Conclusion: Postoperative adjuvant therapy is associated with a 40% improved survival. In contrast to other studies, these data suggest a modest survival advantage to combination therapy compared to CT alone.

 

17.18 Prognostic effect of lymph node ratio after curative-intent resection for distal cholangiocarcinoma

Posted on January 25, 2017

A. Y. Son1, R. Shenoy1, C. G. Ethun2, G. Poultsides3, K. Idrees4, R. C. Fields5, S. M. Weber6, R. C. Martin7, P. Shen11, C. Schmidt9, S. K. Maithel2, T. M. Pawlik10, M. Melis1, E. Newman1, I. Hatzaras1  1New York University School Of Medicine,Surgery,New York, NY, USA 2Emory University School Of Medicine,Surgery,Atlanta, GA, USA 3Stanford University,Surgery,Palo Alto, CA, USA 4Vanderbilt University Medical Center,Surgery,Nashville, TN, USA 5Washington University,Surgery,St. Louis, MO, USA 6University Of Wisconsin,Surgery,Madison, WI, USA 7University Of Louisville,Surgery,Louisville, KY, USA 9Ohio State University,Surgery,Columbus, OH, USA 10Johns Hopkins University School Of Medicine,Surgery,Baltimore, MD, USA 11Wake Forest University School Of Medicine,Surgery,Winston-Salem, NC, USA

Introduction:
The ratio of metastatic to total harvested lymph nodes (LNR) is an important prognostic factor following resection of gastrointestinal malignancies. We assessed the prognostic value of LNR in patients undergoing resection for distal cholangiocarcinoma (DCC).

Methods:
Patients who underwent curative intent resection of DCC in 10 institutions of the US Extrahepatic Biliary Malignancy Collaborative were included. Descriptive statistics were used to evaluate characteristics of demographic data. Multivariate proportional hazards regression was used to identify factors associated with recurrence-free survival and overall survival.

Results:
A total of 265 were included (median age 67 years; 63.4% male): 199 with low-LNR (00.4). The high LNR group was less likely to have undergone a Whipple procedure (85.4% vs. 82.9% vs. 60.0%, p<0.01), had a higher proportion of margin-positive resection (19.6% vs. 19.5% vs. 45.8%, p<0.05), poor differentiation (26.2% vs. 36.6% vs. 52.2%, p<0.05), lymphovascular (44.3% vs. 74.3% vs. 88.2%, p<0.001) and perineural invasion (81.0% vs. 69.2% vs. 91.3%, p>0.05). Multivariate analysis showed high-LNR as an independent predictor of poor RFS (HR 4.6, 95%CI 1.8-11.8, p=0.001) and OS (HR 2.2, 95%CI 1.0-4.6, p<0.05) (Table 1).  Rates of adjuvant chemoradiation in low-moderate LNR and high-LNR were 61.9% and 82.6%, respectively (p=0.07). Nevertheless, stratification by LNR showed no improvements in RFS or OS with either adjuvant chemoradiation.

Conclusion:
LNR can be used as a prognostic factor for recurrence and survival in patients undergoing curative-intent resection for DCC. Every effort should be made to perform an oncologic resection, with negative margins and adequate lymph node harvest, as adjuvant chemoradiation does not appear to provide LNR-specific improvements in long-term prognosis.
 

17.14 Surgical Management of Adolescents and Young Adults with GIST: A Population-Based Analysis

Posted on January 25, 2017

K. E. Fero1, T. M. Coe5, J. D. Murphy4, J. K. Sicklick2  1University Of California – San Diego,School Of Medicine,San Diego, CA, USA 2University Of California – San Diego,Division Of Surgical Oncology And Department Of Surgery,San Diego, CA, USA 3University Of California – San Diego,Division Of Medical Oncology And Department Of Medicine,San Diego, CA, USA 4University Of California – San Diego,Radiation Medicine And Applied Sciences,San Diego, CA, USA 5Massachusetts General Hospital,Department Of Surgery,Boston, MA, USA

Introduction:  There is a dearth of population-based evidence regarding outcomes of the adolescent and young adult (AYA) population with gastrointestinal stromal tumors (GIST). The aim of this study is to describe a large cohort of AYA patients with GIST and investigate the impact of surgery on GIST-specific and overall survival.

Methods:  This is a retrospective cohort study of patients in the Surveillance, Epidemiology and End Results (SEER) database with histologically-diagnosed GIST from 2001-2013, with follow-up through 2015. SEER is a population-based cancer registry with 18 sites covering approximately 30% of the United States. We identified 392 AYA patients among 5,765 patients with GIST; the main exposure variable identified was tumor resection and the primary outcome measure was mortality. Baseline characteristics were compared between AYA (13-39 years old) and older adult (OA; ³40 years old) patients and among AYA patients stratified by operative management. Kaplan-Meier estimates were used for overall survival (OS) analyses. Cumulative incidence functions were used for GIST-specific survival (GSS) analyses. The impact of surgery on survival was evaluated with a multivariable Fine-Gray regression model.

Results: There was no significant difference between AYA and OA patients with regards to sex, race distribution, tumor size or stage. Compared to OA, more AYA patients had small intestine GISTs (35.5% vs 27.3%, P <0.01) and were managed operatively (84.7% vs 78.4%, P < 0.01). Multivariable analysis of AYA patients demonstrated that non-operative management was associated with over a 2-fold increased risk of death from GIST (SDHR 2.271; 95% CI:1.214-2.249). On subset analysis of AYA patients with tumors of the stomach and small intestine (n=349), small intestine location was associated with improved survival (OS: 91.1% vs 77.2%, P=0.01; GSS: 91.8% vs 78.0%, P<0.01). On subset analysis of AYA patients with metastatic disease (n=91), operative management was associated with improved survival (OS: 69.5% vs 53.7%, P=0.04; GSS: 71.5% vs 56.7%, P=0.03).

Conclusion: We report the first population-based analysis of GIST outcomes in the AYA population. These patients are more likely to undergo surgical management than patients in the OA cohort. Operative management is associated with improved overall and GIST-specific survival in AYA patients, including those with metastatic disease.
 

16.21 Use of I2b2 Cohort Discovery Tool to Identify Potentially Unrecognized Primary Hyperparathyroidism

Posted on January 25, 2017

J. Park1, K. Doffek1, T. W. Yen1, K. E. Coan1, T. S. Wang1  1Medical College Of Wisconsin,Surgical Oncology,Milwaukee, WI, USA

Introduction:  The majority of patients with primary hyperparathyroidism (pHPT) present with asymptomatic disease, as nonspecific presenting signs and symptoms are heterogeneous to normal aging or other diseases. As a result, patients with hypercalcemia may not be appropriately referred for further evaluation/treatment of potential pHPT. The purpose of this study was to determine the prevalence and trends of potentially undiagnosed pHPT at a tertiary care institution.

Methods:  This is a retrospective review of de-identified patient data of all patients from a single health system collected within Informatics for Integrating Biology and the Bedside (i2b2) Cohort Discovery Tool between 1/1/15 and 9/30/15. The study cohort was defined as any patient with at least one serum calcium levels >10.2 mg/dL (normal, 8.6-10.2) and PTH level of >30 pg/mL (normal, 16-72) in the study period; labs were not necessarily drawn concurrently. Patients were divided into 4 groups based on the presence or absence of an ICD-9 diagnosis of HPT (pHPT, secondary/tertiary HPT, HPT not otherwise specified, and no diagnosis). The presence of symptoms of pHPT (nephrolithiasis, gastroesophageal reflux disease [GERD] and/or bone-related disease [osteopenia, osteoporosis, or compression fractures]), extent of hypercalcemia and hyperparathyroidism, and referral to Endocrinology or Surgery within the study period were determined and compared between patients with PTH levels between 30-70 and those >70.

Results: Of the 941 patients, 446 (47%) had PTH levels of 30-70 and 495 (53%) had PTH levels >70. Those patients with a PTH >70 were more likely to have a diagnosis of HPT (primary or unspecified) than patients with PTH levels of 30-70 (Table). There was no difference in reported symptoms between the two groups (p=0.521). However, those with a PTH level >70 were more likely to be referred for additional evaluation (262, 53%) than patients with PTH levels of 30-70 (200, 45%; p=0.005). Patients with PTH >70 were also more likely to be referred to Surgery (31% vs. 22%).

Conclusion: Based on the findings of this study, patients with elevated serum calcium levels and PTH levels 30-70 appear to be less frequently referred for evaluation/treatment of potential pHPT than patients with PTH levels >70 pg/mL. Despite the limitations of this de-identified database, this suggests that pHPT may be underdiagnosed and undertreated within the health care system.  Further examination of these data and broader dissemination of the diagnosis and symptoms of pHPT to primary care and other providers should be considered.

 

16.19 Analytic Morphomics And Geriatric Assessment Predict Pancreatic Fistula After Pancreaticoduodenectomy

Posted on January 25, 2017

A. J. Benjamin1, A. Schneider1, M. M. Buschmann2, B. A. Derstine4, S. C. Wang3,4, W. Dale2, K. Roggin1  1University Of Chicago,Surgery,Chicago, IL, USA 2University Of Chicago,Geriatrics & Palliative Medicine,Chicago, IL, USA 3University Of Michigan,Surgery,Ann Arbor, MI, USA 4University Of Michigan,Morphomic Analysis Group,Ann Arbor, MI, USA

Introduction:

Following pancreaticoduodenectomy (PD), pancreatic fistula (PF) remains a significant cause of morbidity, and current models used to predict PF rely on measures which are only available at the time of operation.  Body imaging analysis, such as analytic morphomics (AM), and pre-operative geriatric assessment (GA) have been shown to forecast significant adverse outcomes following PD.  We hypothesized preoperative AM and GA can accurately predict PF.

Methods:

An IRB-approved review identified patients (n=63) undergoing PD by experienced pancreatic surgeons who had a non-contrast computed tomography scan (CT), pre-operative geriatric assessments, and prospectively tracked postoperative 90-day outcomes collected between 10/2007 and 3/2016.  PF were graded according to the International Study Group for PF (ISGPF) criteria.  Pre-operative GA included the Short Physical Performance Battery, self-reported exhaustion on the Center for Epidemiologic Studies Depression Scale (CES-D exhaustion; one of the five criteria of Fried’s frailty), and the Vulnerable Elders Survey (VES-13).  CT scans were processed to measure morphomic variables which included measures of psoas muscle area and Hounsfield units (HU), subcutaneous fat measures, visceral fat measures, and total body dimensions.  Correlations with the development of a PF were obtained using univariate analysis and multivariate elastic net regression models.  

Results:

The median patient age was 67 (37-85) years old and the median BMI was 27.0 (18.9-50.5).  In total, 15/63 patients (23%) had a documented PF: 8 patients had a ISGPF grade A PF (53%), 6 had a grade B PF (40%), and one had a grade C PF (7%). On univariate analysis, PF was associated with CES-D exhaustion (p=0.005), VES-13 (p=0.038), subcutaneous fat HU (p=0.009), visceral fat area (p=0.035), visceral fat HU (p=0.001), average psoas HU (p=0.040) and psoas low density muscle area (p=0.049).  A predictive model based on demographics, analytic morphomics, and GA had a high AUC for predicting PF (AUC=0.915) when compared to a clinical “base model” including age, BMI, ASA class, and Charlson comorbidity index (AUC=0.685).  

Conclusion:

Preoperatively measured AM, in combination with GA, can accurately predict the likelihood of PF following PD.  Validation of this model on a larger cohort would provide surgeons with a practical tool to more accurately risk-stratify patients prior to PD.

16.08 Factors Predicting Radiation Therapy in Early Stage Breast Cancer in Patients Age 70 and Over

Posted on January 25, 2017

S. Larson1, B. Anderson2, G. Leverson3, H. Neuman1, C. Greenberg1, L. Wilke1, J. Steiman1  3University Of Wisconsin,Surgery,Madison, WI, USA 1University Of Wisconsin,General Surgery,Madison, WI, USA 2University Of Wisconsin,Human Oncology,Madison, WI, USA

Introduction:  Radiation therapy (RT) is recommended as standard of care for women undergoing breast conserving surgery (BCS) for an invasive breast cancer as a way to decrease the risk of loco-regional recurrence (LRR). In 2004, Cancer and Leukemia Group B (CALGB) reported the results of a randomized trial (9343) which sought to determine if women with clinical stage I, estrogen receptor (ER) positive breast cancer who were ≥70 years of age could omit radiation in the setting of adjuvant hormonal therapy (HT). Omission of RT resulted in a low rate of LRR at 5 years (4%). Population studies assessing practice patterns after the guideline change (2009-2011) demonstrated that 65-88% of women ≥70 years of age continued to receive RT after BCS. Receipt was often associated with age, tumor size and grade. These studies, however, are limited, as they cannot assess the relationship with other factors that may influence decision making such as Ki67, margin status, and comorbidities. Our objective was to examine receipt of RT for women ≥70 years of age at our institution and identify patient factors associated with its recommendation.

Methods:  Retrospective data was obtained with IRB approval through the institutional cancer registry for women aged ≥70 diagnosed with an invasive BC from January 2014 – December 2015 (n=44). Inclusion criteria were patients with a pathologic stage I, ER+ breast cancer who underwent BCS and received HT. Patient (age), tumor (size, grade, molecular tumor subtype, Ki67), and treatment characteristics (margin status) were abstracted from the patient chart.  Statistical analyses were done using Chi square tests.

Results: Overall, 59% (n=26) were recommended RT (Table 1). Factors associated with a recommendation for RT included Her2neu + status (p=0.05) and grade 3 tumors (0=0.03), with all patients meeting these criteria being recommended RT.  Similarly, all patients with a Ki67 >45% (n=5) were recommended RT. No association amongst age was observed.  Few patients had positive margins, limiting this analysis.

Conclusion: Consistent with prior population studies, the majority of patients ≥70 years of age were recommended RT despite strictly meeting criteria for CALGB 9343. Recommendations appear to be influenced by Her2neu status and grade.  Her2neu was not collected as part of CALGB 9343; thus, further research should focus on the relationship between Her2neu status and outcomes without RT.  Additionally, given the high ongoing use of RT, future studies should identify factors influencing provider decision-making regarding RT and application of CALGB 9343 to patients in their clinical practice. This will allow for opportunities to improve the quality of care provided to older breast cancer patients.

15.15 Pre-Surgical Renal Mass Biopsy Reduces Upfront Treatment Costs for Small Renal Masses (SRMs)

Posted on January 25, 2017

M. C. Rozo1, T. J. Ziemlewicz2, S. L. Best1, S. A. Wells2, M. G. Lubner2, J. Hinshaw1,2, F. Shi1, F. T. Lee2, S. Y. Nakada1, E. Abel1  1University Of Wisconsin School Of Medicine And Public Health,Department Of Urology,Madison, WI, USA 2University Of Wisconsin School Of Medicine And Public Health,Department Of Radiology,Madison, WI, USA

INTRODUCTION AND OBJECTIVES: Approximately 15-20% of incidental renal masses ≤4cm are benign tumors such as oncocytomas or lipid poor angiomyolipomas (AML), which can be managed non-surgically. Increasing utilization of small renal mass biopsy (SRMB) may reduce treatment of benign tumors, decreasing upfront costs and preserving renal function in untreated patients. The objective of this study is to evaluate if increasing SRMB utilization reduces surgical treatment and upfront (30 day) costs of care management for patients with benign small renal masses.

 

Methods: Clinical and pathologic data were reviewed from patients with incidental renal masses ≤4cm who were treated surgically and/or received SRMB from 2003-2015. Patients not considering surgery were excluded. Patients were divided into 2 cohorts (2003-2009 and 2010-2015) for analysis to reflect increased SRMB utilization at our institution since 2010. Institution specific Medicare costs for 2015 were used to calculate costs of surgery and biopsy in all patient cohorts.

 

Results: Of 437 patients with renal masses ≤4cm, SRMB was performed in 6% of 199 patients treated from 2003-2009 and 54% of 238 patients from 2010-2015. The rate of surgery for benign tumors from 2003-2009 was higher than 2010-2015, 19.7% vs. 12.3%, p=0.04. For patients treated without biopsy from 2010-2015, the benign surgery rate was 21.8%. From 2010-2015, 42 patients with benign tumors were identified using SRMB and avoided surgery (10 AML, 32 oncocytoma).   

 

Given the upfront cost of $2,020.44 USD for ultrasound guided biopsy and $12,153.01 USD for partial nephrectomy, the cost of care per patient was calculated for each of the two cohorts.

 

The cost per patient in the 2003-2009 vs. 2010-2015 cohort was $12,274.85 USD vs. $11,094.98 USD. Increased biopsy utilization was associated with $1,179.86 (9.6%) cost savings per patient. For 2010-2015, increased use of biopsy saved $280,840 USD in estimated upfront treatment costs.  

 

Conclusions: Pretreatment biopsy reduces surgery for benign tumors and decreases the upfront cost of care per patient by $1,179.86 USD. Increasing utilization of biopsy for small renal masses decreases overall treatment cost and preserves renal function in patients with benign tumors who avoid treatment.

14.21 Disclosure of Pre-Referral Medical Errors: Cancer Specialists’ Attitudes and Current Practices

Posted on January 25, 2017

H. Singh1, R. M. Kauffman2, M. C. Lee3, G. P. Quinn4, L. A. Dossett1  1University Of Michigan,Department Of Surgery,Ann Arbor, MI, USA 2Vanderbilt University Medical Center,Department Of Surgery,Nashville, TN, USA 3Moffitt Cancer Center And Research Institute,Comprehensive Breast Program,Tampa, FL, USA 4Moffitt Cancer Center And Research Institute,Department Of Health Outcomes And Behavior,Tampa, FL, USA

Introduction:
Physicians are ethically obligated to disclose their own medical errors to patients. Physician-level training and risk management systems facilitate proper disclosure. No guidelines, education, training, or systems address the disclosure of medical errors discovered by specialists that have occurred prior to consultation – “pre-referral errors.” We sought to describe attitudes and practices regarding disclosure of pre-referral errors discovered across hospital systems.

Methods:
We conducted face-to-face semi-structured interviews with fellowship-trained cancer specialists at multiple NCI-designated cancer centers. Interviews (30-60 minutes in duration) were audiotaped, transcribed verbatim, and independently coded for a priori and emergent themes using the constant comparative method. Open and axial coding were applied using content analysis. 

Results:
Subjects were fellowship-trained specialists of many disciplines (n=30, 40% female, 60% surgeons). The mean age was 46 years; and both the median years of post-graduate training and independent practice were 8. Subjects exhibited a wide range of practice patterns, attitudes/beliefs, and barriers regarding the disclosure of pre-referral errors to their new patients (Table 1). Practice patterns included: no disclosure, vague or limited disclosure, event- or factor-dependent disclosure, and explicit disclosure. Attitudes ranged from no perceived added benefit to disclosing to the thought that the majority of errors are not malicious. A wide range of barriers to disclosing also exist, including: concern for referral base, incomplete information, introducing unnecessary stress for the patient, avoiding a “superior ego” image, and potentially damaging another physician’s reputation and/or livelihood.

Conclusion:
Specialists commonly contend with pre-referral errors but practice patterns, attitudes, beliefs, and barriers vary considerably among specialists. Using these data, there is potential to develop and implement disclosing mechanisms that may help mitigate and overcome identified attitudes, beliefs, and barriers.
 

12.17 Focused Parathyroidectomy under Local Anaesthesia – Evaluation of Outcomes and Satisfaction

Posted on January 25, 2017

S. SEN1, K. REKA2, A. J. CHERIAN1, P. RAMAKANT1, P. M. JACOB1, D. T. ABRAHAM1  2CMC HOSPITAL,BIOSTATISTICS,VELLORE, TAMIL NADU, India 1CMC HOSPITAL,ENDOCRINE SURGERY,VELLORE, TAMIL NADU, India

Introduction:

Focused parathyroidectomy is treatment of choice in PHPT (Primary hyperparathyroidism) due to single gland adenoma in patients with concordant imaging on parathyroid scintigraphy and ultrasound.  To avoid delays due to lack of anaesthesia time, this can be performed under local anaesthesia (LA) in a select group of patients

This study was done to evaluate the effectiveness of focused parathyroidectomy under local anaesthesia and mild sedation administered and monitored by surgeon

Methods:

We conducted a prospective observational study of all patients undergoing focused parathyroidectomy under local anesthesia at our institution. All consecutive patients with PHPT from Oct 2015 to July 2016, planned for the same, were evaluated for suitability to perform this procedure under LA after institutional ethics approval. If feasible, they were consented and outcomes were noted.

The study evaluated the following outcomes:

Primary outcomes:Biochemical cure – corrected calcium and PTH in immediate post operative period

Secondary outcomes:Complications – hematoma, nerve injury, hypocalcaemia, failed exploration, wound infection; Scar size; Intra-operative and Post-operative pain – visual analogue score; Post-operative nausea and vomiting; Requirement of analgesia – local anaesthetic used , fentanyl, midazolam dosages; Total duration of procedure – operating time;Overall patient satisfaction- patient satisfaction with anaesthesia, surgery 

Results:

24/46 underwent the procedure under LA with mild sedation.

All patients had a biochemical cure in the immediate post operative period. 1/ 24 patient  was converted to General Anaesthesia (GA) due to bleeding. 1/ 24 patient had voice change post operatively, 14 /24 patients had hypocalcaemia postoperatively requiring oral or intravenous calcium.

The mean length of scar was 4.38 + 0.17 cm. The mean gland weight and maximum dimension were 2502.08 + 466 mg and 2.383+ 0.20 cm respectively. On Visual Analog Score (VAS), the mean score was 2.67+ 0.339and 1.83+ 0.197 in 1st and 2nd post operative day respectively.

Table 1 shows the mean of analgesic requirement

 

The mean ‘operating’ times was 53.33+ 3.453 minutes.

 The mean satisfaction score (1-5, 5 being most satisfied) with LA and surgery were 4.71+ 0.112 and 4.88 +0.069 respectively

Conclusion:

Focused parathyroidectomy under LA could be monitored and performed safely by a surgeon ensuring both biochemical cure and adequate patient satisfaction for a select group of patients

07.19 Molecular Profiling and Primary Location of Melanoma: Experience at an NCI-designated Cancer Center

Posted on January 25, 2017

J. Lou1, M. Renzetti1, I. Soliman1, H. Wu1, B. Luo1, A. J. Olszanski1, S. Movva1, M. Lango1, S. Reddy1, F. Zih1, J. M. Farma1  1Fox Chase Cancer Center,Surgical Oncology,Philadelphia, PA, USA

Introduction:  Molecular profiling is becoming an increasingly important aspect in the interrogation of primary cancers. Next generation sequencing (NGS) is being used at our institution to examine hot-spot mutations in 50 cancer-related genes in various tumors. The principle aim of this investigation is to evaluate molecular profiling of malignant melanoma (MM) and to correlate primary location of the melanoma with genetic mutations.

Methods:  Patients with primary or recurrent MM of all stages were included in the study. Using NGS, we analyzed tissue samples for mutations in targeted regions of 50 cancer-related genes.  Clinical and pathologic data were collected.

Results: Specimens from 138 patients with MM were analyzed, excluding 2 from analysis due to insufficient DNA and 1 due to incomplete profiling. Median age at diagnosis was 65 (range 24-90) and 64% were male (n=86). There were 26 patients with Stage I melanoma, 72 with Stage II, 14 with Stage III, and 12 with Stage IV. Primary tumor locations included head and neck (N=23), upper extremity (N=29), trunk (N=31), lower extremity (N=39), and mucosal sites (N=5). In total, 218 mutations were identified, affecting 30 unique genes. Patients with a primary location at their head and neck had the greatest average number of mutations (x=2.04), with the greatest percentage of mutations in BRAF (including BRAF K601E, G466V, V600E, V600K, V600R) and TP53 genes (Figure 1). Lower extremity sites had the next highest mean number of mutations (x=1.87), with the greatest fraction of mutations in BRAF and NRAS genes (Figure 1).  Mucosal tumors had the lowest mean number of mutations (x=0.4), with only mutations in TP53 (Figure 1). Across all sites, a large percentage of mutations were either in BRAF, NRAS, or TP53 genes, with BRAF being the most common in lower extremity sites and NRAS most common in truncal tumors.

Conclusion: While there is no statistical significance comparing primary tumor site and genetic mutations, the descriptive statistics warrants further investigation with a larger sample size.

 

07.18 Defining Treatment Paradigms for High-Grade Gastroenteropancreatic Neuroendocrine Tumors

Posted on January 25, 2017

R. L. Guyton Jr1, M. W. McMullen2, C. S. Lea2, J. Brinkley2,3, C. Mosquera1, T. L. Fitzgerald1  1East Carolina University Brody School Of Medicine,Division Of Surgical Oncology,Greenville, NC, USA 2East Carolina University Brody School Of Medicine,Department Of Public Health,Greenville, NC, USA 3American Institutes For Research,Chapel Hill, NC, USA

Introduction:  The incidence of high-grade gastroenteropancreatic neuroendocrine tumors (HG GEP-NET) is increasing, but a lack of consensus remains regarding optimal treatment regimens.  This study examines whether surgical resection and adjuvant chemotherapy provide a survival advantage for patients with HG GEP-NET.

Methods:  Incident cases of HG GEP-NET from 2004-2013 were obtained from the National Cancer Data Base.  Data examined included clinical and pathologic characteristics at diagnosis, treatment strategies, and survival outcomes.  Univariate and Cox regression analyses were performed to examine survival outcomes.

Results:  In total, 4,630 HG GEP-NET patients were identified.  The median age of diagnosis was 66 years.  A majority of patients were male (55%), white (84%), and had a colorectal primary (41%).  Surgical resection was associated (p < .0001) with survival on univariate analysis. On Cox regression analysis, surgical resection remained a significant predictor of survival (HR = 0.43, 95% CI 0.37–0.49) after adjusting for age, primary site, tumor size, and regional lymph node (RLN) involvement.  A total of 1,903 HG GEP-NET underwent surgical resection of the primary site.  On Cox regression analysis, primary site (colorectal, referent; appendix, HR = 0.51, 95% CI 0.36–0.71; small intestine, HR = 0.63, 95% CI 0.50–0.77; pancreas, HR = 0.80, 95% CI 0.66–0.96) were associated with improved survival after adjusting for age, tumor size, and RLN involvement, however, adjuvant chemotherapy (HR = 0.90, 95% CI 0.79–1.02) was not.  Multiple models were constructed to define the benefit of chemotherapy based on the primary site: Model 1 – colorectal primaries; Model 2, primaries of the ampulla of Vater, esophagus, hepatobiliary, and stomach; and Model 3 – primaries of the appendix, pancreas, and small intestine.  On Cox regression analysis, adjuvant chemotherapy conferred a survival benefit in Model 1 (HR = 0.68, 95% CI 0.58 – 0.81), indicated no significant difference in survival in Model 2 (HR = 0.90, 95% CI 0.68 – 1.20), and a survival detriment in Model 3 (HR = 1.66, 95% CI 1.30 – 2.13). 

Conclusion:  Surgical resection was associated with a survival advantage over all primary sites for HG GEP-NETs.  Adjuvant chemotherapy may be beneficial for colorectal HG GEP-NET compared to surgery alone; however, the role of adjuvant chemotherapy for other primary sites is unclear.

 

07.17 Comparing Perioperative Chemotherapy to Endocrine Treatment in Breast Cancer Patients : A Meta-analysis

Posted on January 25, 2017

H. Foong1, Y. Cheng1, D. Yakoub1  1University Of Miami,Division Of Surgical Oncology At Department Of Surgery,Miami, FL, USA

Introduction: Current treatment regimens for hormone receptor positive breast cancer patients involve the administration of perioperative chemotherapy or hormonal therapy. However, there are no concluding data as to superiority of one or the other in terms of event free survival.

Methods: Online search of PubMed, Scopus, Embase, Google Scholar was done. Studies comparing neoadjuvant and/or adjuvant chemotherapy to hormonal therapy in both pre and postmenopausal patients with estrogen receptor positive breast cancer were reviewed. Key Bibliographies were reviewed for related articles. Study quality was assessed using STROBE checklist. Pooled odds ratio (OR) along with the 95% confidence intervals (CI) for event free survival at 5 and 9 years were calculated.

Results:A total of 236 studies were identified. Seven met our selection criteria. Total study subjects were 2489 and 2454 for the hormonal therapy and chemotherapy arms respectively. All 7 studies reported on event free survival rates at 5 years, only 4 of them reported on survival rates at 9 years. Meta-analysis of included data showed a trend for better survival in chemotherapy group at 5 years yet this did not reach statistical significance (OR: 1.14; CI: 0.89-1.45). At 9 years, endocrine therapy group seem to have relatively better survival, yet again, the difference did not reach statistical significance (OR: 0.93; CI: 0.78-1.12).

Conclusion:In spite of relatively better survival at 5 years and relatively worse survival at 9 years, there is not enough evidence to claim superiority of perioperative chemotherapy on endocrine therapy in hormone receptor positive pre or post-menopausal breast cancer patients. Further prospective large scale studies are needed to further examine the difference.      

 

07.16 Outpatient vs. Inpatient Mastectomy: An Analysis of Patient Factors in U.S. Women with Breast Cancer

Posted on January 25, 2017

J. Yu1, M. Rendulic2, M. A. Olsen2, A. E. Cyr1, J. A. Margenthaler1  1Washington University,Surgery,St. Louis, MO, USA 2Washington University,Medicine,St. Louis, MO, USA

Introduction:
Despite advances in surgical technique and perioperative care, most women who undergo mastectomy for breast cancer are still commonly admitted as inpatients for pain control, perceived patient satisfaction, and closer monitoring for possible complications.  However, even one night of inpatient admission represents a substantial cost burden to the patient and has not been shown to reduce the odds of 30-day postoperative complications.  It is unclear which patients might be most suitable for same-day or outpatient mastectomy.  We sought to assess patient factors in relation to the utilization of outpatient vs. inpatient mastectomy in U.S. women with breast cancer.

Methods:
Using the Healthcare Cost and Utilization Project State Ambulatory Surgery and Services Databases and State Inpatient Databases for California and Florida from 2006-2011, we analyzed clinical and demographic factors in women over age 18 undergoing unilateral mastectomy for invasive breast cancer, breast cancer in situ, or history of breast cancer.  Clinical data assessment was performed using ICD-9 and CPT codes and the Elixhauser comorbidity index.  Descriptive statistics were performed to analyze the relationship between patient factors and admission status after mastectomy.

Results:
Of 71,619 women who underwent unilateral mastectomy, 23,503 (33%) were treated as an outpatient and 48,116 (67%) were admitted as inpatients postoperatively.  Significant geographic and temporal differences were clear: patients in Florida (9,440; 38%) were much more likely to have outpatient procedures compared to patients in California (14,063; 30%), and fewer outpatient mastectomy procedures were performed in 2010-2011 (6,350; 31%) compared to 2006-2009 (17,153; 33%).  Outpatients were more likely to undergo simple mastectomy (OR 1.61 [95% CI 1.56-1.66]) and less likely to undergo modified radical mastectomy (OR 0.65 [95% CI 0.63-0.67]) or to have simultaneous implant or expander reconstruction (OR 0.77 [95% CI 0.75-0.81]).  Women undergoing mastectomy as outpatients were also more likely to be younger (≤50 years), have private insurance, be Caucasian, and have fewer comorbidities (p<0.05). 

Conclusion:
The utilization of outpatient mastectomy varies widely based on clinical and geographic factors.  Patients with private insurance, fewer comorbidities, and limited disease who do not undergo immediate reconstruction are more likely to undergo mastectomy without inpatient admission.  Assessment of short- and long-term patient outcomes may provide additional evidence to support outpatient mastectomy as a patient-centered and cost-effective approach for certain breast cancer patients.
 

« Previous Page
Next Page »