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Increased intraoperative fluid volume administration is associated with worse outcomes after gastro-esophageal resection for cancer
Vol. 221, No. 4S2, October 2015
metastatic potential of cancer cells. This study was undertaken to examine mechanisms by which mithramycin mediates antitumor effects in thoracic malignancies, and hepatotoxicity in patients with these neoplasms. METHODS: MTT, scratch, soft agar, and murine xenograft experiments were used to evaluate the effects of mithramycin on growth, migration, clonogenicity and tumorigenicity of lung and esophageal cancer and pleural mesothelioma cells (two cell lines from each histology). Flow cytometry and beta-galactosidase staining techniques were used to evaluate cell cycle kinetics, senescence, and apoptosis. Microarray techniques were used to examine gene expression profiles in cultured cancer cells and xenografts following mithramycin exposure, as well as germline pharmacogenomic profiles in patients receiving mithramycin infusions. RESULTS: Mithramycin mediated dramatic dose-dependent inhibition of cancer cell growth in-vitro and in-vivo, inducing G0/G1 arrest and senescence followed by marked apoptosis. Mithramycin induced overlapping effects on stem cell signaling and cell cycle progression. Novel translational endpoints were identified for each tumor histology. Eight of twelve patients receiving mithramycin infusions experienced asymptomatic dose-limiting hepatotoxicity that correlated with SNPs in ABCB4 and ABCB11 (p¼0.002), which encode transporter proteins mediating bile flow. CONCLUSIONS: These findings support further evaluation of mithramycin in thoracic malignancies using precision medicine techniques and pharmacokinetic simulations to optimize patient selection and recapitulate exposure conditions mediating tumor regressions in preclinical models. Impact of neoadjuvant chemotherapy on perioperative outcomes for resected gastric cancer: an analysis of the US National Cancer Data Base Erin K Greenleaf, MD, Susie X Sun, MD, Afif N Kulaylat, MD, Christopher S Hollenbeak, PhD, Joyce Wong, MD Penn State Hershey Medical Center, Hershey, PA INTRODUCTION: Standard of care for patients with advanced gastric cancer includes administration of neoadjuvant chemotherapy (NAC) prior to gastric resection. This study assesses the impact of NAC on perioperative outcomes. METHODS: Using the ACS National Cancer Database, 16,128 patients underwent gastrectomy for cancer from 2003 to 2012. Treatment groups were categorized as: NAC, adjuvant chemotherapy, and surgery only. Univariate and multivariate analyses were performed to estimate the impact of treatment on perioperative outcomes. RESULTS: Of patients undergoing definitive surgical intervention, 36.6% (n¼5,909) received NAC, 19.5% (n¼3,142) received adjuvant chemotherapy, and 43.9% (n¼7,077) underwent surgery only. Patients who received NAC were more frequently younger, male, white, privately insured, and treated at an academic center (p<0.0001, all). After controlling for demographics, comorbidities,
Scientific Poster Presentations: 2015 Clinical Congress
e129
and tumor-related factors, patients who received NAC had a postoperative length of stay 1.8 days shorter than patients who did not receive chemotherapy (5.6 vs 7.4 days, p<0.0001). They had a 62% lower odds of 30-day mortality (OR: 0.38, p<0.0001) and a 47% lower odds of 90-day mortality (OR: 0.53, p<0.0001) relative to patients who underwent surgery alone. Multiple other patient-, treatment facility- and tumor-related factors were also found to have a statistically significant association with postoperative outcomes. CONCLUSIONS: With concerns regarding the preoperative toxic effects of NAC, these findings suggest NAC does not lengthen hospital stay or heighten the risk of postoperative mortality, even after controlling for factors associated with poor prognosis. Further study is necessary, however, to evaluate the long-term impact of NAC. Increased intraoperative fluid volume administration is associated with worse outcomes after gastro-esophageal resection for cancer Antonio Masi, MD, Vincenzo Desiato, MD, Marcovalerio Melis, MD, FACS, Antonio Pinna, MD, Ioannis Hatzaras, MD, Steven M Cohen, DO, Russell S Berman, MD, FACS, Garth H Ballantyne, MD, FACS, Leon H Pachter, MD, FACS, Elliot Newman, MD New York University School of Medicine, New York, NY INTRODUCTION: Liberal intra-operative use of intravenous fluid may increase postoperative complications, but this effect has never been measured taking into account patient’s Body Surface Area (BSA). We examined the influence of intra-operative crystalloid (IOC) volume per BSA on outcomes following Esophago-Gastrectomy (EG) for adenocarcinoma. METHODS: The median fluid administration per Body Surface Area (BSA) across 169 patients who underwent EG for adenocarcinoma (1990e2009) was 2,171 mL/m2/kg. We identified two study groups: Group L received < 2,171 ml/m2/kg and Group M received > 2,171 ml/m2/kg. Differences between groups in length of stay, overall morbidity, and 30-day mortality were evaluated. RESULTS: There were 84 patients in Group L and 85 in Group M. Both groups were similar in terms of age, male proportion, performance status, ASA score, underlying comorbidities, AJCC staging, tumor grading and resection margin status. Group M patients had longer operations, increased blood losses and higher rates of intra-operative blood transfusions. There were one and two postoperative deaths respectively in Group L and M (1.2% vs 2.4%, p¼0.504). Group M patients had higher postoperative morbidity (40.5% vs 58.8%, p¼0.013), longer ICU stays (p 0.019), higher incidence of atrial fibrillation (p¼0.015), pleural effusion (p¼0.005) and deep vein thrombosis (p¼0.030). Length of postoperative stay was similar (11.0 days vs 14.2 days, p¼0.378). There was a trend toward increased overall survical in Group L (52.9 vs 39.1 months, p¼0.078).
e130
Scientific Poster Presentations: 2015 Clinical Congress
CONCLUSIONS: IOC/BSA increased with duration of surgery, intra-operative blood losses, and intra-operative blood transfusion, and correlated with increased postoperative morbidity, ICU stays and cardio-pulmonary complications. Increased size of sentinel lymph node is associated with disease-specific survival for cutaneous melanoma Brandon Chapman, MD, Alessandro Paniccia, MD, Justin Merkow, MD, Edward L Jones, MD, Teresa S Jones, MD, Maggie Hodges, MD, Nicole Kounalakis, MD, Csaba Gajdos, MD, FACS, Martin D McCarter, MD, FACS University of Colorado School of Medicine, Aurora, CO INTRODUCTION: Multiple studies have demonstrated that ulceration, Breslow thickness, patient age and lymph nodes status strongly influence prognosis in patients with cutaneous melanoma. The significance of the sentinel lymph node (SLN) size is unknown. The purpose of this study was to determine if the size of the SLN impacts disease specific survival. METHODS: Retrospective review of a prospectively maintained database of patients undergoing SLN biopsy for cutaneous melanoma between February 1995 and January 2013. The volume of the largest SLN in pathology was approximated to that of an ellipsoid and calculated using the three dimensions. A multivariate Cox’s proportional hazard model was utilized for the analysis. RESULTS: Five-hundred and ninety patients had appropriate pathology for review. The median age was 53.3 years (range 7-86 years) and median SLN volume was 0.74 cc (IQR 0.3-1.5). Nodal metastasis was identified in 107 (18.1%) cases. A positive SLN conferred the strongest risk of melanoma specific death (HR 4.3, p¼<.001). In addition to older age at diagnosis (HR 1.04, p<.001) and ulceration (HR 2.04, p¼.004), SLN volume represented an independent risk of melanoma specific death (HR 1.18, p¼0.047). Depth of primary lesion (HR 1.05, p¼0.161) and male gender (HR 1.69, p¼0.076) were not significantly associated with disease specific survival. CONCLUSIONS: Patients with larger SLN volume have a higher risk of melanoma specific death on multivariate analysis. Surgeons should consider removal of large SLN during biopsy. Is there value in intraoperative frozen section during thyroidectomy for thyroid nodules? Jonathan Allan, Tae H Ro, Subhasis Misra, MB, BS, FACS Northwest Texas Hospital, Amarillo, TX INTRODUCTION: Surgeons debate on the utility of intraoperative frozen section (IOFS) for avoiding potential completion thyroidectomies. We analyzed accuracy and extra time needed for an IOFS. METHODS: Retrospective chart review was conducted after IRB approval from 2007 to 2014 at a single community-based hospital. Thyroidectomies were performed by 4 different surgeons. Operations for simple goiters were excluded from this study. The results of pre-operative Fine Needle Aspirate (FNA), IOFS, and
J Am Coll Surg
postoperative final pathology were analyzed. Lab and surgery inout times were analyzed. RESULTS: Total number of patients with thyroid nodules were 86 and all underwent pre-operative FNA. 53 of these went to surgery. There were 6 males and 47 females, the median age was 50. 22 underwent lobectomy, 30 underwent total or subtotal thyroidectomy, and 1 underwent a further completion thyroidectomy. Average lab IOFS time was 14 minutes. IOFS agreed with final pathology in patients 1, 3, and 7. IOFS missed papillary carcinoma in patients 2 and 5. IOFS incorrectly claimed follicular neoplasm in patients 4 and 6, agreeing with FNA. In patient 5, the surgeon received the IOFS result but withheld clinical judgment until the final pathology. CONCLUSIONS: The use of IOFS had no change in patient outcome, suggesting limited benefit for the patient. In the surgeries in which IOFS was performed, an average of 14 minutes was added to the intraoperative time. Long term survival outcomes in octogenarians and nonagenarians undergoing the Whipple procedure for pancreatic adenocarcinoma: A United States populationbased study (Surveillance, Epidemiology and End Results [SEER] Database, 1998-2011) Sachin Patil, Ronald S Chamberlain, MD, MPA, FACS Saint Barnabas Medical Center, Livingston, NJ INTRODUCTION: Pancreatic cancer is the 4th most common cause of cancer deaths, with peak incidence in 8th decade. Surgical resection offers highest survival. Advanced age reduces the chances of surgery, related to co-morbidities. <7% of elderly patients (>80-years) undergo surgery. We analyzed long term survival outcomes in elderly following the Whipple procedure (WP). METHODS: We used SEER database (1998-2011). Elderly with WP for adenocarcinoma were compared against <79-years old for demographic, clinical and long term survival differences, using standard statistical methodology. RESULTS: Among 11,126 patients undergoing a WP, 9.2% were >80 years old (n¼1,021). Compared to younger patients, elderly patients have a lower M:F ratio at 1:1.2, p<0.001 and a higher Caucasians (p<0.001). No differences in the tumor grade/SEERstage at presentation between groups was noted. Elderly patients were less likely to receive radiation-therapy (17%, p<0.001). Overall mortality was much higher in those >80 years (77.8%, p¼0.004) but there was no difference in cancer specific mortality (63.8%, p¼0.52). The mean survival was lower at 31.01.6 months (p<0.001), as were the 1-year/5-year survival rates analyzed by all stages, p<0.001. Cox regression analysis among the elderly patients identified males, no-RT, high grade tumor and SEER stage II and III were as associated with increased mortality. CONCLUSIONS: Elderly patients accounts for about 10% of patients undergoing WP. There is no significant difference in the
metastatic potential of cancer cells. This study was undertaken to examine mechanisms by which mithramycin mediates antitumor effects in thoracic malignancies, and hepatotoxicity in patients with these neoplasms. METHODS: MTT, scratch, soft agar, and murine xenograft experiments were used to evaluate the effects of mithramycin on growth, migration, clonogenicity and tumorigenicity of lung and esophageal cancer and pleural mesothelioma cells (two cell lines from each histology). Flow cytometry and beta-galactosidase staining techniques were used to evaluate cell cycle kinetics, senescence, and apoptosis. Microarray techniques were used to examine gene expression profiles in cultured cancer cells and xenografts following mithramycin exposure, as well as germline pharmacogenomic profiles in patients receiving mithramycin infusions. RESULTS: Mithramycin mediated dramatic dose-dependent inhibition of cancer cell growth in-vitro and in-vivo, inducing G0/G1 arrest and senescence followed by marked apoptosis. Mithramycin induced overlapping effects on stem cell signaling and cell cycle progression. Novel translational endpoints were identified for each tumor histology. Eight of twelve patients receiving mithramycin infusions experienced asymptomatic dose-limiting hepatotoxicity that correlated with SNPs in ABCB4 and ABCB11 (p¼0.002), which encode transporter proteins mediating bile flow. CONCLUSIONS: These findings support further evaluation of mithramycin in thoracic malignancies using precision medicine techniques and pharmacokinetic simulations to optimize patient selection and recapitulate exposure conditions mediating tumor regressions in preclinical models. Impact of neoadjuvant chemotherapy on perioperative outcomes for resected gastric cancer: an analysis of the US National Cancer Data Base Erin K Greenleaf, MD, Susie X Sun, MD, Afif N Kulaylat, MD, Christopher S Hollenbeak, PhD, Joyce Wong, MD Penn State Hershey Medical Center, Hershey, PA INTRODUCTION: Standard of care for patients with advanced gastric cancer includes administration of neoadjuvant chemotherapy (NAC) prior to gastric resection. This study assesses the impact of NAC on perioperative outcomes. METHODS: Using the ACS National Cancer Database, 16,128 patients underwent gastrectomy for cancer from 2003 to 2012. Treatment groups were categorized as: NAC, adjuvant chemotherapy, and surgery only. Univariate and multivariate analyses were performed to estimate the impact of treatment on perioperative outcomes. RESULTS: Of patients undergoing definitive surgical intervention, 36.6% (n¼5,909) received NAC, 19.5% (n¼3,142) received adjuvant chemotherapy, and 43.9% (n¼7,077) underwent surgery only. Patients who received NAC were more frequently younger, male, white, privately insured, and treated at an academic center (p<0.0001, all). After controlling for demographics, comorbidities,
Scientific Poster Presentations: 2015 Clinical Congress
e129
and tumor-related factors, patients who received NAC had a postoperative length of stay 1.8 days shorter than patients who did not receive chemotherapy (5.6 vs 7.4 days, p<0.0001). They had a 62% lower odds of 30-day mortality (OR: 0.38, p<0.0001) and a 47% lower odds of 90-day mortality (OR: 0.53, p<0.0001) relative to patients who underwent surgery alone. Multiple other patient-, treatment facility- and tumor-related factors were also found to have a statistically significant association with postoperative outcomes. CONCLUSIONS: With concerns regarding the preoperative toxic effects of NAC, these findings suggest NAC does not lengthen hospital stay or heighten the risk of postoperative mortality, even after controlling for factors associated with poor prognosis. Further study is necessary, however, to evaluate the long-term impact of NAC. Increased intraoperative fluid volume administration is associated with worse outcomes after gastro-esophageal resection for cancer Antonio Masi, MD, Vincenzo Desiato, MD, Marcovalerio Melis, MD, FACS, Antonio Pinna, MD, Ioannis Hatzaras, MD, Steven M Cohen, DO, Russell S Berman, MD, FACS, Garth H Ballantyne, MD, FACS, Leon H Pachter, MD, FACS, Elliot Newman, MD New York University School of Medicine, New York, NY INTRODUCTION: Liberal intra-operative use of intravenous fluid may increase postoperative complications, but this effect has never been measured taking into account patient’s Body Surface Area (BSA). We examined the influence of intra-operative crystalloid (IOC) volume per BSA on outcomes following Esophago-Gastrectomy (EG) for adenocarcinoma. METHODS: The median fluid administration per Body Surface Area (BSA) across 169 patients who underwent EG for adenocarcinoma (1990e2009) was 2,171 mL/m2/kg. We identified two study groups: Group L received < 2,171 ml/m2/kg and Group M received > 2,171 ml/m2/kg. Differences between groups in length of stay, overall morbidity, and 30-day mortality were evaluated. RESULTS: There were 84 patients in Group L and 85 in Group M. Both groups were similar in terms of age, male proportion, performance status, ASA score, underlying comorbidities, AJCC staging, tumor grading and resection margin status. Group M patients had longer operations, increased blood losses and higher rates of intra-operative blood transfusions. There were one and two postoperative deaths respectively in Group L and M (1.2% vs 2.4%, p¼0.504). Group M patients had higher postoperative morbidity (40.5% vs 58.8%, p¼0.013), longer ICU stays (p 0.019), higher incidence of atrial fibrillation (p¼0.015), pleural effusion (p¼0.005) and deep vein thrombosis (p¼0.030). Length of postoperative stay was similar (11.0 days vs 14.2 days, p¼0.378). There was a trend toward increased overall survical in Group L (52.9 vs 39.1 months, p¼0.078).
e130
Scientific Poster Presentations: 2015 Clinical Congress
CONCLUSIONS: IOC/BSA increased with duration of surgery, intra-operative blood losses, and intra-operative blood transfusion, and correlated with increased postoperative morbidity, ICU stays and cardio-pulmonary complications. Increased size of sentinel lymph node is associated with disease-specific survival for cutaneous melanoma Brandon Chapman, MD, Alessandro Paniccia, MD, Justin Merkow, MD, Edward L Jones, MD, Teresa S Jones, MD, Maggie Hodges, MD, Nicole Kounalakis, MD, Csaba Gajdos, MD, FACS, Martin D McCarter, MD, FACS University of Colorado School of Medicine, Aurora, CO INTRODUCTION: Multiple studies have demonstrated that ulceration, Breslow thickness, patient age and lymph nodes status strongly influence prognosis in patients with cutaneous melanoma. The significance of the sentinel lymph node (SLN) size is unknown. The purpose of this study was to determine if the size of the SLN impacts disease specific survival. METHODS: Retrospective review of a prospectively maintained database of patients undergoing SLN biopsy for cutaneous melanoma between February 1995 and January 2013. The volume of the largest SLN in pathology was approximated to that of an ellipsoid and calculated using the three dimensions. A multivariate Cox’s proportional hazard model was utilized for the analysis. RESULTS: Five-hundred and ninety patients had appropriate pathology for review. The median age was 53.3 years (range 7-86 years) and median SLN volume was 0.74 cc (IQR 0.3-1.5). Nodal metastasis was identified in 107 (18.1%) cases. A positive SLN conferred the strongest risk of melanoma specific death (HR 4.3, p¼<.001). In addition to older age at diagnosis (HR 1.04, p<.001) and ulceration (HR 2.04, p¼.004), SLN volume represented an independent risk of melanoma specific death (HR 1.18, p¼0.047). Depth of primary lesion (HR 1.05, p¼0.161) and male gender (HR 1.69, p¼0.076) were not significantly associated with disease specific survival. CONCLUSIONS: Patients with larger SLN volume have a higher risk of melanoma specific death on multivariate analysis. Surgeons should consider removal of large SLN during biopsy. Is there value in intraoperative frozen section during thyroidectomy for thyroid nodules? Jonathan Allan, Tae H Ro, Subhasis Misra, MB, BS, FACS Northwest Texas Hospital, Amarillo, TX INTRODUCTION: Surgeons debate on the utility of intraoperative frozen section (IOFS) for avoiding potential completion thyroidectomies. We analyzed accuracy and extra time needed for an IOFS. METHODS: Retrospective chart review was conducted after IRB approval from 2007 to 2014 at a single community-based hospital. Thyroidectomies were performed by 4 different surgeons. Operations for simple goiters were excluded from this study. The results of pre-operative Fine Needle Aspirate (FNA), IOFS, and
J Am Coll Surg
postoperative final pathology were analyzed. Lab and surgery inout times were analyzed. RESULTS: Total number of patients with thyroid nodules were 86 and all underwent pre-operative FNA. 53 of these went to surgery. There were 6 males and 47 females, the median age was 50. 22 underwent lobectomy, 30 underwent total or subtotal thyroidectomy, and 1 underwent a further completion thyroidectomy. Average lab IOFS time was 14 minutes. IOFS agreed with final pathology in patients 1, 3, and 7. IOFS missed papillary carcinoma in patients 2 and 5. IOFS incorrectly claimed follicular neoplasm in patients 4 and 6, agreeing with FNA. In patient 5, the surgeon received the IOFS result but withheld clinical judgment until the final pathology. CONCLUSIONS: The use of IOFS had no change in patient outcome, suggesting limited benefit for the patient. In the surgeries in which IOFS was performed, an average of 14 minutes was added to the intraoperative time. Long term survival outcomes in octogenarians and nonagenarians undergoing the Whipple procedure for pancreatic adenocarcinoma: A United States populationbased study (Surveillance, Epidemiology and End Results [SEER] Database, 1998-2011) Sachin Patil, Ronald S Chamberlain, MD, MPA, FACS Saint Barnabas Medical Center, Livingston, NJ INTRODUCTION: Pancreatic cancer is the 4th most common cause of cancer deaths, with peak incidence in 8th decade. Surgical resection offers highest survival. Advanced age reduces the chances of surgery, related to co-morbidities. <7% of elderly patients (>80-years) undergo surgery. We analyzed long term survival outcomes in elderly following the Whipple procedure (WP). METHODS: We used SEER database (1998-2011). Elderly with WP for adenocarcinoma were compared against <79-years old for demographic, clinical and long term survival differences, using standard statistical methodology. RESULTS: Among 11,126 patients undergoing a WP, 9.2% were >80 years old (n¼1,021). Compared to younger patients, elderly patients have a lower M:F ratio at 1:1.2, p<0.001 and a higher Caucasians (p<0.001). No differences in the tumor grade/SEERstage at presentation between groups was noted. Elderly patients were less likely to receive radiation-therapy (17%, p<0.001). Overall mortality was much higher in those >80 years (77.8%, p¼0.004) but there was no difference in cancer specific mortality (63.8%, p¼0.52). The mean survival was lower at 31.01.6 months (p<0.001), as were the 1-year/5-year survival rates analyzed by all stages, p<0.001. Cox regression analysis among the elderly patients identified males, no-RT, high grade tumor and SEER stage II and III were as associated with increased mortality. CONCLUSIONS: Elderly patients accounts for about 10% of patients undergoing WP. There is no significant difference in the