- Email: [email protected]
Yttrium-90-Labeled Anti-Glypican-3 Antibody Reduces Tumor Growth in an Orthotopic Xenograft Model of Hepatocellular Carcinoma
1025
at a high-volume Institutions, revealing reliable predictors of outcome. Both the AJCC and ENETS staging systems are valid prognostic tools in terms of risk of recurrence.
SURGERY FOR INTRAHEPATIC CHOLANGIOCARCINOMA WITH MULTIPLES NODULES: COMPARISON OF SINGLE TUMOR, SINGLE TUMOR WITH SATELLITES AND MULTIFOCAL TUMORS Simone Conci, Andrea Ruzzenente, Francesca Bertuzzo, Tommaso Campagnaro, Fabio Bagante, Andrea Dore, Calogero Iacono, Alfredo Guglielmi
1027 YTTRIUM-90-LABELED ANTI-GLYPICAN-3 ANTIBODY REDUCES TUMOR GROWTH IN AN ORTHOTOPIC XENOGRAFT MODEL OF HEPATOCELLULAR CARCINOMA Andrew D. Ludwig, Yongwoo D. Seo, Donald K. Hamlin, Holly M. Nguyen, Matthew M. Yeh, Raymond S. Yeung, D S. Wilbur, James O. Park
SSAT Abstracts
Background: The role of surgery in patients with intrahepatic cholangiocarcinoma (ICC) in presence of multiple nodules is still controversial. Although the presence of multiple nodules is included in the T2 stage according to the AJCC staging system, some authors considered it a contraindication for surgery. Aims: The aims of the study were to compare the clinicopathological features and long-term results of patients with ICC undergoing surgery according to the presence of multiple nodules. Methods: A retrospective analysis of clinicopathological features of 122 patients with ICC underwent surgery from 1990 to 2015 was carried out. Patients were further classified according to the pattern of presentation in single tumor (type I), single tumor with satellites (multiple nodules within the same liver segment of the main tumor, type II), or multifocal tumors (multiple nodules in another liver segments, type III). We performed a disease specific (DSS) and disease free survival (DFS) analysis on patients underwent surgery with curative intent. Results: Sixty-six (54.1%) patients presented with type I pattern, 38 (31.1%) with type II and 18 (14.8%) with type III. Curative intent surgery was performed in 90.2% of the patients. Patients with type III pattern showed a higher Ca 19-9 serum level (p=0.001), and poorly differentiation (p= 0.048), and a higher rate of palliative/explorative surgery (p<0.001) compare with type I and type II patients. The 5-year DSS and DFS of the patients undergoing curative surgery were 29.9% and 19.0%, respectively. Patterns of presentation resulted a factor significantly related with both DSS and DFS (p<0.001 and p<0.001, respectively). The 5-year DSS of patients with type I, II and III patients were 40.2%, 19.4% and 0.0%, respectively (figure 1). Pattern of presentation, tumor size >50mm, and lymph-node metastasis were independent factors associated with DSS, p=0.001, p=0.047 and p<0.001, respectively. Patients with type I and type II patterns without lymph-node metastases reached a 5-year DSS of 47.5% and 23.5%, respectively. Conclusion: ICC had three distinct presentation patterns with different prognosis and it should be considered in the therapeutic strategy. Surgery in patients with multifocal ICC should be reserved only for selected cases and after a multidisciplinary discussion.
Background: Hepatocellular carcinoma (HCC) is the second most lethal malignancy and is increasing in incidence in the United States. Unfortunately there are few systemic treatment options, particularly for disseminated disease. Glypican-3 (GPC3) is a proteoglycan cell surface receptor overexpressed in most HCCs and provides a unique target for molecular therapies. We have previously demonstrated that PET imaging using a Zirconium-89-conjugated monoclonal anti-GPC3 antibody can bind to minute tumors and allow imaging with high sensitivity and specificity in an orthotopic xenograft mouse model of HCC and that serum alpha-fetoprotein (AFP) levels are highly correlated with tumor size in this model. In the present study, we conjugated Yttrium-90, a high-energy beta-particle-emitting radionuclide, to our α-GPC3 antibody to develop a novel antibody-directed radiotherapeutic approach for HCC. Methods: Luciferase-expressing HepG2 human hepatoblastoma cells were injected into the left lobe of the liver in athymic nude mice. At 6 weeks after implantation, tumor establishment was verified by imaging and serum AFP levels from tumor-bearing animals were drawn. Our α-GPC3 antibody was labeled with 90Y using the ligand 1,4,7,10tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) and injected via tail vein into the experimental mice at a dose of 200 µCi/mouse (n=9) or 300 µCi/mouse (n=9). Control mice received DOTA-conjugated antibody without radionuclide (n=7). Serum AFP levels were drawn at 14 and 30 days after treatment. The animals were then sacrificed and the livers were removed en bloc and weighed. Immunohistochemistry was performed on the tumors to confirm antibody delivery and evaluate the effect of radiation treatment. Results: Before treatment there was no statistical difference between serum AFP levels or tumor size among any of the three groups. Mean serum AFP levels in control animals increased by 663% over 30 days, while animals treated with 200 µCi 90Y experienced a 28% increase and animals treated with 300 µCi had a 42% reduction in mean serum AFP (p=0.03 and 0.02, respectively), [Fig. 1]. Mean liver weight in control animals reached 2.36g compared to 1.33g in animals that received 200 µCi 90Y and 1.28g in animals that received 300 µCi (p=0.05 and 0.04, respectively), [Fig. 2]. These results were achieved without significant toxicity as measured by body condition scoring and body weight. Conclusions: The results of this pilot experiment demonstrate that GPC3, a cell-surface proteoglycan overexpressed in most HCC, can be used as a target for radioimmunotherapy in an orthotopic mouse model of HCC. These data suggest that this novel targeted approach could be used in the clinical setting, particularly for disseminated HCC.
1026 A SINGLE INSTITUTION'S 27-YEAR SURGICAL EXPERIENCE WITH PANCREATIC NEUROENDOCRINE TUMORS: TIME TRENDS, COMPARISON OF CURRENT STAGING SYSTEMS AND OUTCOME ANALYSIS Giovanni Marchegiani, Tommaso Pollini, Salvatore Paiella, Marco Miotto, Anna Malpaga, Harmony Impellizzeri, Isacco Damoli, Beatrice Bianchi, Tommaso Baroni, Caterina Costanza Zingaretti, Chiara Nessi, Lorenzo Crepaz, Roberto Salvia, Luca Landoni INTRODUCTION and AIM: Because of their rarity and heterogeneity, Pancreatic Neuroendocrine Tumors (Pan-Net) still represent a clinical dilemma. In particular, there is scarcity of data regarding their long term follow-up after surgical resection. Aim of the present analysis is to evaluate an almost three decade long activity at a high-volume pancreatic Institution. We sought to evaluate the time trends in surgical indications, to compare the current staging systems, and to find reliable predictors of postoperative outcome. METHODS: The Institutional PanNET database was queried identifying 587 resected cases from 1988 to 2015. To evaluate the time trends of clinical management, the time span was arbitrarily divided in three clusters allowing for a balanced comparison between groups of patients. Current staging systems (AJCC and ENETS) were evaluated for recurrence prognostication validity as measured by discrimination (Harrel's c-index, HCI). Univariate and multivariate analysis for predictors of both recurrence and survival were performed, together with a conditional survival analysis. RESULTS: Of the 587 resected PanNETs, 75% were nonfunctioning, and 5% syndrome-associated. Mean age was 54 (± 14), and 51% of patients were female. The median tumor size was 20 mm (range 4-140), 62% were G1, 32% G2, and 4% were G3. Time trends analysis revealed that the number of resected PanNETs has constantly increased, while size (from 25 mm to 20 mm) and G1 proportion (from 65% to 49%) of resected tumors decreased during the study period. Comparison of current staging system revealed both AJCC and ENETS to be valid a comparable in terms of recurrence prognostication. After a mean follow-up of 75 moths, recurrence analysis revealed that nonfunctioning tumors, grading, N1 status and vascular invasion were all independent predictors of recurrence. Regardless of tumor size, G1 non-functioning tumors with no lymph node involvement and vascular invasion had a negligible risk of recurrence at 5 years. CONCLUSIONS: PanNETs have been increasingly diagnosed ad resected during the last three decades
SSAT Abstracts
S-1236
Characteristics among Patients with and without Pancreatic Fistula (N = 1452)
1028 PANCREATIC DUCT SIZE AND GLAND TEXTURE DO NOT AFFECT PANCREATIC LEAK RATE AFTER DISTAL PANCREATECTOMY Allison N. Martin, Sowmya Narayanan, Florence E. Turrentine, Todd W. Bauer, Reid B. Adams, George J. Stukenborg, Victor M. Zaydfudim INTRODUCTION: Development of a pancreatic leak and fistula remains a morbid complication after pancreatectomy. Small pancreatic duct size and soft gland texture have been associated with pancreatic fistula after pancreaticoduodenectomy. Since the mechanism of leak and fistula formation are different between pancreatic head resection and distal pancreatectomy, we hypothesized that pancreatic duct size and gland texture are not associated with pancreatic fistula after distal pancreatectomy. METHODS: All patients ≥18 years in the 2014 ACS-NSQIP targeted pancreatectomy dataset were linked to the 2014 ACSNSQIP PUF dataset. Clinical variables included indication for resection (benign vs. malignant), operative approach (open vs. minimally invasive), pancreatic duct size (<3 mm, 3-6 mm, vs. >6 mm) and gland texture (hard, intermediate, vs. soft). Two separate analyses were performed to evaluate associations between pancreatic duct size and gland texture after 1) distal pancreatectomy, and 2) pancreaticoduodenectomy. Additional univariable and multivariable comparisons assessed associations between clinical factors and development of pancreatic fistula after distal pancreatectomy. RESULTS: Among 1452 patients who underwent distal pancreatectomy in 2014, 258 (17.8%) patients developed a postoperative pancreatic fistula in comparison to 534 of 2934 patients (18.2%) who developed a fistula after pancreaticoduodenectomy. Patients who developed a pancreatic fistula after distal pancreatectomy were more commonly male, had higher BMI, had longer operative time, and were more likely to receive perioperative blood transfusion (all p< 0.012) compared to patients who did not develop a fistula. Both pancreatic duct size and gland texture were significantly associated with pancreatic fistula after pancreaticoduodenectomy (both p<0.001). However, there was no association between pancreatic fistula and duct size or gland texture (both p≥0.282) after distal pancreatectomy (Table 1). Operative approach (open 17.5% leak rate vs. minimally invasive 18.5% leak rate) was not associated with pancreatic leak (p=0.612) after distal pancreatectomy. Patients with pancreatic fistula after distal pancreatectomy had increased length of stay, higher rates of readmission and reoperation compared to patients who did not have a pancreatic fistula (all p<0.005). There was no association between pancreatic fistula and mortality (p=0.464). After adjustment for demographic covariates, only operative time was significantly associated with pancreatic fistula formation (p= 0.032) after distal pancreatectomy. CONCLUSION: Unlike among patients who had pancreaticoduodenectomy, pancreatic duct size and gland texture were not associated with development of pancreatic fistula following distal pancreatectomy. Other clinical factors should be considered in this patient population.
IQR: interquartile range; BMI: body mass index; POD: postoperative day
A LONGITUDINAL ASSESSMENT OF ANTHROPOMETRIC CHANGES IN PATIENTS WITH PANCREATIC DUCTAL ADENOCARCINOMA UNDERGOING PREOPERATIVE THERAPY AND PANCREATODUODENECTOMY Jordan M. Cloyd, Laura R. Prakash, Graciela M. Nogueras-González, Maria Petzel, Nathan Parker, An Ngo-Huang, Keri Schadler, David Fogelman, Jason Denbo, Naveen Garg, Michael P. Kim, Jeffrey E. Lee, Ching-Wei Tzeng, Jason B. Fleming, Matthew Katz Introduction: The anthropometric and nutritional changes associated with preoperative therapy and pancreatoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC) have not previously been evaluated. We sought to quantify and to determine the clinical significance of changes that occur over the course of therapy and the first postoperative year. Methods: 127 consecutive patients with PDAC who received preoperative chemotherapy and/or chemoradiation followed by pancreatoduodenectomy (PD) at a single institution between 2009-2012 were longitudinally evaluated. Evolving changes in patients' nutritional profiles and body composition were measured by comparing laboratory parameters and cross-sectional areas of their skeletal muscle (SKM), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) on computed tomography images obtained upon presentation, prior to PD, and approximately 3 and 12 months after surgery. Body mass index (BMI) was calculated using baseline height and weights at each corresponding interval. Results: Prior to therapy, patients' mean baseline BMI was 26.5±4.7 Kg/m2 and 63.0% met established criteria for sarcopenia. Preoperative therapy (12 [9.4%] chemotherapy alone, 44 [34.6%] chemoradiation alone, 71 [55.9%] both) was administered for a mean of 5.4±2.3 months. Only minor changes in VAT and SAT occurred during preoperative therapy, and there was no significant change in SKM or BMI. In contrast, a significant and progressive decline in BMI and a depletion of both muscle and fat were observed following surgery and throughout the first postoperative year (Table). Median overall survival of all patients was 32.8 months. Anthropometric changes during preoperative therapy were not independently associated with survival, but SKM gain between the postoperative period and one year follow-up was associated with improved overall survival (OR 0.50, 95% CI 0.29-0.87). Conclusion: In contrast to the minor changes that occur during preoperative therapy for PDAC, significant losses in key anthropometric and nutritional parameters tend to occur over the first year following PD. Ongoing SKM loss in the postoperative period may represent an early marker for worse outcomes. Therefore, heightened attention to physiologic metrics both prior to and following completion of therapy is warranted.
S-1237
SSAT Abstracts
SSAT Abstracts
1029
at a high-volume Institutions, revealing reliable predictors of outcome. Both the AJCC and ENETS staging systems are valid prognostic tools in terms of risk of recurrence.
SURGERY FOR INTRAHEPATIC CHOLANGIOCARCINOMA WITH MULTIPLES NODULES: COMPARISON OF SINGLE TUMOR, SINGLE TUMOR WITH SATELLITES AND MULTIFOCAL TUMORS Simone Conci, Andrea Ruzzenente, Francesca Bertuzzo, Tommaso Campagnaro, Fabio Bagante, Andrea Dore, Calogero Iacono, Alfredo Guglielmi
1027 YTTRIUM-90-LABELED ANTI-GLYPICAN-3 ANTIBODY REDUCES TUMOR GROWTH IN AN ORTHOTOPIC XENOGRAFT MODEL OF HEPATOCELLULAR CARCINOMA Andrew D. Ludwig, Yongwoo D. Seo, Donald K. Hamlin, Holly M. Nguyen, Matthew M. Yeh, Raymond S. Yeung, D S. Wilbur, James O. Park
SSAT Abstracts
Background: The role of surgery in patients with intrahepatic cholangiocarcinoma (ICC) in presence of multiple nodules is still controversial. Although the presence of multiple nodules is included in the T2 stage according to the AJCC staging system, some authors considered it a contraindication for surgery. Aims: The aims of the study were to compare the clinicopathological features and long-term results of patients with ICC undergoing surgery according to the presence of multiple nodules. Methods: A retrospective analysis of clinicopathological features of 122 patients with ICC underwent surgery from 1990 to 2015 was carried out. Patients were further classified according to the pattern of presentation in single tumor (type I), single tumor with satellites (multiple nodules within the same liver segment of the main tumor, type II), or multifocal tumors (multiple nodules in another liver segments, type III). We performed a disease specific (DSS) and disease free survival (DFS) analysis on patients underwent surgery with curative intent. Results: Sixty-six (54.1%) patients presented with type I pattern, 38 (31.1%) with type II and 18 (14.8%) with type III. Curative intent surgery was performed in 90.2% of the patients. Patients with type III pattern showed a higher Ca 19-9 serum level (p=0.001), and poorly differentiation (p= 0.048), and a higher rate of palliative/explorative surgery (p<0.001) compare with type I and type II patients. The 5-year DSS and DFS of the patients undergoing curative surgery were 29.9% and 19.0%, respectively. Patterns of presentation resulted a factor significantly related with both DSS and DFS (p<0.001 and p<0.001, respectively). The 5-year DSS of patients with type I, II and III patients were 40.2%, 19.4% and 0.0%, respectively (figure 1). Pattern of presentation, tumor size >50mm, and lymph-node metastasis were independent factors associated with DSS, p=0.001, p=0.047 and p<0.001, respectively. Patients with type I and type II patterns without lymph-node metastases reached a 5-year DSS of 47.5% and 23.5%, respectively. Conclusion: ICC had three distinct presentation patterns with different prognosis and it should be considered in the therapeutic strategy. Surgery in patients with multifocal ICC should be reserved only for selected cases and after a multidisciplinary discussion.
Background: Hepatocellular carcinoma (HCC) is the second most lethal malignancy and is increasing in incidence in the United States. Unfortunately there are few systemic treatment options, particularly for disseminated disease. Glypican-3 (GPC3) is a proteoglycan cell surface receptor overexpressed in most HCCs and provides a unique target for molecular therapies. We have previously demonstrated that PET imaging using a Zirconium-89-conjugated monoclonal anti-GPC3 antibody can bind to minute tumors and allow imaging with high sensitivity and specificity in an orthotopic xenograft mouse model of HCC and that serum alpha-fetoprotein (AFP) levels are highly correlated with tumor size in this model. In the present study, we conjugated Yttrium-90, a high-energy beta-particle-emitting radionuclide, to our α-GPC3 antibody to develop a novel antibody-directed radiotherapeutic approach for HCC. Methods: Luciferase-expressing HepG2 human hepatoblastoma cells were injected into the left lobe of the liver in athymic nude mice. At 6 weeks after implantation, tumor establishment was verified by imaging and serum AFP levels from tumor-bearing animals were drawn. Our α-GPC3 antibody was labeled with 90Y using the ligand 1,4,7,10tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) and injected via tail vein into the experimental mice at a dose of 200 µCi/mouse (n=9) or 300 µCi/mouse (n=9). Control mice received DOTA-conjugated antibody without radionuclide (n=7). Serum AFP levels were drawn at 14 and 30 days after treatment. The animals were then sacrificed and the livers were removed en bloc and weighed. Immunohistochemistry was performed on the tumors to confirm antibody delivery and evaluate the effect of radiation treatment. Results: Before treatment there was no statistical difference between serum AFP levels or tumor size among any of the three groups. Mean serum AFP levels in control animals increased by 663% over 30 days, while animals treated with 200 µCi 90Y experienced a 28% increase and animals treated with 300 µCi had a 42% reduction in mean serum AFP (p=0.03 and 0.02, respectively), [Fig. 1]. Mean liver weight in control animals reached 2.36g compared to 1.33g in animals that received 200 µCi 90Y and 1.28g in animals that received 300 µCi (p=0.05 and 0.04, respectively), [Fig. 2]. These results were achieved without significant toxicity as measured by body condition scoring and body weight. Conclusions: The results of this pilot experiment demonstrate that GPC3, a cell-surface proteoglycan overexpressed in most HCC, can be used as a target for radioimmunotherapy in an orthotopic mouse model of HCC. These data suggest that this novel targeted approach could be used in the clinical setting, particularly for disseminated HCC.
1026 A SINGLE INSTITUTION'S 27-YEAR SURGICAL EXPERIENCE WITH PANCREATIC NEUROENDOCRINE TUMORS: TIME TRENDS, COMPARISON OF CURRENT STAGING SYSTEMS AND OUTCOME ANALYSIS Giovanni Marchegiani, Tommaso Pollini, Salvatore Paiella, Marco Miotto, Anna Malpaga, Harmony Impellizzeri, Isacco Damoli, Beatrice Bianchi, Tommaso Baroni, Caterina Costanza Zingaretti, Chiara Nessi, Lorenzo Crepaz, Roberto Salvia, Luca Landoni INTRODUCTION and AIM: Because of their rarity and heterogeneity, Pancreatic Neuroendocrine Tumors (Pan-Net) still represent a clinical dilemma. In particular, there is scarcity of data regarding their long term follow-up after surgical resection. Aim of the present analysis is to evaluate an almost three decade long activity at a high-volume pancreatic Institution. We sought to evaluate the time trends in surgical indications, to compare the current staging systems, and to find reliable predictors of postoperative outcome. METHODS: The Institutional PanNET database was queried identifying 587 resected cases from 1988 to 2015. To evaluate the time trends of clinical management, the time span was arbitrarily divided in three clusters allowing for a balanced comparison between groups of patients. Current staging systems (AJCC and ENETS) were evaluated for recurrence prognostication validity as measured by discrimination (Harrel's c-index, HCI). Univariate and multivariate analysis for predictors of both recurrence and survival were performed, together with a conditional survival analysis. RESULTS: Of the 587 resected PanNETs, 75% were nonfunctioning, and 5% syndrome-associated. Mean age was 54 (± 14), and 51% of patients were female. The median tumor size was 20 mm (range 4-140), 62% were G1, 32% G2, and 4% were G3. Time trends analysis revealed that the number of resected PanNETs has constantly increased, while size (from 25 mm to 20 mm) and G1 proportion (from 65% to 49%) of resected tumors decreased during the study period. Comparison of current staging system revealed both AJCC and ENETS to be valid a comparable in terms of recurrence prognostication. After a mean follow-up of 75 moths, recurrence analysis revealed that nonfunctioning tumors, grading, N1 status and vascular invasion were all independent predictors of recurrence. Regardless of tumor size, G1 non-functioning tumors with no lymph node involvement and vascular invasion had a negligible risk of recurrence at 5 years. CONCLUSIONS: PanNETs have been increasingly diagnosed ad resected during the last three decades
SSAT Abstracts
S-1236
Characteristics among Patients with and without Pancreatic Fistula (N = 1452)
1028 PANCREATIC DUCT SIZE AND GLAND TEXTURE DO NOT AFFECT PANCREATIC LEAK RATE AFTER DISTAL PANCREATECTOMY Allison N. Martin, Sowmya Narayanan, Florence E. Turrentine, Todd W. Bauer, Reid B. Adams, George J. Stukenborg, Victor M. Zaydfudim INTRODUCTION: Development of a pancreatic leak and fistula remains a morbid complication after pancreatectomy. Small pancreatic duct size and soft gland texture have been associated with pancreatic fistula after pancreaticoduodenectomy. Since the mechanism of leak and fistula formation are different between pancreatic head resection and distal pancreatectomy, we hypothesized that pancreatic duct size and gland texture are not associated with pancreatic fistula after distal pancreatectomy. METHODS: All patients ≥18 years in the 2014 ACS-NSQIP targeted pancreatectomy dataset were linked to the 2014 ACSNSQIP PUF dataset. Clinical variables included indication for resection (benign vs. malignant), operative approach (open vs. minimally invasive), pancreatic duct size (<3 mm, 3-6 mm, vs. >6 mm) and gland texture (hard, intermediate, vs. soft). Two separate analyses were performed to evaluate associations between pancreatic duct size and gland texture after 1) distal pancreatectomy, and 2) pancreaticoduodenectomy. Additional univariable and multivariable comparisons assessed associations between clinical factors and development of pancreatic fistula after distal pancreatectomy. RESULTS: Among 1452 patients who underwent distal pancreatectomy in 2014, 258 (17.8%) patients developed a postoperative pancreatic fistula in comparison to 534 of 2934 patients (18.2%) who developed a fistula after pancreaticoduodenectomy. Patients who developed a pancreatic fistula after distal pancreatectomy were more commonly male, had higher BMI, had longer operative time, and were more likely to receive perioperative blood transfusion (all p< 0.012) compared to patients who did not develop a fistula. Both pancreatic duct size and gland texture were significantly associated with pancreatic fistula after pancreaticoduodenectomy (both p<0.001). However, there was no association between pancreatic fistula and duct size or gland texture (both p≥0.282) after distal pancreatectomy (Table 1). Operative approach (open 17.5% leak rate vs. minimally invasive 18.5% leak rate) was not associated with pancreatic leak (p=0.612) after distal pancreatectomy. Patients with pancreatic fistula after distal pancreatectomy had increased length of stay, higher rates of readmission and reoperation compared to patients who did not have a pancreatic fistula (all p<0.005). There was no association between pancreatic fistula and mortality (p=0.464). After adjustment for demographic covariates, only operative time was significantly associated with pancreatic fistula formation (p= 0.032) after distal pancreatectomy. CONCLUSION: Unlike among patients who had pancreaticoduodenectomy, pancreatic duct size and gland texture were not associated with development of pancreatic fistula following distal pancreatectomy. Other clinical factors should be considered in this patient population.
IQR: interquartile range; BMI: body mass index; POD: postoperative day
A LONGITUDINAL ASSESSMENT OF ANTHROPOMETRIC CHANGES IN PATIENTS WITH PANCREATIC DUCTAL ADENOCARCINOMA UNDERGOING PREOPERATIVE THERAPY AND PANCREATODUODENECTOMY Jordan M. Cloyd, Laura R. Prakash, Graciela M. Nogueras-González, Maria Petzel, Nathan Parker, An Ngo-Huang, Keri Schadler, David Fogelman, Jason Denbo, Naveen Garg, Michael P. Kim, Jeffrey E. Lee, Ching-Wei Tzeng, Jason B. Fleming, Matthew Katz Introduction: The anthropometric and nutritional changes associated with preoperative therapy and pancreatoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC) have not previously been evaluated. We sought to quantify and to determine the clinical significance of changes that occur over the course of therapy and the first postoperative year. Methods: 127 consecutive patients with PDAC who received preoperative chemotherapy and/or chemoradiation followed by pancreatoduodenectomy (PD) at a single institution between 2009-2012 were longitudinally evaluated. Evolving changes in patients' nutritional profiles and body composition were measured by comparing laboratory parameters and cross-sectional areas of their skeletal muscle (SKM), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) on computed tomography images obtained upon presentation, prior to PD, and approximately 3 and 12 months after surgery. Body mass index (BMI) was calculated using baseline height and weights at each corresponding interval. Results: Prior to therapy, patients' mean baseline BMI was 26.5±4.7 Kg/m2 and 63.0% met established criteria for sarcopenia. Preoperative therapy (12 [9.4%] chemotherapy alone, 44 [34.6%] chemoradiation alone, 71 [55.9%] both) was administered for a mean of 5.4±2.3 months. Only minor changes in VAT and SAT occurred during preoperative therapy, and there was no significant change in SKM or BMI. In contrast, a significant and progressive decline in BMI and a depletion of both muscle and fat were observed following surgery and throughout the first postoperative year (Table). Median overall survival of all patients was 32.8 months. Anthropometric changes during preoperative therapy were not independently associated with survival, but SKM gain between the postoperative period and one year follow-up was associated with improved overall survival (OR 0.50, 95% CI 0.29-0.87). Conclusion: In contrast to the minor changes that occur during preoperative therapy for PDAC, significant losses in key anthropometric and nutritional parameters tend to occur over the first year following PD. Ongoing SKM loss in the postoperative period may represent an early marker for worse outcomes. Therefore, heightened attention to physiologic metrics both prior to and following completion of therapy is warranted.
S-1237
SSAT Abstracts
SSAT Abstracts
1029