Background. The national comprehensive cancer network defines adequate lymphadenectomy as evaluat... more Background. The national comprehensive cancer network defines adequate lymphadenectomy as evaluation of C 15 lymph nodes in esophageal cancer. However, varying thresholds have been suggested following neoadjuvant therapy. Objectives. Our objectives were to (1) explore trends in adequate lymphadenectomy rates over time; (2) evaluate unadjusted lymphadenectomy yield by treatment characteristics; and (3) identify independent factors associated with adequate lymphadenectomy. Methods. The National Cancer Data Base was used to identify patients who underwent esophagectomy for cancer from 2004 to 2015. Adequate lymphadenectomy trends over time were evaluated using the Cochrane-Armitage test, and lymph node yield by treatment approach was compared using the Mann-Whitney U and Kruskal-Wallis tests. Associations with treatment factors were assessed by multivariable logistic regression. Results. Among 24,413 patients, 9919 (40.6%) had adequate lymphadenectomy. Meeting the nodal threshold increased over time (52.6% in 2015 vs. 26.0% in 2004; p \ 0.01). Lymph node yield did not differ based on neoadjuvant therapy (median 12 [interquartile range 7-19] with and without neoadjuvant therapy; p = 0.44). Adequate lymphadenectomy was not associated with neoadjuvant therapy (40.5% vs. 40.8%, odds ratio [OR] 0.94, 95% confidence interval [CI] 0.82-1.07), but was associated with surgical approach (52.7% of laparoscopic cases, OR 1.28, 95% CI 1.06-1.56; 61.2% of robotic cases, OR 1.71, 95% CI 1.34-2.19, vs. 43.5% of open cases), and increasing annual esophagectomy volume (55.6% in the fourth quartile vs. 32.6% in the first quartile; OR 3.57, 95% CI 2.35-5.43). Conclusions. Despite increases over time, only 50% of patients undergo adequate lymphadenectomy during esophageal cancer resection. Adequate lymphadenectomy was not associated with neoadjuvant therapy. Focusing on surgical approach and esophagectomy volume may further improve adequate lymphadenectomy rates. Esophageal cancer is a common and lethal condition, with 5-year population-based survival rates of \ 20%. 1 Multimodal treatment is recommended based on tumor stage, and may include chemotherapy, radiation, and/or surgical resection. 2 Among patients who undergo surgical resection, adequate lymphadenectomy is essential for accurate staging, which is an important predictor of survival. 3,4 Additionally, several studies have shown that adequate lymphadenectomy is associated with improved survival in esophageal cancer, likely due to improved operative staging. 5-8 Despite the importance of adequate lymphadenectomy, there is not widespread agreement on how adequate lymphadenectomy is defined in esophageal cancer. The National Comprehensive Cancer Network (NCCN)
HPB : the official journal of the International Hepato Pancreato Biliary Association, Jan 27, 2017
Few studies have examined the relation between extent of vascular resection and morbidity followi... more Few studies have examined the relation between extent of vascular resection and morbidity following pancreaticoduodenectomy (PD) with vein resection (PDVR). Patients undergoing PD for malignancy were identified using the American College of Surgeons National Surgical Quality Improvement Project from 2006 to 2013. Current procedural terminology codes were used to characterize PDVR. 9235 patients underwent PD, 977 (10.6%) had PDVR - 640 with direct and 224 with graft repair. PDVR had longer operative times (456 ± 136 vs 374 ± 128 min, p < 0.05) and higher intraoperative transfusions (1.8 ± 3.4 vs 4.3 ± 4.9 units, p < 0.05) than PD alone. On adjusted multivariable regression, PDVR with either direct or graft repairs was associated with higher rates of overall morbidity (OR [odds ratio] 1.50 for direct, 1.74 for graft, p < 0.05), bleeding (OR 2.18 for direct, 3.26 for graft, p < 0.05), and DVT (OR 2.12 for direct, 2.62 for graft, p < 0.05) compared to PD alone. Graft repa...
Objective: To present a case and literature review of gastric MANEC tumor locally invading into t... more Objective: To present a case and literature review of gastric MANEC tumor locally invading into the duodenum and pancreas treated with pancreaticoduodenectomy. Methods: In this report we present a case of a 68 year old male who presents with a locally advanced gastric MANEC tumor with invasion into the duodenum and pancreas treated with pancreaticoduodenectomy. Results: The patient successfully underwent pancreaticoduodenectomy without complications and was discharged post-operative day 11. Pathology was consistent with gastric cancer with mixed adeno and neuroendocrine components. Conclusion: We describe a case of pathologically identified MANEC tumor of the stomach with local duodenal, pancreatic, and peripancreatic lymph node invasion treated with pancreaticoduodenectomy, which to our knowledge has not been described in the literature. Considerations can be made to evaluate MANEC pathology to further delineate the prognosis for patients undergoing R0 resection, due to the rare nature of this disease.
Background While minimally invasive surgery (MIS) to treat liver tumors has increased, data on pe... more Background While minimally invasive surgery (MIS) to treat liver tumors has increased, data on perioperative outcomes of MIS relative to open liver resection (O-LR) are lacking. We sought to compare short-term outcomes among patients undergoing MIS vs. O-LR in a nationally representative database. Methods The National Surgical Quality Improvement Program database was used to identify patients undergoing hepatectomy between January 1 and December 31, 2014. Propensity score matching algorithm was used to balance differences in baseline characteristics among MIS and O-LR groups. Results A total of 3064 patients were included in the study. After propensity matching, the baseline characteristics for O-LR and MIS groups were comparable (minimum p value=0.12). Incidence of superficial surgical site infections, intraoperative or postoperative blood transfusions, and pulmonary embolism was lower among patients in MIS group compared to O-LR (p<0.02). Liver failure and biliary leakage were also less frequent among patients undergoing MIS (p<0.01). Similarly, MIS was associated with a shorter length of hospital stay (LOS) compared to O-LR (p<0.001). Of note, 30-day postoperative mortality and readmission were comparable between the two groups. Conclusions Patients undergoing MIS had a lower postoperative morbidity and shorter LOS compared with patients undergoing O-LR. MIS is safe and may be associated with improved short-term outcomes following hepatic surgery.
Background: National registries have not adequately captured concurrent partial hepatic resection... more Background: National registries have not adequately captured concurrent partial hepatic resections or ablations. Therefore, the aim of this analysis was to describe the patterns of concurrent partial resections and ablations in North America. Methods: Patients undergoing a hepatic resection were identified using the American College of Surgeons-National Surgical Quality Improvement Program Targeted Hepatectomy database. Perioperative outcomes were compared for patients undergoing concurrent "wedge" resections and/or ablations and other subsets. Results: A total of 2714 patients were identified who met inclusion criteria. Major hepatectomy was performed in 1037 patients (38.2%) while partial lobectomy was performed in 1677 (61.8%) patients. Concurrent "wedge" hepatic resections and ablations were undertaken in 56.0% and 14.2% of patients, respectively, and were more frequently performed among patients undergoing a partial lobectomy and among patients undergoing surgery for colorectal liver metastasis (both p < 0.001). While associated with a decreased incidence of postoperative complications (p = 0.027) and liver failure (p = 0.031) among patients undergoing a major hepatectomy, concurrent therapies were associated with comparable 30day outcomes for patients undergoing partial lobectomy. Conclusion: Concurrent "wedge" hepatic resections and ablations are performed in 56.0% and 14.2%, respectively of patients undergoing hepatectomy. Concurrent procedures were not associated with worse clinical outcomes.
Conclusion: By improving implementation of current guidelines recurrence rates following ABP coul... more Conclusion: By improving implementation of current guidelines recurrence rates following ABP could be reduced. Additionally it comes with a cost of V 7313 per patient, added to an already restrained budget in the health care system.
HPB : the official journal of the International Hepato Pancreato Biliary Association, May 1, 2016
Several groups have defined pancreatic surgery quality metrics that identify centers delivering q... more Several groups have defined pancreatic surgery quality metrics that identify centers delivering quality care. Although these metrics are perceived to be associated with good outcomes, their relationship with actual outcomes has not been established. A national cadre of pancreatic surgeons was surveyed regarding perceived quality metrics, which were evaluated against the Central Pancreas Consortium (CPC) database to determine actual performance and relationships with long-term outcomes. The most important metrics were perceived to be participation in clinical trials, appropriate clinical staging, perioperative mortality, and documentation of receipt of adjuvant therapy. Subsequent analysis of 1399 patients in the CPC dataset demonstrated that a R0 retroperitoneal and neck margin was obtained in 79% (n = 1109) and 91.4% (n = 1278) of cases, respectively. 74% of patients (n = 1041) had >10 lymph nodes harvested, and LN positivity was 65% (n = 903). 76% (n = 960) of eligible patients...
The Journal of bone and joint surgery. American volume, Jan 3, 2014
Symptomatic pre-discharge venous thromboembolism (VTE) rates after total or partial hip or knee a... more Symptomatic pre-discharge venous thromboembolism (VTE) rates after total or partial hip or knee arthroplasty have been proposed as patient safety indicators. However, assessing only pre-discharge VTE rates may be suboptimal for quality measurement as the duration of stay is relatively short and the VTE risk extends beyond the inpatient setting. Patients who underwent total or partial hip or knee arthroplasty were identified in the 2008 through 2010 American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) database. Outcomes of interest were the deep venous thrombosis (DVT), pulmonary embolism (PE), and overall VTE rates within thirty days after surgery and the rates during the pre-discharge and post-discharge portions of this time period. Risk-adjusted hospital rankings based on only pre-discharge (inpatient) events were compared with those based on both pre-discharge and post-discharge events within thirty days of surgery. A total of 23,924 patients u...
The objective was to assess the presence and extent of venous thromboembolic (VTE) surveillance b... more The objective was to assess the presence and extent of venous thromboembolic (VTE) surveillance bias using high-quality clinical data. Hospital VTE rates are publicly reported and used in pay-for-performance programs. Prior work suggested surveillance bias: hospitals that look more for VTE with imaging studies find more VTE, thereby incorrectly seem to have worse performance. However, these results have been questioned as the risk adjustment and VTE measurement relied on administrative data. Data (2009-2010) from 208 hospitals were available for analysis. Hospitals were divided into quartiles according to VTE imaging use rates (Medicare claims). Observed and risk-adjusted postoperative VTE event rates (regression models using American College of Surgeons National Surgical Quality Improvement Project data) were examined across VTE imaging use rate quartiles. Multivariable linear regression models were developed to assess the impact of hospital characteristics (American Hospital Assoc...
To compare perioperative outcomes of laparoscopic left-sided pancreatectomy (LLP) with traditiona... more To compare perioperative outcomes of laparoscopic left-sided pancreatectomy (LLP) with traditional open left-sided pancreatectomy (OLP) in a multicenter experience. LLP is being performed more commonly with limited data comparing results with outcomes from OLP. Data from 8 centers were combined for all cases performed between 2002-2006. OLP and LLP cohorts were matched by age, American Society of Anesthesiologists, resected pancreas length, tumor size, and diagnosis. Multivariate analysis was performed using binary logistic regression. Six hundred sixty-seven LPs were performed, with 159 (24%) attempted laparoscopically. Indications were solid lesion in 307 (46%), cystic in 295 (44%), and pancreatitis in 65 (10%) cases. Positive margins occurred in 51 (8%) cases, 335 (50%) had complications, and significant leaks occurred in 108 (16%). Conversion to OLP occurred in 20 (13%) of the LLPs. In the matched comparison, 200 OLPs were compared with 142 LLPs. There were no differences in pos...
Pancreatic adenocarcinoma (PDAC) is one of the most lethal human malignancies, with median surviv... more Pancreatic adenocarcinoma (PDAC) is one of the most lethal human malignancies, with median survival of less than one year and overall five-year survival of less than 5%. There is increasing evidence demonstrating that epithelial-mesenchymal transition (EMT) contributes to pancreatic cancer metastasis and to treatment resistance. In this review, we will examine the data demonstrating the role and regulation of EMT in pancreatic cancer progression, focusing particularly on the transcription factors and microRNAs involved in EMT. We will examine how EMT is involved in the generation and maintenance of stem cells, and the role of EMT in modulating resistance of PDAC cells to drug therapies. We will also identify putative EMT-targeting agents that may help to reduce the morbidity and mortality associated with pancreatic cancer.
Pancreatic ductal adenocarcinoma (PDAC) is associated with a pronounced collagen-rich fibrosis kn... more Pancreatic ductal adenocarcinoma (PDAC) is associated with a pronounced collagen-rich fibrosis known as desmoplastic reaction; however the role of fibrosis in PDAC is poorly understood. In this report we show that collagen can regulate the tumor suppressive let-7 family of microRNAs in pancreatic cancer cells. PDAC cells growing in 3D collagen gels repress mature let-7 without affecting the precursor form of let-7 in part via increased expression of membrane type 1-matrix metalloproteinase (MT1-MMP, MMP-14) and ERK1/2 activation. PDAC cells in collagen also demonstrate increased TGF-β1 signaling, and blocking TGF-β1 signaling attenuated collageninduced MT1-MMP expression, ERK1/2 activation, and repression of let-7 levels. Although MT1-MMP overexpression was not sufficient to inhibit let-7 on 2D tissue culture plastic, overexpression of MT1-MMP in PDAC cells embedded in 3D collagen gels or grown in vivo repressed let-7 levels. Importantly, MT1-MMP expression significantly correlated with decreased levels of let-7 in human PDAC tumor specimens. Overall, our study emphasizes the interplay between the key proteinase MT1-MMP and its substrate type I collagen in modulating microRNA expression, and identifies an additional mechanism by which fibrosis may contribute to PDAC progression.
BACKGROUND: As compared with open distal pancreatectomy (ODP), laparoscopic distal pancreatectomy... more BACKGROUND: As compared with open distal pancreatectomy (ODP), laparoscopic distal pancreatectomy (LDP) affords improved perioperative outcomes. The role of LDP for patients with pancreatic ductal adenocarcinoma (PDAC) is not defined. STUDY DESIGN: Records from patients undergoing distal pancreatectomy (DP) for PDAC from 2000 to 2008 from 9 academic medical centers were reviewed. Short-term (node harvest and margin status) and longterm (survival) cancer outcomes were assessed. A 3:1 matched analysis was performed for ODP and LDP cases using age, American Society of Anesthesiologists (ASA) class, and tumor size. RESULTS: Disclosure Information: Nothing to disclose. The Georgia Cancer Coalition provided financial support for the preparation of this article.
Pancreatic adenocarcinoma remains among the most lethal of human malignancies. Overall 5year surv... more Pancreatic adenocarcinoma remains among the most lethal of human malignancies. Overall 5year survival is less than 5%, and only 20% of patients presenting with localized disease amenable to surgical resection. Even in patients who undergo resection, long-term survival remains extremely poor. A major contributor to the aggressiveness of multiple cancers and pancreatic cancer in particular is the process of epithelial-to-mesenchymal transition (EMT). This review highlights the growing evidence of EMT in pancreatic cancer progression, focusing on the contribution of EMT to the development of cancer stem cells and on interaction of EMT with other pathways central to cancer progression such as Hedgehog signaling, the K-ras oncogene, and transforming growth factor-β (TGF-β). We will also discuss EMT-targeting agents currently in development and in clinical trials that may help to reduce the morbidity and mortality associated with pancreatic cancer.
IMPORTANCE Postoperative venous thromboembolism (VTE) rates are widely reported quality metrics s... more IMPORTANCE Postoperative venous thromboembolism (VTE) rates are widely reported quality metrics soon to be used in pay-for-performance programs. Surveillance bias occurs when some clinicians use imaging studies to detect VTE more frequently than other clinicians. Because they look more, they find more VTE events, paradoxically worsening their hospital's VTE quality measure performance. A surveillance bias may influence VTE measurement if (1) greater hospital VTE prophylaxis adherence fails to result in lower measured VTE rates, (2) hospitals with characteristics suggestive of higher quality (eg, more accreditations) have greater VTE prophylaxis adherence rates but worse VTE event rates, and (3) higher hospital VTE imaging utilization use rates are associated with higher measured VTE event rates. OBJECTIVE To examine whether a surveillance bias influences the validity of reported VTE rates.
Purpose: To assess the clinical and pathologic significance of mast cell infiltration in human pa... more Purpose: To assess the clinical and pathologic significance of mast cell infiltration in human pancreatic cancer and evaluate crosstalk between mast cells and cancer cells in vitro. Experimental Design: Immunohistochemistry for tryptase was done on 53 pancreatic cancer specimens. Mast cell counts were correlated with clinical variables and survival. Serum tryptase activity from patients with cancer was compared with patients with benign pancreatic disease. In vitro, the effect of pancreatic cancer–conditioned medium on mast cell migration was assessed. The effect of conditioned medium from the human mast cell line, LAD-2, on cancer and normal ductal cell proliferation was assessed by thymidine incorporation. Matrigel invasion assays were used to evaluate the effect of mast cell–conditioned medium on cancer cell invasion in the presence and absence of a matrix metalloproteinase inhibitor, GM6001. Results: Mast cell infiltration was significantly increased in pancreatic cancer compare...
Introduction-Although invasive intraductal papillary mucinous neoplasms (IPMN) of the pancreas is... more Introduction-Although invasive intraductal papillary mucinous neoplasms (IPMN) of the pancreas is thought to be more indolent than sporadic pancreatic adenocarcinoma (PAC), the natural history remains poorly defined. We compare survival and identify prognostic factors following resection for invasive IPMN vs. stage-matched PAC. Methods-The Surveillance, Epidemiology, and End Results (SEER) database (1991-2005) was utilized to identify 729 patients with invasive IPMN and 8082 patients with PAC who underwent surgical resection. Results-Patients with resected invasive IPMN experienced improved overall survival when compared to resected PAC (median survival 21mos vs. 14mos, p<0.001). Stratification by nodal status demonstrated no difference in survival among node positive patients, however, median survival of resected, node negative, invasive IPMN was significantly improved compared to node negative PAC (34mos vs. 18mos, p <0.001). On multivariate analysis PAC histology was an adverse predictor of overall survival (HR 1.31, 95% CI 1.15-1.50) compared to invasive IPMN. For patients with invasive IPMN, positive lymph nodes (HR 1.98, 95% CI 1.50-2.60), high tumor grade (HR 1.74, 95% CI 1.31-2.31), tumor size >2cm (HR 1.50, 95% CI 1.04-2.19), and age >66 years (HR 1.33, 95% CI 1.03-1.73) were adverse predictors of survival. Conclusions-Although node negative invasive IPMN shows improved survival following resection compared to node negative PAC, the natural history of node positive invasive IPMN mimics that of node positive PAC. We also identify adverse predictors of survival in invasive IPMN to guide discussions regarding use of adjuvant therapies and prognosis following resection of invasive IPMN.
Background. The national comprehensive cancer network defines adequate lymphadenectomy as evaluat... more Background. The national comprehensive cancer network defines adequate lymphadenectomy as evaluation of C 15 lymph nodes in esophageal cancer. However, varying thresholds have been suggested following neoadjuvant therapy. Objectives. Our objectives were to (1) explore trends in adequate lymphadenectomy rates over time; (2) evaluate unadjusted lymphadenectomy yield by treatment characteristics; and (3) identify independent factors associated with adequate lymphadenectomy. Methods. The National Cancer Data Base was used to identify patients who underwent esophagectomy for cancer from 2004 to 2015. Adequate lymphadenectomy trends over time were evaluated using the Cochrane-Armitage test, and lymph node yield by treatment approach was compared using the Mann-Whitney U and Kruskal-Wallis tests. Associations with treatment factors were assessed by multivariable logistic regression. Results. Among 24,413 patients, 9919 (40.6%) had adequate lymphadenectomy. Meeting the nodal threshold increased over time (52.6% in 2015 vs. 26.0% in 2004; p \ 0.01). Lymph node yield did not differ based on neoadjuvant therapy (median 12 [interquartile range 7-19] with and without neoadjuvant therapy; p = 0.44). Adequate lymphadenectomy was not associated with neoadjuvant therapy (40.5% vs. 40.8%, odds ratio [OR] 0.94, 95% confidence interval [CI] 0.82-1.07), but was associated with surgical approach (52.7% of laparoscopic cases, OR 1.28, 95% CI 1.06-1.56; 61.2% of robotic cases, OR 1.71, 95% CI 1.34-2.19, vs. 43.5% of open cases), and increasing annual esophagectomy volume (55.6% in the fourth quartile vs. 32.6% in the first quartile; OR 3.57, 95% CI 2.35-5.43). Conclusions. Despite increases over time, only 50% of patients undergo adequate lymphadenectomy during esophageal cancer resection. Adequate lymphadenectomy was not associated with neoadjuvant therapy. Focusing on surgical approach and esophagectomy volume may further improve adequate lymphadenectomy rates. Esophageal cancer is a common and lethal condition, with 5-year population-based survival rates of \ 20%. 1 Multimodal treatment is recommended based on tumor stage, and may include chemotherapy, radiation, and/or surgical resection. 2 Among patients who undergo surgical resection, adequate lymphadenectomy is essential for accurate staging, which is an important predictor of survival. 3,4 Additionally, several studies have shown that adequate lymphadenectomy is associated with improved survival in esophageal cancer, likely due to improved operative staging. 5-8 Despite the importance of adequate lymphadenectomy, there is not widespread agreement on how adequate lymphadenectomy is defined in esophageal cancer. The National Comprehensive Cancer Network (NCCN)
HPB : the official journal of the International Hepato Pancreato Biliary Association, Jan 27, 2017
Few studies have examined the relation between extent of vascular resection and morbidity followi... more Few studies have examined the relation between extent of vascular resection and morbidity following pancreaticoduodenectomy (PD) with vein resection (PDVR). Patients undergoing PD for malignancy were identified using the American College of Surgeons National Surgical Quality Improvement Project from 2006 to 2013. Current procedural terminology codes were used to characterize PDVR. 9235 patients underwent PD, 977 (10.6%) had PDVR - 640 with direct and 224 with graft repair. PDVR had longer operative times (456 ± 136 vs 374 ± 128 min, p < 0.05) and higher intraoperative transfusions (1.8 ± 3.4 vs 4.3 ± 4.9 units, p < 0.05) than PD alone. On adjusted multivariable regression, PDVR with either direct or graft repairs was associated with higher rates of overall morbidity (OR [odds ratio] 1.50 for direct, 1.74 for graft, p < 0.05), bleeding (OR 2.18 for direct, 3.26 for graft, p < 0.05), and DVT (OR 2.12 for direct, 2.62 for graft, p < 0.05) compared to PD alone. Graft repa...
Objective: To present a case and literature review of gastric MANEC tumor locally invading into t... more Objective: To present a case and literature review of gastric MANEC tumor locally invading into the duodenum and pancreas treated with pancreaticoduodenectomy. Methods: In this report we present a case of a 68 year old male who presents with a locally advanced gastric MANEC tumor with invasion into the duodenum and pancreas treated with pancreaticoduodenectomy. Results: The patient successfully underwent pancreaticoduodenectomy without complications and was discharged post-operative day 11. Pathology was consistent with gastric cancer with mixed adeno and neuroendocrine components. Conclusion: We describe a case of pathologically identified MANEC tumor of the stomach with local duodenal, pancreatic, and peripancreatic lymph node invasion treated with pancreaticoduodenectomy, which to our knowledge has not been described in the literature. Considerations can be made to evaluate MANEC pathology to further delineate the prognosis for patients undergoing R0 resection, due to the rare nature of this disease.
Background While minimally invasive surgery (MIS) to treat liver tumors has increased, data on pe... more Background While minimally invasive surgery (MIS) to treat liver tumors has increased, data on perioperative outcomes of MIS relative to open liver resection (O-LR) are lacking. We sought to compare short-term outcomes among patients undergoing MIS vs. O-LR in a nationally representative database. Methods The National Surgical Quality Improvement Program database was used to identify patients undergoing hepatectomy between January 1 and December 31, 2014. Propensity score matching algorithm was used to balance differences in baseline characteristics among MIS and O-LR groups. Results A total of 3064 patients were included in the study. After propensity matching, the baseline characteristics for O-LR and MIS groups were comparable (minimum p value=0.12). Incidence of superficial surgical site infections, intraoperative or postoperative blood transfusions, and pulmonary embolism was lower among patients in MIS group compared to O-LR (p<0.02). Liver failure and biliary leakage were also less frequent among patients undergoing MIS (p<0.01). Similarly, MIS was associated with a shorter length of hospital stay (LOS) compared to O-LR (p<0.001). Of note, 30-day postoperative mortality and readmission were comparable between the two groups. Conclusions Patients undergoing MIS had a lower postoperative morbidity and shorter LOS compared with patients undergoing O-LR. MIS is safe and may be associated with improved short-term outcomes following hepatic surgery.
Background: National registries have not adequately captured concurrent partial hepatic resection... more Background: National registries have not adequately captured concurrent partial hepatic resections or ablations. Therefore, the aim of this analysis was to describe the patterns of concurrent partial resections and ablations in North America. Methods: Patients undergoing a hepatic resection were identified using the American College of Surgeons-National Surgical Quality Improvement Program Targeted Hepatectomy database. Perioperative outcomes were compared for patients undergoing concurrent "wedge" resections and/or ablations and other subsets. Results: A total of 2714 patients were identified who met inclusion criteria. Major hepatectomy was performed in 1037 patients (38.2%) while partial lobectomy was performed in 1677 (61.8%) patients. Concurrent "wedge" hepatic resections and ablations were undertaken in 56.0% and 14.2% of patients, respectively, and were more frequently performed among patients undergoing a partial lobectomy and among patients undergoing surgery for colorectal liver metastasis (both p < 0.001). While associated with a decreased incidence of postoperative complications (p = 0.027) and liver failure (p = 0.031) among patients undergoing a major hepatectomy, concurrent therapies were associated with comparable 30day outcomes for patients undergoing partial lobectomy. Conclusion: Concurrent "wedge" hepatic resections and ablations are performed in 56.0% and 14.2%, respectively of patients undergoing hepatectomy. Concurrent procedures were not associated with worse clinical outcomes.
Conclusion: By improving implementation of current guidelines recurrence rates following ABP coul... more Conclusion: By improving implementation of current guidelines recurrence rates following ABP could be reduced. Additionally it comes with a cost of V 7313 per patient, added to an already restrained budget in the health care system.
HPB : the official journal of the International Hepato Pancreato Biliary Association, May 1, 2016
Several groups have defined pancreatic surgery quality metrics that identify centers delivering q... more Several groups have defined pancreatic surgery quality metrics that identify centers delivering quality care. Although these metrics are perceived to be associated with good outcomes, their relationship with actual outcomes has not been established. A national cadre of pancreatic surgeons was surveyed regarding perceived quality metrics, which were evaluated against the Central Pancreas Consortium (CPC) database to determine actual performance and relationships with long-term outcomes. The most important metrics were perceived to be participation in clinical trials, appropriate clinical staging, perioperative mortality, and documentation of receipt of adjuvant therapy. Subsequent analysis of 1399 patients in the CPC dataset demonstrated that a R0 retroperitoneal and neck margin was obtained in 79% (n = 1109) and 91.4% (n = 1278) of cases, respectively. 74% of patients (n = 1041) had >10 lymph nodes harvested, and LN positivity was 65% (n = 903). 76% (n = 960) of eligible patients...
The Journal of bone and joint surgery. American volume, Jan 3, 2014
Symptomatic pre-discharge venous thromboembolism (VTE) rates after total or partial hip or knee a... more Symptomatic pre-discharge venous thromboembolism (VTE) rates after total or partial hip or knee arthroplasty have been proposed as patient safety indicators. However, assessing only pre-discharge VTE rates may be suboptimal for quality measurement as the duration of stay is relatively short and the VTE risk extends beyond the inpatient setting. Patients who underwent total or partial hip or knee arthroplasty were identified in the 2008 through 2010 American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) database. Outcomes of interest were the deep venous thrombosis (DVT), pulmonary embolism (PE), and overall VTE rates within thirty days after surgery and the rates during the pre-discharge and post-discharge portions of this time period. Risk-adjusted hospital rankings based on only pre-discharge (inpatient) events were compared with those based on both pre-discharge and post-discharge events within thirty days of surgery. A total of 23,924 patients u...
The objective was to assess the presence and extent of venous thromboembolic (VTE) surveillance b... more The objective was to assess the presence and extent of venous thromboembolic (VTE) surveillance bias using high-quality clinical data. Hospital VTE rates are publicly reported and used in pay-for-performance programs. Prior work suggested surveillance bias: hospitals that look more for VTE with imaging studies find more VTE, thereby incorrectly seem to have worse performance. However, these results have been questioned as the risk adjustment and VTE measurement relied on administrative data. Data (2009-2010) from 208 hospitals were available for analysis. Hospitals were divided into quartiles according to VTE imaging use rates (Medicare claims). Observed and risk-adjusted postoperative VTE event rates (regression models using American College of Surgeons National Surgical Quality Improvement Project data) were examined across VTE imaging use rate quartiles. Multivariable linear regression models were developed to assess the impact of hospital characteristics (American Hospital Assoc...
To compare perioperative outcomes of laparoscopic left-sided pancreatectomy (LLP) with traditiona... more To compare perioperative outcomes of laparoscopic left-sided pancreatectomy (LLP) with traditional open left-sided pancreatectomy (OLP) in a multicenter experience. LLP is being performed more commonly with limited data comparing results with outcomes from OLP. Data from 8 centers were combined for all cases performed between 2002-2006. OLP and LLP cohorts were matched by age, American Society of Anesthesiologists, resected pancreas length, tumor size, and diagnosis. Multivariate analysis was performed using binary logistic regression. Six hundred sixty-seven LPs were performed, with 159 (24%) attempted laparoscopically. Indications were solid lesion in 307 (46%), cystic in 295 (44%), and pancreatitis in 65 (10%) cases. Positive margins occurred in 51 (8%) cases, 335 (50%) had complications, and significant leaks occurred in 108 (16%). Conversion to OLP occurred in 20 (13%) of the LLPs. In the matched comparison, 200 OLPs were compared with 142 LLPs. There were no differences in pos...
Pancreatic adenocarcinoma (PDAC) is one of the most lethal human malignancies, with median surviv... more Pancreatic adenocarcinoma (PDAC) is one of the most lethal human malignancies, with median survival of less than one year and overall five-year survival of less than 5%. There is increasing evidence demonstrating that epithelial-mesenchymal transition (EMT) contributes to pancreatic cancer metastasis and to treatment resistance. In this review, we will examine the data demonstrating the role and regulation of EMT in pancreatic cancer progression, focusing particularly on the transcription factors and microRNAs involved in EMT. We will examine how EMT is involved in the generation and maintenance of stem cells, and the role of EMT in modulating resistance of PDAC cells to drug therapies. We will also identify putative EMT-targeting agents that may help to reduce the morbidity and mortality associated with pancreatic cancer.
Pancreatic ductal adenocarcinoma (PDAC) is associated with a pronounced collagen-rich fibrosis kn... more Pancreatic ductal adenocarcinoma (PDAC) is associated with a pronounced collagen-rich fibrosis known as desmoplastic reaction; however the role of fibrosis in PDAC is poorly understood. In this report we show that collagen can regulate the tumor suppressive let-7 family of microRNAs in pancreatic cancer cells. PDAC cells growing in 3D collagen gels repress mature let-7 without affecting the precursor form of let-7 in part via increased expression of membrane type 1-matrix metalloproteinase (MT1-MMP, MMP-14) and ERK1/2 activation. PDAC cells in collagen also demonstrate increased TGF-β1 signaling, and blocking TGF-β1 signaling attenuated collageninduced MT1-MMP expression, ERK1/2 activation, and repression of let-7 levels. Although MT1-MMP overexpression was not sufficient to inhibit let-7 on 2D tissue culture plastic, overexpression of MT1-MMP in PDAC cells embedded in 3D collagen gels or grown in vivo repressed let-7 levels. Importantly, MT1-MMP expression significantly correlated with decreased levels of let-7 in human PDAC tumor specimens. Overall, our study emphasizes the interplay between the key proteinase MT1-MMP and its substrate type I collagen in modulating microRNA expression, and identifies an additional mechanism by which fibrosis may contribute to PDAC progression.
BACKGROUND: As compared with open distal pancreatectomy (ODP), laparoscopic distal pancreatectomy... more BACKGROUND: As compared with open distal pancreatectomy (ODP), laparoscopic distal pancreatectomy (LDP) affords improved perioperative outcomes. The role of LDP for patients with pancreatic ductal adenocarcinoma (PDAC) is not defined. STUDY DESIGN: Records from patients undergoing distal pancreatectomy (DP) for PDAC from 2000 to 2008 from 9 academic medical centers were reviewed. Short-term (node harvest and margin status) and longterm (survival) cancer outcomes were assessed. A 3:1 matched analysis was performed for ODP and LDP cases using age, American Society of Anesthesiologists (ASA) class, and tumor size. RESULTS: Disclosure Information: Nothing to disclose. The Georgia Cancer Coalition provided financial support for the preparation of this article.
Pancreatic adenocarcinoma remains among the most lethal of human malignancies. Overall 5year surv... more Pancreatic adenocarcinoma remains among the most lethal of human malignancies. Overall 5year survival is less than 5%, and only 20% of patients presenting with localized disease amenable to surgical resection. Even in patients who undergo resection, long-term survival remains extremely poor. A major contributor to the aggressiveness of multiple cancers and pancreatic cancer in particular is the process of epithelial-to-mesenchymal transition (EMT). This review highlights the growing evidence of EMT in pancreatic cancer progression, focusing on the contribution of EMT to the development of cancer stem cells and on interaction of EMT with other pathways central to cancer progression such as Hedgehog signaling, the K-ras oncogene, and transforming growth factor-β (TGF-β). We will also discuss EMT-targeting agents currently in development and in clinical trials that may help to reduce the morbidity and mortality associated with pancreatic cancer.
IMPORTANCE Postoperative venous thromboembolism (VTE) rates are widely reported quality metrics s... more IMPORTANCE Postoperative venous thromboembolism (VTE) rates are widely reported quality metrics soon to be used in pay-for-performance programs. Surveillance bias occurs when some clinicians use imaging studies to detect VTE more frequently than other clinicians. Because they look more, they find more VTE events, paradoxically worsening their hospital's VTE quality measure performance. A surveillance bias may influence VTE measurement if (1) greater hospital VTE prophylaxis adherence fails to result in lower measured VTE rates, (2) hospitals with characteristics suggestive of higher quality (eg, more accreditations) have greater VTE prophylaxis adherence rates but worse VTE event rates, and (3) higher hospital VTE imaging utilization use rates are associated with higher measured VTE event rates. OBJECTIVE To examine whether a surveillance bias influences the validity of reported VTE rates.
Purpose: To assess the clinical and pathologic significance of mast cell infiltration in human pa... more Purpose: To assess the clinical and pathologic significance of mast cell infiltration in human pancreatic cancer and evaluate crosstalk between mast cells and cancer cells in vitro. Experimental Design: Immunohistochemistry for tryptase was done on 53 pancreatic cancer specimens. Mast cell counts were correlated with clinical variables and survival. Serum tryptase activity from patients with cancer was compared with patients with benign pancreatic disease. In vitro, the effect of pancreatic cancer–conditioned medium on mast cell migration was assessed. The effect of conditioned medium from the human mast cell line, LAD-2, on cancer and normal ductal cell proliferation was assessed by thymidine incorporation. Matrigel invasion assays were used to evaluate the effect of mast cell–conditioned medium on cancer cell invasion in the presence and absence of a matrix metalloproteinase inhibitor, GM6001. Results: Mast cell infiltration was significantly increased in pancreatic cancer compare...
Introduction-Although invasive intraductal papillary mucinous neoplasms (IPMN) of the pancreas is... more Introduction-Although invasive intraductal papillary mucinous neoplasms (IPMN) of the pancreas is thought to be more indolent than sporadic pancreatic adenocarcinoma (PAC), the natural history remains poorly defined. We compare survival and identify prognostic factors following resection for invasive IPMN vs. stage-matched PAC. Methods-The Surveillance, Epidemiology, and End Results (SEER) database (1991-2005) was utilized to identify 729 patients with invasive IPMN and 8082 patients with PAC who underwent surgical resection. Results-Patients with resected invasive IPMN experienced improved overall survival when compared to resected PAC (median survival 21mos vs. 14mos, p<0.001). Stratification by nodal status demonstrated no difference in survival among node positive patients, however, median survival of resected, node negative, invasive IPMN was significantly improved compared to node negative PAC (34mos vs. 18mos, p <0.001). On multivariate analysis PAC histology was an adverse predictor of overall survival (HR 1.31, 95% CI 1.15-1.50) compared to invasive IPMN. For patients with invasive IPMN, positive lymph nodes (HR 1.98, 95% CI 1.50-2.60), high tumor grade (HR 1.74, 95% CI 1.31-2.31), tumor size >2cm (HR 1.50, 95% CI 1.04-2.19), and age >66 years (HR 1.33, 95% CI 1.03-1.73) were adverse predictors of survival. Conclusions-Although node negative invasive IPMN shows improved survival following resection compared to node negative PAC, the natural history of node positive invasive IPMN mimics that of node positive PAC. We also identify adverse predictors of survival in invasive IPMN to guide discussions regarding use of adjuvant therapies and prognosis following resection of invasive IPMN.
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Papers by David Bentrem