Clinical Focus

  • Cancer > GI Oncology
  • Liver Neoplasms
  • Pancreas Neoplasms
  • Gastric Neoplasms
  • Bile Duct Neoplasms
  • Gallbladder Neoplasms
  • Sarcoma
  • Adrenal Neoplasms
  • General Surgery

Academic Appointments

Administrative Appointments

  • Instructor in Surgery, Johns Hopkins University School of Medicine (2008 - 2009)

Honors & Awards

  • John Austin Collins, MD Memorial Award for Outstanding Teaching and Dedication to Resident Training, Department of Surgery, Stanford University (2013)
  • Cancer Innovation Fund Award, Stanford Hospital and Clinics (2012)
  • Ludwig J. Pyrtek, MD Prize for Clinical and Scientific Capabilities, Department of Surgery, Hartford Hospital, University of Connecticut School of Medicine (2007)
  • Henry Mannix, Jr, MD Award for Clinical and Academic Excellence, Saint Francis Hospital & Medical Center, University of Connecticut School of Medicine (2007)
  • Andrew Canzonetti, MD Award, Outstanding 4th Year Surgery Resident, Department of Surgery, University of Connecticut School of Medicine (2006)
  • Charles Polivy, MD Memorial Award, Department of Surgery, Hartford Hospital, University of Connecticut School of Medicine (2005)

Professional Education

  • Fellowship:Memorial Sloan-Kettering Cancer Center (2008) NY
  • Residency:University of Connecticut-School of Medicine (2007) CT
  • Internship:University of Connecticut-School of Medicine (2003) CT
  • MS, Stanford University, Epidemiology (2011)
  • Fellowship:Johns Hopkins School of Medicine (2009) MD
  • Board Certification: General Surgery, American Board of Surgery (2008)
  • Medical Education:University of Athens Medical School (2000) Greece

Research & Scholarship

Current Research and Scholarly Interests

Clinical trials of experimental diagnostics and therapeutics; outcomes analysis following combined modality treatment of hepatic, pancreatic, and gastrointestinal malignancies.

Clinical Trials

  • Prognostic Value of Baseline Computed Tomography (CT) Perfusion Parameters of Pancreatic Cancer for Patients Undergoing Stereotactic Body Radiotherapy or Surgical Resection Not Recruiting

    The purpose of this study is first, to determine whether baseline perfusion characteristics of pancreatic cancer, as characterized by CT perfusion studies, can predict tumor response to treatment by stereotactic body radiotherapy (SBRT). The second goal of this study is to determine whether baseline perfusion characteristics in those patients with resectable pancreatic cancer correlate with immunohistologic markers of angiogenesis such as microvessel density and vascular endothelial growth factor (VEGF) expression.

    Stanford is currently not accepting patients for this trial. For more information, please contact Lindee Burton, (650) 725 - 4712.

    View full details


2014-15 Courses

Graduate and Fellowship Programs


All Publications

  • Hepato-pancreatectomy: how morbid? Results from the national surgical quality improvement project HPB Tran, T. B., Dua, M. M., Spain, D. A., Visser, B. C., Norton, J. A., Poultsides, G. A. 2015; 17 (9): 763-769

    View details for DOI 10.1111/hpb.12426

    View details for Web of Science ID 000359853800004

  • Effect of Perioperative Transfusion on Recurrence and Survival after Gastric Cancer Resection: A 7-Institution Analysis of 765 Patients from the US Gastric Cancer Collaborative JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS Squires, M. H., Kooby, D. A., Poultsides, G. A., Weber, S. M., Bloomston, M., Fields, R. C., Pawlik, T. M., Votanopoulos, K. I., Schmidt, C. R., Ejaz, A., Acher, A. W., Worhunsky, D. J., Saunders, N., Levine, E. A., Jin, L. X., Cho, C. S., Winslow, E. R., Russell, M. C., Staley, C. A., Maithel, S. K. 2015; 221 (3): 767-777
  • Pancreatectomy with vein reconstruction: technique matters HPB Dua, M. M., Tran, T. B., Klausner, J., Hwa, K. J., Poultsides, G. A., Norton, J. A., Visser, B. C. 2015; 17 (9): 824-831

    View details for DOI 10.1111/hpb.12463

    View details for Web of Science ID 000359853800013

  • Impact of Complications on Long-Term Survival After Resection of Intrahepatic Cholangiocarcinoma CANCER Spolverato, G., Yakoob, M. Y., Kim, Y., Alexandrescu, S., Marques, H. P., Lamelas, J., Aldrighetti, L., Gamblin, T. C., Maithel, S. K., Pulitano, C., Bauer, T. W., Shen, F., Poultsides, G. A., Marsh, J. W., Pawlik, T. M. 2015; 121 (16): 2730-2739


    The impact of postoperative complications on the long-term outcomes of patients undergoing surgery for cancer is unclear. The objective of the current study was to define the incidence of complications among patients undergoing surgery for intrahepatic cholangiocarcinoma (ICC) and identify the association between morbidity and long-term outcomes.A total of 583 patients undergoing surgery with curative intent for ICC between 1990 and 2013 at 1 of 12 participating institutions were identified. The association between the occurrence and severity of postoperative complications on long-term survival was analyzed.The median age of the patients was 59.9 years and the majority of patients were male (52.3%). A total of 91 patients (15.6%) and 153 patients (26.2%) developed a major and minor postoperative complication, respectively; 18 patients (3.5%) died within 90 days of surgery. Median, 1-year, 3-year, and 5-year recurrence-free survival were 10.0 months, 43.3%, 16.7%, and 11.1%, respectively. Postoperative complications (hazard ratio [HR], 1.37, 95% confidence interval [95% CI], 1.08-1.73 [P = .01]) and severity of complications (major vs none: HR, 1.55; 95% CI, 1.14-2.11 [P = .01]; minor vs none: HR, 1.30; 95% CI, 0.99-1.70 [P = .06]) independently predicted shorter recurrence-free survival. Median, 1-year, 3-year, and 5-year overall survival was 27.8 months, 76.8%, 39.0%, and 23.4%, respectively. Postoperative complications (HR, 1.64; 95% CI, 1.30-2.08 [P<.001]) and severity of complications (major vs none: HR, 1.79; 95% CI, 1.31-2.44 [P<.001]; minor vs none: HR, 1.50; 95% CI, 1.15-1.95 [P<.01]) independently predicted shorter overall survival.Postoperative complications were found to be independent predictors of worse long-term outcomes. The prevention and management of postoperative complications is crucial to increase both short-term and long-term survival. Cancer 2015;121:2730-2739. © 2015 American Cancer Society.

    View details for DOI 10.1002/cncr.29419

    View details for Web of Science ID 000359190400013

    View details for PubMedID 25903409

  • Prognostic relevance of lymph node ratio and total lymph node count for small bowel adenocarcinoma SURGERY Tran, T. B., Qadan, M., Dua, M. M., Norton, J. A., Poultsides, G. A., Visser, B. C. 2015; 158 (2): 486-493


    Nodal metastasis is a known prognostic factor for small bowel adenocarcinoma. The goals of this study were to evaluate the number of lymph nodes (LNs) that should be retrieved and the impact of lymph node ratio (LNR) on survival.Surveillance, Epidemiology, and End Results was queried to identify patients with small bowel adenocarcinoma who underwent resection from 1988 to 2010. Survival was calculated with the Kaplan-Meier method. Multivariate analysis identified predictors of survival.A total of 2,772 patients underwent resection with at least one node retrieved, and this sample included equal numbers of duodenal (n = 1,387) and jejunoileal (n = 1,386) adenocarcinomas. There were 1,371 patients with no nodal metastasis (N0, 49.4%), 928 N1 (33.5%), and 474 N2 (17.1%). The median numbers of LNs examined for duodenal and jejunoileal cancers were 9 and 8, respectively. Cut-point analysis demonstrated that harvesting at least 9 for jejunoileal and 5 LN for duodenal cancers resulted in the greatest survival difference. Increasing LNR at both sites was associated with decreased overall median survival (LNR = 0, 71 months; LNR 0-0.02, 35 months; LNR 0.21-0.4, 25 months; and LNR >0.4, 16 months; P < .001). Multivariate analysis confirmed number of LNs examined, T-stage, LN positivity, and LNR were independent predictors of survival.LNR has a profound impact on survival in patients with small bowel adenocarcinoma. To achieve adequate staging, we recommend retrieving a minimum of 5 LN for duodenal and 9 LN for jejunoileal adenocarcinomas.

    View details for DOI 10.1016/j.surg.2015.03.048

    View details for Web of Science ID 000358108500023

    View details for PubMedID 26013988

  • Number of Lymph Nodes Removed and Survival after Gastric Cancer Resection: An Analysis from the US Gastric Cancer Collaborative JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS Gholami, S., Janson, L., Worhunsky, D. J., Tran, T. B., Squires, M. H., Jin, L. X., Spolverato, G., Votanopoulos, K. I., Schmidt, C., Weber, S. M., Bloomston, M., Cho, C. S., Levine, E. A., Fields, R. C., Pawlik, T. M., Maithel, S. K., Efron, B., Norton, J. A., Poultsides, G. A. 2015; 221 (2): 291-299


    Examination of at least 16 lymph nodes (LNs) has been traditionally recommended during gastric adenocarcinoma resection to optimize staging, but the impact of this strategy on survival is uncertain. Because recent randomized trials have demonstrated a therapeutic benefit from extended lymphadenectomy, we sought to investigate the impact of the number of LNs removed on prognosis after gastric adenocarcinoma resection.We analyzed patients who underwent gastrectomy for gastric adenocarcinoma from 2000 to 2012, at 7 US academic institutions. Patients with M1 disease or R2 resections were excluded. Disease-specific survival (DSS) was calculated using the Kaplan-Meier method and compared using log-rank and Cox regression analyses.Of 742 patients, 257 (35%) had 7 to 15 LNs removed and 485 (65%) had ≥16 LNs removed. Disease-specific survival was not significantly longer after removal of ≥16 vs 7 to 15 LNs (10-year survival, 55% vs 47%, respectively; p = 0.53) for the entire cohort, but was significantly improved in the subset of patients with stage IA to IIIA (10-year survival, 74% vs 57%, respectively; p = 0.018) or N0-2 disease (72% vs 55%, respectively; p = 0.023). Similarly, for patients who were classified to more likely be "true N0-2," based on frequentist analysis incorporating both the number of positive and of total LNs removed, the hazard ratio for disease-related death (adjusted for T stage, R status, grade, receipt of neoadjuvant and adjuvant therapy, and institution) significantly decreased as the number of LNs removed increased.The number of LNs removed during gastrectomy for adenocarcinoma appears itself to have prognostic implications for long-term survival.

    View details for DOI 10.1016/j.jamcollsurg.2015.04.024

    View details for Web of Science ID 000358384400013

  • Functional microRNA high throughput screening reveals miR-9 as a central regulator of liver oncogenesis by affecting the PPARA-CDH1 pathway BMC CANCER Drakaki, A., Hatziapostolou, M., Polytarchou, C., Vorvis, C., Poultsides, G. A., Souglakos, J., Georgoulias, V., Iliopoulos, D. 2015; 15
  • Is Hepatic Resection for Large or Multifocal Intrahepatic Cholangiocarcinoma Justified? Results from a Multi-Institutional Collaboration ANNALS OF SURGICAL ONCOLOGY Spolverato, G., Kim, Y., Alexandrescu, S., Popescu, I., Marques, H. P., Aldrighetti, L., Gamblin, T. C., Miura, J., Maithel, S. K., Squires, M. H., Pulitano, C., Sandroussi, C., Mentha, G., Bauer, T. W., Newhook, T., Shen, F., Poultsides, G. A., Marsh, J. W., Pawlik, T. M. 2015; 22 (7): 2218-2225


    The role of surgical resection for patients with large or multifocal intrahepatic cholangiocarcinoma (ICC) remains unclear. This study evaluated the long-term outcome of patients who underwent hepatic resection for large (≥7 cm) or multifocal (≥2) ICC.Between 1990 and 2013, 557 patients who underwent liver resection for ICC were identified from a multi-institutional database. Clinicopathologic characteristics, operative details, and long-term survival data were evaluated.Of the 557 patients, 215 (38.6 %) had a small, solitary ICC (group A) and 342 (61.4 %) had a large or multifocal ICC (group B). The patients in group B underwent an extended hepatectomy more frequently (16.9 vs. 30.4 %; P < 0.001). At the final pathology exam, the patients in group B were more likely to show evidence of vascular invasion (22.5 vs. 38.5 %), direct invasion of contiguous organs (6.5 vs. 12.9 %), and nodal metastasis (13.3 vs. 21.0 %) (all P < 0.05). Interestingly, the incidences of postoperative complications (39.3 vs. 46.8 %) and hospital mortality (1.1 vs. 3.7 %) were similar between the two groups (both P > 0.05). The group A patients had better rates for 5-year overall survival (OS) (30.5 vs. 18.7 %; P < 0.05) and disease-free survival (DFS) (22.6 vs. 8.2 %; P < 0.05) than the group B patients. For the patients in group B, the factors associated with a worse OS included more than three tumor nodules [hazard ratio (HR), 1.56], nodal metastasis (HR, 1.47), and poor differentiation (HR, 1.48).Liver resection can be performed safely for patients with large or multifocal ICC. The long-term outcome for these patients can be stratified on the basis of a prognostic score that includes tumor number, nodal metastasis, and poor differentiation.

    View details for DOI 10.1245/s10434-014-4223-3

    View details for Web of Science ID 000355748300017

    View details for PubMedID 25354576

  • Readmission After Liver Resection for Intrahepatic Cholangiocarcinoma: a Multi-Institutional Analysis JOURNAL OF GASTROINTESTINAL SURGERY Spolverato, G., Maqsood, H., Vitale, A., Alexandrescu, S., Marques, H. P., Aldrighetti, L., Gamblin, T. C., Pulitano, C., Bauer, T. W., Shen, F., Poultsides, G., Maithel, S., Marsh, J. W., Pawlik, T. M. 2015; 19 (7): 1334-1341


    The objective of the current study was to define the incidence of 30-day readmission after hepatic resection for intrahepatic cholangiocarcinoma (ICC). In particular, we sought to identify risk factors associated with a higher risk of readmission among patients undergoing resection for ICC.Patients who underwent hepatic resection for ICC at 12 major hepatobiliary centers in the USA, Europe, Australia, and Asia between 1990 and 2013 were identified. Thirty-day readmission and clinicopathologic characteristics associated with higher risk of readmission were examined.Among 602 patients, 401 (68.3 %) patients underwent a major hepatectomy and 256 (43.3 %) experienced at least one post-operative complication. Overall 30-day readmission was 7.8 % (n = 47). Risk factors associated with readmission included pre-operative jaundice (odds ratio (OR) 2.45) and the presence of a major complication (OR 3.38). In fact, 95.7 % of readmitted patients had experienced a post-operative complication versus only 38.8 % of non-readmitted patients (P < 0.001). Among patients who were readmitted, repeat hospitalization was associated with a median LOS of 6.5 days (interquartile range (IQR) 4.0-11.5) and one patient died during readmission.Readmission after hepatic resection for ICC occurred in 1 in 13 patients. Patients with pre-operative jaundice and those who experienced a complication had over a threefold higher risk of being readmitted.

    View details for DOI 10.1007/s11605-015-2826-z

    View details for Web of Science ID 000356458900016

    View details for PubMedID 25903853

  • Cyst Fluid Glucose is Rapidly Feasible and Accurate in Diagnosing Mucinous Pancreatic Cysts. American journal of gastroenterology Zikos, T., Pham, K., Bowen, R., Chen, A. M., Banerjee, S., Friedland, S., Dua, M. M., Norton, J. A., Poultsides, G. A., Visser, B. C., Park, W. G. 2015; 110 (6): 909-914


    Better diagnostic tools are needed to differentiate pancreatic cyst subtypes. A previous metabolomic study showed cyst fluid glucose as a potential marker to differentiate mucinous from non-mucinous pancreatic cysts. This study seeks to validate these earlier findings using a standard laboratory glucose assay, a glucometer, and a glucose reagent strip.Using an IRB-approved prospectively collected bio-repository, 65 pancreatic cyst fluid samples (42 mucinous and 23 non-mucinous) with histological correlation were analyzed.Median laboratory glucose, glucometer glucose, and percent reagent strip positive were lower in mucinous vs. non-mucinous cysts (P<0.0001 for all comparisons). Laboratory glucose<50 mg/dl had a sensitivity of 95% and a specificity of 57% (LR+ 2.19, LR- 0.08). Glucometer glucose<50 mg/dl had a sensitivity of 88% and a specificity of 78% (LR+ 4.05, LR- 0.15). Reagent strip glucose had a sensitivity of 81% and a specificity of 74% (LR+ 3.10, LR- 0.26). CEA had a sensitivity of 77% and a specificity of 83% (LR+ 4.67, LR- 0.27). The combination of having either a glucometer glucose<50 mg/dl or a CEA level>192 had a sensitivity of 100% but a low specificity of 33% (LR+ 1.50, LR- 0.00).Glucose, whether measured by a laboratory assay, a glucometer, or a reagent strip, is significantly lower in mucinous cysts compared with non-mucinous pancreatic cysts.

    View details for DOI 10.1038/ajg.2015.148

    View details for PubMedID 25986360

  • Conditional Probability of Long-term Survival After Liver Resection for Intrahepatic Cholangiocarcinoma A Multi-institutional Analysis of 535 Patients JAMA SURGERY Spolverato, G., Kim, Y., Ejaz, A., Alexandrescu, S., Marques, H., Aldrighetti, L., Gamblin, C., Pulitano, C., Bauer, T. W., Shen, F., Sandroussi, C., Poultsides, G., Maithel, S. K., Pawlik, T. M. 2015; 150 (6): 538-545


    Whereas conventional actuarial overall survival (OS) estimates rely exclusively on static factors determined around the time of surgery, conditional survival (CS) estimates take into account the years that a patient has already survived.To define the CS of patients following liver resection for intrahepatic cholangiocarcinoma (ICC).Between January 1, 1990, and December 31, 2013, a total of 535 patients who underwent resection of ICC were identified from an international multi-institutional database. In this retrospective international study conducted from January to June 2014, clinicopathological characteristics, operative details, and long-term survival data were analyzed. Conditional survival estimates were calculated as the probability of survival for an additional 3 years.Resection of ICC.Overall survival and CS.While actuarial OS decreased over time from 39% at 3 years to 16% at 8 years (P = .002), the 3-year CS (CS3) increased over time among those patients who survived. The CS3 at 5 years-the probability of surviving to postoperative year 8 after having already survived to postoperative year 5-was 65% compared with 8-year OS of 16% (P = .002). Factors that were associated with worse OS included larger tumor size (hazard ratio [HR], 1.02; 95% CI, 1.00-1.05; P = .05), multifocal disease (HR, 1.49; 95% CI, 1.19-1.86; P = .01), lymph node metastasis (HR, 2.21; 95% CI, 1.67-2.93; P < .01), and vascular invasion (HR, 1.39; 95% CI, 1.10-1.75; P = .006). The calculated CS3 exceeded the actuarial survival for all high-risk subgroups. For example, patients with lymph node metastasis had an actuarial OS of 11% at 6 years vs a CS3 of 49% at 3 years (Δ38%). Similarly, patients with vascular invasion had an actuarial OS of 15% at 6 years compared with a CS3 of 50% at 3 years (Δ35%).Conditional survival estimates may provide critical quantitative information about the changing probability of survival over time among patients undergoing liver resection for ICC. Therefore, such estimates can be of significant value to patients and health care professionals.

    View details for DOI 10.1001/jamasurg.2015.0219

    View details for Web of Science ID 000356615400011

    View details for PubMedID 25831462

  • A Nomogram to Predict Overall Survival and Disease-Free Survival After Curative Resection of Gastric Adenocarcinoma ANNALS OF SURGICAL ONCOLOGY Kim, Y., Spolverato, G., Ejaz, A., Squires, M. H., Poultsides, G., Fields, R. C., Bloomston, M., Weber, S. M., Votanopoulos, K., Acher, A. W., Jin, L. X., Hawkins, W. G., Schmidt, C., Kooby, D., Worhunsky, D., Saunders, N., Levine, E. A., Cho, C. S., Maithel, S. K., Pawlik, T. M. 2015; 22 (6): 1828-1835


    The American Cancer Society projects there will be over 22,000 new cases, resulting in nearly 11,000 deaths, related to gastric adenocarcinoma in the US in 2014. The aim of the current study was to find clinicopathologic variables associated with disease-free survival (DFS) and overall survival (OS) following curative resection of gastric adenocarcinoma, and create a nomogram for individual risk prediction.A nomogram to predict DFS and OS following surgical resection of gastric adenocarcinoma was constructed using a multi-institutional cohort of patients who underwent surgery for primary gastric adenocarcinoma at seven major institutions in the US between January 2000 and August 2013. Discrimination and calibration of the nomogram were tested by C-statistic, Kaplan-Meier curves, and calibration plots.A total of 719 patients who underwent surgery for primary gastric adenocarcinoma were included in the study. Using the backward selection of clinically relevant variables with Akaike information criteria, age, sex, tumor site, depth of invasion, and lymph node ratio (LNR) were selected as factors predictive of OS, while age, tumor site, depth of invasion, and LNR were incorporated in the prediction of DFS. A nomogram was constructed to predict OS and DFS using these variables. Discrimination and calibration of the nomogram revealed good predictive abilities (C-index, DFS 0.711; OS 0.702).Independent predictors of recurrence and death following surgery for primary gastric adenocarcinoma were used to create a nomogram to predict DFS and OS. The nomogram was able to stratify patients into prognostic groups, and performed well on internal validation.

    View details for DOI 10.1245/s10434-014-4230-4

    View details for Web of Science ID 000354226600014

    View details for PubMedID 25388061

  • Presentation and Clinical Outcomes of Choledochal Cysts in Children and Adults A Multi-institutional Analysis JAMA SURGERY Soares, K. C., Kim, Y., Spolverato, G., Maithel, S., Bauer, T. W., Marques, H., Sobral, M., Knoblich, M., Tran, T., Aldrighetti, L., Jabbour, N., Poultsides, G. A., Gamblin, T. C., Pawlik, T. M. 2015; 150 (6): 577-584


    Choledochal cysts (CCs) are rare, with risk of infection and cancer.To characterize the natural history, management, and long-term implications of CC disease.A total of 394 patients who underwent resection of a CC between January 1, 1972, and April 11, 2014, were identified from an international multi-institutional database. Patients were followed up through September 27, 2014. Clinicopathologic characteristics, operative details, and outcome data were analyzed from May 1, 2014, to October 14, 2014.Resection of CC.Management, morbidity, and overall survival.Among 394 patients, there were 135 children (34.3%) and 318 women (80.7%). Adults were more likely to present with abdominal pain (71.8% vs 40.7%; P < .001) and children were more likely to have jaundice (31.9% vs 11.6%; P < .001). Preoperative interventions were more commonly performed in adults (64.5% vs 31.1%; P < .001), including endoscopic retrograde pancreatography (55.6% vs 27.4%; P < .001), percutaneous transhepatic cholangiography (17.4% vs 5.9%; P < .001), and endobiliary stenting (18.1% vs 4.4%; P < .001)). Type I CCs were more often seen in children vs adults (79.7% vs 64.9%; P = .003); type IV CCs predominated in the adult population (23.9% vs 12.0%; P = .006). Extrahepatic bile duct resection with hepaticoenterostomy was the most frequently performed procedure in both age groups (80.3%). Perioperative morbidity was higher in adults (35.1% vs 16.3%; P < .001). On pathologic examination, 10 patients (2.5%) had cholangiocarcinoma. After a median follow-up of 28 months, 5-year overall survival was 95.5%. On follow-up, 13 patients (3.3%), presented with biliary cancer.Presentation of CC varied between children and adults, and resection was associated with a degree of morbidity. Although concomitant cancer was uncommon, it occurred in 3.0% of the patients. Long-term surveillance is indicated given the possibility of future development of biliary cancer after CC resection.

    View details for DOI 10.1001/jamasurg.2015.0226

    View details for Web of Science ID 000356615400021

    View details for PubMedID 25923827

  • Extracorporeal Pringle for laparoscopic liver resection SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES Dua, M. M., Worhunsky, D. J., Hwa, K., Poultsides, G. A., Norton, J. A., Visser, B. C. 2015; 29 (6): 1348-1355


    A primary concern during laparoscopic liver resection (lapLR) is hemorrhage during parenchymal transection. Intermittent pedicle clamping is an effective method to minimize blood loss during open liver surgery; however, inflow occlusion techniques are challenging to reproduce during laparoscopy. The purpose of this study is to describe the safety and efficacy of a facile method for Pringle maneuver during lapLR.154 patients who underwent lapLR from 2007 to 2013 were retrospectively reviewed. For Pringle, the hepatoduodenal ligament is encircled with an umbilical tape which is externalized through a flexible Rumel tourniquet running alongside a port used for the operation. The internal end of the catheter is close to the pedicle and the external end is extracorporeal, allowing for easy external occlusion. Patients who underwent Pringle Maneuver (PM, n = 88) were compared to patients who had "No Occlusion" (NO, n = 66) with respect to patient characteristics, operative outcomes, changes in postoperative liver function, and complications.Annual placement of the tourniquet and vascular occlusion increased from 35.7 to 82.8 % (p = 0.004) and 21.4 to 62.1 % (p = 0.02), respectively. Median occlusion time was 24 min (IQR 15-34.3, min 5, max 70). Peak transaminase levels were comparable between groups (AST 298 ± 32 vs 405 ± 47 U/L, p = 0.15; ALT 272 ± 27 vs 372 ± 34 U/L, p = 0.14, NO and PM, respectively). Postoperative transaminase and bilirubin levels for both groups were not significantly different with similar recovery to baseline. Subgroup analysis of cirrhotic patients who underwent Pringle demonstrated similar transaminase profiles compared to non-cirrhotic patients. There were two conversions (1.3 %) and postoperative 30-day mortality was 0.65 %.Extracorporeal tourniquet placement in lapLR is a quick and safe method of gaining control for inflow occlusion. Routine adoption of laparoscopic Pringle maneuver facilitates low conversion rates without liver injury.

    View details for DOI 10.1007/s00464-014-3801-6

    View details for Web of Science ID 000354130200013

    View details for PubMedID 25159645

  • Predictive Factors for Surgery Among Patients with Pancreatic Cysts in the Absence of High-Risk Features for Malignancy JOURNAL OF GASTROINTESTINAL SURGERY Quan, S. Y., Visser, B. C., Poultsides, G. A., Norton, J. A., Chen, A. M., Banerjee, S., Friedland, S., Park, W. G. 2015; 19 (6): 1101-1105


    Without a reliable biopsy technique for pancreatic cysts, consensus-based guidelines are used to guide surgical utilization. The primary objective of this study was to characterize the proportion of operations performed outside of these guidelines.A 5-year retrospective review between July 1, 2007, and June 30, 2012, was performed of consecutive patients seen at a single tertiary medical center for a pancreatic cyst. Manual chart review for relevant clinical variables and cyst characteristics was performed.During this period, 148 patients underwent surgery, and of these, 23 (16 %) patients had no high-risk criteria by the 2006 Sendai criteria. None of these harbored high-grade dysplastic or cancerous lesions. A high cyst carcinoembryonic antigen (CEA) level (35 %), patient anxiety (26 %), and physician concern (22 %) were explicit reasons to proceed to surgery. An elevated cyst CEA level >192 ng/ml was the most significant predictor (OR 5.14 (95 % confidence interval (CI) 1.47-18.0) for surgery without high-risk criteria.A high cyst CEA level was significantly associated with the decision to operate outside of consensus-based guidelines. The misuse of cyst CEA in the management of pancreatic cysts negatively impacts patient anxiety, increases physician uncertainty, and leads to surgery with minimal benefit.

    View details for DOI 10.1007/s11605-015-2786-3

    View details for Web of Science ID 000355344300016

    View details for PubMedID 25749855

  • Leiomyosarcoma: One Disease or Distinct Biologic Entities Based on Site of Origin? JOURNAL OF SURGICAL ONCOLOGY Worhunsky, D. J., Gupta, M., Gholami, S., Tran, T. B., Ganjoo, K. N., van de Rijn, M., Visser, B. C., Norton, J. A., Poultsides, G. A. 2015; 111 (7): 808-812


    Leiomyosarcoma (LMS) can originate from the retroperitoneum, uterus, extremity, and trunk. It is unclear whether tumors of different origin represent discrete entities. We compared clinicopathologic features and outcomes following surgical resection of LMS stratified by site of origin.Patients with LMS undergoing resection at a single institution were retrospectively reviewed. Clinicopathologic variables were compared across sites. Survival was calculated using the Kaplan-Meier method and compared using log-rank and Cox regression analyses.From 1983 to 2011, 138 patients underwent surgical resection for LMS. Retroperitoneal and uterine LMS were larger, higher grade, and more commonly associated with synchronous metastases. However, disease-specific survival, recurrence-free survival, and recurrence patterns were not significantly different across the four sites. Synchronous metastases (HR 3.20, P < 0.001), but not site of origin, size, grade, or margin status, were independently associated with worse DSS. A significant number of recurrences and disease-related deaths were noted beyond 5 years.Although larger and higher grade, retroperitoneal and uterine LMS share similar survival and recurrence patterns with their trunk and extremity counterparts. LMS of various anatomic sites may not represent distinct disease processes based on clinical outcomes. The presence of metastatic disease remains the most important prognostic factor for LMS.

    View details for DOI 10.1002/jso.23904

    View details for Web of Science ID 000353996400003

    View details for PubMedID 25920434

  • Impact of body mass index on perioperative outcomes and survival after resection for gastric cancer JOURNAL OF SURGICAL RESEARCH Ejaz, A., Spolverato, G., Kim, Y., Poultsides, G. A., Fields, R. C., Bloomston, M., Cho, C. S., Votanopoulos, K., Maithel, S. K., Pawlik, T. M. 2015; 195 (1): 74-82


    Among patients undergoing resection for gastric cancer, the impact of body mass index (BMI) on outcomes is not well understood. We sought to define the impact of non-normal BMI on short- and long-term outcomes after gastric cancer resection.We identified 775 patients who underwent gastrectomy for adenocarcinoma between 2000 and 2012 from the multi-institutional US Gastric Cancer Collaborative. Clinicopathologic characteristics, operative details, and oncologic outcomes were collected, and patients were stratified according to BMI.Most patients in the cohort were classified as having normal BMI (n = 338, 43.6%), followed by overweight (n = 229, 29.6%), obese (n = 153, 19.7%), and underweight (n = 55, 7.1%). After stratifying by BMI, there were no significant differences in the incidence of postoperative blood transfusions, perioperative morbidity, postoperative infectious complications, length of stay, perioperative 30-d in-hospital death, or readmission across groups (all P > 0.05). BMI did not impact overall or recurrence-free survival after stratifying by stage (all P > 0.05). However, underweight patients with low preoperative albumin levels had worse overall survival (OS) compared with that of patients of normal BMI.BMI did not impact perioperative morbidity, recurrence-free, or OS in patients undergoing gastric resection for adenocarcinoma. Underweight patients with BMI <18.5 kg/m(2) and low preoperative albumin levels, however, had a significantly decreased OS after gastrectomy for cancer. These high-risk patients should have their nutritional status optimized both before and after gastrectomy in an attempt to modify this risk factor and, in turn, achieve better outcomes.

    View details for DOI 10.1016/j.jss.2014.12.048

    View details for Web of Science ID 000352139900011

    View details for PubMedID 25619462

  • Minimally Invasive Resection of Choledochal Cyst: a Feasible and Safe Surgical Option JOURNAL OF GASTROINTESTINAL SURGERY Margonis, G. A., Spolverato, G., Kim, Y., Marques, H., Poultsides, G., Maithel, S., Aldrighetti, L., Bauer, T. W., Jabbour, N., Gamblin, T. C., Soares, K., Pawlik, T. M. 2015; 19 (5): 858-865


    The use of minimally invasive surgery (MIS) for choledochal cyst (CC) has not been well documented. We sought to define the overall utilization and outcomes associated with the use of the open versus MIS approach for CC. We examined the factors associated with receipt of MIS for CC, as well as characterized perioperative and long-term outcomes following open versus MIS for CC.Between 1972 and 2014, a total of 368 patients who underwent resection for CC were identified from an international, multicenter database. A 2:1 propensity score matching was used to create comparable cohorts of patients to assess the effect of MIS on short-term outcomes.Three hundred thirty-two patients had an open procedure, whereas 36 patients underwent an MIS approach. Children were more likely to be treated with a MIS approach (children, 24.0 % vs. adults, 2.1 %; P<0.001). Conversely, patients who had any medical comorbidity were less likely to undergo MIS surgery (open, 26.2 % vs. MIS, 2.8 %; P=0.002). In the propensity-matched cohort, MIS resection was associated with decreased length of stay (open, 7 days vs. MIS, 5 days), lower estimated blood loss (open, 50 mL vs. MIS, 17.5 mL), and longer operative time (open, 237 min vs. MIS, 301 min) compared with open surgery (all P<0.05). The overall and degree of complication did not differ between the open (grades I-II, n=13; grades III-IV, n=15) versus MIS (grades I-II, n=5; grades III-IV, n=5) cohorts (P=0.85). Five-year overall survival was 98.6 % (open, 98.0 % vs. MIS, 100.0 %; P=0.45); no patient who underwent MIS developed a subsequent cholangiocarcinoma.MIS resection of CC was demonstrated to be a feasible and safe approach with acceptable short-term outcomes in the pediatric population. MIS for benign CC disease was associated with similar perioperative morbidity but a shorter length of stay and a lower blood loss when compared with open resection.

    View details for DOI 10.1007/s11605-014-2722-y

    View details for Web of Science ID 000353198400009

    View details for PubMedID 25519084

  • Is It Time to Abandon the 5-cm Margin Rule During Resection of Distal Gastric Adenocarcinoma? A Multi-Institution Study of the U.S. Gastric Cancer Collaborative. Annals of surgical oncology Squires Iii, M. H., Kooby, D. A., Poultsides, G. A., Pawlik, T. M., Weber, S. M., Schmidt, C. R., Votanopoulos, K. I., Fields, R. C., Ejaz, A., Acher, A. W., Worhunsky, D. J., Saunders, N., Levine, E. A., Jin, L. X., Cho, C. S., Bloomston, M., Winslow, E. R., Russell, M. C., Cardona, K., Staley, C. A., Maithel, S. K. 2015; 22 (4): 1243-1251


    A proximal margin distance of 5 cm is advocated for resection of gastric adenocarcinoma (GAC). We assessed the prognostic value of proximal margin (PM) distance on survival outcomes after resection of distal GAC.All patients who underwent resection of distal GAC (antrum/body) from 2000 to 2012 at seven institutions of the U.S. Gastric Cancer Collaborative were included. Patients with positive distal margins or macroscopic residual disease were excluded. The prognostic value of PM distance (assessed in 0.5-cm increments) on overall (OS) and recurrence-free survival (RFS) was assessed by Kaplan-Meier and multivariate regression analysis.A total of 465 patients underwent resection of distal GAC. Of these, 435 had R0 resections; 30 patients had a positive PM. 143 patients had stage I, and 322 had stage II-III tumors. Median follow-up was 44 months. Average PM distance was 4.8 cm. Median OS for patients with PM of 3.1-5.0 cm (n = 110) was superior to patients with PM ≤ 3.0 cm (n = 176) (48.1 vs. 29.3 months; p = 0.01), while a margin >5.0 cm (n = 179) offered equivalent survival to PM 3.1-5.0 cm (50.6 months, p = 0.72). The prognostic value of margin distance was stage specific. On multivariate analysis of stage I patients, PM 3.1-5.0 cm remained associated with improved OS [hazard ratio (HR), 0.16; 95 % confidence interval (95 % CI), 0.04-0.60; p = 0.01]. In stage II-III, neither PM 3.1-5.0 cm nor PM > 5.0 cm was significantly associated with OS; OS was dictated by T stage and nodal involvement.The prognostic value of proximal margin distance after resection of distal gastric cancer appears stage specific. In stage I, a 3.1- to 5.0-cm proximal margin is associated with the same improved OS as a > 5.0-cm margin. In stage II-III disease, other adverse pathologic factors more strongly impact survival than proximal margin distance.

    View details for DOI 10.1245/s10434-014-4138-z

    View details for PubMedID 25316491

  • Compliance With Gastric Cancer Guidelines is Associated With Improved Outcomes. Journal of the National Comprehensive Cancer Network Worhunsky, D. J., Ma, Y., Zak, Y., Poultsides, G. A., Norton, J. A., Rhoads, K. F., Visser, B. C. 2015; 13 (3): 319-325


    Limited data are available on the implementation and effectiveness of NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Gastric Cancer.We sought to assess rates of compliance with NCCN Guidelines, specifically stage-specific therapy during the initial episode of care, and to determine its impact on outcomes.The California Cancer Registry was used to identify cases of gastric cancer from 2001 to 2006. Logistic regression and Cox proportional hazard models were used to predict guideline compliance and the adjusted hazard ratio for mortality. Patients with TNM staging or summary stage (SS) were also analyzed separately.Compliance with NCCN Guidelines occurred in just 45.5% of patients overall. Patients older than 55 years were less likely to receive guideline-compliant care, and compliance was associated with a median survival of 20 versus 7 months for noncompliant care (P<.001). Compliant care was also associated with a 55% decreased hazard of mortality (P<.001). Further analysis revealed that 50% of patients had complete TNM staging versus an SS, and TNM-staged patients were more likely to receive compliant care (odds ratio, 1.59; P<.001). TNM-staged patients receiving compliant care had a median survival of 25.3 months compared with 15.1 months for compliant SS patients.Compliance with NCCN Guidelines and stage-specific therapy at presentation for the treatment of patients with gastric cancer was poor, which was a significant finding given that compliant care was associated with a 55% reduction in the hazard of death. Additionally, patients with TNM-staged cancer were more likely to receive compliant care, perhaps a result of having received more intensive therapy. Combined with the improved survival among compliant TNM-staged patients, these differences have meaningful implications for health services research.

    View details for PubMedID 25736009

  • Clinicopathological features and prognosis of gastric cardia adenocarcinoma: A multi-institutional U.S. study. Journal of surgical oncology Amini, N., Spolverato, G., Kim, Y., Squires, M. H., Poultsides, G. A., Fields, R., Schmidt, C., Weber, S. M., Votanopoulos, K., Maithel, S. K., Pawlik, T. M. 2015; 111 (3): 285-292


    Potential differences in presentation and outcome of patients with gastric cardia adenocarcinoma (GCA) and non-cardia adenocarcinoma may exist. The aim of the present study was to compare the clinicopathological characteristics and the prognosis of GCA versus non-cardia adenocarcinoma.Patients with gastric adenocarcinoma who underwent gastric resection between 2000-2012 were identified. Clinicopathological characteristics and outcomes were analyzed based on tumor site using a 1:2 matched-control, as well as a multivariable Cox model.Among 743 patients, 80 (10.7%) patients were diagnosed with GCA. Patients with GCA were more likely to have intestinal tumor type (GCA: 80.4% versus non-cardia: 64.2%, P = 0.04) or advanced AJCC T stage tumors (GCA 71.8% versus non-cardia 59.2%, P = 0.03). GCA patients more likely underwent a total gastrectomy (GCA: 85.7% vs. non-cardia: 39.8%) and had a longer length-of-stay (GCA: 10 days vs. non-cardia: 8 days) (both P < 0.05). Outcomes in early stage I patients were worse among GCA (disease-free survival, 44.2%; overall survival, 42.3%) versus non-GCA (disease-free survival, 60.8%; overall survival, 63.0%) patients(both P < 0.05).In general, disease-free survival and overall survival were similar between patients with GCA versus non-cardia adenocarcinoma. However, long-term outcome was worse among patients with GCA and early stage disease. J. Surg. Oncol. 2015 111:285-292. © 2014 Wiley Periodicals, Inc.

    View details for DOI 10.1002/jso.23799

    View details for PubMedID 25308915

  • Mutation profiling of tumor DNA from plasma and tumor tissue of colorectal cancer patients with a novel, high-sensitivity multiplexed mutation detection platform ONCOTARGET Kidess, E., Heirich, K., Wiggin, M., Vysotskaia, V., Visser, B. C., Marziali, A., Wiedenmann, B., Norton, J. A., Lee, M., Jeffrey, S. S., Poultsides, G. A. 2015; 6 (4): 2549-2561


    Circulating tumor DNA (ctDNA) holds promise as a non-invasive means for tumor monitoring in solid malignancies. Assays with high sensitivity and multiplexed analysis of mutations are needed to enable broad application.We developed a new assay based on sequence-specific synchronous coefficient of drag alteration (SCODA) technology, which enriches for mutant DNA to achieve high sensitivity and specificity. This assay was applied to plasma and tumor tissue from non-metastatic and metastatic colorectal cancer (CRC) patients, including patients undergoing surgical resection for CRC liver metastases.Across multiple characterization experiments, the assay demonstrated a limit of detection of 0.001% (1 molecule in 100,000) for the majority of the 46 mutations in the panel. In CRC patient samples (n=38), detected mutations were concordant in tissue and plasma for 93% of metastatic patients versus 54% of non-metastatic patients. For three patients, ctDNA identified additional mutations not detected in tumor tissue. In patients undergoing liver metastatectomy, ctDNA anticipated tumor recurrence earlier than carcinoembryonic antigen (CEA) value or imaging.The multiplexed SCODA mutation enrichment and detection method can be applied to mutation profiling and quantitation of ctDNA, and is likely to have particular utility in the metastatic setting, including patients undergoing metastatectomy.

    View details for Web of Science ID 000352691800047

    View details for PubMedID 25575824

  • Does the extent of resection impact survival for duodenal adenocarcinoma? Analysis of 1,611 cases. Annals of surgical oncology Cloyd, J. M., Norton, J. A., Visser, B. C., Poultsides, G. A. 2015; 22 (2): 573-580


    Because duodenal adenocarcinoma (DA) is relatively rare, few studies have investigated the impact of resection type on long-term outcomes.The Surveillance, Epidemiology, and End Results database was used to identify all patients between 1988 and 2010 with DA. Patients were divided into two groups based on the type of surgery received: simple resection (SR), defined as a simple removal of the primary site, and radical resection (RR), defined as removal of the primary site with a resection in continuity with other organs. Differences in disease-specific survival (DSS) and overall survival (OS) were compared.Of the 1,611 patients included, 746 (46.3 %) underwent SR and 865 (53.7 %) underwent RR. As expected, patients undergoing RR were more likely to present with poorly differentiated and large tumors, as well as advanced stage disease. Despite greater lymph node (LN) retrieval (11.0 vs. 6.8; p < 0.0001), RR was not associated with improved survival (5-year DSS and OS rates of 52.8 and 41.3 % for SR vs. 48.8 and 37.6 % for RR; p > 0.05). On univariate Cox proportional hazards regression analysis, the type of surgery was not associated with OS (odds ratio [OR] 0.98; 95 % confidence interval [CI] 0.87-1.11). Increasing TNM stages, tumor grade, fewer LNs removed, LN ratio, and absence of radiation were associated with worse survival. After controlling for confounding factors, type of surgery still did not influence OS (OR 1.11; 95 % CI 0.97-1.27).Radical resection (e.g., in the form of pancreaticoduodenectomy) does not appear to impact survival compared with simple segmental resection for DA.

    View details for DOI 10.1245/s10434-014-4020-z

    View details for PubMedID 25160736

  • Can the Risk of Non-home Discharge After Resection of Gastric Adenocarcinoma Be Predicted: a Seven-Institution Study of the US Gastric Cancer Collaborative. Journal of gastrointestinal surgery Acher, A. W., Squires, M. H., Fields, R. C., Poultsides, G. A., Schmidt, C., Votanopoulos, K. I., Pawlik, T. M., Jin, L. X., Ejaz, A., Kooby, D. A., Bloomston, M., Worhunsky, D., Levine, E. A., Saunders, N., Winslow, E., Cho, C. S., Meredith, K., Leverson, G., Maithel, S. K., Weber, S. M. 2015; 19 (2): 207-216


    There are no validated methods to preoperatively identify patients with increased risk of discharge to skilled nursing facilities following resection of gastric cancer. We sought to identify preoperative predictors of non-home discharge to optimize transition of care to skilled nursing facility.Patients who underwent resection of gastric cancer from 2000 to 2012 from seven participating institutions of the US Gastric Cancer Collaborative were analyzed. Fisher's exact tests, Student t tests, and logistic regression analyses identified preoperative variables associated with non-home discharge. A prediction tool was created and validated through c-indices. Survival analysis was conducted according to the methods of Kaplan and Meier.Out of the 918 patients identified, 93 (10 %) were discharged to nonhome location. Univariate analysis identified advancing age, American Society of Anesthesiology (ASA) score, hypertension, decreasing preoperative albumin, and lack of neoadjuvant chemotherapy as risk factors for non-home discharge (NHD). Multivariable analysis identified advanced age (odds ratio (OR) = 1.07, 95 % confidence interval (CI) = 1.04-1.10, p < 0.0001), depressed preoperative albumin (OR = 2.17, 95 % CI = 1.47-3.19, p = 0.0001), and total gastrectomy (OR = 2.56, 95 % CI = 1.53-4.3, p = 0.0003) as risk factors for NHD. The c-index of the model and the validation population were 0.76 and 0.8, respectively. Additionally, there was an association of decreased overall survival in patients discharged to nonhome location (35.5 months, home discharge, vs 12 months, NHD, p < 0.0001).Older patients with compromised nutritional status have greater risk of NHD following resection of gastric cancer. The prediction tool can augment preoperative planning to optimize transition of care to skilled nursing facility.

    View details for DOI 10.1007/s11605-014-2690-2

    View details for PubMedID 25373704

  • Conditional Survival after Surgical Resection of Gastric Cancer: A Multi-Institutional Analysis of the US Gastric Cancer Collaborative. Annals of surgical oncology Kim, Y., Ejaz, A., Spolverato, G., Squires, M. H., Poultsides, G., Fields, R. C., Bloomston, M., Weber, S. M., Votanopoulos, K., Acher, A. W., Jin, L. X., Hawkins, W. G., Schmidt, C., Kooby, D., Worhunsky, D., Saunders, N., Cho, C. S., Levine, E. A., Maithel, S. K., Pawlik, T. M. 2015; 22 (2): 557-564


    Survival estimates following surgical resection of gastric adenocarcinoma are traditionally reported as survival from the date of surgery. Conditional survival (CS) estimates, however, may be more clinically relevant by accounting for time already survived. We assessed CS following surgical resection for gastric adenocarcinoma.We analyzed 807 patients who underwent resection for gastric adenocarcinoma from 2000 to 2012 at seven participating institutions in the U.S. Gastric Cancer Collaborative. Cox proportional hazards models were used to evaluate factors associated with overall survival. Three-year CS estimates at "x" year after surgery were calculated as follows: CS3 = S(x+3)/S(x).Overall 1-, 3-, and 5-year overall survival rates after gastric resection were 42, 34, and 30 %, respectively. Using CS estimates, the probability of surviving an additional 3 years given that the patient had survived at 1, 3, and 5 years were 56, 71, and 82 %, respectively. Patients with higher risk at baseline (i.e., stage III or IV disease, lymphovascular invasion) demonstrated the greatest increase in CS over time.Survival estimates following surgical resection of gastric adenocarcinoma is dynamic; the probability of survival increases with time already survived. Patients with worse prognostic features at the time of surgery had the greatest increases in CS over time. Conditional survival estimates provide important information about the changing probability of survival over time and should be used among patients with resected gastric adenocarcinoma to guide subsequent follow-up strategies.

    View details for DOI 10.1245/s10434-014-4116-5

    View details for PubMedID 25287440

  • Use of Endoscopic Ultrasound in the Preoperative Staging of Gastric Cancer: A Multi-Institutional Study of the US Gastric Cancer Collaborative JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS Spolverato, G., Ejaz, A., Kim, Y., Squires, M. H., Poultsides, G. A., Fields, R. C., Schmidt, C., Weber, S. M., Votanopoulos, K., Maithel, S. K., Pawlik, T. M. 2015; 220 (1): 48-56


    Endoscopic ultrasound (EUS) can be used to guide the therapeutic plan for patients with gastric adenocarcinoma (GAC), but data on its use and accuracy remain poorly defined. We sought to define the use of EUS, as well as characterize the diagnostic accuracy of EUS among patients with GAC.We identified 960 patients who underwent resection of GAC between 2000 and 2012 from 7 major academic institutions participating in the US Gastric Cancer Collaborative. Clinicopathologic and EUS data were collected and analyzed using chi and kappa statistics.Of 960 patients, 223 (23.2%) underwent evaluation with preoperative EUS. Among patients who underwent EUS, 74 (33.2%) received neoadjuvant chemotherapy; 149 (66.8%) proceeded directly to resection. Among patients who did not receive neoadjuvant therapy and received curative intent gastric resection, the EUS T classifications were T1 (33.3%), T2 (35.6%), T3 (18.9%), T4 (12.1%) and the N classifications were N0 (68.1%) and N ≥ 1 (31.9%). In contrast, when tumor stage was based on the final surgical specimen, there was a higher proportion of cases with more advanced T stage (T1, 36.4%; T2, 14.4%; T3, 23.5%; T4, 25.7%) and N stage (N0, 51.3%; N ≥ 1, 48.7%). The agreement of preoperative EUS compared with surgical staging for T (kappa = 0.28, p < 0.001) and N (kappa = 0.33, p < 0.001) classification was only fair.Less than one-quarter of patients with GAC underwent preoperative EUS staging. In patients who did not receive preoperative chemotherapy, tumor stage on EUS often did not correlate with T stage and N stage on final pathologic analysis. Endoscopic ultrasound should be combined with other staging modalities to optimize staging of patients with GAC.

    View details for DOI 10.1016/j.jamcollsurg.2014.06.023

    View details for Web of Science ID 000346362800007

    View details for PubMedID 25283742

  • Functional microRNA high throughput screening reveals miR-9 as a central regulator of liver oncogenesis by affecting the PPARA-CDH1 pathway. BMC cancer Drakaki, A., Hatziapostolou, M., Polytarchou, C., Vorvis, C., Poultsides, G. A., Souglakos, J., Georgoulias, V., Iliopoulos, D. 2015; 15: 542-?


    Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths, reflecting the aggressiveness of this type of cancer and the absence of effective therapeutic regimens. MicroRNAs have been involved in the pathogenesis of different types of cancers, including liver cancer. Our aim was to identify microRNAs that have both functional and clinical relevance in HCC and examine their downstream signaling effectors.MicroRNA and gene expression levels were measured by quantitative real-time PCR in HCC tumors and controls. A TargetScan algorithm was used to identify miR-9 downstream direct targets.A high-throughput screen of the human microRNAome revealed 28 microRNAs as regulators of liver cancer cell invasiveness. MiR-9, miR-21 and miR-224 were the top inducers of HCC invasiveness and also their expression was increased in HCC relative to control liver tissues. Integration of the microRNA screen and expression data revealed miR-9 as the top microRNA, having both functional and clinical significance. MiR-9 levels correlated with HCC tumor stage and miR-9 overexpression induced SNU-449 and HepG2 cell growth, invasiveness and their ability to form colonies in soft agar. Bioinformatics and 3'UTR luciferase analyses identified E-cadherin (CDH1) and peroxisome proliferator-activated receptor alpha (PPARA) as direct downstream effectors of miR-9 activity. Inhibition of PPARA suppressed CDH1 mRNA levels, suggesting that miR-9 regulates CDH1 expression directly through binding in its 3'UTR and indirectly through PPARA. On the other hand, miR-9 inhibition of overexpression suppressed HCC tumorigenicity and invasiveness. PPARA and CDH1 mRNA levels were decreased in HCC relative to controls and were inversely correlated with miR-9 levels.Taken together, this study revealed the involvement of the miR-9/PPARA/CDH1 signaling pathway in HCC oncogenesis.

    View details for DOI 10.1186/s12885-015-1562-9

    View details for PubMedID 26206264

  • Utility of the Proximal Margin Frozen Section for Resection of Gastric Adenocarcinoma: A 7-Institution Study of the US Gastric Cancer Collaborative ANNALS OF SURGICAL ONCOLOGY Squires, M. H., Kooby, D. A., Pawlik, T. M., Weber, S. M., Poultsides, G., Schmidt, C., Votanopoulos, K., Fields, R. C., Ejaz, A., Acher, A. W., Worhunsky, D. J., Saunders, N., Jin, L. X., Levine, E., Cho, C. S., Bloomston, M., Winslow, E., Cardona, K., Staley, C. A., Maithel, S. K. 2014; 21 (13): 4202-4210
  • Single-versus Multifraction Stereotactic Body Radiation Therapy for Pancreatic Adenocarcinoma: Outcomes and Toxicity INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Pollom, E. L., Alagappan, M., von Eyben, R., Kunz, P. L., Fisher, G. A., Ford, J. A., Poultsides, G. A., Visser, B. C., Norton, J. A., Kamaya, A., Cox, V. L., Columbo, L. A., Koong, A. C., Chang, D. T. 2014; 90 (4): 918-925
  • Laparoscopic Transgastric Necrosectomy for the Management of Pancreatic Necrosis JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS Worhunsky, D. J., Qadan, M., Dua, M. M., Park, W. G., Poultsides, G. A., Norton, J. A., Visser, B. C. 2014; 219 (4): 735-743
  • Impact of External-Beam Radiation Therapy on Outcomes Among Patients with Resected Gastric Cancer: A Multi-institutional Analysis ANNALS OF SURGICAL ONCOLOGY Ejaz, A., Spolverato, G., Kim, Y., Squires, M. H., Poultsides, G., Fields, R., Bloomston, M., Weber, S. M., Votanopoulos, K., Worhunsky, D. J., Swords, D., Jin, L. X., Schmidt, C., Acher, A. W., Saunders, N., Cho, C. S., Herman, J. M., Maithel, S. K., Pawlik, T. M. 2014; 21 (11): 3412-3421
  • Rates and Patterns of Recurrence after Curative Intent Resection for Gastric Cancer: A United States Multi-Institutional Analysis JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS Spolverato, G., Ejaz, A., Kim, Y., Squires, M. H., Poultsides, G. A., Fields, R. C., Schmidt, C., Weber, S. M., Votanopoulos, K., Maithel, S. K., Pawlik, T. M. 2014; 219 (4): 664-675
  • A Multi-institutional Analysis of Open Versus Minimally-Invasive Surgery for Gastric Adenocarcinoma: Results of the US Gastric Cancer Collaborative JOURNAL OF GASTROINTESTINAL SURGERY Spolverato, G., Kim, Y., Ejaz, A., Valero, V., Squires, M. H., Poultsides, G., Fields, R. C., Bloomston, M., Weber, S. M., Acher, A. W., Votanopoulos, K., Schmidt, C., Cho, C. S., Maithel, S. K., Pawlik, T. M. 2014; 18 (9): 1563-1574


    Surgical experience with minimally invasive surgery (MIS) has increased; however, published reports on MIS resection of gastric adenocarcinoma are limited.Between 2000 and 2012, 880 patients who underwent surgical resection of gastric adenocarcinoma were identified from a multi-institutional database. Clinicopathological characteristics, operative details, and outcomes were stratified by operative approach (open vs. MIS) and analyzed.Overall, 70 (8 %) patients had a MIS approach. Patients who underwent a MIS resection were more likely to have a smaller tumor (open 4.5 cm vs. MIS 3.0 cm, p < 0.001). MIS resections were associated with lower estimated blood loss (open 250 cc vs. MIS 150 cc) and longer operative time (open 232 min vs. MIS 271 min) compared with open surgery (both p < 0.05). An R0 resection was achieved in most patients (open 90.9 % vs. MIS 98.6 %, p = 0.03) and median lymph node yield was good in both groups (open 17 vs. MIS 14, p = 0.10). MIS had a similar incidence of complications (open 33.1 % vs. MIS 20 %, p = 0.07) and a similar length of stay (open 9 days vs. MIS 7 days, p = 0.13) compared with open surgery. In the propensity-matched analysis, median recurrence-free and overall were not impacted by operative approach.An MIS approach to gastric cancer was associated with adequate lymph node retrieval, a high incidence of R0 resection, and comparable long-term oncological outcomes versus open gastrectomy.

    View details for DOI 10.1007/s11605-014-2562-9

    View details for Web of Science ID 000340936300003

    View details for PubMedID 24912915

  • Laparoscopic spleen-preserving distal pancreatectomy: the technique must suit the lesion. Journal of gastrointestinal surgery Worhunsky, D. J., Zak, Y., Dua, M. M., Poultsides, G. A., Norton, J. A., Visser, B. C. 2014; 18 (8): 1445-1451


    Splenic preservation is currently recommended during minimally invasive surgery for benign tumors of the distal pancreas. The aim of this study was to evaluate the outcomes of patients undergoing laparoscopic spleen-preserving distal pancreatectomy, with particular attention paid to the technique used for spleen preservation (splenic vessel ligation vs preservation). A review of consecutive patients who underwent laparoscopic distal pancreatectomy with the intention of splenic preservation was conducted. Patient demographics, operative data, and outcomes were collected and analyzed. Fifty-five consecutive patients underwent laparoscopic distal pancreatectomy with the intention of splenic preservation; 5 required splenectomy (9 %). Of the remaining 50 patients, 31 (62 %) had splenic vessel ligation, and 19 (38 %) had vessel preservation. Patient demographics and tumor size were similar. The vessel ligation group had significantly more pancreas removed (95 vs 52 mm, P < 0.001) and longer operative times (256 vs 201 min, P = 0.008). Postoperative outcomes, complication rates, and splenic viability were similar between groups. Laparoscopic spleen-preserving distal pancreatectomy is a safe operation with a high rate of success (91 %). Vessel ligation was the chosen technical strategy for lesions that required resection of a greater length of pancreas. We found no advantage to either technique with respect to outcomes and splenic preservation. Operative approach should reflect technical considerations including location in the pancreas.

    View details for DOI 10.1007/s11605-014-2561-x

    View details for PubMedID 24939598

  • Pancreatic neuroendocrine tumours: hypoenhancement on arterial phase computed tomography predicts biological aggressiveness HPB Worhunsky, D. J., Krampitz, G. W., Poullos, P. D., Visser, B. C., Kunz, P. L., Fisher, G. A., Norton, J. A., Poultsides, G. A. 2014; 16 (4): 304-311


    Contrary to pancreatic adenocarcinoma, pancreatic neuroendocrine tumours (PNET) are commonly hyperenhancing on arterial phase computed tomography (APCT). However, a subset of these tumours can be hypoenhancing. The prognostic significance of the CT appearance of these tumors remains unclear.From 2001 to 2012, 146 patients with well-differentiated PNET underwent surgical resection. The degree of tumour enhancement on APCT was recorded and correlated with clinicopathological variables and overall survival.APCT images were available for re-review in 118 patients (81%). The majority had hyperenhancing tumours (n = 80, 68%), 12 (10%) were isoenhancing (including cases where no mass was visualized) and 26 (22%) were hypoenhancing. Hypoenhancing PNET were larger, more commonly intermediate grade, and had higher rates of lymph node and synchronous liver metastases. Hypoenhancing PNET were also associated with significantly worse overall survival after a resection as opposed to isoenhancing and hyperenhancing tumours (5-year, 54% versus 89% versus 93%). On multivariate analysis of factors available pre-operatively, only hypoenhancement (HR 2.32, P = 0.02) was independently associated with survival.Hypoenhancement on APCT was noted in 22% of well-differentiated PNET and was an independent predictor of poor outcome. This information can inform pre-operative decisions in the multidisciplinary treatment of these neoplasms.

    View details for DOI 10.1111/hpb.12139

    View details for Web of Science ID 000332989700002

  • Does Chronic Kidney Disease Affect Outcomes after Major Abdominal Surgery? Results from the National Surgical Quality Improvement Program JOURNAL OF GASTROINTESTINAL SURGERY Cloyd, J. M., Ma, Y., Morton, J. M., Tamura, M. K., Poultsides, G. A., Visser, B. C. 2014; 18 (3): 605-612


    The impact of chronic kidney disease (CKD) and end-stage renal disease on outcomes following major abdominal surgery is not well defined.The 2008 NSQIP database was queried to identify adult patients undergoing complex abdominal surgery (major colorectal, hepatobiliary, pancreatic, gastric, and esophageal operations). Thirty-day morbidity and mortality in patients on hemodialysis (HD) versus patients not on HD were compared. The impact of preoperative renal insufficiency, measured by glomerular filtration rate (GFR), on morbidity and mortality was then assessed in non-dialysis patients.Of 24,572 patients who underwent major abdominal operations, excluding emergency cases, only 149 (0.6 %) were on HD preoperatively. Thirty-day mortality in the HD group was 12.8 % compared to 1.8 % for those not on HD (p < 0.0001). Overall complication rate was 23.5 versus 12.3 % (p < 0.0001). In particular, rates of pneumonia (6.7 vs 3.0 %, p < 0.05) and sepsis (12.8 vs 5.3 %, p < 0.001) were higher in patients on HD. In patients not on HD, GFR was significantly predictive of postoperative mortality after controlling for age, gender, race, emergency status, and comorbidities. Compared to patients with normal preoperative kidney function (GFR, 75-90 ml/min/1.73 m(2)), even modest CKD (GFR, 45-60 ml/min/1.73 m(2)) was associated with increased postoperative mortality (odds ratio (OR), 1.62). With greater impairment in kidney function, postoperative mortality was even more marked (GFR, 30-45 ml/min/1.73 m(2) and OR, 2.84; GFR, 15-30 ml/min/1.73 m(2) and OR, 5.56). In addition, CKD was independently associated with increased postoperative complications.Any degree of preoperative kidney impairment, even mild asymptomatic disease, is associated with clinically significant increases in 30-day postoperative morbidity and mortality following major abdominal surgery.

    View details for DOI 10.1007/s11605-013-2390-3

    View details for Web of Science ID 000333124200022

    View details for PubMedID 24241964

  • Molecular assessment of surgical-resection margins of gastric cancer by mass-spectrometric imaging PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Eberlin, L. S., Tibshirani, R. J., Zhang, J., Longacre, T. A., Berry, G. J., Bingham, D. B., Norton, J. A., Zare, R. N., Poultsides, G. A. 2014; 111 (7): 2436-2441


    Surgical resection is the main curative option for gastrointestinal cancers. The extent of cancer resection is commonly assessed during surgery by pathologic evaluation of (frozen sections of) the tissue at the resected specimen margin(s) to verify whether cancer is present. We compare this method to an alternative procedure, desorption electrospray ionization mass spectrometric imaging (DESI-MSI), for 62 banked human cancerous and normal gastric-tissue samples. In DESI-MSI, microdroplets strike the tissue sample, the resulting splash enters a mass spectrometer, and a statistical analysis, here, the Lasso method (which stands for least absolute shrinkage and selection operator and which is a multiclass logistic regression with L1 penalty), is applied to classify tissues based on the molecular information obtained directly from DESI-MSI. The methodology developed with 28 frozen training samples of clear histopathologic diagnosis showed an overall accuracy value of 98% for the 12,480 pixels evaluated in cross-validation (CV), and 97% when a completely independent set of samples was tested. By applying an additional spatial smoothing technique, the accuracy for both CV and the independent set of samples was 99% compared with histological diagnoses. To test our method for clinical use, we applied it to a total of 21 tissue-margin samples prospectively obtained from nine gastric-cancer patients. The results obtained suggest that DESI-MSI/Lasso may be valuable for routine intraoperative assessment of the specimen margins during gastric-cancer surgery.

    View details for DOI 10.1073/pnas.1400274111

    View details for Web of Science ID 000331396500018

  • Reassessment of the Current American Joint Committee on Cancer Staging System for Pancreatic Neuroendocrine Tumors JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS Qadan, M., Ma, Y., Visser, B. C., Kunz, P. L., Fisher, G. A., Norton, J. A., Poultsides, G. A. 2014; 218 (2): 188-195


    Adopting a unified staging system for pancreatic neuroendocrine tumors (PNETs) has been challenging. Currently, the American Joint Committee on Cancer (AJCC) recommends use of the pancreatic adenocarcinoma staging system for PNETs. We sought to explore the prognostic usefulness of the pancreatic adenocarcinoma staging system for PNETs.The Surveillance, Epidemiology, and End Results program data were used to identify patients with PNETs who underwent curative-intent surgical resection from 1983 to 2008. The discriminatory ability of the AJCC system was examined and a new TNM system was devised using extent of disease variables.In 1,202 patients identified, lymph node metastasis was associated with worse 10-year overall survival after resection (51% vs 63%; p < 0.0001), as was the presence of distant metastatic disease (35% vs 62%; p < 0.0001). The current AJCC system (recorded by the Surveillance, Epidemiology, and End Results program in 412 patients since 2004) distinguished 5-year overall survival only between stages I and II (p = 0.01), but not between stages II and III (p = 0.97), or stages III and IV (p = 0.36). By modifying the T stage to be based on size alone (0.1 to 1.0 cm, 1.1 to 2.0 cm, 2.1 to 4.0 cm, and >4.0 cm) and revising the TNM subgroups, we propose a novel TNM system with improved discriminatory ability between disease stages (stages I vs II; p = 0.16; II vs III; p < 0.0001; and III vs IV; p = 0.008).In this study evaluating the current AJCC staging system for PNETs, there were no significant differences detected between stages II and III or stages III and IV. We propose a novel TNM system that might better discriminate between outcomes after surgical resection of PNETs.

    View details for DOI 10.1016/j.jamcollsurg.2013.11.001

    View details for Web of Science ID 000329763900008

  • Postoperative Serum Amylase Predicts Pancreatic Fistula Formation Following Pancreaticoduodenectomy JOURNAL OF GASTROINTESTINAL SURGERY Cloyd, J. M., Kastenberg, Z. J., Visser, B. C., Poultsides, G. A., Norton, J. A. 2014; 18 (2): 348-353


    Early identification of patients at risk for developing pancreatic fistula (PF) after pancreaticoduodenectomy (PD) may facilitate prevention or treatment strategies aimed at reducing its associated morbidity.A retrospective review of 176 consecutive PD performed between 2006 and 2011 was conducted in order to analyze the association between the serum amylase on postoperative day 1 (POD1) and the development of PF.Serum amylase was recorded on POD1 in 146 of 176 PD cases (83.0 %). Twenty-seven patients (18.5 %) developed a postoperative PF: 6 type A, 19 type B, and 2 type C. Patients with a PF had a mean serum amylase on POD1 of 659 ± 581 compared to 246 ± 368 in those without a fistula (p < 0.001). On logistic regression, a serum amylase >140 U/L on POD1 was strongly associated with developing a PF (OR, 5.48; 95 % CI, 1.94-15.44). Sensitivity and specificity of a postoperative serum amylase >140 U/L was 81.5 and 55.5 %, respectively. Positive and negative predictive values were 29.3 and 93.0 %, respectively.An elevated serum amylase on POD1 may be used, in addition to other prognostic factors, to help stratify risk for developing PF following PD.

    View details for DOI 10.1007/s11605-013-2293-3

    View details for Web of Science ID 000331379100038

    View details for PubMedID 23903930

  • False positive 18F-fluorodeoxyglucose positron emission tomography/computed tomography liver lesion mimicking metastasis in 2 patients with gastroesophageal cancer. Practical radiation oncology Paudel, N., Kunz, P. L., Poultsides, G. A., Koong, A. C., Chang, D. T. 2014; 4 (6): 368-371

    View details for DOI 10.1016/j.prro.2013.11.005

    View details for PubMedID 25407856

  • Gastrointestinal Stromal Tumor: An Unusual Cause of Gastrointestinal Bleeding DIGESTIVE DISEASES AND SCIENCES Wong, R. J., Longacre, T. A., Poultsides, G., Park, W., Rothenberg, M. E. 2013; 58 (11): 3112-3116

    View details for DOI 10.1007/s10620-013-2678-x

    View details for Web of Science ID 000326188800011

    View details for PubMedID 23633157

  • Metabolomic-derived novel cyst fluid biomarkers for pancreatic cysts: glucose and kynurenine. Gastrointestinal endoscopy Park, W. G., Wu, M., Bowen, R., Zheng, M., Fitch, W. L., Pai, R. K., Wodziak, D., Visser, B. C., Poultsides, G. A., Norton, J. A., Banerjee, S., Chen, A. M., Friedland, S., Scott, B. A., Pasricha, P. J., Lowe, A. W., Peltz, G. 2013; 78 (2): 295-302 e2


    BACKGROUND: Better pancreatic cyst fluid biomarkers are needed. OBJECTIVE: To determine whether metabolomic profiling of pancreatic cyst fluid would yield clinically useful cyst fluid biomarkers. DESIGN: Retrospective study. SETTING: Tertiary-care referral center. PATIENTS: Two independent cohorts of patients (n = 26 and n = 19) with histologically defined pancreatic cysts. INTERVENTION: Exploratory analysis for differentially expressed metabolites between (1) nonmucinous and mucinous cysts and (2) malignant and premalignant cysts was performed in the first cohort. With the second cohort, a validation analysis of promising identified metabolites was performed. MAIN OUTCOME MEASUREMENTS: Identification of differentially expressed metabolites between clinically relevant cyst categories and their diagnostic performance (receiver operating characteristic [ROC] curve). RESULTS: Two metabolites had diagnostic significance-glucose and kynurenine. Metabolomic abundances for both were significantly lower in mucinous cysts compared with nonmucinous cysts in both cohorts (glucose first cohort P = .002, validation P = .006; and kynurenine first cohort P = .002, validation P = .002). The ROC curve for glucose was 0.92 (95% confidence interval [CI], 0.81-1.00) and 0.88 (95% CI, 0.72-1.00) in the first and validation cohorts, respectively. The ROC for kynurenine was 0.94 (95% CI, 0.81-1.00) and 0.92 (95% CI, 0.76-1.00) in the first and validation cohorts, respectively. Neither could differentiate premalignant from malignant cysts. Glucose and kynurenine levels were significantly elevated for serous cystadenomas in both cohorts. LIMITATIONS: Small sample sizes. CONCLUSION: Metabolomic profiling identified glucose and kynurenine to have potential clinical utility for differentiating mucinous from nonmucinous pancreatic cysts. These markers also may diagnose serous cystadenomas.

    View details for DOI 10.1016/j.gie.2013.02.037

    View details for PubMedID 23566642

  • Metabolomic-derived novel cyst fluid biomarkers for pancreatic cysts: glucose and kynurenine GASTROINTESTINAL ENDOSCOPY Park, W. G., Wu, M., Bowen, R., Zheng, M., Fitch, W. L., Pai, R. K., Wodziak, D., Visser, B. C., Poultsides, G. A., Norton, J. A., Banerjee, S., Chen, A. M., Friedland, S., Scott, B. A., Pasricha, P. J., Lowe, A. W., Peltz, G. 2013; 78 (2): 295-?
  • Colorectal cancer diagnostics: biomarkers, cell-free DNA, circulating tumor cells and defining heterogeneous populations by single-cell analysis EXPERT REVIEW OF MOLECULAR DIAGNOSTICS Kin, C., Kidess, E., Poultsides, G. A., Visser, B. C., Jeffrey, S. S. 2013; 13 (6): 581-599


    Reliable biomarkers are needed to guide treatment of colorectal cancer, as well as for surveillance to detect recurrence and monitor therapeutic response. In this review, the authors discuss the use of various biomarkers in addition to serum carcinoembryonic antigen, the current surveillance method for metastatic recurrence after resection. The clinical relevance of mutations including microsatellite instability, KRAS, BRAF and SMAD4 is addressed. The role of circulating tumor cells and cell-free DNA with regards to their implementation into clinical use is discussed, as well as how single-cell analysis may fit into a monitoring program. The detection and characterization of circulating tumor cells and cell-free DNA in colorectal cancer patients will not only improve the understanding of the development of metastasis, but may also supplant the use of other biomarkers.

    View details for DOI 10.1586/14737159.2013.811896

    View details for Web of Science ID 000331285900014

    View details for PubMedID 23895128

  • Seventh Edition (2010) of the AJCC/UICC Staging System for Gastric Adenocarcinoma: Is there Room for Improvement? ANNALS OF SURGICAL ONCOLOGY Patel, M. I., Rhoads, K. F., Ma, Y., Ford, J. M., Visser, B. C., Kunz, P. L., Fisher, G. A., Chang, D. T., Koong, A., Norton, J. A., Poultsides, G. A. 2013; 20 (5): 1631-1638


    The gastric cancer AJCC/UICC staging system recently underwent significant revisions, but studies on Asian patients have reported a lack of adequate discrimination between various consecutive stages. We sought to validate the new system on a U.S. population database.California Cancer Registry data linked to the Office of Statewide Health Planning and Development discharge abstracts were used to identify patients with gastric adenocarcinoma (esophagogastric junction and gastric cardia tumors excluded) who underwent curative-intent surgical resection in California from 2002 to 2006. AJCC/UICC stage was recalculated based on the latest seventh edition. Overall survival probabilities were calculated using the Kaplan-Meier method.Of 1905 patients analyzed, 54 % were males with a median age of 70 years. Median number of pathologically examined lymph nodes was 12 (range, 1-90); 40 % of patients received adjuvant chemotherapy, and 31 % received adjuvant radiotherapy. The seventh edition AJCC/UICC system did not distinguish outcome adequately between stages IB and IIA (P = 0.40), or IIB and IIIA (P = 0.34). By merging stage II into 1 category and moving T2N1 to stage IB and T2N2, T1N3 to stage IIIA, we propose a new grouping system with improved discriminatory abilityIn this first study validating the new seventh edition AJCC/UICC staging system for gastric cancer on a U.S. population with a relatively limited number of lymph nodes examined, we found stages IB and IIA, as well as IIB and IIIA to perform similarly. We propose a revised stage grouping for the AJCC/UICC staging system that better discriminates between outcomes.

    View details for DOI 10.1245/s10434-012-2724-5

    View details for Web of Science ID 000317308200032

    View details for PubMedID 23149854

  • Iliocaval and aortoiliac reconstruction following en bloc retroperitoneal leiomyosarcoma resection. Journal of vascular surgery Ohman, J. W., Chandra, V., Poultsides, G., Harris, E. J. 2013; 57 (3): 850-?

    View details for DOI 10.1016/j.jvs.2012.01.048

    View details for PubMedID 23446129

  • Hospital readmission after a pancreaticoduodenectomy: an emerging quality metric? HPB Kastenberg, Z. J., Morton, J. M., Visser, B. C., Norton, J. A., Poultsides, G. A. 2013; 15 (2): 142-148


    Hospital readmission has attracted attention from policymakers as a measure of quality and a target for cost reduction. The aim of the study was to evaluate the frequency and patterns of rehospitalization after a pancreaticoduodenectomy (PD).The records of all patients undergoing a PD at an academic medical centre for malignant or benign diagnoses between January 2006 and September 2011 were retrospectively reviewed. The incidence, aetiology and predictors of subsequent readmission(s) were analysed.Of 257 consecutive patients who underwent a PD, 50 (19.7%) were readmitted within 30 days from discharge. Both the presence of any post-operative complication (P = 0.049) and discharge to a nursing/rehabilitation facility or to home with health care services (P = 0.018) were associated with readmission. The most common reasons for readmission were diet intolerance (36.0%), pancreatic fistula/abscess (26.0%) and superficial wound infection (8.0%). Nine (18.0%) readmissions had lengths of stay of 2 days or less and in four of those (8.0%) diagnostic evaluation was eventually negative.Approximately one-fifth of patients require hospital readmission within 30 days of discharge after a PD. A small fraction of these readmissions are short (2 days or less) and may be preventable or manageable in the outpatient setting.

    View details for DOI 10.1111/j.1477-2574.2012.00563.x

    View details for Web of Science ID 000313548400009

    View details for PubMedID 23297725

  • Diagnostic Utility of Metabolomic-Derived Biomarkers for Pancreatic Cysts Park, W. G., Wu, M., Bowen, R., Zheng, M., Fitch, W. L., Pai, R. K., Wodziak, D., Visser, B. C., Poultsides, G. A., NORTON, J. A., Banerjee, S., Chen, A. M., Friedland, S., Pasricha, P. J., Lowe, A. W., Peltz, G. LIPPINCOTT WILLIAMS & WILKINS. 2012: 1394-1394
  • Lymph Nodes and Survival in Pancreatic Neuroendocrine Tumors ARCHIVES OF SURGERY Krampitz, G. W., Norton, J. A., Poultsides, G. A., Visser, B. C., Sun, L., Jensen, R. T. 2012; 147 (9): 820-827


    Lymph node metastases decrease survival in patients with pancreatic neuroendocrine tumors (pNETs).Prospective database searches.National Institutes of Health (NIH) and Stanford University Hospital (SUH).A total of 326 patients underwent surgical exploration for pNETs at the NIH (n = 216) and SUH (n = 110).Overall survival, disease-related survival, and time to development of liver metastases.Forty patients (12.3%) underwent enucleation and 305 (93.6%) underwent resection. Of the patients who underwent resection, 117 (35.9%) had partial pancreatectomy and 30 (9.2%) had a Whipple procedure. Forty-one patients also had liver resections, 21 had wedge resections, and 20 had lobectomies. Mean follow-up was 8.1 years (range, 0.3-28.6 years). The 10-year overall survival for patients with no metastases or lymph node metastases only was similar at 80%. As expected, patients with liver metastases had a significantly decreased 10-year survival of 30% (P < .001). The time to development of liver metastases was significantly reduced for patients with lymph node metastases alone compared with those with none (P < .001). For the NIH cohort with longer follow-up, disease-related survival was significantly different for those patients with no metastases, lymph node metastases alone, and liver metastases (P < .001). Extent of lymph node involvement in this subgroup showed that disease-related survival decreased as a function of the number of lymph nodes involved (P = .004).As expected, liver metastases decrease survival of patients with pNETs. Patients with lymph node metastases alone have a shorter time to the development of liver metastases that is dependent on the number of lymph nodes involved. With sufficient long-term follow-up, lymph node metastases decrease disease-related survival. Careful evaluation of number and extent of lymph node involvement is warranted in all surgical procedures for pNETs.

    View details for Web of Science ID 000308883700011

    View details for PubMedID 22987171

  • Pathologic Response to Preoperative Chemotherapy in Colorectal Liver Metastases: Fibrosis, not Necrosis, Predicts Outcome ANNALS OF SURGICAL ONCOLOGY Poultsides, G. A., Bao, F., Servais, E. L., Hernandez-Boussard, T., DeMatteo, R. P., Allen, P. J., Fong, Y., Kemeny, N. E., Saltz, L. B., Klimstra, D. S., Jarnagin, W. R., Shia, J., D'Angelica, M. I. 2012; 19 (9): 2797-2804


    Pathologic response to preoperative chemotherapy for colorectal liver metastases (CLM) is associated with survival after hepatectomy. Histologically, dominant response patterns include fibrosis, necrosis and/or acellular mucin, but some of these changes can appear without previous chemotherapy and their individual correlation with outcome is unknown.Pathology slides from patients who underwent CLM resection (irrespective of preoperative chemotherapy status) were rereviewed by a blinded pathologist. Pathologic response was recorded as the summation of percentage necrosis, fibrosis and acellular mucin. Associations between pathologic response, its components, preoperative chemotherapy, and survival were analyzed.Pathology slides were rereviewed in 366 patients undergoing CLM resection from 2003 to 2007. Preoperative chemotherapy was administered in 249 (68 %) patients, who, when compared to no preoperative chemotherapy patients, had higher rates of overall pathologic response (57 vs. 46 %, P < .01), fibrosis (21 vs. 12 %, P < .01) and acellular mucin (6 vs. 3 %, P = .05) but similar rates of necrosis (30 vs. 31 %, P = .30). In patients receiving preoperative chemotherapy, overall pathologic response ? 75 % (5 year, 83 vs. 47 %, P < .01) and fibrosis ? 40 % (5 year, 87 vs. 51 %, P < .01) independently correlated with disease-specific survival after hepatectomy. Preoperative hepatic artery infusion chemotherapy (P = .04) and bevacizumab (P = .05) were marginally associated with overall pathologic response and fibrosis, respectively.Fibrosis is the predominant chemotherapy-related pathologic alteration driving the association of treatment response with survival after CLM resection. Necrosis in CLM is not related to chemotherapy or outcome.

    View details for DOI 10.1245/s10434-012-2335-1

    View details for Web of Science ID 000308357100005

    View details for PubMedID 22476753

  • Failure to comply with NCCN guidelines for the management of pancreatic cancer compromises outcomes HPB Visser, B. C., Ma, Y., Zak, Y., Poultsides, G. A., Norton, J. A., Rhoads, K. F. 2012; 14 (8): 539-547


    There are little data available regarding compliance with the National Comprehensive Cancer Network (NCCN) guidelines. We investigated variation in the management of pancreatic cancer (PC) among large hospitals in California, USA, specifically to evaluate whether compliance with NCCN guidelines correlates with patient outcomes.The California Cancer Registry was used to identify patients treated for PC from 2001 to 2006. Only hospitals with ? 400 beds were included to limit evaluation to centres possessing resources to provide multimodality care (n= 50). Risk-adjusted multivariable models evaluated predictors of adherence to stage-specific NCCN guidelines for PC and mortality.In all, 3706 patients were treated for PC in large hospitals during the study period. Compliance with NCCN guidelines was only 34.5%. Patients were less likely to get recommended therapy with advanced age and low socioeconomic status (SES). Using multilevel analysis, controlling for patient factors (including demographics and comorbidities), hospital factors (e.g. size, academic affiliation and case volume), compliance with NCCN guidelines was associated with a reduced risk of mortality [odds ratio (OR) for death 0.64 (0.53-0.77, P < 0.0001)].There is relatively poor overall compliance with the NCCN PC guidelines in California's large hospitals. Higher compliance rates are correlated with improved survival. Compliance is an important potential measure of the quality of care.

    View details for DOI 10.1111/j.1477-2574.2012.00496.x

    View details for Web of Science ID 000305993800007

    View details for PubMedID 22762402

  • Pancreatic Neuroendocrine Tumors: Radiographic Calcifications Correlate with Grade and Metastasis ANNALS OF SURGICAL ONCOLOGY Poultsides, G. A., Huang, L. C., Chen, Y., Visser, B. C., Pai, R. K., Jeffrey, R. B., Park, W. G., Chen, A. M., Kunz, P. L., Fisher, G. A., Norton, J. A. 2012; 19 (7): 2295-2303


    Studies to identify preoperative prognostic variables for pancreatic neuroendocrine tumor (PNET) have been inconclusive. Specifically, the prevalence and prognostic significance of radiographic calcifications in these tumors remains unclear.From 1998 to 2009, a total of 110 patients with well-differentiated PNET underwent surgical resection at our institution. Synchronous liver metastases present in 31 patients (28%) were addressed surgically with curative intent. Patients with high-grade PNET were excluded. The presence of calcifications in the primary tumor on preoperative computed tomography was recorded and correlated with clinicopathologic variables and overall survival.Calcifications were present in 16% of patients and were more common in gastrinomas and glucagonomas (50%), but never encountered in insulinomas. Calcified tumors were larger (median size 4.5 vs. 2.3 cm, P=0.04) and more commonly associated with lymph node metastasis (75 vs. 35%, P=0.01), synchronous liver metastasis (62 vs. 21%, P<0.01), and intermediate tumor grade (80 vs. 31%, P<0.01). On multivariate analysis of factors available preoperatively, calcifications (P=0.01) and size (P<0.01) remained independent predictors of lymph node metastasis. Overall survival after resection was significantly worse in the presence of synchronous liver metastasis (5-year, 64 vs. 86%, P=0.04), but not in the presence of radiographic calcifications.Calcifications on preoperative computed tomography correlate with intermediate grade and lymph node metastasis in well-differentiated PNET. This information is available preoperatively and supports the routine dissection of regional lymph nodes through formal pancreatectomy rather than enucleation in calcified PNET.

    View details for DOI 10.1245/s10434-012-2305-7

    View details for Web of Science ID 000305558000030

    View details for PubMedID 22396008

  • Hybrid Treatment of Celiac Artery Compression (Median Arcuate Ligament) Syndrome DIGESTIVE DISEASES AND SCIENCES Palmer, O. P., Tedesco, M., Casey, K., Lee, J. T., Poultsides, G. A. 2012; 57 (7): 1782-1785

    View details for DOI 10.1007/s10620-011-2019-x

    View details for Web of Science ID 000305746100009

    View details for PubMedID 22212729

  • Duodenal Adenocarcinoma: Clinicopathologic Analysis and Implications for Treatment ANNALS OF SURGICAL ONCOLOGY Poultsides, G. A., Huang, L. C., Cameron, J. L., Tuli, R., Lan, L., Hruban, R. H., Pawlik, T. M., Herman, J. M., Edil, B. H., Ahuja, N., Choti, M. A., Wolfgang, C. L., Schulick, R. D. 2012; 19 (6): 1928-1935


    Duodenal adenocarcinoma is a rare cancer usually studied as a group with periampullary or small bowel adenocarcinoma; therefore, its natural history is poorly understood.Patients with duodenal adenocarcinoma were identified from a single-institution pancreaticoduodenectomy database. Patients with adenocarcinoma arising from the ampulla of Vater were excluded. Univariate and multivariate analyses were performed to identify clinicopathologic variables associated with survival and recurrence after resection.From 1984 to 2006, a total of 122 patients with duodenal adenocarcinoma underwent pancreaticoduodenectomy. Overall survival after resection was 48% at 5 years and 41% at 10 years. Five-year survival decreased as the number of lymph nodes involved by metastasis increased from 0 to 1-3 to ? 4 (68%, 58%, 17%, respectively, P < 0.01) and as the lymph node ratio increased from 0 to >0-0.2 to >0.2-0.4 to >0.4 (68%, 57%, 14%, 14%, respectively, P < 0.01). Lymph node metastasis was the only independent predictor of decreased survival in multivariate analysis. Recurrence after resection was predominantly distant (81%). Adjuvant chemoradiation did not decrease local recurrence or prolong overall survival; however, patients who received chemoradiation more commonly had nodal metastasis (P = 0.03).The prognostic significance of both the absolute number and ratio of involved lymph nodes emphasizes the need for adequate lymphadenectomy to accurately stage duodenal adenocarcinoma. The mostly distant pattern of recurrence underscores the need for the development of effective systemic therapies.

    View details for DOI 10.1245/s10434-011-2168-3

    View details for Web of Science ID 000304209800029

    View details for PubMedID 22167476

  • Intensity-Modulated Radiotherapy for Pancreatic Adenocarcinoma Abelson, J. A., Murphy, J. D., Minn, A. Y., Chung, M., Fisher, G. A., Ford, J. M., Kunz, P., Norton, J. A., Visser, B. C., Poultsides, G. A., Koong, A. C., Chang, D. T. ELSEVIER SCIENCE INC. 2012: E595-E601


    To report the outcomes and toxicities in patients treated with intensity-modulated radiotherapy (IMRT) for pancreatic adenocarcinoma.Forty-seven patients with pancreatic adenocarcinoma were treated with IMRT between 2003 and 2008. Of these 47 patients, 29 were treated adjuvantly and 18 definitively. All received concurrent 5-fluorouracil chemotherapy. The treatment plans were optimized such that 95% of the planning target volume received the prescription dose. The median delivered dose for the adjuvant and definitive patients was 50.4 and 54.0 Gy, respectively.The median age at diagnosis was 63.9 years. For adjuvant patients, the 1- and 2-year overall survival rate was 79% and 40%, respectively. The 1- and 2-year recurrence-free survival rate was 58% and 17%, respectively. The local-regional control rate at 1 and 2 years was 92% and 80%, respectively. For definitive patients, the 1-year overall survival, recurrence-free survival, and local-regional control rate was 24%, 16%, and 64%, respectively. Four patients developed Grade 3 or greater acute toxicity (9%) and four developed Grade 3 late toxicity (9%).Survival for patients with pancreatic cancer remains poor. A small percentage of adjuvant patients have durable disease control, and with improved therapies, this proportion will increase. Systemic therapy offers the greatest opportunity. The present results have demonstrated that IMRT is well tolerated. Compared with those who received three-dimensional conformal radiotherapy in previously reported prospective clinical trials, patients with pancreatic adenocarcinoma treated with IMRT in our series had improved acute toxicity.

    View details for DOI 10.1016/j.ijrobp.2011.09.035

    View details for Web of Science ID 000300980300003

    View details for PubMedID 22197234

  • Diagnostic accuracy of cyst fluid amphiregulin in pancreatic cysts BMC GASTROENTEROLOGY Tun, M. T., Pai, R. K., Kwok, S., Dong, A., Gupta, A., Visser, B. C., Norton, J. A., Poultsides, G. A., Banerjee, S., Van Dam, J., Chen, A. M., Friedland, S., Scott, B. A., Verma, R., Lowe, A. W., Park, W. G. 2012; 12


    Accurate tests to diagnose adenocarcinoma and high-grade dysplasia among mucinous pancreatic cysts are clinically needed. This study evaluated the diagnostic utility of amphiregulin (AREG) as a pancreatic cyst fluid biomarker to differentiate non-mucinous, benign mucinous, and malignant mucinous cysts.A single-center retrospective study to evaluate AREG levels in pancreatic cyst fluid by ELISA from 33 patients with a histological gold standard was performed.Among the cyst fluid samples, the median (IQR) AREG levels for non-mucinous (n = 6), benign mucinous (n = 15), and cancerous cysts (n = 15) were 85 pg/ml (47-168), 63 pg/ml (30-847), and 986 pg/ml (417-3160), respectively. A significant difference between benign mucinous and malignant mucinous cysts was observed (p = 0.025). AREG levels greater than 300 pg/ml possessed a diagnostic accuracy for cancer or high-grade dysplasia of 78% (sensitivity 83%, specificity 73%).Cyst fluid AREG levels are significantly higher in cancerous and high-grade dysplastic cysts compared to benign mucinous cysts. Thus AREG exhibits potential clinical utility in the evaluation of pancreatic cysts.

    View details for DOI 10.1186/1471-230X-12-15

    View details for Web of Science ID 000301923400002

    View details for PubMedID 22333441

  • An HNF4 alpha-miRNA Inflammatory Feedback Circuit Regulates Hepatocellular Oncogenesis CELL Hatziapostolou, M., Polytarchou, C., Aggelidou, E., Drakaki, A., Poultsides, G. A., Jaeger, S. A., Ogata, H., Karin, M., Struhl, K., Hadzopoulou-Cladaras, M., Iliopoulos, D. 2011; 147 (6): 1233-1247


    Hepatocyte nuclear factor 4α (HNF4α) is essential for liver development and hepatocyte function. Here, we show that transient inhibition of HNF4α initiates hepatocellular transformation through a microRNA-inflammatory feedback loop circuit consisting of miR-124, IL6R, STAT3, miR-24, and miR-629. Moreover, we show that, once this circuit is activated, it maintains suppression of HNF4α and sustains oncogenesis. Systemic administration of miR-124, which modulates inflammatory signaling, prevents and suppresses hepatocellular carcinogenesis by inducing tumor-specific apoptosis without toxic side effects. As we also show that this HNF4α circuit is perturbed in human hepatocellular carcinomas, our data raise the possibility that manipulation of this microRNA feedback-inflammatory loop has therapeutic potential for treating liver cancer.

    View details for DOI 10.1016/j.cell.2011.10.043

    View details for Web of Science ID 000298148100014

    View details for PubMedID 22153071

  • Hybrid Resection of Duodenal Tumors JOURNAL OF LAPAROENDOSCOPIC & ADVANCED SURGICAL TECHNIQUES Poultsides, G. A., Pappou, E. P., Bloom, G. P., Orlando, R. 2011; 21 (7): 603-608


    The aim of this study was to review our experience with the hand-assisted laparoscopic management of duodenal tumors with no or low malignant potential and to compare this approach with published case reports of purely laparoscopic local duodenal resection.Eight cases of hand-assisted laparoscopic local duodenal resection performed from 2000 to 2008 were retrospectively reviewed. Hand-assistance was utilized for complete duodenal mobilization, and local duodenal resection was accomplished extracorporeally through the hand-access incision. Patient and tumor characteristics, operative time, length of stay, and complications were compared with 18 cases of totally laparoscopic local excision of duodenal tumors published since 1997. Patients with ampullary tumors were excluded.Compared with the purely laparoscopic approach, the hand-assisted technique was associated with shorter operative time (179 versus 131 minutes, P=.03) and was more commonly used for lesions located in the third portion of the duodenum (0% versus 37.5%, P=.02). Tumor size (2.9 cm versus 3.2 cm, P=.61) and length of hospital stay (5.9 versus 5.9 days, P=.96) were similar between the two groups. The rate of complications was also comparable (0% versus 12.5%, P=.31); 1 of 8 patients in the hand-assisted group developed an incisional hernia at the hand-access site.Hand-assisted laparoscopic local duodenal resection is a feasible, safe, and effective alternative to the totally laparoscopic approach. In addition to being associated with comparable length of hospital stay, hand-assistance can shorten operative time by facilitating duodenal mobilization as well as extracorporeal duodenal resection and closure.

    View details for DOI 10.1089/lap.2010.0387

    View details for Web of Science ID 000294059200006

    View details for PubMedID 21774700

  • Laparoscopic Duodenojejunostomy for Superior Mesenteric Artery Syndrome DIGESTIVE DISEASES AND SCIENCES Magee, G., Slater, B. J., Lee, J. T., Poultsides, G. A. 2011; 56 (9): 2528-2531

    View details for DOI 10.1007/s10620-011-1757-0

    View details for Web of Science ID 000294800100005

    View details for PubMedID 21643740

  • Surgical Management of Neuroendocrine Tumors of the Gastrointestinal Tract ONCOLOGY-NEW YORK Huang, L. C., Poultsides, G. A., Norton, J. A. 2011; 25 (9): 794-803


    Neuroendocrine tumors of the pancreas (islet cell tumors) and of the luminal gastrointestinal tract (carcinoids) are a heterogeneous group of epithelial neoplasms that share certain common characteristics. First, they are similar histologically and are difficult to distinguish under light microscopy. Second, they can be associated with hypersecretory syndromes. Third, they are generally slow-growing and have a better prognosis than adenocarcinomas at the same site; however, they do become incurable when they progress to unresectable metastatic disease. Surgery is the only curative treatment and is recommended for most patients for whom cross-sectional imaging suggests that complete resection is possible. This article reviews the surgical management of gastrointestinal neuroendocrine tumors, including the preoperative control of hormonal symptoms, extent of resection required, postoperative outcomes, and differing management strategies as determined by whether the tumor has arisen sporadically or as part of a familial disorder, such as multiple endocrine neoplasia type 1 (MEN1).

    View details for Web of Science ID 000293651000002

    View details for PubMedID 21936439

  • Ruptured Biliary Cystadenoma Managed by Angiographic Embolization and Interval Partial Hepatectomy DIGESTIVE DISEASES AND SCIENCES Ghole, S. A., Bakhtary, S., Staudenmayer, K., Sze, D. Y., Pai, R. K., Visser, B. C., Norton, J. A., Poultsides, G. A. 2011; 56 (7): 1949-1953

    View details for DOI 10.1007/s10620-011-1677-z

    View details for Web of Science ID 000291481800006

    View details for PubMedID 21445579

  • Pancreatic Endocrine Tumors With Major Vascular Abutment, Involvement, or Encasement and Indication for Resection ARCHIVES OF SURGERY Norton, J. A., Harris, E. J., Chen, Y., Visser, B. C., Poultsides, G. A., Kunz, P. C., Fisher, G. A., Jensen, R. T. 2011; 146 (6): 724-732


    Surgery for pancreatic endocrine tumors (PETs) with blood vessel involvement is controversial.Resection of PETs with major blood vessel involvement can be beneficial.The combined databases of the National Institutes of Health and Stanford University hospitals were queried.Operation, pathologic condition, complications, and disease-free and overall survival.Of 273 patients with PETs, 46 (17%) had preoperative computed tomography evidence of major vascular involvement. The mean size for the primary PET was 5.0 cm. The involved major vessel was as follows: portal vein (n = 20), superior mesenteric vein or superior mesenteric artery (n = 16), inferior vena cava (n = 4), splenic vein (n = 4), and heart (n = 2). Forty-two of 46 patients had a PET removed: 12 (27%) primary only, 30 (68%) with lymph nodes, and 18 (41%) with liver metastases. PETs were removed by either enucleation (n = 7) or resection (n = 35). Resections included distal or subtotal pancreatectomy in 23, Whipple in 10, and total in 2. Eighteen patients had concomitant liver resection: 10 wedge resection and 8 anatomic resections. Nine patients had vascular reconstruction: each had reconstruction of the superior mesenteric vein and portal vein, and 1 had concomitant reconstruction of the superior mesenteric artery. There were no deaths, but 12 patients had complications. Eighteen patients (41%) were immediately disease free, and 5 recurred with follow-up, leaving 13 (30%) disease-free long term. The 10-year overall survival was 60%. Functional tumors were associated with a better overall survival (P < .001), and liver metastases decreased overall survival (P < .001).These findings suggest that surgical resection of PETs with vascular abutment/invasion and nodal or distant metastases is indicated.

    View details for Web of Science ID 000291851500018

    View details for PubMedID 21690450

  • Colloid Carcinoma of the Pancreas DIGESTIVE DISEASES AND SCIENCES Plerhoples, T. A., Ahdoot, M., DiMaio, M. A., Pai, R. K., Park, W. G., Poultsides, G. A. 2011; 56 (5): 1295-1298

    View details for DOI 10.1007/s10620-011-1573-6

    View details for Web of Science ID 000289899200008

    View details for PubMedID 21253833

  • Reassessing the need for primary tumor surgery in unresectable metastatic colorectal cancer: overview and perspective. Therapeutic advances in medical oncology Poultsides, G. A., Paty, P. B. 2011; 3 (1): 35-42


    In the absence of symptoms, primary tumor resection in patients who present with unresectable metastatic colorectal cancer is of uncertain benefit. Prophylactic surgery has been traditionally considered in this setting in order to prevent subsequent complications of perforation, obstruction, or bleeding later during the treatment course, which may require urgent surgery associated with higher mortality. However, recent data have called into question the efficacy of this upfront surgical strategy. We provide a brief overview of how current combinations of systemic chemotherapy including fluorouracil, oxaliplatin, irinotecan, and targeted biologic agents have allowed improved local (in addition to distant) tumor control, significantly decreasing the incidence of late primary-related complications requiring surgery from roughly 20% in the era of single-agent fluoropyrimidine chemotherapy to almost 7% in the era of modern triple-drug chemotherapy. In addition, we attempt to highlight those factors most associated with subsequent primary tumor-related complications in an effort to identify the subset of patients with synchronous metastatic colorectal cancer who might benefit from a surgery-first approach. Finally, we discuss modern nonsurgical options available for palliation of the primary colorectal tumor and review the outcome of patients for which emergent surgery is eventually required to address primary-related symptoms.

    View details for DOI 10.1177/1758834010386283

    View details for PubMedID 21789154

  • Intrahepatic Cholangiocarcinoma SURGICAL CLINICS OF NORTH AMERICA Poultsides, G. A., Zhu, A. X., Choti, M. A., Pawlik, T. M. 2010; 90 (4): 817-?


    Intrahepatic cholangiocarcinoma (ICC) is a primary cancer of the bile ducts, arising from malignant transformation of the epithelial cells that line the biliary apparatus. ICC is relatively uncommon, but its incidence is on the increase. ICC is frequently discovered as an incidental, indeterminate liver mass. Surgical resection of ICC represents the only potentially curative therapeutic option. The role of routine hilar lymphadenectomy is controversial, but should be considered to optimize staging. Although adjuvant chemotherapy and radiotherapy is probably not supported by current data, each should strongly be considered in patients with lymph node metastasis or an R1 resection. For those patients with inoperable disease, locoregional therapy with transarterial chemoembolization can be considered.

    View details for DOI 10.1016/j.suc.2010.04.011

    View details for Web of Science ID 000280985500015

    View details for PubMedID 20637950

  • Histopathologic Basis for the Favorable Survival after Resection of Intraductal Papillary Mucinous Neoplasm-Associated Invasive Adenocarcinoma of the Pancreas ANNALS OF SURGERY Poultsides, G. A., Reddy, S., Cameron, J. L., Hruban, R. H., Pawlik, T. M., Ahuja, N., Jain, A., Edil, B. H., Iacobuzio-Donahue, C. A., Schulick, R. D., Wolfgang, C. L. 2010; 251 (3): 470-476


    To identify pathologic features that may account for the favorable survival after resection of invasive pancreatic adenocarcinoma arising in the setting of intraductal papillary mucinous neoplasm (IPMN) compared with standard pancreatic ductal adenocarcinoma (PDA) in the absence of IPMN.The 5-year survival after resection of IPMN-associated invasive adenocarcinoma is reported to be between 40% and 60%, which is superior to the 10-25%, typically cited after resection of standard PDA. It remains unclear whether this represents distinct biology or simply a tendency for earlier presentation of IPMN-associated invasive adenocarcinoma.A single institution's prospective pancreatic resection database was retrospectively reviewed to identify patients with invasive pancreatic adenocarcinoma who underwent pancreatectomy with curative intent. Log rank and Cox regression analysis were used to identify factors associated with survival.From 1995 to 2006, 1260 consecutive patients were identified, 132 (10%) with IPMN-associated invasive adenocarcinoma and 1128 (90%) with standard PDA. Actuarial 5-year survival was 42% after resection for IPMN-associated versus 19% for standard PDA (P < 0.001). However, compared with standard PDA, invasive adenocarcinoma arising within an IPMN was associated with a lower incidence of (1) advanced T stage (T2-T4, 96% vs. 73%, P < 0.001); (2) regional lymph node metastasis (78% vs. 51%, P < 0.001); (3) poor tumor differentiation (44% vs. 26%, P < 0.001); (4) vascular invasion (54% vs. 33%, P < 0.001); (5) perineural invasion (92% vs. 63%, P < 0.001); and (6) microscopic margin involvement (28% vs. 14%, P < 0.001). Specifically, in the presence of any one of the aforementioned adverse pathologic characteristics, outcomes after resection for IPMN-associated and standard PDA were not significantly different.The favorable biologic behavior of IPMN-associated compared with standard PDA is based on its lower rate of advanced T stage, lymph node metastasis, high tumor grade, positive resection margin, perineural, and vascular invasion. In the presence of any one of the aforementioned adverse pathologic characteristics, however, survival outcomes after resection of IPMN-associated and after resection of standard pancreatic adenocarcinoma are similar.

    View details for DOI 10.1097/SLA.0b013e3181cf8a19

    View details for Web of Science ID 000275060800014

    View details for PubMedID 20142731

  • Hepatic resection for colorectal metastases: the impact of surgical margin status on outcome HPB Poultsides, G. A., Schulick, R. D., Pawlik, T. M. 2010; 12 (1): 43-49


    An R0 margin width of 1 cm has traditionally been considered a prerequisite to minimize local recurrence and optimize survival following hepatic resection for metastatic colorectal cancer. However, recent data have called into question the prognostic importance of the '1-cm rule'. Specifically, several studies have noted that, although an R0 resection is important, the actual margin width may not be as critical. We provide a brief overview of the impact of an R1 vs. an R0 resection on local recurrence and overall survival. In addition, we specifically review the impact of margin width in patients who have undergone an R0 resection. Finally, we highlight those factors most associated with an increased likelihood of an R1 resection and provide recommendations for avoiding and dealing with microscopic carcinoma discovered intraoperatively at the cut parenchymal transection margin.

    View details for DOI 10.1111/j.1477-2574.2009.00121.x

    View details for Web of Science ID 000286434900007

    View details for PubMedID 20495644

  • Outcome of Primary Tumor in Patients With Synchronous Stage IV Colorectal Cancer Receiving Combination Chemotherapy Without Surgery As Initial Treatment JOURNAL OF CLINICAL ONCOLOGY Poultsides, G. A., Servais, E. L., Saltz, L. B., Patil, S., Kemeny, N. E., Guillem, J. G., Weiser, M., Temple, L. K., Wong, W. D., Paty, P. B. 2009; 27 (20): 3379-3384


    The purpose of this study was to describe the frequency of interventions necessary to palliate the intact primary tumor in patients who present with synchronous, stage IV colorectal cancer (CRC) and who receive up-front modern combination chemotherapy without prophylactic surgery.By using a prospective institutional database, we identified 233 consecutive patients from 2000 through 2006 with synchronous metastatic CRC and an unresected primary tumor who received oxaliplatin- or irinotecan-based, triple-drug chemotherapy (infusional fluorouracil, leucovorin, and oxaliplatin; bolus fluorouracil, leucovorin, and irinotecan; or fluorouracil, leucovorin, and irinotecan) with or without bevacizumab as their initial treatment. The incidence of subsequent use of surgery, radiotherapy, and/or endoluminal stenting to manage primary tumor complications was recorded.Of 233 patients, 217 (93%) never required surgical palliation of their primary tumor. Sixteen patients (7%) required emergent surgery for primary tumor obstruction or perforation, 10 patients (4%) required nonoperative intervention (ie, stent or radiotherapy), and 213 (89%) never required any direct symptomatic management for their intact primary tumor. Of those 213 patients, 47 patients (20%) ultimately underwent elective colon resection at the time of metastasectomy, and eight patients (3%) underwent this resection during laparotomy for hepatic artery infusion pump placement. Use of bevacizumab, location of the primary tumor in the rectum, and metastatic disease burden were not associated with increased intervention rate.Most patients with synchronous, stage IV CRC who receive up-front modern combination chemotherapy never require palliative surgery for their intact primary tumor. These data support the use of chemotherapy, without routine prophylactic resection, as the appropriate standard practice for patients with neither obstructed nor hemorrhaging primary colorectal tumors in the setting of metastatic disease.

    View details for DOI 10.1200/JCO.2008.20.9817

    View details for Web of Science ID 000267821400019

    View details for PubMedID 19487380

  • Image of the Month Left Paraduodenal Hernia ARCHIVES OF SURGERY Poultsides, G. A., Zani, S., Bloom, P., Tishler, D. S. 2009; 144 (3): 287-288

    View details for Web of Science ID 000264218700021

    View details for PubMedID 19289672

  • Epigenetic regulation of hTERT promoter in hepatocellular carcinomas INTERNATIONAL JOURNAL OF ONCOLOGY Iliopoulos, D., Satra, M., Drakaki, A., Poultsides, G. A., Tsezou, A. 2009; 34 (2): 391-399


    Although hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide, the molecular pathogenesis of the disease has not been elucidated. Several studies have shown that telomerase activity and hTERT expression are increased in HCCs. In the present study we tried to elucidate hTERT transcriptional and epigenetic regulatory mechanisms in HCC. hTERT expression was tested by real-time PCR and DNA methylation status was assessed by MethyLight and DNA bisulfite sequencing analyses in 106 tissues (64 with HCC and 42 without liver disorders) and also in 7 hepatocarcinoma cell lines (HepG2, HepG3B2, C3A, SNU-182, SNU-398, SBU-449 and SNU-475). hTERT expression levels were inversely correlated with DNA methylation levels in HCC and normal tissues (r=-0.859). hTERT expression was found to be regulated by DNA methylation and histone H3-K9 modifications, affecting the ability of c-myc binding in E-box 1 site in hTERT promoter. Additionally, c-myc siRNA liposomal down-regulation inhibited significantly hTERT expression (p<0.05). Thus, we propose that hTERT is regulated by a combination of epigenetic mechanisms (DNA methylation and histone modifications) and by the transcription factor c-myc in HCC.

    View details for DOI 10.3892/ijo_00000162

    View details for Web of Science ID 000262619500012

    View details for PubMedID 19148473

  • Angiographic embolization for gastroduodenal hemorrhage ARCHIVES OF SURGERY Poultsides, G. A., Kim, C. J., Orlando, R., Peros, G., Halliscy, M. J., Vignati, P. V. 2008; 143 (5): 457-461


    To examine the safety, efficacy, and predictors of outcome of angiographic embolization in the management of gastroduodenal hemorrhage.Retrospective record review.University-affiliated tertiary care center.All of the patients were referred after endoscopic treatment failure. Surgery was not immediately considered because of poor surgical risk, refusal to consent, or endoscopist's decision. Patients with coagulopathy, hemobilia, and variceal or traumatic upper gastrointestinal tract bleeding were excluded from review.Between January 1, 1996, and December 31, 2006, 70 embolization procedures were performed in 57 patients.Technical success rate (target vessel devascularization), clinical success rate (in-hospital cessation of bleeding without further endoscopic, radiologic, or surgical intervention), and complications.The technical success rate was 94% (66 of 70 angiographies). The primary clinical success rate was 51% (29 of 57 patients), and the clinical success rate after repeat embolization was 56% (32 of 57 patients). Two factors were found to be independent predictors of poor outcome by multivariate analysis: recent duodenal ulcer suture ligation (P = .03) and blood transfusion of more than 6 units prior to the procedure (P = .04). There was no predictive value for angiographic failure based on age, sex, prior coagulopathy, renal failure at presentation, immunocompromised status, multiple organ system failure, empirical (blind) embolization, and use of permanent vs temporary embolic agents. Repeat embolizations were helpful for postsphincterotomy bleeding. Major ischemic complications (4 patients [7%]) were associated with previous foregut surgery.Angiographic embolization for gastroduodenal hemorrhage was associated with in-hospital rebleeding in almost half of the patients. Angiographic failure can be predicted if embolization is performed late, following blood transfusion of more than 6 units, or for rehemorrhage from a previously suture-ligated duodenal ulcer.

    View details for Web of Science ID 000255691800004

    View details for PubMedID 18490553

  • Hand-assisted laparoscopic management of liver tumors SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES Poultsides, G., Brown, M., Orlando, R. 2007; 21 (8): 1275-1279


    Laparoscopy has clearly advanced the treatment of many diseases related to the liver and biliary tree. The addition of hand assistance can further facilitate minimally invasive liver surgery by providing tactile feedback, atraumatic and versatile retraction, finger-fracture parenchyma dissection, and more precise placement of probes and staplers.Over a 7-year period, 28 patients with liver tumors underwent 31 hand-assisted laparoscopic operations at a tertiary care center. The candidates for hand-assisted laparoscopic resection were patients with lesions involving two hepatic segments or fewer located at the inferior edge of the liver (segments 5 and 6), or confined to the left lateral segment (segments 2 and 3). Ablation was reserved for patients with poor functional status or limited hepatic reserve, and hand-assistance was added for laparoscopic ablation of centrally located tumors (segments 7, 8, and 4a).The selection criteria were met by 52 patients, 6 of whom had benign lesions. The remaining 46 patients had malignant disease, and 15 of these patients (33%) were found to have extrahepatic disease: 11 at initial laparoscopy and 4 at hand-assisted abdominal exploration. Manual exploration also detected additional intrahepatic treatable lesions in two cases. A total of 19 patients (68%) had metastatic disease, and 3 (11%) had primary liver cancer. The most extensive resections were five left lateral segmentectomies. All margins were negative. The mean operative time was 2.75 h, and the mean blood loss was 230 ml. Two diaphragmatic injuries occurred during ablation of segment 8 lesions. Three cases were converted to open surgery because of adhesions. The mean hospital stay was 3.7 days. A group of 15 patients who had metastatic colorectal cancer treated with resection and/or ablation had a mean follow-up period of 24 months (range, 2-61 months) and a mean survival time of 36 months.For selected patients, the hand-assisted technique can be applied safely and effectively to laparoscopic liver surgery and may identify the presence of previously undetectable intrahepatic or extrahepatic disease.

    View details for DOI 10.1007/s00464-006-9174-8

    View details for Web of Science ID 000248737700003

    View details for PubMedID 17479339

  • Carcinoid of the ampulla of Vater: Morpholdgic features and clinical implications WORLD JOURNAL OF GASTROENTEROLOGY Poultsides, G. A., Frederick, W. A. 2006; 12 (43): 7058-7060


    Carcinoids involving the ampulla of Vater are rare lesions that may produce painless jaundice. The published data indicate that these tumors, in contrast to their midgut counterparts, metastasize in approximately half of cases irrespective of primary tumor size. Therefore, radical excision in the form of pancreaticoduodenectomy is recommended regardless of tumor size. As with other gastrointestinal carcinoid tumors, biological treatment with octreotide analogues can be applied to symptomatic patients. Tumor-targeted radioactive therapy is a newly emerging treatment option. We here report case of a carcinoid tumor of the ampulla of Vater presenting as painless jaundice in a 65-year old man and review the relevant literature, giving special attention to the morphologic features, clinical characteristics, and treatment modalities associated with this disease process.

    View details for Web of Science ID 000242299300026

    View details for PubMedID 17109507

  • Range of movement in the wrist as a diagnostic tool in radial-sided wrist pain SCANDINAVIAN JOURNAL OF PLASTIC AND RECONSTRUCTIVE SURGERY AND HAND SURGERY Wollstein, R., Watson, H. K., Poultsides, G., Wear-Maggitti, K., Carlson, L. 2006; 40 (4): 230-233


    Kienböck disease is diagnosed by imaging studies, and is often difficult to diagnose in its early stages. Our clinical impression is that wrist movement is more limited in Kienböck disease than when radial-sided wrist pain is caused by other conditions. The purpose of this study was to determine the use of wrist movement in differentiating between early Kienböck disease and radial-sided sprained wrist. We retrospectively reviewed 62 cases of Kienböck disease and 49 patients with radial-sided wrist sprain. Wrist movement at presentation was recorded. The two groups differed significantly in flexion and extension (p<0.001). The ability of movement of the affected wrist relative to the normal side to distinguish between the groups was excellent (AUC = 0.96, 0.97, respectively). The ability of wrist movement measurements to differentiate between early Kienböck disease and radial-sided wrist sprain emphasises that wrist movement should be measured prior to invasive or expensive testing.

    View details for DOI 10.1080/02844310600679590

    View details for Web of Science ID 000239816700007

    View details for PubMedID 16911997

  • Portal vein thrombosis after laparoscopic colectomy: Thrombolytic therapy via the superior mesenteric vein AMERICAN SURGEON Poultsides, G. A., Lewis, W. C., Feld, R., Walters, D. L., Cherry, D. A., Ruby, S. T. 2005; 71 (10): 856-860


    Portal vein thrombosis is a rare but well-reported complication after laparoscopic surgery. We present a case of portomesenteric venous thrombosis that occurred 8 days after a laparoscopic-assisted right hemicolectomy. Systemic anticoagulation failed to improve symptoms. The early postoperative state precluded the use of transarterial thrombolytic therapy. Transjugular intrahepatic catheter-directed infusion of urokinase into the superior mesenteric vein resulted in clearance of thrombus and resolution of symptoms. The published data on laparoscopy-induced splanchnic venous thrombosis and transjugular intrahepatic intramesenteric thrombolysis are discussed.

    View details for Web of Science ID 000232812000013

    View details for PubMedID 16468535

  • Common origins of carotid and subclavian arterial systems: Report of a rare aortic arch variant ANNALS OF VASCULAR SURGERY Poultsides, G. A., Lolis, E. D., VASQUEZ, J., Drezner, A. D., Venieratos, D. 2004; 18 (5): 597-600


    An aberrant right subclavian artery (aSA) arising from the proximal descending aorta is one of the most common anomalies of the aortic arch. We present our experience with an asymptomatic atypical aSA variant found during routine anatomic dissection. This aortic arch variant had two branches, the first being a bicarotid trunk and the second being a common trunk for both subclavian arteries. The right subclavian artery traveled behind the esophagus to reach the right upper extremity, thus forming an incomplete vascular ring around the trachea and the esophagus. The literature has been silent about the existence of this exact aSA variation. A plausible embryologic explanation is provided. An aSA is rarely symptomatic, but when symptoms do occur and intervention is warranted, it is important for surgeons and radiologists alike to be aware of the vascular anomalies that may potentially coexist with this entity. The surgical and endovascular options associated with this unique vascular anomaly are also discussed.

    View details for DOI 10.1007/s10016-004-0060-3

    View details for Web of Science ID 000223785100014

    View details for PubMedID 15534741

  • Double trisomy (48,XXY,+21) in monozygotic twins: case report and review of the literature ANNALES DE GENETIQUE Iliopoulos, D., Poultsides, G., Peristeri, V., KOURI, G., Andreou, A., Voyiatzis, N. 2004; 47 (1): 95-98


    The occurrence of double aneuploidy in the same individual is a relatively rare phenomenon. We describe twin newborns with typical clinical features of Down's syndrome, of which one revealed 48,XXY,+21 GTG-band karyotype. The second newborn died 2 days after its birth, and was clinically diagnosed having Down syndrome. Due to the same clinical features of the twins, the common placenta and amniotic sac, we speculate that they were monozygotics and as a result the second newborn should also be a Klinefelter. The purpose of this report is to present a rare case of possible coincidence of double aneuploidy in newborn twins. A review of the literature showed that double trisomy (48,XXY,+21) in a twin newborn infant has never occurred.

    View details for DOI 10.1016/j.anngen.2003.08.025

    View details for Web of Science ID 000221069400010

    View details for PubMedID 15050879

  • Endovascular stent-graft placement for nonaneurysmal infrarenal aortic rupture: A case report and review of the literature JOURNAL OF VASCULAR SURGERY VASQUEZ, J., Poultsides, G. A., Lorenzo, A. C., Foster, J. E., Drezner, A. D., Gallagher, J. 2003; 38 (4): 836-839


    Penetrating atheromatous ulceration of the infrarenal aorta is a rare entity. There are few reported cases of this lesion, and most of the published data is in regards to the thoracic aorta. Spontaneous rupture of a nonaneurysmal noninfected atherosclerotic infrarenal aorta is a rare event. We report the eleventh case of this occurrence and present the first reported case of endovascular stent-graft placement in treating this entity. We review the literature regarding ulcerative disease of the aorta and specifically discuss the published data on spontaneous rupture of the nondilated, noninfected infrarenal aorta secondary to penetrating atheromatous ulceration.

    View details for DOI 10.1016/S0741-5214(03)00557-3

    View details for Web of Science ID 000185858700035

    View details for PubMedID 14560239

  • Distal trapezius musculocutaneous flap for upper thoracic back wounds associated with spinal instrumentation and radiation ANNALS OF PLASTIC SURGERY Chun, J. K., Lynch, M. J., Poultsides, G. A. 2003; 51 (1): 17-22


    Upper thoracic wounds with exposed hardware from spinal instrumentation and previous radiation presents a subset of back wound coverage problems that lend themselves to a unique opportunity to use the distal trapezius musculocutaneous flap. The unradiated, healthy skin paddle can be transposed between the radiated skin edges to seal and cover the exposed hardware and achieve early primary healing of the back wound without the need for a skin graft. The authors review their series of the upper back radiated wounds reconstructed with the trapezius musculocutaneous flaps, immediately at the time of the spinal surgery and secondarily after the incisional wound breakdown, to cover the exposed hardware. Their contiguous skin flap design strategy, results, and complications are discussed.

    View details for Web of Science ID 000184132000004

    View details for PubMedID 12838120

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