Ronald P DeMatteo

Weill Cornell Medical College, New York, New York, United States

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Publications (395)2153.41 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Endoscopic biliary drainage (EBD) and percutaneous transhepatic biliary drainage (PTBD) are both used to resolve jaundice before surgery for perihilar cholangiocarcinoma (PHC). PTBD has been associated with seeding metastases. The aim of this study was to compare overall survival (OS) and the incidence of initial seeding metastases that potentially influence survival in patients with preoperative PTBD versus EBD. Between 1991 and 2012, a total of 278 patients underwent preoperative biliary drainage and resection of PHC at 2 institutions in the Netherlands and the United States. Of these, 33 patients were excluded for postoperative mortality. Among the 245 included patients, 88 patients who underwent preoperative PTBD (with or without previous EBD) were compared to 157 patients who underwent EBD only. Survival analysis was done with Kaplan-Meier and Cox regression with propensity score adjustment. Unadjusted median OS was comparable between the PTBD group (35 months) and EBD-only group (41 months; P = 0.26). After adjustment for propensity score, OS between the PTBD group and EBD-only group was similar (hazard ratio, 1.05; 95 % confidence interval, 0.74-1.49; P = 0.80). Seeding metastases in the laparotomy scar occurred as initial recurrence in 7 patients, including 3 patients (3.4 %) in the PTBD group and 4 patients (2.7 %) in the EBD-only group (P = 0.71). No patient had an initial recurrence in percutaneous catheter tracts. The present study found no effect of PTBD on survival compared to patients with EBD and no increase in seeding metastases that developed as initial recurrence. These data suggest that PTBD can safely be used in preoperative management of PHC.
    Annals of Surgical Oncology 06/2015; DOI:10.1245/s10434-015-4676-z · 3.94 Impact Factor
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    ABSTRACT: Reports show that FOLFIRINOX therapy for pancreatic ductal adenocarcinoma (PDAC) results in objective response rates two to threefold higher than those of other regimens. This study aimed to assess response and resection rates for locally unresectable (stage 3) patients initially treated with induction FOLFIRINOX. The institutional cancer database was queried for patients treated with induction FOLFIRINOX therapy between 2010 and 2013. Patients were included in the study if they were treated at the authors' institution for stage 3 PDAC (locally unresectable) that had been adjudicated at a weekly multidisciplinary tumor board. The study identified 101 patients. The median age was 64 years (range 37-81 years), and the median follow-up period was 12 months (range 3-37 months). The patients received a median of six cycles (range 1-20 cycles) of induction FOLFIRINOX. No grade 4 or 5 toxicity was recorded. At the initial restaging (median of 3 months after diagnosis), 23 patients (23 %) had developed distant metastases, 15 patients (15 %) had undergone resection, and 63 patients (63 %) had proceeded to chemoradiation. In the group of 63 patients who had proceeded to chemoradiation (median of 9 months after diagnosis), an additional 16 patients (16 %) had undergone resection, and 5 patients (5 %) had developed metastases. A partial radiographic response was observed in 29 % of all the patients, which was associated with ability to perform resection (p = 0.004). The median overall survival time was 11 months for the group that progressed with FOLFIRINOX and 26 months for the group that did not progress. Nearly one third of the patients who had been initially identified as having stage 3 pancreatic carcinoma and had been treated with FOLFIRINOX responded radiographically and underwent tumor resection.
    Annals of Surgical Oncology 06/2015; DOI:10.1245/s10434-015-4647-4 · 3.94 Impact Factor
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    ABSTRACT: To evaluate the use of locoregional therapy in patients with hepatocellular carcinoma (HCC) with and without extrahepatic disease (EHD). Patients who underwent locoregional therapy for HCC were identified from institutional databases. Clinicopathologic and treatment characteristics were compared between patients with and without EHD. Survival and progression were assessed using the Kaplan-Meier method, and multivariate analysis was completed. Of 224 patients, 39 (17%) had radiologic evidence of EHD. Patients without EHD were older than patients with EHD (68.8 y ± 10.1 vs 65.0 y ± 11.7, P = .04); underlying liver disease/function and tumor characteristics were not different. Type of locoregional therapy (hepatic artery embolization vs drug-eluting bead transarterial chemoembolization, P = .12; radiofrequency ablation + embolization, P = .07) was similar. Progression occurred in 75% (169/224) of patients. Progression-free survival (PFS) did not differ between the 2 groups (13 [10.3-15.7] mo EHD vs18 [14.6-21.4] mo no EHD, P = .13). Overall survival (OS) was 13 (4.1-21.9) months and 25 (20.4-29.6) months in the EHD and no EHD groups, respectively (P = .02). On multivariate analysis, systemic therapy after locoregional treatment was the only variable independently associated with PFS (hazard ratio [HR] 0.70 [0.49-1.00], P = .04); EHD (HR 1.60 [1.02-2.50], P = .04) and tumor size (HR 1.77 [1.21-2.58], P = .003) were independently associated with worse OS. Patients with HCC and limited EHD treated with locoregional therapy had worse OS than patients without EHD; PFS was not different. Use of systemic therapy after locoregional therapy was independently associated with improved PFS in this cohort. Further prospective studies of locoregional, systemic, and combination therapies are necessary to improve outcome in these high-risk patients. Copyright © 2015 SIR. Published by Elsevier Inc. All rights reserved.
    Journal of vascular and interventional radiology: JVIR 05/2015; DOI:10.1016/j.jvir.2015.04.006 · 2.15 Impact Factor
  • Gastrointestinal Endoscopy 05/2015; 81(5):AB234. DOI:10.1016/j.gie.2015.03.1324 · 4.90 Impact Factor
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    ABSTRACT: Background The prognostic and predictive abilities of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) coupled with conventional computed tomography (CT) have not been studied in patients with unresectable colorectal liver metastases (uCRLM) treated with combined hepatic arterial infusion (HAI) and systemic chemotherapy.Objectives The ability of PET-CT metabolic response parameters to predict conversion to resectability and oncologic outcome in this setting was evaluated.Methods Thirty-eight patients undergoing serial PET-CT as part of a Phase II trial of HAI and systemic chemotherapy for uCRLM were included. Metabolic response was determined as the percentage change in standard uptake value (SUV) and total lesion glycolysis (TLG). Conversion to resection, overall survival (OS), progression-free survival (PFS) and recurrence-free survival were evaluated using standard statistics.ResultsVolumetric response sufficient to facilitate resection was seen in 53% of patients after a median of 5 months of therapy. Median follow-up was 38 months (range: 32–52 months). Median OS was not reached [95% confidence interval (CI) 32 months–unknown] and 3-year OS was 54% (range: 33–71%). Median PFS was 13 months (95% CI 6–21 months) and 3 year PFS was 10% (range: 3–20%). Neither baseline values nor the percentage change in any of the metabolic parameters evaluated correlated with conversion to resection, survival variables or hepatic recurrence on Cox regression analysis.Conclusions Pre- and post-treatment PET-related metabolic parameters do not predict conversion to resection or oncologic outcome in patients with uCRLM treated with HAI and systemic chemotherapy. Metabolic parameters should not be used to monitor response or to determine prognosis in these patients.
    HPB 05/2015; 17(7). DOI:10.1111/hpb.12421 · 2.05 Impact Factor
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    ABSTRACT: Lymphoepithelioma-like carcinomas are distinctive epithelial derived malignant neoplasms that have a syncytial growth pattern and lymphoid stroma. The majority of tumors with this appearance are Epstein Barr virus (EBV)-associated. We report a patient with a clinical presentation concerning for lymphoma who was diagnosed with an EBV-associated pancreatic carcinoma with a lymphoepithelioma-like pattern. Targeted sequencing analysis showed a molecular profile distinct from conventional ductal adenocarcinoma of the pancreas. Copyright © 2015 IAP and EPC. Published by Elsevier B.V. All rights reserved.
    Pancreatology 04/2015; 15(3). DOI:10.1016/j.pan.2015.03.016 · 2.50 Impact Factor
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    ABSTRACT: Chimeric antigen receptor-modified T cell (CAR-T) technology, a promising immunotherapeutic tool, has not been applied specifically to treat liver metastases (LM). While CAR-T delivery to LM can be optimized by regional intrahepatic infusion, we propose that liver CD11b+Gr-1+ myeloid-derived suppressor cells (L-MDSC) will inhibit the efficacy of CAR-T in the intrahepatic space. We studied anti-CEA CAR-T in a murine model of CEA+ LM and identified mechanisms through which L-MDSC expand and inhibit CAR-T function. We established CEA+ LM in mice and studied purified L-MDSC and responses to treatment with intrahepatic anti-CEA CAR-T infusions. L-MDSC expanded threefold in response to LM, and their expansion was dependent on GM-CSF, which was produced by tumor cells. L-MDSC utilized PD-L1 to suppress anti-tumor responses through engagement of PD-1 on CAR-T. GM-CSF, in cooperation with STAT3, promoted L-MDSC PD-L1 expression. CAR-T efficacy was rescued when mice received CAR-T in combination with MDSC depletion, GM-CSF neutralization to prevent MDSC expansion, or PD-L1 blockade. As L-MDSC suppressed anti-CEA CAR-T, infusion of anti-CEA CAR-T in tandem with agents targeting L-MDSC is a rational strategy for future clinical trials.
    Cancer Immunology and Immunotherapy 04/2015; DOI:10.1007/s00262-015-1692-6 · 3.94 Impact Factor
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    ABSTRACT: Gastrointestinal stromal tumors (GIST) are the most common adult sarcomas and the oncogenic driver is usually a KIT or PDGFRA mutation. While GIST are often initially sensitive to imatinib or other tyrosine kinase inhibitors, resistance generally develops necessitating backup strategies for therapy. In this study, we determined that a subset of human GIST specimens that acquired imatinib resistance acquired expression of activated forms of the MET oncogene. MET activation also developed after imatinib therapy in a mouse model of GIST (KitV558del/+ mice), where it was associated with increased tumor hypoxia. MET activation also occurred in imatinib-sensitive human GIST cell lines after imatinib treatment in vitro. MET inhibition by crizotinib or RNA interference was cytotoxic to an imatinib-resistant human GIST cell population. Moreover, combining crizotinib and imatinib was more effective than imatinib alone in imatinib-sensitive GIST models. Lastly, cabozantinib,a dual MET and KIT small molecule inhibitor, was markedly more effective than imatinib in multiple preclinical models of imatinib-sensitive and imatinib-resistant GIST. Collectively, our findings showed that activation of compensatory MET signaling by KIT inhibition may contribute to tumor resistance. Furthermore, our work offered a preclinical proof of concept for MET inhibition by cabozantinib as an effective strategy for GIST treatment. Copyright © 2015, American Association for Cancer Research.
    Cancer Research 04/2015; 75(10). DOI:10.1158/0008-5472.CAN-14-2564 · 9.28 Impact Factor
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    ABSTRACT: The aim of this study is to determine the prevalence of diabetes mellitus (DM) in patients with intraductal papillary mucinous neoplasm of the pancreas (IPMN) and compare rates of new/progressive DM between IPMN patients undergoing pancreatectomy versus observation. Patients diagnosed with IPMN were identified from institutional databases, divided into two groups based on treatment type, pancreatectomy versus clinical observation, and subsequently evaluated. Standard demographic and clinicopathologic variables, fasting glucose, diabetic status, and pancreatic volume data, were obtained and compared between groups. One hundred thirty-four IPMN patients were identified; 103 (77 %) underwent pancreatectomy and 31 (23 %) were observed. Baseline DM rate was 18 % (24/134). This was not different between groups [17 % (17/103) resected vs. 23 % (7/31) observed, p = 0.51]. Median follow-up was 53 months and new/progressive DM occurred in 37 (28 %) patients with no difference between groups [29 (28 %) resected vs. 8 (26 %) observed, p = 0.74]. Among resected patients, degree of dysplasia was associated with increase risk of new/progressive DM [moderate dysplasia OR 5.76 (1.24-26.79) and severe dysplasia OR 9.43 (1.54-57.74), p = 0.04], while procedure type and remnant volume were not. The incidence and prevalence of DM among patients with IPMN was high and did not differ between resected and observed groups. Degree of dysplasia, not the amount of resected pancreas, was associated with increased risk of DM, suggesting that the presence or development of DM may be a marker of malignant progression. Confirmatory studies are required.
    Gastroenterology 04/2015; 148(4):S-1113. DOI:10.1016/S0016-5085(15)33792-6 · 13.93 Impact Factor
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    ABSTRACT: The optimal perioperative fluid resuscitation strategy for liver resections remains undefined. Goal-directed therapy (GDT) embodies a number of physiologic strategies to achieve an ideal fluid balance and avoid the consequences of over- or under-resuscitation. In a prospective randomized trial, patients undergoing liver resection were randomized to GDT using stroke volume variation as an end point or to standard perioperative resuscitation. Primary outcomes measure was 30-day morbidity. Between 2012 and 2014, one hundred and thirty-five patients were randomized (GDT: n = 69; standard perioperative resuscitation: n = 66). Median age was 57 years and 56% were male. Metastatic disease comprised 81% of patients. Overall (35% GDT vs 36% standard perioperative resuscitation; p = 0.86) and grade 3 morbidity (28% GDT vs 18% standard perioperative resuscitation; p = 0.22) were equivalent. Patients in the GDT arm received less intraoperative fluid (mean 2.0 L GDT vs 2.9 L standard perioperative resuscitation; p < 0.001). Perioperative transfusions were required in 4% (6% GDT vs 2% standard perioperative resuscitation; p = 0.37) and boluses in the postanesthesia care unit were administered to 24% (29% GDT vs 20% standard perioperative resuscitation; p = 0.23). Mortality rate was 1% (2 of 135 patients; both in GDT). On multivariable analysis, male sex, age, combined procedures, higher intraoperative fluid volume, and fluid boluses in the postanesthesia care unit were associated with higher 30-day morbidity. Stroke volume variation-guided GDT is safe in patients undergoing liver resection and led to less intraoperative fluid. Although the incidence of postoperative complications was similar in both arms, lower intraoperative resuscitation volume was independently associated with decreased postoperative morbidity in the entire cohort. Future studies should target extensive resections and identify patients receiving large resuscitation volumes, as this population is more likely to benefit from this technique. Copyright © 2015 American College of Surgeons. Published by Elsevier Inc. All rights reserved.
    Journal of the American College of Surgeons 04/2015; 221(2). DOI:10.1016/j.jamcollsurg.2015.03.050 · 4.45 Impact Factor
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    ABSTRACT: Nomograms are widely used as prognostic devices in oncology and medicine. With the ability to generate an individual probability of a clinical event by integrating diverse prognostic and determinant variables, nomograms meet our desire for biologically and clinically integrated models and fulfill our drive towards personalised medicine. Rapid computation through user-friendly digital interfaces, together with increased accuracy, and more easily understood prognoses compared with conventional staging, allow for seamless incorporation of nomogram-derived prognosis to aid clinical decision making. This has led to the appearance of many nomograms on the internet and in medical journals, and an increase in nomogram use by patients and physicians alike. However, the statistical foundations of nomogram construction, their precise interpretation, and evidence supporting their use are generally misunderstood. This issue is leading to an under-appreciation of the inherent uncertainties regarding nomogram use. We provide a systematic, practical approach to evaluating and comprehending nomogram-derived prognoses, with particular emphasis on clarifying common misconceptions and highlighting limitations. Copyright © 2015 Elsevier Ltd. All rights reserved.
    The Lancet Oncology 04/2015; 16(4):e173-e180. DOI:10.1016/S1470-2045(14)71116-7 · 24.73 Impact Factor
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    ABSTRACT: Hospital readmission rates after surgery are increasingly used as a measure of quality of care. Numerous efforts to decrease these rates have been established by care providers and insurance companies. There is sparse information available regarding readmission rates after liver resection for metastatic colorectal cancer (mCRC). Data from hospital readmissions occurring within 30 days after liver resection and/or open ablation for mCRC between 2005 and 2010 were captured from the urgent care center (emergency room) database and were compared with data from the institutional database. Complications during the primary stay and those leading to readmission were analyzed and graded with an established scoring system. The time course of complications and their therapeutic management were analyzed as well. Of 746 patients who underwent surgery during this period, 277 (37%) developed medical or surgical complications within 30 days, and 97 (13%) required readmission after discharge. The most common causes for readmission were perihepatic or intra-abdominal collections (40%), wound issues (13%), and gastrointestinal issues (12%). Forty-four patients had complications grade 3 or higher during readmission, thus representing 34% of all major complications (grade 3 or higher). Seventy-four readmitted patients (27% of all patients with complications) had a complication of lesser grade during their primary stay. The median postoperative day of readmission was 15 (range, 6-30) with wide variation among complication types. Readmission is common after liver resection and/or ablation for mCRC. One quarter of patients who develop complications postoperatively will have their most significant complication as an outpatient and require rehospitalization. Copyright © 2015 Elsevier Inc. All rights reserved.
    Surgery 02/2015; 157(2):231-8. DOI:10.1016/j.surg.2014.09.016 · 3.11 Impact Factor
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    ABSTRACT: Background/purpose: Fibrolamellar hepatocellular carcinoma (FL-HCC) arises in pediatric/adolescent patients without cirrhosis. We retrospectively evaluated the impact of resection, nodal status, metastasis, and PRETEXT stage on overall survival (OS). Methods: With IRB approval, we reviewed records of 25 consecutive pediatric patientswith FL-HCC treated at our institution from 1981 to 2011. We evaluated associations between OS and PRETEXT stage, nodal involvement, metastasis, and complete resection. Results: Median age at diagnosis was 17.1 years (range, 11.6-20.5). Median follow-up was 2.74 years (range, 5-9.5). Five (28%) patients had PRETEXT stage 1 disease, 10 (56%) had stage 2, 2 (11%) had stage 3, and 2 (11%) had stage 4 disease. On presentation, 17 (68%) patients had N1 disease, and 7 (28%) had parenchymal metastases. Complete resection was achieved in 17 (80.9%) of 21 patients who underwent resection. Five-year OS was 42.6%. Survival was positively associated with complete resection (P = 0.003), negative regional lymph nodes (P = 0.044), and lower PRETEXT stage (P < 0.001), with a trend for metastatic disease (P= 0.05). Conclusions: In young patients with FL-HCC, lower PRETEXT stage and complete resection correlated with prolonged survival, while metastatic disease and positive lymph node status were associated with poor prognosis. Thus, we recommend complete resection and regional lymphadenectomy whenever possible.
    Journal of Pediatric Surgery 01/2015; 50(1). DOI:10.1016/j.jpedsurg.2014.10.039 · 1.31 Impact Factor
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    ABSTRACT: Though immune responses correlate with prognosis in primary colorectal cancer, the role of tumor immunity in metastatic disease is less clear. We hypothesized that patient survival and tumor recurrence correlate with transcriptional evidence of lymphocyte proliferation/activation in resected colorectal cancer liver metastases (CRLM). Microarray gene analysis was performed on liver tumor specimens from 96 patients who underwent resection for CRLM. A Cox proportional hazards model identified genes associated with overall (OS) and recurrence-free survival (RFS). Conventional gene ontology (GO) enrichment analysis ranked biologically relevant processes. Survival probabilities of prioritized processes were assessed. Protein expression was validated with immunohistochemistry in an independent set of patients. GO analysis identified and ranked unique biologic processes that correlated with survival. Genes that specifically functioned in the biologic process of "T-cell proliferation" were significant predictors of OS (p = 0.01) and both "T-cell proliferation" and "activation" were highly associated with RFS (p≤0.01). Analysis of genes in these GO categories identified increased TNFSF14/LIGHT expression to be most associated with improved OS and RFS (p≤0.0006). Immunohistochemistry of an independent validation set of CRLM confirmed that both increased tumor infiltrating lymphocytes (TIL) and higher LIGHT expression on TIL were associated with improved OS and RFS. Differential expression of genes involved in T-cell proliferation/activation were associated with survival outcomes in a large number of surgical patients who underwent resection of CRLM. These biologic functions determined by GO analysis of the tumor microenvironment have identified specific immune-related genes that may be involved in an anti-tumor immune response. Copyright © 2015, American Association for Cancer Research.
    01/2015; 3(4). DOI:10.1158/2326-6066.CIR-14-0212
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    ABSTRACT: The role of carcinoembryonic antigen (CEA) in surveillance and follow-up of patients with colorectal cancer continues to be debated. The objective of this study was to assess the utility of postoperative CEA as a predictor of recurrence for patients with resected colorectal liver metastases (CLM). Patients were identified from a prospectively maintained CLM database, and were studied retrospectively. Patients with extrahepatic disease or initially unresectable CLM were excluded. All patients in this study received adjuvant systemic chemotherapy after resection. Between 1997 and 2007, a total of 318 consecutive patients were studied, with 168 patients (53 %) experiencing recurrence within 2 years. Various postoperative CEA cutoffs were tested as independent predictors of recurrence. A postoperative CEA ≥15 ng/ml obtained the highest hazard ratio (1.87; 95 % CI 1.09-3.2; p = 0.023) and was chosen to be included in the survival analysis in the multivariate model. A postoperative CEA ≥15 ng/ml had a specificity of 96 % and positive predictive value of 82 % for recurrence. On multivariate analysis, age ≥70 years, the presence of positive lymph node at primary tumor resection, disease-free interval ≤12 months, number of lesions >1, largest lesion ≥5 cm, presence of positive margins, and postoperative CEA ≥15 ng/ml were independent predictors of recurrence within 2 years. This study demonstrates a postoperative CEA ≥15 ng/ml to be a predictive test for recurrence.
    Annals of Surgical Oncology 01/2015; DOI:10.1245/s10434-014-4358-2 · 3.94 Impact Factor
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    ABSTRACT: Patients with recurrence after complete resection of colorectal liver metastases (CLM) are considered for repeat resection as a potential salvage therapy (PST). However, outcomes for this approach are not well defined. We sought to analyze the natural history of recurrence and PST in a large cohort of patients with long-term follow-up. Recurrence patterns, treatments, and outcomes in consecutive patients undergoing resection for colorectal liver metastases were analyzed retrospectively. PST was defined as repeat resection of all recurrent disease and effective salvage therapy (EST) as free of disease for 36 months after last PST. Factors associated with PST, EST, and outcomes were analyzed. Of 952 patients who underwent resection, 594 (62 %) experienced recurrence (median interval = 13 months). Initial recurrences involved liver (n = 157,26 %), lung (n = 167,28 %), multiple sites (n = 171,29 %), and other single sites (n = 99,17 %). PST was performed in 160 (27 %) of 594, most commonly with a single site of recurrence (n = 149). Young age (p = 0.01), negative initial resection margin (p = 0.003), initial tumor size <5 cm (p = 0.006), and recurrence pattern (p < 0.001) were independently associated with PST. Thirty-six patients experienced EST (25 % of PSTs). Overall median survival was 61 and 43 months in those with recurrence. Median survival of patients undergoing PST was 87 months compared to 34 months for those who did not. Recurrence is common after CLM resection, but 27 % of patients were able to undergo PST. Approximately one-quarter of these experienced EST and may be cured. PST is associated with long-term survival and possible cure, and therefore active surveillance after CLM resection is justified.
    Annals of Surgical Oncology 01/2015; DOI:10.1245/s10434-015-4370-1 · 3.94 Impact Factor
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    ABSTRACT: The incidence of other primary neoplasms in gastrointestinal stromal tumor (GIST) patients is relatively high. Our aim was to better characterize the clinicopathologic and molecular relationships in a cohort of GIST patients. All GIST patients with tumor samples sent for molecular testing were identified via electronic medical records. Clinicopathologic characteristics of GIST and additional primary malignancies were analyzed. Of 260 patients, 50 (19 %) had at least one additional primary malignancy. In 33 patients, separate primary neoplasms predated their GIST diagnosis and most commonly included: prostate (n = 9), breast (n = 8), and hematologic (n = 5). Renal (n = 4) and hematologic (n = 3) malignancies were the most frequent cancers identified after GIST diagnosis. The majority (8 of 12, 66 %) of malignancies diagnosed after GIST were found incidentally. Patients who developed other malignancies after GIST more often had KIT exon 11 mutations (100 vs. 66 %, P = 0.01). In comparison to patients with only GIST, patients with a second primary neoplasm of any chronology had GISTs with increased mitotic rate (≥5 per 50 high-power fields) (P = 0.0006). Literature review revealed colorectal cancer, gastric, prostate, renal, leukemia, and desmoid-type fibromatosis as the most common secondary neoplasms. Nineteen percent of GIST patients develop other malignancies. This is the first report to describe a relationship between additional primary malignancy and both mutation and mitotic rate of GIST. Although the basis of these relationships remains to be investigated, caution in the clinical management of GIST patients with additional lesions is warranted.
    Annals of Surgical Oncology 01/2015; DOI:10.1245/s10434-014-4332-z · 3.94 Impact Factor
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    ABSTRACT: OBJECTIVES:: To evaluate the association of tumor-associated neutrophils (TANs) with malignant progression in intraductal papillary mucinous neoplasms (IPMNs) and to study the cyst fluid from these lesions for biomarkers of the inflammation-carcinogenesis association. BACKGROUND:: There is a strong link between TANs and malignant progression. Inflammatory mediators released by these cells may be a measurable surrogate marker of this progression. METHODS:: We evaluated 78 resected IPMNs (2004-2013). Lesions were divided into the low-risk (low- and intermediate-grade dysplasia: n = 48) and high-risk (high-grade dysplasia and invasive carcinoma: n = 30) groups. TANs were assessed and categorized (negative, low, and high). A multiplexed assay was performed to evaluate 87 different cyst fluid proteins, including cyst fluid inflammatory markers (CFIMs), as possible surrogate markers for parenchymal inflammation. RESULTS:: Significant positive correlation between grade of dysplasia and TANs was found. High levels of TANs were identified in 2%, 33%, and 89% of the lesions when stratified by grade of dysplasia into low/intermediate-grade dysplasia, high-grade dysplasia, and invasive carcinoma, respectively (P < 0.001). Higher grades of dysplasia were also found to have positive correlation with 29 of the measured proteins, of which 23 (79%) were CFIMs. Higher levels of TANs correlated with higher levels of 18 CFIMs, of which 16 (89%) were also found to be associated with higher grades of dysplasia. CONCLUSIONS:: In this study, TANs were strongly associated with malignant progression in IPMNs. Measurement of CFIMs may be a surrogate marker for IPMN progression and allow for the identification of high-risk disease.
    Annals of Surgery 01/2015; DOI:10.1097/sla.0000000000001044 · 8.33 Impact Factor
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    ABSTRACT: Liver resection is used to treat primary and secondary malignancies. Historically, these procedures were associated with significant complications, which may affect cancer-specific outcomes. This study analyzed the changes in morbidity and mortality after hepatic resection over time. Records of all patients undergoing liver resection for a malignant diagnosis from 1993 to 2012 at Memorial Sloan Kettering were analyzed. Patients were divided into early (1993 to 1999), middle (2000 to 2006), and recent (2007 to 2012) eras. Major hepatectomy was defined as resection of 3 or more segments. Univariate and multivariate analyses were made with t-tests or Mann-Whitney tests. There were 3,875 patients who underwent 4,152 resections for malignancy. The most common diagnosis was metastatic colorectal cancer (n = 2,476, 64% of patients). Over the study period, 90-day mortality rate decreased from 5% to 1.6% (p < 0.001). Perioperative morbidity decreased from 53% to 20% (p < 0.001). The percentage of major hepatectomies decreased from 66% to 36% (p < 0.001). The rate of perioperative transfusion decreased from 51% to 21% (p < 0.001). The spectrum of perioperative morbidity changed markedly over time, with abdominal infections (43% of complications) overtaking cardiopulmonary complications (22% of complications). Peak postoperative bilirubin (odds ratio [OR] 1.1, p < 0.001), blood loss (OR 1.5, p = 0.001), major hepatectomy (OR 1.3, p = 0.031), and concurrent partial colectomy (OR 2.4, p < 0.001) were independent predictors of perioperative morbidity. The mortality associated with trisectionectomy (6%) and right hepatectomy (3%) remained unchanged over time. Morbidity and mortality rates after partial hepatectomy for cancer have decreased substantially as the major hepatectomy rate has dropped. Encouraging parenchymal preservation and preventing abdominal infections are vital for continued improvement of liver resection outcomes. Copyright © 2015 American College of Surgeons. Published by Elsevier Inc. All rights reserved.
    Journal of the American College of Surgeons 12/2014; 220(4). DOI:10.1016/j.jamcollsurg.2014.12.026 · 4.45 Impact Factor
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    ABSTRACT: We report a case of safe and successful yttrium-90 resin microsphere radioembolization in a patient with a long history of multiple recurrent colon cancer hepatic metastases progressing after hepatic resections, hepatic arterial chemotherapy, and multiple regimens of systemic chemotherapy. One month prior to radioembolization, a biliary stent was placed above the level of the ampulla to relieve tumor-related biliary obstruction and normalize bilirubin levels.
    12/2014; 2014:921406. DOI:10.1155/2014/921406

Publication Stats

16k Citations
2,153.41 Total Impact Points


  • 2010–2015
    • Weill Cornell Medical College
      New York, New York, United States
  • 2000–2015
    • Memorial Sloan-Kettering Cancer Center
      • • Department of Surgery
      • • Hepatopancreatobiliary Service
      • • Department of Radiology
      New York, New York, United States
  • 2013
    • Duke University
      Durham, North Carolina, United States
    • Emory University
      • Department of Surgery
      Atlanta, Georgia, United States
  • 2011
    • Memorial Hospital, TN
      Chattanooga, Tennessee, United States
  • 2004
    • Yale-New Haven Hospital
      New Haven, Connecticut, United States
    • Harvard University
      Cambridge, Massachusetts, United States
  • 2003
    • University of Louisville
      Louisville, Kentucky, United States
  • 1996–1998
    • Hospital of the University of Pennsylvania
      • Department of Surgery
      Philadelphia, Pennsylvania, United States
  • 1995–1996
    • William Penn University
      Filadelfia, Pennsylvania, United States
    • University of Pennsylvania
      Filadelfia, Pennsylvania, United States