Ronald P DeMatteo

Memorial Sloan-Kettering Cancer Center, New York, New York, United States

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Publications (377)2039.16 Total impact

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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; DOI:10.1158/0008-5472.CAN-14-2564 · 9.28 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.
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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 · 7.19 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; DOI:10.1016/j.jamcollsurg.2014.12.026 · 4.45 Impact Factor
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    ABSTRACT: One quarter of colorectal cancer patients will present with liver metastasis at the time of diagnosis. Recent studies have shown that simultaneous resections are safe and feasible for stage IV colon cancer. Limited data are available for simultaneous surgery in stage IV rectal cancer patients. One hundred ninety-eight patients underwent surgical treatment for stage IV rectal cancer. In 145 (73%) patients, a simultaneous procedure was performed. Fifty-three (27%) patients underwent staged liver resection. A subpopulation of 69 (35%) patients underwent major liver resection (3 segments or more) and 30 (44%) patients with simultaneous surgery. The demographics of the 2 groups were similar. Complication rates were comparable for simultaneous or staged resections, even in the group subjected to major liver resection. Total hospital stay was significantly shorter for the simultaneously resected patients (P < .01). Simultaneous resection of rectal primaries and liver metastases is a safe procedure in carefully selected patients at high-volume institutions, even if major liver resections are required. Copyright © 2015 Elsevier Inc. All rights reserved.
    The American Journal of Surgery 12/2014; DOI:10.1016/j.amjsurg.2014.09.024 · 2.41 Impact Factor
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    ABSTRACT: In patients with colorectal cancer liver metastases (CRCLM), chemotherapy-induced hepatic injury is associated with increased splenic volume, thrombocytopenia, and decreased long-term survival. The current study investigates the relationship between change in splenic volume after preoperative chemotherapy and development of postoperative complications. The study group consisted of 80 patients who underwent resection of CRCLM; half received neoadjuvant chemotherapy for 6 months before resection (n = 40) and the other half did not (n = 40). The study group was compared with two control groups: a normal group composed of patients undergoing cholecystectomy for benign disease (n = 40) and a group of untreated, nonmetastatic colorectal cancer (CRC) patients (n = 40). Splenic volume was measured by CT/MRI volumetry. In the study group, the nontumoral liver was graded for steatosis and sinusoidal injury; operative and outcomes characteristics were also analyzed. Before chemotherapy, CRCLM patients had normalized spleen volumes of 3.2 ± 1.1 mL/kg, significantly higher than normal (2.5 ± 0.8 mL/kg; p < 0.001) and nonmetastatic CRC (2.6 ± 1.3 mL/kg; p < 0.05) patients, with higher splenic volume after 6 months of chemotherapy (4.2 ± 1.7 mL/kg; p < 0.01). After chemotherapy, splenic volume increase was associated with any perioperative complication (p < 0.01) and major complications (p < 0.05). Patients with ≥39% splenic volume increase (maximal chi-square test) were significantly more likely to have major complications (p < 0.01). Spleen volume changes were not correlated with change in platelet count (R(2) = 0.03; p = 0.301). In patients with CRCLM, the presence of liver metastases and chemotherapy are associated with higher splenic volume. Percent splenic volume increase after 6 months of chemotherapy can aid preoperative risk stratification, as it was an independent predictor of major postoperative complications. Copyright © 2015 American College of Surgeons. Published by Elsevier Inc. All rights reserved.
    Journal of the American College of Surgeons 12/2014; 220(3). DOI:10.1016/j.jamcollsurg.2014.12.008 · 4.45 Impact Factor
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    ABSTRACT: Combined intra-operative ablation and resection (CARe) is proposed to treat extensive colorectal liver metastases (CLM). This multicenter study was conducted to evaluate overall survival (OS), local recurrence-free survival (LRFS), hepatic recurrence-free survival (HRFS) and progression-free survival (PFS), to identify factors associated with survival, and to report complications. Four centers combined retropectively their clinical experiences regarding CLM treated by CARe. CLM characteristics, pre- and post-operative chemotherapy regimens, surgical procedures, complications and survivals were analyzed. Of the 288 patients who received CARe, 210 (73%) had synchronous and 255 (88%) had bilateral CLM. Twenty-two patients (8%) had extrahepatic disease. Median follow-up was 3.17 years (95%CI 2.83-4.08). Median OS was 3.33 years (95%CI 3.08-4.17) and 5-year OS was 37% (95%CI 29-45). One- and 5-year LRFS from ablated lesions were 87.9% (95%CI 83.3-91.2) and 78.0% (95%CI 71-83), respectively. Median HRFS and PFS were 14 months (95%CI 11-18) and 9 months (95%CI 8-11), respectively. One hundred patients experienced complications: 29 grade I, 68 grade II-III-IV, and three deaths. In the multivariate models adjusted for center, the occurrence of complications was confirmed as a major independent factor associated with 3-year OS (HR 1.80; P = 0.008). Five-year OS was 25.6% (95%CI 14.9-37.6) for patients with complications and 45% (95%CI 33.3-53.4) for patients without. Recent strategies facing advanced CLM include non-anatomic resections, portal-induced hypertrophy of the future remnant liver and aggressive medical preoperative treatments. CARe has the qualities of an approach that allows effective tumor clearance while maintaining good tolerance for the patient.
    PLoS ONE 12/2014; 9(12):e114404. DOI:10.1371/journal.pone.0114404 · 3.53 Impact Factor
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    ABSTRACT: Texture analysis is a promising method of analyzing imaging data to potentially enhance diagnostic capability. This approach involves automated measurement of pixel intensity variation that may offer further insight into disease progression than do standard imaging techniques alone. We postulated that postoperative liver insufficiency, a major source of morbidity and mortality, correlates with preoperative heterogeneous parenchymal enhancement that can be quantified with texture analysis of cross-sectional imaging. A retrospective case-matched study (waiver of informed consent and HIPAA authorization, approved by the Institutional Review Board) was performed comparing patients who underwent major hepatic resection and developed liver insufficiency (n = 12) with a matched group of patients with no postoperative liver insufficiency (n = 24) by procedure, remnant volume, and year of procedure. Texture analysis (with gray-level co-occurrence matrices) was used to quantify the heterogeneity of liver parenchyma on preoperative CT scans. Statistical significance was evaluated using Wilcoxon's signed rank and Pearson's chi-square tests. No statistically significant differences were found between study groups for preoperative patient demographics and clinical characteristics, with the exception of sex (p < 0.05). Two texture features differed significantly between the groups: correlation (linear dependency of gray levels on neighboring pixels) and entropy (randomness of brightness variation) (p < 0.05). In this preliminary study, the texture of liver parenchyma on preoperative CT was significantly more varied, less symmetric, and less homogeneous in patients with postoperative liver insufficiency. Therefore, texture analysis has the potential to provide an additional means of preoperative risk stratification. Copyright © 2015 American College of Surgeons. Published by Elsevier Inc. All rights reserved.
    Journal of the American College of Surgeons 12/2014; 220(3). DOI:10.1016/j.jamcollsurg.2014.11.027 · 4.45 Impact Factor
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    ABSTRACT: Low central venous pressure (LCVP)-assisted hepatectomy is associated with decreased blood loss and lower transfusion rates. Concerns about its impact on renal function have prevented widespread application. This study was conducted to review the dynamics of renal function after LCVP-assisted hepatectomy.
    HPB 11/2014; DOI:10.1111/hpb.12347 · 2.05 Impact Factor
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    ABSTRACT: Introduction Primary pancreatic lymphoma (PPL) is a rare tumor that is often misdiagnosed. Clinicopathologic features, optimal therapy, and outcomes are not well defined. We reviewed our institutional experience with PPL. Methods Search of our institutional database identified that between 1987–2012, 21,760 patients with lymphoma and 11,286 patients with a primary pancreatic tumor were evaluated. There were 44 patients with pathologically confirmed PPL. Clinical data were obtained by chart review and survival distributions were estimated using the Kaplan–Meier method and compared using the log-rank test. Results At baseline, LDH was elevated in 55 % of the patients, CA 19-9 in 25 %, and CEA in 20 %. Imaging characteristics included large, unresectable tumors (67 %), and lymphadenopathy inferior to the renal vein (50 %). Twenty-three patients underwent surgery for resection (5), diagnosis (13), or palliation (5). Chemotherapy alone achieved a 75 % complete response rate. Eight patients experienced relapse, 88 % of which occurred at distant sites. Median overall survival was 6.1 years and 10-year disease-specific survival (DSS) was 69 %. Patients with a low risk International Prognostic Index (IPI) and those with a follicular histologic subtype demonstrated 5-year DSS of 100 %. Conclusions Chemotherapy for PPL results in a high complete response rate and long DSS, which is similar to nodal non-Hodgkin’s lymphoma (NHL). A favorable outcome is expected for IPI low risk patients and follicular histologic subtype. Systemic therapy should generally be the initial therapy when the diagnosis is known. Prolonged follow up is recommended to detect relapses. Surgery alone should be reserved for non-curative intent (i.e. diagnostic or palliative).
    Annals of Surgical Oncology 10/2014; 22(4). DOI:10.1245/s10434-014-4176-6 · 3.94 Impact Factor
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    ABSTRACT: Background Studying surgical secondary events is an evolving effort with no current established system for database design, standard reporting, or definitions. Using the Clavien–Dindo classification as a guide, in 2001 we developed a Surgical Secondary Events database based on grade of event and required intervention to begin prospectively recording and analyzing all surgical secondary events (SSE). Methods Events are prospectively entered into the database by attending surgeons, house staff, and research staff. In 2008 we performed a blinded external audit of 1,498 operations that were randomly selected to examine the quality and reliability of the data. Results Of 4,284 operations, 1,498 were audited during the third quarter of 2008. Of these operations, 79 % (N = 1,180) did not have a secondary event while 21 % (N = 318) had an identified event; 91 % of operations (1,365) were correctly entered into the SSE database. Also 97 % (129 of 133) of missed secondary events were grades I and II. There were 3 grade III (2 %) and 1 grade IV (1 %) secondary event that were missed. There were no missed grade 5 secondary events. Conclusions Grade III–IV events are more accurately collected than grade I–II events. Robust and accurate secondary events data can be collected by clinicians and research staff, and these data can safely be used for quality improvement projects and research.
    Annals of Surgical Oncology 10/2014; 22(4). DOI:10.1245/s10434-014-4141-4 · 3.94 Impact Factor
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    ABSTRACT: Background The indications for minimally invasive (MIS) pancreatectomy have slowly increased as experience, techniques and technology have improved and evolved to manage malignant lesions in selected patients without compromising safety and oncologic principles. There are sparse data comparing laparoscopic, robotic and open distal pancreatectomy (DP). Study Design All patients undergoing DP at Memorial Sloan Kettering Cancer Center between 2000 and 2013 were analyzed from a prospective database. Clinicopathological and survival data were analyzed to compare perioperative and oncological outcomes in patients who underwent DP via open, laparoscopic and robotic approaches. Results Eight hundred and five DP were performed during the study period, comprising 37 robotic distal pancreatectomies (RDP), 131 laparoscopic distal pancreatectomies (LPD) and 637 open distal pancreatectomies (ODP). The 3 groups were similar with respect to American Society of Anesthesiologists (ASA) score, gender ratio, body mass index, pancreatic fistula rate and 90-day morbidity and mortality. Patients in the ODP group were generally older (p=0.001), had significantly higher intraoperative blood loss (p<0.001) and had a trend towards a longer hospital stay(p=0.05). Of the significant pre-operative variables, visceral fat was predictive of conversion on multivariate analysis (p=0.003). Oncologic outcomes in the adenocarcinoma cases were similar for the 3 groups with high rates of R0 resection (88-100%). The ODP group had a higher lymph node yield than the LDP and RDP groups [15.4, standard deviation (SD) 8.7 vs. 10.4(SD 8.0) vs. 12(SD 7.2),p = 0.04]. Conclusions RDP and LDP were comparable with respect to most perioperative outcomes, with no clear advantage of one approach over the other. Both of these MIS techniques may have advantages over ODP in well-selected patients. All approaches achieved a similar high rate of R0 resection for patients with adenocarcinoma.
    Journal of the American College of Surgeons 10/2014; DOI:10.1016/j.jamcollsurg.2014.10.004 · 4.45 Impact Factor
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    ABSTRACT: Choledochal cysts (CDCs) are believed to represent a risk factor for the development of neoplasia. However, the frequency and morphology of neoplastic changes have not been systematically studied, especially in North America. Our aims were to study the frequency and morphology of preneoplastic/neoplastic changes of CDCs. 36 cysts were subjected to clinicopathological analyses. Metaplasia was found in 14/35, of which 9 had Biliary Intraepithelial Neoplasia (BilIN). Of the 14 with metaplasia, 13 showed pyloric gland (PG), 5 intestinal (IN), and 2 squamous. BilINs included 6 BilIN-1, 2 BilIN-2, and 2 BilIN-3. Carcinoma was identified in 5 cases of which 3 were associated with metaplasia and BilIN. Only 1/18 cases without metaplasia had BilIN and none had carcinoma (p=0.0008). There was a trend towards more BilIN and carcinoma with intestinal rather than with pyloric gland metaplasia. All cases with metaplasia or/and BilIN were negative for MUC1. All cases with intestinal metaplasia were positive for CK20, CDX2, and MUC2, whereas cases with pyloric gland were positive for MUC6. MUC1, CEA and B72.3 were positive only in carcinoma. There was a trend toward increasing p53 and ki-67 from metaplasia to BilIN to carcinoma. 4/5 patients with carcinoma died and one was alive with disease. All others were free of disease except for one who developed new cysts. CDCs are associated with a high rate of BilIN (28.5%) and carcinoma (14.3%). CDCs show a sequence of tumor progression from metaplasia to BilIN and carcinoma.
    Human pathology 10/2014; 45(10). DOI:10.1016/j.humpath.2014.06.016 · 2.81 Impact Factor

Publication Stats

14k Citations
2,039.16 Total Impact Points


  • 2000–2015
    • Memorial Sloan-Kettering Cancer Center
      • • Department of Surgery
      • • Hepatopancreatobiliary Service
      • • Department of Radiology
      New York, New York, United States
  • 2010–2014
    • Weill Cornell Medical College
      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