Mithat Gonen

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

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Publications (307)1868.6 Total impact

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    ABSTRACT: Clinical decision making for patients with intraductal papillary mucinous neoplasms (IPMN) of the pancreas is challenging. Even with strict criteria for resection, most resected lesions lack high-grade dysplasia (HGD) or invasive carcinoma. We evaluated patients who underwent resection of histologically confirmed IPMN and had preoperative imaging available for review. A hepatobiliary radiologist blinded to histopathologic subtype reviewed preoperative imaging and recorded cyst characteristics. Patients with mixed-type IPMN were grouped with main-duct lesions for this analysis. Based on an ordinal logistic regression model, we devised two independent nomograms to predict the findings of adenoma, high-grade dysplasia (HGD-CIS), and invasive carcinoma, separately in both main and branch-duct IPMN. Bootstrap validation was used to evaluate the performance of these models, and a concordance index was derived from this internal validation. There were 219 patients who met criteria for this study. Branch-duct IPMN (bdIPMN) comprised 56 % of the resected lesions. The proportion of HGD-CIS was 15 % for bdIPMN and 33 % for main-duct lesions (mdIPMN); P = 0.003. Invasive carcinoma was identified in 15 % of bdIPMN and 41 % of main-duct lesions (P < 0.001). On multivariate regression, patient gender, history of prior malignancy, presence of solid component, and weight loss were found to be significantly associated with the ordinal outcome for patients with mdIPMN and built into the nomogram (concordance index 0.74). For patients with bdIPMN weight loss, solid component, and lesion diameter were associated with the outcome; (concordance index 0.74). Based on the analysis of patients selected for resection, two nomograms were created that predict a patient's individual likelihood of harboring HGD or invasive malignancy in radiologically diagnosed IPMN. External validation is ongoing.
    Annals of Surgical Oncology 09/2013; 20(13). DOI:10.1245/s10434-013-3207-z · 3.94 Impact Factor
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    ABSTRACT: To explore whether pre-reoperative dynamic contrast-enhanced (DCE)-MRI findings correlate with clinical outcome in patients who undergo surgical treatment for recurrent rectal carcinoma. A retrospective study of DCE-MRI in patients with recurrent rectal cancer was performed after obtaining an IRB waiver. We queried our PACS from 1998 to 2012 for examinations performed for recurrent disease. Two radiologists in consensus outlined tumour regions of interest on perfusion images. We explored the correlation between K(trans), Kep, Ve, AUC90 and AUC180 with time to re-recurrence of tumour, overall survival and resection margin status. Univariate Cox PH models were used for survival, while univariate logistic regression was used for margin status. Among 58 patients with pre-treatment DCE-MRI who underwent resection, 36 went directly to surgery and 18 had positive margins. K(trans) (0.55, P = 0.012) and Kep (0.93, P = 0.04) were inversely correlated with positive margins. No significant correlations were noted between K(trans), Kep, Ve, AUC90 and AUC180 and overall survival or time to re-recurrence of tumour. K(trans) and Kep were significantly associated with clear resection margins; however overall survival and time to re-recurrence were not predicted. Such information might be helpful for treatment individualisation and deserves further investigation. • Morphological MRI features are not sufficiently predictive of complete rectal tumour resection. • Survival and time to re-recurrence of tumour were not predicted by DCE-MRI. • But perfusion data from dynamic enhanced MRI may provide more helpful information. • Ktrans/Kep were shown to be significantly associated with clear resection margins. • Functional information from DCE-MRI might be helpful for treatment individualisation.
    European Radiology 08/2013; 23(12). DOI:10.1007/s00330-013-2984-x · 4.34 Impact Factor
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    ABSTRACT: Progress in adoptive T-cell therapy for cancer and infectious diseases is hampered by the lack of readily available, antigen-specific, human T lymphocytes. Pluripotent stem cells could provide an unlimited source of T lymphocytes, but the therapeutic potential of human pluripotent stem cell-derived lymphoid cells generated to date remains uncertain. Here we combine induced pluripotent stem cell (iPSC) and chimeric antigen receptor (CAR) technologies to generate human T cells targeted to CD19, an antigen expressed by malignant B cells, in tissue culture. These iPSC-derived, CAR-expressing T cells display a phenotype resembling that of innate γδ T cells. Similar to CAR-transduced, peripheral blood γδ T cells, the iPSC-derived T cells potently inhibit tumor growth in a xenograft model. This approach of generating therapeutic human T cells 'in the dish' may be useful for cancer immunotherapy and other medical applications.
    Nature Biotechnology 08/2013; 31(10). DOI:10.1038/nbt.2678 · 39.08 Impact Factor
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    ABSTRACT: The objective of this work was to evaluate the feasibility of histopathological analysis of tissue extracted on multitined electrodes and assess whether tissue characteristics can be used as biomarkers of oncologic outcomes after lung tumor radiofrequency (RF) ablation. Treatment-related data regarding RF ablation of lung malignancies at our institution was collected using a Health Insurance Portability and Accountability Act-compliant ablation database. Institutional review board waiver was obtained for this study. Immunohistochemical analysis of tissue extracted from the electrodes after lung tumor RF ablation was performed for proliferation (Ki-67) and apoptosis (caspase-3). Patient, tumor demographics, and ablation parameters were recorded. Local tumor progression-free survival (LPFS), disease-specific survival (DSS), and overall survival (OS) were assessed using Kaplan-Meier methodology. Multivariate analysis determined factors affecting these oncological outcomes. A total of 47 lung tumors in 42 patients were ablated; 30 specimens were classified as coagulation necrosis (CN) and 17 as Ki-67-positive (+) tumor cells (viable). Tumor sizes were similar in the CN and Ki-67+ groups (P = 0.32). Median LPFS was 10 versus 16 months for Ki-67+ and CN groups, and 1-year LPFS was 34 and 75 %, respectively (P = 0.003). Median OS was 20 and 46 months (P = 0.12), and median DSS was 20 and 68 months (P = 0.01) for the Ki-67 + and CN groups, respectively. Identification of Ki-67+ tumor cells more than tripled the risk of death from cancer [hazard ratio (HR) = 3.65; 95 % confidence interval (95 % CI), 1.34-9.95; P = 0.01] and tripled the risk of local tumor progression (LTP) (HR = 3.01; 95 % CI, 1.39-6.49; P = 0.005). Ki-67+ tumor cells on the electrode after pulmonary tumor RF ablation is an independent predictor of LTP, shorter LPFS, and DSS.
    Annals of Surgical Oncology 07/2013; 20. DOI:10.1245/s10434-013-3140-1 · 3.94 Impact Factor
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    ABSTRACT: Additional chemotherapy in patients with resectable colorectal liver metastases (CRLM) likely improves outcomes. Whether to administer chemotherapy as perioperative or adjuvant therapy remains controversial. We analyzed outcomes between these two treatment strategies. Patients were identified from a prospective CRLM database and studied retrospectively. Patients with extrahepatic disease or initially unresectable CRLM were excluded. Only patients receiving oxaliplatin- and/or irinotecan-containing chemotherapy regimens were included. Univariate and Cox regression models were developed for recurrence and death. Between 1998 and 2007, 236 patients (57.4 %) in the adjuvant group and 175 patients (42.6 %) in the perioperative group were compared. The perioperative group was younger and had more tumors, shorter disease-free intervals, and higher clinical risk scores (CRS), but had smaller tumors. The overall survival was similar between the groups (perioperative 72.9 months vs. adjuvant 71.5 months; p = 0.48). When the comparison was adjusted for other clinicopathologic factors and CRS, the differences remained insignificant. On univariate analysis, there was a significant difference in recurrence-free survival between the groups (perioperative 17.2 months vs. adjuvant 27.4 months, p = 0.036). However, when the recurrence-free survival was adjusted for other clinicopathologic factors and the CRS, differences were not significant. The timing of additional chemotherapy for resectable CRLM is not associated with outcomes. Trials comparing adjuvant and perioperative chemotherapy would have to be powered for small differences in outcome.
    Annals of Surgical Oncology 07/2013; 20(13). DOI:10.1245/s10434-013-3162-8 · 3.94 Impact Factor
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    ABSTRACT: It has become commonplace to use receiver operating curve (ROC) methodology to evaluate the incremental predictive accuracy of new markers in the presence of existing predictors. However, concerns have been raised about the validity of this practice. We have evaluated this issue in detail. Simulations have been used that show clearly that use of risk predictors from nested models as data in subsequent tests comparing areas under the ROC curves of the models leads to grossly invalid inferences. Careful examination of the issue reveals two major problems: (1) the data elements are strongly correlated from case to case and (2) the model that includes the additional marker has a tendency to interpret predictive contributions as positive information regardless of whether observed effect of the marker is negative or positive. Both of these phenomena lead to profound bias in the test. We recommend strongly against the use of ROC methods derived from risk predictors from nested regression models to test the incremental information of a new marker.
    Clinical Trials 07/2013; DOI:10.1177/1740774513496490 · 1.94 Impact Factor
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    ABSTRACT: Donor criteria for liver grafts have been expanded because of organ shortage. Currently, no exact definitions for extended donor grafts have been established. The aim of this study was to analyze the impact of donor-specific risk factors, independent of recipient characteristics. In collaboration with Eurotransplant and European Liver Transplant Register, solely donor-specific parameters were correlated with 1-year survival following liver transplantation. Analyses of 4701 donors between 2000 and 2005 resulted in the development of a nomogram to estimate graft survival for available grafts. Predictions by nomogram were compared to those by Donor Risk Index (DRI). In the multivariate analysis, cold ischemic time (CIT), highest sodium, cause of donor death, γ-glutamyl transferase (γ-GT), and donor sex (female) were statistically significant factors for 3 months; CIT, γ-GT, and cause of donor death for 12-month survival. The median DRI of this study population was 1.45 (Q1: 1.17; Q3: 1.67). The agreement between the nomogram and DRI was weak (kappa = 0.23). Several donor-specific risk factors were identified for early survival after liver transplantation. The provided nomogram will support quick organ quality assessment. Nevertheless, this study showed the difficulties of determining an exact definition of extended criteria donors.
    Transplant International 07/2013; DOI:10.1111/tri.12156 · 3.16 Impact Factor
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    ABSTRACT: Measures of prognosis are typically estimated from the time of diagnosis. However, these estimates become less relevant as the time from diagnosis increases for a patient. Conditional survival measures the probability that a cancer patient will survive some additional number of years, given that the patient has already survived for a certain number of years. In the current study, the authors analyzed data regarding patients with stage III melanoma to demonstrate that survival estimates from the time of diagnosis underestimate long-term survival as the patient is followed over time. The probability of surviving to year 5 for patients at the time of presentation compared with patients who had already survived for 4 years increased from 72% to 95%, 48% to 90%, and 29% to 86%, respectively, for patients with substage IIIA, IIIB, and IIIC disease. Considering the major role played by survival estimates during follow-up in patient counseling and the development of survivorship programs, the authors strongly recommend the routine use of conditional survival estimates. Cancer 2013. © 2013 American Cancer Society.
    Cancer 07/2013; 119(20). DOI:10.1002/cncr.28273 · 4.90 Impact Factor
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    ABSTRACT: BACKGROUND: For patients undergoing liver resection for colorectal metastases, specific clinico-pathological variables have been shown to be prognostic at baseline. This study analyses how the prognostic capability of these variables changes in a conditional survival model. METHODS: Retrospective review of a prospectively maintained database of patients who underwent an R0 resection of colorectal liver metastases from 1994 to 2004 at a single institution. RESULTS: In total, 807 patients were identified, with an 87-month median follow-up for survivors. Five- and 10-year disease-specific survivals (DSS) were 68% and 55%, respectively. The probability of further survival increased as the survival time increased. For 3-year survivors (n = 504), DSS were no longer significantly different between patients with a low (0-2) or high (3-5) clinical risk score (CRS, P = 0.19). On multivariate analysis, independent predictors of DSS for 3-year survivors were recurrence within the first 3 years after a liver resection, a pre-operative carcinoembryonic antigen (CEA) >200 ng/ml and disease-free interval <12 months prior to the diagnosis of liver metastasis. However, for those patients who were recurrence free at 1 year, no clinico-pathological variables retained prognostic significance. DISCUSSION: After 3 years of DSS and 1 year of recurrence-free survival, baseline clinico-pathological variables have a limited ability to predict future survival. Early post-operative recurrence appears to be the most useful single clinical feature in estimating conditional DSS.
    HPB 06/2013; DOI:10.1111/hpb.12136 · 2.05 Impact Factor
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    ABSTRACT: BACKGROUND: When feasible, surgical treatment of colorectal liver metastases (CRLM) is the treatment of choice. Regional hepatic artery infusional (HAI) chemotherapy effectively treats CRLM. The combination of HAI and systemic chemotherapy may downsize tumors and allow for complete resection and/or ablation (R/A). This study analyzes the combination of HAI and systemic chemotherapy for treating unresectable CRLM, focusing on conversion to complete R/A. METHODS: All patients with unresectable CRLM treated with HAI and systemic chemotherapy from 2000 to 2009 were included. Patients who responded sufficiently to undergo complete R/A were compared to those who did not convert. Survival was compared using a landmark analysis to account for bias. RESULTS: A total of 373 patients were included; 93 patients (25 %) subsequently underwent complete R/A. The percentage of patients submitted to complete R/A increased from 16 % during 2000-2003 to 30 % during 2004-2009. Factors associated with conversion on multivariate analysis were more recent treatment (2004-2009), no prior chemotherapy, clinical risk score <3, treatment on clinical protocol, and younger age. Median and predicted 5-year survival from the time of HAI pump placement was 59 months and 47 %, respectively, in the patients who converted to complete R/A, compared with 16 months and 6 %, respectively in those who did not (p < 0.001). CONCLUSIONS: Despite extensive disease, 25 % of patients with unresectable CRLM responded sufficiently to undergo complete R/A following HAI plus systemic chemotherapy. Combination HAI and systemic chemotherapy is an effective strategy to convert patients to complete resection with an associated excellent long-term survival.
    Annals of Surgical Oncology 06/2013; 20(9). DOI:10.1245/s10434-013-3009-3 · 3.94 Impact Factor
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    ABSTRACT: IMPORTANCE Ablative therapies extend the capability of delivering potentially curative treatment for bilateral hepatic colorectal metastases. OBJECTIVE To compare the long-term effectiveness of ablation with that of resection in patients with bilateral hepatic colorectal metastases. DESIGN Review of a prospective database of 2123 operative cases of hepatic colorectal metastases. SETTING A large institution with expertise in ablation and resection. PATIENTS Patients with bilateral colorectal liver metastases undergoing operation with a curative intent. A total of 141 patients had been treated with bilateral resection (BR) and 95 had undergone ablation. INTERVENTIONS Radiofrequency or microwave ablation alone or in combination with resection (A/R) compared with BR. MAIN OUTCOMES AND MEASURES We compared tumor characteristics and operative and postoperative outcomes using χ2 or Wilcoxon tests as appropriate and assessed overall survival differences between the 2 groups using the log-rank test. RESULTS During the study, 141 patients were treated with BR and 95 patients with A/R. The A/R group was a significantly poorer prognostic group than the BR group as judged by the Clinical Risk Score (P < .01). There was no difference in median operative time (A/R: 280 minutes, BR: 282 minutes; P = .52), but a lower blood loss (A/R: 300 mL, BR: 500 mL; P < .01) and a shorter length of stay (A/R: 7 days, BR: 9 days; P < .01) was achieved in the A/R group. Long-term outcome was not significantly different between the groups (5-year overall survival, A/R: 56%, BR: 49%; P = .16). CONCLUSIONS AND RELEVANCE Treatment of bilateral, multiple hepatic metastases with combined resection and ablation was associated with improved perioperative outcomes without compromising long-term survival compared with bilateral resection. Ablative therapies extend the capability of delivering potentially curative treatment for bilateral hepatic colorectal metastases.
    JAMA SURGERY 05/2013; 148(7):1-4. DOI:10.1001/jamasurg.2013.1431 · 4.30 Impact Factor
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    ABSTRACT: OBJECTIVE: This study aimed to use intravoxel incoherent motion (IVIM) imaging for investigating differences between primary head and neck tumors and nodal metastases and to evaluate IVIM efficacy in predicting outcome. METHODS: Sixteen patients with head and neck cancer underwent IVIM diffusion-weighted imaging on a 1.5-T magnetic resonance imaging scanner. The significance of parametric difference between primary tumors and metastatic nodes were tested. Probabilities of progression-free survival and overall survival were estimated using the Kaplan-Meier method. RESULTS: In comparison with metastatic nodes, the primary tumors had significantly higher vascular volume fraction (f) (P < 0.0009) and lower diffusion coefficient (D) (P < 0.0002). Patients with lower SD for D had prolonged progression-free survival and overall survival (P < 0.05). CONCLUSIONS: Pretreatment IVIM measures were feasible in investigating the physiologic differences between the 2 tumor tissues. After appropriate validation, these findings might be useful in optimizing treatment planning and improving patient care.
    Journal of computer assisted tomography 05/2013; 37(3):346-352. DOI:10.1097/RCT.0b013e318282d935 · 1.60 Impact Factor
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    ABSTRACT: BACKGROUND AND OBJECTIVES: Disease-specific survival (DSS) for GC patients differs in Eastern and Western countries. The aim is to compare outcomes of US and Korean patients following resection of early-stage, node-negative gastric carcinoma (GC). METHODS: All patients (1995-2005) with T1N0 gastric carcinoma, excluding gastroesophageal tumors, were evaluated. DSS was compared by adjusting for prognostic variables from an internationally validated GC nomogram. RESULTS: The cohort included 598 Korean patients and 159 US patients. Age and BMI were significantly higher in US patients. Distal tumor location was more frequent in Korea (60% vs. 52%) and proximal location in the US (19% vs. 5%, P < 0.0001). Five-year DSS did not differ significantly between Korea and the US. After multivariate analysis, DSS of Korean patients persisted, with no significant differences when compared to US patients (HR = 1.2, 95% CI: 0.3-5.2, P = 0.83). CONCLUSIONS: Despite widespread speculations that GC differs in the East and West, when we compare similarly staged, node-negative GC patients, survival did not differ significantly between Korea and the US. This suggests that GC is a heterogeneous disease and when similar subtypes of gastric cancer are compared, these differences disappear. This study suggests more similarities than previously hypothesized between US and Korean GC patients. J. Surg. Oncol © 2012 Wiley Periodicals, Inc.
    Journal of Surgical Oncology 05/2013; 107(6). DOI:10.1002/jso.23288 · 2.84 Impact Factor
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    ABSTRACT: BACKGROUND: Splenectomy is performed for a variety of indications in haematological disorders. This study was undertaken to analyse outcomes, and morbidity and mortality rates associated with this procedure. METHODS: Patients undergoing splenectomy for the treatment or diagnosis of haematological disease were included. Indications for operation, preoperative risk, intraoperative variables and short-term outcomes were evaluated. RESULTS: From January 1997 to December 2010, 381 patients underwent splenectomy for diagnosis or treatment of haematological disease. Some 288 operations were performed by an open approach, 83 laparoscopically, and there were ten conversions. Overall 136 patients (35·7 per cent) experienced complications. Postoperative morbidity was predicted by age more than 65 years (odds ratio (OR) 1·63, 95 per cent confidence interval 1·05 to 2·55), a Karnofsky performance status (KPS) score lower than 60 (OR 2·74, 1·35 to 5·57) and a haemoglobin level of 9 g/dl or less (OR 1·74, 1·09 to 2·77). Twenty-four patients (6·3 per cent) died within 30 days of surgery. Postoperative mortality was predicted by a KPS score lower than 60 (OR 16·20, 6·10 to 42·92) and a platelet count of 50 000/µl or less (OR 3·34, 1·25 to 8·86). The objective of the operation was achieved in 309 patients (81·1 per cent). The success rate varied for each indication: diagnosis (106 of 110 patients, 96·4 per cent), thrombocytopenia (76 of 115, 66·1 per cent), anaemia (10 of 16, 63 per cent), to allow further treatment (46 of 59, 78 per cent) and primary treatment (16 of 18, 89 per cent). CONCLUSION: Splenectomy is an effective procedure in the diagnosis and treatment of haematological disease in selected patients.
    British Journal of Surgery 05/2013; 100(6). DOI:10.1002/bjs.9067 · 5.21 Impact Factor
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    ABSTRACT: Purpose To investigate the impact of newly identified chromosome 3p21 epigenetic tumor suppressors PBRM1, SETD2, and BAP1 on cancer specific survival (CSS) of 609 clear cell renal cell carcinoma (ccRCC) patients from two distinct cohorts. Patients and Methods Select sequencing on 3p tumor suppressors of 188 patients who underwent resection of primary ccRCC at the Memorial Sloan-Kettering Cancer Center (MSKCC) was performed to interrogate the genotype-phenotype associations. These findings were compared to analyses of the genomic and clinical dataset from our non-overlapping The Cancer Genome Atlas (TCGA) cohort of 421 primary ccRCC patients. Results 3p21 tumor suppressors are frequently mutated in both the MSKCC (PBRM1, 30.3%; SETD2, 7.4%; BAP1, 6.4%) and the TCGA (PBRM1, 33.5%; SETD2, 11.6%; BAP1, 9.7%) cohorts. BAP1 mutations are associated with worse CSS in both cohorts (MSKCC, p=0.002, HR 7.71 (2.08-28.6); TCGA, p=0.002, HR 2.21 (1.35-3.63)). SETD2 are associated with worse CSS in the TCGA cohort (p=0.036, HR 1.68 (1.04-2.73)). On the contrary, PBRM1 mutations, the second most common gene mutations of ccRCC, have no impact on CSS. Conclusion The chromosome 3p21 locus harbors three frequently mutated ccRCC tumor suppressor genes. BAP1 and SETD2 mutations (6-12%) are associated with worse CSS, suggesting their roles in disease progression. PBRM1 mutations (30-34%) do not impact CSS, implicating its principal role in the tumor initiation. Future efforts should focus on therapeutic interventions and further clinical, pathologic and molecular interrogation of this novel class of tumor suppressors.
    Clinical Cancer Research 04/2013; 19(12). DOI:10.1158/1078-0432.CCR-12-3886 · 8.19 Impact Factor
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    ABSTRACT: BACKGROUND: Perioperative outcomes, such as blood loss, transfusions, and morbidity, have been linked to cancer-specific survival, but this is largely unsupported by prospective data. METHODS: Patients from a previous, randomized trial that evaluated acute normovolemic hemodilution during major hepatectomy (≥3 segments) were reevaluated and those with metastatic colorectal cancer (n = 90) were selected for analysis. Survival data were obtained from the medical record. Disease extent was measured using a clinical-risk score (CRS). Log-rank test and Cox proportional hazard model were used to evaluate recurrence-free survival (RFS) and overall survival (OS). RESULTS: Median follow-up was 71 months. The CRS was ≥3 in 45 % of patients; 59 % had extrahepatic procedures. Morbidity and mortality were 33 and 2 %, respectively. Postoperative chemotherapy was given to 87 % of patients (78/90) starting at a median of 6 weeks. RFS and OS were 29 and 60 months, respectively. Postoperative morbidity significantly reduced RFS (23 vs. 69 months; P < 0.001) and OS (28 vs. 74 months; P < 0.001) on uni- and multi-variate analysis; positive resection margins and high CRS also were significant factors. Delayed initiation of postoperative chemotherapy (≥8 weeks) was common in patients with complications (37 vs. 12 %; P = 0.01). CONCLUSIONS: In this selected cohort of patients from a previous RCT, perioperative morbidity was strongly (and independently) associated with cancer-specific outcome. It also was associated with delayed initiation of postoperative chemotherapy, the impact of which on survival is unclear.
    Annals of Surgical Oncology 04/2013; DOI:10.1245/s10434-013-2975-9 · 3.94 Impact Factor
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    ABSTRACT: PURPOSE: To identify changes in plasma cytokine levels after image-guided thermal ablation of human tumors and to identify the factors that independently predict changes in plasma cytokine levels. MATERIALS AND METHODS: Whole-blood samples were collected from 36 patients at three time points: before ablation, after ablation (within 48 hours), and at follow-up (1-5 weeks after ablation). Plasma levels of interleukin (IL)-1α, IL-2, IL-6, IL-10, and tumor necrosis factor (TNF)-α were measured using a multiplex immunoassay. Univariate and multivariate analyses were performed using cytokine level as the dependent variable and sample collection, time, age, sex, primary diagnosis, metastatic status, ablation site, and ablation type as the independent variables. RESULTS: There was a significant increase in the plasma level of IL-6 after ablation compared with before ablation (9.6-fold±31-fold, P<.002). IL-10 also showed a significant increase after ablation (1.9-fold±2.8-fold, P<.02). Plasma levels of IL-1α, IL-2, and TNF-α were not significantly changed after ablation. Cryoablation resulted in the largest change in IL-6 level (>54-fold), whereas radiofrequency ablation and microwave ablation showed 3.6-fold and 3.4-fold changes, respectively. Ablation of melanomas showed the largest change in IL-6 48 hours after ablation (92×), followed by ablation of kidney (26×), liver (8×), and lung (6×) cancers. Multivariate analysis revealed that ablation type (P<.0003) and primary diagnosis (P<.03) were independent predictors of changes to IL-6 after ablation. Age was the only independent predictor of IL-10 levels after ablation (P< .019). CONCLUSIONS: Image-guided thermal ablation of tumors increases plasma levels of IL-6 and IL-10, without increasing plasma levels of IL-1α, IL-2, or TNF-α.
    Journal of vascular and interventional radiology: JVIR 04/2013; DOI:10.1016/j.jvir.2013.02.015 · 2.15 Impact Factor
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    ABSTRACT: OBJECTIVES:Controversy exists regarding whether to place a plastic or a metal endobiliary stent in patients with resectable pancreatic cancer who require biliary drainage. Although self-expandable metal stents (SEMS) provide better drainage compared with plastic stents, concerns remain that SEMS may compromise resection and increase postoperative complications. Our objective was to compare surgical outcomes of patients undergoing pancreaticoduodenectomy (PD) with SEMS in place vs. plastic endoscopic stents (PES) and no stents (NS).METHODS:We performed a retrospective analysis from a prospective database of all patients undergoing either attempted or successful PD with SEMS, PES, or NS in place at the time of operation. Patients were compared with regard to perioperative complications, margin status, and the rate of intraoperative determination of unresectability.RESULTS:A total of 593 patients underwent attempted PD. Of these, 84 patients were locally unresectable intraoperatively and 509 underwent successful PD, of which 71 had SEMS, 149 had PES, and 289 had NS. Among patients who had a preoperative stent, SEMS did not increase overall or serious postoperative complications, 30-day mortality, length of stay, biliary anastomotic leak, or positive margin, but was associated with more wound infections and longer operative times. In those with adenocarcinoma, intraoperative determination of local unresectability was similar in the SEMS group compared with other groups, with 16 (19.3%) in SEMS compared with 29 (17.7%) in PES (P=0.862), and 31 (17.5%) in NS (P=0.732).CONCLUSIONS:Placement of SEMS is not contraindicated in patients with resectable pancreatic cancer who require preoperative biliary drainage.Am J Gastroenterol advance online publication, 2 April 2013; doi:10.1038/ajg.2013.93.
    The American Journal of Gastroenterology 04/2013; 108(7). DOI:10.1038/ajg.2013.93 · 9.21 Impact Factor
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    ABSTRACT: BACKGROUND: Considerable debate exists as to appropriate perioperative fluid management. Data from several studies suggest that the amount of fluid administered perioperatively influences surgical outcome. Pancreatic resection is a major procedure in which complications are common. We examined 1,030 sequential patients who had undergone pancreatic resection at Memorial Sloan-Kettering Cancer Center. We documented the prevalence and nature of their complications, and then correlated complications to intraoperative fluid administration. METHODS: We retrospectively examined 1,030 pancreatic resections performed at Memorial Sloan-Kettering Cancer Center between May 2004 and December 2009 from our pancreatic database. Intraoperative administration of colloid and crystalloid was obtained from anesthesia records, and complication data from our institutional database. RESULTS: The overall in-hospital mortality was 1.7%. Operative mortality was due predominantly to intraabdominal infection. Sixty percent of the mortality resulted from intraabdominal complications related to the procedure. We did not demonstrate a clinically significant relationship between intraoperative fluid administration and complications, although minor statistical significance was suggested. CONCLUSIONS: In this retrospective review of intraoperative fluid administration we were not able to demonstrate a clinically significant association between postoperative complications and intraoperative crystalloid and colloid fluid administration. A randomized controlled trial has been initiated to address this question. J. Surg. Oncol © 2012 Wiley Periodicals, Inc.
    Journal of Surgical Oncology 04/2013; 107(5). DOI:10.1002/jso.23287 · 2.84 Impact Factor

Publication Stats

13k Citations
1,868.60 Total Impact Points

Institutions

  • 2002–2015
    • Memorial Sloan-Kettering Cancer Center
      • • Epidemiology & Biostatistics Group
      • • New York Branch at Memorial Sloan-Kettering Cancer Center
      • • Department of Surgery
      • • Department of Radiology
      New York, New York, United States
  • 2013
    • Lenox Hill Hospital
      New York City, New York, United States
  • 2011
    • Dana-Farber Cancer Institute
      • Department of Biostatistics and Computational Biology
      Boston, MA, United States
  • 2008
    • Columbia University
      • Herbert Irving Comprehensive Cancer Center
      New York City, NY, United States
  • 2005
    • State University of New York Downstate Medical Center
      • Department of Urology
      Brooklyn, NY, United States
  • 2004
    • Cornell University
      Ithaca, New York, United States
    • Canadian Society for Epidemiology and Biostatistics 
      Canada