Milind Javle

University of Texas MD Anderson Cancer Center, Houston, Texas, United States

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Publications (136)607.09 Total impact

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    ABSTRACT: Background: Preoperative/neoadjuvant therapy (NT) is increasingly utilized for the treatment of pancreatic ductal adenocarcinoma (PDAC). However, little data exist regarding information on the use of additional postoperative therapy following NT. The lymph node ratio (LNR) is a prognostic marker of oncologic outcomes after NT and resection. In this study, we evaluated the effectiveness of postoperative therapy following NT, stratified by LNR. Methods: A prospective tumor registry database was queried to identify patients with PDAC who underwent resection following NT from 1990 to 2008. Clinicopathologic factors were compared to identify associations with overall survival (OS) and time to recurrence (TTR) based on postoperative chemotherapy status. Results: Thirty-six (14 %) of the 263 patients received additional postoperative therapy. No differences were observed in the pathologic characteristics between patients who received postoperative chemotherapy and those who did not. The median LNR was 0.12 for patients with N + disease. Following NT, the administration of postoperative therapy was associated with improved median OS (72 vs. 33 months; p = 0.008) for patients with an LNR < 0.15. There was no association between postoperative chemotherapy and OS for patients with LNR ≥ 0.15. Multivariate analysis demonstrated that the administration of postoperative systemic therapy in patients with a low LNR was associated with a reduced risk of death (hazard ratio 0.49; p = 0.02). Conclusion: Postoperative chemotherapy after NT in patients with low LNR is associated with improved oncologic outcomes.
    Annals of Surgical Oncology 09/2015; DOI:10.1245/s10434-015-4854-z · 3.93 Impact Factor
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    ABSTRACT: PTEN is a tumor suppressor gene that regulates the PTEN/PI3k/AKT/mTOR pathway, which is frequently altered in human cancers including gallbladder cancer (GBC). To determine the frequency of PTEN expression in GBC and to establish its relation to clinical and morphological parameters and survival in GBC. The immunohistochemical expression of PTEN was studied in 108 GBC. All the cases included areas of non-tumor mucosa adjacent to the tumor. The group was comprised of 108 patients, 91 women (84.3 %) and 17 men (15.7 %) with an average age of 65.2 years (SD ± 12.3 years). Thirty-five cases (33 %) were early carcinomas (EC) and the remaining 73 (67 %) were advanced cases (AC). All the internal controls were positive (moderate or intense in 96.3 %). Only in three AC (4.1 %) was there a complete absence of PTEN immunohistochemical expression. There were no significant differences in relation between PTEN expression and tumor infiltration or degree of differentiation. The three patients with PTEN inactivation died before 10 months; however, the other patients with AC had a survival of 53 % at 10 months. Loss of PTEN expression was observed in 4.1 % of the advanced GBC. All the patients with this alteration died before 10 months. PTEN inactivation could be a rare event, but with a poor prognosis in advanced GBC.
    Diagnostic Pathology 08/2015; 10(1):148. DOI:10.1186/s13000-015-0381-2 · 2.60 Impact Factor
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    ABSTRACT: An American Hepato-Pancreato-Biliary Association (AHPBA)-sponsored consensus meeting of expert panellists was convened on 15 January 2014 to review current evidence on the management of gallbladder carcinoma in order to establish practice guidelines. In summary, within high incidence areas, the assessment of routine gallbladder specimens should include the microscopic evaluation of a minimum of three sections and the cystic duct margin; specimens with dysplasia or proven cancer should be extensively sampled. Provided the patient is medically fit for surgery, data support the resection of all gallbladder polyps of >1.0 cm in diameter and those with imaging evidence of vascular stalks. The minimum staging evaluation of patients with suspected or proven gallbladder cancer includes contrasted cross-sectional imaging and diagnostic laparoscopy. Adequate lymphadenectomy includes assessment of any suspicious regional nodes, evaluation of the aortocaval nodal basin, and a goal recovery of at least six nodes. Patients with confirmed metastases to N2 nodal stations do not benefit from radical resection and should receive systemic and/or palliative treatments. Primary resection of patients with early T-stage (T1b-2) disease should include en bloc resection of adjacent liver parenchyma. Patients with T1b, T2 or T3 disease that is incidentally identified in a cholecystectomy specimen should undergo re-resection unless this is contraindicated by advanced disease or poor performance status. Re-resection should include complete portal lymphadenectomy and bile duct resection only when needed to achieve a negative margin (R0) resection. Patients with preoperatively staged T3 or T4 N1 disease should be considered for clinical trials of neoadjuvant chemotherapy. Following R0 resection of T2-4 disease in N1 gallbladder cancer, patients should be considered for adjuvant systemic chemotherapy and/or chemoradiotherapy. © 2015 International Hepato-Pancreato-Biliary Association.
    HPB 08/2015; 17(8):681-90. DOI:10.1111/hpb.12444 · 2.68 Impact Factor
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    ABSTRACT: Metastatic pancreatic adenocarcinoma is considered a uniformly fatal disease with a median survival of 1 year with modern chemotherapy. While a subset of patients achieve prolonged survival, few of the factors that define this group of patients are known. For the determination of overall survival (OS), 549 patients with histologically confirmed metastatic pancreatic adenocarcinoma were evaluated. Emphasis was placed on treatment history and family history of breast, ovarian, and pancreatic cancers. To ensure a uniform metastatic population, patients treated with prior locoregional therapies (i.e., surgery or radiotherapy) were excluded as were patients with a prior history of stage I-III disease. Patients with family history or pedigree history of cancer had superior OS. This was especially true in patients with three or more relatives with either breast, ovarian, or pancreatic cancers [hazard ratio (HR) 0.49, 95 % confidence interval (CI) 0.30-0.80, p = 0.003]. First-line platinum chemotherapy was associated with a poor survival (hazard ratio for death 1.74, 95 % CI 1.12-2.71, p = 0.01) for patients without a family history of these cancers but not for those without such a history (p = 0.31). In fact, as the number of relatives with these cancers increased, the OS survival improved for individuals receiving first-line platinum therapy (HR 0.76, 95 % CI 0.65-0.89, p = 0.0004), which was not the case for those receiving other therapies (p = 0.98). Treatment with platinum chemotherapy in patients with a family history of breast, ovarian, or pancreatic cancers was associated with a longer survival, whereas platinum use in patients without such a family history of cancer was associated with poor survival. These findings suggest that family history may serve as a predictive marker for platinum use in patients with metastatic pancreatic adenocarcinoma.
    Cancer Chemotherapy and Pharmacology 07/2015; 76(3). DOI:10.1007/s00280-015-2788-6 · 2.77 Impact Factor
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    ABSTRACT: Biliary cancers are highly aggressive tumors that are often diagnosed an advanced disease stage and have a poor outcome with systemic therapy. Recent efforts towards molecular characterization have identified a subset of biliary patients that have HER2/neu amplification or mutation. HER2/neu amplification is associated with response to HER2/neu-directed therapy in breast and gastric cancers. However, the efficacy of HER2/neu-targeted therapy in biliary cancers is unknown. We retrospectively reviewed cases of advanced gallbladder cancer and cholangiocarcinoma with HER2/neu genetic aberrations or protein overexpression who received HER2/neu-directed therapy between 2007 and 2014. Clinical data were retrieved from medical records, and imaging studies were independently reviewed. Nine patients with gallbladder cancer and five patients with cholangiocarcinoma had received HER2/neu-directed therapy (trastuzumab, lapatinib, or pertuzumab) during the study period. In the gallbladder cancer group, HER2/neu gene amplification or overexpression was detected in eight cases. These patients experienced disease stability (n = 3), partial response (n = 4), or complete response (n = 1) with HER2/neu-directed therapy. One patient had HER2/neu mutation and experienced a mixed response after lapatinib therapy. The duration of response varied from 8+ to 168 weeks (median 40 weeks), and three patients are still on therapy. One patient developed HER2/neu amplification as a secondary event after FGFR-directed therapy for FGF3-TACC3 gene fusion. The cholangiocarcinoma cases treated in this series had a higher proportion of HER2/neu mutations, and no radiological responses were seen in these patients despite HER2/neu-directed therapy. HER2/neu blockade is a promising treatment strategy for gallbladder cancer patients with gene amplification and deserves further exploration in a multi-center study.
    Journal of Hematology & Oncology 05/2015; 8(1):58. DOI:10.1186/s13045-015-0155-z · 4.81 Impact Factor
  • Gastroenterology 04/2015; 148(4):S-1024. DOI:10.1016/S0016-5085(15)33503-4 · 16.72 Impact Factor
  • Mingxin Zuo · Chenglong Li · Jiayuh Lin · Milind Javle
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    ABSTRACT: ABSTRACT The constitutive activation of signal transducer and activator of transcription 3 (STAT3) is frequently detected in clinical incidences of hepatocellular carcinoma (HCC) but not in normal human hepatocytes. STAT3 signaling plays pivotal roles in angiogenesis, survival, metastasis, and growth of HCC. Recent evidence suggests that the blockade of aberrant STAT3 pathways can be exploited as a therapeutic strategy for HCC. We have developed the novel small molecular STAT3 inhibitor LLL12 on the basis of curcumin structure using computer-aided rational design. LLL12 has shown antitumor activity in various solid tumors including breast, brain, pancreatic cancer, and glioblastoma in vitro and in vivo. In this study, we hypothesized LLL12 inhibits STAT3 phosphorylation at tyrosine 705 (Y705) in HCC and show antitumor activity in HCC in vitro and in vivo. Our results show that LLL12 selectively inhibited HCC cell proliferation and induced apoptosis in SNU387, SNU398, SNU449, and Hep3B HCC cells in vitro. Furthermore, LLL12 at 5 mg/kg/day significantly inhibited the growth of SNU398 xenografts in nude mice. Collectively, our results indicate that LLL12 could be used to target STAT3 for the effective prevention or treatment of HCC.
    Oncotarget 03/2015; 6(13). DOI:10.18632/oncotarget.3458 · 6.36 Impact Factor
  • M Zuo · A Rashid · C Churi · J-N Vauthey · P Chang · Y Li · M-C Hung · D Li · M Javle
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    ABSTRACT: Background: Activation of the PI3K/mTOR and Hedgehog (Hh) signalling pathways occurs frequently in biliary tract cancer (BTC). Crosstalk between these pathways occurs in other gastrointestinal cancers. The respective signalling inhibitors rapamycin and vismodegib may inhibit BTC synergistically and suppress cancer stem cells (CSCs). Methods: Gene expression profiling for p70S6k and Gli1 was performed with BTC cell lines. Tumour and pathway inhibitory effects of rapamycin and vismodegib were investigated in BTC preclinical models and CSCs. Results: Rapamycin and vismodegib synergistically reduced BTC cell viability and proliferation. This drug combination arrested BTC Mz-ChA-1 cells in the G1 phase but had no significant effect on the cell cycle of BTC Sk-ChA-1 cells. Combined treatment inhibited the proliferation of CSCs and ALDH-positive cells. Nanog and Oct-4 expression in CSCs was decreased by the combination treatment. Western blotting results showed the p-p70S6K, p-Gli1, p-mTOR, and p-AKT protein expression were inhibited by the combination treatment in BTC cells. In an Mz-ChA-1 xenograft model, combination treatment resulted in 80% inhibition of tumour growth and prolonged tumour doubling time. In 4 of 10 human BTC specimens, tumour p-p70S6K and Gli1 protein expression levels were decreased with the combination treatment. Conclusions: Targeted inhibition of the PI3K/mTOR and Hhpathways indicates a new avenue for BTC treatment with combination therapy.
    British Journal of Cancer 03/2015; 112(6). DOI:10.1038/bjc.2014.625 · 4.84 Impact Factor
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    ABSTRACT: Background and aims: Platelets are believed to promote tumor growth and metastasis but their prognostic role in locally advanced pancreatic cancer (LAPC) remains largely unknown. We assessed whether pretreatment platelet counts independently predict survival outcomes in patients with LAPC treated with chemoradiation (CRT). Methods: We retrospectively reviewed the MD Anderson pancreatic cancer database and identified 199 patients with LAPC treated with CRT between 2006 and 2012. Induction chemotherapy was used prior to consolidative CRT in 177 (89%) patients. Median radiation dose was 50.4 Gy. Concurrent radiosensitizers were gemcitabine-based (13%) or capecitabine-based (84%) regimens. Actuarial univariate and multivariate statistical methods were used to determine significant prognostic factors for overall survival (OS) and progression-free survival (PFS) calculated from the start of treatment. Results: Median follow-up was 9.9 months. Median OS and PFS durations were 17.7 and 10.7 months, respectively. On univariate analysis, platelet count > 300 K/μl, KPS ≤ 80, ≥ 5% weight loss and pretreatment CA19-9 above the median were associated with inferior OS or PFS. Median OS was lower in patients with platelet count > 300 K/μl compared to patients with platelet count ≤ 300 K/μl (10.2 vs. 19 months; p = 0.0002). Corresponding median PFS times were 7.8 months and 11.1 months (p = 0.004), respectively. On multivariate analysis, platelet count > 300 K/μl (p = 0.012), ≥ 5% weight loss (p = 0.002) and elevated pretreatment CA19-9 (p = 0.005) were independent prognostic factors for OS. Platelet count > 300 K/μl (p = 0.03) and KPS ≤ 80 (p = 0.05) independently predicted PFS. Conclusions: Our analysis suggests that pretreatment thrombocytosis independently predicts inferior OS and PFS in LAPC.
    Acta oncologica (Stockholm, Sweden) 01/2015; 54(7):1-8. DOI:10.3109/0284186X.2014.1000466 · 3.00 Impact Factor
  • 2015 American Society of Clinical Oncology Gastrointestinal Cancers Symposium, San Francisco; 01/2015
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    ABSTRACT: Cholangiocarcinoma (CCA) is clinically heterogeneous; intra and extrahepatic CCA have diverse clinical presentations. Next generation sequencing (NGS) technology may identify the genetic differences between these entities and identify molecular subgroups for targeted therapeutics. We describe successful NGS-based testing of 75 CCA patients along with the prognostic and therapeutic implications of findings. Mutation profiling was performed using either a) NGS panel of hotspot regions in 46 cancer-related genes using a 318-chip on Ion PGM Sequencer or b) Illumina HiSeq 2000 sequencing platform for 3,769 exons of 236 cancer-related genes plus 47 introns from 19 genes to an average depth of 1000X. Clinical data was abstracted and correlated with clinical outcome. Patients with targetable mutations were referred to appropriate clinical trials. There were significant differences between intrahepatic (n = 55) and extrahepatic CCA (n = 20) in regard to the nature and frequency of the genetic aberrations (GAs). IDH1 and DNA repair gene alterations occurred more frequently in intrahepatic CCA, while ERBB2 GAs occurred in the extrahepatic group. Commonly occurring GAs in intrahepatic CCA were TP53 (35%), KRAS (24%), ARID1A (20%), IDH1 (18%), MCL1 (16%) and PBRM1 (11%). Most frequent GAs in extrahepatic CCA (n = 20) were TP53 (45%), KRAS (40%), ERBB2 (25%), SMAD4 (25%), FBXW7 (15%) and CDKN2A (15%). In intrahepatic CCA, KRAS, TP53 or MAPK/mTOR GAs were significantly associated with a worse prognosis while FGFR GAs correlated with a relatively indolent disease course. IDH1 GAs did not have any prognostic significance. GAs in the chromatin modulating genes, BAP1 and PBRM1 were associated with bone metastases and worse survival in extrahepatic CCA. Radiologic responses and clinical benefit was noted with EGFR, FGFR, C-met, B-RAF and MEK inhibitors. There are significant genetic differences between intra and extrahepatic CCA. NGS can potentially identify disease subsets with distinct prognostic and therapeutic implications.
    PLoS ONE 12/2014; 9(12):e115383. DOI:10.1371/journal.pone.0115383 · 3.23 Impact Factor
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    ABSTRACT: Gemcitabine plus platinum (GEM-P) combination chemotherapy is standard treatment for first-line advanced cholangiocarcinoma (aCC). GEM-P first-line therapy reports a progression-free survival (PFS) of 8 months and overall survival (OS) of 11.7 months. Treatment in the second-line setting is less clear. Five-year survival for aCC remains dismal at 5-10%. The purpose of this study was to describe the outcomes with second-line systemic treatment at our institution. This study was a single institution retrospective chart review of aCC patients who initiated second-line systemic treatment during 1/1/2009 to 12/31/2012. The primary objective was to evaluate PFS with second-line systemic treatment. Secondary objectives were OS and disease control rate. Second-line systemic regimens were classified into four treatment groups: GEM-P, gemcitabine + fluoropyrimidine (GEM-FU), other FU combination (FU-combo), and others. Fifty-six patients were included and the majority had intrahepatic aCC. A total of 80% received first-line gemcitabine-based therapy. Second-line therapy consisted of GEM-P (19.6%), GEM-FU (28.6%), FU-combo (37.5%), and others (14.3%). Median PFS was 2.7-month (95% CI, 2.3-3.8 months) with a median OS of 13.8 months (95% CI, 12-19.3 months) and a disease control rate of 50%. No significant difference in survival was identified between the four treatment groups. This study revealed a 2.7-month PFS, 50% disease control rate, and potential survival benefit with second-line treatment. Options for second-line systemic therapy include GEM-FU, FU-combo, GEM-P if not given in the first-line setting. Targeted therapy with erlotinib or bevacizumab could be considered in addition to chemotherapy.
    Journal of gastrointestinal oncology 12/2014; 5(6):408-413. DOI:10.3978/j.issn.2078-6891.2014.072
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    ABSTRACT: There is substantial heterogeneity in the clinical behavior of pancreatic cancer and in its response to therapy. Some of this variation may be due to differences in delivery of cytotoxic therapies between patients and within individual tumors. Indeed, in 12 patients with resectable pancreatic cancer, we previously demonstrated wide inter-patient variability in the delivery of gemcitabine as well as in the mass transport properties of tumors as measured by computed tomography (CT) scans. However, the variability of drug delivery and transport properties within pancreatic tumors is currently unknown. Here, we analyzed regional measurements of gemcitabine DNA incorporation in the tumors of the same 12 patients to understand the degree of intra-tumoral heterogeneity of drug delivery. We also developed a volumetric segmentation approach to measure mass transport properties from the CT scans of these patients and tested inter-observer agreement with this new methodology. Our results demonstrate significant heterogeneity of gemcitabine delivery within individual pancreatic tumors and across the patient cohort, with gemcitabine DNA incorporation in the inner portion of the tumors ranging from 38 to 74% of the total. Similarly, the CT-derived mass transport properties of the tumors had a high degree of heterogeneity, ranging from minimal difference to almost 200% difference between inner and outer portions of the tumor. Our quantitative method to derive transport properties from CT scans demonstrated less than 5% difference in gemcitabine prediction at the average CT-derived transport value across observers. These data illustrate significant inter-patient and intra-tumoral heterogeneity in the delivery of gemcitabine, and highlight how this variability can be reproducibly accounted for using principles of mass transport. With further validation as a biophysical marker, transport properties of tumors may be useful in patient selection for therapy and prediction of therapeutic outcome.
    Physical Biology 12/2014; 11(6):065002. DOI:10.1088/1478-3975/11/6/065002 · 2.54 Impact Factor
  • Sidra Anwar · Wei Tan · Jinhee Yu · Alan Hutson · Milind Javle · Renuka Iyer
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    ABSTRACT: Pancreatic cancer is rapidly fatal with median survival of only 6 months (mo). Quality-of-life (QoL) was analyzed prospectively in a phase 2 study of gemcitabine (G), capecitabine (C) and bevacizumab (B) in APC patients. A total of 50 patients with APC received B 15 mg/kg, C 1,300 mg/m(2) daily for 2 weeks and G 1,000 mg/m(2) weekly 2 times; cycles were repeated every 21 days. Endpoints: progression free survival (PFS), overall survival (OS) and assessment of QoL prior to each cycle using the European organization for research and treatment of cancer (EORTC) PAN-26 QoL questionnaire. An exact 95% confidence interval (CI) (Clopper-Pearson method) was used to assess rate of improved QoL (defined as >5% decrease in two consecutive scores compared with baseline). Patient characteristics- Stage IIB/III/IV: 3/5/42; Sex: 28 M/22 F; Median age: 64 years. QoL in patients- improved: 56%, no improvement: 24%; unevaluable: 20%. Median PFS: 5.8 mo, OS: 9.8 mo. QoL improvement rate: 28/40=0.7 (95% CI: 0.53-0.83) in evaluable patients. Using QoL improvement rate, no significant difference was seen in patients with OS ≥6 mo compared to OS <6 mo. However QoL scores at 3 and 6 weeks from start of treatment correlated strongly with ≥6 mo survival (P value 0.0092 and 0.0081, respectively). Baseline score and change in QoL scores of patients on G, C and B were not predictive of survival ≥6 mo. Post treatment scores at 3 and 6 weeks from start of therapy however, were predictive of survival ≥6 mo suggesting the potential predictive value of this tool for use in future studies.
    Journal of gastrointestinal oncology 12/2014; 5(6):433-439. DOI:10.3978/j.issn.2078-6891.2014.070
  • Milind Javle · Smyth EC · Ian Chau
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    ABSTRACT: Gastric cancer is the fourth most common cancer globally and represents the second most common cause of cancer mortality. Early detection, aggressive surgical resection and postoperative adjuvant therapy has led to survival improvement for early stage gastric cancer, particularly in Asian countries. Unfortunately, advanced gastric cancer continues to pose a formidable challenge with few gains being reported recently. Trastuzumab was the first targeted agent to be approved for the treatment of advanced gastric cancer in 2010. The failure of the AVAGAST trial was a setback for anti-angiogenic therapy for this disease. Ramucirumab is a monoclonal antibody that binds to VEGF-R2 and prevents its activation. The recent REGARD trial was a randomized phase III trial of ramucirumab vs. placebo for patients with advanced, pre-treated gastric cancer that met its primary endpoint of increased overall survival. The toxicity of ramucirumab was modest in this setting, with an increased risk of grade 3 or higher hypertension (8% vs. 3%, with ramucirumab and placebo, respectively). The subsequent RAINBOW trial of paclitaxel plus ramucirumab vs. paclitaxel plus placebo for advanced pretreated gastric cancer confirmed the survival advantage of this antiangiogenic agent in gastric cancer. Ramucirumab is the first FDA approved therapy for advanced gastric cancer after prior chemotherapy.
    Clinical Cancer Research 10/2014; 20(23). DOI:10.1158/1078-0432.CCR-14-1071 · 8.72 Impact Factor
  • Cancer Research 10/2014; 74(19 Supplement):5361-5361. DOI:10.1158/1538-7445.AM2014-5361 · 9.33 Impact Factor
  • Cancer Research 10/2014; 74(19 Supplement):2784-2784. DOI:10.1158/1538-7445.AM2014-2784 · 9.33 Impact Factor
  • F Huguet · S Mukherjee · M Javle
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    ABSTRACT: At the time of diagnosis, around 20% of patients with pancreatic cancer present at a resectable stage, 50% have metastatic disease and 30% have locally advanced tumour, non-metastatic but unresectable because of superior mesenteric artery or coeliac encasement. Despite advances in chemoradiotherapy and improved systemic chemotherapeutic agents, patients with locally advanced pancreatic cancer suffer from high rates of distant metastatic failure and from local progression, with a median survival time ranging from 5 to 11 months. In the past 30 years, modest improvements in median survival have been attained for these patients treated by chemoradiotherapy or chemotherapy protocols. The optimal therapy for patients with locally advanced pancreatic carcinoma remains controversial. This review aims to evaluate the role of radiotherapy for these patients.
    Clinical Oncology 07/2014; 26(9). DOI:10.1016/j.clon.2014.06.002 · 3.40 Impact Factor
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    ABSTRACT: Pancreatic adenosquamous carcinoma (ASC) is an enigmatic and aggressive tumor that has a worse prognosis and higher metastatic potential than its adenocarcinoma counterpart. Here we report that ASC tumors frequently harbor somatically acquired mutations in the UPF1 gene, which encodes the core component of the nonsense-mediated RNA decay (NMD) pathway. These tumor-specific mutations alter UPF1 RNA splicing and perturb NMD, leading to upregulated levels of NMD substrate mRNAs. UPF1 mutations are, to our knowledge, the first known unique molecular signatures of pancreatic ASC.
    Nature Medicine 05/2014; 20(6). DOI:10.1038/nm.3548 · 27.36 Impact Factor
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    ABSTRACT: Objective: To determine the prognostic impact of tumor location in gallbladder cancer. Background: Depth of tumor is a strong predictor of survival after curative resection of gallbladder cancer. However, the gallbladder has a unique anatomical relationship with the liver, and the clinical significance of tumor location remains unclear. Methods: For 437 patients with gallbladder cancer who underwent resection at 4 international institutions, clinicopathologic characteristics and their association with survival were analyzed. Tumor location was defined as "hepatic side" or "peritoneal side," and the prognostic significance of tumor location was evaluated. Results: Among the 252 patients with T2 disease, patients with tumors on the hepatic side (T2h, n = 99) had higher rates of vascular invasion, neural invasion, and nodal metastasis than patients with tumors on the peritoneal side (T2p, n = 153) (51% vs 19%, 33% vs 8%, and 40% vs 17%, respectively; P < 0.01 for all). After a median follow-up of 58.9 months, 3-year and 5-year survival rates were 52.1% and 42.6%, respectively, for T2h tumors and 73.7% and 64.7%, respectively, for T2p tumors (P = 0.0006). No such differences were observed in T1 or T3 tumors. Multivariate analysis confirmed the independent association of hepatic-side location with survival in T2 tumors (hazard ratio, 2.7; 95% confidence interval, 1.7-4.2; P < 0.001). This subclassification of T2 tumors predicted recurrence in the liver (23% vs 3%; P = 0.003) and distant lymph nodes (16% vs 3%; P = 0.019) even after radical resection. Conclusions: After curative resection of T2 gallbladder cancer, tumor location predicts the pattern of recurrence and survival.
    Annals of Surgery 05/2014; 261(4). DOI:10.1097/SLA.0000000000000728 · 8.33 Impact Factor

Publication Stats

2k Citations
607.09 Total Impact Points


  • 2007–2015
    • University of Texas MD Anderson Cancer Center
      • Department of Surgical Oncology
      Houston, Texas, United States
  • 2007–2011
    • University of Houston
      Houston, Texas, United States
  • 2003–2010
    • Roswell Park Cancer Institute
      • • Department of Medicine
      • • Roswell Park Cancer Institute, Elm and Carlton Streets
      • • Department of Medical Oncology
      Buffalo, New York, United States
  • 2005–2006
    • University at Buffalo, The State University of New York
      • Department of Medicine
      Buffalo, New York, United States
    • Erie County Medical Center
      New York City, New York, United States
  • 2004
    • State University of New York
      New York City, New York, United States