James D Luketich

University of Pittsburgh, Pittsburgh, Pennsylvania, United States

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Publications (415)1446.46 Total impact

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    ABSTRACT: Although the benefits of ex vivo lung perfusion (EVLP) have been globally advocated, the potentially deleterious effects of applying EVLP, in particular activation of proinflammatory cascades and alteration of metabolic profiles, are rarely discussed. This study examined proinflammatory events and metabolic profiles in lung grafts on EVLP and tested whether preconditioning lung grafts with inhaled hydrogen, a potent, cytoprotective gaseous signaling molecule, would alter the lungs' response to EVLP.
    Transplantation 07/2014; · 3.78 Impact Factor
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    ABSTRACT: Although anatomic segmentectomy has been considered a compromised procedure by many surgeons, recent retrospective, single-institution series have demonstrated tumor recurrence and patient survival rates that approximate those achieved by lobectomy. The primary objective of this study was to use propensity score matching to compare outcomes after these anatomic resection approaches for stage I non-small-cell lung cancer.
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 06/2014;
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    ABSTRACT: This investigation was aimed to see whether PJ34(TM), a PARP inhibitor, could exert cytotoxicity in six nonsmall cell lung cancer cell lines developed from surgically resected tissues. Using various biochemical assays, we have seen that PJ34(TM) effects are consistent between untreated and treated samples but still somewhat variable between each cell line. Changes in protein expression and mitochondrial membrane potential between treated and untreated cells were indicating the possibility of apoptosis induction through an intrinsic pathway which causes cytotoxicity. Present results open the possibility of elucidating a decisive mechanism and effectiveness of chemotherapeutics specific to a patient.
    Cancer Investigation 06/2014; · 2.24 Impact Factor
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    ABSTRACT: A shortage of donors has compelled the use of extended-criteria donor organs in lung transplantation. The purpose of this study was to evaluate the impact of using older donors on outcomes after lung transplantation using current protocols. From January 2003 to August 2009, 593 lung transplants were performed at our institution. We compared 87 patients (14.7%) who received lungs from donors aged 55 years or older with 506 patients who received lungs from donors less than 55 years old. We also examined risk factors for mortality in recipients of lungs from older donors. The incidence of major complications including severe primary graft dysfunction and early mortality rates were similar between the groups. However, posttransplant peak FEV1 was lower in the patients who received lungs from older donors (71.7% vs. 80.7%, P<0.05). In multivariate analysis, recipient pulmonary hypertension (transpulmonary pressure gradient >20 mm Hg) and prolonged intraoperative cardiopulmonary bypass were significant risk factors for mortality in the recipients of lungs from older donors. This large, single-center experience demonstrated that transplanting lungs from donors older than 55 years did not yield worse short- or long-term outcomes as compared with transplanting lungs from younger donors. However, transplanting lungs from older donors into recipients with pulmonary hypertension or recipients who required prolonged cardiopulmonary bypass increased the risk for mortality. Although lungs from older donors should not be excluded because of donor age alone, surgeons should carefully consider their patient selection criteria and surgical plans when transplanting lungs from older donors.
    Transplantation 05/2014; · 3.78 Impact Factor
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    ABSTRACT: The treatment approach for superficial (stage T1) esophageal adenocarcinoma critically depends on the pre-operative assessment of metastatic risk. Part of that assessment involves evaluation of the primary tumor for pathologic characteristics known to predict nodal metastasis: depth of invasion (intramucosal vs submucosal), angiolymphatic invasion, tumor grade, and tumor size. Tumor budding is a histologic pattern that is associated with poor prognosis in early-stage colorectal adenocarcinoma and a predictor of nodal metastasis in T1 colorectal adenocarcinoma. In a retrospective study, we used a semi-quantitative histologic scoring system to categorize 210 surgically resected, superficial (stage T1) esophageal adenocarcinomas according to the extent of tumor budding (none, focal, and extensive) and also evaluated other known risk factors for nodal metastasis, including depth of invasion, angiolymphatic invasion, tumor grade, and tumor size. We assessed the risk of nodal metastasis associated with tumor budding in univariate analyses and controlled for other risk factors in a multivariate logistic regression model. In all, 41% (24 out of 59) of tumors with extensive tumor budding (tumor budding in ≥3 20X microscopic fields) were metastatic to regional lymph nodes, compared with 10% (12 out of 117) of tumors with no tumor budding, and 15% (5 out of 34) of tumors with focal tumor budding (P<0.001). When controlling for all pathologic risk factors in a multivariate analysis, extensive tumor budding remains an independent risk factor for lymph node metastasis in superficial esophageal adenocarcinoma associated with a 2.5-fold increase (95% CI=1.1-6.3, P=0.039) in the risk of nodal metastasis. Extensive tumor budding is also a poor prognostic factor with respect to overall survival and time to recurrence in univariate and multivariate analyses. As an independent risk factor for nodal metastasis and poor prognosis after esophagectomy, tumor budding should be evaluated in superficial (T1) esophageal adenocarcinoma as a part of a comprehensive pathologic risk assessment.Modern Pathology advance online publication, 25 April 2014; doi:10.1038/modpathol.2014.66.
    Modern Pathology 04/2014; · 5.25 Impact Factor
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    ABSTRACT: Cyclin E is a cell cycle regulator which is critical for driving G1/S transition. Abnormal levels of cyclin E have been found in many cancers. However, the level changes of cyclin E in esophageal adenocarcinoma and its precancerous lesion have not been well studied. Here, we focus on the gene amplification and expression of cyclin E in these lesions, and aim to ascertain the relationship with clinicopathological characteristics. Genomic DNA was analyzed from 116 esophageal adenocarcinoma and 26 precancerous lesion patients using Affymetrix SNP 6.0 arrays. The protein overexpression of cyclin E was also detected using immunohistochemistry from tissue microarrays containing esophageal adenocarcinoma and precancerous lesions. Patient survival and other clinical data were collected and analyzed. The intensity and percentage of the cyclin E expressing cells in tissue microarrays were scored by two pathologists. Fisher exact tests and Kaplan-Meier methods were used to analyze data. By genomic analysis, cyclin E was amplified in 19.0% of the EAC samples. By immunohistochemistry, high expression of cyclin E was observed in 2.3% of squamous mucosa tissues, 3.7% in columnar cell metaplasia, 5.8% in Barrett's esophagus, 19.0% in low grade dysplasia, 35.7% in high grade dysplasia, and 16.7% in esophageal adenocarcinoma. The differences in cyclin E high expression between neoplastic groups and non-dysplasia groups are statistically significant (p < 0.05). The prognosis for patients with high cyclin E expression appeared slightly better than for those with low cyclin E expression although this was not statistically significant (p = 0.13). The expression of cyclin E significantly increases from non-dysplasia esophageal lesion to low and high grade dysplasia, suggesting that cyclin E plays an important role in the early stage of carcinogenesis. Importantly, cyclin E is also amplified and highly expressed in a subset of esophageal adenocarcinoma patients, but this increase is not associated with worse prognosis.
    BMC Gastroenterology 04/2014; 14(1):78. · 2.11 Impact Factor
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    ABSTRACT: Rac3 is a small GTPase multifunctional protein that regulates cell adhesion, migration, and differentiation. It has been considered as an oncogene in breast cancer; however, its role in esophageal cancer and the regulation of its stability have not been studied. F-box proteins are major subunits within the Skp1-Cullin-1-F-box (SCF) E3 ubiquitin ligases that recognize particular substrates for ubiquitination and proteasomal degradation. Recently, we have shown that SCFFBXL19 targets Rac1 and RhoA, thus regulating Rac1 and RhoA ubiquitination and degradation. Here, we demonstrate the role of FBXL19 in the regulation of Rac3 site-specific ubiquitination and stability. Expression of TGFbeta1 is associated with poor prognosis of esophageal cancer. TGFbeta1 reduces tumor suppressor, E-cadherin, expression in various epithelial-derived cancers. Here we investigate the role of FBXL19-mediated Rac3 degradation in TGFbeta1-induced E-cadherin down-regulation in esophageal cancer cells. FBXL19-regulated endogenous and over-expressed Rac3 stability were determined by immunoblotting and co-immunoprecipitation. Esophageal cancer cells (OE19 and OE33) were used to investigate TGFbeta1-induced E-cadherin down-regulation by Immunoblotting and Immunostaining. Overexpression of FBXL19 decreased endogenous and over-expressed Rac3 expression by interacting and polyubiquitinating Rac3, while down-regulation of FBXL19 suppressed Rac3 degradation. Lysine166 within Rac3 was identified as an ubiquitination acceptor site. The FBXL19 variant with truncation at the N-terminus resulted in an increase in Rac3 degradation; however, the FBXL19 variant with truncation at the C-terminus lost its ability to interact with Rac3 and ubiquitinate Rac3 protein. Further, we found that Rac3 plays a critical role in TGFbeta1-induced E-cadherin down-regulation in esophageal cancer cells. Over-expression of FBXL19 attenuated TGFbeta1-induced E-cadherin down-regulation and esophageal cancer cells elongation phenotype. Collectively these data unveil that FBXL19 functions as an antagonist of Rac3 by regulating its stability and regulates the TGFbeta1-induced E-cadherin down-regulation. This study will provide a new potential therapeutic strategy to regulate TGFbeta1 signaling, thus suppressing esophageal tumorigenesis.
    Molecular Cancer 04/2014; 13(1):76. · 5.13 Impact Factor
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    ABSTRACT: Thoracic surgeons are commonly consulted to provide anterior thoracic exposure for infection and malignant neoplasms involving the thoracolumbar spine. These cases can present significant technical and management challenges secondary to the underlying pathology, associated anatomic inflammation, and impaired functional status. In this study, we review the perioperative outcomes in patients undergoing anterior spinal exposure for infection and neoplasm. 130 consecutive patients (61 women, 69 men) undergoing corpectomy, debridement, or debulking for osteomyelitis (n = 50) or neoplasms (n = 80) with decompression/stabilization at a single institution were analyzed. Primary endpoints included morbidity, mortality, and perioperative neurologic outcomes. The mean age was 61.1 years. A cervical/sternotomy (n = 8) approach was used for levels C7 to T2, thoracotomy (n = 79) for levels T3 to T10, and thoracoabdominal (n = 43) for T11 to L2 involvement. Primary spinal neoplasms (n = 22, 16.9 %) and metastases (n = 58, 44.6%) were treated with corpectomy and prosthetic stabilization and were associated with increased operative time (310 vs 243 minutes, p = 0.02) and blood loss (825 vs 500 mL, p = 0.002). Osteomyelitis was associated with longer hospital stays (12 vs 7 days, p < 0.001). The 30-day and 90-day mortality was 9.2% and 20.8%, respectively. The major complication rate was 27.7%. The median length of stay was 9 days. Surgical intervention resulted in significant improvement in pain, numbness, weakness, and bowel and bladder dysfunction. Anterior spinal exposure represents an important modality in facilitating the treatment of patients with osteomyelitis, pathologic fractures, and spinal cord compression syndromes. These procedures are associated with a significant risk of morbidity and mortality, but they are effective in achieving spinal stabilization and alleviating neurologic symptoms.
    The Annals of thoracic surgery 03/2014; · 3.45 Impact Factor
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    ABSTRACT: Enumeration of T-lymphocytic sub-population of sheep sensitized with sheep pox virus.. (2005) Notch ligand (Delta-like-1) can support the development of bone marrow stem, presented at 16th Annual Fanconi Anemia Scientific Symposium held at Geneva, Switzerland, September 29th through October 2nd, 2005. 4.. (2006) Lymphocyte progenitor cells can facilitate syngeneic and allogeneic bone marrow transplantation.. (2008) Bone marrow derived lymphocyte progenitor cells (CD8 + TCR
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    ABSTRACT: To determine and compare the frequency of cancer-associated genetic abnormalities in esophageal metaplasia biopsies with and without goblet cells. Barrett's esophagus is associated with increased risk of esophageal adenocarcinoma (EAC), but the appropriate histologic definition of Barrett's esophagus is debated. Intestinal metaplasia (IM) is defined by the presence of goblet cells whereas nongoblet cell metaplasia (NGM) lacks goblet cells. Both have been implicated in EAC risk but this is controversial. Although IM is known to harbor genetic changes associated with EAC, little is known about NGM. We hypothesized that if NGM and IM infer similar EAC risk, then they would harbor similar genetic aberrations in genes associated with EAC. Ninety frozen NGM, IM, and normal tissues from 45 subjects were studied. DNA copy number abnormalities were identified using microarrays and fluorescence in situ hybridization. Targeted sequencing of all exons from 20 EAC-associated genes was performed on metaplasia biopsies using Ion AmpliSeq DNA sequencing. Frequent copy number abnormalities targeting cancer-associated genes were found in IM whereas no such changes were observed in NGM. In 1 subject, fluorescence in situ hybridization confirmed loss of CDKN2A and amplification of chromosome 8 in IM but not in a nearby NGM biopsy. Targeted sequencing revealed 11 nonsynonymous mutations in 16 IM samples and 2 mutations in 19 NGM samples. This study reports the largest and most comprehensive comparison of DNA aberrations in IM and NGM genomes. Our results show that IM has a much higher frequency of cancer-associated mutations than NGM.
    Annals of surgery 02/2014; · 7.90 Impact Factor
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    ABSTRACT: This retrospective study aims to assess the usefulness of SUVmax from FDG-PET imaging as a prognosticator for primary biopsy-proven stage I NSCLC treated with SBRT. This study includes 95 patients of median age 77 years, with primary, biopsy-confirmed peripheral stage IA/IB NSCLC. All patients were treated with 60Gy in 3 fractions with a median treatment time of six days. Local, regional, and distant failures were evaluated independently according to the terms of RTOG1021. Local, regional, and distant control, overall- and progression-free survival were estimated by the Kaplan-Meier method. Cox proportional hazards regression was performed to determine whether SUVmax, age, KPS, gender, tumor size/T stage, or smoking history influenced outcomes. SUVmax was evaluated as both a continuous and as a dichotomous variable using a cutoff of <5 and >=5. Median follow-up for the cohort was 16 months. Median OS and PFS were 25.3 and 40.3 months, respectively. SUV with a cutoff value of 5 predicted for OS and PFS (p = .024 for each) but did not achieve significance for LC (p = .256). On Cox univariate regression analysis, SUV as a dichotomous variable predicted for both OS and PFS (p = .027 and p = .030, respectively). Defined as a continuous variable, SUVmax continued to predict for OS and PFS (p = .032 and p = .003), but also predicted LC (p = .045) and trended toward significance for DC (p = .059).SUVmax did not predict for OS as a dichotomous or continuous variable. It did, however, predict for PFS as a continuous variable (p = .008), neared significance for local control (p = .057) and trended towards, significance for distant control (p = .092). SUVmax appears to be a statistically and clinically significant independent prognostic marker for progression-free survival in patients with stage I NSCLC treated with SBRT. Prospective studies to more accurately define the role of tumor FDG uptake in the prognosis of NSCLC are warranted.
    Radiation Oncology 01/2014; 9(1):41. · 2.11 Impact Factor
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    ABSTRACT: Prognostic biomarkers are needed for superficial gastroesophageal adenocarcinoma (EAC) to predict clinical outcomes and select therapy. Although recurrent mutations have been characterized in EAC, little is known about their clinical and prognostic significance. Aneuploidy is predictive of clinical outcome in many malignancies but has not been evaluated in superficial EAC. We quantified copy number changes in 41 superficial EAC using Affymetrix SNP 6.0 arrays. We identified recurrent chromosomal gains and losses and calculated the total copy number abnormality (CNA) count for each tumor as a measure of aneuploidy. We correlated CNA count with overall survival and time to first recurrence in univariate and multivariate analyses. RECURRENT SEGMENTAL GAINS AND LOSSES INVOLVED MULTIPLE GENES, INCLUDING: HER2, EGFR, MET, CDK6, KRAS (recurrent gains); and FHIT, WWOX, CDKN2A/B, SMAD4, RUNX1 (recurrent losses). There was a 40-fold variation in CNA count across all cases. Tumors with the lowest and highest quartile CNA count had significantly better overall survival (p = 0.032) and time to first recurrence (p = 0.010) compared to those with intermediate CNA counts. These associations persisted when controlling for other prognostic variables. SNP arrays facilitate the assessment of recurrent chromosomal gain and loss and allow high resolution, quantitative assessment of segmental aneuploidy (total CNA count). The non-monotonic association of segmental aneuploidy with survival has been described in other tumors. The degree of aneuploidy is a promising prognostic biomarker in a potentially curable form of EAC.
    PLoS ONE 01/2014; 9(1):e79079. · 3.53 Impact Factor
  • The Journal of thoracic and cardiovascular surgery 01/2014; · 3.41 Impact Factor
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    ABSTRACT: Ex vivo lung perfusion (EVLP) strategies represent a new frontier in lung transplantation technology, and there have been many clinical studies of EVLP in lung transplantation. The establishment of a reliable EVLP model in small animals is crucial to facilitating translational research using an EVLP strategy. The main objective of this study was to develop a reproducible rat EVLP (R-EVLP) model that enables prolonged evaluation of the explanted lung during EVLP and successful transplantation after EVLP. The donor heart-lung blocks were procured with cold low-potassium dextran solution and immersed in the solution for 1 h at 4°C. And then, the heart-lung blocks were flushed retrogradely and warmed up to 37°C in a circuit perfused antegradely with acellular perfusate. The perfusate was deoxygenated with a gas mixture (6% O2, 8% CO2, 86% N2). The perfusion flow was maintained at 20% of the entire cardiac output. At 37°C, the lungs were mechanically ventilated and perfusion continued for 4 h. Every hour, the perfused lung was evaluated for gas exchange, dynamic lung compliance (Cdyn) and pulmonary vascular resistance (PVR). R-EVLP was performed for 4 h. Pulmonary oxygenation ability (pO2/pCO2) was stable for 4 h during EVLP. It was noted that Cdyn and PVR were also stable. After 4 h of EVLP, pO2 was 303 ± 19 mmHg, pCO2 was 39.6 ± 1.2 mmHg, PVR was 1.75 ± 0.10 mmHg/ml/min and Cdyn was 0.37 ± 0.03 ml/cmH2O. Lungs that were transplanted after 2 h of R-EVLP resulted in significantly better post-transplant oxygenation and compliance when compared with those after standard cold static preservation. Our R-EVLP model maintained stable lung oxygenation, compliance and vascular resistance for up to 4 h of perfusion duration. This reliable model should facilitate further advancement of experimental work using EVLP.
    European journal of cardio-thoracic surgery: official journal of the European Association for Cardio-thoracic Surgery 01/2014; · 2.40 Impact Factor
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    ABSTRACT: Background Delayed chest closure (DCC) following lung transplantation is a viable option to be taken in the cases of prolonged cardiopulmonary bypass time, prolonged ischemic time, coagulopathic problems, or oversized donor lung grafts. Decision-making for DCC in the operating room remains challenging to surgeons, because the impact of DCC on outcomes after lung transplantation has not yet been fully elucidated. Methods We performed a retrospective review of 90 lung transplantations with DCC and 783 cases with primary chest closure to clarify the reasons for DCC, complications of DCC, and the risk factors for adverse outcomes. Results The 30- and 90-day mortality in the DCC group were 7.8% and 9.9%, respectively. Early postoperative bleeding and severe primary graft dysfunction (PGD) were higher in the DCC group (p<0.05). In multivariate analysis, prolonged cardiopulmonary bypass use (>4 hours), postoperative extracorporeal oxygen requirement, and use of a DCC technique with open skin and retracted ribs were significantly associated with mortality (p<0.05) whereas prolonged duration of DCC was not. In a matched cohort study to compare the results of a DCC technique with skin closure to similarly matched controls with primary closure, DCC contributed to significantly decreased incidence of severe PGD (9.6% vs. 26%, p<0.05), leading to an improved posttransplant survival and functional status as compared to primary closure. Conclusions Our technical tricks to prevent possible problems in DCC cases are described. DCC can be safely performed with acceptable procedure-related risks. DCC should not be considered a suboptimal option after lung transplantation.
    The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 01/2014; · 3.54 Impact Factor
  • PLoS ONE 01/2014; · 3.53 Impact Factor
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    ABSTRACT: Objectives Prognosis for locally advanced esophagogastric adenocarcinoma (EAC) is poor with surgery alone and adjuvant therapy after open esophagectomy is frequently not tolerated. After minimally invasive esophagectomy (MIE), however, earlier return to normal function may render patients better able to receive adjuvant therapy. This study examined whether primary MIE followed by adjuvant chemotherapy impacted survival compared to propensity-matched patients treated with neoadjuvant therapy. Methods Patients with stage II or higher EAC treated with MIE (n=375) were identified. Using 30 pretreatment covariates, propensity for assignment to either neoadjuvant followed by MIE (n=183; 54%) or MIE as primary therapy (n=156; 46%) was calculated, generating 97 closely-matched pairs. Hazard ratios were adjusted for age, sex, BMI, smoking, comorbidity and final pathologic stage. Results In propensity-matched pairs, adjusted hazard ratio for death did not differ significantly for primary MIE compared to neoadjuvant (HR 0.83; 95% CI 0.60-1.16). Recurrence patterns were similar between groups and 65% of patients with IIb or greater pathologic stage received adjuvant therapy. Clinical staging was inaccurate in 37/105 (35%) patients who underwent primary MIE (n=18 upstaged and n=19 downstaged). Conclusions Primary MIE followed by adjuvant chemotherapy guided by pathologic findings did not negatively impact survival and allowed for accurate staging of the patient compared to clinical staging. Our data suggest that primary MIE in patients with resectable EAC may be a reasonable approach, improving stage-based prognostication and potentially minimizing overtreatment in patients with early-stage disease through accurate stage assignments. A randomized controlled trial testing this hypothesis is needed.
    The Journal of Thoracic and Cardiovascular Surgery. 01/2014;
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    ABSTRACT: Sublobar wedge resection is associated with an increased risk of locoregional recurrence (15-20%) compared with lobectomy for early non-small cell lung cancer (NSCLC). We have previously shown that the addition of brachytherapy mesh at the time of sublobar resection might decrease the risk of local recurrence in this setting, equivalent to that of lobectomy [Santos et al. Surgery 2003;134:691-7]. In the current study, we evaluated the impact of brachytherapy mesh implantation after formal anatomic segmentectomy on local recurrence rates in the management of clinical stage I NSCLC. We undertook a retrospective review of 369 patients undergoing anatomic segmentectomy for clinical stage I NSCLC from 2002 to 2010 with (n = 155) or without (n = 214) the use of I(131) brachytherapy mesh applied over the staple line. The primary end point was local recurrence. Secondary end points included morbidity, mortality, and recurrence-free survival. Patients undergoing brachytherapy mesh implantation were older (71.0 vs 69.0 years, P = .03) and had larger tumors (2.3 cm vs 2.0 cm, P = .001) compared with those treated without mesh. There were no differences noted in sex, histology, or tumor stage. Overall mortality was 1.1% (mesh, 0.6%; no mesh 1.4%). Perioperative morbidity was similar in patients receiving mesh (45.8% vs 37.4%, P = .11). At a mean follow-up of 32.9 months, the overall local recurrence rate was 5.4% (mesh: 6.4% vs no mesh: 4.6%, P = .49). Five-year actuarial freedom from local recurrence was 92% in the mesh group, and 90% in patients undergoing segmentectomy without mesh (P = .24). It appears that the local recurrence noted with non-anatomic wedge resection is not an equivalent concern when anatomic segmentectomy with adequate margins are obtained. This implies that adjuvant brachytherapy after anatomic segmentectomy is not required for local control, thus avoiding the costs of radiation therapy and its associated potential toxicity. These data also suggest that proper anatomic segmentectomy alone may be associated with local recurrence rates similar to those of anatomic lobectomy in the setting of clinical stage I NSCLC.
    Surgery 12/2013; · 3.37 Impact Factor
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    ABSTRACT: Mucin core proteins (MUCs) are expressed in tissue-specific patterns in the gastrointestinal tract and expression is deregulated in Barrett's metaplasia. Based on differential expression, MUCs have been used to classify adenocarcinomas into distinct phenotypes (eg, intestinal, gastric, pancreaticobiliary, etc). Because MUC expression patterns carry prognostic significance in other tumors, we evaluated MUC expression in superficial adenocarcinomas of the gastroesophageal junction and esophagus (EAC) to determine whether there are differences in outcome associated with MUC subtype in this potentially curable subset of EAC. We classified 142 resected, superficial (T1) EAC based on their pattern of expression of MUC2, MUC5AC, MUC6 and MUC1. The association between survival and MUC expression pattern was determined in univariate and multivariate analyses. The MUC2 positive "intestinal" phenotype was associated with significantly worse prognosis in submucosal EAC (hazard ratio 2.2, 95% confidence interval 1.2-4.2), independent of node stage and other prognostic factors. MUC2 expression in submucosal EAC also showed significantly accelerated time to recurrence (hazard ratio 2.8, 95% confidence interval 1.2-6.8) after adjusting for node stage. The classification of superficial EAC by MUC protein expression has prognostic significance. MUC2 expression is an adverse prognostic indicator in submucosal EAC, independent of node stage and other prognostic factors.
    Human pathology 10/2013; · 3.03 Impact Factor
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    ABSTRACT: Unusual Problems and Thoracic Surgical SolutionsSESSION TYPE: Original Investigation SlidePRESENTED ON: Tuesday, October 29, 2013 at 04:30 PM - 05:30 PMPURPOSE: Complete (R0) anatomic resection affords the best opportunity for cure in patients with resectable NSCLC. Some tumors exhibit more aggressive tumor biology, resulting in encroachment on bronchial and vascular surgical margins of resection. Margin involvement determined only on final pathologic analysis several days after surgery poses a particular management dilemma. We evaluate the impact on recurrence and survival of microscopically positive surgical margins found on final pathology in resected NSCLC.METHODS: Retrospective review of 2,466 patients undergoing anatomic lung resection for NSCLC from 1998-2012 to identify all patients with microscopically positive resection margins noted only on final pathology. A matched cohort of patients with negative margins was identified accounting for age, gender, tumor size, tumor location, clinical stage, use of induction therapy and operation performed. Primary outcomes were incidence and patterns of recurrence. Kaplan-Meier actuarial freedom from recurrence and overall survival estimates were performed.RESULTS: Microscopically positive final pathologic margins were identified in 63 patients (2.6%) - lobectomy=42 (66.7%), bi-lobectomy=4(6.3%), sleeve resection=7(11.1%), pneumonectomy=10(15.9%). The median age was 67.2y (range: 35-87), mean tumor size was 4.8 ± 2.4cm. 76.1% stage 2B or above. 44.4% were adenocarcinoma and 41.3% squamous carcinoma. Involved margins were bronchial (n=39, 61.9%), vascular (n=20, 31.7%), parenchymal (n=6, 9.5%) or peribronchial/perivascular (n=5, 7.9%). 15 patients (23.8%) received neoadjuvant therapy and 52 (82.5%) adjuvant therapy. Margin positive patients had significantly increased rates of pathologic upstaging (66.7% vs 30.2%, p=0.0001) and use of adjuvant therapy (82.5% vs 41.3%, p=0.0001). No significant difference was noted in the patterns of recurrence between groups. Despite more aggressive therapy, patients with positive margins had significantly worse median (36 vs 19 months) and five year (37% vs 12%, p=0.009) overall survival.CONCLUSIONS: Microscopically positive surgical margins (R1) on final pathology are associated with increased rates of pathological upstaging and a worse overall survival. This finding portends aggressive disease biology and a poor prognosis irrespective of treatment strategy.CLINICAL IMPLICATIONS: Positive final pathologic margin appears to be a harbinger of advanced disease rather than a by-product of inadequate surgical therapy. Aggressive surgical re-resection may not be warranted in these patients.DISCLOSURE: The following authors have nothing to disclose: David Odell, Joseph Wizorek, Matthew Schuchert, Kristen McCormick, David Wilson, Jill Siegfried, James Luketich, Rodney LandreneauNo Product/Research Disclosure Information.
    Chest 10/2013; 144(4_MeetingAbstracts):116A. · 7.13 Impact Factor

Publication Stats

8k Citations
1,446.46 Total Impact Points

Institutions

  • 1996–2014
    • University of Pittsburgh
      • • Department of Thoracic and Foregut Surgery
      • • Division of Trauma and General Surgery
      • • Department of Surgery
      • • Department of Radiation Oncology
      • • Department of Radiology
      • • Department of Environmental and Occupational Health
      Pittsburgh, Pennsylvania, United States
  • 2013
    • UPMC
      Pittsburgh, Pennsylvania, United States
  • 2012
    • University of North Carolina at Chapel Hill
      • Department of Medicine
      Chapel Hill, NC, United States
  • 2011–2012
    • University of Rochester
      • • Department of Surgery
      • • Department of Pathology and Laboratory Medicine
      Rochester, NY, United States
    • University College London
      • UCL Cancer Institute
      London, ENG, United Kingdom
    • University Center Rochester
      • Department of Surgery
      Rochester, Minnesota, United States
  • 2009
    • Mayo Foundation for Medical Education and Research
      • Division of Pulmonary and Critical Care Medicine
      Scottsdale, AZ, United States
  • 2007–2009
    • Mount Sinai School of Medicine
      • Department of Pathology
      Manhattan, NY, United States
    • Shadyside Hospital
      Pittsburgh, Pennsylvania, United States
    • Thomas Jefferson University
      • Division of Cardiothoracic Surgery
      Philadelphia, PA, United States
    • St. Paul's Hospital
      Saskatoon, Saskatchewan, Canada
    • Massachusetts General Hospital
      • Division of Thoracic Surgery
      Boston, MA, United States
    • Childrens Hospital of Pittsburgh
      Pittsburgh, Pennsylvania, United States
    • University of Utah
      • Department of Surgery
      Salt Lake City, UT, United States
  • 2008
    • Mount Sinai Medical Center
      New York City, New York, United States
  • 2006
    • Medical University of South Carolina
      • Department of Surgery
      Charleston, SC, United States
    • Boston Medical Center
      Boston, Massachusetts, United States
  • 2004–2006
    • University of California, Irvine
      • Department of Surgery
      Irvine, CA, United States
  • 2005
    • University of Massachusetts Boston
      Boston, Massachusetts, United States
  • 1993–2001
    • Memorial Sloan-Kettering Cancer Center
      • • Thoracic Service
      • • Thoracic Oncology Service
      • • Department of Surgery
      New York City, NY, United States
  • 2000
    • California State University, Sacramento
      Sacramento, California, United States
    • Pennsylvania State University
      • Department of Pharmacology
      University Park, MD, United States
  • 1999–2000
    • University of California, Davis
      • Department of Surgery
      Davis, CA, United States