James D Luketich

University of Pittsburgh, Pittsburgh, Pennsylvania, United States

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Publications (454)1811.17 Total impact

  • Gastroenterology 04/2015; 148(4):S-1139. DOI:10.1016/S0016-5085(15)33884-1 · 13.93 Impact Factor
  • Gastroenterology 04/2015; 148(4):S-134. DOI:10.1016/S0016-5085(15)30463-7 · 13.93 Impact Factor
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    ABSTRACT: The lungs are dually perfused by the pulmonary artery and the bronchial arteries. This study aimed to test the feasibility of dual-perfusion techniques with the bronchial artery circulation and pulmonary artery circulation synchronously perfused using ex vivo lung perfusion (EVLP) and evaluate the effects of dual-perfusion on posttransplant lung graft function. Using rat heart-lung blocks, we developed a dual-perfusion EVLP circuit (dual-EVLP), and compared cellular metabolism, expression of inflammatory mediators, and posttransplant graft function in lung allografts maintained with dual-EVLP, standard-EVLP, or cold static preservation. The microvasculature in lung grafts after transplant was objectively evaluated using microcomputed tomography angiography. Lung grafts subjected to dual-EVLP exhibited significantly better lung graft function with reduced proinflammatory profiles and more mitochondrial biogenesis, leading to better posttransplant function and compliance, as compared with standard-EVLP or static cold preservation. Interestingly, lung grafts maintained on dual-EVLP exhibited remarkably increased microvasculature and perfusion as compared with lungs maintained on standard-EVLP. Our results suggest that lung grafts can be perfused and preserved using dual-perfusion EVLP techniques that contribute to better graft function by reducing proinflammatory profiles and activating mitochondrial respiration. Dual-EVLP also yields better posttransplant graft function through increased microvasculature and better perfusion of the lung grafts after transplantation. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.
    American Journal of Transplantation 03/2015; 15(5). DOI:10.1111/ajt.13109 · 6.19 Impact Factor
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    ABSTRACT: Development of a tracheopharyngeal fistula after pharyngeal perforation is an uncommon occurrence. As a result, published guidance for management of this rare type of aerodigestive tract fistula is limited. We describe the workup and management of a traumatic tracheopharyngeal fistula caused by foreign body impaction. A conservative, endoscopic treatment strategy with broad-spectrum antibiotics, transnasal drainage, and covered tracheal stent placement was used. The stent was removed after 4 weeks, and complete closure of the fistula tract was confirmed by endoscopy and contrast esophagram. Although tracheopharyngeal fistulae are rare and operative treatment can be complex, this case demonstrates that conservative management with antibiotics, drainage, and endoscopic stenting can be successful in select patients. Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
    The Annals of Thoracic Surgery 02/2015; 99(2):e31-e35. DOI:10.1016/j.athoracsur.2014.11.016 · 3.63 Impact Factor
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    ABSTRACT: Previously regarded as a rare neoplasm, the incidence of esophageal adenocarcinoma has risen rapidly in recent decades. It is often discovered late in the disease process and has a dismal prognosis. Current prognostic markers including clinical, radiographic, and histopathologic findings have limited utility and do not consider the biology of this deadly disease. Genome-wide analyses have identified SMAD4 inactivation in a subset of tumors. Although Smad4 has been extensively studied in other gastrointestinal malignancies, its role in esophageal adenocarcinoma remains to be defined. Herein, we show, in a large cohort of esophageal adenocarcinomas, Smad4 loss by immunohistochemistry in 21 of 205 (10%) tumors and that Smad4 loss correlated with increased postoperative recurrence (P=0.040). Further, patients whose tumors lacked Smad4 had shorter time to recurrence (TTR) (P=0.007) and poor overall survival (OS) (P=0.011). The median TTR and OS of patients with Smad4-negative tumors was 13 and 16 months, respectively, as compared with 23 and 22 months, respectively, among patients with Smad4-positive tumors. In multivariate analyses, Smad4 loss was a prognostic factor for both TTR and OS, independent of histologic grade, lymphovascular invasion, perineural invasion, tumor stage, and lymph node status. Considering Smad4 loss correlated with postoperative locoregional and/or distant metastases, Smad4 was also assessed in a separate cohort of 5 locoregional recurrences and 43 metastatic esophageal adenocarcinomas. In contrast to primary tumors, a higher prevalence of Smad4 loss was observed in metastatic disease (44% vs. 10%). In summary, loss of Smad4 protein expression is an independent prognostic factor for TTR and OS that correlates with increased propensity for disease recurrence and poor survival in patients with esophageal adenocarcinoma after surgical resection.
    American Journal of Surgical Pathology 01/2015; 39(4). DOI:10.1097/PAS.0000000000000356 · 4.59 Impact Factor
  • Annals of Surgery 01/2015; DOI:10.1097/SLA.0000000000000864 · 7.19 Impact Factor
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    ABSTRACT: The primary aim of this trial was to assess the feasibility of minimally invasive esophagectomy (MIE) in a multi-institutional setting. Esophagectomy is an important, potentially curative treatment for localized esophageal cancer, but is a complex operation. MIE may decrease the morbidity and mortality of resection, and single-institution studies have demonstrated successful outcomes with MIE. We conducted a multicenter, phase II, prospective, cooperative group study (coordinated by the Eastern Cooperative Oncology Group) to evaluate the feasibility of MIE. Patients with biopsy-proven high-grade dysplasia or esophageal cancer were enrolled at 17 credentialed sites. Protocol surgery consisted of either 3-stage MIE or Ivor Lewis MIE. The primary end point was 30-day mortality. Secondary end points included adverse events, duration of hospital-stay, and 3-year outcomes. Protocol surgery was completed in 95 of the 104 patients eligible for the primary analysis (91.3%). The 30-day mortality in eligible patients who underwent MIE was 2.1%; perioperative mortality in all registered patients eligible for primary analysis was 2.9%. Median intensive care unit and hospital stay were 2 and 9 days, respectively. Grade 3 or higher adverse events included anastomotic leak (8.6%), acute respiratory distress syndrome (5.7%), pneumonitis (3.8%), and atrial fibrillation (2.9%). At a median follow-up of 35.8 months, the estimated 3-year overall survival was 58.4% (95% confidence interval: 47.7%-67.6%). Locoregional recurrence occurred in only 7 patients (6.7%). This prospective multicenter study demonstrated that MIE is feasible and safe with low perioperative morbidity and mortality and good oncological results. This approach can be adopted by other centers with appropriate expertise in open esophagectomy and minimally invasive surgery.
  • Journal of Thoracic and Cardiovascular Surgery 12/2014; 149(4). DOI:10.1016/j.jtcvs.2014.12.029 · 3.99 Impact Factor
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    ABSTRACT: Undifferentiated carcinoma of the esophagus is a rare histologic variant of esophageal carcinoma. Using criteria based on studies of undifferentiated carcinomas arising at other sites, we have collected 16 cases of resected esophageal undifferentiated carcinomas. Patients ranged in age from 39 to 84 years (mean, 65.5 years) and were predominantly male (94%). The tumors were characterized by an expansile growth pattern of neoplastic cells organized in solid sheets and without significant glandular, squamous, or neuroendocrine differentiation. The neoplastic cells had a syncytial-like appearance, little intervening stroma, and patchy tumor necrosis. In a subset of cases, the tumor cells adopted a sarcomatoid (n = 2), rhabdoid (n = 1), or minor component (<5%) of glandular morphology (n = 3). In 1 case, reactive osteoclast-like giant cells were found interspersed among the neoplastic cells. Lymphovascular invasion, perineural invasion, and lymph node metastases were identified in 88%, 56%, and 81% of cases, respectively. In 12 (75%) specimens, the background esophageal mucosa was notable for Barrett esophagus. Consistent with the epithelial nature of these neoplasms, cytokeratin positivity was identified in all cases. In addition, SALL4 expression was present in 8 (67%) of 12 cases. Follow-up information was available for 15 (94%) of 16 patients, all of whom were deceased. Survival after surgery ranged from 1 to 50 months (mean, 11.9 months). Before death, 67% patients had documented locoregional recurrence and/or distant organ metastases. In summary, esophageal undifferentiated carcinomas are aggressive neoplasms and associated with a high incidence of recurrence and/or metastases and a dismal prognosis. Copyright © 2014 Elsevier Inc. All rights reserved.
    Human pathology 12/2014; 46(3). DOI:10.1016/j.humpath.2014.11.021 · 2.81 Impact Factor
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    ABSTRACT: Intractable gastroesophageal reflux disease (GERD) after antireflux operations presents a challenge-particularly in obese patients and patients with esophageal dysmotility-and increases the complexity of the redo operation. This study evaluated the results of Roux-en-Y near esophagojejunostomy (RNYNEJ) in the management of recurrent GERD after antireflux operations. We conducted a retrospective review of overweight patients with intractable GERD who underwent RNYNEJ for failed antireflux operations. We evaluated perioperative outcomes, dysphagia (ranging from 1 = no dysphagia to 5 = unable to swallow saliva), and quality of life (QOL) (assessed using the GERD health-related quality-of-life instrument (HRQOL). Over a 12-year period, 105 patients with body mass index (BMI) greater than 25 underwent RNYNEJ for failed antireflux operations. Most were obese (BMI > 30; 82 patients [78%]); esophageal dysmotility was demonstrated in more than one-third of patients. Forty-eight (46%) patients had multiple antireflux operations before RNYNEJ, and 27 patients had undergone a previous Collis gastroplasty. There was no perioperative mortality. Major complications, including anastomotic leak requiring surgical intervention (n = 3 [2.9%]), were noted in 25 patients (24%).The median length of stay was 6 days. During follow-up (mean, 23.39 months), median BMI decreased from 35 to 27.6 (p < 0.0001), and the mean dysphagia score decreased from 2.9 to 1.5 (p < 0.0001). The median GERD HRQOL score, assessed in a subset of patients, was 9 (classified as excellent). RNYNEJ for persistent GERD after antireflux operations in appropriately selected patients can be performed safely with good results in experienced centers. RNYNEJ should be considered an important option for the treatment of intractable recurrent symptoms after antireflux operations, particularly in obese patients. Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
    The Annals of Thoracic Surgery 12/2014; 98(6):1905-13. DOI:10.1016/j.athoracsur.2014.07.004 · 3.63 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.
    Journal of Thoracic and Cardiovascular Surgery 10/2014; 149(2). DOI:10.1016/j.jtcvs.2014.10.044 · 3.99 Impact Factor
  • Journal of the American College of Surgeons 09/2014; 219(3):S29. DOI:10.1016/j.jamcollsurg.2014.07.060 · 4.45 Impact Factor
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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; 98(5). DOI:10.1097/TP.0000000000000254 · 3.78 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 07/2014; DOI:10.1016/j.healun.2014.03.003 · 5.61 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 06/2014; 32(23). DOI:10.1200/JCO.2013.50.8762 · 17.88 Impact Factor
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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; DOI:10.3109/07357907.2014.919303 · 2.06 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; 98(8). DOI:10.1097/TP.0000000000000134 · 3.78 Impact Factor
  • Gastroenterology 05/2014; 146(5):S-1062. DOI:10.1016/S0016-5085(14)63876-2 · 13.93 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; DOI:10.1038/modpathol.2014.66 · 6.36 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. DOI:10.1186/1471-230X-14-78 · 2.11 Impact Factor

Publication Stats

10k Citations
1,811.17 Total Impact Points

Institutions

  • 1996–2015
    • University of Pittsburgh
      • • Department of Cardiothoracic Surgery
      • • Department of Thoracic and Foregut Surgery
      • • Division of Trauma and General Surgery
      • • Department of Surgery
      • • Department of Radiology
      Pittsburgh, Pennsylvania, United States
  • 2014
    • University of Queensland
      Brisbane, Queensland, Australia
  • 2013
    • UPMC
      Pittsburgh, Pennsylvania, United States
  • 2008
    • University of Texas MD Anderson Cancer Center
      • Division of Radiation Oncology
      Houston, Texas, United States
  • 2007
    • Shadyside Hospital
      Pittsburgh, Pennsylvania, United States
    • Childrens Hospital of Pittsburgh
      Pittsburgh, Pennsylvania, United States
    • Mount Sinai School of Medicine
      • Department of Pathology
      Manhattan, New York, United States
    • University of Utah
      • Department of Surgery
      Salt Lake City, UT, United States
    • Boston University
      Boston, Massachusetts, United States
  • 2006
    • Medical University of South Carolina
      • Department of Surgery
      Charleston, SC, United States
  • 2005
    • Nevada cancer institute
      Las Vegas, Nevada, United States
  • 2004–2005
    • University of California, Irvine
      • Department of Surgery
      Irvine, CA, United States
    • Allegheny General Hospital
      Pittsburgh, Pennsylvania, United States
  • 2001
    • University of Maryland, Baltimore
      Baltimore, Maryland, United States
  • 2000
    • California State University, Sacramento
      Sacramento, California, United States
  • 1990–1998
    • Hospital of the University of Pennsylvania
      • Department of Surgery
      Filadelfia, Pennsylvania, United States
  • 1993–1997
    • Memorial Sloan-Kettering Cancer Center
      • Department of Surgery
      New York, New York, United States