Alexander S Krupnick

Washington University in St. Louis, San Luis, Missouri, United States

Are you Alexander S Krupnick?

Claim your profile

Publications (144)741.88 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: This study evaluated the cost-effectiveness of combination chemotherapy, radiotherapy, and surgical intervention (CRS) vs definitive chemotherapy and radiotherapy (CR) in clinical stage IIIA non-small cell lung cancer (NSCLC) patients at academic and nonacademic centers. Methods: Patients with clinical stage IIIA NSCLC receiving CR or CRS from 1998 to 2010 were identified in the National Cancer Data Base. Propensity score matching on patient, tumor, and treatment characteristics was performed. Medicare allowable charges were used for treatment costs. The incremental cost-effectiveness ratio (ICER) was based on probabilistic 5-year survival and calculated as cost per life-year gained. Results: We identified 5,265 CR and CRS matched patient pairs. Surgical resection imparted an increased effectiveness of 0.83 life-years, with an ICER of $17,618. Among nonacademic centers, 1,634 matched CR and CRS patients demonstrated a benefit with surgical resection of 0.86 life-years gained, for an ICER of $17,124. At academic centers, 3,201 matched CR and CRS patients had increased survival of 0.81 life-years with surgical resection, for an ICER of $18,144. Finally, 3,713 CRS patients were matched between academic and nonacademic centers. Academic center surgical patients had an increased effectiveness of 1.5 months gained and dominated the model with lower surgical cost estimates associated with lower 30-day mortality rates. Conclusions: In stage IIIA NSCLC, the selective addition of surgical resection to CR is cost-effective compared with definitive chemoradiation therapy at nonacademic and academic centers. These conclusions are valid over a range of clinically meaningful variations in cost and treatment outcomes.
    No preview · Article · Dec 2015 · The Annals of Thoracic Surgery
  • Alexander Sasha Krupnick

    No preview · Article · Dec 2015 · The Journal of thoracic and cardiovascular surgery
  • Hsi-Min Hsao · Wenjun Li · Andrew E. Gelman · Alexander S. Krupnick · Daniel Kreisel

    No preview · Article · Nov 2015
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: The value of adjuvant chemotherapy for patients with positive lymph nodes (+LNs) after induction therapy and resection of esophageal cancer is controversial. This study assesses survival benefit of adjuvant chemotherapy in this cohort. Methods: We analyzed our single-institution database for patients with +LNs after induction therapy and resection of primary esophageal cancer between 2000 and 2013. Factors associated with survival were analyzed using a Cox proportional hazards model. Results: A total of 101 of 764 esophagectomy patients received induction and had +LNs on final pathologic examination. Forty-five also received adjuvant therapy: 37 of 45 (82%) received chemotherapy alone, 1 of 45 (2%) received radiation alone, and 7 of 45 (16%) received both. Pathologic stage was IIB in 21 (47%), IIIA in 19 (42%), and IIIB in 5 (11%). In 56 node-positive patients with induction but not adjuvant therapy, pathologic stage was IIB in 28 (50%), IIIA in 18 (32%), IIIB in 7 (13%), and IIIC in 3 (5%). Neither age nor comorbidity score differed between cohorts. Adjuvant patients experienced a shorter hospital length of stay (mean, 10 days [range, 6 to 33 days] versus 11 days [range, 7 to 67 days]; p = 0.03]. Median survival favored the adjuvant group: 24.0 months (95% confidence interval, 16.6 to 32.2 months) versus 18.0 months (95% confidence interval, 11.1 to 25.0 months); p = 0.033). Multivariate Cox regression identified adjuvant therapy, length of stay, and number of +LNs as influential for survival. Conclusions: Optimal management of node-positive patients after induction therapy and esophagectomy remains unclear, but in this series, adjuvant therapy, length of stay, and number of +LNs impacted survival. A prospective trial may reduce potential bias and guide the evaluation of adjuvant therapy in this patient population.
    No preview · Article · Oct 2015 · The Annals of thoracic surgery
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective: The study objective was to study the incidence, predictors, and implications of unanticipated early postoperative readmission after lung resection for non-small cell lung cancer. Methods: Patients undergoing surgery for clinical stage I to III non-small cell lung cancer were abstracted from the National Cancer Database. Regression models were fitted to identify predictors of 30-day readmission and to study the association of unplanned readmission with 30-day and long-term survival. Results: Between 1998 and 2010, 129,893 patients underwent resection for stage I to III non-small cell lung cancer. Of these, 5624 (4.3%) were unexpectedly readmitted within 30 days. In a multivariate regression model, increasing age, male gender, preoperative radiation, and pneumonectomy (odds ratio, 1.77; 95% confidence interval, 1.56-2.00) were associated with unexpected readmissions. Longer index hospitalization and higher Charlson comorbidity score were also predictive of readmission. The 30-day mortality for readmitted patients was higher (3.9% vs 2.8%), as was the 90-day mortality (7.0% vs 3.3%, both P < .001). In a multivariate Cox proportional hazards model of long-term survival, increasing age, higher Charlson comorbidity score, and higher pathologic stage (hazard ratio, for stage III 1.81; 95% confidence interval, 1.42-2.29) were associated with greater risk of mortality. Unplanned readmission was independently associated with a higher risk of long-term mortality (hazard ratio, 1.40; 95% confidence interval, 1.34-1.47). The median survival for readmitted patients was significantly shorter (38.7 vs 58.5 months, P < .001). Conclusions: Unplanned readmissions are not rare after resection for non-small cell lung cancer. Such events are associated with a greater risk of short- and long-term mortality. With the renewed national focus on readmissions and potential financial disincentives, greater resource allocation is needed to identify patients at risk and develop measures to avoid the associated adverse outcomes.
    No preview · Article · Sep 2015 · The Journal of thoracic and cardiovascular surgery
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: The role of pneumonectomy after neoadjuvant therapy for stage IIIA non-small cell lung cancer (NSCLC) remains uncertain. Methods: Patients who underwent pneumonectomy for clinical stage IIIA NSCLC were abstracted from the National Cancer Database. Individuals treated with neoadjuvant therapy, followed by resection, were compared with those who underwent resection, followed by adjuvant therapy. Logistic regression was performed to identify factors associated with 30-day mortality. A Cox proportional hazards model was fitted to identify factors associated with survival. Results: Pneumonectomy for stage IIIA NSCLC with R0 resection was performed in 1,033 patients; of these, 739 (71%) received neoadjuvant therapy, and 294 (29%) underwent resection, followed by adjuvant therapy. The two groups were well matched for age, gender, race, income, Charlson comorbidity score, and tumor size. The 30-day mortality rate in the neoadjuvant group was 7.8% (57 of 739). Median survival was similar between the two groups: 25.9 months neoadjuvant vs 31.3 months adjuvant (p = 0.74). A multivariable logistic regression model for 30-day mortality demonstrated that increasing age, annual income of less than $35,000, nonacademic facility, and right-sided resection were associated with an elevated risk of 30-day mortality. A multivariable Cox model for survival demonstrated that increasing age was predictive of shorter survival and that administration of neoadjuvant therapy did not confer a survival advantage over adjuvant therapy (p = 0.59). Conclusions: Most patients who require pneumonectomy for clinical stage IIIA NSCLC receive neoadjuvant chemoradiotherapy, without an improvement in survival. In these patients, primary resection, followed by adjuvant chemoradiotherapy, may provide equivalent long-term outcomes.
    No preview · Article · Sep 2015 · The Annals of thoracic surgery
  • [Show abstract] [Hide abstract]
    ABSTRACT: The relative roles of surgery and stereotactic body radiation therapy in stage I non-small cell lung cancer (NSCLC) are evolving particularly for marginally operable patients. Since there is limited prospective comparative data for these treatment modalities, we evaluated their relative use and outcomes at the population level using a national database. Patient variables and treatment-related outcomes were abstracted for patients with clinical stage I NSCLC from the National Cancer Database. Patients receiving surgery were compared to those undergoing SBRT in exploratory unmatched and subsequent propensity matched analyses. Between 1998 and 2010, 117618 patients underwent surgery or SBRT for clinical stage I NSCLC. Of these, 111731 (95%) received surgery while 5887 (5%) underwent SBRT. Patients in the surgery group were younger, more likely to be males, and had higher Charlson comorbidity scores. SBRT patients were more likely to have T1 (vs.T2) tumors and receive treatment at academic centers. Thirty-day surgical mortality was 2596/109485 (2.4%). Median overall survival favored the surgery group in both unmatched (68.4 months vs. 33.3 months, p<.001) and matched analysis based on patient characteristics (62.3 months vs. 33.1months, p<.001). Disease specific survival was unavailable from the dataset. In a propensity matched comparison, patients selected for surgery have improved survival compared with SBRT. In the absence of information on cause of death and with limited variables to characterize comorbidity, it is not possible to assess the relative contribution of patient selection or better cancer control towards the improved survival. Rigorous prospective studies are needed to optimize patient selection for SBRT in the high-risk surgical population.
    No preview · Article · Sep 2015 · Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer
  • [Show abstract] [Hide abstract]
    ABSTRACT: A substantial proportion of patients with clinical stage I non-small cell lung cancer (NSCLC) have more advanced disease on final pathologic review. We studied potentially modifiable factors that may predict pathologic upstaging. Data of patients with clinical stage I NSCLC undergoing resection were obtained from the National Cancer Database. Univariate and multivariate analyses were performed to identify variables that predict upstaging. From 1998 to 2010, 55,653 patients with clinical stage I NSCLC underwent resection; of these, 9,530 (17%) had more advanced disease on final pathologic review. Of the 9,530 upstaged patients, 27% had T3 or T4 tumors, 74% had positive lymph nodes (n > 0), and 4% were found to have metastatic disease (M1). Patients with larger tumors (38 mm vs 29 mm, p < 0.001) and a delay greater than 8 weeks from diagnosis to resection were more likely to be upstaged. Upstaged patients also had more lymph nodes examined (10.9 vs 8.2, p < 0.001) and were more likely to have positive resection margins (10% vs 2%, p < 0.001). Median survival was lower in upstaged patients (39 months vs 73 months). Predictors of upstaging in multivariate regression analysis included larger tumor size, delay in resection greater 8 weeks, positive resection margins, and number of lymph nodes examined. There was a linear relationship between the number of lymph nodes examined and the odds of upstaging (1 to 3 nodes, odds ratio [OR] 2.01; >18 nodes OR 6.14). Pathologic upstaging is a common finding with implications for treatment and outcomes in clinical stage I NSCLC. A thorough analysis of regional lymph nodes is critical to identify patients with more advanced disease. Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
    No preview · Article · Aug 2015 · The Annals of thoracic surgery
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective: The study objective was to validate the National Surgical Quality Improvement Program (NSQIP) Risk Calculator in stratifying risk estimates for patients who received surgery or stereotactic body radiation therapy for clinical stage I non-small cell lung cancer. Methods: A retrospective analysis of patients with clinical stage I non-small cell lung cancer undergoing surgery (N = 279) or stereotactic body radiation therapy (N = 206) from 2009 to 2012 was performed. NSQIP complication risk estimates were calculated for both surgical and stereotactic body radiation therapy cases using the NSQIP Surgical Risk Calculator. NSQIP complication risk estimates were compared as continuous variables and by quartile ranges. Results: Compared with patients undergoing video-assisted thoracoscopic surgery wedge resection, patients receiving stereotactic body radiation therapy were older, had larger tumors, had lower forced expiratory volume (FEV1) in 1 second and diffusing capacity of the lungs (DLCO) for carbon monoxide values, had higher American Society of Anesthesiologists scores, had higher rates of dyspnea, and had higher NSQIP serious complication risk estimates (all P < .05). Compared with patients undergoing video-assisted thoracoscopic surgery lobectomy, patients receiving stereotactic body radiation therapy had similar disparities, along with higher Adult Comorbidity Evaluation-27 (ACE) scores comorbidity scores, higher rates of cardiac comorbidities, and worse functional status (all P < .05). Variables associated with receiving stereotactic body radiation therapy treatment, rather than wedge resection, included increasing age, higher Adult Comorbidity Evaluation (ACE)-27 comorbidity score, dyspnea status, and decreasing FEV1 in 1 second and DLCO for carbon monoxide, but NSQIP serious complication risk score. In addition, surgical patients' actual serious complication rate (16.6% vs 8.8%) and pneumonia rate (6.0% vs 3.2%) were significantly higher than the NSQIP risk calculator predicted (all P < .05). Conclusions: The National Surgical Quality Improvement Program risk calculator does not effectively classify or stratify risk in patients with stage I non-small cell lung cancer. Continued efforts are needed to assess risk in this population and develop more tailored treatment decision aids.
    No preview · Article · Aug 2015 · The Journal of thoracic and cardiovascular surgery
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Improved survival of patients with early-stage non-small cell lung cancer (NSCLC) undergoing resection at high-volume centers has been reported. However, the effect of institution is unclear in stage IIIA NSCLC, where a variety of neoadjuvant and adjuvant therapies are used. Treatment and outcomes data of clinical stage IIIA NSCLC patients undergoing resection as part of multimodality therapy was obtained from the National Cancer Database. Multivariable regression models were fitted to evaluate variables influencing 30-day mortality and overall survival. From 1998 to 2010, 11,492 clinical stage IIIA patients underwent resection at community centers, and 7,743 patients received resection at academic centers. Academic center patients were more likely to be younger, female, non-Caucasian, have a lower Charlson-Deyo comorbidity score, and to receive neoadjuvant chemotherapy (49.6% vs 40.6%; all p < 0.001). Higher 30-day mortality was associated with increasing age, male gender, preoperative radiotherapy, and pneumonectomy. Patients undergoing operations at academic centers experienced lower 30-day mortality (3.3% vs 4.5%; odds ratio, 0.75; 95% confidence interval [CI], 0.60 to 0.93; p < 0.001). Decreased long-term survival was associated with increasing age, male gender, higher Charlson-Deyo comorbidity score, and larger tumors. Neoadjuvant chemotherapy (hazard ratio, 0.66; 95% CI, 0.62 to 0.70), surgical intervention at an academic center (hazard ratio, 0.92; 95% CI, 0.88 to 0.97), and lobectomy (hazard ratio, 0.72; 95% CI, 0.67 to 0.77) were associated with improved overall survival. Stage IIIA NSCLC patients undergoing resection at academic centers had lower 30-day mortality and increased overall survival compared with patients treated at community centers, possibly due to higher patient volume and an increased rate of neoadjuvant chemotherapy. Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
    Full-text · Article · Jul 2015 · The Annals of thoracic surgery
  • [Show abstract] [Hide abstract]
    ABSTRACT: Cytopathologic interpretation of endobronchial ultrasound with fine needle aspiration (EBUS-FNA) samples by a pathologist can be time-consuming and costly, and an onsite cytopathologist may not always be readily available. A telecytopathology system was instituted and evaluated to examine the effect on operative time for EBUS. A prospective study was performed of sequential patients undergoing EBUS-FNA for the evaluation of mediastinal lymphadenopathy. Specimens for the control group were transported to the pathology laboratory, followed by remote cytologic interpretation. In a subsequent cohort, a telecytopathology system was used with intraoperative transmission of real-time live video microscopy to a remote cytopathologist (TCP group). The primary outcome was time to confirmation of cytology results. Of 46 patients entered into the study, 23 underwent traditional analysis (control group), and 20 were analyzed using telecytopathology (TCP group). Lung cancer was the most common malignancy in both groups (12 TCP, 12 control). There was no difference in mean number of lymph node stations sampled (1.3 TCP vs 1.8 control, p = 0.76). Use of TCP was associated with fewer needle passes (4.9 vs 7.3, p = 0.02) and fewer slides for interpretation (8.4 vs 13.5, p = 0.01) per procedure. Time to result confirmation was significantly shorter in the TCP group (19.0 vs 46.7 minutes, p < 0.001). A diagnostic specimen was obtained in 70% of patients in the TCP group compared with 65% in the control group (p = 0.5). False-negative rates in patients undergoing EBUS-FNA and mediastinoscopy were similar between the two groups (0 in TCP vs 2 in control, p = 0.49). Mean procedural costs (excluding cost of the telecytology system and operating room time) were equivalent between the two groups ($888 TCP vs $887 control). Telecytopathology provides rapid interpretation of EBUS-FNA samples with diagnostic accuracy comparable to traditional methods, shortens procedure time, and is a more efficient model for delivery of on-site EBUS-FNA interpretation. Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
    No preview · Article · May 2015 · The Annals of thoracic surgery
  • Source

    Full-text · Article · Apr 2015 · Science translational medicine
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Hyperammonemia syndrome is a fatal complication affecting immunosuppressed patients. Frequently refractory to treatment, it is characterized by progressive elevations in serum ammonia of unknown etiology, ultimately leading to cerebral edema and death. In mammals, ammonia produced during amino acid metabolism is primarily cleared through the hepatic production of urea, which is eliminated in the kidney. Ureaplasma species, commensals of the urogenital tract, are Mollicutes dependent on urea hydrolysis to ammonia and carbon dioxide for energy production. We hypothesized that systemic infection with Ureaplasma species might pose a unique challenge to human ammonia metabolism by liberating free ammonia resulting in the hyperammonemia syndrome. We used polymerase chain reaction, specialized culture, and molecular resistance profiling to identify systemic Ureaplasma infection in lung transplant recipients with hyperammonemia syndrome, but did not detect it in any lung transplant recipients with normal ammonia concentrations. Administration of Ureaplasma-directed antimicrobials to patients with hyperammonemia syndrome resulted in biochemical and clinical resolution of the disorder. Relapse in one patient was accompanied by recurrent Ureaplasma bacteremia with antimicrobial resistance. Our results provide evidence supporting a causal relationship between Ureaplasma infection and hyperammonemia, suggesting a need to test for this organism and provide empiric antimicrobial treatment while awaiting microbiological confirmation. Copyright © 2015, American Association for the Advancement of Science.
    Full-text · Article · Apr 2015 · Science translational medicine
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Conflicting evidence currently exists regarding the causes and effects of delay of care in non-small cell lung cancer (NSCLC). We hypothesized that delayed surgery in early-stage NSCLC is associated with worse short-term and long-term outcomes. Methods: Treatment data of clinical stage I NSCLC patients undergoing surgical resection were obtained from the National Cancer Data Base (NCDB). Treatment delay was defined as resection 8 weeks or more after diagnosis. Propensity score matching for patient and tumor characteristics was performed to create comparable groups of patients receiving early (less than 8 weeks from diagnosis) and delayed surgery. Multivariable regression models were fitted to evaluate variables influencing delay of surgery. Results: From 1998 to 2010, 39,995 patients with clinical stage I NSCLC received early surgery, while 15,658 patients received delayed surgery. Of these, 27,022 propensity-matched patients were identified. Those with a delay in care were more likely to be pathologically upstaged (18.3% stage 2 or higher versus 16.6%, p < 0.001), have an increased 30-day mortality (2.9% vs 2.4%, p = 0.01), and have decreased median survival (57.7 ± 1.0 months versus 69.2 ± 1.3 months, p < 0.001). Delay in surgery was associated with increasing age, non-white race, treatment at an academic center, urban location, income less than $35,000, and increasing Charlson comorbidity score (p < 0.0001 for all). Delayed patients were more likely to receive a sublobar resection (17.2% vs 13.1%, p < 0.001). Conclusions: Patients receiving delayed resection for clinical stage I NSCLC have higher comorbidity scores that may affect ability to perform lobectomy and result in higher perioperative mortality. However, delay in resection is independently associated with increased rates of upstaging and decreased median survival. Strategies to minimize delay while medically optimizing higher risk patients are needed.
    No preview · Article · Apr 2015 · The Annals of thoracic surgery
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Neutrophils are critical mediators of innate immune responses and contribute to tissue injury. However, immune pathways that regulate neutrophil recruitment to injured tissues during noninfectious inflammation remain poorly understood. DAP12 is a cell membrane-associated protein that is expressed in myeloid cells and can either augment or dampen innate inflammatory responses during infections. To elucidate the role of DAP12 in pulmonary ischemia/reperfusion injury (IRI), we took advantage of a clinically relevant mouse model of transplant-mediated lung IRI. This technique allowed us to dissect the importance of DAP12 in tissue-resident cells and those that infiltrate injured tissue from the periphery during noninfectious inflammation. Macrophages in both mouse and human lungs that have been subjected to cold ischemic storage express DAP12. We found that donor, but not recipient, deficiency in DAP12 protected against pulmonary IRI. Analysis of the immune response showed that DAP12 promotes the survival of tissue-resident alveolar macrophages and contributes to local production of neutrophil chemoattractants. Intravital imaging demonstrated a transendothelial migration defect into DAP12-deficient lungs, which can be rescued by local administration of the neutrophil chemokine CXCL2. We have uncovered a previously unrecognized role for DAP12 expression in tissue-resident alveolar macrophages in mediating acute noninfectious tissue injury through regulation of neutrophil trafficking. Copyright © 2015 by The American Association of Immunologists, Inc.
    Full-text · Article · Mar 2015 · The Journal of Immunology
  • [Show abstract] [Hide abstract]
    ABSTRACT: To investigate the impact of modern postoperative radiotherapy (PORT) on overall survival (OS) for patients with N2 non-small-cell lung cancer (NSCLC) treated nationally with surgery and adjuvant chemotherapy. Patients with pathologic N2 NSCLC who underwent complete resection and adjuvant chemotherapy from 2006 to 2010 were identified from the National Cancer Data Base and stratified by use of PORT (≥ 45 Gy). A total of 4,483 patients were identified (PORT, n = 1,850; no PORT, n = 2,633). The impact of patient and treatment variables on OS was explored using Cox regression. Median follow-up time was 22 months. On univariable analysis, improved OS correlated with younger age, treatment at an academic facility, female sex, urban population, higher income, lower Charlson comorbidity score, smaller tumor size, multiagent chemotherapy, resection with at least a lobectomy, and PORT. On multivariable analysis, improved OS remained independently predicted by younger age, female sex, urban population, lower Charlson score, smaller tumor size, multiagent chemotherapy, resection with at least a lobectomy, and PORT (hazard ratio, 0.886; 95% CI, 0.798 to 0.988). Use of PORT was associated with an increase in median and 5-year OS compared with no PORT (median OS, 45.2 v 40.7 months, respectively; 5-year OS, 39.3% [95% CI, 35.4% to 43.5%] v 34.8% [95% CI, 31.6% to 38.3%], respectively; P = .014). For patients with N2 NSCLC after complete resection and adjuvant chemotherapy, modern PORT seems to confer an additional OS advantage beyond that achieved with adjuvant chemotherapy alone. © 2015 by American Society of Clinical Oncology.
    No preview · Article · Feb 2015 · Journal of Clinical Oncology
  • [Show abstract] [Hide abstract]
    ABSTRACT: The study objective was to evaluate the influence of surgeon experience on outcomes in early-stage non-small cell lung cancer. In an institutional database, patients undergoing operations for pathologic stage I non-small cell lung cancer were categorized by surgeon experience: within 5 years of completion of training, the low experience group; with 5 to 15 years of experience, the moderate experience group; and with more than 15 years, the high experience group. From 2000 to 2012, 800 operations (638 lobectomies, 162 sublobar resection) were performed with the following distribution: low experience 178 (22.2%), moderate experience 224 (28.0%), and high experience 398 (49.8%). Patients in the groups were similar in age and comorbidities. The use of video-assisted thoracoscopic surgery was higher in the moderate experience group (low experience: 62/178 [34.8%], moderate experience: 151/224 [67.4%], and high experience: 133/398 [33.4%], P < .001), as was the mean number of mediastinal (N2) lymph node stations sampled (low experience: 2.8 ± 1.6, moderate experience: 3.5 ± 1.7, high experience: 2.3 ± 1.4, P < .001). The risk of perioperative morbidity was similar across all groups (low experience: 54/178 [30.3%], moderate experience: 51/224 [22.8%], and high experience: 115/398 [28.9%], P = .163). Five-year overall survival in the moderate experience group was 76.9% compared with 67.5% in the low experience group (P < .001) and 71.4% in the high experience group (P = .006). In a Cox proportional hazard model, increasing age, male gender, prior cancer, and R1 resection were associated with an elevated risk of mortality, whereas being operated on by surgeons with moderate experience and having a greater number of mediastinal (N2) lymph node stations sampled were protective. The experience of the surgeon does not affect perioperative outcomes after resection for pathologic stage I non-small cell lung cancer. At least moderate experience after fellowship is associated with improved long-term survival. Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.
    No preview · Article · Dec 2014 · Journal of Thoracic and Cardiovascular Surgery
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective Controversy persists regarding appropriate radiographic surveillance strategies following lung cancer resection. We compared the impact of surveillance CT scan (CT) vs. chest radiograph (CXR) in patients who underwent resection for stage I lung cancer. Methods A retrospective analysis was performed of all patients undergoing resection for pathologic stage I lung cancer from January 2000-April 2013. After resection, follow-up included routine history and physical exam in conjunction with CXR or CT at the discretion of the treating physician. Identification of successive lung malignancy (i.e. recurrence at any new site or new primary) and survival were recorded. Results There were 554 evaluable patients with 232 undergoing routine postoperative CT and 322 receiving routine CXR. Postoperative five-year survival was 67.8% in the CT group vs. 74.8% in the CXR group (p = 0.603). Successive lung malignancy was found in 27% (63/232) of patients undergoing CT vs. 22% (72/322) receiving CXR (p = 0.19). The mean time from surgery to diagnosis of successive malignancy was 1.93 years for CT vs. 2.56 years for CXR (p = 0.046). For the CT group, 41% (26/63) of successive malignancies were treated with curative intent vs. 40% (29/72) in the CXR group (p = 0.639). Cox-proportional hazard analysis indicated imaging modality (CT vs. CXR) was not associated with survival (p = 0.958). Conclusion Surveillance CT may result in earlier diagnosis of successive malignancy vs. CXR in stage I lung cancer, although no difference in survival was demonstrated. A randomized trial would help determine the impact of postoperative surveillance strategies on survival.
    No preview · Article · Dec 2014 · Journal of Thoracic and Cardiovascular Surgery
  • [Show abstract] [Hide abstract]
    ABSTRACT: Introduction There is accumulating evidence that extracellular adenosine triphosphate (eATP) promotes many of the underlying mechanisms that exacerbate acute lung injury. However, much of this data is from inbred rodent models indicating the need for further investigation in higher vertebrates to better establish clinical relevance. To this end we evaluated a human recombinant apyrase therapy in a canine warm pulmonary ischemia-reperfusion injury (IRI) model and measured eATP levels in human lung recipients with or without primary lung allograft dysfunction (PGD). Methods Warm ischemia was induced for 90 minutes in the left lung of 14 mongrel dogs. Seven minutes after reperfusion, the apyrase APT102 (1 mg/kg, N=7) or saline vehicle (N=7) was injected into the pulmonary artery. Arterial blood gases were obtained every 30 minutes up to 180 minutes after reperfusion. Bronchioalveolar lavage fluid (BALF) was analyzed for eATP concentration, cellularity and inflammatory mediator accumulation. Thirty bilateral human lung transplant recipients were graded for immediate early PGD and assessed for BALF eATP levels. Results APT102-treated dogs had progressively better lung function and less pulmonary edema over the 3-hour reperfusion period when compared to vehicle-treated controls. Protection from IRI was observed with lower BALF eATP levels, fewer airway leukocytes and blunted inflammatory mediator expression. Additionally, human lung recipients with moderate to severe PGD had significantly higher eATP levels when compared to recipients without this injury. Conclusions Extracellular ATP accumulates in acutely injured canine and human lungs. Strategies that target eATP reduction may help protect lung recipients from IRI.
    No preview · Article · Oct 2014 · The Journal of Heart and Lung Transplantation
  • [Show abstract] [Hide abstract]
    ABSTRACT: The prevalence of mediastinal lymph node metastases is unknown for patients with clinical N0 lung cancer who are thought to be at high risk for occult nodal metastases. Further, the utility of mediastinoscopy in these patients is unknown. We performed a prospective trial to evaluate the utility of routine cervical mediastinoscopy for patients who may be at high risk of occult nodal metastases. From January 1, 2008, July 31, 2013, 90 patients with lung cancer with clinical stage T2N0 or T1N0 with standardized uptake value greater than 10 by positron emission tomography/computed tomography underwent routine cervical mediastinoscopy before lung resection. Biopsy of a minimum of 3 nodal stations at mediastinoscopy and a minimum of 4 nodal stations with lung resection was advised. The prevalence of nodal metastases at mediastinoscopy and lung resection was recorded. Some 64% of patients with lung cancer were male with a mean age of 67.3 years. A total of 81 patients had clinical T2N0 and 9 patients had T1N0 with standardized uptake value greater than 10. Mean tumor size was 4.3 ± 1.7 cm, and mean standardized uptake value was 13.5 ± 6.8. One patient (1.1%) had occult metastases detected at mediastinoscopy. A total of 86 patients underwent surgical resection; 4 patients (4.6%) were upstaged to pN2, and 18 patients (21%) were upstaged to pN1. Of 90 patients with clinically staged N0 lung cancer by positron emission tomography/computed tomography, 5.6% (5) were upstaged to pN2 and 20% (18) were upstaged to pN1 (total nodal upstaging = 25.6%). Mediastinoscopy seems to have limited utility in these patients with T1 and T2 clinically staged N0 by positron emission tomography/computed tomography. Selective use of mediastinoscopy is recommended, along with thorough mediastinal lymph node evaluation in all patients at the time of lung cancer resection. Copyright © 2014 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.
    No preview · Article · Sep 2014 · Journal of Thoracic and Cardiovascular Surgery

Publication Stats

2k Citations
741.88 Total Impact Points

Institutions

  • 2005-2015
    • Washington University in St. Louis
      • • Department of Surgery
      • • Division of Cardiothoracic Surgery
      San Luis, Missouri, United States
  • 2012
    • Sun Yat-Sen University
      Shengcheng, Guangdong, China
  • 2007
    • Cedars-Sinai Medical Center
      • Cedars Sinai Medical Center
      Los Ángeles, California, United States
  • 2000-2004
    • Hospital of the University of Pennsylvania
      • • Department of Surgery
      • • Division of Vascular Surgery
      • • Division of Cardiothoracic Surgery
      Philadelphia, PA, United States
  • 2002-2003
    • William Penn University
      Filadelfia, Pennsylvania, United States
  • 2001-2003
    • University of Pennsylvania
      • Department of Surgery
      Filadelfia, Pennsylvania, United States