Bio

Bio

Dr. Lui studied physics as an undergraduate at Harvard before attending medical school at Johns Hopkins. She completed a general surgery residency at the University of California San Francisco, which included two years of research in the UCSF Thoracic Oncology Laboratory and completion of a Master in Advanced Studies in clinical research. Dr. Lui went on to hold a fellowship in Thoracic Surgery at Massachusetts General Hospital, during which she participated in visiting rotations at Memorial Sloan Kettering and the Mayo Clinic.

Dr. Lui specializes in minimally invasive thoracic surgery, including robotic thoracic surgery. Her clinical focus extends to all aspects of general thoracic surgical diseases, including lung and esophageal cancer and airway diseases such as tracheomalacia. Her research focus is clinical and translational, including intraoperative fluorescence imaging. She is happy to be back in California and enjoys the warm weather, good food, and beautiful outdoors.

Clinical Focus

  • Lung cancer
  • Esophageal cancer
  • Mediastinal tumors
  • Airway tumors
  • Tracheomalacia
  • Hyperhidrosis
  • Minimally invasive surgery
  • Robotic surgery
  • Thoracic Surgery (Cardiothoracic Vascular Surgery)

Academic Appointments

Administrative Appointments

  • Unit-Based Medical Director, J6, Stanford Hospital (2019 - Present)

Honors & Awards

  • Dwight C. McGoon Teaching Award, Thoracic Surgery Residents Association (2020)
  • Donald B. Doty Educational Award, Western Thoracic Surgical Association (2019)
  • Carolyn E. Reed Traveling Fellowship Award, Thoracic Surgery Foundation (2018)

Professional Education

  • Board Certification: American Board of Thoracic Surgery, Thoracic Surgery (Cardiothoracic Vascular Surgery) (2019)
  • BA, Harvard University, Physics (2002)
  • MD, Johns Hopkins School of Medicine, Medicine (2007)
  • MAS, University of California San Francisco, Clinical research (2012)
  • Residency, University of California San Francisco, General surgery (2014)
  • Fellowship, Massachusetts General Hospital, Thoracic surgery (2016)

Contact

    • Tel: (650) 721-2086
    Fax: (650) 724-6259
  • Cardiothoracic Surgery 300 Pasteur Dr Falk Bldg CVRB MC 5407 Stanford, CA 94305
    • Tel: (650) 721-2086
    Fax: (650) 724-6259

Links

Research & Scholarship

Clinical Trials

  • Panitumumab-IRDye800 in Detecting Cancer in Participants With Lung Cancer During Surgery Not Recruiting

    This phase I/II trial studies the best dose and timing of panitumumab-IRDye800 in detecting cancer in participants with lung cancer during the surgery. Panitumumab-IRDye800 is a combination of the antibody drug panitumumab and IRDye800CW, an investigational dye that can be seen using a special camera. Panitumumab-IRDye800 may attach to tumor cells and make them more visible during surgery in patients with lung cancer.

    Stanford is currently not accepting patients for this trial. For more information, please contact Nicholas Oberhelman, 650-724-3866.

    View full details

Teaching

2020-21 Courses

Publications

All Publications

  • Strong for Surgery: Association Between Bundled Risk Factors and Outcomes After Major Elective Surgery in the VA Population. World journal of surgery Liou, D. Z., Patel, D. C., Bhandari, P., Wren, S. M., Marshall, N. J., Harris, A. H., Shrager, J. B., Berry, M. F., Lui, N. S., Backhus, L. M. 2021

    Abstract

    BACKGROUND: Strong for Surgery (S4S) is a public health campaign focused on optimizing patient health prior to surgery by identifying evidence-based modifiable risk factors. The potential impact of S4S bundled risk factors on outcomes after major surgery has not been previously studied. This study tested the hypothesis that a higher number of S4S risk factors is associated with an escalating risk of complications and mortality after major elective surgery in the VA population.METHODS: The Veterans Affairs Surgical Quality Improvement Program (VASQIP) database was queried for patients who underwent major non-emergent general, thoracic, vascular, urologic, and orthopedic surgeries between the years 2008 and 2015. Patients with complete data pertaining to S4S risk factors, specifically preoperative smoking status, HbA1c level, and serum albumin level, were stratified by number of positive risk factors, and perioperative outcomes were compared.RESULTS: A total of 31,285 patients comprised the study group, with 16,630 (53.2%) patients having no S4S risk factors (S4S0), 12,323 (39.4%) having one (S4S1), 2,186 (7.0%) having two (S4S2), and 146 (0.5%) having three (S4S3). In the S4S1 group, 60.3% were actively smoking, 35.2% had HbA1c>7, and 4.4% had serum albumin<3. In the S4S2 group, 87.8% were smokers, 84.8% had HbA1c>7, and 27.4% had albumin<3. Major complications, reoperations, length of stay, and 30-day mortality increased progressively from S4S0 to S4S3 groups. S4S3 had the greatest adjusted mortality risk (adjusted odds radio [AOR] 2.56, p=0.04) followed by S4S2 (AOR 1.58, p=0.02) and S4S1 (AOR 1.34, p=0.02).CONCLUSION: In the VA population, patients who had all three S4S risk factors, namely active smoking, suboptimal nutritional status, and poor glycemic control, had the greatest risk of postoperative mortality compared to patients with fewer S4S risk factors.

    View details for DOI 10.1007/s00268-021-05979-8

    View details for PubMedID 33598723

  • Smooth Muscle Operator: Robotic-Assisted Enucleation of an Esophageal Leiomyoma. Digestive diseases and sciences Elliott, I. A., Forgó, E., Lui, N. S. 2021

    View details for DOI 10.1007/s10620-020-06703-7

    View details for PubMedID 33479860

  • Examination of factors associated with lymph node metastases in lung carcinoids: Results from a single institution retrospective cohort study. Lung cancer (Amsterdam, Netherlands) Pathipati, M. P., Yohannan, T. K., Tian, L., Hornbacker, K., Benson, J. A., Berry, G. J., Lui, N. S., Kunz, P. L., Padda, S. K. 2021

    Abstract

    Well-differentiated lung neuroendocrine tumors (NETs), also known as typical and atypical carcinoids, have a decreased incidence of lymph node (LN) and distant metastases compared to poorly differentiated lung NETs. We aimed to (i) examine the clinicopathologic features associated with LN involvement in lung carcinoids and (ii) describe the postoperative management of patients with LN metastases.We identified 98 patients who underwent surgical resection and lymph node sampling at Stanford University. We assessed the following and used AJCC staging version 7: clinical features (age, sex, race, prior malignancy, smoking history), tumor features (functional syndrome, histology, size, location, laterality), pre-operative workup performed (imaging and suspicion of LN metastases), surgery (nodes and stations sampled, margin status, surgical approach, and type of surgery), and recurrence outcome. These features were examined between patients with and without LN metastases using the Wilcoxon test (continuous variables) and Fisher's exact test (categorical variables).87 patients (89%) had typical carcinoid and 11 patients (11%) had atypical carcinoid. 17 patients were found to have at least one positive lymph node, with 11 having N1 disease and 6 having N2 disease. In the univariable analysis, patients with lymph node disease were more likely to have recurrence of lung carcinoid (29% vs. 6%, p=0.01). In the multivariable logistic regression, there was a trend towards performance of preoperative SSTR imaging and lymph node involvement (OR = 3.06, p=0.07). No patients received adjuvant therapy.We found a trend for the performance of SSTR imaging and association of lymph node metastases in both univariable and multivariable analysis. A large proportion (41%) of patients with lymph node positive disease had < 2 cm tumors. This suggests the potential importance of incorporating SSTR imaging into routine practice and not restricting the use of this staging modality in patients with small tumors.

    View details for DOI 10.1016/j.lungcan.2021.01.017

    View details for PubMedID 33551175

  • Intracardiac paragangliomas: surgical approach and perioperative management. General thoracic and cardiovascular surgery Guenthart, B. A., Trope, W., Keeyapaj, W., Weiel, J. J., Edmonson, A., MacArthur, J. W., Annes, J. P., Woo, Y. J., Lui, N. S. 2020

    Abstract

    Intracardiac paragangliomas most commonly arise from the left atrium and are often infiltrative and densely adherent to surrounding structures. Given their rarity, only scattered reports exist in the literature and standardized perioperative and surgical management is not well established. We describe a case of a 60-year-old woman with a mildly functioning intracardiac paraganglioma in which division of the superior vena cava improved exposure and enabled a complex limited resection. Further, we provide an overview of the diagnostic workup, perioperative medical management, surgical approach, and surveillance strategy in patients with these challenging tumors.

    View details for DOI 10.1007/s11748-020-01503-2

    View details for PubMedID 33074472

  • Early Discharge Does Not Equate to Early Return for Patients Undergoing Lobectomy for Lung Cancer: A National Analysis Patel, D. C., Leipzig, M., Yang, C., Wang, Y., Shrager, J. B., Backhus, L. M., Lui, N. S., Liou, D. Z., Berry, M. F. ELSEVIER SCIENCE INC. 2020: S288

    View details for Web of Science ID 000582792300534

  • Greater Ipsilateral Rectus Muscle Atrophy after Robotic Thoracic Surgery Compared to Open and VATS Approaches Wang, Y., Bhandari, P., Trope, W., Guenthart, B. A., Guo, H., Liou, D., Backhus, L. M., Berry, M., Ben Shrager, J., Lui, N. ELSEVIER SCIENCE INC. 2020: S289

    View details for Web of Science ID 000582792300536

  • Bilateral Elastofibroma Dorsi Mistaken For Lipoma. Mayo Clinic proceedings Benson, J., Lui, N. 2020; 95 (8): 1709

    View details for DOI 10.1016/j.mayocp.2020.03.017

    View details for PubMedID 32753144

  • IMPLEMENTATION OF AN ELECTRONIC AUTO-REFERRAL PROGRAM TO IMPROVE LUNG CANCER SCREENING Patel, D., Levchuk, A., Dang, J., Ramsey, M., Lui, N., Phadke, A. SPRINGER. 2020: S658

    View details for Web of Science ID 000567143602147

  • Overview of robotic surgery for lung cancer VIDEO-ASSISTED THORACIC SURGERY Wightman, S. C., Lui, N. S. 2020; 5

    View details for DOI 10.21037/vats.2020.01.08

    View details for Web of Science ID 000534549000001

  • Socioeconomic, rural, and insurance-based inequities in robotic lung cancer resections VIDEO-ASSISTED THORACIC SURGERY Erhunmwunsee, L., Bhandari, P., Sosa, E., Sur, M., Ituarte, P. G., Lui, N. S. 2020; 5

    View details for DOI 10.21037/vats.2020.02.01

    View details for Web of Science ID 000534549000003

  • Resident education in robotic thoracic surgery VIDEO-ASSISTED THORACIC SURGERY Guenthart, B. A., Lui, N. S. 2020; 5

    View details for DOI 10.21037/vats.2020.01.01

    View details for Web of Science ID 000534549000008

  • Discovery of a novel shared tumor antigen in human lung cancer. Tseng, D., Chiou, S., Yang, X., Reuben, A., Wilhelmy, J., McSween, A., Conley, S., Sinha, R., Nabet, B., Wang, C., Shrager, J. B., Berry, M. F., Backhus, L., Lui, n., Wakelee, H. A., Neal, J. W., Zhang, J., Garcia, K., Mackall, C., Davis, M. AMER SOC CLINICAL ONCOLOGY. 2020

    View details for Web of Science ID 000560368301343

  • Cancer diagnoses and survival rise as 65-year-olds become Medicare eligible. Patel, D. C., He, H., Berry, M. F., Yang, C., Trope, W., Lui, N., Liou, D. Z., Backhus, L., Shrager, J. B. AMER SOC CLINICAL ONCOLOGY. 2020

    View details for Web of Science ID 000560368301130

  • Sub-solid lung adenocarcinoma in Asian versus Caucasian patients: different biology but similar outcomes JOURNAL OF THORACIC DISEASE Lui, N. S., Benson, J., He, H., Imielski, B. R., Kunder, C. A., Liou, D. Z., Backhus, L. M., Berry, M. F., Shrager, J. B. 2020; 12 (5): 2161?71

    View details for DOI 10.21037/jtd.2020.04.37

    View details for Web of Science ID 000537461900045

  • Integrating genomic features for non-invasive early lung cancer detection NATURE Chabon, J. J., Hamilton, E. G., Kurtz, D. M., Esfahani, M. S., Moding, E. J., Stehr, H., Schroers-Martin, J., Nabet, B. Y., Chen, B., Chaudhuri, A. A., Liu, C., Hui, A. B., Jin, M. C., Azad, T. D., Almanza, D., Jeon, Y., Nesselbush, M. C., Keh, L., Bonilla, R. F., Yoo, C. H., Ko, R. B., Chen, E. L., Merriott, D. J., Massion, P. P., Mansfield, A. S., Jen, J., Ren, H. Z., Lin, S. H., Costantino, C. L., Burr, R., Tibshirani, R., Gambhir, S. S., Berry, G. J., Jensen, K. C., West, R. B., Neal, J. W., Wakelee, H. A., Loo, B. W., Kunder, C. A., Leung, A. N., Lui, N. S., Berry, M. F., Shrager, J. B., Nair, V. S., Haber, D. A., Sequist, L. V., Alizadeh, A. A., Diehn, M. 2020

    View details for DOI 10.1038/s41586-020-2140-0

    View details for Web of Science ID 000521531000011

  • Spontaneous Bleeding from Multiple Intercostal Arteries in a Patient with Coarctation of the Aorta. The Annals of thoracic surgery Wightman, S. C., Wang, Y., Rohr, A. M., Greene, C. L., Hwang, G. L., Watkins, A. C., Lui, N. S. 2020

    Abstract

    A 59-year-old man with a history of coarctation repair, mechanical aortic valve, and warfarin therapy presented with right flank pain. Computerized tomography (CT) scan showed a large hematoma encircling an intact descending thoracic aorta. CT angiogram demonstrated multiple areas of intercostal artery extravasation. Interventional radiology performed angiography and embolization. His course was complicated by an effusion and hypoxia; but no further bleeding was noted. We hypothesize coarctation association aneurysms and potential vessel wall weakness and as cause of hematoma in our case. We present the first case with history of repaired coarctation with multiple spontaneous intercostal artery aneurysmal rupture.

    View details for DOI 10.1016/j.athoracsur.2019.12.042

    View details for PubMedID 32035043

  • Transcervical Thymectomy is the Most Cost-Effective Surgical Approach in Myasthenia Gravis. The Annals of thoracic surgery Sholtis, C., Teymourtash, M., Berry, M., Backhus, L., Bhandari, P., He, H., Benson, J., Wang, Y. Y., Yevudza, E., Lui, N., Shrager, J. 2020

    Abstract

    Extended thymectomy is now proven to improve the course of myasthenia gravis. Retrospective studies demonstrate that several techniques for thymectomy achieve overlapping remission rates. We therefore compared perioperative outcomes and costs among 3 approaches to thymectomy: sternotomy; video/robot assisted; transcervical.To ensure similar study groups, we excluded patients with >4cm or invasive tumors and those who underwent less than an extended thymectomy or concurrent procedures. Hospital costs were collected and analyzed by blinded finance personnel.The final study group consisted of 25 transcervical, 23 video/robotic, and 14 sternotomy subjects. There was a higher incidence of myasthenia gravis in the transcervical and sternotomy groups (p<0.01) and of thymoma in the video/robotic and sternotomy groups (p<0.01). Mean modified Charlson co-morbidity score was higher for sternotomy (2.7±2.1) than transcervical (1.00±.58; p<0.001) and video/robotic (1.13±.97; p=0.001). There was no difference in complication rates between approaches (p=0.83). The cost of transcervical thymectomy was 45% of the cost of sternotomy (p<0.001) and 58% of the cost of video/robotic (p=0.018) approaches; these differences remained highly significant on multivariate analysis. Transcervical thymectomy had shorter mean length of stay (1.2±.5 days) than median sternotomy (4.4±3.5; p<0.001) and video/robot assisted thymectomy (2.6±.96; p=0.045), and "bed cost" was the major contributor to cost difference between the groups.Transcervical thymectomy, which provides overlapping myasthenia gravis remission rates vs. more invasive approaches, is equally safe and far less costly than sternotomy and video/robotic approaches.

    View details for DOI 10.1016/j.athoracsur.2020.01.047

    View details for PubMedID 32135150

  • Does size matter? A national analysis of the utility of induction therapy for large thymomas. Journal of thoracic disease Liou, D. Z., Ramakrishnan, D., Lui, N. S., Shrager, J. B., Backhus, L. M., Berry, M. F. 2020; 12 (4): 1329?41

    Abstract

    Tumor size of 8 cm or greater is a risk factor for recurrence after thymoma resection, but the role of induction therapy for large thymomas is not well defined. This study tested the hypothesis that induction therapy for thymomas 8 cm and larger improves survival.The use of induction therapy for patients treated with surgical resection for Masaoka stage I-III thymomas in the National Cancer Database between 2006-2013 was evaluated using logistic regression, Kaplan-Meier analysis, and Cox-proportional hazards methods.Of the 1,849 patients who met inclusion criteria, 582 (31.5%) had tumors ?8 cm. Five-year survival was worse in patients with tumors ?8 cm compared to smaller tumors [84.6% (95% CI: 81.2-88.1%) vs. 89.4% (95% CI: 87.2-91.7%), P=0.003]. Induction therapy was used in 166 (9.0%) patients overall and was more likely in patients with tumors ?8 cm [adjusted odds ratio (AOR) 3.257, P<0.001]. Induction therapy was not associated with improved survival in the subset of patients with tumors ?8 cm in either univariate [80.9% (95% CI: 72.6-90.1%) vs. 85.4% (95% CI: 81.8-89.3%), P=0.27] or multivariable analysis [hazard ratio (HR) 1.54, P=0.10]. Increasing age (HR 1.56/decade, P<0.001) and Masaoka stage III (HR 1.76, P=0.04) were associated with worse survival in patients with tumors ?8 cm.Survival after thymoma resection is worse for tumors 8 cm or larger compared to smaller tumors and is not improved by induction therapy. Size alone should not be a criterion for using induction therapy prior to thymoma resection.

    View details for DOI 10.21037/jtd.2020.02.63

    View details for PubMedID 32395270

    View details for PubMedCentralID PMC7212162

  • Integrating genomic features for non-invasive early lung cancer detection. Nature Chabon, J. J., Hamilton, E. G., Kurtz, D. M., Esfahani, M. S., Moding, E. J., Stehr, H., Schroers-Martin, J., Nabet, B. Y., Chen, B., Chaudhuri, A. A., Liu, C. L., Hui, A. B., Jin, M. C., Azad, T. D., Almanza, D., Jeon, Y. J., Nesselbush, M. C., Co Ting Keh, L., Bonilla, R. F., Yoo, C. H., Ko, R. B., Chen, E. L., Merriott, D. J., Massion, P. P., Mansfield, A. S., Jen, J., Ren, H. Z., Lin, S. H., Costantino, C. L., Burr, R., Tibshirani, R., Gambhir, S. S., Berry, G. J., Jensen, K. C., West, R. B., Neal, J. W., Wakelee, H. A., Loo, B. W., Kunder, C. A., Leung, A. N., Lui, N. S., Berry, M. F., Shrager, J. B., Nair, V. S., Haber, D. A., Sequist, L. V., Alizadeh, A. A., Diehn, M. 2020; 580 (7802): 245?51

    Abstract

    Radiologic screening of high-risk adults reduces lung-cancer-related mortality1,2; however, a small minority of eligible individuals undergo such screening in the United States3,4. The availability of blood-based tests could increase screening uptake. Here we introduce improvements to cancer personalized profiling by deep sequencing (CAPP-Seq)5, a method for the analysis of circulating tumour DNA (ctDNA), to better facilitate screening applications. We show that, although levels are very low in early-stage lung cancers, ctDNA is present prior to treatment in most patients and its presence is strongly prognostic. We also find that the majority of somatic mutations in the cell-free DNA (cfDNA) of patients with lung cancer and of risk-matched controls reflect clonal haematopoiesis and are non-recurrent. Compared with tumour-derived mutations, clonal haematopoiesis mutations occur on longer cfDNA fragments and lack mutational signatures that are associated with tobacco smoking. Integrating these findings with other molecular features, we develop and prospectively validate a machine-learning method termed 'lung cancer likelihood in plasma' (Lung-CLiP), which can robustly discriminate early-stage lung cancer patients from risk-matched controls. This approach achieves performance similar to that of tumour-informed ctDNA detection and enables tuning of assay specificity in order to facilitate distinct clinical applications. Our findings establish the potential of cfDNA for lung cancer screening and highlight the importance of risk-matching cases and controls in cfDNA-based screening studies.

    View details for DOI 10.1038/s41586-020-2140-0

    View details for PubMedID 32269342

  • KEAP1/NFE2L2 mutations predict lung cancer radiation resistance that can be targeted by glutaminase inhibition. Cancer discovery Binkley, M. S., Jeon, Y. J., Nesselbush, M., Moding, E. J., Nabet, B. Y., Almanza, D., Kunder, C., Stehr, H., Yoo, C. H., Rhee, S., Xiang, M., Chabon, J. J., Hamilton, E., Kurtz, D. M., Gojenola, L., Owen, S. G., Ko, R. B., Shin, J. H., Maxim, P. G., Lui, N. S., Backhus, L. M., Berry, M. F., Shrager, J. B., Ramchandran, K. J., Padda, S. K., Das, M., Neal, J. W., Wakelee, H. A., Alizadeh, A. A., Loo, B. W., Diehn, M. 2020

    Abstract

    Tumor genotyping is not routinely performed in localized non-small cell lung cancer (NSCLC) due to lack of associations of mutations with outcome. Here, we analyze 232 consecutive patients with localized NSCLC and demonstrate that KEAP1 and NFE2L2 mutations are predictive of high rates of local recurrence (LR) after radiotherapy but not surgery. Half of LRs occurred in KEAP1/NFE2L2 mutation tumors, indicating they are major molecular drivers of clinical radioresistance. Next, we functionally evaluate KEAP1/NFE2L2 mutations in our radiotherapy cohort and demonstrate that only pathogenic mutations are associated with radioresistance. Furthermore, expression of NFE2L2 target genes does not predict LR, underscoring the utility of tumor genotyping. Finally, we show that glutaminase inhibition preferentially radiosensitizes KEAP1 mutant cells via depletion of glutathione and increased radiation-induced DNA damage. Our findings suggest that genotyping for KEAP1/NFE2L2 mutations could facilitate treatment personalization and provide a potential strategy for overcoming radioresistance conferred by these mutations.

    View details for DOI 10.1158/2159-8290.CD-20-0282

    View details for PubMedID 33071215

  • Commentary: Lung cancer outcomes reporting within the VA system: room for improvement. Seminars in thoracic and cardiovascular surgery Guenthart, B. A., Backhus, L. M., Lui, N. S. 2020

    View details for DOI 10.1053/j.semtcvs.2020.06.008

    View details for PubMedID 32569647

  • Paradoxical Motion on Sniff Test Predicts Greater Improvement Following Diaphragm Plication. The Annals of thoracic surgery Patel, D. C., Berry, M. F., Bhandari, P., Backhus, L. M., Raees, S., Trope, W., Nash, A., Lui, N. S., Liou, D. Z., Shrager, J. B. 2020

    Abstract

    Diaphragm plication (DP) improves pulmonary function and quality of life for those with diaphragm paralysis/dysfunction. It is unknown whether differing degrees of diaphragm dysfunction as measured by sniff testing impact results after plication.Patients who underwent minimally invasive DP from 2008-2019 were dichotomized based on sniff test results: paradoxical motion (PM) vs. no paradoxical motion (NPM) - the latter including normal/decreased/no motion. Preoperative and postoperative pulmonary function testing (PFT) after DP was compared between the two groups. The impact of diaphragm height index (DHI), a measure of diaphragm elevation, was also assessed.Twenty-six patients underwent preoperative sniff testing, DP, and postoperative PFTs. Including all patients, DP resulted in a 17.8 ± 5.5% (p<0.001) improvement in forced expiratory volume at 1 second (FEV1), a 14.4 ± 5.3% (p<0.001) improvement in forced vital capacity (FVC), and a 4.7 ± 4.6% (p=0.539) improvement in diffusing capacity (DLCO). There were greater improvements in the PM group (n=16) vs. NPM group (n=10) for FEV1 (27.2 ± 6.0% vs. 3.9 ± 6.2%, p=0.017) and FVC (28.1 ± 5.3% vs. -0.5 ± 3.3%, p=0.001). There was no difference in ?DLCO between groups. There were no differences between patients with PM and NPM in postoperative course/complications. No value for DHI predicted improvement in PFTs following DP.Patients with PM on sniff test have dramatically greater objective improvements in pulmonary function following plication than those without PM. Most patients without PM do not demonstrate improvement in standard PFTs. Improvements in dyspnea require additional study.

    View details for DOI 10.1016/j.athoracsur.2020.07.049

    View details for PubMedID 33031777

  • Safety and Stability of Antibody-Dye Conjugate in Optical Molecular Imaging. Molecular imaging and biology Pei, J., Juniper, G., van den Berg, N. S., Nisho, N., Broadt, T., Welch, A. R., Yi, G. S., Raymundo, R. C., Chirita, S. U., Lu, G., Krishnan, G., Lee, Y. J., Kapoor, S., Zhou, Q., Colevas, A. D., Lui, N. S., Poultsides, G. A., Li, G., Zinn, K. R., Rosenthal, E. L. 2020

    Abstract

    The development of molecularly targeted tracers is likely to improve the accuracy of diagnostic, screening, and therapeutic tools. Despite the many therapeutic antibodies that are FDA-approved with known toxicity, only a limited number of antibody-dye conjugates have been introduced to the clinic. Thorough evaluation of the safety, stability, and pharmacokinetics of antibody conjugates in the clinical setting compared with their parental components could accelerate the clinical approval of antibodies as agents for molecular imaging. Here we investigate the safety and stability of a near-infrared fluorescent dye (IRDye800CW) conjugated panitumumab, an approved therapeutic antibody, and report on the product stability, pharmacokinetics, adverse events, and QTc interval changes in patients.Panitumumab-IRDye800CW was made under good manufacturing practice (GMP) conditions in a single batch on March 26, 2014, and then evaluated over 4.5 years at 0, 3, and 6 months, and then at 6-month intervals thereafter. We conducted early phase trials in head and neck, lung, pancreas, and brain cancers with panitumumab-IRDye800CW. Eighty-one patients scheduled to undergo standard-of-care surgery were infused with doses between 0.06 to 2.83 mg/kg of antibody. Patient ECGs, blood samples, and adverse events were collected over 30-day post-infusion for analysis.Eighty-one patients underwent infusion of the study drug at a range of doses. Six patients (7.4 %) experienced an adverse event that was considered potentially related to the drug. The most common event was a prolonged QTc interval which occurred in three patients (3.7 %). Panitumumab-IRDye800CW had two OOS results at 42 and 54 months while meeting all other stability testing criteria.Panitumumab-IRDye800CW was safe and stable to administer over a 54-month window with a low rate of adverse events (7.4 %) which is consistent with the rate associated with panitumumab alone. This data supports re-purposing therapeutic antibodies as diagnostic imaging agents with limited preclinical toxicology studies.

    View details for DOI 10.1007/s11307-020-01536-2

    View details for PubMedID 32880818

  • A National Analysis of Treatment Patterns and Outcomes for Patients 80 Years or Older with Esophageal Cancer. Seminars in thoracic and cardiovascular surgery Yang, C. J., Wang, Y., Raman, V., Patel, D., Lui, N., Backhus, L., Shrager, J., Berry, M. F., Liou, D. 2020

    Abstract

    The purpose of this study was to evaluate practice patterns and outcomes for patients 80 years or older with esophageal cancer using a nationwide cancer database. Practice patterns for patients 80 years or older with stage I-IV esophageal cancer in the National Cancer Database from 2004-2014 were analyzed. Overall survival associated with different treatment strategies were evaluated using the Kaplan-Meier method and multivariable Cox proportional hazard models. In the study period, 40.5% and 46.2% of patients with stage I adenocarcinoma and squamous cell carcinoma, respectively, did not receive any treatment at all. Less than 11% (196/1,865) of patients with stage I-II disease underwent esophagectomy, even though surgery was associated with a better 5-year survival compared to no treatment (stage I: 47.3% [95% CI 36.2%-57.6%] vs 14.9% [95% CI: 11.2%-19.1%]; stage II: 29.3% [95% CI 20.1%-39.1%] vs 1.2% [95% CI: 0.1%-5.5%]). Of the 1,596 (37.7%) patients with stage III disease who received curative-intent treatment (surgery or chemoradiation), the 5-year survival was significantly better than that of patients who received no treatment (11.9% [95% CI: 9.7%-14.4% vs 4.3% [95% CI: 1.9%-8.3%]). In this national analysis of patients 80 years and older with esophageal cancer, over 40% of patients with stage I disease did not receive treatment. Patients with stage I-III disease had better survival and risks and benefits of treatment for elderly patients should be discussed in a multidisciplinary setting.

    View details for DOI 10.1053/j.semtcvs.2020.09.004

    View details for PubMedID 32977014

  • The Oldest Old: A National Analysis of Outcomes for Patients 90 Years or Older With Lung Cancer. The Annals of thoracic surgery Yang, C. J., Brown, A. B., Deng, J. Z., Lui, N. S., Backhus, L. M., Shrager, J. B., D'Amico, T. A., Berry, M. F. 2019

    Abstract

    BACKGROUND: Most clinicians will encounter patients 90 years or older with non-small cell lung cancer (NSCLC), but evidence that informs treatment decisions for this extremely elderly population is lacking. This study evaluated outcomes associated with treatment strategies for this nonagenarian population.METHODS: Treatment and overall survival for patients 90 years and older with NSCLC in the National Cancer Data Base (2004-2014) were evaluated using logistic regression, the Kaplan-Meier method, and multivariable Cox proportional hazard models.RESULTS: The majority (n = 4152, 57.6%) of the 7205 patients 90 years or older with stage I-IV NSCLC did not receive any therapy. For the entire cohort, receiving treatment was associated with significantly better survival when compared with no therapy (5-year survival, 9.3% [95% confidence interval [CI], 8.0%-10.7%] vs 1.7% [95% CI, 1.2%-2.2%]; multivariable adjusted hazard ratio, 0.53; P < .001). Stage I patients had the most pronounced survival benefit with treatment (median survival, 27.4 months vs 10.0 months with no treatment; P < .001). Among this subset of patients with stage I disease (n= 1430), only 12.7% (n= 182) had surgery and 33% (n= 471) had no therapy. In these stage I patients surgery was associated with significantly better 5-year survival (33.7% [95% CI, 25.4%-42.1%]) than nonoperative therapy (17.1% [95% CI, 13.7%-20.8%]) and no therapy (6.2% [95% CI, 3.8%-9.4%]).CONCLUSIONS: Therapy for nonagenarians with NSCLC is associated with a significant survival benefit but is not used in most patients. Treatment should not be withheld for these "oldest old" patients based on their age alone but should be considered based on stage and patient preferences in a multidisciplinary setting.

    View details for DOI 10.1016/j.athoracsur.2019.09.027

    View details for PubMedID 31757356

  • National Evaluation of Short-Term and Intermediate-Term Readmission after Esophagectomy Yang, C. J., Wang, Y., He, H., Liou, D., Lui, N., Berry, M. F., Shrager, J., Backhus, L. ELSEVIER SCIENCE INC. 2019: S279?S280

    View details for Web of Science ID 000492740900545

  • Management of Benign Esophageal Perforation in the National Inpatient Sample Lui, N., Bhandari, P., Backhus, L., Liou, D., Shrager, J., Berry, M. F. ELSEVIER SCIENCE INC. 2019: E209

    View details for Web of Science ID 000492749600500

  • Single-Lumen Endotracheal Tube and Bronchial Blocker for Airway Management During Tracheobronchoplasty for Tracheobronchomalacia: A Case Report. A&A practice Lui, N. S., Guo, H. H., Sung, A. W., Peterson, A., Kulkarni, V. N. 2019

    Abstract

    We present a case of a 69-year-old man who underwent tracheobronchoplasty for tracheobronchomalacia using a single-lumen endotracheal tube and a Y-shaped bronchial blocker for airway management. Tracheobronchoplasty is performed by sewing mesh to plicate the posterior, membranous wall of the distal trachea and main bronchi through a right posterolateral thoracotomy. The goals of airway management include continuous left-lung ventilation and lung protection from aspiration. Ideally, only conventional airway management tools are used. This case demonstrates that a single-lumen endotracheal tube with a bronchial blocker can be a straightforward strategy for airway management during tracheobronchoplasty.

    View details for DOI 10.1213/XAA.0000000000001076

    View details for PubMedID 31385817

  • Unconscious Bias: Addressing the Hidden Impact on Surgical Education. Thoracic surgery clinics Backhus, L. M., Lui, N. S., Cooke, D. T., Bush, E. L., Enumah, Z., Higgins, R. 2019; 29 (3): 259?67

    Abstract

    Unconscious (or implicit) biases are learned stereotypes that are automatic, unintentional, deeply engrained, universal, and able to influence behavior. Several studies have documented the effects of provider biases on patient care and outcomes. This article provides a framework for exploring the implications for unconscious bias in surgical education and highlights best practices toward minimizing its impact. Presented is the background related to some of the more common unconscious biases and effects on medical students, resident trainees, and academic faculty. Finally, targeted strategies are highlighted for individuals and institutions for identification of biases and the means to address them.

    View details for DOI 10.1016/j.thorsurg.2019.03.004

    View details for PubMedID 31235294

  • A National Analysis of Short-term Outcomes and Long-term Survival Following Thoracoscopic Versus Open Lobectomy for Clinical Stage II Non-Small-Cell Lung Cancer. Annals of surgery Yang, C. J., Kumar, A., Deng, J. Z., Raman, V., Lui, N. S., D'Amico, T. A., Berry, M. F. 2019

    Abstract

    MINI: In this national analysis, thoracoscopic lobectomy was associated with shorter hospital stay and no significant difference in long-term survival when compared to open lobectomy for cT1-2N1M0 non-small-cell lung cancer (NSCLC). These results suggest that thoracoscopic techniques are feasible in the treatment of stage II (cN1) NSCLC.OBJECTIVE: To compare outcomes after open versus thoracoscopic (VATS) lobectomy for clinical stage II (cN1) non-small-cell lung cancer (NSCLC).BACKGROUND: There have been no published studies evaluating the impact of a VATS approach to lobectomy for N1 NSCLC on short-term outcomes and survival.METHODS: Outcomes of patients with clinical T1-2, N1, M0 NSCLC who underwent lobectomy without induction therapy in the National Cancer Data Base (2010-2012) were evaluated using multivariable Cox proportional hazards modeling and propensity score-matched analysis.RESULTS: Median follow-up of 1559 lobectomies (1204 open and 355 VATS) was 43.2 months. The VATS approach was associated with a shorter median hospitalization (5 vs 6 d, P < 0.001) than the open approach. There were no significant differences between the VATS and open approach with regard to nodal upstaging (12.0% vs 10.5%, P = 0.41), 30-day mortality (2.3% vs 3.1%, P = 0.31), and overall survival (5-yr survival: 48.6% vs 48.7%, P = 0.76; multivariable-adjusted HR for VATS approach: 1.08, 95% CI: 0.90-1.30, P = 0.39). A propensity score-matched analysis of 334 open and 334 VATS patients who were well matched by 14 common prognostic covariates, including tumor size, and comorbidities, continued to show no significant differences in nodal upstaging, 30-day mortality, and 5-year survival between the VATS and open groups.CONCLUSION: In this national analysis, VATS lobectomy was used in the minority of N1 NSCLC cases but was associated with shorter hospitalization and similar nodal upstaging rates, 30-day mortality, and long-term survival when compared to open lobectomy. These findings suggest thoracoscopic techniques are feasible for the treatment of stage II (cN1) NSCLC.

    View details for PubMedID 30946089

  • Examination of Factors Associated With Lymph Node Metastases in Lung Carcinoids Pathipati, M. P., Yohannan, T. K., Tian, L., Benson, J. A., Hornbacker, K., Berry, G. J., Lui, N., Kunz, P. L., Padda, S. K. LIPPINCOTT WILLIAMS & WILKINS. 2019: 447

    View details for Web of Science ID 000462541800096

  • The influence of hormone replacement therapy on lung cancer incidence and mortality. The Journal of thoracic and cardiovascular surgery Titan, A. L., He, H., Lui, N., Liou, D., Berry, M., Shrager, J. B., Backhus, L. M. 2019

    Abstract

    Data regarding the effects of hormone replacement therapy (HRT) on non-small cell lung cancer (NSCLC) are mixed. We hypothesized HRT would have a protective benefit with reduced NSCLC incidence among women in a large, prospective cohort.We used data from the multicenter randomized Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (1993-2001). Participants were women aged 50 to 74 years followed prospectively for up to 13 years for cancer screening. The influence of HRT on the primary outcome of NSCLC incidence and secondary outcomes of all-cause and disease-specific mortality were assessed with Kaplan-Meier analysis and Cox proportional hazard models adjusting for covariates.In the overall cohort of 75,587 women, 1147 women developed NSCLC after a median follow-up of 11.5 years. HRT use was characterized as 49.4% current users, 17.0% former users, and 33.6% never users. Increased age, smoking, comorbidities, and family history were associated with increased risk of NSCLC. On multivariable analysis, current HRT use was associated with reduced risk of NSCLC compared with never users (hazard ratio, 0.80; 95% confidence interval, 0.70-0.93; P = .009). HRT or oral contraception use was not associated with significant differences in all-cause mortality or disease-specific mortality.These data represent among the largest prospective cohorts suggesting HRT use may have a protective effect on the development of NSCLC among women; the physiological basis of this effect merits further study; however, the results may influence discussion surrounding HRT use in women.

    View details for DOI 10.1016/j.jtcvs.2019.10.070

    View details for PubMedID 31866083

  • A national analysis of open versus minimally invasive thymectomy for stage I to III thymoma. The Journal of thoracic and cardiovascular surgery Yang, C. J., Hurd, J., Shah, S. A., Liou, D., Wang, H., Backhus, L. M., Lui, N. S., D'Amico, T. A., Shrager, J. B., Berry, M. F. 2019

    Abstract

    The oncologic efficacy of minimally invasive thymectomy for thymoma is not well characterized. We compared short-term outcomes and overall survival between open and minimally invasive (video-assisted thoracoscopic and robotic) approaches using the National Cancer Data Base.Perioperative outcomes and survival of patients who underwent open versus minimally invasive thymectomy for clinical stage I to III thymoma from 2010 to 2014 in the National Cancer Data Base were evaluated using multivariable Cox proportional hazards modeling and propensity score-matched analysis. Predictors of minimally invasive use were evaluated using multivariable logistic regression. Outcomes of surgical approach were evaluated using an intent-to-treat analysis.Of the 1223 thymectomies that were evaluated, 317 (26%) were performed minimally invasively (141 video-assisted thoracoscopic and 176 robotic). The minimally invasive group had a shorter median length of stay when compared with the open group (3 [2-4] days vs 4 [3-6] days, P < .001). In a propensity score-matched analysis of 185 open and 185 minimally invasive (video-assisted thoracoscopic + robotic) thymectomy, the minimally invasive group continued to have a shorter median length of stay (3 vs 4 days, P < .01) but did not have significant differences in margin positivity (P = .84), 30-day readmission (P = .28), 30-day mortality (P = .60), and 5-year survival (89.4% vs 81.6%, P = .20) when compared with the open group.In this national analysis, minimally invasive thymectomy was associated with shorter length of stay and was not associated with increased margin positivity, perioperative mortality, 30-day readmission rate, or reduced overall survival when compared with open thymectomy.

    View details for DOI 10.1016/j.jtcvs.2019.11.114

    View details for PubMedID 32245668

  • Commentary: Pleomorphic carcinoma: An aggressive type of non-small cell lung cancer that should be treated like the others. The Journal of thoracic and cardiovascular surgery Lui, N. S. 2019

    View details for DOI 10.1016/j.jtcvs.2019.04.074

    View details for PubMedID 31196757

  • Cut it out! Thoracic Surgeon's Approach to Pulmonary Mucormycosis and the Role of Surgical Resection in Survival. Mycoses Multani, A., Reveron-Thornton, R., Garvert, D. W., Gomez, C. A., Montoya, J. G., Lui, N. S. 2019

    Abstract

    Mucormycosis portends a poor prognosis with mortality rates ranging from 50-70% in pulmonary mucormycosis (PM) and up to 95% in disseminated disease. However, detailed outcomes data have been lacking. It remains unknown how to identify patients who would benefit from surgical resection.We present our experience with patients undergoing surgical resection for PM, including an analysis of factors affecting postoperative survival. We also describe a thoracic surgeon's approach through illustrative cases.We conducted a single-center retrospective study of all adult patients with PM who received antifungal therapy and underwent surgical resection or who received antifungal therapy alone at Stanford between January 2004 and June 2018.Twelve patients received antifungal therapy and underwent surgical resection and 13 patients received antifungal therapy alone. From infection onset to death (or right-censoring if still alive), patients who underwent surgical resection had a median survival of 406 days (mean, 561.3; range, 22-2,510), and patients who received antifungal therapy alone had a median survival of 28 days (mean, 66.7; range, 8-447). In patients who underwent surgical resection, median postoperative survival time was 154 days (range, 11-2,495), in-hospital mortality was 16.7%, and 1-year mortality was 50.0%. Age, primary disease, ASA status, extrapulmonary dissemination, laterality, multilobar involvement, number of lesions, largest lesion size, platelet count, surgical approach, type of resection, or extent of resection were not significantly associated with postoperative survival.Surgical resection significantly increases survival and should be strongly considered for selected patients with PM. This article is protected by copyright. All rights reserved.

    View details for DOI 10.1111/myc.12954

    View details for PubMedID 31173415

  • Surgical Management for Aortoesophageal Fistula After Endovascular Aortic Repair. The Annals of thoracic surgery Zhu, Y., MacArthur, J. W., Lui, N., Lee, A. M. 2019

    Abstract

    This case demonstrates successful surgical management of a 6 cm-long aortoesophageal fistula from an infected stent graft. A 69-year-old woman with a penetrating descending thoracic aortic ulcer underwent endovascular aortic repair. Two weeks later, she presented with nausea and melena, and was found to have an infected stent graft on imaging. She underwent a two-stage procedure encompassing aortic arch debranching and extra-anatomic aortic bypass in stage one, and stent graft resection, primary esophageal repair, intercostal and omental flap and jejunostomy tube placement in stage two. She was discharged one month later and is doing well 1.5 years after the operation.

    View details for DOI 10.1016/j.athoracsur.2019.08.076

    View details for PubMedID 31586613

  • Commentary: Should lung cancer screening guidelines go up in smoke? The Journal of thoracic and cardiovascular surgery Lui, N. S. 2019

    View details for DOI 10.1016/j.jtcvs.2019.05.039

    View details for PubMedID 31255344

  • Neoadjuvant chemotherapy versus chemoradiotherapy for esophageal cancer: a tradeoff between dysphagia and pathologic response VIDEO-ASSISTED THORACIC SURGERY Lui, N. 2018; 3

    View details for DOI 10.21037/vats.2018.12.02

    View details for Web of Science ID 000457104600002

  • Yellow nail syndrome with chylothorax after coronary artery bypass grafting. Journal of cardiothoracic surgery Waliany, S., Chandler, J., Hovsepian, D., Boyd, J., Lui, N. 2018; 13 (1): 93

    Abstract

    BACKGROUND: Yellow nail syndrome is a rare condition considered secondary to functional anomalies of lymphatic drainage. Yellow nail syndrome is diagnosed through the triad of intrathoracic findings (30% being pleural effusions), nail discoloration, and lymphedema, with any two features sufficient for diagnosis. We report the second case of post-operative yellow nail syndrome.CASE PRESENTATION: After coronary artery bypass grafting, our patient presented with chylothorax on post-operative day 13 and yellow toenail discoloration on post-operative day 28, diagnosing yellow nail syndrome. Initial conservative management with pigtail catheter drainage and low-fat diet with medium-chain triglycerides reduced chylous drainage from 350mL/day on post-operative day 14 to <100mL/day on post-operative day 17. However, by post-operative day 18, drainage returned to 350mL/day that persisted despite attempts to readjust the catheter position, replacement of catheter with chest tube, and transition to total parenteral nutrition and octreotide while nil per os. Lymphangiogram on post-operative day 32 did not identify the thoracic duct or cisterna chyli, precluding embolization. Talc and doxycycline pleurodeses performed on post-operative days 33 and 38, respectively, resolved his chylothorax and nail discoloration.CONCLUSIONS: Both yellow nail syndrome and chylothorax as a complication of coronary artery bypass grafting are rare entities. The proposed mechanism of post-operative chylothorax is iatrogenic injury to thoracic duct or collateral lymphatic vessels. Diagnosing yellow nail syndrome in patients with post-operative chylothorax (through co-existing yellow nail discoloration and/or lymphedema) may suggest predisposition to impaired lymphatic drainage, portending a difficult recovery and potentially indicating need for surgical management.

    View details for PubMedID 30201014

  • Induction therapy for locally advanced distal esophageal adenocarcinoma: Is radiation Always necessary? The Journal of thoracic and cardiovascular surgery Liou, D. Z., Backhus, L. M., Lui, N. S., Shrager, J. B., Berry, M. F. 2018

    Abstract

    OBJECTIVE: To compare outcomes between induction chemotherapy alone (ICA) and induction chemoradiation (ICR) in patients with locally advanced distal esophageal adenocarcinoma.METHODS: Patients in the National Cancer Database treated with ICA or ICR followed by esophagectomy between 2006 and 2012 for cT1-3N1M0 or T3N0M0 adenocarcinoma of the distal esophagus were compared using logistic regression, Kaplan-Meier analysis, and Cox proportional hazards methods.RESULTS: The study group included 4763 patients, of whom 4323 patients (90.8%) received ICR and 440 patients (9.2%) received ICA. There were no differences in age, sex, race, Charlson Comorbidity Index, treatment facility type, clinical T or N status between the 2 groups. Tumor size ?5cm (odds ratio, 1.46; P=.006) was the only factor that predicted ICR use. Higher rates of T downstaging (39.7% vs 33.4%; P=.012), N downstaging (32.0% vs 23.4%; P<.001), and complete pathologic response (13.1% vs 5.9%; P<.001) occurred in ICR patients. Positive margins were seen more often in ICA patients (9.6% vs 5.5%; P=.001), but there was no difference in 5-year survival (ICR 35.9% vs ICA 37.2%; P=.33), and ICR was not associated with survival in multivariable analysis (hazard ratio=1.04; P=.61).CONCLUSIONS: ICR for locally advanced distal esophageal adenocarcinoma is associated with a better local treatment effect, but not improved survival compared with ICA, which suggests that radiation can be used selectively in this clinical situation.

    View details for PubMedID 29530567

  • Ground-glass opacity heralding invasive lung adenocarcinoma with prodromal dermatomyositis: a case report JOURNAL OF CARDIOTHORACIC SURGERY Beel, A. J., Demos, D. S., Chung, A., Liao, C., Lui, N. S. 2018; 13: 20

    Abstract

    Dermatomyositis, an inflammatory myopathy with cutaneous involvement, is associated with malignancy and often manifests paraneoplastically. While co-occurrence with small cell carcinoma is well attested, primary lung adenocarcinoma, which may present as focal ground-glass opacification on computed tomography of the thorax, is less frequently coincident.We report the case of a 72-year-old female patient with dermatomyositis - treated with a combination of prednisone, methotrexate, and intravenous immunoglobulin - and an indolent, subsolid, non-hypermetabolic pulmonary lesion, which was determined to be invasive primary lung adenocarcinoma. Supporting a paraneoplastic basis, immunosuppressive therapy was discontinued following tumor excision without relapse of signs or symptoms of dermatomyositis.While dermatomyositis prodromal to lung adenocarcinoma is not without precedent, association with an indolent, subsolid lesion has, to the best of our knowledge, not been reported. The case described herein illustrates the importance of maintaining a high index of suspicion for malignancy in the setting of dermatomyositis.

    View details for PubMedID 29415746

  • A Novel and Successful Repair of a Left Atriogastric Fistula After Esophagectomy. The Annals of thoracic surgery Panda, N., Feins, E. N., Axtell, A., Lui, N., Melnitchouk, S. I., Donahue, D. M. 2017; 104 (2): e157?e159

    Abstract

    Atriogastric fistulas remain a rare adverse event in patients who undergo esophagectomy with gastric pullthrough. The presentation of an atriogastric fistula ranges from self-limited gastrointestinal bleeding to life-threatening hemorrhage, end-organ dysfunction from septic emboli, or both. These fistulas are associated with significant mortality. Previous reports describe successful repairs of gastrocardiac fistulas with the use of cardiopulmonary bypass. This report describes a patient with a significant burden of cerebral embolic disease, which therefore required a unique approach to fistula repair.

    View details for DOI 10.1016/j.athoracsur.2017.02.079

    View details for PubMedID 28734441

  • SULF2 Expression Is a Potential Diagnostic and Prognostic Marker in Lung Cancer PLOS ONE Lui, N. S., Yang, Y., van Zante, A., Buchanan, P., Jablons, D. M., Lemjabbar-Alaoui, H. 2016; 11 (2)

    Abstract

    Lung cancer is one of the most deadly cancers; median survival from diagnosis is less than one year in those with advanced disease. Novel lung cancer biomarkers are desperately needed. In this study, we evaluated SULF2 expression by immunohistochemistry and its association with overall survival in a cohort of patients with non-small cell lung cancer (NSCLC). We also looked for the presence of SULF2 protein in plasma to evaluate its potential as an early detection biomarker for NSCLC.We identified patients who underwent surgical resection for pulmonary adenocarcinoma or squamous cell carcinoma at our institution. A section from each paraffin-embedded specimen was stained with a SULF2 antibody. A pathologist determined the percentage and intensity of tumor cell staining. Survival analysis was performed using a multivariate Cox proportional hazards model. Using a novel SULF2 ELISA assay, we analyzed plasma levels of SULF2 in a small cohort of healthy donors and patients with early stage NSCLC.SULF2 staining was present in 82% of the lung cancer samples. Squamous cell carcinomas had a higher mean percentage of staining than adenocarcinomas (100% vs. 60%; p<0.0005). After adjusting for age, sex, race, histologic type, stage, and neoadjuvant therapy, there was a non-significant (31%; p = 0.65) increase in the risk of death for patients with adenocarcinoma with SULF2 staining in tumor cells. In contrast, there was a significant decrease in the risk of death (89%; p = 0.02) for patients with squamous cell carcinoma with SULF2 staining in tumor cells. SULF2 protein was present in plasma of patients with early stage NSCLC, and soluble SULF2 levels increased with age. Finally, plasma SULF2 levels were significantly elevated in early stage NSCLC patients, compared to healthy controls.Tumor expression of SULF2 may affect prognosis in NSCLC, while blood SULF2 levels may have a significant role in the diagnosis of this fatal disease.

    View details for DOI 10.1371/journal.pone.0148911

    View details for Web of Science ID 000371219000032

    View details for PubMedID 26882224

  • Intraoperative Tracheal Injury THORACIC SURGERY CLINICS Lui, N., Wright, C. 2015; 25 (3): 249-?

    Abstract

    Intraoperative tracheal injury is a rare but potentially devastating complication. Transhiatal esophagectomy should be avoided in patients with proximal esophageal tumors who underwent neoadjuvant therapy, and percutaneous tracheostomy should be avoided in patients with short, thick necks. Early recognition leads to improved outcomes. Patients present with a sudden loss in airway pressure, air leaking into the operative field, or mediastinal and subcutaneous emphysema. Treatment starts with airway control. Primary buttressed repair is recommended, through either a left cervical incision for proximal injuries or a right thoracotomy for distal injuries. Nonoperative management has been used safely in select patients injured during intubation or tracheostomy.

    View details for DOI 10.1016/j.thorsurg.2015.04.008

    View details for Web of Science ID 000359891100004

    View details for PubMedID 26210921

  • Wnt7A is a putative prognostic and chemosensitivity marker in human malignant pleural mesothelioma. Oncology reports Hirata, T., Zheng, Q., Chen, Z., Kinoshita, H., Okamoto, J., Kratz, J., Li, H., Lui, N., Do, H., Cheng, T., Tseng, H. K., Koizumi, K., Shimizu, K., Zhou, H. M., Jablons, D., He, B. 2015; 33 (4): 2052?60

    Abstract

    Malignant pleural mesothelioma (MPM) is a highly aggressive tumor that has a poor prognosis, limited treatment options, and a worldwide incidence that is expected to increase in the next decade. We evaluated Wnt7A expression in 50 surgically resected tumor specimens using quantitative PCR. The expression values, were assessed by clinicopathological factors and K-M and Cox's regression with OS. The mean level of Wnt7A expression had a significant correlation with International Mesothelioma Interest Group (IMIG) stage (P<0.034), gender, smoking history and ethnicity, respectively (P=0.020, P=0.014, P=0.039). In the univariate analysis, low Wnt7A expression was a significant negative factor for overall survival (P=0.043, HR=2.30). However, multivariate Cox's regression revealed no significant factors for overall survival (low Wnt7A: P=0.051, HR=2.283; non-epithelioid subtype: P=0.050, HR=2.898). In patients with epithelioid tumors, those with low Wnt7A expression had significantly worse prognosis (P=0.019, HR=2.98). In patients with epithelioid tumors, females had significantly better prognosis than males (P=0.035). In patients who did not have neoadjuvant chemotherapy, prognosis was significantly more favorable for patients with high Wnt7A expression than for those with low Wnt7A expression (P=0.031). Among the patients with low Wnt7A-expressing tumors, those who received neoadjuvant chemotherapy had better prognosis than those who did not (P=0.024). The results of our study suggest that Wnt7A expression is a putative prognostic factor and a predictor of chemosensitivity.

    View details for DOI 10.3892/or.2015.3771

    View details for PubMedID 25632963

    View details for PubMedCentralID PMC4358089

  • Gli as a Novel Therapeutic Target in Malignant Pleural Mesothelioma PLOS ONE Li, H., Lui, N., Cheng, T., Tseng, H. K., Yue, D., Giroux-Leprieur, E., Do, H. T., Sheng, Q., Jin, J. Q., Luh, T. W., Jablons, D. M., He, B. 2013; 8 (3)

    Abstract

    Malignant pleural mesothelioma (MPM) is a highly aggressive tumor with poor prognosis. Current treatment is rarely curative, thus novel meaningful therapies are urgently needed. Inhibition of Hedgehog (Hh) signaling at the cell membrane level in several cancers has shown anti-cancer activity in recent clinical studies. Evidence of Hh-independent Gli activation suggests Gli as a more potent therapeutic target. The current study is aimed to evaluate the potential of Gli as a therapeutic target to treat MPM. The expression profiles of Gli factors and other Hh signaling components were characterized in 46 MPM patient tissue samples by RT-PCR and immunohistochemistry. Cultured cell lines were employed to investigate the requirement of Gli activation in tumor cell growth by inhibiting Gli through siRNA or a novel small molecule Gli inhibitor (Gli-I). A xenograft model was used to evaluate Gli-I in vivo. In addition, a side by side comparison between Gli and Smoothened (Smo) inhibition was conducted in vitro using siRNA and small molecule inhibitors. Our study reported aberrant Gli1 and Gli2 activation in a large majority of tissues. Inhibition of Gli by siRNAs or Gli-I suppressed cell growth dramatically both in vitro and in vivo. Inhibition of Gli exhibited better cytotoxicity than that of Smo by siRNA and small molecule inhibitors vismodegib and cyclopamine. Combination of Gli-I and pemetrexed, as well as Gli-I and vismodegib demonstrated synergistic effects in suppression of MPM proliferation in vitro. In summary, Gli activation plays a critical role in MPM. Inhibition of Gli function holds strong potential to become a novel, clinically effective approach to treat MPM.

    View details for DOI 10.1371/journal.pone.0057346

    View details for Web of Science ID 000316936100019

    View details for PubMedID 23483902

    View details for PubMedCentralID PMC3590216

  • SMO expression level correlates with overall survival in patients with malignant pleural mesothelioma. Journal of experimental & clinical cancer research : CR Zhang, Y., He, J., Zhang, F., Li, H., Yue, D., Wang, C., Jablons, D. M., He, B., Lui, N. 2013; 32: 7

    Abstract

    Malignant mesothelioma is an aggressive, treatment-resistant tumor arising from mesothelium of pleura, peritoneum and pericardium. Despite current combined regimen, its prognosis remains dismal, calling for more effective targeted therapies. We investigated whether aberrant Hh activation may play a role in mesothelioma.SMO and SHH expression levels were analyzed in 46 mesothelioma tissue specimens with real-time RT-PCR, and correlation with survival was analyzed with univariate and multivariate Cox proportional hazards models, Kaplan-Meier survival curves, and the log-rank test. We also examined multiple mesothelioma cell lines for SMO expression and the effect of Hh inhibition by a specific SMO antagonist on cell proliferation by MTS assay.We observed strong correlation between higher SMO and SHH expression levels with poorer overall survival. Remarkably, Hh inhibition by a specific SMO inhibitor significantly suppressed cell proliferation in the mesothelioma cell lines examined.Our data strongly support that Hh signaling deregulation plays critical roles in proliferation of mesothelioma, and consistently exerts significant impact on prognosis of the disease. Therefore our findings revealed the hitherto unappreciated role of Hh activation in mesothelioma, and pinpointed Hh signaling antagonist as a potential new therapy against this devastating disease.

    View details for DOI 10.1186/1756-9966-32-7

    View details for PubMedID 23379358

    View details for PubMedCentralID PMC3622612

  • SULF2 expression by immunohistochemistry and overall survival in oesophageal cancer: a cohort study BMJ OPEN Lui, N. S., van Zante, A., Rosen, S. D., Jablons, D. M., Lemjabbar-Alaoui, H. 2012; 2 (6)

    Abstract

    Oesophageal cancer is the eighth most commonly diagnosed cancer worldwide, and there is a need for biomarkers to improve diagnosis, prognosis and treatment. Sulfatases 2 (SULF2) is an extracellular endosulphatase that regulates several signalling pathways in carcinogenesis and has been associated with poor prognosis. This study evaluates the relationship between SULF2 expression by immunohistochemistry and overall survival in patients with oesophageal cancer.Cohort study.Single tertiary care centre.We included patients who underwent esophagectomy for invasive oesophageal adenocarcinoma and squamous cell carcinoma at a tertiary care centre from 1997 to 2006. We excluded patients with recurrent oesophageal cancer or less than 3 mm invasive tumour on H&E stained slide. A section from each paraffin-embedded tissue specimen was stained with an anti-SULF2 monoclonal antibody.A pathologist blinded to overall survival determined the percentage and intensity of tumour cells staining. Vital status was obtained through the Social Security Death Master File, and overall survival was calculated from the date of surgery.One-hundred patients with invasive oesophageal cancer were identified, including 75 patients with adenocarcinoma and 25 patients with squamous cell carcinoma. The squamous cell carcinoma samples had a higher mean percentage and intensity of tumour cells staining compared with the adenocarcinoma samples. After adjusting for age, sex, race, histological type, stage and neoadjuvant therapy, for every 10% increase in percentage of tumour cells staining for SULF2, the HR for death increased by 13% (95% CI 1.01 to 1.25; p=0.03).The majority of adenocarcinoma samples and all of the squamous cell carcinoma samples had SULF2 staining. The percentage of tumour cells staining for SULF2 was significantly associated with overall survival. Thus, SULF2 is a potential biomarker in oesophageal cancer and may have an important role in the management of patients with this disease.

    View details for DOI 10.1136/bmjopen-2012-001624

    View details for Web of Science ID 000315081400071

    View details for PubMedID 23180455

  • A somatic TSHR mutation in a patient with lung adenocarcinoma with bronchioloalveolar carcinoma, coronary artery disease and severe chronic obstructive pulmonary disease. Oncology reports Kim, J. W., Lee, S., Lui, N., Choi, H., Mulvihill, M., Fang, L. T., Kang, H. C., Kwon, Y. W., Jablons, D., Kim, I. J. 2012; 28 (4): 1225?30

    Abstract

    In a screen for thoracic malignancy-associated markers, thyroid stimulating hormone receptor (TSHR) was identified as a candidate as it binds to the previously-characterized lung cancer marker NKX2-1. We screened for mutations in all coding regions of the TSHR gene in 96 lung adenocarcinoma samples and their matched adjacent normal lung samples. We found one patient with a somatic mutation at codon 458 (exon 10), which is located at the transmembrane domain where most TSHR mutations have been found in thyroid-related diseases. This patient had lung adenocarcinoma with BAC (bronchioloalveolar carcinoma) features in the setting of a prior medical history significant for carotid stenosis and severe chronic obstructive pulmonary disease (COPD). In order to characterize the genetic features of TSHR in lung cancer, we checked for TSHR expression and copy number in the 96 lung cancer tissues. TSHR protein expression was generally overexpressed in multiple thoracic malignancies (adenocarcinoma, squamous cell carcinoma and malignant pleural mesothelioma) by immunohistochemistry. Our data suggest that aberrant TSHR function may contribute to lung cancer development or a subgroup of lung cancer with specific clinical phenotypes.

    View details for DOI 10.3892/or.2012.1938

    View details for PubMedID 22842620

Footer Links:

Stanford Medicine Resources: