Natalie Shaubie Lui

All Publications

• JAK inhibition with tofacitinib rapidly increases contractile force in human skeletal muscle. Life science alliance Shrager, J. B., Randle, R., Lee, M., Ahmed, S. S., Trope, W., Lui, N., Poultsides, G., Liou, D., Visser, B., Norton, J. A., Nesbit, S. M., He, H., Kapula, N., Wallen, B., Fatodu, E., Sadeghi, C. A., Konsker, H. B., Elliott, I., Guenthart, B., Backhus, L., Cooke, R., Berry, M., Tang, H. 2024; 7 (11)

  Abstract

  Reduction in muscle contractile force associated with many clinical conditions incurs serious morbidity and increased mortality. Here, we report the first evidence that JAK inhibition impacts contractile force in normal human muscle. Muscle biopsies were taken from patients who were randomized to receive tofacitinib (n = 16) or placebo (n = 17) for 48 h. Single-fiber contractile force and molecular studies were carried out. The contractile force of individual diaphragm myofibers pooled from the tofacitinib group (n = 248 fibers) was significantly higher than those from the placebo group (n = 238 fibers), with a 15.7% greater mean maximum specific force (P = 0.0016). Tofacitinib treatment similarly increased fiber force in the serratus anterior muscle. The increased force was associated with reduced muscle protein oxidation and FoxO-ubiquitination-proteasome signaling, and increased levels of smooth muscle MYLK. Inhibition of MYLK attenuated the tofacitinib-dependent increase in fiber force. These data demonstrate that tofacitinib increases the contractile force of skeletal muscle and offers several underlying mechanisms. Inhibition of the JAK-STAT pathway is thus a potential new therapy for the muscle dysfunction that occurs in many clinical conditions.

  View details for DOI 10.26508/lsa.202402885

  View details for PubMedID 39122555

  View details for PubMedCentralID PMC11316201

• The Role of Primary Care Providers in Lung Cancer Screening: A Cross-Sectional Survey. Clinical lung cancer Wong, L. Y., Kapula, N., Kang, A., Phadke, A. J., Schechtman, A. D., Elliott, I. A., Guenthart, B. A., Liou, D. Z., Backhus, L. M., Berry, M. F., Shrager, J. B., Lui, N. S. 2024

  Abstract

  Multidisciplinary lung cancer screening (LCS) programs that perform shared decision-making visits (SDMV) and follow up annual low dose computed tomography (LDCT) have been emerging. We hypothesize that primary care providers (PCPs) prefer to refer patients to LCS programs instead of facilitating the screening process themselves.This is a mixed-methods, cross-sectional study in which an online survey was administered to PCPs between April 2023 and June 2023.58 PCPs in the same hospital network participated in the study with a median age of 43 (34-51), predominance of women (77.6%), and clinicians of white and Asian race (44.8% and 48.3%). Respondents estimated that 26.1% (SD 32.4%) of their eligible patients participate in LCS screening. PCPs thought that an LCS program was equally convenient to performing screening themselves for identifying eligible patients and ordering LDCT. However, 63.8% of participants preferred an LCS program for performing SDMVs, 62.1% for ensuring annual follow-up on negative LDCTs, 70.7% for deciding next steps on positive LDCTs, and 60.4% for performing smoking cessation counseling. PCPs agreed that an LCS program saves time (69%), allows patients to receive specialty care (65.6%), addresses patient concerns (70.7%), ensures annual follow-up (77.6%), and manages abnormal findings (79.3%). However, they also expressed concerns about an additional visit for the patient (48.2%) and patient cost (46.5%).Most PCPs believe that formal LCS programs have many benefits including providing specialized care and follow up, although there were concerns about patient time and cost.

  View details for DOI 10.1016/j.cllc.2024.10.002

  View details for PubMedID 39472235

• Comparative effectiveness of perioperative physical activity in older adults with lung cancer and their family caregivers: design of a multicenter pragmatic randomized trial. BMC cancer Sun, V., Guthrie, K. A., Arnold, K. B., Antonoff, M., Erhunmwunsee, L., Borondy-Kitts, A., Johnson, J., Jones, L., Ramirez, M., Tong, B. C., Moremen, J. R., Yang, C. J., Ng, T., Kim, S. S., Brown, L. M., Blasberg, J. D., Lui, N. S., Kneuertz, P. J., Toloza, E. M., Kim, J. Y., Raz, D. J. 2024; 24 (1): 976

  Abstract

  With a median age at diagnosis of 70, lung cancer remains a significant public health challenge for older Americans. Surgery is a key component in treating most patients with non-metastatic lung cancer. These patients experience postoperative pain, fatigue, loss of respiratory capacity, and decreased physical function. Data on quality of life (QOL) in older adults undergoing lung cancer surgery is limited, and few interventions are designed to target the needs of older adults and their family caregivers (FCGs). The primary aim of this comparative effectiveness trial is to determine whether telephone-based physical activity coaching before and after surgery will be more beneficial than physical activity self-monitoring alone for older adults and their FCGs.In this multicenter comparative effectiveness trial, 382 older adults (≥ 65 years) with lung cancer and their FCGs will be recruited before surgery and randomized to either telephone-based physical activity coaching or physical activity self-monitoring alone. Participants allocated to the telephone-based coaching comparator will receive five telephone sessions with coaches (1 pre and 4 post surgery), an intervention resource manual, and a wristband pedometer. Participants in the self-monitoring only arm will receive American Society of Clinical Oncology (ASCO) physical activity information and wristband pedometers. All participants will be assessed at before surgery (baseline), at discharge, and at days 30, 60, and 180 post-discharge. The primary endpoint is the 6-minute walk test (6MWT) at 30 days post-discharge. Geriatric assessment, lower extremity function, self-reported physical function, self-efficacy, and QOL will also be assessed.The trial will determine whether this telephone-based physical activity coaching approach can enhance postoperative functional capacity and QOL outcomes for older adults with lung cancer and their FCGs. Trial results will provide critical findings to inform models of postoperative care for older adults with cancer and their FCGs.ClinicalTrials.gov Identifier: NCT06196008.

  View details for DOI 10.1186/s12885-024-12660-5

  View details for PubMedID 39118035

  View details for PubMedCentralID 6465423

• Greater ipsilateral rectus muscle atrophy after robotic thoracic surgery compared with open and video-assisted thoracoscopic surgery approaches. JTCVS open Wang, Y., Randle, R. J., Bhandari, P., He, H., Trope, W. L., Guenthart, B. A., Guo, H. H., Liou, D. Z., Backhus, L. M., Berry, M. F., Shrager, J. B., Lui, N. S. 2024; 20: 202-209

  Abstract

  Robotic thoracic surgery provides another minimally invasive approach in addition to video-assisted thoracoscopic surgery (VATS) that yields less pain and faster recovery compared with open surgery. However, robotic incisions are generally placed more inferiorly, which may increase the risk of intercostal nerve injury that affects the abdominal wall. We hypothesized that a robotic approach causes greater ipsilateral rectus muscle atrophy compared with open and VATS approaches.The cross-sectional area and density of bilateral rectus abdominis muscles were measured on computed tomography scans in patients who underwent lobectomy in 2018. The differences between the contralateral and ipsilateral muscles were compared between preoperative and 6-month surveillance scans. Changes were compared among the open, VATS, and robotic approaches through a mixed effects model after adjustments of correlation and covariates.Of 99 lobectomies, 25 (25.3%) were open, 56 (56.6%) VATS, and 18 (18.1%) robotic. The difference between the contralateral and ipsilateral rectus muscle cross-sectional area was significantly larger at 6 months after robotic surgery compared with open (31.4% vs 9.5%, P = .049) and VATS (31.4% vs 14.1%, P = .021). There were no significant differences in the cross-sectional area between the open and VATS approach.In this retrospective analysis, there was greater ipsilateral rectus muscle atrophy associated with robotic thoracic surgery compared with open or VATS approaches. These findings should be correlated with clinical symptoms and followed to assess for resolution or persistence.

  View details for DOI 10.1016/j.xjon.2024.05.011

  View details for PubMedID 39296450

  View details for PubMedCentralID PMC11405974

• Robotic Surgery in Thoracic Training Programs: A National Needs Assessment. The Annals of thoracic surgery Kim, S. S., Mitzman, B., Lui, N. S., Rochefort, M., D'Souza, D., Sancheti, M., Manerikar, A., Logan, C., Yang, S. 2024

  Abstract

  The cardiothoracic surgical trainees perceive a need for more instruction and exposure to robotic-assisted thoracoscopic surgery (RATS) during their training. We sought to assess utilization and trainee exposure to robotic surgery in thoracic residency programs to identify areas for improvement.A voluntary electronic survey of 10 questions was distributed to surgeons working in all thoracic surgery residency programs in the United States. The survey asked to provide the size of the residency, the availability and utilization of robots, and the trainee's adoption of robotic surgery in their practice after graduation. Multivariable logistic regression was performed with Stata MP version 17.0 (College Station, TX).Of a total of 76 cardiothoracic surgery training programs, surgeons from 69 training programs completed the survey (90.8%). The majority of pulmonary lobectomy was performed using robotic surgery (55%). About half of the training programs (35/69) have a formal robotic curriculum for the residents. Of 121 thoracic-track trainees, 118 trainees (97.5%) performed robotic surgery as part of their practice, while 62 of 110 (56.4%) cardiothoracic (CT) track and 16 of 158 (10.1%) cardiac-track trainees performed robotic surgery. In a multivariate analysis, the adoption of robotic surgery was associated with having an established robotic training curriculum (OR 5.82, 95% CI 1.32 - 35.7), and a larger training program (OR 3.78, 95% CI 1.34 - 10.6).A disparity exists in robotic surgical training among the training programs. A standardized curriculum and formal case requirements may be needed to ensure optimal preparation for future graduates.

  View details for DOI 10.1016/j.athoracsur.2024.07.016

  View details for PubMedID 39067629

• Clinical impact of EGFR and KRAS mutations in surgically treated unifocal and multifocal lung adenocarcinoma. Translational lung cancer research Jiang, J., Berry, M. F., Lui, N. S., Liou, D. Z., Trope, W. L., Backhus, L. M., Shrager, J. B. 2024; 13 (6): 1222-1231

  Abstract

  Epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma (KRAS) are the two most common oncogenic drivers in lung adenocarcinoma, and their roles still need further exploration. Here we aimed to compare the clinical impact of EGFR and KRAS mutations on disease progression in resected unifocal and multifocal lung adenocarcinoma.Clinicopathologic and genomic data were collected for patients who underwent resection of lung adenocarcinoma from 2008 to 2022 at Stanford University Hospital. Retrospective review was performed in 241 patients whose tumors harbored EGFR (n=150, 62.2%) or KRAS (n=91, 37.8%) mutations. Clinical outcome was analyzed with special attention to the natural history of secondary nodules in multifocal cases wherein the dominant tumor had been resected.We confirm that compared with EGFR mutations, patients with KRAS mutations had more smokers, larger tumor size, higher TNM stage, higher positron emission tomography (PET)/computed tomography (CT) standard uptake value max, higher tumor mutation burden, and worse disease-free survival and overall survival on univariate analysis. For patients with multifocal pulmonary nodules, the median follow-up of unresected secondary nodules was 55 months. Secondary nodule progression-free survival (SNPFS) was significantly worse for patients with KRAS mutations than those with EGFR mutations (mean 40.3±6.6 vs. 67.7±6.5 months, P=0.004). Univariate analysis showed tumor size, tumor morphology, pathologic TNM stage, and KRAS mutations were significantly associated with SNPFS, while multivariate analysis showed only KRAS mutations were independently associated with worse SNPFS (hazard ratio 1.752, 95% confidence interval: 1.017-3.018, P=0.043).Resected lung adenocarcinomas with KRAS mutations have more aggressive clinicopathological features and confer worse prognosis than those with EGFR mutations. Secondary pulmonary nodules in multifocal cases with dominant KRAS-mutant tumors have more rapid progression of the secondary nodules.

  View details for DOI 10.21037/tlcr-24-165

  View details for PubMedID 38973951

  View details for PubMedCentralID PMC11225054

• Impacts of Positive Margins and Surgical Extent on Outcomes after Early-Stage Lung Cancer Resection. The Annals of thoracic surgery Wong, L. Y., Dale, R., Kapula, N., Elliott, I. A., Liou, D. Z., Backhus, L. M., Lui, N. S., Shrager, J. B., Berry, M. F. 2024

  Abstract

  Sublobar resection of early-stage non-small cell lung cancer (NSCLC) is increasingly considered appropriate but may compromise margins compared to lobectomy. This study evaluated resection extent, margin status, and survival for clinical stage I NSCLC patients.Clinical T1-2N0M0 NSCLC patients in the National Cancer Database (2006-2020) treated with primary surgery were compared stratified by margin status. The potential benefit of radiation was explored in subgroup analysis of sublobar resection patients with positive margins.Positive margins occurred in 5,089 (2.8%) of 181,824 patients and were more common in sublobar resections compared to lobectomy (4.3% vs 2.4%,p<0.001). Sublobar resection had the strongest association with positive margins in multivariable analysis (OR 2.06 [95% CI 1.91-2.23],p<0.001). Patients with positive margins were more likely to undergo both adjuvant chemotherapy (16% vs 13%,p<0.001) and radiation (17% vs 1%,p<0.001) but had worse survival in univariate (44.0% 5-year OS vs 69.2%,p<0.001) and multivariable Cox analysis (HR 1.71 [95% CI 1.63-1.78, p<0.001) in the entire cohort, as well as in univariate subset analysis of lobectomy (46.9% vs 70.4%, p<0.001) and sublobar (37.5% vs 64.1%,p<0.001). Postoperative radiation for sublobar patients with positive margins did not improve 5-year OS (36.3% for irradiated patients vs 38.3% for non-irradiated patients,p=0.57), and positive margin sublobar patients treated with radiation had inferior survival to negative margin lobectomy patients.Positive margins occur more frequently after sublobar resection of clinical stage I NSCLC compared to lobectomy. Patients with positive margins have worse survival than complete resection patients and are not rescued by post-operative radiation.

  View details for DOI 10.1016/j.athoracsur.2024.05.032

  View details for PubMedID 38866199

• Harnessing Opportunity: Pilot Intervention to Improve Lung Cancer Screening for Women Undergoing Breast Screening Mammography. JTO clinical and research reports Wong, L., Yue, T., Aghagoli, G., Baiu, I., Shula, L., Lee, A., Lui, N. S., Backhus, L. M. 2024; 5 (6): 100671

  Abstract

  Introduction: The screening mammogram could be a "teachable moment" to improve lung cancer screening (LCS) uptake. The aim of our project was to combine patient self-referral with eligibility identification by providers as a two-pronged approach to increase rates of LCS among eligible women.Methods: LCS education materials were created to stimulate patient education and encourage self-referral. Chart review of patients scheduled for screening mammography was performed to identify patients who met LCS criteria. The primary outcome was rate of acceptance of targeted interventions as measured by qualitative survey material and rate of LCS uptake.Results: Between August 2022 and August 2023, 116 patients were identified by providers for potential eligibility for LCS and 34 patients (29.3%) deemed eligible based on the U.S. Preventative Services Task Force 2021 guidelines. There were 19 patients (56%) who completed LCS with three patients (16%) with screen-detected nodules that led to further workup. Post-implementation qualitative survey results reveal that 100% of the participants rated their shared decision-making visit experience as "very helpful" and 67% responded "very likely" to seek simultaneous breast and LCS in the future. Informational materials were rated as 80% favorable among all respondents; however, the rate of self-referral alone was 0%. The combined rates of eligible patients lost to follow-up or refusal was 24%.Conclusion: The self-referral aspect of the intervention revealed that patients are unlikely to self-refer for LCS. Nevertheless, patients undergoing screening mammograms individually identified for LCS were very responsive to learning more about dual screening.

  View details for DOI 10.1016/j.jtocrr.2024.100671

  View details for PubMedID 38799132

• ASO Visual Abstract: Complications of Outpatient Chest Tube Management for Prolonged Air Leaks After Pulmonary Surgery. Annals of surgical oncology Randle, R. J., Bhandari, P., He, H., Berry, M. F., Backhus, L. M., Lui, N. S., Liou, D. Z., Shrager, J. B. 2024

  View details for DOI 10.1245/s10434-024-15405-7

  View details for PubMedID 38743281

• What is an Adequate Margin During Sublobar Resection of ≤3cm N0 Subsolid Lung Adenocarcinomas? The Annals of thoracic surgery Kamtam, D. N., Berry, M. F., Lui, N. S., Satoyoshi, M., Elliott, I. A., Liou, D. Z., Guenthart, B., Backhus, L. M., Shrager, J. B. 2024

  Abstract

  Sublobar resection offers non-inferior survival vs. lobectomy for ≤2cm NSCLC and is commonly employed for subsolid tumors. While data exists for solid tumors, the minimum adequate margin of resection for subsolid adenocarcinomas remains unclear.Retrospective review of 1101 adenocarcinoma resections at our institution, 2006-2022.tumors≤3cm with ≥10% radiographic ground glass, excised by sublobar resection.positive nodes, positive or unreported margin. The primary outcome was rate of local recurrence(LR) at multiple thresholds of margin distance. Relationship between margin distance and solid-component size was also explored.194 patients met inclusion criteria. Median(IQR) tumor diameter and margin distance were 12(9-17)mm and 10(5-17)mm, respectively. Median follow-up was 42.5 months. There was a progressive increase in LR with diminishing margin (0.1cm decrements) from 1.5cm to 0.5cm. The difference in the rate of LR between "over"(n=143) and "under"(n=51) was most significant at 0.5cm [8/51(15.7%) vs. 6/143(4.2%),p=0.01] but did not reach α adjusted for multiple comparisons. On Cox regression for LR-free survival (LRFS), margin ≤0.5cm(p=0.19) and %solid component (p=0.14) trended to significance. Combining these using margin-distance-to-solid-component-size ratio, a ratio≤1 did show a significantly higher rate of local recurrence [7(14.3%) vs. 2(2.0%),p=0.009]. Treatment of local recurrences provided at least intermediate-term survival in 87% of recurrences (median post-recurrence follow-up 44 months).During sublobar resection of subsolid lung adenocarcinomas, margin-to-solid-component-size ratio>1.0 appears to be a more reliable factor than margin distance alone to minimize local recurrence. Local recurrence, however, may not impact survival in patients with subsolid adenocarcinomas if timely treatment is administered.

  View details for DOI 10.1016/j.athoracsur.2024.04.018

  View details for PubMedID 38734402

• Management of Paraesophageal Hernias. Thoracic surgery clinics Randle, R. J., Liou, D. Z., Lui, N. S. 2024; 34 (2): 163-170

  Abstract

  Paraesophageal hernias are classified according to the altered anatomic relationships between the gastroesophageal junction or stomach and the diaphragmatic hiatus. Herniation of these structures into the mediastinum may produce common complaints such as reflux, chest pain, and dysphagia. The elective repair of these hernias is well tolerated and significantly improves quality of life among patients with symptomatic disease. The hallmarks of a quality repair include the circumferential mobilization of the esophagus to generate 3cm of tension-free intra-abdominal length and the performance of a fundoplication.

  View details for DOI 10.1016/j.thorsurg.2024.01.005

  View details for PubMedID 38705664

• Barriers to Completing Low Dose Computed Tomography Scan for Lung Cancer Screening. Clinical lung cancer Wong, L. Y., Choudhary, S., Kapula, N., Lin, M., Elliott, I. A., Guenthart, B. A., Liou, D. Z., Backhus, L. M., Berry, M. F., Shrager, J. B., Lui, N. S. 2024

  Abstract

  Annual low-dose computed tomography (LDCT) screening has been shown to reduce lung cancer mortality in high-risk individuals by detecting the disease at an earlier stage. This study aims to assess the barriers to completing LDCT in a cohort of patients who were determined eligible for lung cancer screening (LCS).We performed a single institution, mixed methods, cross-sectional study of patients who had a LDCT ordered from July to December 2022. We then completed phone surveys with patients who did not complete LDCT to assess knowledge, attitude, and perceptions toward LCS.We identified 380 patients who met inclusion criteria, including 331 (87%) who completed LDCT and 49 (13%) who did not. Patients who completed a LDCT and those who did not were similar regarding age, sex, race, primary language, household income, body mass index, median pack years, and quit time. Positive predictors of LDCT completion were: meeting USPSTF guidelines (97.9% vs 81.6%), being married (58.3% vs 44.9%), former versus current smokers (55% vs 41.7%), personal history of emphysema (60.4% vs 42.9%), and family history of lung cancer (13.9% vs 4.1%) (all P < .05). Of the patients who participated in the phone survey, only 7% of respondents thought they were high risk for developing lung cancer despite attending a shared decision-making visit and only 10% wanted to re-schedule their LDCT.There exist barriers to completing LDCT even after patients are identified as eligible and complete a shared decision-making visit secondary to knowledge barriers, misperceptions, and patient disinterest.

  View details for DOI 10.1016/j.cllc.2024.04.014

  View details for PubMedID 38749902

• Complications of Outpatient Chest Tube Management for Prolonged Air Leaks After Pulmonary Surgery. Annals of surgical oncology Randle, R. J., Bhandari, P., He, H., Berry, M. F., Backhus, L. M., Lui, N. S., Liou, D. Z., Shrager, J. B. 2024

  Abstract

  Air leaks are common after pulmonary surgery. Prolonged air leaks (PALs) may persist through discharge and often are managed with one-way valve devices (OWD). We sought to determine the course and complications of patients discharged with OWDs, risk factors for complications, and to evaluate the utility of clamp trials before chest tube (CT) removal.Single-institution, retrospective review of patients discharged with a OWD after pulmonary surgery between 2008 and 2022. Charts were examined for the presence of complications and CT duration. Differences in CT duration were compared by using the Wilcoxon rank-sum test.Sixty-four of 1917 (3.3%) pulmonary surgeries resulted in OWD use. Twelve of 64 (19%) patients discharged with a OWD suffered a complication. Nine of 64 (14%) had a CT-related readmission, and seven of 64 (11%) required PAL intervention. Patients sustaining a complication demonstrated longer CT durations before complication compared with duration in patients without complications, with median days of 13 [IQR 6-21] vs. 7 [IQR 6-12], p = 0.04). Five (7.8%) OWD patients developed an empyema; only one (20%) occurred before a CT duration of 14 days. Sixteen of 64 (25%) patients underwent a clamp trial before CT removal. One of ten (10%) failed even with no air leak present, whereas one of six (17%) failed with a present/questionable air leak.One-way valve device use has a substantial complication rate, and chest tube duration is a risk factor. In-hospital interventions might benefit patients with larger leaks that likely require prolonged OWD use. Because clamp trials occasionally fail, we contend that a clamp trial is the safest course before CT removal.

  View details for DOI 10.1245/s10434-024-15219-7

  View details for PubMedID 38536584

  View details for PubMedCentralID 6026238

• Lepidic-Type Lung Adenocarcinomas: Is It Safe to Observe for Growth Prior to Treating? The Annals of thoracic surgery Wong, L. Y., Elliott, I. A., Liou, D. Z., Backhus, L. M., Lui, N. S., Shrager, J. B., Berry, M. F. 2024

  Abstract

  Lepidic-type adenocarcinomas (LPA) can be multi-focal, and treatment is often deferred until there is observed growth. This study investigated the potential downside of that strategy by evaluating the relationship of nodal involvement with tumor size and survival.The impact of tumor size on lymph node involvement and survival was evaluated for National Cancer Database patients who received surgery without induction therapy as primary treatment for cT1-3N0M0 histologically confirmed LPA from 2006-2019 using logistic regression, Kaplan-Meier, and Cox analyses.Positive nodes occurred in 442 (5.3%) of 8,286 patients. The incidence of having positive nodes approximately doubled with each 1cm increment increase in size. Patients with positive nodes were more likely to have larger tumors (27mm vs 20mm,p<0.001) and clinical T2+ disease (40.7% vs 26.8%,p<0.001) compared to node-negative patients, but tumor size was the only significant independent predictor of having positive nodal disease in logistic regression analysis; this association grew stronger with each incremental centimeter increase in size. Patients with positive nodes were more likely to undergo adjuvant radiation (23.5% vs 1.1%,p<0.001) and chemotherapy (72.9% vs 7.9%,p<0.001), and expectedly had worse survival compared to the node negative group in univariate (5-year overall survival 50.9% vs 81.1%,p<0.001) and multivariable (Hazard ratio 2.56 [95% CI 2.14-3.05],p<0.001) analyses.Nodal involvement is relatively uncommon in early-stage LPAs but steadily increases with tumor size and is associated with dramatically worse survival. This data can be used to inform treatment decisions when evaluating LPA patients.

  View details for DOI 10.1016/j.athoracsur.2024.03.003

  View details for PubMedID 38490310

• The Impact of Immunotherapy Use in Stage IIIA (T1-2N2) NSCLC: A Nationwide Analysis. JTO clinical and research reports Wong, L. Y., Liou, D. Z., Roy, M., Elliott, I. A., Backhus, L. M., Lui, N. S., Shrager, J. B., Berry, M. F. 2024; 5 (3): 100654

  Abstract

  Multiple clinical trials have revealed the benefit of immunotherapy (IO) for NSCLC, including unresectable stage III disease. Our aim was to investigate the impact of IO use on treatment and outcomes of potentially resectable stage IIIA NSCLC in a broader nationwide patient cohort.We queried the National Cancer Database (2004-2019) for patients with stage IIIA (T1-2N2) NSCLC. Treatment and survival were evaluated with descriptive statistics, logistic regression, Kaplan-Meier analysis, and Cox proportional hazards modeling.Overall, 5.5% (3777 of 68,335) of patients received IO. IO use was uncommon until 2017, but by 2019, it was given to 40.1% (1544 of 2308) of stage IIIA patients. The increased use of IO after 2017 was associated with increased definitive chemoradiation treatment (54.2% [6800 of 12,535] from years 2017 to 2019 versus 46.9% [26,251 of 55,914] from 2004 to 2016, p < 0.001) and less use of surgery (18.1% [2266 of 12,535] from years 2017 to 2019 versus 22.0% [12,300 of 55,914] from 2004 to 2016, p < 0.001). IO treatment was associated with significantly better 5-year survival in the entire cohort (36.9% versus 23.4%, p < 0.001) and the subsets of patients treated with chemoradiation (37.2% versus 22.7%, p < 0.001) and surgery (48.6% versus 44.3%, p < 0.001). Pneumonectomy use decreased with increased IO treatment (5.1% of surgical patients [116 of 2266] from years 2017 to 2019 versus 9.2% [1127 of 12,300] from 2004 to 2016, p < 0.001).Increased use of IO was associated with a change in treatment patterns and improved survival for patients with stage IIIA(N2) NSCLC.

  View details for DOI 10.1016/j.jtocrr.2024.100654

  View details for PubMedID 38496376

  View details for PubMedCentralID PMC10941003

• VENTILATOR WAVEFORM ANALYSIS: THE SQUARE ROOT SIGN IN A PATIENT WITH A TRACHEAL-PLEURAL FISTULA Rozenbaum, D., Wingo, M., Patel, P., Nassar, A., Bedi, H., Lui, N. LIPPINCOTT WILLIAMS & WILKINS. 2024

  View details for Web of Science ID 001131541101594

• Impact of guideline therapy on survival of patients with stage I-III epithelioid mesothelioma. Journal of thoracic disease Liou, D. Z., Wang, Y., Bhandari, P., Shrager, J. B., Lui, N. S., Backhus, L. M., Berry, M. F. 2023; 15 (12): 6661-6673

  Abstract

  Modern treatment guidelines recommend multimodal therapy with at least chemotherapy and surgery for patients with potentially resectable epithelioid mesothelioma. This study evaluated guideline compliance for patients with stage I-III epithelioid mesothelioma and tested the hypothesis that guideline-concordant therapy improved survival.The National Cancer Database was queried for patients with stage I-III epithelioid malignant pleural mesothelioma between 2004 and 2016. The impact of therapy was evaluated using logistic regression, Kaplan-Meier analysis, Cox-proportional hazards analysis, and propensity-scoring methods.During the study period, guideline-concordant therapy was used in 677 patients (19.1%), and 2,857 patients (80.8%) did not have guideline-concordant therapy. Younger age, being insured, living in a census tract with a higher income, clinical stage, and being treated at an academic or research program were all predictors of receiving guideline-concordant therapy in multivariable analysis. Guideline-concordant therapy yielded improved median survival [24.7 (22.4-26.1) vs. 13.7 (13.2-14.4) months] and 5-year survival [17.7% (14.7-21.3%) vs. 8.0% (7.0-9.3%)] (P<0.001), and continued to be associated with better survival in both multivariable analysis and propensity-matched analysis. In the patients who received guideline therapy, median survival [24.9 (21.9-27.2) vs. 24.5 (21.7-28.1) months] and 5-year survival [14.9% (10.9-20.2%) vs. 20.1% (16.0-25.4%)] was not significantly different between patients who underwent induction (n=304) versus adjuvant (n=373) chemotherapy (P=0.444).Guideline-concordant therapy for potentially resectable epithelioid mesothelioma is associated with significantly improved survival but used in a minority of patients. The timing of chemotherapy with surgery in this study did not have a significant impact on overall survival.

  View details for DOI 10.21037/jtd-23-1334

  View details for PubMedID 38249900

  View details for PubMedCentralID PMC10797401

• Risk of developing subsequent primary lung cancer after receiving radiation for breast cancer. JTCVS open Wong, L., Kapula, N., He, H., Guenthart, B. A., Vitzthum, L. K., Horst, K., Liou, D. Z., Backhus, L. M., Lui, N. S., Berry, M. F., Shrager, J. B., Elliott, I. A. 2023; 16: 919-928

  Abstract

  Background: Radiotherapy (RT) is integral to breast cancer treatment, especially in the current era that emphasizes breast conservation. The aim of our study was to determine the incidence of subsequent primary lung cancer after RT exposure for breast cancer over a time span of 3decades to quantify this risk over time as modern oncologic treatment continues to evolve.Methods: The SEER (Surveillance, Epidemiology, and End Results) database was queried from 1988 to 2014 for patients diagnosed with nonmetastatic breast cancer. Patients who subsequently developed primary lung cancer were identified. Multivariable regression modeling was performed to identify independent factors associated with the development of lung cancer stratified by follow up intervals of 5 to 9years, 10 to 15years, and >15years after breast cancer diagnosis.Results: Of the 612,746 patients who met our inclusion criteria, 319,014 (52%) were irradiated. primary lung cancer developed in 5556 patients (1.74%) in the RT group versus 4935 patients (1.68%) in the non-RT group. In a multivariable model stratified by follow-up duration, the overall HR of developing subsequent ipsilateral lung cancer in the RT group was 1.14 (P=.036) after 5 to 9years of follow-up, 1.28 (P=.002) after 10 to 15years of follow-up, and 1.30 (P=.014) after >15years of follow-up. The HR of contralateral lung cancer was not increased at any time interval.Conclusions: The increased risk of developing a primary lung cancer secondary to RT exposure for breast cancer is much lower than previously published. Modern RT techniques may have contributed to the improved risk profile, and this updated study is important for counseling and surveillance of breast cancer patients.

  View details for DOI 10.1016/j.xjon.2023.10.031

  View details for PubMedID 38204675

• Comparison of failure to rescue in younger versus elderly patients following lung cancer resection. JTCVS open Wang, Y., Kapula, N., Yang, C. J., Manapat, P., Elliott, I. A., Guenthart, B. A., Lui, N. S., Backhus, L. M., Berry, M. F., Shrager, J. B., Liou, D. Z. 2023; 16: 855-872

  Abstract

  Objective: Failure to rescue (FTR), defined as in-hospital death following a major complication, has been increasingly studied in patients who undergo cardiothoracic surgery. This study tested the hypothesis that elderly patients undergoing lung cancer resection have greater rates of FTR compared with younger patients.Methods: Patients who underwent surgery for primary lung cancer between 2011 and 2020 and had at least 1 major postoperative complication were identified using the National Surgical Quality Improvement Program database. Patients who died following complications (FTR) were compared with those who survived in an elderly (80+ years) and younger (<80years) cohort.Results: Of the 2823 study patients, the younger cohort comprised 2497 patients (FTR: n=139 [5.6%]), whereas the elderly cohort comprised 326 patients (FTR: n=39 [12.0%]). Pneumonia was the most common complication in younger (877/2497, 35.1%) and elderly patients (118/326, 36.2%) but was not associated with FTR on adjusted analysis. Increasing age was associated with FTR (adjusted odds ratio [AOR], 1.55 per decade, P<.001), whereas unplanned reoperation was associated with reduced risk (AOR, 0.55, P=.01). Within the elderly cohort, surgery conducted by a thoracic surgeon was associated with lower FTR risk (AOR, 0.29, P=.028).Conclusions: FTR following lung cancer resection was more frequent with increasing age. Pneumonia was the most common complication but not a predictor of FTR. Unplanned reoperation was associated with reduced FTR, as was treatment by a thoracic surgeon for elderly patients. Surgical therapy for complications after lung cancer resection and elderly patients managed by a thoracic specialist may mitigate the risk of death following an adverse postoperative event.

  View details for DOI 10.1016/j.xjon.2023.08.002

  View details for PubMedID 38204720

• The impact of refusing esophagectomy for treatment of locally advanced esophageal adenocarcinoma. JTCVS open Wong, L., Elliott, I. A., Liou, D. Z., Backhus, L. M., Lui, N. S., Shrager, J. B., Berry, M. F. 2023; 16: 987-995

  Abstract

  Objective: Patients with esophageal cancer may be reluctant to proceed with surgery due to high complication rates. This study aims to compare outcomes between eligible surgical candidates who proceeded with surgery versus those who refused surgery.Methods: Characteristics and survival of patients with locally advanced (cT3N0M0, cT1-3N+M0) mid-/distal esophageal adenocarcinoma in the National Cancer Database (2006-2019) who either proceeded with or refused surgery after chemoradiotherapy were evaluated with logistic regression, Kaplan-Meier curves, and Cox proportional hazards methods.Results: Of the 13,594 patients included in the analysis, 595 (4.4%) patients refused esophagectomy. Patients who refused surgery were older, had less distance to travel to their treatment facility, were more likely to have cN0 disease, and were more likely to be treated at a community rather than academic or integrated network program, but did not have significantly different comorbid disease distributions. On multivariable analysis, refusing surgery was independently associated with older age, uninsured, lower income, less distance to a hospital, and treatment in a community program versus an academic/research or integrated network program. Esophagectomy was associated with better survival (5-year survival 40.1% [39.2-41] vs 23.6% [19.9-27.9], P<.001) and was also independently associated with better survival in the Cox model (hazard rate, 0.78 [95% confidence interval, 0.7-0.87], P<.001).Conclusions: The results of this study can inform selected patients with resectable esophageal adenocarcinoma that their survival will be significantly diminished if surgery is not pursued. Many factors associated with refusing surgery are non-clinical and suggest that access to or support for care could influence patient decisions.

  View details for DOI 10.1016/j.xjon.2023.09.006

  View details for PubMedID 38204633

• Impact of hyperthermic intrathoracic chemotherapy (HITHOC) during resection of pleural mesothelioma on patient survival. Journal of thoracic disease Elliott, I. A., He, H., Lui, N. S., Liou, D. Z., Guenthart, B. A., Shrager, J. B., Berry, M. F., Backhus, L. M. 2023; 15 (11): 6140-6150

  Abstract

  Pleural mesothelioma (PM) is rare but portends a poor prognosis. Multimodal treatment, including aggressive surgical resection, may offer the best chance of treatment response and improved survival. Single-center studies suggest that hyperthermic intrathoracic chemotherapy (HITHOC) during surgical resection improves outcomes, but the impact of HITHOC on postoperative morbidity and survival has not been examined on a larger scale.The National Cancer Database was queried for patients undergoing resection for PM from 2006-2017. Patients were excluded if staging or survival data was incomplete. After propensity-score matching, patients who underwent HITHOC were compared to patients who did not (case-control study). Perioperative outcomes and survival were analyzed.The final cohort consisted of 3,232 patients; of these, 365 patients underwent HITHOC. After propensity-score matching, receipt of HITHOC was associated with increased length of stay (12 vs. 7 days, P<0.001) and increased 30-day readmissions (9.9% vs. 4.9%, P=0.007), but decreased 30-day mortality (3.2% vs. 6.0%, P=0.017) and 90-day mortality (7.5% vs. 10.9%). Kaplan-Meier modeling demonstrated that HITHOC was associated with improved survival in the overall cohort (median 20.5 vs. 16.8 months, P=0.001). In multivariable analysis, HITHOC remained associated with improved overall survival [hazard ratio (HR) =0.80; 95% confidence interval (CI): 0.69-0.92; P=0.002], and this persisted in the propensity-matched analysis (HR =0.73; 95% CI: 0.61-0.88; P=0.001).Using a large national database, we describe the impact of HITHOC on survival in patients with PM. Despite observed increased short-term morbidity, in multivariable analysis HITHOC was associated with an overall survival advantage for patients undergoing surgical resection of PM.

  View details for DOI 10.21037/jtd-23-466

  View details for PubMedID 38090290

  View details for PubMedCentralID PMC10713319

• Impact of hyperthermic intrathoracic chemotherapy (HITHOC) during resection of pleural mesothelioma on patient survival JOURNAL OF THORACIC DISEASE Elliott, I. A., He, H., Lui, N. S., Liou, D. Z., Guenthart, B. A., Shrager, J. B., Berry, M. F., Backhus, L. M. 2023

  View details for DOI 10.21037/jtd-23-466

  View details for Web of Science ID 001101361100001

• Second Primary Lung Cancer Among Lung Cancer Survivors Who Never Smoked. JAMA network open Choi, E., Su, C. C., Wu, J. T., Aredo, J. V., Neal, J. W., Leung, A. N., Backhus, L. M., Lui, N. S., Le Marchand, L., Stram, D. O., Liang, S. Y., Cheng, I., Wakelee, H. A., Han, S. S. 2023; 6 (11): e2343278

  Abstract

  Lung cancer among never-smokers accounts for 25% of all lung cancers in the US; recent therapeutic advances have improved survival among patients with initial primary lung cancer (IPLC), who are now at high risk of developing second primary lung cancer (SPLC). As smoking rates continue to decline in the US, it is critical to examine more closely the epidemiology of lung cancer among patients who never smoked, including their risk for SPLC.To estimate and compare the cumulative SPLC incidence among lung cancer survivors who have never smoked vs those who have ever smoked.This population-based prospective cohort study used data from the Multiethnic Cohort Study (MEC), which enrolled participants between April 18, 1993, and December 31, 1996, with follow-up through July 1, 2017. Eligible individuals for this study were aged 45 to 75 years and had complete smoking data at baseline. These participants were followed up for IPLC and further SPLC development through the Surveillance, Epidemiology, and End Results registry. The data were analyzed from July 1, 2022, to January 31, 2023.Never-smoking vs ever-smoking exposure at MEC enrollment.The study had 2 primary outcomes: (1) 10-year cumulative incidence of IPLC in the entire study cohort and 10-year cumulative incidence of SPLC among patients with IPLC and (2) standardized incidence ratio (SIR) (calculated as the SPLC incidence divided by the IPLC incidence) by smoking history.Among 211 414 MEC participants, 7161 (3.96%) developed IPLC over 4 038 007 person-years, and 163 (2.28%) developed SPLC over 16 470 person-years. Of the participants with IPLC, the mean (SD) age at cohort enrollment was 63.6 (7.7) years, 4031 (56.3%) were male, and 3131 (43.7%) were female. The 10-year cumulative IPLC incidence was 2.40% (95% CI, 2.31%-2.49%) among ever-smokers, which was 7 times higher than never-smokers (0.34%; 95% CI, 0.30%-0.37%). However, the 10-year cumulative SPLC incidence following IPLC was as high among never-smokers (2.84%; 95% CI, 1.50%-4.18%) as ever-smokers (2.72%; 95% CI, 2.24%-3.20%), which led to a substantially higher SIR for never-smokers (14.50; 95% CI, 8.73-22.65) vs ever-smokers (3.50; 95% CI, 2.95-4.12).The findings indicate that SPLC risk among lung cancer survivors who never smoked is as high as among those with IPLC who ever-smoked, highlighting the need to identify risk factors for SPLC among patients who never smoked and to develop a targeted surveillance strategy.

  View details for DOI 10.1001/jamanetworkopen.2023.43278

  View details for PubMedID 37966839

• Outcomes of a Failed Observation Approach for Paraesophageal Hernia Wong, L., Leipzig, M., Elliott, I. A., Lui, N., Liou, D., Backhus, L. M., Shrager, J. B., Berry, M. LIPPINCOTT WILLIAMS & WILKINS. 2023: S483

  View details for Web of Science ID 001100379000036

• Outcomes of a Failed Observation Approach for Paraesophageal Hernia Wong, L., Leipzig, M., Elliott, I. A., Lui, N., Liou, D., Backhus, L. M., Shrager, J. B., Berry, M. LIPPINCOTT WILLIAMS & WILKINS. 2023: S483

  View details for Web of Science ID 001094086301454

• Risk Model-Based Lung Cancer Screening and Racial and Ethnic Disparities in the US. JAMA oncology Choi, E., Ding, V. Y., Luo, S. J., Ten Haaf, K., Wu, J. T., Aredo, J. V., Wilkens, L. R., Freedman, N. D., Backhus, L. M., Leung, A. N., Meza, R., Lui, N. S., Haiman, C. A., Park, S. L., Le Marchand, L., Neal, J. W., Cheng, I., Wakelee, H. A., Tammemägi, M. C., Han, S. S. 2023

  Abstract

  The revised 2021 US Preventive Services Task Force (USPSTF) guidelines for lung cancer screening have been shown to reduce disparities in screening eligibility and performance between African American and White individuals vs the 2013 guidelines. However, potential disparities across other racial and ethnic groups in the US remain unknown. Risk model-based screening may reduce racial and ethnic disparities and improve screening performance, but neither validation of key risk prediction models nor their screening performance has been examined by race and ethnicity.To validate and recalibrate the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial 2012 (PLCOm2012) model-a well-established risk prediction model based on a predominantly White population-across races and ethnicities in the US and evaluate racial and ethnic disparities and screening performance through risk-based screening using PLCOm2012 vs the USPSTF 2021 criteria.In a population-based cohort design, the Multiethnic Cohort Study enrolled participants in 1993-1996, followed up through December 31, 2018. Data analysis was conducted from April 1, 2022, to May 19. 2023. A total of 105 261 adults with a smoking history were included.The 6-year lung cancer risk was calculated through recalibrated PLCOm2012 (ie, PLCOm2012-Update) and screening eligibility based on a 6-year risk threshold greater than or equal to 1.3%, yielding similar eligibility as the USPSTF 2021 guidelines.Predictive accuracy, screening eligibility-incidence (E-I) ratio (ie, ratio of the number of eligible to incident cases), and screening performance (sensitivity, specificity, and number needed to screen to detect 1 lung cancer).Of 105 261 participants (60 011 [57.0%] men; mean [SD] age, 59.8 [8.7] years), consisting of 19 258 (18.3%) African American, 27 227 (25.9%) Japanese American, 21 383 (20.3%) Latino, 8368 (7.9%) Native Hawaiian/Other Pacific Islander, and 29 025 (27.6%) White individuals, 1464 (1.4%) developed lung cancer within 6 years from enrollment. The PLCOm2012-Update showed good predictive accuracy across races and ethnicities (area under the curve, 0.72-0.82). The USPSTF 2021 criteria yielded a large disparity among African American individuals, whose E-I ratio was 53% lower vs White individuals (E-I ratio: 9.5 vs 20.3; P < .001). Under the risk-based screening (PLCOm2012-Update 6-year risk ≥1.3%), the disparity between African American and White individuals was substantially reduced (E-I ratio: 15.9 vs 18.4; P < .001), with minimal disparities observed in persons of other minoritized groups, including Japanese American, Latino, and Native Hawaiian/Other Pacific Islander. Risk-based screening yielded superior overall and race and ethnicity-specific performance to the USPSTF 2021 criteria, with higher overall sensitivity (67.2% vs 57.7%) and lower number needed to screen (26 vs 30) at similar specificity (76.6%).The findings of this cohort study suggest that risk-based lung cancer screening can reduce racial and ethnic disparities and improve screening performance across races and ethnicities vs the USPSTF 2021 criteria.

  View details for DOI 10.1001/jamaoncol.2023.4447

  View details for PubMedID 37883107

• Intraoperative Molecular Imaging of Lung Cancer. Thoracic surgery clinics Wong, L., Lui, N. S. 2023; 33 (3): 227-232

  Abstract

  Intraoperative molecular imaging innovations have been propelled by the development of fluorescent contrast agents that specifically target tumor tissues and advanced camera systems that can detect the specified fluorescence. The most promising agent to date is OTL38, a targeted and near-infrared agent that was recently approved by the Food and Drug Administration for intraoperative imaging for lung cancer.

  View details for DOI 10.1016/j.thorsurg.2023.04.013

  View details for PubMedID 37414478

• Tracheal stenosis and airway complications in the Coronavirus Disease-19 era. Annals of thoracic surgery short reports Krishnan, A., Guenthart, B. A., Choi, A., Trope, W., Berry, G. J., Pinezich, M. R., Vunjak-Novakovic, G., Shaller, B., Sung, C. K., Liou, D. Z., Damrose, E. J., Lui, N. S. 2023

  Abstract

  Severe Coronavirus Disease 2019 (COVID-19) infection is associated with prolonged intubation and its complications. Tracheal stenosis is one such complication that may require specialized surgical management. We aimed to describe the surgical management of post-COVID-19 tracheal stenosis.This case series describes consecutive patients with tracheal stenosis from intubation for severe COVID-19 infection at our single, tertiary academic medical center between January 1st, 2021, and December 31st, 2021. Patients were included if they underwent surgical management with tracheal resection and reconstruction, or bronchoscopic intervention. Operative through six-month, symptom-free survival and histopathological analysis of resected trachea were reviewed.Eight patients are included in this case series. All patients are female, and most (87.5%) are obese. Five patients (62.5%) underwent tracheal resection and reconstruction (TRR), while three patients (38.5%) underwent non-resection-based management. Among patients who underwent TRR, six-month symptom free survival is 80%; one patient (20%) required tracheostomy after TRR due to recurrent symptoms. Two of the three (66.7%) of patients who underwent non-resection-based management experienced durable relief from symptoms of tracheal stenosis with tracheal balloon dilation, and the remaining patient required laser excision of tracheal tissue prior to experiencing symptomatic relief.The incidence of tracheal stenosis may increase as patients recover from severe COVID-19 infection requiring intubation. Management of tracheal stenosis with TRR is safe and effective, with comparable rates of success to TRR for non-COVID-19 tracheal stenosis. Non-resection-based management is an option to manage tracheal stenosis in patients with less severe stenosis or in poor surgical candidates.

  View details for DOI 10.1016/j.atssr.2023.05.013

  View details for PubMedID 37360840

  View details for PubMedCentralID PMC10246306

• The impact of neoadjuvant immunotherapy on perioperative outcomes and survival after esophagectomy for esophageal cancer. JTCVS open Wong, L., Liou, D. Z., Backhus, L. M., Lui, N. S., Shrager, J. B., Berry, M. F. 2023; 14: 547-560

  Abstract

  Objective: Immunotherapy for esophageal cancer is relatively novel but increasingly used. This study evaluated the early use of immunotherapy as an adjunct to neoadjuvant chemoradiotherapy before esophagectomy for locally advanced disease.Methods: Perioperative morbidity (composite of mortality, hospitalization ≥21days, or readmission) and survival of patients with locally advanced (cT3N0M0, cT1-3N + M0) distal esophageal cancer in the National Cancer Database from 2013 to 2020 who underwent neoadjuvant immunotherapy plus chemoradiotherapy or chemoradiotherapy alone followed by esophagectomy were evaluated using logistic regression, Kaplan-Meier curves, Cox proportional hazards methods, and propensity-matched analysis.Results: Immunotherapy was used in 165 (1.6%) of 10,348 patients. Younger age (odds ratio, 0.66; 95% confidence interval, 0.53-0.81; P<.001) predicted immunotherapy use, which slightly delayed time from diagnosis to surgery versus chemoradiation alone (immunotherapy 148 [interquartile range, 128-177] days vs chemoradiation 138 [interquartile range, 120-162] days, P<.001). There were no statistically significant differences between the immunotherapy and chemoradiation groups for the composite major morbidity index (14.5% [24/165] vs 15.6% [1584/10,183], P=.8). Immunotherapy was associated with a significant improvement in median overall survival (69.1months vs 56.3months, P=.005) and 3-year overall survival in univariate analysis (65.6% [95% confidence interval, 57.7-74.5] vs 55.0% [53.9-56.1], P=.005), and independently predicted improved survival in multivariable analysis (hazard ratio 0.68 [95% confidence interval, 0.52-0.89], P=.006). Propensity-matched analysis also showed that immunotherapy use was not associated with increased surgical morbidity (P=.5) but was associated with improved survival (P=.047).Conclusions: Neoadjuvant immunotherapy use before esophagectomy for locally advanced esophageal cancer did not lead to worse perioperative outcomes and shows promising results on midterm survival.

  View details for DOI 10.1016/j.xjon.2023.03.015

  View details for PubMedID 37425457

• Characterization of Epidural Analgesia Interruption and Associated Outcomes After Esophagectomy. The Journal of surgical research Byrd, C. T., Kim, R. K., Manapat, P., He, H., Tsui, B. C., Shrager, J. B., Berry, M. F., Backhus, L. M., Lui, N. S., Liou, D. Z. 2023; 290: 92-100

  Abstract

  Interruption of thoracic epidural analgesia may impact the postoperative course following esophagectomy. This study investigates the incidence and causes of epidural interruption in esophagectomy patients along with associated postoperative outcomes.This single-institution retrospective analysis examined patients undergoing esophagectomy who received a thoracic epidural catheter from 2016 to 2020. Patients were stratified according to whether epidural catheter infusion was interrupted or not postoperatively. Outcomes were compared between the two groups, and predictors of epidural interruption and postoperative complications were estimated using multivariable logistic regression.Of the 168 patients who received a thoracic epidural before esophagectomy, 60 (35.7%) required epidural interruption and 108 (64.3%) did not. Interruption commonly occurred on postoperative day 1 and was due to hypotension 80% of the time. Heart failure (10.0% versus 0.9%, P = 0.009), atrial fibrillation (20.0% versus 3.7%, P = 0.002), preoperative opioid use (30.0% versus 16.7%, P = 0.043), and higher American Society of Anesthesiology classification (88.4% versus 70.4%, P = 0.008) were more prevalent in the epidural interruption cohort. The female gender was associated with epidural interruption on multivariable logistic regression (adjusted odds ratio [AOR] 2.45, P = 0.039). Patients in the epidural interruption cohort had a higher incidence of delirium (30.5% versus 13.9%, P = 0.010), sepsis (13.6% versus 3.7%, P = 0.028), and severe anastomotic leak (18.3% versus 7.4%, P = 0.032). On adjusted analysis, heart disease (AOR 4.26, P = 0.027), BMI <18.5 (AOR 9.83, P = 0.031), and epidural interruption due to hypotension (AOR 3.51, P = 0.037) were associated with severe anastomotic leak.Early epidural interruption secondary to hypotension in esophagectomy patients may be a harbinger of postoperative complications such as sepsis and severe anastomotic leak. Patients requiring epidural interruption due to hypotension should have a low threshold for additional workup and early intervention.

  View details for DOI 10.1016/j.jss.2023.04.009

  View details for PubMedID 37224609

• Surgical Management of Esophageal Perforation: Examining Trends in a Multi-Institutional Cohort. Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract Wong, L. Y., Leipzig, M., Liou, D. Z., Backhus, L. M., Lui, N. S., Shrager, J. B., Berry, M. F. 2023

  Abstract

  Esophageal perforations historically are associated with significant morbidity and mortality and generally require emergent intervention. The influence of improved diagnostic and therapeutic modalities available in recent years on management has not been examined. This study examined the surgical treatments and outcomes of a modern cohort.Patients with esophageal perforation management in the 2005-2020 American College of Surgeons National Surgical Quality Improvement Program database were stratified into three eras (2005-2009, 2010-2014, and 2015-2020). Surgical management was classified as primary repair, resection, diversion, or drainage alone based on procedure codes. The distribution of procedure use, morbidity, and mortality across eras was examined.Surgical management of 378 identified patients was primary repair (n=193,51%), drainage (n=89,24%), resection (n=70,18%), and diversion (n=26,7%). Thirty-day mortality in the cohort was 9.5% (n=36/378) and 268 patients (71%) had at least one complication. The median length of stay was 15 days. Both morbidity (Era 1 65% [n=42/60] versus Era 2 69% [n=92/131] versus Era 3 72% [n=135/187], p=0.3) and mortality (Era 1 11% [n=7/65] versus Era 2 9% [n=12/131] versus Era 3 10% [n=19/187], p=0.9) did not change significantly over the three defined eras. Treatment over time evolved such that primary repair was more frequently utilized (43% in Era 1 to 51% in Era 3) while diversion was less often performed (13% in Era 1 to 7% in Era 3) (p=0.009).Esophageal perforation management in recent years uses diversion less often but remains associated with significant morbidity and mortality.

  View details for DOI 10.1007/s11605-023-05700-1

  View details for PubMedID 37165161

  View details for PubMedCentralID 7330325

• Surgical resection of mediastinal ectopic thyroid tissue: a case series. Journal of thoracic disease Motlaghzadeh, Y., Nesbit, S., Guo, H. H., Yang, E., Desai, K., Lui, N. S. 2023; 15 (3): 1473-1481

  Abstract

  Ectopic thyroid tissue (ETT) is characterized by the presence of thyroid tissue in any location other than its normal anatomic position. Mediastinal ectopic thyroid gland is a rare entity, accounting for 1% of all ETT cases. In this article, we present seven cases with mediastinal ETT over the last 26 years admitted to Stanford hospital.Searching Stanford pathology database for specimens that contained term "ectopic thyroid" between 1996 and 2021, a total of 202 patients were collected. Among those seven were classified as mediastinal ETT. Patients' electronic medical records were reviewed for data collection purposes. The mean age of our seven cases was 54 years on the day of surgery, and four were female. Chest pressure, cough, and neck pain were most reported presenting symptoms. Four of our patients had thyroid stimulating hormone (TSH) checks all within normal limits. All patients in our study had computed tomography (CT) imaging of the chest detecting the mediastinal mass. Histopathology of the mass revealed ectopic thyroid tissue negative for malignancy in all cases.Ectopic mediastinal thyroid tissue is a rare clinical entity that should be considered in the differential diagnosis of all mediastinal masses as it usually requires different management and treatment.

  View details for DOI 10.21037/jtd-22-479

  View details for PubMedID 37065554

  View details for PubMedCentralID PMC10089840

• Surgical resection of mediastinal ectopic thyroid tissue: a case series JOURNAL OF THORACIC DISEASE Motlaghzadeh, Y., Nesbit, S., Guo, H., Yang, E., Desai, K., Lui, N. S. 2023

  View details for DOI 10.21037/jtd-22-479

  View details for Web of Science ID 000942495700001

• ASO Visual Abstract: Impact of Delaying Surgery After Chemoradiation on Outcomes for Locally Advanced Esophageal Squamous Cell Carcinoma. Annals of surgical oncology Wong, L. Y., Liou, D. Z., Vitzthum, L. K., Backhus, L. M., Lui, N. S., Chang, D., Shrager, J. B., Berry, M. F. 2023

  View details for DOI 10.1245/s10434-023-13156-5

  View details for PubMedID 36759429

• Does delaying surgery following induction chemotherapy compromise survival in patients with mesothelioma? JOURNAL OF CANCER METASTASIS AND TREATMENT Wong, L., Baiu, I., Leipzig, M., Titan, A., Liou, D. Z., Lui, N., Berry, M., Shrager, J. B., Backhus, L. 2023; 9

  View details for DOI 10.20517/2394-4722.2023.57

  View details for Web of Science ID 001072777600001

• Impact of Delaying Surgery After Chemoradiation on Outcomes for Locally Advanced Esophageal Squamous Cell Carcinoma. Annals of surgical oncology Wong, L., Liou, D. Z., Vitzthum, L. K., Backhus, L. M., Lui, N. S., Chang, D., Shrager, J. B., Berry, M. F. 2022

  Abstract

  BACKGROUND: Performing selective esophagectomy for locally advanced squamous cell carcinoma may spare patients morbidity, but delayed surgery may infer higher risks. This study evaluated the impact of length of time between chemoradiation and esophagectomy on perioperative outcomes and long-term survival.METHODS: The impact of surgical timing, stratified by surgery performed < 180 and ≥ 180 days from starting radiation, on perioperative outcomes and survival in patients treated with chemoradiation and esophagectomy for cT1N + M0 and cT2-4, any N, M0 squamous cell carcinoma of the mid-distal esophagus in the National Cancer Database (2006-2016) was evaluated with logistic regression, Kaplan-Meier curves, Cox proportional-hazards methods, and propensity-matched analysis.RESULTS: Median time between starting radiation and esophagectomy in 1641 patients was 93 (IQR 81-114) days. Most patients (96.8%, n = 1589) had surgery within 180 days of starting radiation, while 52 patients (3.2%) had delayed surgery. Black race and clinical T stage were associated with delayed surgery. Rates of pathologic upstaging, downstaging, complete response, and positive margins were not significantly different between the groups. Patients with delayed surgery had increased major morbidity as measured by a composite of length of hospital stay, readmission, and 30-day mortality [42.3% (22/52) vs 22.3% (355/1589), p = 0.001]. However, delayed surgery was not associated with a significant difference in survival in both univariate [5-year survival 32.8% (95% CI 21.1-50.7) vs 47.3% (44.7-50.1), p = 0.19] and multivariable analysis [hazard ratio (HR) 1.23 (0.85-1.78), p = 0.26].CONCLUSIONS: Delaying surgery longer than 180 days after starting chemoradiation for esophageal squamous cell carcinoma is associated with worse perioperative outcomes but not long-term survival.

  View details for DOI 10.1245/s10434-022-12980-5

  View details for PubMedID 36572807

• Improving lung cancer screening rates among patients with head and neck cancer in a radiation oncology clinic. Journal of thoracic disease Soto, L., Nesbit, S., Ramsey, M., Gensheimer, M. F., Le, Q. T., Beadle, B. M., Lui, N. S. 2022; 14 (12): 4633-4640

  Abstract

  The United States Preventive Services Task Force (USPSTF) recommends lung cancer screening via annual low dose computed tomography (LDCT) for high risk patients. Despite the strong evidence of a mortality benefit from several randomized clinical trials, rates of lung cancer screening remain low. We plan to assess how screening guidelines are implemented in a radiation oncology clinic for patients with head and neck cancer.A single institution, retrospective chart review was used to identify patients with head and neck cancer seen in a radiation oncology clinic who were potentially eligible for lung cancer screening under the current USPSTF guidelines. Patients who were potentially screening-eligible were enrolled in a phone survey to assess their knowledge about lung cancer screening and willingness to be screened.Of the 184 patients with head and neck cancer seen in the clinic, 8 (4%) patients were eligible for lung cancer screening under the previous USPSTF recommendations, including 1 (0.5%) patient already being screened. One patient (0.5%) became eligible under the expanded guidelines. All 184 patients had smoking history documented. Of the 87 current or former smokers, there were 24 (28%) who did not have pack-years documented; of the 82 former smokers, there were 8 (10%) who did not have quit date documented. Among the 16 phone survey participants (response rate: 70%) only 6 (38%) were aware there is a way to screen for lung cancer and 12 (75%) patients would be interested in screening if they are found to be eligible.These findings highlight a potential opportunity to increase rates of lung cancer screening among patients with head and neck cancer by both enhancing provider awareness as well as patient education at the community level.

  View details for DOI 10.21037/jtd-22-787

  View details for PubMedID 36647458

  View details for PubMedCentralID PMC9840013

• Single-port robotic transcervical long-segment thoracic tracheal reconstruction: Cadaveric proof-of-concept study. JTCVS techniques Lui, N. S., Holsinger, F. C., Ma, M. R., Janus, J. R., Balakrishnan, K. 2022; 16: 231-236

  Abstract

  Slide tracheoplasty is the standard technique to repair congenital long-segment tracheal stenosis. This operation most commonly requires median sternotomy, which has drawbacks in young children. We hypothesized that a transcervical approach without sternotomy would be feasible if done with a single-port robotic system.This proof-of concept study was performed in 2 small adult cadavers using a single-port robotic surgical system via a small neck incision. Relevant information, including operative time and details of operative technique, were recorded.Long-segment slide tracheoplasty was completed successfully in 2 cadavers using a small neck incision and a single-port robotic surgical system. Strengths and pitfalls of the technique were identified, including technical refinements from the first attempt to the second. Operative time for robotic mobilization, incision, and anastomosis of the trachea was comparable to standard open approaches.Small-incision transcervical slide tracheoplasty, assisted by a single-port surgical robotic system, is feasible in a human cadaver. More work is needed to determine safety and applicability in live patients, particularly in children.

  View details for DOI 10.1016/j.xjtc.2022.08.025

  View details for PubMedID 36510525

  View details for PubMedCentralID PMC9735391

• Risk of adenocarcinoma in patients with a suspicious ground-glass opacity: a retrospective review. Journal of thoracic disease Roy, E., Shrager, J., Benson, J., Trope, W. L., Bhandari, P., Lui, N., Liou, D., Backhus, L., Berry, M. F. 2022; 14 (11): 4236-4245

  Abstract

  Both primary lung adenocarcinoma and benign processes can have a ground-glass opacity (GGO) appearance on imaging. This study evaluated the incidence of and risk factors for malignancy in a diverse cohort of patients who underwent resection of a GGO suspicious for lung cancer.All patients who underwent resection of a pulmonary nodule with a GGO component and suspected to be primary lung cancer at a single institution from 2001-2017 were retrospectively reviewed. Risk factors for malignancy were evaluated using multivariable logistic regression analysis that included nodule size, age, sex, and race as potential predictors.The incidence of pulmonary adenocarcinoma in the 243 patients who met inclusion criteria was 86% (n=208). The most common pathologic findings in 35 patients with a benign pathology was granulomatous inflammation (n=14, 40%). Risk factors for adenocarcinoma in multivariable logistic regression were age [odds ratio (OR) 1.06, P=0.003], GGO size (OR 2.76, P<0.001), female sex (OR 4.47, P=0.002), and Asian race (OR 8.35, P=0.002). In this cohort, adenocarcinoma was found in 100% (44/44) of Asian females, 86% (25/29) of Asian males, 84% (98/117) of non-Asian females, and 77% (41/53) of non-Asian males.The likelihood of adenocarcinoma in lung nodules with a ground-glass component is influenced by sex and race. Asian females with a GGO have a much higher likelihood of having adenocarcinoma than men and non-Asians. This data can be used when deciding whether to pursue nodule resection or surveillance in a patient with a GGO.

  View details for DOI 10.21037/jtd-22-583

  View details for PubMedID 36524073

  View details for PubMedCentralID PMC9745528

• Oncology Imaging: Updates and Advancements. Surgical oncology clinics of North America Lui, N. S. 2022; 31 (4): xiii-xiv

  View details for DOI 10.1016/j.soc.2022.07.012

  View details for PubMedID 36243505

• Applications of Three-Dimensional Printing in Surgical Oncology. Surgical oncology clinics of North America Byrd, C. T., Lui, N. S., Guo, H. H. 2022; 31 (4): 673-684

  Abstract

  A variety of three-dimensional (3D) printing techniques and materials facilitate the creation of customized models that promise to improve surgical procedures and patient outcomes. Three-dimensional-printed models allow patients, trainees, and experienced surgeons to explore anatomy through direct visualization and tactile feedback. Although 3D-printed models serve a range of purposes including preoperative planning, education, skills refinement, patient-specific intraprocedural guides, and implants, much work remains to decrease the turnaround time and cost of printing models, collect long-term effectiveness data, and refine regulatory oversight of 3D printing in medicine.

  View details for DOI 10.1016/j.soc.2022.06.005

  View details for PubMedID 36243500

• Intraoperative Molecular Imaging of Lung Cancer: A Review. Surgical oncology clinics of North America Lui, N. S., Singhal, S. 2022; 31 (4): 685-693

  Abstract

  Intraoperative molecular imaging shows great promise in the surgical treatment of lung cancer, in particular tumor localization, margin assessment, identification of additional nodules, and even potentially lymph node assessment. Advances in imaging agents and fluorescence surgical cameras will be the key. Although no imaging agent is currently Food and Drug Administration approved, targeted, near-infrared agents such as OTL38 are in phase III trials.

  View details for DOI 10.1016/j.soc.2022.06.006

  View details for PubMedID 36243501

• Lobar versus sublobar resection in clinical stage IA primary lung cancer with occult N2 disease. European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery Liou, D. Z., Chan, M., Bhandari, P., Lui, N. S., Backhus, L. M., Shrager, J. B., Berry, M. F. 2022

  Abstract

  Sublobar resection is increasingly being utilized for early-stage lung cancers, but optimal management when final pathology shows unsuspected mediastinal nodal disease is unclear. This study tested the hypothesis that lobectomy has improved survival compared to sublobar resection for clinical stage IA tumors with occult N2 disease.The use of sublobar resection and lobectomy for patients in the National Cancer Database who underwent primary surgical resection for clinical stage IA non-small cell lung cancer with pathologic N2 disease between 2010 and 2017 was evaluated using logistic regression. Survival was assessed with Kaplan-Meier analysis, log-rank test, and Cox proportional hazards model.A total of 2,419 patients comprised the study cohort, including 320 sublobar resections (13.2%) and 2,099 lobectomies (86.8%). Older age, female sex, smaller tumour size, and treatment at an academic facility predicted the use of sublobar resection. Patients undergoing lobectomy had larger tumors (2.40 vs 2.05 cm, p < 0.001) and more lymph nodes examined (11 vs 5, p < 0.001). Adjuvant chemotherapy use was similar between the two groups (sublobar 79.4% vs lobectomy 77.4%, p = 0.434). Sublobar resection was not associated with worse survival compared to lobectomy in both univariate (5-year survival 46.6% vs 45.2%, p = 0.319) and multivariable Cox proportional hazards analysis (HR 0.97, p = 0.789).Clinical stage IA non-small cell lung cancer patients with N2 disease on final pathology have similar long-term survival with either sublobar resection or lobectomy. Patients with occult N2 disease after sublobar resection may not require reoperation for completion lobectomy but should instead proceed to adjuvant chemotherapy.

  View details for DOI 10.1093/ejcts/ezac440

  View details for PubMedID 36063054

• Risk of adenocarcinoma in patients with a suspicious ground-glass opacity: a retrospective review JOURNAL OF THORACIC DISEASE Roy, E., Shrager, J., Benson, J., Trope, W., Bhandari, P., Lui, N., Liou, D., Backhus, L., Berry, M. F. 2022

  View details for DOI 10.21037/jtd-22-583

  View details for Web of Science ID 000869953800001

• Eligibility for Lung Cancer Screening Among Women Receiving Screening for Breast Cancer. JAMA network open Titan, A. L., Baiu, I., Liou, D., Lui, N. S., Berry, M., Shrager, J., Backhus, L. 2022; 5 (9): e2233840

  View details for DOI 10.1001/jamanetworkopen.2022.33840

  View details for PubMedID 36178692

• Virtual Surgical Skills Training in a High School Summer Program. The Annals of thoracic surgery Bajaj, S. S., Patel, H. H., Fann, J. I., Ma, M., Lui, N. S. 2022

  Abstract

  BACKGROUND: The COVID-19 pandemic has disrupted components of traditional education with shifts toward virtual platforms. Here, we describe the virtual approach to basic surgical skills training during our high school program in the summers of 2020 and 2021.METHODS: Two 2-week sessions were held via Zoom with 99 students in 2020 and 198 students in 2021. Each student was sent surgical supplies and instruments. Interactive lectures were held each morning and basic surgical skills instruction each afternoon. After the session, survey links were distributed to students to complete an anonymous 37-item questionnaire regarding surgical skills confidence, simulation kit satisfaction, and technical difficulties.RESULTS: Of the 297 students, 270 (90.9%) completed the questionnaire, including 91 (91.9%) in 2020 and 179 (90.4%) in 2021. On a scale of 1 (fair) to 5 (excellent), students in 2020 and 2021 reported similar confidence in instrument handling (4-5: 90.0% vs 86.3%, p=0.38), suturing skin (4-5: 88.9% vs 82.8%, p=0.19), and thoracic aorta suturing (4-5: 73.3% vs 73.6%, p=0.97). Students reported greater confidence in 2020 on knot-tying (4-5: 98.9% vs 87.9%, p=0.002), coronary vessel suturing (4-5: 82.2% vs 65.5%, p<0.001), and valve model suturing (4-5: 68.5% vs 50.3%, p=0.005) than students in 2021. Students had similar satisfaction rates with the program (extremely or somewhat satisfied: 92.3% vs 86.0%, p=0.51) between 2020 and 2021.CONCLUSIONS: Virtual education carries the potential for basic surgical skills training for a more widespread audience with less access to direct surgical education. Further research is needed to optimize teaching finer surgical skills.

  View details for DOI 10.1016/j.athoracsur.2022.07.034

  View details for PubMedID 35934065

• Genomic Profiling of Bronchoalveolar Lavage Fluid in Lung Cancer. Cancer research Nair, V. S., Hui, A. B., Chabon, J. J., Shahrokh Esfahani, M., Stehr, H., Nabet, B. Y., Zhou, L., Chaudhuri, A. A., Benson, J. A., Ayers, K., Bedi, H., Ramsey, M. C., Van Wert, R., Antic, S., Lui, N. S., Backhus, L. M., Berry, M. F., Sung, A. W., Massion, P. P., Shrager, J. B., Alizadeh, A. A., Diehn, M. 2022

  Abstract

  Genomic profiling of Bronchoalveolar Lavage (BAL) samples may be useful for tumor profiling and diagnosis in the clinic. Here, we compared tumor-derived mutations detected in BAL samples from subjects with non-small cell lung cancer (NSCLC) to those detected in matched plasma samples. CAncer Personalized Profiling by deep Sequencing (CAPP-Seq) was used to genotype DNA purified from BAL, plasma and tumor samples from patients with NSCLC. The characteristics of cell-free DNA (cfDNA) isolated from BAL fluid were first characterized to optimize the technical approach. Somatic mutations identified in tumor were then compared to those identified in BAL and plasma, and the potential of BAL cfDNA analysis to distinguish lung cancer patients from risk-matched controls was explored. In total, 200 biofluid and tumor samples from 38 cases and 21 controls undergoing BAL for lung cancer evaluation were profiled. More tumor variants were identified in BAL cfDNA than plasma cfDNA in all stages (p<0.001) and in stage I-II disease only. Four of 21 controls harbored low levels of cancer-associated driver mutations in BAL cfDNA (mean VAF=0.5%), suggesting the presence of somatic mutations in non-malignant airway cells. Finally, using a Random Forest model with leave-one-out cross validation, an exploratory BAL genomic classifier identified lung cancer with 69% sensitivity and 100% specificity in this cohort and detected more cancers than BAL cytology. Detecting tumor-derived mutations by targeted sequencing of BAL cfDNA is technically feasible and appears to be more sensitive than plasma profiling. Further studies are required to define optimal diagnostic applications and clinical utility.

  View details for DOI 10.1158/0008-5472.CAN-22-0554

  View details for PubMedID 35748739

• Commentary: American Association for Thoracic Surgery foundation research grants: An opportunity to shape the future of cardiothoracic surgery. JTCVS open Reveron-Thornton, R. F., Lui, N. S. 2022; 10: 291-292

  View details for DOI 10.1016/j.xjon.2022.01.025

  View details for PubMedID 36004258

• Three-dimensional-printed model of surgically resectable angioinvasive pulmonary mucormycosis. JTCVS techniques Byrd, C. T., Vyas, D., Guo, H. H., Lui, N. S. 2022; 13: 244-246

  View details for DOI 10.1016/j.xjtc.2022.04.013

  View details for PubMedID 35711220

• Career Progression and Research Productivity of Women in Academic Cardiothoracic Surgery. The Annals of thoracic surgery Williams, K. M., Wang, H., Bajaj, S. S., Hironaka, C. E., Kasinpila, P., O'Donnell, C. T., Sanchez, M., Watkins, A. C., Lui, N. S., Backhus, L. M., Boyd, J. 2022

  Abstract

  The objective of this work was to delineate career progression and research productivity of women practicing cardiothoracic surgery in the academic setting.Cardiothoracic surgeons at the 79 accredited U.S. cardiothoracic surgery training programs in 2020 were included in this cross-sectional analysis. Data regarding sub-specialization, training, practice history, and publications were gathered from public sources including department websites, CTSNet, and Scopus.A total of 1065 surgeons (51.3% cardiac, 32.1% thoracic, 16.6% congenital) were identified. Women accounted for 10.6% (113) of the population (7.9% of cardiac, 15.5% of thoracic, 9.6% of congenital surgeons). The median number of cardiothoracic surgeons per institution was 12 [IQR 10-17], with a median of one woman [IQR 0-2]. Fifteen of 79 (19%) programs had zero women. Among women faculty, 5.3% were clinical instructors, 51.3% were assistant professors, 23.0% were associate professors, 16.8% were full professors, and 3.5% had unspecified titles (vs. 2.0%, 32.9%, 23.0%, 37.5%, and 4.6% among men, respectively, p<0.001). Women and men authored a comparable number of first-author (0.4 [0.0-1.3] vs. 0.5 [0.0-1.1], p=0.56) publications per year, but fewer last-author (0.1 [0.0-0.7] vs. 0.4 [0.0-1.3], p<0.0001) and total publications per year (2.7 [1.0-6.2] vs. 3.7 [1.3-7.8], p=0.05) than men. H-index was lower for women than for men overall (8.0 [3.0-15.0] vs. 15.0 [7.0-28.0], p<0.001), but was similar between men and women who had been practicing for 10-20 years.Gender disparities persist in academic cardiothoracic surgery. Efforts should be made to support women in achieving senior roles and academic productivity.

  View details for DOI 10.1016/j.athoracsur.2022.04.057

  View details for PubMedID 35643331

• Half of Anastomotic Leaks after Esophagectomy are Undetected on Initial Postoperative Esophagram. The Annals of thoracic surgery Elliott, I. A., Berry, M. F., Trope, W., Lui, N. S., Guenthart, B. A., Liou, D. Z., Whyte, R. I., Backhus, L. M., Shrager, J. B. 2022

  Abstract

  The sensitivity of fluoroscopic esophagrams with oral contrast to exclude anastomotic leak after esophagectomy is not well-documented, and the consequences of missing a leak in this setting have not been previously described.We performed a retrospective cohort study of a prospectively maintained institutional database of patients undergoing esophagectomy with esophagogastric anastomosis 2008-2020. Relevant details regarding leaks, management, and outcomes were obtained from the database and formal chart review. Statistical analysis was performed to compare patients with and without leaks, and those with false negative versus positive esophagrams.There were 384 patients who underwent esophagectomy with gastric reconstruction: the majority were Ivor-Lewis (82%), and 51% were wholly or partially minimally-invasive. Using a broad definition of leak, 55 patients (16.7%) developed an anastomotic leak. Twenty-seven of the 55 patients (49%) who ultimately were found to have a leak initially had a negative esophagram (performed on average on postoperative day 6). Those with a negative initial esophagram were more likely to have an uncontained leak (81% vs. 29%, p<0.01), require unplanned readmission (70% vs. 39%, p=0.02), and undergo reoperation (44% vs. 11%, p<0.01).Early postoperative esophagrams intended to evaluate anastomotic integrity have a low sensitivity of 51%, and leaks missed on initial esophagram have greater clinical consequences than those identified on initial esophagram. These findings suggest a high index of suspicion must be maintained even after a normal esophagram and calls into question the common practice of using this test to triage patients for diet advancement.

  View details for DOI 10.1016/j.athoracsur.2022.04.053

  View details for PubMedID 35618049

• Positron emission tomography/computed tomography differentiates resectable thymoma from anterior mediastinal lymphoma. The Journal of thoracic and cardiovascular surgery Byrd, C. T., Trope, W. L., Bhandari, P., Konsker, H. B., Moradi, F., Lui, N. S., Liou, D. Z., Backhus, L. M., Berry, M. F., Shrager, J. B. 2022

  Abstract

  OBJECTIVE: Discrete anterior mediastinal masses most often represent thymoma or lymphoma. Lymphoma treatment is nonsurgical and requires biopsy. Noninvasive thymoma is ideally resected without biopsy, which may potentiate pleural metastases. This study sought to determine if clinical criteria or positron emission tomography/computed tomography could accurately differentiate the 2, guiding a direct surgery versus biopsy decision.METHODS: A total of 48 subjects with resectable thymoma and 29 subjects with anterior mediastinal lymphoma treated from 2006 to 2019 were retrospectively examined. All had pretreatment positron emission tomography/computed tomography and appeared resectable (solitary, without clear invasion or metastasis). Reliability of clinical criteria (age and B symptoms) and positron emission tomography/computed tomography maximum standardized uptake value were assessed in differentiating thymoma and lymphoma using Wilcoxon rank-sum test, chi-square test, and logistic regression. Receiver operating characteristic analysis identified the maximum standardized uptake value threshold most associated with thymoma.RESULTS: There was no association between tumor type and age group (P=.183) between those with thymoma versus anterior mediastinal lymphoma. Patients with thymoma were less likely to report B symptoms (P<.001). The median maximum standardized uptake value of thymoma and lymphoma differed dramatically: 4.35 versus 18.00 (P<.001). Maximum standardized uptake value was independently associated with tumor type on multivariable regression. On receiver operating characteristic analysis, lower maximum standardized uptake value was associated with thymoma. Maximum standardized uptake value less than 12.85 was associated with thymoma with 100.00% sensitivity and 88.89% positive predictive value. Maximum standardized uptake value less than 7.50 demonstrated 100.00% positive predictive value for thymoma.CONCLUSIONS: Positron emission tomography/computed tomography maximum standardized uptake value of resectable anterior mediastinal masses may help guide a direct surgery versus biopsy decision. Tumors with maximum standardized uptake value less than 7.50 are likely thymoma and thus perhaps appropriately resected without biopsy. Tumors with maximum standardized uptake value greater than 7.50 should be biopsied to rule out lymphoma. Lymphoma is likely with maximum standardized uptake value greater than 12.85.

  View details for DOI 10.1016/j.jtcvs.2022.02.055

  View details for PubMedID 35568521

• Factors for differential outcome across cancers in clinical molecular-targeted fluorescence imaging. Journal of nuclear medicine : official publication, Society of Nuclear Medicine Zhou, Q., van den Berg, N. S., Kang, W., Pei, J., Nishio, N., van Keulen, S., Engelen, M. A., Lee, Y. J., Hom, M., Vega Leonel, J. C., Hart, Z., Vogel, H., Cayrol, R., Martin, B. A., Roesner, M., Shields, G., Lui, N., Hayden Gephart, M., Raymundo, R. C., Yi, G., Granucci, M., Grant, G. A., Li, G., Rosenthal, E. L. 2022

  Abstract

  Clinical imaging performance using a fluorescent antibody was compared across three cancers to elucidate physical and biological factors contributing to differential translation of epidermal growth factor receptor (EGFR) expression to macroscopic fluorescence in tumors. Methods: Thirty-one patients with high-grade glioma (HGG, n = 5), head-and-neck squamous cell carcinoma (HNSCC, n = 23) or lung adenocarcinoma (LAC, n = 3) were systemically infused with 50 mg panitumumab-IRDye800, 1 - 3 days prior to surgery. Intraoperative open-field fluorescent images of the surgical field were acquired, where imaging device settings and operating room lighting conditions were tested on tissue-mimicking phantoms. Fluorescence contrast and margin size were measured on resected specimen surface. Antibody distribution and EGFR immunoreactivity were characterized in macroscopic and microscopic histological structures. Integrity of the blood-brain barrier (BBB) was examined via tight junction protein (claudin-5) expression with immunohistochemistry. Stepwise multivariate linear regression of biological variables was performed to identify independent predictors of panitumumab-IRDye800 concentration in tissue. Results: Optimally acquired at the lowest gain for tumor detection with ambient light, intraoperative fluorescence imaging enhanced tissue-size dependent tumor contrast by 5.2-fold, 3.4-fold and 1.4-fold in HGG, HNSCC and LAC, respectively. Tissue surface fluorescence target-to-background ratio correlated with margin size and identified 78 - 97% of at-risk resection margins ex vivo. In 4 µm-thick tissue sections, fluorescence detected tumor with 0.85 - 0.89 areas under the receiver operating characteristic curves. Preferential breakdown of BBB in HGG improved tumor specificity of intratumoral antibody distribution relative to that of EGFR (96% vs 80%) despite its reduced concentration (3.9 ng/mg tissue) compared to HNSCC (8.1 ng/mg) and LAC (6.3 ng/mg). Cellular EGFR expression, tumor cell density, plasma antibody concentration and delivery barrier were independently associated with local intratumoral panitumumab-IRDye800 concentration with 0.62 goodness-of-fit of prediction. Conclusion: In multi-cancer clinical imaging of receptor-ligand based molecular probe, plasma antibody concentration, delivery barrier, as well as intratumoral EGFR expression driven by cellular biomarker expression and tumor cell density, led to heterogeneous intratumoral antibody accumulation and spatial distribution while tumor size, resection margin, and intraoperative imaging settings substantially influenced macroscopic tumor contrast.

  View details for DOI 10.2967/jnumed.121.263674

  View details for PubMedID 35332092

• Social Disparities in Lung Cancer. Thoracic surgery clinics Elliott, I., Gonzalez, C., Backhus, L., Lui, N. 2022; 32 (1): 33-42

  Abstract

  Social disparities in lung cancer diagnosis, treatment, and survival have been studied using national databases, statewide registries, and institution-level data. Some disparities emerge consistently, such as lower adherence to treatment guidelines and worse survival by race and socioeconomic status, whereas other disparities are less well studied. A critical appraisal of current data is essential to increasing equity in lung cancer care.

  View details for DOI 10.1016/j.thorsurg.2021.09.009

  View details for PubMedID 34801193

• Induction therapy is not associated with improved survival in large cT4N0 non-small cell lung cancers. The Annals of thoracic surgery Sun, B. J., Bhandari, P., Jeffrey Yang, C., Berry, M. F., Shrager, J. B., Backhus, L. M., Lui, N. S., Liou, D. Z. 2021

  Abstract

  BACKGROUND: The 8th edition staging for non-small cell lung cancer reclassified tumors >7 cm as stage IIIA (T4N0); previously, such tumors without nodal disease were considered stage IIB (T3N0). This study tested the hypothesis that induction chemotherapy for these stage IIIA patients does not improve survival compared to primary surgery.METHODS: The National Cancer Database was queried for non-small cell lung cancer patients with tumor size >7 cm who underwent surgical resection from 2010 - 2015. Patients with clinically node-positive disease or tumor invasion of major structures were excluded. Patients undergoing induction chemotherapy followed by surgery (IC) were compared to patients undergoing primary surgery (PS). Propensity-score matching was performed.RESULTS: In total, 1,610 patients with cT4N0 disease based on tumor size >7 cm and no tumor invasion underwent surgical resection: 1,346 (83.6%) comprised the PS group and 264 (16.4%) the IC group. After propensity-score matching, IC had a higher rate of pN0 (78.4% vs 66.0%, p<0.001) and less lymphovascular invasion (13.9% vs 26.3%, p<0.001), but longer postoperative stay (6 vs 5 days, p<0.001) and higher 30-day mortality (3.5% vs 0%, p=0.002). Median 5-year survival was similar between IC and PS (53.5% vs 62.2%, p=0.075), and IC was not independently associated with survival (HR 1.45, p=0.146).CONCLUSIONS: Patients with cT4N0 non-small cell lung cancer based on tumor size >7 cm and no tumor invasion of major structures have similar overall survival with either IC or PS. IC should not be routinely given for this subset of stage IIIA patients.

  View details for DOI 10.1016/j.athoracsur.2021.07.058

  View details for PubMedID 34425099

• Commentary: Inspiring a New Generation of Healthcare Workers. Seminars in thoracic and cardiovascular surgery Baiu, I., Lui, N. S. 2021

  View details for DOI 10.1053/j.semtcvs.2021.08.006

  View details for PubMedID 34407436

• Commentary: American Association for Thoracic Surgery Summer Intern Scholarship: Captivating the interest of medical students. The Journal of thoracic and cardiovascular surgery Byrd, C. T., Lui, N. S. 2021

  View details for DOI 10.1016/j.jtcvs.2021.08.022

  View details for PubMedID 34456053

• Surgical resection for patients with pulmonary aspergillosis in the national inpatient sample. Journal of thoracic disease Patel, D. C., Bhandari, P., Epstein, D. J., Liou, D. Z., Backhus, L. M., Berry, M. F., Shrager, J. B., Lui, N. S. 2021; 13 (8): 4977-4987

  Abstract

  The role of lung resection in patients with pulmonary aspergillosis is generally reserved for those with localized disease who fail medical management. We used a national database to investigate the influence of preoperative patient comorbidities on inpatient mortality and need for surgery.Patients admitted with pulmonary aspergillosis between 2007 to 2015 were identified in the National Inpatient Sample dataset. Inpatient mortality rates were compared between patients treated medically and surgically. Predictors of mortality, surgical intervention, and non-elective admission were evaluated using multivariable logistic regression.Among a population estimate of 112,998 patients with pulmonary aspergillosis, 107,606 (95.2%) underwent medical management alone and 5,392 (4.8%) underwent surgical resection. Positive predictors for surgery included hemoptysis, and history of lung cancer or chronic pulmonary diseases. Surgically treated patients had a lower inpatient mortality when compared to those treated medically (11.5% vs. 15.1%, P<0.001) in univariate analysis, but this finding did not persist in multivariable analysis (AOR 0.97, P=0.509). The odds of mortality were lower in patients undergoing video assisted thoracoscopic surgery compared to an open approach (AOR 0.77, P=0.001). Among patients treated surgically, mortality was higher in those with a history of lung cancer, solid organ transplantation, liver disease, human immunodeficiency virus infection, hematologic diseases, chronic pulmonary diseases, and those admitted non-electively requiring surgery.In this generalizable study, medical and surgical management of pulmonary aspergillosis were comparable in terms of inpatient mortality. However, non-elective admission and patients with select comorbidities have significantly worse outcomes after surgical intervention.

  View details for DOI 10.21037/jtd-21-151

  View details for PubMedID 34527336

  View details for PubMedCentralID PMC8411153

• Short-term and intermediate-term readmission after esophagectomy. Journal of thoracic disease Wang, Y., Yang, C. J., He, H., Buchan, J. M., Patel, D. C., Liou, D. Z., Lui, N. S., Berry, M. F., Shrager, J. B., Backhus, L. M. 2021; 13 (8): 4678-4689

  Abstract

  The objective of this study was to characterize short- and intermediate-term readmissions following esophagectomy and to identify predictors of readmission in these two groups.Patients who underwent esophagectomy in the National Readmissions Database (2013-2014) were grouped according to whether first readmission was "short-term" (readmitted <30 days) or "intermediate-term" (readmitted 31-90 days) following index admission for esophagectomy. Predictors of readmission were evaluated using multivariable logistic regression modeling.Of the 3,005 patients who underwent esophagectomy, 544 (18.1%) had a short-term readmission and 305 (10.1%) had an intermediate-term readmission. The most frequent reasons for short-term readmission were post-operative infection (7.5%), dysphagia (6.3%) and pneumonia (5.1%). The most common intermediate-term complications were pneumonia (7.2%), gastrointestinal stricture/stenosis (6.9%) and dysphagia (5.9%). In multivariable analysis, being located in a micropolitan area, increasing number of comorbidities and higher severity of illness score were associated with an increased likelihood of having a short-term readmission while being discharged to a facility (as opposed to directly home) was associated with increased likelihood of both short- and intermediate-term readmission (all P<0.05).In this analysis, postoperative infection was the most common reason for short-term readmission. Dysphagia and pneumonia were common reasons for both short- and intermediate-term readmission of patients following esophagectomy. Interventions focused on reducing the risk of postoperative infection and pneumonia may reduce hospital readmissions. Gastrointestinal stricture and dysphagia were associated with increased risk of intermediate readmission and should be examined in the context of morbidity associated with pyloric procedures (e.g., pyloromyotomy) at the time of esophagectomy.

  View details for DOI 10.21037/jtd-21-637

  View details for PubMedID 34527309

  View details for PubMedCentralID PMC8411130

• Surgical resection for patients with pulmonary aspergillosis in the national inpatient sample JOURNAL OF THORACIC DISEASE Patel, D. C., Bhandari, P., Epstein, D. J., Liou, D. Z., Backhus, L. M., Berry, M. F., Shrager, J. B., Lui, N. S. 2021

  View details for DOI 10.21037/jtd-21-151

  View details for Web of Science ID 000684526500001

• Short-term and intermediate-term readmission after esophagectomy JOURNAL OF THORACIC DISEASE Wang, Y., Yang, C., He, H., Buchan, J. M., Patel, D. C., Liou, D. Z., Lui, N. S., Berry, M. F., Shrager, J. B., Backhus, L. M. 2021

  View details for DOI 10.21037/jtd-21-637

  View details for Web of Science ID 000682802900001

• Early Discharge after Lobectomy for Lung Cancer does not Equate to Early Readmission. The Annals of thoracic surgery Patel, D. C., Leipzig, M., Jeffrey Yang, C., Wang, Y., Shrager, J. B., Backhus, L. M., Lui, N. S., Liou, D. Z., Berry, M. F. 2021

  Abstract

  BACKGROUND: Enhanced recovery after surgery (ERAS) pathways in several specialties reduce length of stay, but accelerated discharge after thoracic surgery is not well characterized. This study tested the hypothesis that patients discharged on post-operative day 1 (POD1) after lobectomy for lung cancer have an increased risk of readmission.METHODS: Patients who underwent a lobectomy for lung cancer between 2011-2019 in the American College of Surgeons National Surgical Quality Improvement Program database were identified. Readmission rates were compared between patients discharged on postoperative day 1 (POD1) and patients discharged POD 2-6. Early discharge and readmission predictors were evaluated using multivariable logistic regression analysis.RESULTS: Only 854 (3.8%) of 22,585 patients that met inclusion criteria were discharged on POD1, though POD1 discharge rates increased from 2.3% to 8.1% (p< 0.001) from 2011 to 2019. Median hospitalization for POD2-6 patients was 4 days (IQR: 3-5). Patient characteristics associated with a lower likelihood of POD1 discharge were increasing age, smokers, or history of dyspnea, while a minimally invasive approach was the strongest predictor of early discharge (AOR 5.42, p<0.001). Readmission rates were not significantly different for POD1 and POD2-6 groups in univariate analysis (6.0% vs 7.0%, p=0.269). Further, POD1 discharge was not a risk factor for readmission in multivariable analysis (AOR 1.10, p=0.537).CONCLUSIONS: Select patients can be discharged on POD1 after lobectomy for lung cancer without an increased readmission risk, supporting this accelerated discharge target inclusion in lobectomy ERAS protocols.

  View details for DOI 10.1016/j.athoracsur.2021.05.053

  View details for PubMedID 34126077

• Influence of facility volume on long-term survival of patients undergoing esophagectomy for esophageal cancer. The Journal of thoracic and cardiovascular surgery Patel, D. C., Jeffrey Yang, C., He, H., Liou, D. Z., Backhus, L. M., Lui, N. S., Shrager, J. B., Berry, M. F. 2021

  Abstract

  OBJECTIVE: This study investigated the influence of facility volume on long-term survival in patients with esophageal cancer treated with esophagectomy.METHODS: Patients treated with esophagectomy for cT1 3N0 3M0 adenocarcinoma or squamous cell carcinoma of the mid-distal esophagus in the National Cancer Database between 2006 and 2013 were stratified by annual facility esophagectomy volume dichotomized as more/less than both 6 and 20. Patient characteristics associated with facility volume were evaluated using logistic regression, and the influence of facility volume on survival was evaluated with Kaplan-Meier curves, Cox proportional hazards methods, and propensity matched analysis.RESULTS: Of 11,739 patients who had esophagectomy at 1018 facilities where annual volume ranged from 1 to 47.6 cases, 4262 (36.3%) were treated at 44 facilities with annual esophagectomy volume>6 and 1515 (12.9%) were treated at 7 facilities with annual volume>20. Higher volume was associated with significantly better 5-year survival for both annual volume > 6 (47.6% vs 40.2%; P<.001) and annual volume>20 (47.2% vs 42.3%; P<.001), which persisted in propensity matched analyses as well as Cox multivariable analysis (hazard ratio, 0.81; 95% confidence interval, 0.74-0.89; P<.001 for facility volume>6 and hazard ratio, 0.78; 95% confidence interval, 0.65-0.95; P=.01 for facility volume>20). In Cox multivariable analysis that considered facility volume as a continuous variable, higher volume continued to be associated with better survival (hazard ratio, 0.93 per 5 cases; 95% CI, 0.91-0.96; P<.001).CONCLUSIONS: Esophageal cancer patients treated with esophagectomy at higher volume facilities have significantly better long-term survival than patients treated at lower volume facilities.

  View details for DOI 10.1016/j.jtcvs.2021.05.048

  View details for PubMedID 34247867

• A new model using artificial intelligence to predict recurrence after surgical resection of stage I-II non-small cell lung cancer. Lui, N., Wei, N., Trope, W., Nesbit, S., Bhandari, P., Lee, C., Hu, H., Guo, H., Liou, D. Z., Shrager, J. B., Backhus, L., Berry, M. F., Yang, E. LIPPINCOTT WILLIAMS & WILKINS. 2021

  View details for DOI 10.1200/JCO.2021.39.15_suppl.8537

  View details for Web of Science ID 000708120604251

• Cancer diagnoses and survival rise as 65-year-olds become Medicare-eligible. Cancer Patel, D. C., He, H., Berry, M. F., Yang, C. J., Trope, W. L., Wang, Y., Lui, N. S., Liou, D. Z., Backhus, L. M., Shrager, J. B. 2021

  Abstract

  BACKGROUND: A Medicare effect has been described to account for increased health care utilization occurring at the age of 65 years. The existence of such an effect in cancer care, where it would be most likely to reduce mortality, has been unclear.METHODS: Patients aged 61 to 69 years who were diagnosed with lung, breast, colon, or prostate cancer from 2004 to 2016 were identified with the Surveillance, Epidemiology, and End Results database and were dichotomized on the basis of eligibility for Medicare (61-64 vs 65-69 years). With age-over-age (AoA) percent change calculations, trends in cancer diagnoses and staging were characterized. After matching, uninsured patients who were 61 to 64 years old (pre-Medicare group) were compared with insured patients who were 65 to 69 years old (post-Medicare group) with respect to cancer-specific mortality.RESULTS: In all, 134,991 patients were identified with lung cancer, 175,558 were identified with breast cancer, 62,721 were identified with colon cancer, and 238,823 were identified with prostate cancer. The AoA growth in the number of cancer diagnoses was highest at the age of 65 years in comparison with all other ages within the decade for all 4 cancers (P < .01, P < .001, P < .01, and P < .001, respectively). In a comparison of diagnoses at the age of 65 years with those in the 61- to 64-year-old cohort, the greatest difference for all 4 cancers was seen in stage I. In matched analyses, the 5-year cancer-specific mortality was worse for lung (86.3% vs 78.5%; P < .001), breast (32.7% vs 11.0%; P < .001), colon (57.1% vs 35.6%; P < .001), and prostate cancer (16.9% vs 4.8%; P < .001) in the uninsured pre-Medicare group than the insured post-Medicare group.CONCLUSIONS: The age threshold of 65 years for Medicare eligibility is associated with more cancer diagnoses (particularly stage I), and this results in lower long-term cancer-specific mortality for all cancers studied.LAY SUMMARY: Contributing to the current debate regarding Medicare for all, this study shows that the expansion of Medicare would improve cancer outcomes for the near elderly.

  View details for DOI 10.1002/cncr.33498

  View details for PubMedID 33778953

• 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., Kumar, A., Deng, J. Z., Raman, V., Lui, N. S., D'Amico, T. A., Berry, M. F. 2021; 273 (3): 595–605

  View details for DOI 10.1097/SLA.0000000000003231

  View details for Web of Science ID 000613888300046

• 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

• Global analysis of shared T cell specificities in human non-small cell lung cancer enables HLA inference and antigen discovery. Immunity Chiou, S. H., Tseng, D. n., Reuben, A. n., Mallajosyula, V. n., Molina, I. S., Conley, S. n., Wilhelmy, J. n., McSween, A. M., Yang, X. n., Nishimiya, D. n., Sinha, R. n., Nabet, B. Y., Wang, C. n., Shrager, J. B., Berry, M. F., Backhus, L. n., Lui, N. S., Wakelee, H. A., Neal, J. W., Padda, S. K., Berry, G. J., Delaidelli, A. n., Sorensen, P. H., Sotillo, E. n., Tran, P. n., Benson, J. A., Richards, R. n., Labanieh, L. n., Klysz, D. D., Louis, D. M., Feldman, S. A., Diehn, M. n., Weissman, I. L., Zhang, J. n., Wistuba, I. I., Futreal, P. A., Heymach, J. V., Garcia, K. C., Mackall, C. L., Davis, M. M. 2021; 54 (3): 586–602.e8

  Abstract

  To identify disease-relevant T cell receptors (TCRs) with shared antigen specificity, we analyzed 778,938 TCRβ chain sequences from 178 non-small cell lung cancer patients using the GLIPH2 (grouping of lymphocyte interactions with paratope hotspots 2) algorithm. We identified over 66,000 shared specificity groups, of which 435 were clonally expanded and enriched in tumors compared to adjacent lung. The antigenic epitopes of one such tumor-enriched specificity group were identified using a yeast peptide-HLA A∗02:01 display library. These included a peptide from the epithelial protein TMEM161A, which is overexpressed in tumors and cross-reactive epitopes from Epstein-Barr virus and E. coli. Our findings suggest that this cross-reactivity may underlie the presence of virus-specific T cells in tumor infiltrates and that pathogen cross-reactivity may be a feature of multiple cancers. The approach and analytical pipelines generated in this work, as well as the specificity groups defined here, present a resource for understanding the T cell response in cancer.

  View details for DOI 10.1016/j.immuni.2021.02.014

  View details for PubMedID 33691136

• Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH): clinical characteristics and progression to carcinoid tumor. The European respiratory journal Yang Sun, T., Hwang, G., Pancirer, D., Hornbacker, K., Codima, A., Lui, N. S., Raj, R., Kunz, P., Padda, S. K. 2021

  View details for DOI 10.1183/13993003.01058-2021

  View details for PubMedID 34795035

• Perioperative Outcomes After Combined Esophagectomy and Lung Resection. The Journal of surgical research Patel, D. C., Bhandari, P., Shrager, J. B., Berry, M. F., Backhus, L. M., Lui, N. S., Liou, D. Z. 2021; 270: 413-420

  Abstract

  The impact of concomitant lung resection during esophagectomy on short-term outcomes is not well characterized. This study tests the hypothesis that lung resection at the time of esophagectomy is not associated with increased perioperative morbidity or mortality.Perioperative outcomes for esophageal cancer patients who underwent esophagectomy alone (EA) were compared to patients who had concurrent esophagectomy and lung resection (EL) using the NSQIP database between 2006-2017. Predictors of morbidity and mortality, including combined surgery, were evaluated using multivariable logistic regression.Among the 6,225 study patients, 6,068 (97.5%) underwent EA and 157 (2.5%) underwent EL. There were no differences in baseline characteristics between the two groups. Operating time for EL was longer than EA (median 416 versus 371 minutes, P < 0.01). Median length of stay was 10 d for both groups. Perioperative mortality was not significantly different between EL and EA patients (5.1% versus 2.8%, P = 0.08). EL patients had higher rates of postoperative pneumonia (22.3% versus 16.2%, P = 0.04) and sepsis (11.5% versus 7.1%, P = 0.03), however major complication rates overall were similar (40.8% versus 35.3%, P = 0.16). Combining lung resection with esophagectomy was not independently associated with increased postoperative morbidity (AOR 1.21 [95% CI 0.87-1.69]) or mortality (AOR 1.63 [95% CI 0.74-3.58]).Concurrent lung resection during esophagectomy is not associated with increased mortality or overall morbidity, but is associated with higher rates of pneumonia beyond esophagectomy alone. Surgeons considering combined lung resection with esophagectomy should carefully evaluate the patient's risk for pulmonary complications and pursue interventions preoperatively to optimize respiratory function.

  View details for DOI 10.1016/j.jss.2021.09.037

  View details for PubMedID 34775148

• 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. n., Hornbacker, K. n., 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

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

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

  View details for PubMedID 33479860

• Use of a Personalized Multimedia Education Platform Improves Preoperative Teaching for Lung Cancer Patients. Seminars in thoracic and cardiovascular surgery Benson, J. n., Bhandari, P. n., Lui, N. n., Berry, M. n., Liou, D. Z., Shrager, J. n., Ayers, K. n., Backhus, L. M. 2021

  Abstract

  We sought to develop and evaluate a personalized multimedia education (ME) tool for pre-operative patient education to improve patient health knowledge, quality of life and satisfaction with care in thoracic surgery. The ME tool was developed and deployed in outpatient clinic during preoperative teaching for patients undergoing surgical resection for lung cancer for quality improvement. Patients were given an electronic survey prior to preoperative teaching and at initial post-operative visit to assess teaching effectiveness and care satisfaction. Sequential patients received either standard preoperative teaching or teaching using the ME tool. Pre- and postoperative survey responses were compared using independent sample paired t-test and multivariable linear regression modeling for adjustment. The final ME tool was an iPad application that incorporated real-time annotations of 3-dimensional, interactive anatomic diagrams. The tool featured video tours of operations, and radiology image import for annotation by the surgeon. Forty-eight patients were included in this pilot study (standard education (SE) n=26; ME, n=22). ME patients had significantly higher satisfaction scores compared to SE patients with respect to length of education materials, clarity of content, supportiveness of content and willingness to recommend materials to others. There was no difference in length of clinic visit between groups. Both patient and provider input can be used to create an innovative electronic preoperative educational tool that prepares and empowers patients in shared decision-making before surgery. Improvements in health literacy and self-efficacy may be more difficult to achieve but remain important as multimedia teaching tools are further developed.

  View details for DOI 10.1053/j.semtcvs.2021.03.003

  View details for PubMedID 33711462

• Commentary: An innovative, minimally-invasive approach to post-pneumonectomy bronchopleural fistula Comment JTCVS TECHNIQUES Elliott, I. A., Bedi, H. S., Lui, N. S. 2020; 4: 351-352

  View details for DOI 10.1016/j.xjtc.2020.08.032

  View details for Web of Science ID 000655724800132

• Commentary: An innovative, minimally-invasive approach to post-pneumonectomy bronchopleural fistula. JTCVS techniques Elliott, I. A., Bedi, H. S., Lui, N. S. 2020; 4: 351-352

  View details for DOI 10.1016/j.xjtc.2020.08.032

  View details for PubMedID 34318072

  View details for PubMedCentralID PMC8304844

• 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. 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): 245-251

  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

• 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. n., 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. n., Teymourtash, M. n., Berry, M. n., Backhus, L. n., Bhandari, P. n., He, H. n., Benson, J. n., Wang, Y. Y., Yevudza, E. n., Lui, N. n., Shrager, J. n. 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. n., 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

• 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. n., Moding, E. J., Nabet, B. Y., Almanza, D. n., Kunder, C. n., Stehr, H. n., Yoo, C. H., Rhee, S. n., Xiang, M. n., Chabon, J. J., Hamilton, E. n., Kurtz, D. M., Gojenola, L. n., 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. n., Neal, J. W., Wakelee, H. A., Alizadeh, A. A., Loo, B. W., Diehn, M. n. 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. n., Backhus, L. M., Raees, S. n., Trope, W. n., Nash, A. n., 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 ΔDLCO 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. n., Juniper, G. n., van den Berg, N. S., Nisho, N. n., Broadt, T. n., Welch, A. R., Yi, G. S., Raymundo, R. C., Chirita, S. U., Lu, G. n., Krishnan, G. n., Lee, Y. J., Kapoor, S. n., Zhou, Q. n., Colevas, A. D., Lui, N. S., Poultsides, G. A., Li, G. n., 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. n., Raman, V. n., Patel, D. n., Lui, N. n., Backhus, L. n., Shrager, J. n., Berry, M. F., Liou, D. n. 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. n., Lui, N. n., Liou, D. n., Berry, M. n., 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. n., Shah, S. A., Liou, D. n., Wang, H. n., 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. n., Reveron-Thornton, R. n., 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. n., MacArthur, J. W., Lui, N. 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

• 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

• 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