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2.
Ann Thorac Surg ; 113(1): 200-208, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-33971174

RESUMO

BACKGROUND: Whether extrapleural pneumonectomy (EPP) or extended pleurectomy/decortication (P/D) is the optimal resection for malignant pleural mesothelioma remains controversial. We therefore compared perioperative outcomes and long-term survival of patients who underwent EPP versus P/D. METHODS: Patients with the diagnosis of malignant pleural mesothelioma who underwent either EPP or P/D from 2000 to 2019 were identified from our departmental database. Propensity score matching was performed to minimize potential confounders for EPP or P/D. Survival analysis was performed by the Kaplan-Meier method and Cox multivariable analysis. RESULTS: Of 282 patients, 187 (66%) underwent EPP and 95 (34%) P/D. Even with propensity score matching, perioperative mortality was significantly higher for EPP than for P/D (11% vs 0%; P = .031); when adjusted for perioperative mortality, median overall survival between EPP and P/D was 15 versus 22 months, respectively (P = .276). Cox multivariable analysis for the matched cohort identified epithelioid histology (hazard ratio [HR], 0.56; P = .029), macroscopic complete resection (HR, 0.41; P = .004), adjuvant radiation therapy (HR, 0.57; P = .019), and more recent operative years (HR, 0.93; P = .011)-but not P/D-to be associated with better survival. Asbestos exposure (HR, 2.35; P = .003) and pathologic nodal disease (HR, 1.61; P = .048) were associated with worse survival. CONCLUSIONS: In a multimodality treatment setting, P/D and EPP had comparable long-term oncologic outcomes, although P/D had much lower perioperative mortality. The goal of surgical cytoreduction should be macroscopic complete resection achieved by the safest operation a patient can tolerate.


Assuntos
Mesotelioma Maligno/cirurgia , Pleura/cirurgia , Neoplasias Pleurais/cirurgia , Pneumonectomia/métodos , Idoso , Feminino , Humanos , Masculino , Mesotelioma Maligno/mortalidade , Pessoa de Meia-Idade , Neoplasias Pleurais/mortalidade , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de Tempo
3.
Ann Thorac Surg ; 113(3): 975-983, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-33838123

RESUMO

BACKGROUND: Whether robotic segmentectomies are advantageous is unclear. We describe our experience with the robot, comparing patient populations and outcomes with video-assisted thoracoscopic surgery (VATS) and open resection. METHODS: Patients who underwent anatomic segmentectomy from 2004 to 2019 were reviewed. Resection methods were categorized as robotic, VATS, or open. Segmentectomies were categorized as simple or complex. Baseline characteristics and perioperative outcomes were analyzed from 2015 to 2019 due to implementation of the Enhanced Recovery After Surgery pathway for all thoracic surgery patients and to thus minimize confounders resulting from the Enhanced Recovery After Surgery protocol. RESULTS: Since 2004, an increase has occurred in segmentectomies, including robotic and complex segmentectomies. Of the 222 segmentectomies performed from 2015 to 2019, 77 (35%) were robotic, 40 VATS (18%), and 105 open (47%). More complex segmentectomies were performed in the robotic group compared with VATS and open (45% vs 15% vs 22%; P < .001). Operative time for robotic resections were longer compared with VATS and open (205 vs 147 vs 147 minutes; P < .001) but had lower blood loss (50 vs 75 vs 100 mL; P < .001) and shorter chest tube days (2 vs 2 vs 3 days; P = .004) and lengths of stay (3 vs 3 vs 4 days; P < .001). Perioperative mortality was low in all groups. No robotic segmentectomy was converted to open compared with 7.5% for VATS (P = .038). Prolonged air leak was lower for robotic compared with open (4% vs 13%; P = .038). CONCLUSIONS: Robotic segmentectomy has increased in our institution, with a concurrent rise in atypical segmentectomies. Despite performing more complex procedures, there were no conversions and low perioperative morbidity and mortality. Our results suggest that the robotic platform can facilitate performance of complex anatomic segmentectomies.


Assuntos
Neoplasias Pulmonares , Procedimentos Cirúrgicos Robóticos , Humanos , Neoplasias Pulmonares/cirurgia , Mastectomia Segmentar , Seleção de Pacientes , Pneumonectomia/métodos , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/métodos , Cirurgia Torácica Vídeoassistida/métodos
4.
Ann Thorac Surg ; 113(3): 1008-1014, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-33774003

RESUMO

BACKGROUND: Psychiatric comorbidities (PCs) have been associated with poor surgical outcomes in several malignancies. However, the impact of PCs on surgical outcomes for non-small cell lung cancer (NSCLC) remains largely unknown. METHODS: NSCLC patients who underwent pulmonary resection at a single institution between 2006 and 2017 were included. Presence of preoperative PCs was identified by documented diagnostic codes. Demographic, histopathologic, perioperative, and survival data were analyzed. Categorical variables were compared using the χ2 or Fisher exact test. Overall and disease-free survival was analyzed using Kaplan-Meier method. Univariable and multivariable logistic regression analyses were performed for 30-day readmission. RESULTS: Among 2907 patients, PCs were present preoperatively in 180 (6%), including anxiety, 130 (72%); depression, 52 (29%); adjustment disorder, 28 (16%); alcohol abuse, 16 (9%); sleep disorder, 8 (4%); and schizophrenia, 3 (2%). Patients with PCs were younger, with fewer cardiovascular complications. There were no differences in length of stay. However, PCs led to increased 30-day readmission (12% vs 6%, P = .004). Reasons for readmission did not differ between groups (P = .679). Multivariable analysis showed PCs independently predicted 30-day readmission (odds ratio, 2.00; P = .005). Importantly, there were no differences in 30- or 90-day mortality (P = .495 and P = .748, respectively), overall survival (P = .439), or disease-free survival (P = .924). CONCLUSIONS: NSCLC patients with and without PCs experienced similar perioperative and long-term outcomes, suggesting that individuals should not be denied surgical care on the basis of such comorbidities. However, further research should seek to identify reasons for increased risk of readmission for patients with PCs and validate these findings in other settings.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/complicações , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Humanos , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/cirurgia , Razão de Chances , Readmissão do Paciente , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
5.
Am Surg ; 87(12): 1934-1945, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34553636

RESUMO

BACKGROUND: Little is known regarding the impact of operating room (OR) personnel generation on their perceptions to various surgeon behaviors. We aimed to characterize these relationships by evaluating their responses to 5 realistic intraoperative scenarios. METHODS: Operating room personnel were asked to assess surgeon OR behavior across a standardized set of 5 scenarios via an online survey. For each scenario, respondents were asked to identify the behavior as either acceptable, unacceptable but would ignore, unacceptable and would confront the surgeon, or unacceptable and would report to management. Chi-squared analyses were used to compare responses to surgeon behavior with respondent generation. RESULTS: There were 3101 respondents, of which 41% of respondents were baby boomers (n = 1280), 31% were generation (Gen) X (n = 955), and 28% were Gen Y (n = 866). Overall, when compared to Gen X or Gen Y, baby boomers were significantly more likely to find surgeon behaviors of impatience (P < .001), being late for a case (P < .001), swearing in the OR (P < .001), and shouting with a bleeding patient (P = .001) to be inappropriate and would talk to the surgeon. Alternatively, Gen Y respondents were more likely to find fault with surgeon behaviors that deviate from rules and regulations, such as forgetting a time-out (P = .001), when compared to baby boomers and Gen X respondents. DISCUSSION: Results of our study demonstrate that OR personnel generation affects their perceptions and response to surgeon behavior. Understanding these tendencies can guide efforts to improve OR interactions among team members.


Assuntos
Atitude do Pessoal de Saúde , Comportamento , Corpo Clínico Hospitalar/psicologia , Recursos Humanos de Enfermagem Hospitalar/psicologia , Salas Cirúrgicas , Cirurgiões/psicologia , Estudos Transversais , Feminino , Humanos , Relação entre Gerações , Masculino , Equipe de Assistência ao Paciente
6.
J Surg Oncol ; 124(4): 699-703, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34057733

RESUMO

BACKGROUND AND OBJECTIVES: Adoptive T-cell therapies (ACTs) using expansion of tumor-infiltrating lymphocyte (TIL) populations are of great interest for advanced malignancies, with promising response rates in trial settings. However, postoperative outcomes following pulmonary TIL harvest have not been widely documented, and surgeons may be hesitant to operate in the setting of widespread disease. METHODS: Patients who underwent pulmonary TIL harvest were identified, and postoperative outcomes were studied, including pulmonary, cardiovascular, infectious, and wound complications. RESULTS: 83 patients met inclusion criteria. Pulmonary TIL harvest was undertaken primarily via a thoracoscopy with a median operative blood loss and duration of 30 ml and 65 min, respectively. The median length of stay was 2 days. Postoperative events were rare, occurring in only five (6%) patients, including two discharged with a chest tube, one discharged with oxygen, one episode of urinary retention, and one blood transfusion. No reoperations occurred. The median time from TIL harvest to ACT infusion was 37 days. CONCLUSIONS: Pulmonary TIL harvest is safe and feasible, without major postoperative events in our cohort. All patients were able to receive intended ACT infusion without delays. Therefore, thoracic surgeons should actively participate in ongoing ACT trials and aggressively seek to enroll patients on these protocols.


Assuntos
Imunoterapia Adotiva/métodos , Neoplasias Pulmonares/terapia , Linfócitos do Interstício Tumoral/imunologia , Melanoma/terapia , Procedimentos Cirúrgicos Pulmonares/métodos , Adulto , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/secundário , Masculino , Melanoma/imunologia , Melanoma/patologia , Pessoa de Meia-Idade , Cuidados Pós-Operatórios , Prognóstico , Estudos Prospectivos
7.
Semin Thorac Cardiovasc Surg ; 33(4): 1158-1168, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33711460

RESUMO

Duty-hour restrictions have implications on trainee operative exposure necessary to meet minimum case-volume requirements. We utilized a previously validated simulation model to evaluate the effect of program volume, trainee numbers and complement, and rotation schedule on the probability of achieving adequate esophagectomy case numbers for cardiothoracic surgery trainees. A ProModel simulator centered on probabilistic distributions of operative cases was utilized. Historical data from five 2-year cardiothoracic surgery training programs were obtained from 2016-2018 and used as inputs to the simulator that generated 10,000 "trainee 2-year periods" per program. Programs varied in annual average esophagectomy volume (12-91 per year), with 2-4 trainees graduating over a 2-year training period. If esophagectomy cases were distributed solely based on scheduling and institutional volume, only 60% of evaluated programs could adequately expose all trainees in esophagectomy to meet case requirements. The 3 programs with adequate esophagectomy volumes had averaged 3.3 times (range 3.0-3.6) the minimum number of board-required cases for their programs' trainees. The ability of programs to provide trainees with adequate esophagectomy volume is challenging based on institutional volume and scheduling. Through simulation, we demonstrate that programs need >2 times the expected minimum number of esophagectomies to ensure that >90% of trainees meet case-volume requirements. Programs may consider strategies such as allowing trainees to select cases based on personal need, train fewer fellows, or enable trainees to seek subspecialty exposure externally to achieve minimum esophagectomy case-load requirements.


Assuntos
Internato e Residência , Cirurgia Torácica , Competência Clínica , Educação de Pós-Graduação em Medicina , Esofagectomia/efeitos adversos , Humanos , Resultado do Tratamento
8.
J Thorac Dis ; 13(1): 464-472, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33569233

RESUMO

Social media serves as a tool to fill gaps in current efforts to promote women in cardiothoracic surgery, and, given its global reach, may be a particularly effective modality. Social media has an important role in networking and mentorship, especially for women seeking careers in specialties with relatively sparse female representation, such as cardiothoracic surgery. In addition, social media may facilitate professional interactions, collaboration, growth of online reputations, engagement in continued education, communication of novel research findings, and patient education. Herein, we review the evidence for social media in the networking and mentorship of women in cardiothoracic surgery. Future studies are needed to establish the durability of social media efforts and predictors in its effectiveness in achieving its goals.

9.
J Gastrointest Surg ; 25(9): 2185-2191, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33555525

RESUMO

BACKGROUND: Most patients undergoing esophagectomy will experience intermittent reflux of gastric and biliary content into the remnant esophagus postoperatively. The incidence of new or recurrent intestinal metaplasia following chemoradiation and surgery has not been well-described. Furthermore, post-resection guidelines do not exist regarding surveillance for metaplasia in the esophageal remnant. METHODS: Patients undergoing Ivor Lewis esophagectomy after concurrent chemoradiation for a diagnosis of esophageal adenocarcinoma from 2006 to 2018 were identified. Pathology records were reviewed for the presence of intestinal metaplasia on pretreatment biopsies, surgical specimen, or post-resection biopsies. RESULTS: In total, 619 patients met inclusion criteria, including 267 (43%) who had intestinal metaplasia noted either prior to or at the time of esophagectomy. The median duration of metaplastic disease prior to resection was 4.4 months. During a median follow-up time of 28 months (interquartile range, 12-60), intestinal metaplasia was noted in the remnant esophagus in 12 (2%) patients, 7 of whom had a prior history of metaplasia. Local recurrence of adenocarcinoma was also uncommon, and occurred in 37/577 (6%) of patients with complete resections, with similar event rates among those with and without a prior history of metaplasia (14/249 [6%] vs. 23/328 [7%], p = 0.614). CONCLUSIONS: Our findings suggest that despite several factors predisposing to mucosal damage following esophagectomy, occurrence of new intestinal metaplasia after trimodality therapy in our patient population appears to be rare, even among patient with a previous history of this pathologic finding, which may have significant implications for surveillance and cost-savings after resection.


Assuntos
Esôfago de Barrett , Neoplasias Esofágicas , Esôfago de Barrett/cirurgia , Neoplasias Esofágicas/cirurgia , Esofagectomia/efeitos adversos , Esofagoscopia , Humanos , Metaplasia , Recidiva Local de Neoplasia
11.
Ann Thorac Surg ; 111(4): 1111-1117, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-32980327

RESUMO

BACKGROUND: As strategies promoting enhanced recovery protocols and opioid minimization techniques are increasingly prioritized, use of nonsteroidal antiinflammatory drugs continues to rise. Whether this prevalent use poses increased risk for bleeding or renal dysfunction in surgical populations after extensive dissection and fluid shifts is unclear. METHODS: We reviewed records of patients undergoing esophagectomy for a diagnosis of esophageal adenocarcinoma at a single institution from 2006 to 2018 for ketorolac administration during the postoperative hospital admission, as well as the occurrence of postoperative events, defined as the need for blood product transfusion and/or acute kidney injury. RESULTS: We identified 1019 patients, 123 of whom experienced postoperative events (12%). Ketorolac was administered to 686 (67%). Furthermore, ketorolac use steadily increased over the study period; 36 of 72 patients received this medication in 2006 (49%), and 76 of 83 in 2018 (92%). Multivariable logistic regression failed to identify a relationship between ketorolac administration (assessed as a binary covariate) and postoperative events (P = .657). Additional examination for a dose-response relationship using the cumulative total dose from the time of surgery to discharge also did not demonstrate a relationship with postoperative events (P = .829). In an effort to evaluate a more homogeneous population, we performed a subgroup analysis using only patients treated with trimodality therapy, which showed similar findings. CONCLUSIONS: Ketorolac has become a staple of multimodal postesophagectomy analgesic regimens. Importantly, this medication does not pose risk for acute kidney injury or bleeding after surgery.


Assuntos
Injúria Renal Aguda/etiologia , Neoplasias Esofágicas/terapia , Esofagectomia/efeitos adversos , Hemorragia Pós-Operatória/etiologia , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/epidemiologia , Idoso , Neoplasias Esofágicas/diagnóstico , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Hemorragia Pós-Operatória/diagnóstico , Hemorragia Pós-Operatória/epidemiologia , Estudos Retrospectivos , Estados Unidos/epidemiologia
13.
J Thorac Cardiovasc Surg ; 162(1): 296-305, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-32713636

RESUMO

OBJECTIVES: Although colorectal cancer bowel segment location has been shown to independently predict the outcomes in early stage disease, it has not been previously studied in the setting of pulmonary metastases. We sought to determine whether colorectal cancer location affects survival after pulmonary metastasectomy. METHODS: Patients who had undergone pulmonary metastasectomy for colorectal cancer at a single institution from 2011 to 2018 were reviewed. Univariable and multivariable Cox regression analyses were performed to identify predictors of overall survival and disease-free survival. The Kaplan-Meier survival method was used to determine differences between groups. RESULTS: A total of 194 patients were evaluated. The median follow-up, survival time, and 5-year survival rate were 36.8 months, 75.8 months, and 57%, respectively, and 122 patients (63%) had experienced disease recurrence at any location. On univariable analysis, age, primary tumor location, pulmonary nodule size, ≥3 pulmonary nodules, and intrathoracic nodal disease were associated with overall survival. On multivariable analysis, patients with left-sided tumors experienced a survival benefit (hazard ratio, 0.31; P = .036). Kaplan-Meier analysis revealed a median survival time of 90 months (95% confidence interval, 82 months to not reached) compared with 55 months (95% confidence interval, 49 months to not reached) for patients with left-sided and rectal tumors, respectively, after metastasectomy (P = .078). Location was not associated with disease-free survival on Cox multivariable regression. CONCLUSIONS: We found that left-sided colorectal cancer is associated with prolonged survival after pulmonary metastasectomy. Future investigations are required to determine the validity of such findings, including the effect of location in the prognostication for patients who are candidates for pulmonary metastasectomy.


Assuntos
Neoplasias Colorretais , Neoplasias Pulmonares , Pneumonectomia/mortalidade , Idoso , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
14.
Eur J Cardiothorac Surg ; 59(1): 100-108, 2021 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-32864702

RESUMO

OBJECTIVES: Major pathological response (MPR) is prognostic of outcomes for patients with non-small-cell lung cancer following neoadjuvant chemotherapy and is used as the primary end point in neoadjuvant immunotherapy trials. We studied the influence of pathological nodal disease on patterns and timing of recurrence among patients with MPR. METHODS: Patients treated with neoadjuvant chemotherapy for stages I-III non-small-cell lung cancer were identified. Surgical specimens were histopathologically examined for tumour viability, categorized as ≤10% viability (MPR) or >10% (NoMPR). Overall survival and disease-free survival were evaluated with emphasis upon MPR and pathological nodal disease. RESULTS: Among 307 patients, 58 (19%) had MPR within primary tumour and 42 (14%) had MPRypN0. In the MPR group, the frequency of cN0 and cN+ disease was 18 (31%) and 40 (69%); similarly, the frequency of ypN0, ypN1 and ypN2 was 72% (42/58), 16% (9/58) and 12% (7/58), respectively. When evaluating only those with MPR, recurrence rates among those with MPRypN0, MPRypN1 and MPRypN2 were 33% (14/42), 44% (4/9) and 71% (5/7) (P = 0.16). The median time-to-recurrence in MPRypN0, MPRypN1 and MPRypN2 was 40, 10 and 14 months (P = 0.006). Distant recurrences were less common among those with MPRypN0 [MPRypN0, 26% (11/42); MPRypN1, 44% (4/9); MPRypN2, 71% (5/7); P = 0.047]. Though the median disease-free survival was prolonged among those with MPR vs NoMPR (120 vs 25 months, P < 0.0001), only those with MPRypN0 had prolonged disease-free survival in comparison to other groups upon pairwise comparisons, while MPRypN+ experienced no benefit. CONCLUSIONS: MPRypN0 represents the most favourable surrogate end point following neoadjuvant chemotherapy. Patients with ypN1-2 are at the risk of early recurrence regardless of primary tumour MPR, warranting intensive surveillance and consideration for additional adjuvant therapy. We highlight that MPRypN0 is the most rigorous end point and should be considered as a surrogate end point in future neoadjuvant trials.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Quimioterapia Adjuvante , Intervalo Livre de Doença , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/epidemiologia , Linfonodos , Terapia Neoadjuvante , Recidiva Local de Neoplasia/epidemiologia , Estadiamento de Neoplasias
15.
Ann Thorac Surg ; 111(4): 1133-1140, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-32857997

RESUMO

BACKGROUND: Surgeons have shifted away from the practice of en bloc esophagectomy, particularly in the era of neoadjuvant therapies. Although some still advocate for this radical approach, contemporary data establishing its superiority are sparse. We hypothesized that a more complete, radical resection could be completed in the setting of chemoradiation without adding morbidity. METHODS: Patients undergoing esophagectomy after neoadjuvant chemoradiation for esophageal adenocarcinoma from 2006-2018 were evaluated. Outcomes after right transthoracic en bloc esophagectomy were compared with standard esophagectomy to determine the impact on outcomes. A Cox proportional hazard model was evaluated, and logistic regression was performed to determine the impact of en bloc resection on postoperative morbidity. RESULTS: A total of 604 patients were identified, including 133 (22%) who underwent modified en bloc esophagectomy. Positive margins were most likely to occur in standard esophagectomy (35 of 471, 7%) vs en bloc (3 of 133, 2%) (P = .026). En bloc resection yielded a greater lymph node harvest (27; interquartile range, 22-36), as compared to standard esophagectomy (22; interquartile range, 17-28), P < .001. Multivariable analysis demonstrated prolonged progression-free survival with en bloc resection (hazard ratio, 0.74; P = .041), with 3-year freedom from locoregional recurrences of 78% and 90% for standard and en bloc approaches (P = .044). There were no differences in cardiopulmonary, gastrointestinal, or wound complications, as well as leak or chylothorax. CONCLUSIONS: Our experience demonstrates improved locoregional disease control with en bloc esophagectomy, with equivalent morbidity. Although these results may be multifactorial, including adequate clearance of both primary tumor and nodal micrometastases, this approach is safe and feasible.


Assuntos
Adenocarcinoma/terapia , Neoplasias Esofágicas/terapia , Esofagectomia/métodos , Estadiamento de Neoplasias , Adenocarcinoma/diagnóstico , Idoso , Quimiorradioterapia , Neoplasias Esofágicas/diagnóstico , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estudos Prospectivos , Resultado do Tratamento
16.
J Thorac Oncol ; 16(1): 127-139, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33096269

RESUMO

INTRODUCTION: The combination of programmed cell death protein-1 or programmed death-ligand 1 immune checkpoint blockade and chemotherapy has revolutionized the treatment of advanced NSCLC, but the mechanisms underlying this synergy remain incompletely understood. In this study, we explored the relationships between neoadjuvant chemotherapy and the immune microenvironment (IME) of resectable NSCLC to identify novel mechanisms by which chemotherapy may enhance the effect of immune checkpoint blockade. METHODS: Genomic, transcriptomic, and immune profiling data of 511 patients treated with neoadjuvant chemotherapy followed by surgery (NCT) versus upfront surgery (US) were compared with determined differential characteristics of the IMEs derived from whole-exome sequencing (NCT = 18; US = 73), RNA microarray (NCT = 45; US = 202), flow cytometry (NCT = 17; US = 39), multiplex immunofluorescence (NCT = 10; US = 72), T-cell receptor sequencing (NCT = 16 and US = 63), and circulating cytokines (NCT = 18; US = 73). RESULTS: NCT was associated with increased infiltration of cytotoxic CD8+ T cells and CD20+ B cells. Moreover, NCT was associated with increases in CD8+CD103+ and CD4+CD103+PD-1+TIM3- tissue resident memory T cells. Gene expression profiling supported memory function of CD8+ and CD4+ T cells. However, NCT did not affect T-cell receptor clonality, richness, or tumor mutational burden. Finally, NCT was associated with decreased plasma BDNF (TrkB) at baseline and week 4 after surgery. CONCLUSIONS: Our study supports that, in the context of resectable NSCLC, neoadjuvant chemotherapy promotes antitumor immunity through T and B cell recruitment in the IME and through a phenotypic change toward cytotoxic and memory CD8+ and CD4+ memory helper T cells.


Assuntos
Neoplasias Pulmonares , Terapia Neoadjuvante , Linfócitos B , Linfócitos T CD8-Positivos , Humanos , Memória Imunológica , Neoplasias Pulmonares/tratamento farmacológico , Microambiente Tumoral
17.
Ann Thorac Surg ; 112(2): 423-429, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33129774

RESUMO

BACKGROUND: We have previously demonstrated that Enhanced Recovery After Surgery protocols are associated with a reduction in pulmonary complications. As a component of enhanced recovery pathways, intercostal nerve blocks with liposomal bupivacaine are increasingly utilized, but the extent to which this element may contribute to such outcomes has not been evaluated. METHODS: Patients undergoing lung resection for stage I to III non-small cell lung cancer at a single institution from 2006 to 2017 were examined for major postoperative pulmonary morbidity, defined as pneumonia, acute respiratory distress syndrome, respiratory arrest, reintubation, bronchoscopy, or need for discharge with oxygen. Pharmacy records were queried for administration of liposomal bupivacaine via posterior intercostal nerve block. Patients treated with and without liposomal bupivacaine were compared in a logistic regression to determine the impact on pulmonary morbidity. RESULTS: A total of 2865 patients were identified, including 860 (30%) who were treated with liposomal bupivacaine via posterior intercostal block. Pulmonary morbidity occurred in 455 (16%). Adoption of liposomal bupivacaine analgesia occurred over several years, beginning in 2012 to full adoption by 2017. Liposomal bupivacaine management was associated with a reduction in pulmonary complications, as compared with nonuse (odds ratio, 0.63; P = .006). Additional factors associated with the occurrence of pulmonary morbidity were age, body mass index, smoking, spirometry values, and operative blood loss. CONCLUSIONS: As a component of an active enhanced recovery program, liposomal bupivacaine is associated with a reduction in major pulmonary complications, and utilization should be evaluated on a hospital-by-hospital basis.


Assuntos
Bupivacaína/administração & dosagem , Manejo da Dor/métodos , Dor Pós-Operatória/tratamento farmacológico , Pneumonectomia/efeitos adversos , Idoso , Anestésicos Locais/administração & dosagem , Feminino , Seguimentos , Humanos , Incidência , Nervos Intercostais , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Bloqueio Nervoso/métodos , Medição da Dor/métodos , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/epidemiologia , Estudos Retrospectivos , Estados Unidos/epidemiologia
18.
J Thorac Cardiovasc Surg ; 161(4): 1497-1504.e2, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32331820

RESUMO

OBJECTIVES: Comprehensive local consolidative therapy led to improved overall survival in oligometastatic non-small cell lung cancer in a recent phase II trial, yet the role of pulmonary resection in ongoing oligometastatic trials is a matter of controversy. We sought to examine outcomes after pulmonary resection with radiotherapy used as a benchmark comparator. METHODS: Patients treated at a single institution (2000-2017) with cT1-3N0-2M1 non-small cell lung cancer, 3 or less synchronous metastases, and performance status 0 to 1, and who received comprehensive local consolidative therapy were analyzed according to local consolidative therapy modality for the primary lesion. Progression was analyzed with death as a competing risk. RESULTS: Of 88 patients meeting inclusion criteria, 63 (71.6%) received radiotherapy for local consolidative therapy modality for the primary lesion and 25 (28.4%) underwent surgery (lobectomy 20/25 [80.0%], pneumonectomy 3/25 [12.0%], sublobar 2/25 [8.0%]). Time from diagnosis to local consolidative therapy modality for the primary lesion was similar. Surgical patients were younger and had lower intrathoracic disease burden. Ninety-day post-treatment mortality was low (surgery 0/25 [0.0%], radiotherapy 1/63 [1.6%]). Median postoperative survival time was 55.2 months (95% confidence interval, 20.1 to not reached), with 1- and 5-year overall survivals of 95.7% and 48.0%, respectively. After radiotherapy, median postoperative survival time was 23.4 months (confidence interval, 17.2-35.9); 1- and 5-year overall survivals were 74.3% and 24.2%, respectively. No differences were observed between modalities in site of first failure, cumulative incidence of locoregional failure (P = .635), or systemic progression (P = .747). CONCLUSIONS: Pulmonary resection is feasible and associated with long-term survival in selected patients with synchronous oligometastatic non-small cell lung cancer. Surgery should remain a local consolidative therapeutic option for patients with operable oligometastatic non-small cell lung cancer enrolled in ongoing and future randomized clinical trials.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/cirurgia , Pneumonectomia , Idoso , Carcinoma Pulmonar de Células não Pequenas/secundário , Estudos de Coortes , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Seleção de Pacientes , Taxa de Sobrevida , Resultado do Tratamento
19.
J Thorac Cardiovasc Surg ; 162(5): 1404-1412.e2, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33010880

RESUMO

BACKGROUND: Multiple investigations have shown inferior outcomes for esophageal cancer patients with signet ring cell (SRC) histology. Traditionally, SRC adenocarcinoma has been defined by ≥50% of the tumor composed of SRC. We hypothesized that patients with SRC even <50% would show resistance to standard multimodality therapy with poorer long-term outcomes. METHODS: Patients treated with trimodality therapy for adenocarcinoma from 2006 to 2018 were evaluated for SRC on pretreatment biopsy specimens. Available hematoxylin and eosin slides containing SRC tumors were re-reviewed by an esophageal pathologist to quantify the percent composition of SRC. RESULTS: SRC histology was identified on at least 1 pathologic specimen in 106 of 819 (13%) patients. Rates of pathologic complete response (pCR) among usual-type and SRC tumors were 25% (177/713) and 10% (11/106), respectively (P = .006). The pretreatment SRC components did not independently affect the rate of pCR (1%-10% SRC: 4% [2/46] pCR; 11%-49% SRC: 25% [7/28] pCR; 50%-100% SRC: 7% [2/30] pCR). Kaplan-Meier analysis demonstrated worse survival among patients with any degree of SRC present on pretreatment biopsy, as compared with usual-type esophageal adenocarcinoma (P < .0001). Cox multivariable analysis failed to identify a relationship between increasing SRC component and poorer survival. CONCLUSIONS: We present the only known evaluation of the percentage of SRC component in esophageal carcinoma. Our data support the hypothesis that esophageal adenocarcinoma with any component of SRC are more resistant to chemoradiation with poorer survival. Pathologic reporting of esophageal adenocarcinoma should include any component of SRC. Alternative therapies in patients with any SRC component may be indicated.


Assuntos
Adenocarcinoma/terapia , Carcinoma de Células em Anel de Sinete/terapia , Quimiorradioterapia Adjuvante , Neoplasias Esofágicas/terapia , Esofagectomia , Terapia Neoadjuvante , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Idoso , Biópsia , Carcinoma de Células em Anel de Sinete/mortalidade , Carcinoma de Células em Anel de Sinete/patologia , Quimiorradioterapia Adjuvante/efeitos adversos , Quimiorradioterapia Adjuvante/mortalidade , Bases de Dados Factuais , Resistencia a Medicamentos Antineoplásicos , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Esofagectomia/efeitos adversos , Esofagectomia/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/efeitos adversos , Terapia Neoadjuvante/mortalidade , Valor Preditivo dos Testes , Tolerância a Radiação , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
20.
J Thorac Cardiovasc Surg ; 161(2): 448-454, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32340809

RESUMO

OBJECTIVES: Recent evidence has shown an association between postoperative ketorolac use and anastomotic leak in patients undergoing intestinal and colorectal operations, but this relationship has been minimally explored after esophagectomy. As the use of nonopioid pain control and enhanced recovery protocols is increasingly prioritized, determination of a possible correlation between perioperative ketorolac use and leak is essential. METHODS: Records of patients undergoing esophagectomy for adenocarcinoma at a single institution from 2006 to 2018 reviewed for occurrence of anastomotic leak. Institutional pharmacy records were queried for ketorolac administration during the surgical case through the time of discharge. Multivariable logistic regression was used to determine the relationship between ketorolac administration and anastomotic leak. RESULTS: A total of 1019 patients met inclusion criteria, the majority of whom were male (907, 89%) with a median age of 62 years. Patients predominantly presented with locoregionally advanced disease and were treated with initial chemoradiation. Ketorolac was administered to 686 patients (67%); use was observed to increase over the study period from 49% in 2006 to 92% in 2016. Conversely, anastomotic leak occurred in 87 patients (9%) overall and decreased over time from 15% (11/72) in 2006 to 2% (2/83) in 2018. Upon multivariable analysis, neither ketorolac administration evaluated as a categoric variable (odds ratio, 0.99; P = .958) or as a continuous variable using dose (odds ratio, 1.00; P = .843) demonstrated an association with anastomotic leak. CONCLUSIONS: Ketorolac in the postoperative period after esophagectomy has become an integral component of enhanced recovery pathways and does not appear to be associated with anastomotic leak.


Assuntos
Adenocarcinoma/cirurgia , Anti-Inflamatórios não Esteroides/efeitos adversos , Endoleak/induzido quimicamente , Neoplasias Esofágicas/cirurgia , Cetorolaco/efeitos adversos , Idoso , Anastomose Cirúrgica/efeitos adversos , Anastomose Cirúrgica/métodos , Anti-Inflamatórios não Esteroides/uso terapêutico , Recuperação Pós-Cirúrgica Melhorada , Esofagectomia/efeitos adversos , Esofagectomia/métodos , Feminino , Humanos , Cetorolaco/uso terapêutico , Masculino , Pessoa de Meia-Idade , Cuidados Pós-Operatórios/efeitos adversos , Cuidados Pós-Operatórios/métodos , Estudos Retrospectivos
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