Effect of Thoracic Surgery Regionalization on 1- and 3-Year Survival after Cancer Esophagectomy.

OBJECTIVE: The aim of this study was to investigate whether our previously reported improvements in short-term cancer esophagectomy outcomes after large-scale regionalization in the United States translated to longer-term survival benefit. BACKGROUND: Regionalization is associated with better early postoperative outcomes following cancer esophagectomy; however, data regarding its effect on long-term survival are mixed. METHODS: We retrospectively reviewed 461 patients undergoing cancer esophagectomy before (2009-2013, N = 272) and after (2014-2016, N = 189) regionalization. Kaplan-Meier curves and chi-square tests were used to describe 1- and 3-year survival in each era. Hierarchical logistic regression models examined the adjusted effect of regionalization on mortality. RESULTS: Compared to pre-regionalization patients, post-regionalization patients had significantly higher 1-year survival (83.1% vs 73.9%, P = 0.02) but not 3-year survival (52.9% vs 58.2%, P = 0.26).Subgroup analysis by cancer stage revealed that 1-year survival benefit was only significant among mid-stage (IIB-IIIB) patients, whereas differences in 3-year survival only approached significance among early-stage (IA-IIA) patients.In multivariable analysis, only regionalization was a predictor of lower mortality at 1 year [odds ratio (OR) 0.54, 95% confidence interval (CI) 0.29-1.00], and only thoracic specialty at 3years (OR 0.62, 95% CI 0.38-0.99). Older age, more advanced stage, and complications were associated with higher 1- and 3-year mortality. Comorbidity, minimally invasive approach, surgeon volume, facility volume, and neoadjuvant treatment were not significant in this model. CONCLUSIONS: Regionalization was associated with improved 1-year survival after cancer esophagectomy, independent of factors such as morbidity or volume in our adjusted models. This survival benefit did not persist at 3 years, likely due to the aggressive nature of the disease.

Utilization and Outcomes of Observation for Spontaneous Pneumothorax at an Integrated Health System.

INTRODUCTION: Though limited, recent evidence supports observation rather than intervention for spontaneous pneumothorax management. We sought to compare the utilization and outcomes between observation and intervention for patients with primary and secondary spontaneous pneumothoraces. METHODS: A retrospective cohort study of all adults presenting to Kaiser Permanente Northern California emergency rooms with spontaneous pneumothorax from 2016 to 2020 was performed. Those with prior pneumothoraces, tension physiology, bilateral pneumothoraces, effusions, and prior thoracic procedures or surgery on the affected side were excluded. Groups included observation versus intervention. Baseline clinicodemographic variables and outcomes were compared. Treatment was considered successful if further interventions were not required for pneumothorax resolution. Wilcoxon rank-sum tests, chi-square tests, Fischer exact tests, and multivariable logistic regression models were performed. RESULTS: Of the 386 patients with primary spontaneous pneumothorax, age, race/ethnicity, body mass index, smoking status, and the Charlson comorbidity index were not different between treatment groups. Of 86 patients with secondary spontaneous pneumothorax, age, gender, and smoking status were not different between treatment groups. Among patients with primary pneumothoraces, 83 underwent observation while 303 underwent intervention. The success rate was 92.8% for observation and 60.4% for intervention (P < 0.0001). Among patients with secondary pneumothoraces, 15 underwent observation while 71 underwent intervention, with a successful rate of 73.3% for observation and 32.4% for intervention (P = 0.003). CONCLUSIONS: Given the high success rates for observation of both small and moderate primary and secondary pneumothoraces, observation should be considered for clinically stable patients. Observation may be the superior choice for decreasing morbidity and healthcare costs.

Association of Surgical Timing with Outcomes in Early Stage Lung Cancer.

BACKGROUND: Optimal time to surgery for lung cancer is not well established. We aimed to assess whether time to surgery correlates with outcomes. METHODS: We assessed patients 18-84 years old who were diagnosed with stage I/II lung cancer at our integrated healthcare system from 2009 to 2019. Time to surgery was defined to start with disease confirmation (imaging or biopsy) prior to the surgery scheduling date. Outcomes of unplanned return to care within 30 days of lung cancer surgery, all-cause mortality, and disease recurrence were compared based on time to surgery before and after 2, 4, and 12 weeks. RESULTS: Of 2861 included patients, 70% were over 65 years old and 61% were female. Time to surgery occurred in 1-2 weeks for 6%, 3-4 weeks for 31%, 5-12 weeks for 58%, and 13-26 weeks for 5% of patients. Patients with time to surgery > 4 (vs. ≤ 4) weeks had greater risk of both death (hazard ratio (HR) 1.18, 95% confidence interval (CI) 1.00-1.39) and recurrence (HR 1.33, 95% CI 1.10-1.62). Associations were not statistically significant when dichotomizing time to surgery at 2 or 12 weeks for death (2 week HR 1.23, 95% CI 0.93-1.64; 12 week HR 1.35, 95% CI 0.97-1.88) and recurrence (2 week HR 1.54, 95% CI 0.85-2.80; 12 week HR 2.28, 95% CI 0.80-6.46). CONCLUSIONS: Early stage lung cancer patients with time to surgery within 4 weeks experienced lower rates of recurrence. Optimal time to surgical resection may be shorter than previously reported.

A clinical review of spontaneous pneumomediastinum.

Primary spontaneous pneumomediastinum is a rare, often benign and self-limited condition defined by air within the mediastinum. However, correctly distinguishing primary spontaneous pneumomediastinum from secondary causes, especially esophageal perforation, remains a diagnostic challenge. There is significant debate regarding the balance of completing a thorough but not overly invasive and costly diagnostic workup. This clinical review aims to gather the limited data regarding spontaneous pneumomediastinum management from case series and retrospective cohort studies, and presents an evaluation algorithm and treatment plan stratified by clinical history. Understanding specifically if the patient presents with coughing versus forceful vomiting is critical to help elucidate the etiology and guide management of pneumomediastinum. Patients who present with forceful vomiting or retching should be considered with higher degree of suspicion for secondary causes of pneumomediastinum, specifically esophageal perforation. However, especially in children, aggressive diagnostic workup is not warranted in every case. After ruling out other etiologies of pneumomediastinum, spontaneous pneumomediastinum can be commonly treated with symptomatic management without the aggressive use of antibiotics or diet restriction. Hospital length of stay may also be minimized on a case-by-case basis. Overall, recurrence of spontaneous pneumomediastinum is rare and outpatient follow up may be safely limited to those at highest risk of recurrence.

Are routine, daily chest radiographs (CXR) necessary following (VATS and RATS) lobectomies?

Background: Consensus guidelines regarding the amount and necessity of post-operative imaging in thoracic surgery are lacking. The efficacy of daily chest radiographs (CXR) following video-assisted (VATS) and robotic-assisted (RATS) thoracoscopic surgery in directing management has not been previously studied. We hypothesize that abnormal clinical findings, rather than abnormal imaging findings, better predict post-operative complications in patients undergoing VATS/RATS lobectomies. Methods: A retrospective review of VATS and RATS lobectomy patients were performed at a tertiary referral center from 1/1/2019-12/31/2021. Demographics, hospital course, and imaging were evaluated. Descriptive statistics, Chi-Square test, Fisher's exact, Wilcoxon rank sum, and multivariable logistic regression were performed. Our outcomes were post-operative complications requiring a procedure and extended length of stay (LOS) (>2 days post-operatively). Results: Out of 362 VATS/RATS lobectomy patients, 15 patients had post-operative complications requiring a procedure. Almost all patients who required a procedure had abnormal clinical signs and symptoms (14/15; p < 0.001) while 70 % had expected post-operative day (POD) one CXR findings (11/15; p = 0.463). Multivariable logistic regression demonstrated clinical signs and symptoms independently predicted procedural requirement (odds ratio [OR] = 48, 95 % Confidence Interval [CI]:8.5-267) while abnormal POD one imaging did not. For extended LOS, a positive smoking history (OR = 4.4, 95 % CI:1.4-14.1), number of CXRs (OR = 2.4, 95 % CI:1.8-3.2) and thoracostomy tubes (OR = 5.3, 95 % CI:1.0-27.3) were independent predictors while clinical signs and symptoms was not. Conclusion: Abnormal clinical findings may guide management more predictably than abnormal CXRs after VATS/RATS. Routine CXR in the post-operative setting may be unnecessary in those without clinical signs or symptoms. Key message: There are no consensus guidelines regarding the efficacy of routine, post-operative diagnostic studies after major thoracic lobar resections. The presence of abnormal signs or symptoms after minimally invasive lobectomies may better predict those who will require additional procedures better than the presence of abnormal routine, post-operative chest radiographs.

Differences in outcomes by race/ethnicity after thoracic surgery in a large integrated health system.

Background: Disparities exist throughout surgery. We aimed to assess for racial/ethnic disparities among outcomes in a large thoracic surgery patient population. Methods: We reviewed all thoracic surgery patients treated at our integrated health system from January 1, 2016-December 31, 2020. Post-operative outcomes including length of stay (LOS), 30-day return to the emergency department (30d-ED), 30-day readmission, 30- and 90-day outpatient appointments, and 30- and 90-day mortality were compared by race/ethnicity. Bivariate analyses and multivariable logistic regression were performed. Our multivariable models adjusted for age, sex, body mass index, Charlson Comorbidity Index, surgery type, neighborhood deprivation index, insurance, and home region. Results: Of 2730 included patients, 59.4 % were non-Hispanic White, 15.0 % were Asian, 11.9 % were Hispanic, 9.6 % were Black, and 4.1 % were Other. Median (Q1-Q3) LOS (in hours) was shortest among non-Hispanic White (37.3 (29.2-76.1)) and Other (36.5 (29.3-75.4)) patients followed by Hispanic (46.8 (29.9-78.1)) patients with Asian (51.3 (30.7-81.9)) and Black (53.7 (30.6-101.6)) patients experiencing the longest LOS (p < 0.01). 30d-ED rates were highest among Hispanic patients (21.3 %), followed by Black (19.2 %), non-Hispanic White (18.1 %), Asian (13.4 %), and Other (8.0 %) patients (p < 0.01). On multivariable analysis, Hispanic ethnicity (Odds Ratio (OR) 1.43 (95 % CI 1.03-1.97)) and Medicaid insurance (OR 2.37 (95 % CI 1.48-3.81)) were associated with higher 30d-ED rates. No racial/ethnic disparities were found among other outcomes. Conclusions: Despite parity across multiple surgical outcomes, disparities remain related to patient encounters within our system. Health systems must track such disparities in addition to standard clinical outcomes. Key message: While our large integrated health system has been able to demonstrate parity across many major surgical outcomes among our thoracic surgery patients, race/ethnicity disparities persist including in the number of post-operative return trips to the emergency department. Tracking outcome disparities to a granular level such as return visits to the emergency department and number of follow up appointments is critical as health systems strive to achieve equitable care.

Video-Assisted vs Robotic-Assisted Lung Lobectomies for Operating Room Resource Utilization and Patient Outcomes.

Importance: With increased use of robots, there is an inadequate understanding of minimally invasive modalities' time costs. This study evaluates the operative durations of robotic-assisted vs video-assisted lung lobectomies. Objective: To compare resource utilization, specifically operative time, between video-assisted and robotic-assisted thoracoscopic lung lobectomies. Design, Setting, and Participants: This retrospective cohort study evaluated patients aged 18 to 90 years who underwent minimally invasive (robotic-assisted or video-assisted) lung lobectomy from January 1, 2020, to December 31, 2022, with 90 days' follow-up after surgery. The study included multicenter electronic health record data from 21 hospitals within an integrated health care system in Northern California. Thoracic surgery was regionalized to 4 centers with 14 board-certified general thoracic surgeons. Exposures: Robotic-assisted or video-assisted lung lobectomy. Main Outcomes and Measures: The primary outcome was operative duration (cut to close) in minutes. Secondary outcomes were length of stay, 30-day readmission, and 90-day mortality. Comparisons between video-assisted and robotic-assisted lobectomies were generated using the Wilcoxon rank sum test for continuous variables and the χ2 test for categorical variables. The average treatment effects were estimated with augmented inverse probability treatment weighting (AIPTW). Patient and surgeon covariates were adjusted for and included patient demographics, comorbidities, and case complexity (age, sex, race and ethnicity, neighborhood deprivation index, body mass index, Charlson Comorbidity Index score, nonelective hospitalizations, emergency department visits, a validated laboratory derangement score, a validated institutional comorbidity score, a surgeon-designated complexity indicator, and a procedural code count), and a primary surgeon-specific indicator. Results: The study included 1088 patients (median age, 70.1 years [IQR, 63.3-75.8 years]; 704 [64.7%] female), of whom 446 (41.0%) underwent robotic-assisted and 642 (59.0%) underwent video-assisted lobectomy. The median unadjusted operative duration was 172.0 minutes (IQR, 128.0-226.0 minutes). After AIPTW, there was less than a 10% difference in all covariates between groups, and operative duration was a median 20.6 minutes (95% CI, 12.9-28.2 minutes; P < .001) longer for robotic-assisted compared with video-assisted lobectomies. There was no difference in adjusted secondary patient outcomes, specifically for length of stay (0.3 days; 95% CI, -0.3 to 0.8 days; P = .11) or risk of 30-day readmission (adjusted odds ratio, 1.29; 95% CI, 0.84-1.98; P = .13). The unadjusted 90-day mortality rate (1.3% [n = 14]) was too low for the AIPTW modeling process. Conclusions and Relevance: In this cohort study, there was no difference in patient outcomes between modalities, but operative duration was longer in robotic-assisted compared with video-assisted lung lobectomy. Given that this elevated operative duration is additive when applied systematically, increased consideration of appropriate patient selection for robotic-assisted lung lobectomy is needed to improve resource utilization.

The impact of minimally-invasive esophagectomy operative duration on post-operative outcomes.

Background: Esophagectomy, an esophageal cancer treatment mainstay, is a highly morbid procedure. Prolonged operative time, only partially predetermined by case complexity, may be uniquely harmful to minimally-invasive esophagectomy (MIE) patients for numerous reasons, including anastomotic leak, tenuous conduit perfusion and protracted single-lung ventilation, but the impact is unknown. This multi-center retrospective cohort study sought to characterize the relationship between MIE operative time and post-operative outcomes. Methods: We abstracted multi-center data on esophageal cancer patients who underwent MIE from 2010 to 2021. Predictor variables included age, sex, comorbidities, body mass index, prior cardiothoracic surgery, stage, and neoadjuvant therapy. Outcomes included complications, readmissions, and mortality. Association analysis evaluated the relationship between predictor variables and operative time. Multivariate logistic regression characterized the influence of potential predictor variables and operative time on post-operative outcomes. Subgroup analysis evaluated the association between MIE >4 h vs. ≤4 h and complications, readmissions and survival. Results: For the 297 esophageal cancer patients who underwent MIE between 2010 and 2021, the median operative duration was 4.8 h [IQR: 3.7-6.3]. For patients with anastomotic leak (5.1%) and 1-year mortality, operative duration was elevated above the median at 6.3 h [IQR: 4.8-8.6], p = 0.008) and 5.3 h [IQR: 4.4-6.8], p = 0.04), respectively. In multivariate logistic regression, each additional hour of operative time increased the odds of anastomotic leak and 1-year mortality by 39% and 19%, respectively. Conclusions: Esophageal cancer is a poor prognosis disease, even with optimal treatment. Operative efficiency, a modifiable surgical variable, may be an important target to improve MIE patient outcomes.

Pneumonectomy in an elderly patient with congenital unilateral lung hypoplasia and recurrent Aspergillus: a case report.

Background: Congenital lung disorders encompass a spectrum of several conditions, one of which is lung hypoplasia. While hypoplasia is typically identified and intervened upon in the neonatal period, some patients can remain asymptomatic or even be diagnosed as adults. Given the rarity of the condition persisting in adults though, it is not clear what medical or surgical interventions may be helpful if respiratory status declines. Case Description: In this report, we describe an elderly man with a history of right lung hypoplasia, pulmonary artery agenesis, and bronchial atresia who developed progressive dyspnea and worsening cough. His condition was complicated by multiple Aspergillus infections for which he received prolonged courses of anti-fungal therapy. He was also treated for bacterial pneumonia many times over a 10-year period. However, as his symptoms remained refractory to medical management, he underwent pneumonectomy, which revealed diffuse cystic changes in the right lung. He is currently doing well post-operatively with resolution of his dyspnea. Conclusions: Although hypoplastic lung disorders have been described in asymptomatic adults, this report highlights the successful utilization of pneumonectomy in an individual with refractory symptoms much later in adulthood. This case additionally describes possible complications of cystic lung disease in this patient population, serving as further rationale for aggressive intervention.

Clinical Adjuncts to Lung Cancer Screening: A Narrative Review.

The updated US Preventive Services Task Force guidelines on lung cancer screening have significantly expanded the population of screening eligible adults, among whom the balance of benefits and harms associated with lung cancer screening vary considerably. Clinical adjuncts are additional information and tools that can guide decision-making to optimally screen individuals who are most likely to benefit. Proposed adjuncts include integration of clinical history, risk prediction models, shared-decision-making tools, and biomarker tests at key steps in the screening process. Although evidence regarding their clinical utility and implementation is still evolving, they carry significant promise in optimizing screening effectiveness and efficiency for lung cancer.

Case report on the role of aggressive palliative surgery in lung NUT carcinoma after induction chemoimmunotherapy.

INTRODUCTION AND IMPORTANCE: NUT (nuclear protein in testis) carcinoma of the lung is an aggressive, poorly differentiated squamous cell carcinoma that has a poor prognosis. Currently, there are no recommended guidelines with limited literature regarding the management of primary NUT carcinoma of the lung. CASE PRESENTATION: A 28-year-old male presented with 2 weeks of intractable chest pain and shortness of breath and was found to have Stage IV pleural NUT carcinoma. After 2 cycles of chemoimmunotherapy, the patient's symptoms persisted with worsening functional status. Palliative surgery was performed via an extrapleural pneumonectomy with significant improvement in symptoms and activities of daily living. CLINICAL DISCUSSION: With no current treatment guidelines, we demonstrate the benefit of surgical resection of advanced pleural NUT carcinoma to improve quality of life. Prognosis is poor with a median survival around 7 months and 3 months with an associated mass. The patient presented pre-operatively with intractable pleuritic chest pain and shortness of breath, limiting activities of daily living that persisted despite chemoimmunotherapy. Our surgical goal was to improve the patient's respiratory status and mitigate pain symptoms via extensive surgical debulking. The patient was able to achieve a higher quality of life and survived longer than the median average, passing away 1 year after diagnosis. CONCLUSION: The management of NUT carcinoma of the lung remains challenging. The role of surgical resection for palliation in advanced tumors has not been previously described and may provide improved quality of life in carefully selected patients.

Comparable Esophagectomy Outcomes by Surgeon Specialty: A NSQIP Analysis.

BACKGROUND: A few observational studies have found that outcomes after esophagectomies by thoracic surgeons are better than those by general surgeons. METHODS: Non-emergent esophagectomy cases were identified in the 2016-2017 American College of Surgeons NSQIP database. Associations between patient characteristics and outcomes by thoracic versus general surgeons were evaluated with univariate and multivariate logistic regression. RESULTS: Of 1,606 cases, 886 (55.2%) were performed by thoracic surgeons. Those patients differed from patients treated by general surgeons in race (other/unknown 19.3% vs 7.8%; P<.001) but not in other baseline characteristics (age, sex, BMI, and comorbidities). Thoracic surgeons performed an open approach more frequently (48.9% vs 30.8%, P<.001) and had operative times that were 30 minutes shorter (P<.001). General surgeons had lower rates of reoperation (11.8% vs 17.2%; P=.003) and were more likely to treat postoperative leak with interventional means (6.3% vs 3.4%, P=.01). Thoracic surgeons were more likely to treat postoperative leak with reoperation (5.9% vs 3.6%, P=.01). There were no other differences in univariate comparison of outcomes between the two groups, including leak, readmission, and death. General surgery specialty was associated with lower risk of reoperation. Our multivariable model also found no relationship between general surgeon and risk of any complication (odds ratio 1.10; 95% CI .86 to 1.42). DISCUSSION: In our large, national database study, we found that outcomes of esophagectomies by general surgeons were comparable with those by thoracic surgeons. General surgeons managed postoperative leaks differently than thoracic surgeons.

Trends in Smoking-Specific Lung Cancer Incidence Rates Within a US Integrated Health System, 2007-2018.

BACKGROUND: At least 10% of lung cancers arise in adults who have never used tobacco. Data remain inconclusive on whether lung cancer incidence has been increasing among adults who have never used tobacco. RESEARCH QUESTION: How have age-adjusted incidence rates of lung cancer changed temporally, especially among adults who have never used tobacco? STUDY DESIGN AND METHODS: Trends in lung cancer incidence were examined using linked electronic health record and cancer registry data on a dynamic cohort of adults ≥ 30 years of age at risk of incident lung cancer between January 1, 2007, and December 31, 2018, from an integrated health-care system in northern California. Truncated age-adjusted lung cancer incidence rates and average annual percentage change (AAPC) in rates were estimated, overall and separately for adults who have ever and never used tobacco by age, sex, and race or ethnicity. RESULTS: The cohort included 3,751,348 adults (52.5% female, 48.0% non-Hispanic White, 63.1% have never used tobacco), among whom 18,627 (52.7% female, 68.6% non-Hispanic White, 15.4% have never used tobacco) received a diagnosis of lung cancer. The overall lung cancer incidence rate declined from 91.1 to 63.7 per 100,000 person-years between 2007 and 2009 and between 2016 and 2018 (AAPC, -3.9%; 95% CI, -4.2% to -3.6%). Among adults who have ever used tobacco, incidence rates declined overall from 167.0 to 113.4 per 100,000 person-years (AAPC, -4.2%; 95% CI, -4.4% to -3.9%) and, to varying degrees, within all age, sex, and racial or ethnic groups. Among adults who have never used tobacco, incidence rates were relatively constant, with 3-year-period estimates ranging from 19.9 to 22.6 per 100,000 person-years (AAPC, 0.9%; 95% CI, -0.3% to 2.1%). Incidence rates for adults who have never used tobacco seemed stable over time, within age, sex, and racial or ethnic groups, except for those of Asian and Pacific Islander (API) origin (AAPC, 2.0%; 95% CI, 0.1%-3.9%), whose rates were about twice as high compared with their counterparts. INTERPRETATION: These observed trends underscore the need to elucidate further the cause of lung cancer in adults who have never used tobacco, including why incidence is higher and rising in API adults who have never used tobacco.

Adjuvant Immunotherapy in Curative Intent Esophageal Cancer Resection Patients: Real-World Experience within an Integrated Health System.

BACKGROUND: Adjuvant immunotherapy has been shown in clinical trials to prolong the survival of patients with esophageal cancer. We report our initial experience with immunotherapy within an integrated health system. METHODS: A retrospective cohort study was performed reviewing patients undergoing minimally invasive esophagectomy at our institution between 2017 and 2021. The immunotherapy cohort was assessed for completion of treatment, adverse effects, and disease progression, with emphasis on patients who received surgery in 2021 and their eligibility to receive nivolumab. RESULTS: There were 39 patients who received immunotherapy and 137 patients who did not. In logistic regression, immunotherapy was not found to have a statistically significant impact on 1-year overall survival after adjusting for age and receipt of adjuvant chemoradiation. Only seven patients out of 39 who received immunotherapy successfully completed treatment (18%), with the majority failing therapy due to disease progression or side effects. Of the 17 patients eligible for nivolumab, 13 patients received it (76.4%), and three patients completed a full course of treatment. CONCLUSIONS: Despite promising findings of adjuvant immunotherapy improving the survival of patients with esophageal cancer, real-life practice varies greatly from clinical trials. We found that the majority of patients were unable to complete immunotherapy regimens with no improvement in overall 1-year survival.

Fostering a High-Functioning Team in Cancer Care Using the 4R Oncology Model: Assessment in a Large Health System and a Blueprint for Other Institutions.

PURPOSE: Delivering cancer care by high-functioning multidisciplinary teams promises to address care fragmentation, which threatens care quality, affects patient outcomes, and strains the oncology workforce. We assessed whether the 4R Oncology model for team-based interdependent care delivery and patient self-management affected team functioning in a large community-based health system. METHODS: 4R was deployed at four locations in breast and lung cancers and assessed along four characteristics of high-functioning teams: recognition as a team internally and externally; commitment to an explicit shared goal; enablement of interdependent work to achieve the goal; and engagement in regular reflection to adapt objectives and processes. RESULTS: We formed an internally and externally recognized team of 24 specialties committed to a shared goal of delivering multidisciplinary care at the optimal time and sequence from a patient-centric viewpoint. The team conducted 40 optimizations of interdependent care (22 for breast, seven for lung, and 11 for both cancers) at four points in the care continuum and established an ongoing teamwork adaptation process. Half of the optimizations entailed low effort, while 30% required high level of effort; 78% resulted in improved process efficiency. CONCLUSION: 4R facilitated development of a large high-functioning team and enabled 40 optimizations of interdependent care along the cancer care continuum in a feasible way. 4R may be an effective approach for fostering high-functioning teams, which could contribute to improving viability of the oncology workforce. Our intervention and taxonomy of results serve as a blueprint for other institutions motivated to strengthen teamwork to improve patient-centered care.

Progenitor-like exhausted SPRY1+CD8+ T cells potentiate responsiveness to neoadjuvant PD-1 blockade in esophageal squamous cell carcinoma.

Neoadjuvant immune checkpoint blockade (ICB) demonstrates promise in operable esophageal squamous cell carcinoma (ESCC), but lacks available efficacy biomarkers. Here, we perform single-cell RNA-sequencing of tumors from patients with ESCC undergoing neoadjuvant ICB, revealing a subset of exhausted CD8+ T cells expressing SPRY1 (CD8+ Tex-SPRY1) that displays a progenitor exhausted T cell (Tpex) phenotype and correlates with complete response to ICB. We validate CD8+ Tex-SPRY1 cells as an ICB-specific predictor of improved response and survival using independent ICB-/non-ICB cohorts and demonstrate that expression of SPRY1 in CD8+ T cells enforces Tpex phenotype and enhances ICB efficacy. Additionally, CD8+ Tex-SPRY1 cells contribute to proinflammatory phenotype of macrophages and functional state of B cells, which thereby promotes antitumor immunity by enhancing CD8+ T cell effector functions. Overall, our findings unravel progenitor-like CD8+ Tex-SPRY1 cells' role in effective responses to ICB for ESCC and inform mechanistic biomarkers for future individualized immunotherapy.

Interleukin-17 accelerates allograft rejection by suppressing regulatory T cell expansion.

BACKGROUND: Interleukin-17 (IL-17), which is predominantly produced by T helper 17 cells distinct from T helper 1 or T helper 2 cells, participates in the pathogenesis of infectious, autoimmune, and allergic disorders. However, the precise role in allograft rejection remains uncertain. In the present study, we investigated the role of IL-17 in acute allograft rejection using IL-17-deficient mice. METHODS AND RESULTS: Donor hearts from FVB mice were heterotopically transplanted into either C57BL/6J-IL-17-deficient (IL-17(-/-)) or -wild-type mice. Allograft survival was significantly prolonged in IL-17(-/-) recipient mice due to reduced local inflammation accompanied by decreased inflammatory cell recruitment and cytokine/chemokine expression. IL-17(-/-) recipient mice exhibited decreased IL-6 production and reciprocally enhanced regulatory T cell expansion, suggesting a contribution of regulatory T cells to prolonged allograft survival. Indeed, allografts transplanted into anti-CD25 mAb-treated IL-17(-/-) recipient mice (regulatory T cell-depleted) developed acute rejection similar to wild-type recipient mice. Surprisingly, we found that gamma delta T cells rather than CD4(+) and CD8(+) T cells were key IL-17 producers in the allografts. In support, equivalent allograft rejection was observed in Rag-2(-/-) recipient mice engrafted with either wild-type or IL-17(-/-) CD4(+) and CD8(+) T cells. Finally, hearts transplanted into gamma delta T cell-deficient mice resulted in decreased allograft rejection compared with wild-type controls. CONCLUSIONS: During heart transplantation, (1) IL-17 is crucial for acceleration of acute rejection; (2) IL-17-deficiency enhances regulatory T cell expansion; and (3) gamma delta T cells rather than CD4(+) and CD8(+) T cells are a potential source of IL-17. IL-17 neutralization may provide a potential target for novel therapeutic treatment for cardiac allograft rejection.

Video-assisted thoracoscopic resection of a thoracic inlet schwannoma with neuroforaminal involvement: a case report.

Tumors of the posterior mediastinum, particularly when involving the neural foramina, are typically resected via thoracotomy or by a hybrid method with a combination of video-assisted thoracoscopy and open surgery. However, in the appropriate anatomic and clinical context, a video-assisted thoracoscopic approach may be feasible, and such an approach may decrease postoperative pain and hospital length of stay. We present a patient with a benign schwannoma of the thoracic inlet and posterior mediastinum with symptomatic mass effect on surrounding structures. Extensive interdisciplinary discussion with the patient resulted in a minimally invasive, anterior surgical approach. We discuss the unusual surgical approach, complications, and recommendations for future similar cases.

Extrapleural pneumonectomy for recurrent thymoma diagnosed after return of paraneoplastic Morvan syndrome.

A 50-year-old male with history of HIV, syphilis, paraneoplastic Morvan syndrome secondary to thymoma resected in 2013 presented recently with tachycardia, tremors, diarrhea, hyperhidrosis and bilateral lower extremity pain leading to the discovery of thymoma recurrence. He initially developed Morvan Syndrome after thymectomy in 2013 and gradually improved with negative anti-contactin-associated protein-like 2 antibody testing in 2017 and symptom resolution in 2018. Upon return of dysautonomia symptoms, subsequent imaging revealed widespread disease recurrence diffusely in the right lung parenchyma and pleura for which he underwent right extrapleural pneumonectomy. He was managed with low-dose prednisone perioperatively, but when his symptoms worsened, he was started on rituximab and methylprednisolone. Nearly 3 months from surgery, he died from urinary sepsis. This represents a unique case of recurrent paraneoplastic Morvan syndrome leading to the diagnosis of metastatic thymoma as well as the challenges of symptom control during the surgical management of the underlying disease.

A step-up approach to management of complex bronchopleural fistula.

Bronchopleural fistula (BPF) is a sinus tract between a mainstem, lobar or segmental bronchus and the pleural space. We present a 68-year-old male with a 13 mm spiculated left lower lobe nodule who underwent video-assisted thoracoscopic surgery left lower lobe wedge resection followed by persistent BPF requiring open window thoracostomy. We present a step-up approach to management of persistent BPF with discussion of conservative, operative and reconstructive techniques for closure.