How Much Delay Matters? How Time to Treatment Impacts Overall Survival in Early Stage Lung Cancer.

OBJECTIVES: The aim of this study was to identify drivers of time from diagnosis to treatment (TTT) of surgically resected early stage non-small cell lung cancer (NSCLC) and determine the effect of TTT on post-resection survival. SUMMARY BACKGROUND DATA: Large database studies that lack relevant comorbidity data have identified longer TTT asa driver of worse overall survival. METHODS: From January 1, 2014 to April 1, 2018, 599 patients underwent lung resection for clinical stage I and II NSCLC. Random forest classification, regression, and survival were used to estimate likelihood of TTT = 0 (tissue diagnosis obtained at surgery), >0 (diagnosis obtained pre-resection), and effect of TTT on all-cause mortality. RESULTS: Patients with TTT > 0 (n = 413) had median TTT of 42 days (25-75 th percentile: 27-59 days). Patients with TTT = 0 (n = 186) had smaller tumors and higher percent predicted forced expiratory volume in 1 second (FEV 1 %). Patients with history of stroke, oncology consultation, invasive mediastinal staging, low and high extremes of FEV 1 % had longer TTT. Higher clinical stage, lack of preoperative stress test, anemia, older age, lower FEV1% and diffusion lung capacity, larger tumor size, and longer TTT were the most important predictors of all-cause mortality. One- and 5-year overall survival decreased when TTT was >50 days. CONCLUSIONS: Preoperative physiologic workup and multidisciplinary evaluation were the predominant drivers of longer TTT. Patients with TTT = 0have more favorable presentation and should be considered in TTT analyses for early stage lung cancer populations. The time needed to clinically stage and optimize patients for resection is not deleterious to overall survival until resection is performed after 50 days from diagnosis.

Airway Injury Caused by Aspiration of Iron Sulfate Pills: A Series of 11 Cases.

It is not widely recognized that iron (ferrous sulfate) pill aspiration causes airway damage. Clinical diagnosis is challenging because patients are often unaware that they have aspirated a pill. The literature on this entity consists mainly of case reports. The aim of this study is to describe the clinical and pathologic features of iron pill aspiration in a series of 11 patients. A retrospective review of our pathology archives was performed to identify cases of iron pill aspiration (2013-2023). All available histologic and cytologic material was rereviewed. Clinical information was collected from the electronic medical record, and imaging studies were rereviewed. Eighteen endobronchial biopsies were identified from 11 patients (7 women and 4 men; mean age, 70 years; range, 44-82 years). Eight patients had corresponding cytology (20 specimens). Medication history was available in 9 of 11 patients, all of whom were taking iron sulfate pills. Two patients reported possible aspiration episodes; 4 had risk factors for aspiration. The diagnosis of iron pill aspiration was suspected prior to biopsy in only 1 case. Histologically, iron pill particles were yellow, golden brown, or gray, were elongated and crystal or fiber like, and stained strongly with an iron stain. Common histologic findings included mucosal ulceration, acute and/or chronic inflammation, fibrosis, and squamous metaplasia. Iron pill particles were also identified in 11 cytology specimens from 6 patients. On Papanicolaou staining, iron pill particles were yellow to golden, fiber like, refractile, and crystalline. Reactive epithelial cells, squamous metaplasia, and acute inflammation were common. The combination of iron pill intake and discolored mucosa on bronchoscopy is a potential clue to the diagnosis of iron pill aspiration. Pathologists should familiarize themselves with the appearance of iron pill particles in endobronchial biopsies and cytology specimens from the respiratory tract as this diagnosis is seldom suspected on clinical grounds, and most patients lack a history of aspiration.

Harmonized Outcome Measures for Use in Non-Small Cell Lung Cancer Patient Registries and Clinical Practice.

BACKGROUND: Lung cancer is the leading cause of cancer-related death in the United States and globally, and many questions exist about treatment options. Harmonizing data across registries and other data collection efforts would yield a robust data infrastructure to help address many research questions. The purpose of this project was to develop a minimum set of patient and clinician relevant harmonized outcome measures that can be collected in non-small cell lung cancer (NSCLC) patient registries and clinical practice. METHODS: Seventeen lung cancer registries and related efforts were identified and invited to submit outcome measures. Representatives from medical specialty societies, government agencies, health systems, health information technology groups, patient advocacy organizations, and industry formed a stakeholder panel to categorize the measures and harmonize definitions using the Agency for Healthcare Research and Quality's supported Outcome Measures Framework (OMF). RESULTS: The panel reviewed 66 outcome measures and identified a minimum set of 8 broadly relevant measures in the OMF categories of patient survival, clinical response, events of interest, and resource utilization. The panel harmonized definitions for the 8 measures through in-person and virtual meetings. The panel did not reach consensus on 1 specific validated instrument for capturing patient-reported outcomes. The minimum set of harmonized outcome measures is broadly relevant to clinicians and patients and feasible to capture across NSCLC disease stages and treatment pathways. A pilot test of these measures would be useful to document the burden and value of the measures for research and in clinical practice. CONCLUSIONS: By collecting the harmonized measures consistently, registries and other data collection systems could contribute to the development research infrastructure and learning health systems to support new research and improve patient outcomes.

Considerations for the Surgical Management of Diaphragmatic Endometriosis.

STUDY OBJECTIVE: The objective of this video is to review relevant surgical anatomy, resection and ablation methods, and techniques to optimize management of diaphragmatic endometriosis. DESIGN: Video footage of surgical anatomy and surgical technique. Institutional review board approval was not required. SETTING: Thoracic endometriosis lesions can involve the pleura, the lung, and the diaphragm. The prevalence of thoracic endometriosis is unknown, but most cases involve the diaphragm. A large percentage of patients are asymptomatic. Those who are symptomatic can present with cyclic shoulder pain, right upper quadrant pain, or catamenial pneumothorax. Symptomatic cases refractory to medical management or recurrence require surgical management [1,2]. Safe and efficient management of these cases depends on an experienced multidisciplinary team. In this video, the experiences and management tools used by our team are described. INTERVENTIONS: Laparoscopic management of primary and recurrent symptomatic diaphragmatic endometriosis. CONCLUSION: A multidisciplinary skilled team approach to the surgical management of diaphragmatic endometriosis to optimize outcomes is preferred.

Intercostal Blocks with Liposomal Bupivacaine in Thoracic Surgery: A Retrospective Cohort Study.

OBJECTIVE: Assess the efficacy of adding liposomal bupivacaine (LB) to bupivacaine-containing intercostal nerve blocks (ICNBs) to improve analgesia and decrease opioid consumption and hospital length of stay compared with bupivacaine-only ICNBs. DESIGN: This retrospective, observational investigation compared pain intensity scores and cumulative opioid consumption within the first 72 postoperative hours in patients who received ICNBs with bupivacaine plus LB (LB group) versus bupivacaine only (control group) after minimally invasive anatomic pulmonary resection. LB was tested for noninferiority on pain scores and opioid consumption. If LB was noninferior, superiority of LB was tested on both outcomes. SETTING: Academic tertiary care medical center. PARTICIPANTS: Adult patients undergoing minimally invasive anatomic pulmonary resection. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: For the secondary analysis, hospital length of stay was compared through the Cox regression model. Of 396 patients, 178 (45%) received LB and 218 (55%) did not. The mean (standard deviation) pain score was three (one) in the LB group and three (one) in the control group, with a difference of -0.10 (97.5% confidence interval [-0.39 to 0.18]; p = 0.41). The mean (standard deviation) cumulative opioid consumption (intravenous morphine equivalents) was 198 (208) mg in the LB group and 195 (162) mg in the control group. Treatment effect in opioid consumption was estimated at a ratio of geometric mean of 0.94 (97.5% confidence interval [0.74-1.20]; p = 0.56). Pain control and opioid consumption were noninferior with LB but not superior. Hospital discharge was not different between groups. CONCLUSIONS: LB with bupivacaine in ICNBs did not demonstrate superior postoperative analgesia or affect the rate of hospital discharge.

Breast Implant-Associated Anaplastic Large Cell Lymphoma With Invasive Chest Wall Masses.

BACKGROUND: Breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL) might occur in any patient with a history of textured breast devices, and often presents as a spectrum of disease: from a simple late-onset seroma, to complex advanced locally aggressive disease with chest wall involvement. The combination of medical therapy and surgical implant removal with complete capsulectomy is believed to be curative. OBJECTIVES: In patients with advanced cases, however, and although generalized recommendations exist, no consensus exists regarding the ideal medical and surgical management of those presenting with invasive disease. METHODS: This preliminary report describes 2 distinct presentations of rare invasive chest wall BIA-ALCL, both treated successfully, by using a combined medical and surgical multidisciplinary team approach. Subsequently, we discuss considerations and the current literature surrounding the treatment of advanced BIA-ALCL with chest wall and adjacent structure involvement. RESULTS: All patients necessitated chest wall resection and composite reconstruction due to tumor involvement of the thorax with residual hypermetabolic activity, despite chemotherapeutic pretreatment with different neoadjuvant medical therapies. All healed well after surgery and experienced resolution of symptoms without signs of relapse on regular follow-up. CONCLUSIONS: In the rare subset of patients presenting with invasive BIA-ALCL, the question persists as to which systemic treatment remains optimal. However, the evidence supports multiple, particularly in combination with surgical extirpation and reconstruction. Here we present 2 proven treatments, both in timing and modalities chosen, as part of the first step to establish a formally accepted treatment paradigm for advanced BIA-ALCL patients with invasive chest wall involvement.

Intraoperative Percutaneous Microcoil Localization of Small Peripheral Pulmonary Nodules Using Cone-Beam CT in a Hybrid Operating Room.

OBJECTIVE. Thoracoscopic surgical resection of small peripheral pulmonary nodules can be challenging, and often preoperative localization techniques are needed to avoid conversion to open thoracotomy. In this article, we show the feasibility and benefits of performing intraoperative percutaneous microcoil localization with C-arm cone-beam CT in a hybrid operating room immediately before video-assisted thoracoscopic surgery for wedge resection of a small pulmonary nodule. CONCLUSION. This technique can provide safe and accurate localization while minimizing patient discomfort and thus enhancing the patient's experience.

Correction to: Largely Unchanged Annual Incidence and Overall Survival of Pleural Mesothelioma in the USA.

The following disclaimer is missing from the original article.

Largely Unchanged Annual Incidence and Overall Survival of Pleural Mesothelioma in the USA.

BACKGROUND: Projections based on regulations curtailing asbestos use in the USA suggest that peak incidence of pleural mesothelioma would occur between 2000 and 2005 and then decline. We analyzed the National Cancer Database (NCDB) to assess current trends in disease incidence, patient demographics, cancer treatment, and survival. METHODS: The NCDB was queried to identify patients diagnosed with pleural mesothelioma from 2004 through 2014. Clinical and pathologic characteristics, treatments, and survival were analyzed. Risk factors for death were identified by multivariable Cox regression. RESULTS: A total of 20,988 patients with pleural mesothelioma were reported to the NCDB. The number of cases per year increased from 1783 to 1961, accounting for roughly 0.3% of all reported cancers each year. The proportion of elderly patients increased from 75 to 80%, but distribution by sex remained constant (20% female). The proportion of patients undergoing treatment increased from 34 to 54%. One-year survival increased from 37 to 47% and 3-year survival from 9 to 15% (p < 0.001). Factors associated with improved survival included younger age, female sex, epithelioid histology, treatment in an academic center, health insurance, higher income, and multimodality therapy. CONCLUSIONS: The annual incidence of mesothelioma has not declined this century and remains stable. Reporting of histologic and clinical staging has improved. National trends suggest that survival is slowly increasing despite an aging cohort. Multimodal therapy and treatment at academic centers are modifiable risk factors associated with improved survival.

Video-Assisted Thoracic Surgery Resection without Intraoperative Fluoroscopy after CT-Guided Microcoil Localization of Peripheral Pulmonary Nodules.

The aim of this brief report is to determine the safety and reliability of minimally invasive video-assisted thoracic surgery (VATS) resection without the aid of intraoperative fluoroscopy after computed tomography (CT)-guided microcoil localization of small peripheral pulmonary nodules. Twenty patients with peripheral lung nodules underwent percutaneous needle localization with a microcoil that was tagged back to the visceral pleural surface. Same-day VATS resection was performed without the use of intraoperative fluoroscopy. All 20 nodules were successfully localized in the CT procedure room, and all 20 nodules were resected with negative margins and no major complications.

Against the Odds: Syringe Exchange Policy Implementation in Indiana.

Indiana recently passed legislation allowing local governments to establish syringe exchanges. While the effectiveness of syringe exchange programming is established, there is a dearth of studies about associated policy adoption and implementation. This study documents the experiences of 24 Indiana counties engaged in the process of establishing syringe exchange programming under new state law. A mixed method, qualitative, exploratory case study was conducted from May 2015 to April 2016. We observed rapid and widespread policy adoption interest, and yet counties reported significant policy ambiguity, epidemiologic and resource capacity issues. The emergence of health commons involving information and tangible resource sharing networks allowed institutional rearrangement in the midst of resource scarcity; however, such rearrangement appeared to be a central threat to policy adoption and implementation given state structural barriers. The emerging commons could be a critical policy success factor, as it would achieve efficiencies not possible in the current resource environment, and can help achieve institutional rearrangement for the improvement of population health. Several recommendations for improvement are offered.

Evaluating soluble Axl as a biomarker for glioblastoma: A pilot study.

With current imaging, discriminating tumor progression from treatment effect following immunotherapy or oncolytic virotherapy of glioblastoma (GBM) is challenging. A blood based diagnostic biomarker would therefore be helpful. Axl is a receptor tyrosine kinase that is highly expressed by many cancers including GBM. Axl expression is regulated through enzymatic cleavage of its extracellular domain. The resulting fragment can be detected in serum as soluble Axl (sAxl). sAxl levels can distinguish patients with melanoma, hepatocellular carcinoma, and pancreatic ductal adenocarcinoma from healthy controls. This is a pilot study to determine if sAxl is a candidate biomarker for GBM. The sAxl levels in the serum of 40 healthy volunteers and 20 GBM patients were determined using an enzyme-linked immunosorbent assay (ELISA). Pre- and post- operative sAxl levels were obtained. Volumetric MRI evaluation provided GBM tumor volume metrics. There was no significant difference in the sAxl levels of the volunteers (30.16±1.88 ng/ml) and GBM patients (30.74±1.96 ng/ml) p = 0.27. The postoperative sAxl levels were significantly higher than preoperative levels (32.32±2.26 ng/ml vs 30.74±1.96 ng/ml, p = 0.03). We found no correlation between tumor volume and sAxl levels. Axl expression was low or absent in 6 of 11 (55%) patient derived GBM cell lines. Given the wide range of Axl expression by GBM tumors, sAxl may not be a reliable indicator of GBM. However, given the small sample size in this study, a larger study may be considered.

Novel Repair of Clamshell Thoracotomy Sternal Dehiscence after Lung Transplant: A Case Report.

Bilateral transverse thoracosternotomy, or "clamshell" thoracotomy, can be complicated by dehiscence. A 65-year-old male underwent lung transplantation via clamshell thoracotomy, with subsequent sternal dehiscence on postoperative day 11. Upon repair, the previous sternal wires had pulled through, so a Sternal Talon connected to a Recon Talon was utilized to re-approximate the inferior sternum. On follow-up at 3 months, the patient recovered well. Use of the Sternal Talon provides an effective technique for repairing transverse sternal dehiscence.

Development and validation of a universal esophageal patient-reported outcome measure: The Cleveland Clinic Esophageal Questionnaire (CEQ).

OBJECTIVE: Currently, there is no validated patient-reported outcome measure (PROM) applicable to all esophageal diseases. Our objective was to create a psychometrically robust, validated universal esophageal PROM that can also objectively assess patients' quality of life (QoL). METHODS: The pilot PROM constructed based on expert opinions, literature review, and previous unpublished institutional research had 27 items covering 8 domains. It was completed by 30 patients in the outpatient clinic followed by a structured debriefing interview, which allowed for refining the PROM. The final PROM: Cleveland Clinic Esophageal Questionnaire (CEQ) included 34 items across 6 domains (Dysphagia, Eating, Pain, Reflux & Regurgitation, Dyspepsia, Dumping), each accompanied by a corresponding QoL component. Further psychometric assessment of the PROM was conducted by evaluating (1) acceptability, (2) construct validity, (3) reliability, and (4) responsiveness. RESULTS: Five hundred forty-six unique patients (median 63.7 years [54.3-71.7], 53% male [287], 86% White) completed CEQ at >90% completion within 5 minutes. Construct validity was demonstrated by differentiating scores across esophageal cancer (n = 146), achalasia (n = 170), hiatal hernia (n = 160), and other diagnoses (n = 70). Internal reliability (Cronbach alpha 0.83-0.89), and test-retest reliability (intraclass correlation coefficients 0.63-0.85) were strong. Responsiveness was demonstrated through CEQ domains improving for 53 patients who underwent surgery for achalasia or hiatal hernia (Cohen d 0.86-2.59). CONCLUSIONS: We have constructed a psychometrically robust, universal esophageal PROM that allows concise, consistent, objective quantification of symptoms and their effect on the patient. The CEQ is valuable in prognostication and tracking of longitudinal outcomes in both benign and malignant esophageal diseases.

Combined pectoralis and serratus anterior plane blocks with or without liposomal bupivacaine for minimally invasive thoracic surgery: A randomized clinical trial.

BACKGROUND: Minimally invasive thoracic surgery is associated with substantial pain that can impair pulmonary function. Fascial plane blocks may offer a favorable alternative to opioids, but conventional local anesthetics provide a limited duration of analgesia. We therefore tested the primary hypothesis that a mixture of liposomal bupivacaine and plain bupivacaine improves the overall benefit of analgesia score (OBAS) during the first three postoperative days compared to bupivacaine alone. Secondarily, we tested the hypotheses that liposomal bupivacaine improves respiratory mechanics, and decreases opioid consumption. METHODS: Adults scheduled for robotically or video-assisted thoracic surgery with combined ultrasound-guided pectoralis II and serratus anterior plane block were randomized to bupivacaine or bupivacaine combined with liposomal bupivacaine. OBAS was measured on postoperative days 1-3 and was analyzed with a linear mixed regression model. Postoperative respiratory mechanics were estimated using a linear mixed model. Total opioid consumption was estimated with a simple linear regression model. RESULTS: We analyzed 189 patients, of whom 95 were randomized to the treatment group and 94 to the control group. There was no significant treatment effect on total OBAS during the initial three postoperative days, with an estimated geometric mean ratio of 0.93 (95% CI: 0.76, 1.14; p = 0.485). There was no observed treatment effect on respiratory mechanics, total opioid consumption, or pain scores. Average pain scores were low in both groups. CONCLUSIONS: Liposomal bupivacaine did not improve OBAS during the initial postoperative three days following minimally invasive thoracic procedures. Furthermore, there was no improvement in respiratory mechanics, no reduction in opioid consumption, and no decrease in pain scores. Thus, the data presented here does not support the use of liposomal bupivacaine over standard bupivacaine to enhance analgesia after minimally invasive thoracic surgery. SUMMARY STATEMENT: For minimally invasive thoracic procedures, addition of liposomal bupivacaine to plain bupivacaine for thoracic fascial plane blocks does not improve OBAS, reduce opioid requirements, improve postoperative respiratory mechanics, or decrease pain scores.

Clinical T2 N0 M0 Esophageal Cancer: Identifying Predictive Factors of Upstaging.

BACKGROUND: Inaccuracy of clinical staging renders management of clinical T2 N0 M0 (cT2 N0 M0) esophageal cancer difficult. When an underlying advanced-stage disease is understaged to cT2 N0 M0, patients miss the opportunity to gain the potential benefits of neoadjuvant therapy. This study aimed to identify preoperative factors that predict underlying advanced-stage esophageal cancer. METHODS: From 2000 to 2020, 1579 patients with esophageal cancer underwent esophagectomy. Sixty patients who underwent upfront surgery for cT2 N0 M0 esophageal cancer were included in this study. The median age was 62.5 years, and 78% (n = 47) of these patients were male. Radiologic, clinical, and endoscopic factors were evaluated as preoperative markers. The Fisher exact and the Wilcoxon rank sum tests were used for categoric and continuous variables, respectively. Random forest classification was used to identify preoperative factors for predicting upstaging and downstaging. RESULTS: Of the 60 patients, 8 (13%) were found to have pathologic T2 N0 M0 esophageal cancer. Sixteen (27%) patients had cancer that was pathologically downstaged, and 36 (60%) had upstaged disease. Seven (19%) patients had upstaged cancer on the basis of the pathologic T stage, 14 (39%) had upstaging on the basis of the pathologic N stage, and 15 (42%) had upstaging on the basis of both T and N stages. Dysphagia (P = .003) and tumor maximum standardized uptake value (P = .048) were predictors of upstaging, with a combined predictive value of up to 75%. CONCLUSIONS: The presence of dysphagia and of high maximum standardized uptake value (≥5) of the tumor is predictive of more advanced underlying disease for patients with cT2 N0 M0 esophageal cancer, and these patients should be considered for neoadjuvant therapy.

The Society of Thoracic Surgeons Expert Consensus Document on the Management of Pleural Drains After Pulmonary Lobectomy: Expert Consensus Document.

The Society of Thoracic Surgeons Workforce on Evidence-Based Surgery provides this document on management of pleural drains after pulmonary lobectomy. The goal of this consensus document is to provide guidance regarding pleural drains in 5 specific areas: (1) choice of drain, including size, type, and number; (2) management, including use of suction vs water seal and criteria for removal; (3) imaging recommendations, including the use of daily and postpull chest roentgenograms; (4) use of digital drainage systems; and (5) management of prolonged air leak. To formulate the consensus statements, a task force of 15 general thoracic surgeons was invited to review the existing literature on this topic. Consensus was obtained using a modified Delphi method consisting of 2 rounds of voting until 75% agreement on the statements was reached. A total of 13 consensus statements are provided to encourage standardization and stimulate additional research in this important area.

Clinical Nomogram Using Novel Computed Tomography-Based Radiomics Predicts Survival in Patients With Non-Small-Cell Lung Cancer Treated With Stereotactic Body Radiation Therapy.

PURPOSE: Improved survival prediction and risk stratification in non-small-cell lung cancer (NSCLC) would lead to better prognosis counseling, adjuvant therapy selection, and clinical trial design. We propose the persistent homology (PHOM) score, the radiomic quantification of solid tumor topology, as a solution. MATERIALS AND METHODS: Patients diagnosed with stage I or II NSCLC primarily treated with stereotactic body radiation therapy (SBRT) were selected (N = 554). The PHOM score was calculated for each patient's pretreatment computed tomography scan (October 2008-November 2019). PHOM score, age, sex, stage, Karnofsky Performance Status, Charlson Comorbidity Index, and post-SBRT chemotherapy were predictors in the Cox proportional hazards models for OS and cancer-specific survival. Patients were split into high- and low-PHOM score groups and compared using Kaplan-Meier curves for overall survival (OS) and cumulative incidence curves for cause-specific death. Finally, we generated a validated nomogram to predict OS, which is publicly available at Eashwarsoma.Shinyapps. RESULTS: PHOM score was a significant predictor for OS (hazard ratio [HR], 1.17; 95% CI, 1.07 to 1.28) and was the only significant predictor for cancer-specific survival (1.31; 95% CI, 1.11 to 1.56) in the multivariable Cox model. The median survival for the high-PHOM group was 29.2 months (95% CI, 23.6 to 34.3), which was significantly worse compared with the low-PHOM group (45.4 months; 95% CI, 40.1 to 51.8; P < .001). The high-PHOM group had a significantly greater chance of cancer-specific death at post-treatment month 65 (0.244; 95% CI, 0.192 to 0.296) compared with the low-PHOM group (0.171; 95% CI, 0.123 to 0.218; P = .029). CONCLUSION: The PHOM score is associated with cancer-specific survival and predictive of OS. Our developed nomogram can be used to inform clinical prognosis and assist in making post-SBRT treatment considerations.