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.

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 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.

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.

Preoperative predictors of spread through air spaces in lung cancer.

OBJECTIVE: Spread through air spaces (STAS) is a new histologic feature of invasion of non-small cell lung cancer that lacks sensitivity and specificity on frozen sections and is associated with higher recurrence and worse survival with sublobar resections. Our objective is to identify preoperative characteristics that are predictive of STAS to guide operative decisions. METHODS: From January 2018 through December 2021, 439 cT1-3N0 M0 patients with non-small cell lung cancer and a median age of 68 years, 255 (58%) women, who underwent primary surgery at our institution were included. Patients who received neoadjuvant therapy and whose STAS status was not documented were excluded. Age, sex, smoking status, tumor size, ground-glass opacities, maximum standardized uptake values, and molecular markers on preoperative biopsy were evaluated as preoperative markers. Comparisons between groups were conducted using standardized mean differences and random forest classification was used for prediction modeling. RESULTS: Of the 439 patients, 177 had at least 1 STAS-positive tumor, and 262 had no STAS-positive tumors. Overall, 179 STAS tumors and 293 non-STAS tumors were evaluated. Younger age (50 years or younger), solid tumor, size ≥2 cm, and maximum standardized uptake value ≥2.5 were independently predictive of STAS with prediction probabilities of 50%, 40%, 38%, and 40%, respectively. STAS tumors were more likely to harbor KRAS mutations and be PD-L1 negative. CONCLUSIONS: Young age (50 years or younger), larger (≥2 cm) solid tumors, high maximum standardized uptake values, and presence of KRAS mutation, are risk factors for STAS and can be considered for lobectomy. Smoking status and gender are still controversial risk factors for STAS.

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.

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.

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.

Non-iatrogenic esophageal trauma: a narrative review.

Background and Objective: Non-iatrogenic esophageal trauma is a rare entity that has a high morbidity and mortality. The diagnosis can often be quite challenging, however is critical to perform in a timely manner. The workup and management of non-iatrogenic trauma continues to evolve, with new innovative approaches available for both diagnosis and treatment. The aim of this narrative review is to comprehensively describe the incidence, presentation, workup, treatment approaches and outcomes of non-iatrogenic esophageal trauma. Methods: A thorough literature review was performed using full length articles available in English via PubMed between January 1, 1960 to September 30, 2021, focusing on the epidemiology, workup and treatment of non-iatrogenic esophageal trauma, including current surgical techniques. Key Content and Findings: Injuries to the cervical esophagus are more common than injuries to the thoracic esophagus, occurring more in young males, with significant racial disparity. Penetrating trauma via gunshot wounds are the most common forms of injury, followed by stab wounds and blunt trauma. Workup is multimodal and involves a combination of plain radiographs, computed tomography (CT) scans, endoscopy and fluoroscopy depending of the stability of the patient and associated injuries. Conclusions: Workup and management of non-iatrogenic esophageal trauma depends on the location and extent of esophageal injury, and can include observation, debridement and drainage, esophageal diversion, endoscopic approaches or esophagectomy, with indications, techniques and outcomes described in further detail in this review.

Select octogenarians with stage IIIa non-small cell lung cancer can benefit from trimodality therapy.

Objectives: Currently, more than 36% of patients diagnosed with lung cancer are 75 years of age or older. Management of stage IIIA cancer is variable, especially for octogenarians who might not be offered surgery because of questionable benefit. In this study we investigated the outcomes of definitive chemoradiotherapy (CR) and trimodality therapy (TM) management (CR and surgery) for clinical stage IIIA non-small cell lung cancer (NSCLC) in patients 80 years of age or older. Methods: The National Cancer Data Base was queried for stage IIIA NSCLC in patients 80 years of age or older between 2004 and 2015. Patients were divided according to treatment type: definitive CR and TM. Patient demographic characteristics, facility type, Charlson-Deyo score, final tumor pathology, and survival data were extracted. Univariate analysis was performed, followed by 3:1 propensity matching to analyze overall survival differences. Unadjusted and adjusted Kaplan-Meier survival analyses were performed. Results: From the database, 6048 CR and 190 TM octogenarians were identified. Patients in the TM group were younger (82 years old [TM] vs 83 years old [CR]; P < .0001), more likely to be treated at an academic/research institution (36% [TM] vs 26% [CR]; P = .003), had greater proportion of adenocarcinoma (52% [TM] vs 34% [CR]; P < .001), and a smaller tumor size (38 mm [TM] vs 33 mm [CR]; P = .025). After 3:1 matching, the 5-year overall survival for the TM group was 29% (95% CI, 22%-38%) versus 15% (95% CI, 11%-20%) for the CR group. Conclusions: Selected elderly patients with stage IIIa NSCLC can benefit from an aggressive TM approach.

Thymomas With Intravascular and Intracardiac Growth.

Thymomas are derived from the epithelial component of the thymus and constitute the most common tumor of the anterior mediastinum. These neoplasms are considered malignant for their potential for invasion and metastases. Several histopathologic subclassification schemes have been proposed over the years, however, correlation of histotypes with prognosis remains controversial. In contrast, studies invariably have shown that staging and resection status correlate with oncologic behavior and disease outcomes. In this regard, several staging systems have been presented, though transcapsular invasion and degree of involvement of adjacent anatomic structures are common denominators of all schemes. Involvement of the great vessels and heart most commonly results from direct invasion, which may lead to unusual clinical presentations such as superior vena cava syndrome. Moreover, intravascular and intracardiac growth with or without direct mural invasion rarely occurs. We provide an overview of thymomas with intravascular and intracardiac involvement.

A Phase 1 Study of Concurrent Neoadjuvant Pembrolizumab Plus Chemoradiation Followed by Consolidation Pembrolizumab in Patients With Resectable Stage IIIA NSCLC.

Introduction: Evidence supports the addition of immunotherapy to definitive chemoradiation for unresectable stage IIIA NSCLC. Adding pembrolizumab to neoadjuvant chemoradiation in patients with resectable stage IIIA NSCLC requires study for safety and feasibility. Methods: Patients with resectable stage IIIA NSCLC received neoadjuvant cisplatin, etoposide, and pembrolizumab concurrently with thoracic radiotherapy of 45 Gy in 25 fractions. Patients without progression underwent resection followed by 6 months of consolidation pembrolizumab. Safety and feasibility were defined as less than or equal to 30% grade 3 or higher pulmonary toxicity or any grade 4 or 5 nonhematologic toxicity. A total of 10 patients were to be enrolled initially. If less than or equal to two patients had events, another 10 were to be enrolled. Results: The study closed after enrolling nine patients. The median age was 66 (range: 49-76) years. A total of 67% were female. Median follow-up was 38.3 months. Serious adverse events occurred in seven patients, including two grade 5 events: one sudden cardiac arrest in the neoadjuvant phase and one fatal pneumocystis pneumonia after resection. Eight patients were assessable for response. The overall response rate was 67%. Six underwent complete resection. Four achieved pathologic complete response, whereas one additional patient had complete nodal clearance. Median progression-free survival has not been reached. The 3-year overall survival was 64%. Conclusions: Adding pembrolizumab to neoadjuvant concurrent cisplatin, etoposide, and radiotherapy in resectable stage IIIA NSCLC resulted in an encouraging pathologic complete response rate. Higher-than-expected toxicities necessitated trial closure after meeting the rule for infeasibility. The relationship of grade 5 events to the addition of pembrolizumab is unclear.

Multidisciplinary Approach to Isolated Pulmonary Vein Compression by an Enlarging Vertebral Osteophyte.

Compression of mediastinal structures by vertebral osteophytes is rare. We report a case of pulmonary vein compression by a vertebral osteophyte that failed stenting. A minimally invasive approach to osteophyte removal with subsequent re-expansion angioplasty yielded an optimal outcome, negating the need for cardiopulmonary bypass, stent removal, and pulmonary venoplasty. (Level of Difficulty: Intermediate.).