Deciphering the clonal relationship between glandular and squamous components in adenosquamous carcinoma of the lung using whole exome sequencing.

Adenosquamous carcinoma of the lung (ASC) is a rare subtype of non-small cell lung cancer, consisting of lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) components. ASC shows morphological characteristics of classic LUAD and LUSC but behaves more aggressively. Although ASC can serve as a model of lung cancer heterogeneity and transdifferentiation, its genomic background remains poorly understood. In this study, we sought to explore the genomic landscape of macrodissected LUAD and LUSC components of three ASC using whole exome sequencing (WES). Identified truncal mutations included the pan-cancer tumor-suppressor gene TP53 but also EGFR, BRAF, and MET, which are characteristic for LUAD but uncommon in LUSC. No truncal mutation of classical LUSC driver mutations were found. Both components showed unique driver mutations that did not overlap between the three ASC. Mutational signatures of truncal mutations differed from those of the branch mutations in their descendants LUAD and LUSC. Most common signatures were related to aging (1, 5) and smoking (4). Truncal chromosomal copy number aberrations shared by all three ASC included losses of 3p, 15q and 19p, and an amplified region in 5p. Furthermore, we detected loss of STK11 and SOX2 amplification in ASC, which has previously been shown to drive transdifferentiation from LUAD to LUSC in preclinical mouse models. Conclusively, this is the first study using WES to elucidate the clonal evolution of ASC. It provides strong evidence that the LUAD and LUSC components of ASC share a common origin and that the LUAD component appears to transform to LUSC.

Lung resection in hematologic patients with pulmonary invasive fungal disease.

BACKGROUND: Pulmonary invasive fungal disease is a frequent complication in patients with hematologic malignancies. Surgical resection in addition to antifungal therapy is an option for selected cases but often feared because of immunosuppression. METHODS: We analyzed the outcome of 71 patients undergoing lung resection for pulmonary invasive fungal disease. Most patients had leukemia, 44 underwent high-dose chemotherapy, and 18 underwent stem cell transplantation. RESULTS: On the day of surgery, 44 patients were neutropenic, and 41 had a platelet count < 50 × 109/L. Forty-five nonanatomic (atypical) resections and 26 lobectomies were performed. Fungal infection was histologically proven in 53 patients. Reoperation was needed in four patients (bronchial stump dehiscence, persistent air leak, chylothorax, and seroma). Minor complications at the site of surgery occurred in 14 patients. In only two, there was an uncontrolled disseminated fungal infection. Overall, mortality at 30 days was 7% (five of 71). Long-term survival was mainly influenced by the underlying hematologic disease. CONCLUSIONS: Lung resection is a therapeutic option for hematologic patients with pulmonary fungal infection. Despite immunosuppression, the perioperative morbidity and mortality is acceptable, and, therefore, the prognosis is not determined by the surgical intervention.

Predicting outcome after lung resection for invasive pulmonary aspergillosis in patients with neutropenia.

STUDY OBJECTIVES: To investigate the factors that predict survival after lung resection for invasive pulmonary aspergillosis (IPA) in patients with neutropenia, in order to assist the selection of patients who are most likely to have a successful outcome. DESIGN: Retrospective single-center study. SETTING: University hospital hemato-oncologic isolation unit and division of thoracic surgery. PATIENTS: Forty-one patients with hematologic disease and suspected IPA who underwent lung resection. INTERVENTIONS: Lobectomy (n = 23), wedge resection (n = 16), and enucleation (n = 2). RESULTS: Mortality within 30 days was 10% (4 of 41 patients). Major perioperative complications occurred in 10%. One death was possibly related to surgery (pleural aspergillosis). Of the patients with proven aspergillosis, 87.1% were cleared of infection, but fungal relapse occurred in 10%. Overall survival was 65% at 6 months, 58% at 12 months, and 40% at 5 years after surgery. Baseline characteristics and intraoperative data did not differ significantly between survivors and nonsurvivors at 6 months or 12 months after surgery. Perioperative complications did not significantly influence the outcome. Multivariate analysis of 12-month survival revealed that the variables, progression, or recurrence of the underlying hematologic disease (relative risk [RR], 4.64; 95% confidence interval [CI], 3.51 to 5.77; p < 0.0001), fungal relapse (RR, 5.06; 95% CI, 3.83 to 6.28; p < 0.0001), and to a minor extent the type of the underlying hematologic disease (p < 0.018) were the most important predictors of patient survival. CONCLUSIONS: Lung resection for IPA is feasible with an acceptable operative risk. While at 10%, the perioperative mortality is considerable; the nonsurgical mortality is reported to be between 30% and 90%. Fungal infection is cleared in > 80% of patients. Mid- to long-term survival can be achieved if the underlying hematologic disease is under control. It is not yet possible to define a group of patients with IPA who are most likely to benefit from lung resection.

Mediastinal lymph node clearance after docetaxel-cisplatin neoadjuvant chemotherapy is prognostic of survival in patients with stage IIIA pN2 non-small-cell lung cancer: a multicenter phase II trial.

PURPOSE: A multicenter, phase II trial investigated the efficacy and toxicity of neoadjuvant docetaxel-cisplatin in locally advanced non-small-cell lung cancer (NSCLC) and examined prognostic factors for patients not benefiting from surgery. PATIENTS AND METHODS: Ninety patients with previously untreated, potentially operable stage IIIA (mediastinoscopically pN2) NSCLC received three cycles of docetaxel 85 mg/m2 day 1 plus cisplatin 40 mg/m2 days 1 and 2, with subsequent surgical resection. RESULTS: Administered dose-intensities were docetaxel 85 mg/m2/3 weeks (range, 53 to 96) and cisplatin 95 mg/m2/3 weeks (range, 0 to 104). The 265 cycles were well tolerated, and the overall response rate was 66% (95% confidence interval [CI], 55% to 75%). Seventy-five patients underwent tumor resection with positive resection margin and involvement of the uppermost mediastinal lymph node in 16% and 35% of patients, respectively (perioperative mortality, 3%; morbidity, 17%). Pathologic complete response occurred in 19% of patients with tumor resection. In patients with tumor resection, downstaging to N0-1 at surgery was prognostic and significantly prolonged event-free survival (EFS) and overall survival (OS; P =.0001). At median follow-up of 32 months, the median EFS and OS were 14.8 months (range, 2.4 to 53.4) and 33 months (range, 2.4 to 53.4), respectively. Local relapse occurred in 27% of patients with tumor resection, with distant metastases in 37%. Multivariate analyses identified mediastinal clearance (hazard ratio, 0.22; P =.0003) and complete resection (hazard ratio, 0.26; P =.0006) as strongly prognostic for increased survival. CONCLUSION: Neoadjuvant docetaxel-cisplatin is effective and tolerable in stage IIIA pN2 NSCLC. Resection is recommended only for patients with mediastinal downstaging after chemotherapy.

Prediction of functional reserves after lung resection: comparison between quantitative computed tomography, scintigraphy, and anatomy.

BACKGROUND AND OBJECTIVES: We prospectively compared five techniques to estimate predicted postoperative function (ppo F) after lung resection: recently proposed quantitative CT scans (CT), perfusion scans (Q), and three anatomical formulae based on the number of segments (S), functional segments (FS), and subsegments (SS) to be removed. METHODS: Four parameters were assessed: FEV(1), FVC, DL(CO) and VO(2max), measured preoperatively and 6 months postoperatively in 44 patients undergoing pulmonary resection, comparing their ppo value to the postoperatively measured value. RESULTS: The correlations (r) obtained with the five methods were for CT: FEV(1) = 0.91, FVC = 0.86, DL(CO) = 0.84, VO(2max) = 0.77; for Q: 0.92, 0.90, 0.85, 0.85; for S: 0.88, 0.86, 0.84, 0.75; for FS: 0.88, 0.85, 0.85, 0.75, and for SS: 0.88, 0.86, 0.85, 0.75, respectively. The mean difference between ppo values and postoperatively measured values was smallest for Q estimates and largest for anatomical estimates using S. Stratification of the extent of resection into lobectomy (n = 30) + wedge resections (n = 4) versus pneumonectomy (n = 10) resulted in persistently high correlations for Q and CT estimates, whereas all anatomical correlations were lower after pneumonectomy. CONCLUSIONS: We conclude that both Q- and CT-based predictions of postoperative cardiopulmonary function are useful irrespective of the extent of resection, but Q-based results were the most accurate. Anatomically based calculations of ppo F using FS or SS should be reserved for resections not exceeding one lobe.

Late Aspergillus fumigatus endomyocarditis with brain abscess as a lethal complication after heart transplantation.

We report the case of a 65-year-old male patient who died from lethal Aspergillus fumigatus endomyocarditis and multiple cerebral septic emboli 6 months after cardiac transplantation. This complication developed 4 weeks after diagnosis of bilateral pulmonary aspergillosis, which was immediately treated by surgical removal and intravenous amphotericin B. Preceding colonization with Aspergillus spp was not identified. Primary cytomegalovirus infection (donor+/recipient-) and toxoplasmosis reactivation (donor+/recipient+) occurring at 1 and 2 months post-transplantation were successfully treated.

CT-guided radiofrequency ablation of a pulmonary metastasis followed by surgical resection.

Outpatient CT-guided radiofrequency ablation (RFA) of a pulmonary metastasis followed by surgical resection and histopathological analysis was performed in a 72-year-old lady suffering from a peritoneal leiomyosarcoma. Histological workup 3 weeks post-ablation showed complete devitalization of the metastasis. This case report demonstrates that complete thermal destruction of a pulmonary metastasis by percutaneous image-guided RFA is possible.