Candidate tumor-specific CD8+ T cell subsets identified in the malignant pleural effusion of advanced lung cancer patients by single-cell analysis.

Isolation of tumor-specific T cells and their antigen receptors (TCRs) from malignant pleural effusions (MPE) may facilitate the development of TCR-transduced adoptive cellular immunotherapy products for advanced lung cancer patients. However, the characteristics and markers of tumor-specific T-cells in MPE are largely undefined. To this end, to establish the phenotypes and antigen specificities of CD8+ T cells, we performed single-cell RNA and TCR sequencing of samples from three advanced lung cancer patients. Dimensionality reduction on a total of 4,983 CD8+ T cells revealed 10 clusters including naïve, memory, and exhausted phenotypes. We focused particularly on exhausted T cell clusters and tested their TCR reactivity against neoantigens predicted from autologous cancer cell lines. Four different TCRs specific for the same neoantigen and one orphan TCR specific for the autologous cell line were identified from one of the patients. Differential gene expression analysis in tumor-specific T cells relative to the other T cells identified CXCL13, as a candidate gene expressed by tumor-specific T cells. In addition to expressing CXCL13, tumor-specific T cells were present in a higher proportion of T cells co-expressing PDCD1(PD-1)/TNFRSF9(4-1BB). Furthermore, flow cytometric analyses in advanced lung cancer patients with MPE documented that those with high PD-1/4-1BB expression have a better prognosis in the subset of 57 adenocarcinoma patients (p = .039). These data suggest that PD-1/4-1BB co-expression might identify tumor-specific CD8+ T cells in MPE, which are associated with patients' prognosis. (233 words).

The Comprehensive Characterization of B7-H3 Expression in the Tumor Microenvironment of Lung Squamous Cell Carcinoma: A Retrospective Study.

Lung squamous cell carcinoma (LSCC) is refractory to various therapies for non-small cell cancer; therefore, new therapeutic approaches are required to improve the prognosis of LSCC. Although immunotherapies targeting B7 family molecules were explored as treatments for several cancer types, the expression and significance of B7-H3 in the tumor microenvironment (TME) and its relationship with other immune checkpoint molecules have not yet been investigated in detail. We used high-throughput quantitative multiplex immunohistochemistry to examine B7-H3 expression in the TME. We investigated the relationship between B7-H3 expression and prognosis as well as changes in the TME with B7-H3 expression using 110 surgically resected pathological specimens retrospectively. We examined the correlation between B7-H3 and programmed cell death-ligand 1 (PD-L1) expression in single cells. High B7-H3 expression in tumor cells was associated with a better prognosis and a significant increase in the number of CD163+PD-L1+ macrophages. Quantitative analysis revealed that there is a positive correlation between B7-H3 and PD-L1 expression in tumor and stromal cells, as well as in intratumoral tumor-infiltrating lymphocytes and tumor-associated macrophages in the same cells. CD68+, CD163+, and CK+ cells with PD-L1+ phenotypes had higher B7-H3 expression compared to PD-L1- cells. Our findings demonstrate a correlation between B7-H3 and PD-L1 expression in the same cells, indicating that therapies targeting B7-H3 could provide additional efficacy in patients refractory to PD-L1-targeting therapies.

Bilateral thoracotomy for horseshoe lung complicated with severe aspergilloma: a case report.

BACKGROUND: Horseshoe lung is a rare congenital malformation in which the lung protrudes from the mediastinum to the other side. Owing to the high frequency of other fatal cardiovascular complications, it is often diagnosed in childhood and rarely unnoted until adulthood. We report a case of horseshoe lung in an older patient who underwent thoracotomy. CASE PRESENTATION: The patient was a 69-year-old man with chronic obstructive pulmonary disease (COPD) and a history of heavy smoking. The patient was admitted to the hospital because of acute exacerbation of COPD. Computed tomography revealed horseshoe lung and pulmonary sequestration with pneumonia. This was the first time that he was diagnosed with horseshoe lung; however, he had been treated for pneumonia multiple times before. Surgery for the horseshoe lung was recommended; however, the patient declined it because his symptoms of acute COPD exacerbation were relieved by medication. Aspergillus infection of the horseshoe lung led to frequent bloody sputum, and the patient's respiratory condition gradually worsened. Two years after the initial diagnosis, the patient decided to undergo the surgery. Surgery was performed in the order of left and right thoracotomies, with posterolateral thoracotomies performed bilaterally. Surgery was difficult because of strong adhesions around the inflamed lung; however, the lung was removed in one lump. The patient was extubated on postoperative day (POD) 1, and rehabilitation was initiated. His high sputum volume caused postoperative pneumonia, and the patient was again placed on a ventilator on POD 9. He underwent open-window surgery for concomitant pyothorax. The patient was weaned off the ventilator when the inflammation improved and was discharged on POD 133. The patient lived at home, developed severe pneumonia 4 months later, and died of respiratory failure. CONCLUSION: Pulmonary sequestration and horseshoe lungs are congenital malformations that require surgery. The selection of the optimal time for surgery is important.

Usefulness of the Global Leadership Initiative on malnutrition (GLIM) criteria in preoperative nutritional assessment of patients with primary lung cancer.

BACKGROUND AND AIMS: The Global Leadership Initiative on Malnutrition (GLIM) developed a new method for evaluating malnutrition; however, no consensus has been reached regarding the use of these criteria. Therefore, this study aimed to investigate the association between nutritional status assessed using the GLIM criteria and outcomes of lung cancer after surgery. METHODS: Patients with non-small cell lung cancer who underwent lung resection and bioelectrical impedance analysis to estimate muscle mass before surgery were included. Their background, pathological stage, recurrence, and prognosis were investigated. Patients were divided into two groups according to the GLIM criteria: normal nutrition and malnutrition groups. RESULTS: The normal and malnutrition groups comprised 110 and 88 patients, respectively. Malnutrition was significantly associated with poor overall survival after surgery (P = 0.025) but not with disease-free survival. Multivariate analysis showed that malnutrition (hazard ratio [HR]:2.374, P = 0.020), advanced pathological stage of lung cancer (HR: 1.919, P = 0.002), and the presence of postoperative complications (HR: 2.035, P = 0.047) were significantly associated with poor overall survival. CONCLUSION: Malnutrition assessed using the GLIM criteria was associated with the prognosis of patients with postoperative non-small cell lung cancer. Preoperative assessment using the GLIM criteria would allow for effective nutritional and rehabilitative interventions to improve prognosis.

Pulmonary Artery Aneurysm in a Patient with Nontuberculous Mycobacteria Infection.

Nontuberculous mycobacterial (NTM) infection sometimes leads to the development of pulmonary artery aneurysm (PAA), a rare but life-threatening complication. We herein report a 64-year-old woman with a history of NTM infection who presented with severe hemoptysis. Computed tomography revealed a ruptured PAA, which was treated successfully with pulmonary artery embolization. Subsequent right total pneumonectomy was performed to control infection. This case emphasizes the need to consider PAA in patients with NTM infection who present with hemoptysis. Early detection and appropriate management are critical for preventing this fatal complication.

The possibility of mutations of RAS signaling genes and/or TP53 in combination as a negative prognostic impact on pathological stage I non-small cell lung cancer.

BACKGROUND: The recurrence rate of non-small cell lung cancer (NSCLC) is as high as 30%, even in the cancer with pathological stage I disease. Therefore, identifying factors predictive of high-risk pathological recurrence is important. However, few studies have examined the genetic status of these tumors and its relationship to prognosis. MATERIALS AND METHODS: A cohort of 328 cases of primary lung cancer that underwent complete resection at Tokyo Medical and Dental University (TMDU) was screened for 440 cancer-associated genes using panel testing. Further analyses included 92 cases of pathological stage I NSCLC who did not receive adjuvant chemotherapy. Ridge regression was performed to identify association studies mutational status and postoperative recurrence. These data were then validated using clinical and genetic data from 56 patients in The Cancer Genome Atlas (TCGA). RESULTS: Mutations in TP53, RAS signaling genes KRAS and HRAS, and EGFR were recurrently detected. Ridge regression analysis relevant to recurrence, as well as survival analysis, performed using data from the TMDU cohort revealed significantly shorter relapse-free survival (RFS) for patients with RAS signaling or TP53 gene mutations than for those without (log-rank test, p = 0.00090). This statistical trend was also suggested in the TCGA cohort (log-rank test, p = 0.10). CONCLUSION: Mutations in RAS signaling genes and/or TP53 could be useful for the prediction of shorter RFS of patients with stage I NSCLC.

Low-Rank Combinatorial Optimization and Statistical Learning by Spatial Photonic Ising Machine.

The spatial photonic Ising machine (SPIM) [13D. Pierangeli et al., Large-Scale Photonic Ising Machine by Spatial Light Modulation, Phys. Rev. Lett. 122, 213902 (2019).PRLTAO0031-900710.1103/PhysRevLett.122.213902] is a promising optical architecture utilizing spatial light modulation for solving large-scale combinatorial optimization problems efficiently. The primitive version of the SPIM, however, can accommodate Ising problems with only rank-one interaction matrices. In this Letter, we propose a new computing model for the SPIM that can accommodate any Ising problem without changing its optical implementation. The proposed model is particularly efficient for Ising problems with low-rank interaction matrices, such as knapsack problems. Moreover, it acquires the learning ability of Boltzmann machines. We demonstrate that learning, classification, and sampling of the MNIST handwritten digit images are achieved efficiently using the model with low-rank interactions. Thus, the proposed model exhibits higher practical applicability to various problems of combinatorial optimization and statistical learning, without losing the scalability inherent in the SPIM architecture.

[Minimally Invasive Surgery for Mediastinal Tumor].

We have been performing multiport thoracoscopic surgery as a minimally invasive procedure for mediastinal tumors. The criteria for thoracoscopic surgery are as follow;tumor under 6 cm without invasion of great vessels, chest wall, or lung. We started one port surgery since 2017 and robot-assisted thoracoscopic surgery since 2018. We retrospectively reviewed these three approaches for mediastinal tumor for 12 years. 269 patients underwent surgery for mediastinal tumor, 141 patients by multiport surgery, 21 patients by one port surgery, and 38 patients by robot-assisted thoracoscopic surgery. Of 203 patients with anterior mediastinal tumors, 141 patients underwent thymectomy for thymic tumors (72 patients by multiport surgery, 9 patients by one port surgery, 17 patients by robot-assisted thoracoscopic surgery, and 43 patients by open surgery). There was no difference in tumor size, but the operating time and blood loss were significantly less in one port surgery than in multiport surgery or robot-assisted thoracoscopic surgery. The approaches have become more diverse, with a wider choice of surgical techniques, allowing us to offer more radical minimally invasive surgeries.

A case of repeat oligoprogressive castration-resistant prostate cancer treated with pulmonary metastasectomy.

Introduction: Several retrospective studies have demonstrated the efficacy of progressive site-directed therapy for oligoprogressive castration-resistant prostate cancer. However, eligible patients for progressive site-directed therapy in these studies were limited to oligoprogressive castration-resistant prostate cancer with bone or lymph node metastases without visceral metastases, and little is known about the efficacy of progressive site-directed therapy for oligoprogressive castration-resistant prostate cancer with visceral metastases. Case presentation: We report a case with castration-resistant prostate cancer previously treated with enzalutamide and docetaxel, in which only a solitary lung metastasis was identified throughout the course of treatment. The patient underwent thoracoscopic pulmonary metastasectomy with a diagnosis of repeat oligoprogressive castration-resistant prostate cancer. Only androgen deprivation therapy was continued and his prostate-specific antigen levels remained undetectable for 9 months after surgery. Conclusion: Our case suggests that progressive site-directed therapy may be effective for carefully selected repeat OP-CRPC with a lung metastasis.

Detecting the location of lung cancer on thoracoscopic images using deep convolutional neural networks.

OBJECTIVES: The prevalence of minimally invasive surgeries has increased the need for tumor detection using thoracoscopic images during lung cancer surgery. We conducted this study to analyze the efficacy of a deep convolutional neural network (DCNN) for tumor detection using recorded thoracoscopic images of pulmonary surfaces. MATERIALS AND METHODS: We collected 644 intraoperative thoracoscopic images of changes in pulmonary appearance from 427 patients with lung cancer between 2012 and 2021. The lesion areas on the thoracoscopic images were detected by bounding boxes using an advanced version of YOLO, a well-known DCNN for object detection. The DCNN model was trained and evaluated by a 15-fold cross-validation scheme. Each predicted bounding box was considered successful detection when it overlapped more than 50% of the lesion areas annotated by board-certified surgeons. RESULTS AND CONCLUSIONS: Precision, recall, and F1-measured values of 91.9%, 90.5%, and 91.1%, respectively, were obtained. The presence of lymphatic vessel invasion was associated with successful detection (p = 0.045). The presence of pathological pleural invasion also showed a tendency toward successful detection (p = 0.081). The proposed DCNN-based algorithm yielded an accuracy of more than 90% tumor detection. These algorithms will help surgeons detect lung cancer displayed on a screen automatically.

High density and proximity of CD8+ T cells to tumor cells are correlated with better response to nivolumab treatment in metastatic pleural mesothelioma.

BACKGROUND: The efficacy of immune checkpoint inhibitors (ICIs) in pleural mesothelioma has recently been established. The response to ICIs can be predicted by quantitative analysis of cells and their spatial distribution in the tumor microenvironment (TME). However, the detailed composition of the TME in pleural mesothelioma has not been reported. We evaluated the association between the TME and response to ICIs in this cancer. METHODS: A retrospective analysis of 22 pleural mesothelioma patients treated with nivolumab in different centers was performed using surgical specimens. Four patients had a partial response to nivolumab (response group) and 18 patients had stable or progressive disease (nonresponse group). The number of CD4, CD8, FoxP3, CK, and PD-L1 positive cells, cell density, and cell-to-cell distance were analyzed by multiplex immunofluorescence. RESULTS: PD-L1 expression did not differ significantly between the response and nonresponse groups. The density of total T cells and of CD8+ T cells was significantly higher in the response than in the nonresponse group. CD8+ T cells were more clustered and located closer to tumor cells, whereas regulatory T cells were located further from tumor cells in the response than in the nonresponse group. CONCLUSIONS: High density and spatial proximity of CD8+ T cells to tumor cells were associated with better response to nivolumab, whereas the proximity of regulatory T cells to tumor cells was associated with worse response, suggesting that the distinct landscape of the TME could be a potential predictor of ICI efficacy in pleural mesothelioma.

Extubation by supraglottic airway after lobectomy prevents cough-associated air leaks and prolonged coughing or sore throat.

OBJECTIVES: Double-lumen endobronchial tubes (DLTs) are essential for differential lung ventilation during pulmonary lobectomy, but they are more rigid, longer, larger in diameter and irritable. Coughing at extubation sometimes causes airway and lung injury, which causes severe air leaks, prolonged cough and sore throat. We examined the prevalence of cough-associated air leaks at extubation and postoperative cough or sore throat after lobectomy and evaluated the efficacy of supraglottic airway (SGA) in preventing these complications. METHODS: Patient characteristics and operative and postoperative factors data were collected from patients who underwent pulmonary lobectomy between January 2013 and March 2022. After propensity score matching, these data were compared between the SGA and DLT groups. RESULTS: A total of 1069 patients with lung cancer (SGA, 641; DLTs, 428) were enrolled and coughing at extubation occurred in 100 (23.4%) patients in the DLT group, 65 (65.0%) showed increased cough-associated air leaks at extubation and 20 (30.8%) showed prolonged air leaks. Coughing at extubation occurred in 6 (0.9%) in the SGA group. In 193 patients from each group after propensity score matching, coughing at extubation and the associated air leak increase were significantly lower in the SGA group. Visual analogue scale of postoperative cough and sore throat on postoperative days 2, 7 and 30 were significantly lower in the SGA group. CONCLUSIONS: SGA is effective and safe for preventing cough-associated air leaks and prolonged postoperative cough or sore throat at extubation following pulmonary lobectomy.

Association between socioeconomic status and net survival after primary lung cancer surgery: a tertiary university hospital retrospective observational study in Japan.

BACKGROUND: Inequalities in opportunities for primary lung cancer surgery due to socioeconomic status exist. We investigated whether socioeconomic inequalities exist in net survival after curative intent surgery at a tertiary university hospital, in Japan. METHODS: Data from the hospital-based cancer registry on primary lung cancer patients who received lung resection between 2010 and 2018 were linked to the surgical dataset. An area deprivation index, calculated from small area statistics and ranked into tertiles based on Japan-wide distribution, was linked with the patient's address as a proxy measure for individual socioeconomic status. We estimated net survival of up to 5 years by deprivation tertiles. Socioeconomic inequalities in cancer survival were analyzed using an excess hazard model. RESULTS: Of the 1039 patient-sample, advanced stage (Stage IIIA+) was more prevalent in the most deprived group (28.1%) than the least deprived group (18.0%). The 5-year net survival rates (95% confidence interval) from the least to the most deprived tertiles were 82.1% (76.2-86.6), 77.6% (70.8-83.0) and 71.4% (62.7-78.4), respectively. The sex- and age-adjusted excess hazard ratio of 5-year death was significantly higher in the most deprived group than the least deprived (excess hazard ratio = 1.64, 95% confidence interval: 1.09-2.47). The hazard ratio reduced toward null after additionally accounting for disease stage, suggesting that the advanced stage may explain the poor prognosis among the deprived group. CONCLUSION: There was socioeconomic inequality in the net survival of patients who received curative intent surgery for primary lung cancer. The lower socioeconomic status group might be less likely to receive early curative surgery.

Extended pleurectomy/decortication and hyperthermic intraoperative intrapleural cisplatin perfusion for malignant pleural mesothelioma.

Objective: To evaluate the efficacy of multimodality treatment including extended pleurectomy/decortication (P/D) and hyperthermic intraoperative chemotherapy (HIOC) with cisplatin for malignant pleural mesothelioma (MPM), we investigated the pharmacokinetics of platinum, adverse events after HIOC, and survival outcome. Methods: Fifty-three patients with pathologically diagnosed MPM (cT1-3N0-1M0, excluding sarcomatoid) underwent an extended P/D and HIOC (cisplatin 80 mg/m2 in saline 2 L, 42°C, 60 minutes) since 2011. The protocol includes postoperative 4 cycles of cisplatin and pemetrexed. Platinum concentrations in the perfusate (before and after) and the serum (1, 2, 4, 8, 24, 48, 72 hours after perfusion) were measured in 10 patients. Mortality and morbidity, especially adverse events of renal function, were investigated, and survival and affecting factors were examined. Results: All patients obtained macroscopic complete resection and pathologic staging revealed as follows: T1/2/3/4: 12/8/23/10, N0/1: 36/17, stage 1A/1B-3A/3B: 12/31/10, respectively. Platinum concentrations in the perfusate indicated that 28% of the dose remained in the pleural cavity, and the maximum concentration in the serum was 0.91 µg/mL. Six patients (11%) showed elevated max-creatinine (>2 mg/dL) postoperatively. Two patients (4%) received renal-replacement therapy, and one was weaned before discharge. There was no 30-day mortality and one in-hospital death (1.9%). Forty-six patients (87%) received multiple cycles of perioperative systemic chemotherapy. Median overall survival (OS) and disease-free survival (DFS) were 52.4 months and 18.7 months. Patents with stage 1A demonstrated a 5-year OS of 67.3% and a median DFS of 67.1 months, and patients with stage 1B-3A demonstrated a 5-year OS of 50.1% and a median DFS of 20.4 months. Univariate analysis showed histological subtype, p-T, p-stage, and multimodality treatment as significant factors affecting OS. Multivariate analysis revealed histology, p-stage, and multimodality as independent. Conclusions: Extended P/D and HIOC with cisplatin for MPM is acceptable with limited acute kidney injury. This multimodality protocol provides promising favorable survival for stage 1A-3A disease.

Spatial-photonic Ising machine by space-division multiplexing with physically tunable coefficients of a multi-component model.

This paper proposes a space-division multiplexed spatial-photonic Ising machine (SDM-SPIM) that physically calculates the weighted sum of the Ising Hamiltonians for individual components in a multi-component model. Space-division multiplexing enables tuning a set of weight coefficients as an optical parameter and obtaining the desired Ising Hamiltonian at a time. We solved knapsack problems to verify the system's validity, demonstrating that optical parameters impact the search property. We also investigated a new dynamic coefficient search algorithm to enhance search performance. The SDM-SPIM would physically calculate the Hamiltonian and a part of the optimization with an electronics process.

PHOX2B is a Sensitive and Specific Marker for the Histopathological Diagnosis of Pheochromocytoma and Paraganglioma.

Pheochromocytomas (PCCs) and paragangliomas (PGLs) are non-epithelial neuroendocrine neoplasms originating from the adrenal medulla and paraganglion of the sympathetic and parasympathetic nervous system, respectively. PCCs and PGLs show histological similarities with other epithelial neuroendocrine neoplasms and olfactory neuroblastomas (ONBs), and the differential diagnosis of PGLs is particularly difficult. Therefore, we compared the sensitivity of PHOX2A, PHOX2B, and tyrosine hydroxylase (TH) in the histopathological diagnosis of PCCs and PGLs immunohistochemically using the tissue microarrays of 297 neoplasms including PCCs, PGLs, neuroblastomas, ganglioneuromas, epithelial neuroendocrine neoplasms, and ONBs. Using cutoff values of 25%, 5%, and 5% of tumor cells expressing PHOX2A, PHOX2B, and TH, respectively, as positive, 40 of 51 PCCs, 32 of 33 parasympathetic/head and neck PGLs (HNPGLs), 17 of 19 sympathetic/thoracoabdominal PGLs (TAPGLs), and 12 of 152 epithelial neuroendocrine neoplasms, including 123 well-differentiated and 29 poorly differentiated neuroendocrine neoplasms, were PHOX2A-positive. All 51 PCCs, 33 HNPGLs, and 19 TAPGLs were PHOX2B-positive, while all 152 epithelial neuroendocrine neoplasms were PHOX2B-negative. Moreover, 50 of 51 PCCs, 13 of 33 HNPGLs, all TAPGLs, and 12 of 152 epithelial neuroendocrine neoplasms were TH-positive. All ONBs were negative for PHOX2A, PHOX2B, and TH. PHOX2B was the most sensitive and specific diagnostic marker for PCCs and PGLs among PHOX2A, PHOX2B, and TH. PHOX2B can facilitate identification of PCCs and PGLs from epithelial neuroendocrine neoplasms and ONBs, especially in the case of HNPGLs, in which TH is often negative.

Reconstruction of the Bifurcation of Right Upper Bronchus Using Miyamoto's Technique for Typical Carcinoid.

A 41-year-old woman presented with productive cough and exertional dyspnea. Bronchoscopy revealed an endobronchial tumor arising from the membrane proximal to the bifurcation of right upper bronchus, and the tumor was a typical carcinoid. The right main bronchus, right upper lobe bronchus, and intermediate bronchus were resected along with the tumor. Intraoperative pathological diagnosis of the bronchial stumps was negative, and bronchial reconstruction was subsequently performed. Two-thirds of the circumference of the right main bronchus and the right intermediate bronchus were anastomosed. The right upper lobe bronchus was anastomosed in an end-to-side fashion. The anastomotic site was covered by the intercostal muscles.

Endovascular Treatment for Acute Ischemic Stroke After Video-Assisted Thoracoscopic Pulmonary Lobectomy in Patients With Lung Cancer: A Report of Four Cases and Literature Review.

BACKGROUND: Postoperative cerebral embolic stroke is a serious complication of pulmonary lobectomy, occurring in 1.1% of patients undergoing lobectomy through video-assisted thoracoscopic surgery (VATS). The mechanism of this complication is thought to be embolic stroke caused by thrombus formed due to stagnation in the pulmonary vein stump after VATS lobectomy. There have been few reports demonstrating the utility of endovascular treatment (EVT) for cerebral embolic stroke after VATS lobectomy. CASE DESCRIPTION: In our case series, cerebral embolic stroke occurred after VATS pulmonary lobectomy for lung cancer, including the left upper lobe in three cases and the right lobe in one. The median duration of ischemic stroke after VATS was 4.5 days (interquartile range, 2-9 days). The median time from stroke onset to puncture was 130 min. Successful recanalization was achieved in all cases, and two patients achieved favorable clinical outcomes (modified Rankin scale, 0-2). CONCLUSION: We report a case series of four patients who underwent EVT for acute embolic stroke after VATS lobectomy for lung cancer. EVT is considered a reasonable and feasible therapeutic option for this condition.

Sensitivity to dabrafenib and trametinib treatments in patients with non-small-cell cancer harboring BRAF compound mutations: A pooled analysis of BRAF p.V600E-positive advanced non-small-cell lung cancer.

PURPOSE: The present study clarified the sensitivity of the BRAF tyrosine kinase inhibitor mechanism in patients with BRAF compound mutation and predicted the sensitivity using molecular dynamics simulation. METHODS: We examined 16 BRAF tumors with p.V600E-positive non-small-cell lung cancer. RESULTS: One patient (6.2%) had a BRAF p.V600E and p.K601_W604 compound mutation with a good clinical response to dabrafenib and trametinib. Molecular dynamics simulation also complemented the effect. CONCLUSIONS: The combination of a genetic analysis and computational simulation model may help predict the sensitivity for dabrafenib in cases with a rare BRAF compound mutation. The construction of a genomic and simulation fused database is important for the development of personalized medicine in this field.

Pulmonary Mucormycosis Involving the Left Main Bronchus and the Pulmonary Artery.

Pulmonary mucormycosis is an extremely rare disease. It often occurs in immunocompromised patients, such as patients with diabetes and those on long-term steroid use. The prognosis of the disease is poor despite the administration of antifungal agents and removal of the necrotic tissue. Herein, we present a successfully treated case of pulmonary mucormycosis in a patient with type 2 diabetes who underwent left pneumonectomy because of the involvement of the left main pulmonary artery and the left main bronchus. Irrespective of the infected organ, complete debridement of the infected tissue and treatment with antifungal agents are essential for treating mucormycosis.