Effect of mTOR inhibitors on the mortality and safety of patients with lymphangioleiomyomatosis on the lung transplantation waitlist: A retrospective cohort study.

BACKGROUND: Although lung transplantation (LTx) is the last resort for patients with end-stage lymphangioleiomyomatosis (LAM), the high waitlist mortality is a source of concern in Japan. Discontinuation of mechanistic target of rapamycin (mTOR) inhibitors prior to LTx is recommended due to the incidence of severe adverse events. Therefore, we hypothesized that mTOR inhibitors may affect the mortality of patients with LAM on the LTx waitlist. METHODS: We retrospectively compared the characteristics of consecutive patients with LAM on the LTx waitlist who were and were not receiving mTOR inhibitors. RESULTS: Twenty-nine consecutive patients with LAM who listed our center between January 2004 and December 2021 were selected from the database and enrolled in the present study. Seventeen patients (58.6%) were receiving a mTOR inhibitor, sirolimus (treatment group). During a median listing period of 1277 days, 12 patients (41.4%) were hospitalized, six patients (20.7%) died from disease before LTx, and 15 patients underwent LTx. Among the deceased patients, four patients (66.6%) had pneumothoraces. The waitlist mortality in the treatment group was significantly lower than that in the non-treatment group (p = 0.03). Among the six patients who discontinued sirolimus in the treatment group, four patients (66.6%) were hospitalized with respiratory complications after the discontinuation of sirolimus. No mTOR inhibitor-related complications arose in the treatment group undergoing LTx (n = 7), including those on a reduced sirolimus dose. CONCLUSIONS: Administration of an mTOR inhibitor until LTx may decrease waitlist mortality. Due to life-threatening events after discontinuing sirolimus pre-LTx, a reduced dose until LTx is permissible.

[Preoperative Virtual Reality Simulation Regarding the Appropriate Port Location for Thoracoscopic Surgery for the Mediastinal or Chest Wall Lesions].

In thoracoscopic surgery for mediastinal or chest wall lesions the suitable position of ports( trocars) are required depending on the position of a target lesion in a particular patient. We have therefore developed a virtual reality (VR) simulation system using the specific data of each individual patient. The model data generation system, PASS-GEN, is customized for thoracic surgery. The chest wall and organs around the tumor are extracted from DICOM image data of computed tomography (CT) scan, and three-dimensional (3D) virtual images are constructed. Rehearsal of ports insertion is carried out by locating the scope and the forceps anywhere on the chest wall on PC monitor. The constructed VR images clearly show three dimensional relationships between the target and surrounding structures. This system also simulates circumstances where on the chest wall a thoracoscope and tools should be inserted for the better view and more comfortable manipulation. Particularly in mediastinal or chest wall surgery VR simulation is more practical because those structures would be less transformed during operation.

G-CSF-producing left lung squamous cell carcinoma positive for ROS1 rearrangements completely resected after neoadjuvant radiation chemotherapy: A case report.

Granulocyte colony-stimulating factor (G-CSF) promotes neutrophil production. G-CSF-producing tumors have a feature of neutrophilia without infection, and most patients with G-CSF-producing tumors show an aggressive clinical course and poor prognosis. A 71-year-old woman was diagnosed with left lung cancer, cT4N1M0, stage IIIA. Severe neutrophilia and bone marrow uptake in 18-fluorodeoxyglucose-positron emission tomography suggested the possibility of G-CSF-producing lung cancer. Following neoadjuvant radiation chemotherapy, left lower lobectomy and left upper lobe partial resection were performed. According to pathology findings of the resected specimen, the patient was diagnosed with G-CSF-producing left lung squamous cell carcinoma. Moreover, genetic tests showed that the tumor cells were positive for c-ros oncogene 1 (ROS1) rearrangements. To our knowledge, this is the first reported case of G-CSF-producing lung cancer with ROS1 rearrangements, and complete resection was performed successfully after neoadjuvant radiation chemotherapy.

The Association of Vacuum-Assisted Closure Therapy with Dynamic Volume Change of a Muscle Flap Transposed in an Empyema Cavity for Chronic Empyema: A Case Report.

A 62-year-old woman with a history of lung resection for lung cancer was admitted to our hospital due to cough, which became progressively more severe. She was diagnosed with chronic empyema with bronchopleural fistula (BPF) of the right upper bronchial stump. Although a pedicled muscle flap was transposed to the empyema cavity, the fistula remained. We used a vacuum-assisted closure system after open-window thoracotomy and observed the cavity reduction with expansion of the transposed muscle flap. We quantitatively evaluated the dynamics of the cavity change using a three-dimensional image analysis system. A reduction of the volume of the muscle flap by prolonged empyema and expansion of the muscle flap was observed immediately after vacuum-assisted management. However, expansion of the right residual lung was not recognized. Pedicled muscle flap transposition followed by vacuum-assisted management after open-window thoracotomy may be effective for treating chronic empyema caused by BPF.

Reduced risk of recurrent pneumothorax for sirolimus therapy after surgical pleural covering of entire lung in lymphangioleiomyomatosis.

BACKGROUND: Patients with lymphangioleiomyomatosis (LAM) frequently experience pneumothorax. Although sirolimus is the standard therapy for LAM, its effect on pneumothorax is controversial. Recently, total pleural covering (TPC) and modified TPC (mTPC) were introduced as surgical treatment options for pneumothorax for patients with LAM. However, the effect of sirolimus on the recurrence of pneumothorax in patients who underwent the treatments is still uncertain. We hypothesized that some clinical factors including sirolimus treatment could predict postoperative recurrence of pneumothorax. In order to clarify this hypothesis, we retrospectively analyzed the clinical data from 18 consecutive patients with LAM who underwent 24 surgical pleural covering of entire lung (SPC) as 17 TPC and 7 mTPC against pneumothoraces from surgical database between January 2005 and January 2019, and we determined the predictors of postoperative recurrence. RESULTS: Of the 24 surgeries of SPC, 14 surgeries (58.3%) had a history of two or more ipsilateral pneumothoraces, and 11 surgeries (45.8%) had a history of ipsilateral pleural procedures before SPC. Sixteen surgeries (66.6%) in 12 patients received treatment of sirolimus after SPC (sirolimus group). With a median follow-up time of 69.0 months after SPC, four surgeries (16.6%) in three patients had a postoperative recurrence, and the 5-year recurrence-free survival (RFS) after SPC was 82.9%. In patients with postoperative recurrence, serum level of vascular endothelial growth factors D was significantly higher than that in those with non-recurrence (3260.5 vs. 892.7 pg/mL, p = 0.02), and the rate of sirolimus treatment in the recurrence group was significantly lower than that in the no-recurrence group (0 vs. 80%, p = 0.006). The log-rank test showed that the RFS of the sirolimus group (sirolimus use after SPC) was significantly better than that of the non-sirolimus group (p = 0.001), and no significant difference was observed for other factors. CONCLUSION: We first reported sirolimus might effectively suppress the recurrence of pneumothoraces in LAM patients who received SPC. Sirolimus induction after SPC (TPC or mTPC) might be a feasible option for frequent pneumothorax in LAM.

Histologically Proven Dendriform Pulmonary Ossification: A Five-case Series.

Dendriform pulmonary ossification (DPO) is a rare condition characterized by metaplastic bone formation in the lung parenchyma. It has been reported to be often associated with primary lung diseases, such as usual interstitial pneumonia (UIP) or chronic aspiration of gastric acid; however, its clinical features and pathophysiology remain unclear, especially in idiopathic cases. We herein report five DPO cases, including three with an idiopathic origin. In all cases of idiopathic DPO, the pathological and radiological examinations showed localized pulmonary lesions suggesting inflammation or hemorrhaging.

Adenocarcinoma with fetal features invading the right superior sulcus treated with neoadjuvant chemoradiotherapy followed by complete video-assisted thoracoscopic right upper lobectomy: a case report.

BACKGROUND: Fetal adenocarcinoma of the lung is a rare lung neoplasm that accounts for only 0.5% of all primary lung cancers. Because of its rarity, effective treatments for the management of the tumor are poorly understood. We herein report a case of adenocarcinoma with fetal features of the lung with invasion of the right superior sulcus that was treated with neoadjuvant chemoradiotherapy followed by surgical resection. CASE PRESENTATION: A 54-year-old man was referred to a medical institution due to right inner forearm pain. On computed tomography of the chest, a 56-mm mass with invasion of right superior sulcus was discovered. Bronchoscopic biopsy revealed non-small cell lung carcinoma. We performed concurrent chemotherapy (2 cycles of cisplatin and vinorelbine) and thoracic radiation therapy (40 Gy in 20 fractions). As the result of extreme tumor reduction after neoadjuvant chemoradiotherapy, we could perform right upper lobectomy by complete video-assisted thoracoscopic surgery. Since no viable cancer cells were detected from the pathological examination of the resected tissue, the specimen obtained by bronchoscopic biopsy was reexamined by immunohistochemistry. The analysis supported a pathologic diagnosis of adenocarcinoma with fetal features. CONCLUSIONS: We experienced a case of adenocarcinoma with fetal features of the lung in which the patient showed a complete response to neoadjuvant chemoradiotherapy. In addition, the tumor invading the right superior sulcus was completely resected by video-assisted thoracoscopic lobectomy. Neoadjuvant chemoradiotherapy followed by surgery may be also an effective treatment for advanced-stage high-grade fetal adenocarcinoma of the lung, similarly to other subtypes of advanced-stage primary lung cancer.

Epithelioid sarcoma in the chest wall: a case report and literature review.

BACKGROUND: Epithelioid sarcoma (ES) is a rare variant of soft tissue sarcoma. The proximal type of ES occurs in various locations. We present a resected case with proximal-type ES that occurred in the chest wall and discuss the relevant literature. CASE PRESENTATION: A 47-year-old woman was referred for a 6-month history of a right anterior chest mass with tenderness. Chest computed tomography showed an invasive chest wall mass with calcification surrounding the third rib. Aspiration biopsy cytology suggested malignancy. We performed wide resection, including the middle part of the pectoralis major muscle, the pectoralis minor muscle, the third and fourth ribs, and reconstruction of the chest wall, using a 2-mm polytetrafluoroethylene patch. Severe deformation of the chest wall was avoided. Postoperative physical therapy of the shoulder was effective for the continuous pain and weakness of the arm. She has remained alive for 1 year and 10 months without recurrence. Our literature review showed five previously reported cases of ES in the chest wall, and all of these were surgically resected. Two of these patients suffered from frequent local recurrence and died of disease. CONCLUSIONS: ES in the chest wall is rare. Previous reports have indicated that surgical resection with tumor-free margins is essential for treatment. We performed complete resection of the tumor in our case, and a polytetrafluoroethylene patch was effective for reconstructing the deficit in the chest wall.

Thymoma in middle mediastinum that induced tracheal compression-Case report and literature review.

BACKGROUND: A thymoma, an epithelial neoplasm of the thymus, mainly occurs in the anterior mediastinum, while few are seen in the middle mediastinum. CASE PRESENTATION: An 83-year-old male was referred for an incidental mass in the middle mediastinum. He had severe dementia and denied symptoms. Our follow-up computed tomography (CT) examinations had revealed the progress of tracheal compression along with tumor enlargement for 2 years. At 85 years old, we performed a thymomectomy via a median sternotomy to avoid complete trachea obstruction. The pathological diagnosis was WHO type A thymoma, Masaoka stage II. One year after surgery, the patient was free of disease. DISCUSSION: Thymomas occurring in the middle mediastinum are rare. In our review of 13 such cases, none were Masaoka stage III or IV, while the majority (9/13, 69.2%) were WHO type A or AB. CONCLUSION: We encountered a thymoma in the middle mediastinum that showed enlargement over a 2-year period, inducing severe tracheal compression. Thymomas can occur widely in pharyngeal pouch-derived locations and should be considered in differential diagnosis of a middle mediastinum tumor.

Minimally invasive anterior chest wall lifting technique for thoracoscopic mediastinal approach.

Anterior chest wall lifting facilitates a wide view and allows easy access during thoracoscopic surgery in a supine position for anterior mediastinal lesions. We previously reported an anterior chest wall lifting method for a thymectomy that utilizes our original costal hooks. Here, we present a less invasive method that can be performed with only a needle puncture, i.e., a metal plate placed under the ribs is lifted with a wire inserted through the anterior chest wall. We have applied this novel 'T-lifting method' for 5 different cases with anterior mediastinal tumors, and found it to be simple and easy to perform, as well as less invasive for patients undergoing thoracoscopic surgery.