The Clinical Course and Treatment of a Case of Refractory Systemic Juvenile Myasthenia Gravis Successfully Treated with Thymectomy.

Juvenile myasthenia gravis (JMG) exhibits a more favorable response to glucocorticoids and has a better prognosis than adult myasthenia gravis. However, no established treatment exists for refractory JMG. Although thymectomy has been performed in several patients with refractory systemic JMG, there are few detailed clinical descriptions of patients who underwent thymectomy. Here, we present the case of a 10-year-old boy with refractory systemic JMG who was successfully treated with thymectomy. The patient developed symptoms, including dysphagia, malaise, diurnal ptosis, and weakness in the trunk muscles, and he was diagnosed with generalized JMG. Despite undergoing various treatments, including steroids, tacrolimus, steroid pulse therapy, intravenous immunoglobulin, azathioprine (AZT), and rituximab, his symptoms did not improve. Therefore, he underwent a thoracoscopic thymectomy 24 months after disease onset. Thymectomy led to remission, as demonstrated by a significant reduction in the quantitative myasthenia gravis score and anti-acetylcholine receptor antibody levels, which persisted for 43 months after surgery. Our case demonstrates the effectiveness of thymectomy in systemic JMG patients with positive anti-acetylcholine receptor antibodies, despite therapeutic failure with AZT and rituximab, within 2 years of disease onset.

LAG3 is an independent prognostic biomarker and potential target for immune checkpoint inhibitors in malignant pleural mesothelioma: a retrospective study.

BACKGROUND: Lymphocyte-activation gene 3 (LAG3) is an immune checkpoint receptor; novel LAG3 immune checkpoint inhibitors (ICIs) exhibit therapeutic activity in melanoma. The role of LAG3and ICIs of LAG3 are unknown in malignant pleural mesothelioma (MPM). This study aimed to uncover the prognostic landscape of LAG3 in multiple cancers and investigate the potential of using LAG3 as an ICIs target in patients with MPM. METHODS: We used The Cancer Genome Atlas (TCGA) cohort for assessing mRNA expression and our cohort for immunohistochemical expression. TCGA cohort were analyzed using the Wilcoxon rank-sum test to compare mRNA expression between normal and tumor tissues in multiple cancers. We used 86 MPM cases from TCGA and 38 MPM cases from our cohort to analyze the expression of LAG3 in tumor-infiltrating lymphocytes. The mean LAG3 mRNA expression was set as the cut-off and samples were classified as positive/negative for immunohistochemical expression. Overall survival (OS) of patients with MPM was determined using the Kaplan-Meier method based on LAG3 mRNA and immunohistochemical expression. OS analysis was performed using the multivariate Cox proportional hazards model. The correlation of LAG3 expression and mRNA expression of tumor immune infiltration cells (TIICs) gene markers were estimated using Spearman correlation. To identify factors affecting the correlation of LAG3 mRNA expression, a multivariate linear regression model was performed. RESULTS: LAG3 mRNA was associated with prognosis in multiple cancers. Elevated LAG3 mRNA expression was correlated with a better prognosis in MPM. LAG3 expression was detected immunohistochemically in the membrane of infiltrating lymphocytes in MPM. LAG3 immunohistochemical expression was correlated with a better prognosis in MPM. The multivariate Cox proportional hazards model revealed that elevated LAG3 immunohistochemical expression indicated a better prognosis. In addition, LAG3 mRNA expression was correlated with the expression of various gene markers of TIICs, the most relevant to programmed cell death 1 (PD-1) with the multivariate linear regression model in MPM. CONCLUSIONS: LAG3 expression was correlated with prognosis in multiple cancers, particularly MPM; LAG3 is an independent prognostic biomarker of MPM. LAG3 regulates cancer immunity and is a potential target for ICIs therapy. PD-1 and LAG3 inhibitors may contribute to a better prognosis in MPM. TRIAL REGISTRATION: This study was registered with UMIN000049240 (registration day: August 19, 2022) and approved by the Institutional Review Board (approval date: August 22, 2022; approval number: 2022-0048) at Tokyo Women's Medical University.

[Improved Surgical Technique for Closing the Tracheocutaneous Fistula].

The tracheocutaneous fistula is a late complication after tracheotomy decannulation, which decreases the quality of life. Though several procedures to close tracheocutaneous fistula were reported, postoperative wound dehiscence was frequently noted. We developed new surgical technique to prevent this complication and report a case in which the technique was successfully applied. This surgical technique is useful simple method to be effective, and safe.

[Outcomes of Surgical Cases of Solitary Rib Metastases in Renal Cell Carcinoma].

BACKGROUND: Aggressive surgical treatment for renal cell carcinoma (RCC) bone metastasis has shown good results. METHODS: Since January 1995, four patients underwent surgery at our institution for rib metastasis of operated RCCs. Of these patients, three were male and one was female. The patients had a mean age of 67.5 years. Except one patient who presented with rib metastasis at the time of diagnosis of RCC, the average period of metastasis to the ribs after RCC surgery was 24.3 months. All patients underwent resection of metastasized tumors involving the ribs, with or without chest wall involvement. The clinical features of the surgical treatment for RCC bone metastasis were retrospectively analyzed. RESULTS: The mean time to tumor recurrence was 22.3 months postmetastasectomy. All patients developed other bone metastases and underwent multidisciplinary therapy. After metastasectomy, the four patients survived for 19~93 months. CONCLUSION: Surgical treatment for patients with rib metastases of RCC may contribute in prolonging survival.

[Surgical Cases of Solitary Lesion after Surgery for Primary Lung Cancer].

Lung nodules during postoperative follow-up of lung cancer are generally suspected to be its recurrence, but some cases are diagnosed as non-malignant disease. From January 2001 to November 2018, we experienced 5( 4.5%) new non-malignant lesions in 112 lung cancer patients who underwent a lung resection. The average period from first to second lung surgery was 36.2 months (range:3-64), and computed tomography findings before the second surgery were solid nodules in four cases and groundglass opacity in one case. The average maximum standardized uptake value of the lesions on fluorodeoxyglucose positron emission tomography was 4.29 (range:0-10.85). The diagnosis after the second surgery was pulmonary cryptococcosis in 2 cases, nontuberculous mycobacteriosis in 1 case, inflammatory mass in 1 case, and pneumonia in 1 case. The differential diagnosis between these diseases and lung cancer recurrence is discussed in the present study.

Mediastinal paraganglioma successfully resected by robot-assisted thoracoscopic surgery with en bloc chest wall resection: a case report.

BACKGROUND: Robot-assisted thoracoscopic surgery (RATS) is useful for surgery in the apical region of the chest cavity, as it narrows towards the head. Here, we describe a nonfunctional, rib-invasive paraganglioma arising in the posterior mediastinum that was successfully removed using RATS combined with chest wall resection. CASE PRESENTATION: A 31-year-old woman presented with a posterior mediastinal mass on chest computed tomography (CT) scan during a medical check-up 2 years prior. Positron emission tomography/computed tomography scan with F-18 fluorodeoxyglucose revealed a mass associated with standardized uptake maximum value of 2.69. With a preoperative diagnosis of neurogenic tumor by CT-guided percutaneous fine-needle aspiration biopsy, we performed robot-assisted tumor resection combined with chest wall resection. The wristed instruments of the robotic surgical system have increased range of motion and enabled the tumor resection without organ injury in the thoracic cavity. Histopathology examination revealed a non-functional paraganglioma with rib invasion. CONCLUSIONS: RATS is a useful technique, enabling safer and easier resection of a mediastinal tumor adjacent to surrounding organs.

[Surgical Treatment and Perioperative Management for Lung and Mediastinal Surgical Patient with Cerebrovascular Diseases].

The Japanese Joint Committee of Lung Cancer Registry reported that 1,091 patients( 5.8%) had cerebrovascular diseases as comorbidities in "A report from the Japanese Joint Committee of Lung Cancer Registry;a study of 18,973 surgical cases in 2010;secondary publication". They reported that 24 patients caused cerebral hemorrhage or cerebral infarction within 30 days after surgery. Since the elderly patient surgery is increasing, the incidence their perioperative stroke is increasing too, often leading to severe conditions. It is necessary to evaluate the risk factors and history of cerebrovascular disease prior to surgery. As most perioperative strokes occur within 3 days after surgery, and the recurrence rate is higher in patients with a history of cerebrovascular diseases, systematic perioperative management should be treated to prevent recurrence in the perioperative period. If patient taking antithrombotic drugs undergo surgery, it is necessary to be informed of the risks such as intraoperative stroke associated with pausing and resuming antithrombotic drugs. Patient with cerebrovascular disease must be diagnosed accurately and promptly, as cerebrovascular disease involves the conditions of ischemia and hemorrhage.

[Usefulness of Long Shaft Stapler in Robot-assisted Thoracic Surgery Lung Resection].

Since national health insurance began to cover robot-assisted thoracoscopic surgery (RATS) for malignant lung tumors, malignant mediastinal tumors, and benign mediastinal tumors in Japan starting in 2018, the number of RATS performed domestically has increased rapidly. In the case of undiagnosed lung tumor, it is necessary to perform a thoracoscopic lung biopsy in the port arrangement for RATS lung resection in the case of undiagnosed lung tumor. The 2 ports are placed in the same 8th intercostal space and a 3 cm utility thoracotomy is added to the 4th or 5th intercostal space for the thoracoscopic lung biopsy. Because the assistant uses the stapler from the port, the distance to the target area increases. When it is converted to RATS for malignant lung diseases, the utility thoracotomy is often hidden by the robot arm and all ports placed in the 8th intercostal space are far from the target area. Furthermore, the assistant working space outside the patient's body is limited by the robot arms. The Signia stapling system has an adapter to extend the shaft. By attaching the adapter, the shaft can be extended by 10 cm. This permits easy handling of the stapler during both thoracoscopic biopsy and RATS lung resection.

Comparison of tumor cell numbers and 22C3 PD-L1 expression between cryobiopsy and transbronchial biopsy with endobronchial ultrasonography-guide sheath for lung cancer.

BACKGROUND: We previously reported cryobiopsy (Cryo) with endobronchial ultrasonography-guide sheath (EBUS-GS) for peripheral pulmonary lesions (PPLs) provides significantly larger tissues than transbronchial biopsy (TBB) and provides high quantity and quality DNA for gene analysis by next generation sequencing. However, the tumor cell yields and programmed death ligand 1 (PD-L1) expression between each approach have not been compared. Here, we assessed the tumor cell numbers and PD-L1 expression for Cryo with EBUS-GS for PPLs and TBB in patients with lung cancer. METHODS: Sixteen patients were enrolled in this prospective study from June to November 2017 at Tokyo Women's Medical University Hospital. The number of tumor cells from a single biopsy, total number of tumor cells, average number of tumor cells, and 22C3 PD-L1 expression (≥ 50% and ≥ 1%) were compared between Cryo and TBB. RESULTS: The numbers of tumor cells from a single biopsy, total numbers of tumor cells, and average numbers of tumor cells obtained by Cryo were significantly larger than those obtained by TBB (Cryo [means ± standard errors of the means]: 1321 ± 303.7, 1981 ± 411.7, and 1406 ± 310.3; TBB: 208.8 ± 38.24, 1044 ± 189.0, and 208.8 ± 37.81; P < 0.0001, P = 0.0474, P = 0.0006, respectively). PD-L1 ≥ 50% and ≥ 1% patients for Cryo were 18.8 and 56.3%, respectively, whereas those for TBB were 12.5 and 37.5%, respectively. The sensitivity, specificity, positive predictive value, negative predictive value, concordance, and κ coefficient based on Cryo for TBB were 66.7, 100, 100, 92.9, 93.8%, and 0.7647, respectively, for PD-L1 ≥ 50%; and 44.4, 71.4, 66.7, 50, 56.3%, and 0.1515, respectively, for PD-L1 ≥ 1%. CONCLUSION: Cryo with EBUS-GS may be a useful diagnostic approach for lung cancer, with advantages over TBB for gene analysis and whole exon sequencing. Particularly, it could contribute to patients taking pembrolizumab as first-line therapy when PD-L1 was negative by evaluating TBB specimens. It could also provide ample tissue for PD-L1 expression analysis in addition to accurate diagnosis and gene analysis.

Current status of robot-assisted thoracoscopic surgery for lung cancer.

The robotic surgical system was designed to overcome the drawbacks of conventional endoscopic surgery. Since national health insurance in Japan began covering robotic-assisted thoracoscopic surgery (RATS) for malignant lung and mediastinal tumors in 2018, the number of RATS procedures being performed domestically has increased rapidly. This review evaluates the advantages and disadvantages of RATS for patients with lung cancers, based on an electronic literature search of PubMed. The main advantages of RATS are its ability to achieve excellent lymph-node removal with low morbidity and mortality, and minimal postoperative pain. Conversely, its disadvantages include a long operation time and the need for specialized instruments. However, the learning curve for RATS is reported to be shorter than that for VATS: some studies recommend that a surgeon needs to perform 18-22 robotic operations to attain sufficient skill. RATS for lung cancer is more expensive than VATS and the cost of training is high. Although the main disadvantage of RATS is that it reduces operator's tactile senses, the endoscope, which is directly manipulated by the surgeon at the console, using various magnifications, and 3D HD images on the monitor, may compensate for this. Ultimately, RATS offers better maneuverability, accuracy, and stability over VATS.

Thoracoscopic surgical case of an ectopic mediastinal parathyroid adenoma detected by chance: a case report.

BACKGROUND: Ectopic mediastinal parathyroid tumor (EMPT) is a rare cause of primary hyperparathyroidism (PHPT); it is difficult to resect using the cervical approach. We describe a case of using video-assisted thoracic surgery (VATS) for EMPT resection. CASE PRESENTATION: A 67-year-old woman with a history of postoperative thyroid cancer had no symptoms. She was diagnosed with PHPT and underwent thyroid cancer surgery. She had serum calcium and intact parathyroid hormone (PTH) levels of 11.1 mg/dL and 206 pg/mL, respectively. Chest computed tomography showed a 10-mm nodule in the anterior mediastinum. Technetium-99 m methoxyisobutyl isonitrile scintigraphy showed an abnormal uptake lesion in the anterior mediastinum. She was diagnosed with PHPT caused by EMPT and underwent VATS. The pathological examination confirmed parathyroid adenoma. Her serum calcium and intact PTH levels were normal from 15 min after tumor resection. She has had no recurrence of EMPT. CONCLUSIONS: The VATS approach was effective for the resection of EMPT.

[Presurgical Planning and Intraoperative Management of Segmental Vessels and Bronchi during Lung Segmentectomies].

Lung segmentectomy is one of the important options for early lung cancers and metastatic lung tumors. And, segmentectomy is expected to preserve pulmonary functions. However, sometimes it is difficult to identify segmental branches of vessels and bronchi and intersegmental planes during segmentectomies, because segmental anatomies are different from patient to patient and intersegmental plane is not visible. Therefore, preoperative and intraoperative confirmation of the segmental anatomy is important to perform segmentectomies safely and precisely. In this paper, we describe the preoperative 3-dimensional(3D) simulations and intraoperative 3D navigations to understand precise segmental anatomies of patients. Also, we introduce some major techniques for identification of intersegmental planes, and how to cut intersegmental planes.

[Reinforcement Materials for Thoracic Surgery].

Recently, various types of artificial and biological materials have been used for hemostasis or control of air leakage in thoracic surgery. These reinforcement materials are essential for thoracic surgery. Therefore, surgeons must know their characteristics and appropriate usage. In this review, the authors describe the recent development of reinforcement materials in thoracic surgery.

[Usefulness of Continuous Suction Unit in Detecting Air Leakage for Pneumothorax].

A 66-year-old male with spontaneous pneumothorax underwent chest tube drainage in other hospital. After tube drainage, chest X-ray showed that the lung fully expanded and an air leakage was not visible. However, clamping the chest tube led to the collapse of the lung, and he transferred to our hospital. A continuous suction unit with pressure and bubbling time history monitoring system was used to detect intermittent air leakages( MS-009T). He underwent video-assisted thoracoscopic surgery. An air leakage from the right lung successfully closed. A new continuous suction unit was useful in detecting an air leakage which could not be confirmed by visual inspection.

Effect of collagen vascular disease-associated interstitial lung disease on the outcomes of lung cancer surgery.

PURPOSE: This study compared the effect of collagen vascular disease-associated interstitial lung disease (CVD-ILD) with that of idiopathic interstitial pneumonias (IIPs) on the outcomes of lung cancer surgery. METHODS: This study retrospectively reviewed the medical records of patients who underwent surgery for non-small cell lung cancer (NSCLC) and compared the data of 16 patients with CVD-ILD with those of 70 patients with IIPs. The patterns of interstitial lung disease (ILD) on chest computed tomography were classified into usual interstitial pneumonia (UIP) and non-specific interstitial pneumonia (NSIP) patterns. RESULTS: The numbers of UIP and NSIP patterns were 10 (62.5%) and 6 (37.5%) patients in CVD-ILD group, and 62 (88.6%) and 8 (11.4%) patients in IIPs group, respectively. A postoperative acute exacerbation (AE) appeared in 1 patient (6.3%) in the CVD-ILD group and 6 patients (8.6%) in the IIPs group. No significant differences in the incidence of postoperative AE and mortalities were observed between the two groups. The five-year overall survival rates of the CVD-ILD and IIPs groups were 37.5 and 49.2%, respectively. CONCLUSIONS: Surgery for NSCLC in CVD-ILD patients appear to cause no increase in postoperative AE and mortality in comparison to that seen in IIPs patients. Similar to IIPs, CVD-ILD might therefore affect the prognosis of resected NSCLC.

Surgery for non-small cell lung cancer in patients with a history of cardiovascular surgery.

PURPOSE: To clarify if previous cardiovascular surgery (CVS) affects the postoperative outcome of surgery for non-small cell lung cancer (NSCLC). METHODS: We reviewed, retrospectively, the medical records of 36 patients with a history of CVS, who underwent lung cancer surgery at a single institution (study group; SG) and compared their characteristics and postoperative outcomes with those of patients without a history of CVS history (control group; CG), and also with those of patients with coexisting cardiovascular diseases in the CG (specified control group; SCG). Finally, we used a thoracic revised cardiac risk index (ThRCRI) to evaluate the risk of perioperative cardiovascular events. RESULTS: There was a significant difference in the ThRCRI classifications between the SG and the SCG (p < 0.0001). There were no significant differences in the incidence of intraoperative and postoperative complications between the SG and CG, or between the SG and SCG. The 5-year survival rates of the SG, CG, and SCG were 69.3, 73.9, and 65.4 % in all stages, and 83.5, 82.2, and 70.4 % in stage I, respectively. CONCLUSIONS: Previous CVS did not increase the number of perioperative cardiovascular events in this study and had no significant influence on the prognosis of patients undergoing resection of NSCLC.

[Application of Ultrasonography in Detecting Multiple Schwannomas from a Single Intercostal Nerve;Report of a Case].

A 31-year-old man was referred to our hospital for chest abnormal shadow on a routine health checkup. Two nodular lesions were found at the 2nd intercostal space by computed tomography. Chest wall ultrasonography showed 2 masses suspecting tumors. Tumors were resected through 3-cm skin incision with the assistance of thoracoscope. Pathological diagnosis was both schwannomas. Ultrasonography was useful in resecting chest wall tumor.

[Outcomes of Surgical Treatment by Modified Transmanubrial Approach].

OBJECTIVE: The aim of this study is to evaluate the useful and safety of surgical treatment by modified transmanubrial approach(MTA). METHODS: Between January 2000 and May 2014, 10 patients underwent surgical treatment by MTA. Among these patients, we retrospectively reviewed the medical records of 6 patients who had vascular invasion of tumor. We evaluated postoperative outcomes of MTA. RESULTS: All patients were men, with a median age of 56 years. Pathological diagnoses were as follows:thymic carcinoma in 2, thyroid cancer in 2, primary lung cancer in 1, mediastinal lymph node metastasis of thyroid cancer in 1 patient. The median operative time was 468 minutes. The median bleeding was 1,723.5 ml. Four patients underwent angioplasty, including direct suture in 1, graft replacement artificial blood vessel in 3 patients. Right auricle-innominate vein bypass was performed in 3 patients. The median hospitalization term was 29 days. R0 resection was archived in all cases. CONCLUSION: The surgical treatment by MTA is useful and safety for anterior apical tumor and mediastinal tumor invading adjacent vessels. Because of a small number of sample size, further investigation well be needed.

Binocular stereo-navigation for three-dimensional thoracoscopic lung resection.

BACKGROUND: This study investigated the efficacy of binocular stereo-navigation during three-dimensional (3-D) thoracoscopic sublobar resection (TSLR). METHODS: From July 2001, the authors' department began to use a virtual 3-D pulmonary model on a personal computer (PC) for preoperative simulation before thoracoscopic lung resection and for intraoperative navigation during operation. From 120 of 1-mm thin-sliced high-resolution computed tomography (HRCT)-scan images of tumor and hilum, homemade software CTTRY allowed sugeons to mark pulmonary arteries, veins, bronchi, and tumor on the HRCT images manually. The location and thickness of pulmonary vessels and bronchi were rendered as diverse size cylinders. With the resulting numerical data, a 3-D image was reconstructed by Metasequoia shareware. Subsequently, the data of reconstructed 3-D images were converted to Autodesk data, which appeared on a stereoscopic-vision display. Surgeons wearing 3-D polarized glasses performed 3-D TSLR. RESULTS: The patients consisted of 5 men and 5 women, ranging in age from 65 to 84 years. The clinical diagnoses were a primary lung cancer in 6 cases and a solitary metastatic lung tumor in 4 cases. Eight single segmentectomies, one bi-segmentectomy, and one bi-subsegmentectomy were performed. Hilar lymphadenectomy with mediastinal lymph node sampling has been performed in 6 primary lung cancers, but four patients with metastatic lung tumors were performed without lymphadenectomy. The operation time and estimated blood loss ranged from 125 to 333 min and from 5 to 187 g, respectively. There were no intraoperative complications and no conversion to open thoracotomy and lobectomy. Postoperative courses of eight patients were uneventful, and another two patients had a prolonged lung air leak. The drainage duration and hospital stay ranged from 2 to 13 days and from 8 to 19 days, respectively. The tumor histology of primary lung cancer showed 5 adenocarcinoma and 1 squamous cell carcinoma. All primary lung cancers were at stage IA. The organs having metastatic pulmonary tumors were kidney, bladder, breast, and rectum. No patients had macroscopically positive surgical margins. CONCLUSIONS: Binocular stereo-navigation was able to identify the bronchovascular structures accurately and suitable to perform TSLR with a sufficient margin for small pulmonary tumors.

New findings on the three-dimensional anatomical relations between the bronchi and pulmonary blood vessels at the pulmonary hilum.

During the 1940s, considerable knowledge was acquired about the anatomy of pulmonary segments, and anatomical terms were proposed and have been widely accepted. In recent years, minimally invasive and thoracoscopic segmentectomy has been performed with a versatile sublobar resection approach on patients with early peripheral lung cancer, metastatic lung tumors, and undiagnosed nodules. The three-dimensional (3D) anatomy of the bronchi and the pulmonary vessels has also been studied in individual patients. Three-dimensional models of the bronchi and pulmonary vessels were prepared using homemade software from computed tomograms (CT) of the chests of patients scheduled to undergo surgical procedures. Using these models, the authors examined the 3D positional relationships of the segmental broncho-arterial triangle (SBAT) created by three points defined by the origins and courses of the bronchi and the pulmonary arteries, which are located apart from each other at the pulmonary hilum, and the segmental pulmonary veins (SPV), which run near the SBAT. In the left and right upper lobes, many branches of the pulmonary arteries and parallel bronchi in subsegments were widely separated at the origin of the pulmonary hilum, creating a relatively large SBAT. However, as an exceptional case, an SPV passed through an SBAT in only one of 158 patients. To our knowledge, no similar findings have been documented previously. Our findings could help to determine resection surfaces for thoracoscopic segmentectomy in the future, and provide new insights into the 3D anatomy and development of the lung.