Primary Pleural Angiosarcoma Treated with Nivolumab and Ipilimumab: A Case Report.

Primary pleural angiosarcoma (PPA) is a rare and clinically fatal pleural tumor originating from vascular endothelial cells. Herein, we presented the case of a 73-year-old man who was referred to our emergency room with complaints of right chest and back pain for a few days. Chest computed tomography revealed massive pleural effusion and a large mass in the right chest cavity. Thoracoscopic examination demonstrated a large hemorrhagic tumor on the parietal pleura whose pathological analysis indicated PPA. The patient received immunotherapy combined with nivolumab and ipilimumab. A cycle of nivolumab and ipilimumab improved his hemorrhagic anemia and reduced the pleural effusion and tumor size. This treatment outcome suggests that nivolumab and ipilimumab comprise a vital treatment option for PPA.

Dual-scopic robotic thymectomy for a large thymic malignant tumor.

Minimally invasive surgery for large thymic malignant tumors remains challenging. Here, we demonstrate dual-scopic robotic thymectomy for a challenging malignant thymic tumor. An asymptomatic 70-year-old woman clinically diagnosed with a large thymic malignant tumor invading the left phrenic nerve and pericardium underwent surgery. After dissecting the left phrenic nerve and pericardium under left unilateral video-assisted thoracic surgery, a robotic subxiphoid approach was conducted to achieve complete thymectomy. During robotic surgery, the large tumor sometimes limited the surgical view. To overcome this limitation, we added a conventional thoracoscope and utilized both images of the conventional thoracoscopic view and robotic camera via TilePro display to achieve complete resection of the thymic epithelial tumor. The patient was discharged with no complications except left phrenic palsy. The pathological diagnosis was a thymic neuroendocrine tumor invading the left phrenic nerve. This approach is potentially useful in surgery for challenging thymic malignant tumors.

Pleural nodule with osteal protrusion anterior to the rib tubercle: a case report.

Pleural soft tissue density nodules with osteal protrusions are often detected at their characteristic site, the anterior portion of the rib tubercle. Herein, we report a pathologically proven case of this lesion. A 65-year-old man underwent surgery for primary lung cancer in the right middle lobe. Preoperative computed tomography showed a 10-mm pleural soft tissue density nodule with osteal protrusion anterior to the tubercle of the right sixth rib, and this lesion was concomitantly resected. Intraoperative findings showed that this pleural lesion originated from the parietal pleura and was pathologically diagnosed as a benign fibrous tissue. We can avoid unnecessary invasive examinations such as biopsies by recognizing these benign fibrous lesions.

Initial experience of virtual-assisted lung mapping utilizing both indocyanine green and indigo carmine.

Virtual-assisted lung mapping is a bronchoscopic multiple dye marking technique that facilitates sublobar lung resections for unidentifiable pulmonary tumors. Marking failure reportedly occurs in 10% of cases. To overcome this limitation, we developed indocyanine green virtual-assisted lung mapping that uses indocyanine green in addition to indigo carmine. Here, we report our initial experience of indocyanine green virtual-assisted lung mapping.

Hybrid technique of virtual-assisted lung mapping and systemic indocyanine green injection for extended segmentectomy.

BACKGROUND: Various approaches have been used to assist and facilitate segmentectomy with favorable oncological outcomes. We describe a hybrid approach comprising virtual-assisted lung mapping (VAL-MAP), which is a preoperative bronchoscopic dye-marking technique, combined with systemic indocyanine green (ICG) injection. CLINICAL PRESENTATION: An asymptomatic 64-year-old man was referred to our department because of a lung nodule detected during his annual medical checkup. The chest computed-tomography image revealed a 16-mm, partly solid, ground-glass nodule in the left segment 4. Because the nodule was hardly palpable and deeply located between the left upper division segment and the left lingular segment, we performed VAL-MAP to facilitate extended left lingulectomy. Five dye markings were undertaken preoperatively. Surgery to remove the nodule was then conducted via complete three-port video-assisted thoracic surgery. The VAL-MAP markings were easily identified intraoperatively and helped locate the nodule. The intersegmental plane was identified by the ICG injection. The resection line was determined based on the intersegmental plane identified by the ICG injection and the site of the nodule suggested by the VAL-MAP markings. Following the resection line, we thoracoscopically achieved extended lingulectomy with sufficient surgical margins. The patient was discharged with no complications. The pathological diagnosis was adenocarcinoma in situ. CONCLUSION: The hybrid technique of VAL-MAP and systemic ICG injection can be useful for accomplishing successful extended segmentectomy.

Left apicoposterior segmentectomy for lung cancer with displaced segmental bronchus: a case report.

BACKGROUND: Pulmonary segmentectomy can be challenging when thoracic surgeons encounter anatomical anomalies. A displaced left apicoposterior bronchus is a rare bronchial anomaly that makes lung anatomical resection challenging. We herein present a case of successful left apicoposterior segmentectomy for lung cancer in a patient with an anomalous segmental bronchus. CASE PRESENTATION: A 70-year-old man was clinically diagnosed with early-stage lung cancer for which segmentectomy was indicated. A preoperative image revealed a displaced left apicoposterior bronchus that branched behind the left main pulmonary artery. With the aid of three-dimensional reconstruction imaging and systemic indocyanine green injection, we successfully performed left apicoposterior segmentectomy under complete video-assisted thoracic surgery. The pathological diagnosis was adenocarcinoma. The patient was alive without recurrence 8 months after segmentectomy. CONCLUSION: Preoperative three-dimensional imaging and systemic indocyanine green injection enabled us to successfully conduct challenging segmentectomy in a patient with an anomalous bronchus.

Bronchosubcutaneous fistula manifesting as massive subcutaneous emphysema treated successfully by endobronchial Watanabe spigots.

A bronchosubcutaneous fistula (BF) is an abnormal communication between the bronchus, pleural cavity, and subcutaneous tissue. Treatment of BF has been documented rarely. We describe a successful endoscopic bronchial occlusion using endobronchial Watanabe spigots (EWSs) for BF manifesting as massive subcutaneous emphysema (SE). A 78-year-old woman developed delayed localized SE following a surgical pleural biopsy for the diagnosis of primary lung cancer. Computed tomography (CT) of the chest revealed BFs resulting from pleural biopsy. The affected bronchi were identified using chest CT. We inserted EWSs into the affected bronchi with the aid of virtual bronchoscopic navigation. This bronchoscopic procedure achieved complete resolution of the SE by sealing the BFs without the need for surgical interventions.

[The Current Status and Future of Robot-assisted Thoracic Surgery].

In the pursuit of minimally invasive surgery, there is no objection to the replacement of conventional open surgery with robotic surgery in highly difficult cases of pulmonary and mediastinal tumors. However, compared to video-assisted thoracoscopic surgery, the benefits of performing robotic surgery in standard lung cancer cases are few. A surgeon with master robotic skills, in addition to excellent 3-dimensional( 3D) camera control, can effectively use a retraction arm instead of increasing the number of the port. We think that such a surgeon can have an extremely high success rate. We started performing robotic surgery in September 2018 and have had more than 70 cases since then. We developed a manual to promote patient safety and common understanding between the operator and surgical assistants. In this manuscript, we introduce our current robotic surgery technique for lung cancer. The current status, problems, and the future of robotic thoracic surgery are also described.

Progressively increasing density of the solid center of a ground-glass nodule in a solitary pulmonary capillary hemangioma: A case report.

Solitary pulmonary capillary hemangiomas (SPCHs) are recently recognized, rare benign lesions that form solitary nodules owing to capillary proliferation. These lesions are usually detected incidentally as small ground-glass nodules (GGNs) on computed tomography (CT), and progressively enlarge over time. The radiological distinction from peripheral lung cancers is particularly challenging. However, to date, there have been no reports on progressive changes in the central density of SPCH on CT. An asymptomatic 49-year-old man was referred to our hospital for an abnormal shadow that was detected on chest CT during medical check-up. He was subsequently followed-up with chest CT. The nodule increased in size, and the central area became progressively denser. He underwent surgery 5 years and 10 months after the first visit owing to suspicion of lung cancer. Despite the collapse of the surgical specimen by artifacts, histopathological examination revealed a diagnosis of SPCH; collagenous fibers were found in the walls of the intralesional capillaries. The patient is presently alive without any recurrence, 6 months after the operation. In this case, the SPCH demonstrated a GGN with progressively increasing density of the central solid area on the CT. This remarkable feature made the preoperative distinction from lung cancer particularly difficult.

Arteritis and Plexiform Lesion in Intralobar Pulmonary Sequestration: The First Case With Such Two Distinct Complex Lesions Associated With Local Pulmonary Hypertension.

In intralobar pulmonary sequestrations, vascular changes similar to those in pulmonary hypertension (PH) are generally observed, such as intimal proliferation and plexiform lesions. However, to our knowledge, a sequestrated lung manifesting vascular changes with both arteritis and a plexiform lesion has never been reported. A 25-year-old man was diagnosed with intralobar pulmonary sequestration. Pathologically, both arteritis and a plexiform lesion were observed in the sequestrated lung. Systemic vasculitis syndrome was clinically excluded, and the pathological findings appeared to be associated with local PH. Arteritis is an extremely rare finding; only one case of arteritis associated with local PH has been reported in intralobar sequestration. In this case, the artery near the plexiform lesion had milder inflammation and fibrosis, suggesting that the arteritis formed prior to the plexiform lesion. This is the first case of arteritis and a plexiform lesion co-occurring in intralobar pulmonary sequestration associated with local PH. This case may shed light on the formation of plexiform lesions and their association with arteritis.

Altered editing level of microRNAs is a potential biomarker in lung adenocarcinoma.

Adenosine-to-inosine (A-to-I) microRNA editing is associated with tumor phenotypes in various cancer types. Recent analyses of The Cancer Genome Atlas (TCGA) dataset have shown several microRNAs that undergo A-to-I editing in human cancers, some of which have been reported to be associated with prognosis. Herein, we examined published small RNA deep sequencing data of 74 cases of lung adenocarcinoma (AD) and the corresponding normal counterpart (NC) specimen in silico in order to identify A-to-I microRNA editing events. Editing levels of miR-379-5p, miR-99a-5p, and miR-497-5p were lower in AD than in NC and, in a large number of cases, the editing level of miR-200b-3p was higher in AD than in NC. Difference in the editing level between AD and NC was largest for miR-99a-5p. Then, we examined the editing level of miR-99a-5p in 50 surgically resected lung adenocarcinoma cases at our institution by a conventional sequence-based method, and its association with clinical outcomes. The editing level of miR-99a-5p was significantly lower in 19 cases of AD (38%) than in corresponding NC. These cases showed a shorter overall survival as assessed using the log-rank test (P = .047). This trend was consistent with previous analyses of TCGA dataset. The altered editing level of microRNAs in lung adenocarcinoma could serve as a potential biomarker.

The three peaks in age distribution of females with pneumothorax: a nationwide database study in Japan.

OBJECTIVES: Women are the minority among patients with spontaneous pneumothorax, but catamenial pneumothorax (CP) is unique to them. We aimed to clarify the clinical characteristics of female patients with spontaneous pneumothorax using a nationwide database. METHODS: Medical records from the Japanese Diagnosis Procedure Combination database for inpatients with pneumothorax between July 2010 and March 2016 were retrospectively reviewed. Age, underlying diseases, body mass index, smoking status, laterality, number of hospitalizations and treatments were studied. RESULTS: We identified 157 087 patients with pneumothorax, including 27 716 (17.6%) women and 129 371 (82.4%) men. The age distribution of female patients with pneumothorax had 3 peaks: 18 years, around 40 years and 80 years; male patients had 2 peaks: 18 years and 79 years. We identified 873 patients with CP; this number was not sufficient to account for the female-specific peak around 40 years. The characteristics of female patients of reproductive age were significantly different between those with and without CP. The patients with CP were older (average age: 37.9 ± 7.7 years vs 31.3 ± 11.5 years, P < 0.001), were right side dominant (right: 64.9%, left: 6.5%), had more hospitalizations (average number of hospitalizations: 1.6 ± 0.9 vs 1.3 ± 0.6, P < 0.001) and had more frequently undergone surgery (57.1% vs 37.3%, P < 0.001). CONCLUSIONS: The age distribution of women with pneumothorax had 3 distinct peaks while that of men had 2. CP has different characteristics from other types of pneumothorax, thus requiring different treatment strategies for women of reproductive age.

Glutamate-cysteine ligase catalytic subunit is associated with cisplatin resistance in lung adenocarcinoma.

BACKGROUND: Cisplatin is a key drug for treating lung adenocarcinoma, and its sensitivity to cisplatin is directly related to prognosis. We aimed to reveal the roles of genes related to glutathione synthesis (glutamate-cysteine ligase catalytic subunit, GCLC) and cystine uptake (cystine/glutamate transporter, xCT and CD44v8-10) in cisplatin resistance and prognosis in lung adenocarcinoma. METHODS: We established cell lines stably expressing GCLC, xCT, standard isoform of CD44, and CD44v8-10, and investigated their sensitivities to cisplatin. We also measured mRNA expression levels of these genes in the tumor tissues from 92 lung adenocarcinoma patients. Patients were divided into high-expression (upper quartile, N = 23) and low-expression groups (remaining patients, N = 69). Recurrence-free survival, overall survival (N = 92), and post-recurrence survival (N = 22) were selected as endpoints. RESULTS: Compared with the control green fluorescent protein-expressing cell line (inhibitory concentration 50:6.9 µM), all the stable cell lines were more resistant to cisplatin (12.9 µM, P = 0.025; 13.9 µM, P = 0.028; 26.7 µM, P = 0.001; 17.7 µM, P = 0.008, respectively). In contrast, there was no significant difference in recurrence-free or overall survival between the high- and low-expression groups for any of the genes. However, high expression of GCLC was a risk factor for poorer post-recurrence survival (hazard ratio, 6.26; 95% confidence interval, 1.37-28.7; P = 0.018). CONCLUSION: High expression levels of genes related to glutathione synthesis and cystine uptake promote cisplatin resistance in lung adenocarcinoma cell lines. High expression of GCLC in tumor tissue may be a potential predictor of treatment failure.

High expression of IRE1 in lung adenocarcinoma is associated with a lower rate of recurrence.

OBJECTIVE: Recent reports have shown that endoplasmic reticulum stress is associated with cancer. However, the impacts of endoplasmic reticulum stress on the prognosis of lung cancer are unknown. Therefore, in this study, we sought to reveal the relationship between the expression of endoplasmic reticulum stress-related genes (endoplasmic reticulum oxidoreductase 1L, protein kinase RNA-like endoplasmic reticulum kinase, activating transcription factor 6 and inositol-requiring kinase 1) and the outcome of lung adenocarcinoma. METHODS: One hundred and twenty-six patients with surgically resected lung adenocarcinomas were subjected to an endoplasmic reticulum stress-related mRNA expression analysis using quantitative RT-PCR. The following parameters were analyzed for all the study patients: age, sex, disease stage, smoking status, lymph node invasion (ly), vascular invasion (v) and EGFR mutation status. We assigned patients to either a high-expression group or a low-expression group according to the expression levels of endoplasmic reticulum stress-related genes. RESULTS: High expressions of endoplasmic reticulum stress-related genes were observed in patients with lower stages of lung adenocarcinoma and minimal vascular invasion. A Kaplan-Meier analysis showed significant differences in recurrence-free survival and overall survival between high-expression group and low-expression group. High inositol-requiring kinase 1 expression was an independent predictor of recurrence-free survival among patients with lung adenocarcinoma (hazard ratio, 0.396; 95% confidence interval, 0.188-0.834; P = 0.015). CONCLUSIONS: Inositol-requiring kinase 1 may be a useful biomarker to predict recurrence in surgically resected lung adenocarcinoma patients.

Mediastinal seminoma associated with multilocular thymic cyst.

An asymptomatic 26-year-old man received an annual medical check-up, and chest X-ray showed a protrusion of the aortopulmonary window. Chest computed tomography (CT) revealed an anterior mediastinal tumor and cysts with thin wall and septum enhancement. The preoperative diagnosis was cystic thymoma or malignant lymphoma. We performed total resection of the tumor through a median sternotomy. The pathological findings revealed seminoma, positive for c-kit stain, and multilocular thymic cysts. Cysts were lined by normal squamous epithelium and no seminoma cells were located on their surface. So, cysts were probably secondary changes caused by seminoma cells themselves or inflammatory stimulations. No invasion to adjacent structures was seen. After the surgery, testicular ultrasound imaging and abdominal, pelvic, and cerebral CT showed no apparent tumor or enlarged lymph nodes; however, an abnormal uptake in the right mesenteric lymph node was pointed out by 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) scan. The patient received four courses of bleomycin, etoposide, and cisplatin (BEP) as adjuvant chemotherapy. Follow-up PET scan revealed no uptake in the right mesenteric lymph node. To date, no recurrence or metastasis has been identified for 16 months.

Identification of Individual Cancer-Specific Somatic Mutations for Neoantigen-Based Immunotherapy of Lung Cancer.

INTRODUCTION: Two strategies for selecting neoantigens as targets for non-small cell lung cancer vaccines were compared: (1) an "off-the-shelf" approach starting with shared mutations extracted from global databases and (2) a personalized pipeline using whole-exome sequencing data on each patient's tumor. METHODS: The Catalogue of Somatic Mutations in Cancer database was used to create a list of shared missense mutations occurring in more than 1% of patients. These mutations were then assessed for predicted binding affinity to HLA alleles of 15 lung cancer patients, and potential neoantigens (pNeoAgs) for each patient were selected on this basis. In the personalized approach, pNeoAgs were selected from missense mutations detected by whole-exome sequencing of the patient's own samples. RESULTS: The list of shared mutations included 22 missense mutations for adenocarcinoma and 18 for squamous cell carcinoma (SCC), resulting in a median of 10 off-the-shelf pNeoAgs for each adenocarcinoma (range 5-13) and 9 (range 5-12) for each SCC. In contrast, a median of 59 missense mutations were identified by whole-exome sequencing (range 33-899) in adenocarcinoma and 164.5 (range 26-232) in SCC. This resulted in a median of 46 pNeoAgs (range 13-659) for adenocarcinoma and 95.5 (range 10-145) for SCC in the personalized set. We found that only one or two off-the-shelf pNeoAgs were included in the set of personalized pNeoAgs-and then in only three patients, with no overlap seen in the remaining 12 patients. CONCLUSIONS: Use of an off-the-shelf pipeline is feasible but may not be satisfactory for most patients with non-small cell lung cancer. We recommend identifying personal mutations by comprehensive genome sequencing for developing neoantigen-targeted cancer immunotherapies.

[Small intestinal perforation due to metastasis from pulmonary pleomorphic carcinoma; report of a case].

A 63-year-old male patient was referred to our department for an abnormal shadow in the left middle lung field. The patient underwent trans bronchial lung biopsy and pathological finding was adenocarcinoma. Computed tomography( CT) showed mass in the left lower lobe, nodules in the bilateral adrenal glands, liver, pancreas and lumbar bone. When he was admitted to our hospital for chemotherapy, chest X-ray showed left pneumothorax and a chest tube was placed. Several days later, he complained of sudden abdominal pain and abdominal CT revealed free air around small intestine. Emergency operation was done and the perforation of the small intestine due to metastasis was found. He underwent partial resection of small intestine and left lower lobectomy. Pathological diagnosis was pulmonary pleomorphic carcinoma and small intestine metastasis.

Mixed squamous cell and glandular papilloma of the lung: a case study and literature review.

Mixed squamous cell and glandular papilloma (mixed papilloma) of the lung is an extremely rare neoplasm, with only 10 cases reported so far in the English literature. We present a case study of endobronchial mixed papilloma with immunohistochemical and etiological investigations. A 49-year-old male with a smoking history complained of hemoptysis, presented with a lung mass closely adjacent to large vessels in the computed tomography findings, and underwent lobectomy. The 3.0-cm sized polypoid tumor was histologically diagnosed as endobronchial mixed papilloma. Immunohistochemically, intracellular mucin was positive for MUC5AC, which is expressed in tracheobronchial goblet cells. CAM5.2 and CK19 were diffusely positive, indicating that the tumor originated from the columnar epithelium by squamous metaplasia. CEA and CA19-9 were focally positive. A human papillomavirus (HPV) investigation with in situ hybridization using a wide spectrum probe and a newly-developed PCR system did not detect any HPV infection. Including this case with a detailed HPV investigation, all of the reported cases of mixed papilloma were HPV-negative, and a literature review including newly-reported cases indicated a high frequency of smoking in such cases. Endobronchial mixed papillomas might have a smoking-related etiology.