Serum immunogloblins might be useful predictors of immune-related adverse events after immune checkpoint inhibitor usage in lung cancer.

We herein report a 79-year-old woman who underwent surgery had recurred non-small cell lung cancer and developed irAEs following ICI treatment. During ICI treatment, we conducted monthly measurements of the serum antibody levels in this patient, including those which were both tumor- (anti-p53 antibody) and nonspecific (immunoglobulins). Anti-p53 antibodies and IgM had not increased during ICI treatment, but the serum levels of IgG and IgA had gradually increased before the occurrence of irAEs. These results suggest that monitoring serum immunoglobulin levels might enable the early detection of ICI-induced immune responses in patients with lung cancer.

Efficacy and safety of immune checkpoint inhibitor monotherapy in elderly patients with non-small cell lung cancer.

The efficacy and safety of immune checkpoint inhibitor (ICI) monotherapy in elderly patients with non-small cell lung cancer (NSCLC) remain unclear, especially in patients older than 80 years. We retrospectively reviewed the records of 10 patients older than 80 years with NSCLCs treated by ICIs. The median age was 85 years (range, 82-93 years), and 7 patients were men. The median length of follow-up was 13 months (range, 4.5-23 months). Eight patients had adenocarcinoma (3 of whom had exon 19 deletions), and two had squamous cell carcinoma. Expression of programmed cell death ligand 1 (PD-L1) was ≥ 50% in 3 patients, between 1% and 49% in 4 patients, < 1% in 1 patient, and undetected in 2 patients. Patients with undetected PD-L1 underwent transbronchial lung biopsy. Performance status was graded zero, one, and two in two, seven, and one patients, respectively. First-, second-, and third-line treatments were administered to three, three, and four patients, respectively. The 2-year overall survival rate was 30.0% (median, 285 days). Time to treatment failure rate on the 2 years was 10.0% (median, 167 days). One patient achieved a partial response, and one achieved a complete response. ICI-associated adverse events occurred in five patients. In summary, ICIs were effective in some patients older than 80 years; however, some experienced adverse effects. Elderly patients must be selected carefully for ICI treatment.

Mediastinal lymph node metastases in lung cancer presenting as pure ground-glass nodules: A surgical case report.

INTRODUCTION: Generally, lung cancer representing as Ground-glass nodules is associated with an early stage and good prognosis. However, we herein report a rare case of pure ground-glass nodules with mediastinal lymph node metastases. PRESENTATION OF CASE: A 69-year-old man underwent video assisted thoracic surgery right upper lobectomy with mediastinal lymph node dissection due to multifocal Ground-glass nodules in the right upper lobe of the lung. Histopathologically, six lung adenocarcinomas were present simultaneously. Furthermore, we detected mediastinal lymph nodes metastases that contain micropapillary component. The lung lesion containing micropapillary component was a pure Ground-glass nodule that adjoining pulmonary bulla on CT findings. DISCUSSION: Generally, lung cancer presenting as pure ground-glass nodules is associated with an early stage and good prognosis. However, the necessity of evaluating the mediastinal lymph nodes in pure ground-glass nodules is controversial. It is reported that lung cancer adjoining the wall of a bulla tends to have a poor prognosis, even when small in size. Therefore, Ground-glass nodules with metastases might have a different pathogenesis than other nodules. CONCLUSION: Adenocarcinoma appearing as pure Ground-glass nodules is associated with early stage lung cancer and a good prognosis. However, the findings in our patient indicate the importance and necessity of evaluating the mediastinal lymph nodes for metastases intraoperatively.

Difficulty of treatment for pleural epithelioid hemangioendothelioma: a report of a case.

We herein report the case of a 62-year-old man who underwent extrapleural pneumonectomy (EPP) for pleural epithelial hemangioendothelioma (EHE) diagnosed by a pleural biopsy. Pre-operative computed tomography revealed diffuse pleural thickening and pleural effusion in the right thoracic cavity, although metastasis to neither the lymph nodes nor distant organs was detected. We decided to perform EPP based on surgical findings that the tumor had invaded the lung parenchyma. A pathological examination revealed tumor invasion of the lung parenchyma, blood vessel, pericardium, diaphragm and bronchial wall. Despite aggressive treatment, tumor recurrence was detected about 1 month after surgery. Although we controlled the tumor progression using pazopanib, the patient ultimately died 3.5 months after the operation. Pleural EHE is a very rare disease that has a poor prognosis due to its high malignant potential. It is important to formulate strategies matched to individual cases based on disease progression and invasiveness of treatment.

What is the best treatment strategy for primary spontaneous pneumothorax? A retrospective study.

BACKGROUND: Several treatment strategies are available for primary spontaneous pneumothorax (PSP). Surgical procedures are also performed in patients with PSP without an absolute indication for surgery. This study was performed to investigate the best treatment strategy for PSP by comparison of the recurrence rate. MATERIALS AND METHODS: From January 2006 to December 2013, 149 patients with PSP aged ≤50 years were treated in our institution. We reviewed the recurrence rate of PSP for each treatment strategy and evaluated the association between the recurrence rate of PSP with the clinicopathological characteristics. We also compared the surgery and non-surgery groups. RESULTS: A significant difference in the PSP recurrence rate was found between the surgery and non-surgery groups (22% vs. 52%, respectively; p < 0.001), patients aged ≥22 and < 22 years (16% vs. 44%, respectively; p < 0.001), and smokers and nonsmokers (13% vs. 43%, respectively; p < 0.001). There were also significant differences in the multivariate analysis (p < 0.001, p = 0.050, and p = 0.001, respectively). In the surgery group, the PSP recurrence rate was significantly different between patients aged ≥22 and < 22 years (7% vs. 38%, respectively; p < 0.001) and smokers and nonsmokers (5% vs. 33%, respectively; p = 0.002). No significant differences were found in the non-surgery group. CONCLUSIONS: In the surgical treatment of PSP, it is desirable that smokers stop using tobacco and that patients are ≥22 years old. Moreover, when surgery is being considered, the best timing seems to be when air leakage is present because the air leakage sites can be resected.

Prognostic factors of advanced or postoperative recurrent non-small cell lung cancer targeted with immune check point inhibitors.

BACKGROUND: Although immune checkpoint inhibitors (ICIs) for non-small cell lung cancer (NSCLC) have been established as one of standard therapy, the prognostic factors of ICIs remain unclear, aside from the programed cell death-ligand 1 (PD-L1) expression of tumor cells. The aim of this study was to determine the prognostic factors of ICIs. METHODS: We analyzed the clinicopathological data of 44 cases of advanced NSCLC targeted with ICIs in our hospital, between February 2016 and February 2018, in order to determine the prognostic factors of ICIs. We also reviewed the literature regarding ICIs. RESULT: We retrospectively analyzed the 44 cases (26 nivolumab and 18 pembrolizumab cases). These patients were 38 men and 6 women, comprising 13 cases of adenocarcinoma, 29 squamous cell carcinoma and 2 unclassified types. Seven patients were using first-line therapy and while the others were using second-line therapy or later. Epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) mutations were negative in all the cases. The response rate and disease control rate were 20.5% and 51.3%, respectively. The median progression-free survival time and median survival time were 146 days and 257 days, respectively. We observed five severe adverse effects (AEs) (three cases of interstitial pneumonia, one of liver dysfunction and one of adrenal failure), that were resolved by steroid pulse therapy. In multivariate analyses, the Eastern Cooperative Oncology Group performance status (ECOG PS), pathological type, standardized uptake value (SUV) on positron emission tomography (PET), white blood cell (WBC) count, neutrophil, neutrophil-to-lymphocyte ratio (NLR), lactate dehydrogenase (LDH) and albumin were independently prognostic factors. There were no significant differences in the prognosis between nivolumab and pembrolizumab. CONCLUSIONS: ICIs were effective in 44 treated NSCLC cases. Our analysis suggests that while ICIs are effective in treating patients, candidates must be carefully selected and cautiously observed.

Thymic papillary adenocarcinoma coexisting with type A thymoma: A case report.

INTRODUCTION: Thymic papillary adenocarcinoma is rare. Further, thymic papillary adenocarcinoma coexisting with type A thymoma is extremely rare. Surgery remains the only effective treatment for this disease. PRESENTATION OF CASE: An 84-year-old Japanese woman presented to our institute due to abnormal chest computed tomography (CT) findings showing a 45 × 40 × 40-mm tumor located in the anterior mediastinum. A malignant tumor was suspected based on the CT findings and high serum levels of carcinoembryonic antigen. Mediastinal tumor resection was performed via video-assisted thoracic surgery through the left thoracic approach. This patient was discharged from our institute without any problems at six days post-operation. DISCUSSION: This report has three major implications. First, one of the tumors was papillary adenocarcinoma. Primary papillary adenocarcinoma of the thymus is exceedingly rare. Second, papillary adenocarcinoma and type A thymoma coexisted in this tumor. Third, epithelial thymic tumor should be resected completely, since complete resection has been reported to be associated with an improved prognosis. CONCLUSION: We encountered a rare case of thymic papillary adenocarcinoma coexisting with type A thymoma.

Detection of circulating tumor cells with a novel microfluidic system in malignant pleural mesothelioma.

Detection of rare tumor cells circulating in the blood (CTCs) presents technical challenges. CellSearch, the only approved system for clinical use, fails to capture epithelial cell adhesion molecule-negative CTCs such as malignant pleural mesothelioma (MPM). We have developed a novel microfluidic device (CTC-chip) in which any Ab to capture CTCs is conjugated. The CTC-chip was coated with an Ab against podoplanin that is abundantly expressed on MPM. Circulating tumor cell-detection performance was evaluated in experimental models in which MPM cells were spiked in blood sampled from a healthy volunteer and in clinical samples drawn from MPM patients. The CTC-chip showed superior CTC-detection performance over CellSearch in experimental models (sensitivity, 63.3%-64.5% vs 0%-1.1%; P < .001) and in clinical samples (CTC-positivity, 68.8% vs 6.3%; P < .001). A receiver operating characteristic (ROC) analysis showed that the CTC test provided a significant diagnostic performance in discrimination of unresectable disease from resectable disease (area under the ROC curve, 0.851; P = .003). The higher CTC count (≥2 cells/mL) was significantly associated with a poor prognosis (P = .030). The novel CTC-chip enabled sensitive detection of CTCs, which provided significant diagnostic and prognostic information in MPM.

Effect of erlotinib plus bevacizumab on brain metastases in patients with non-small cell lung cancer.

BACKGROUND: The standard therapy for brain metastasis (BM) in non-small cell lung cancer (NSCLC) is radiation therapy (RT), although it is associated with complications such as leukoencephalopathy. In the current report, we retrospectively review data from eight patients who had NSCLC and harbored epidermal growth factor receptor (EGFR) mutations, and who were received erlotinib plus bevacizumab (E+B) as first-line therapy for BM. METHODS: Patients were given E+B as first therapy for BM until August 2017 at our institution. Patients receiving local therapy for BM, such as surgery or radiotherapy, were excluded. Patients were administered erlotinib orally (once daily at 150 mg/body) plus bevacizumab by intravenous infusion (15 mg/kg on day 1 of a 21- or 28-day cycle). RESULTS: Eight NSCLC patients who were diagnosed with BM received E+B, including 2 men and 6 women with a median age of 65 years (range, 46-84 years). Four patients had an L858R EGFR mutation, while the other four had an exon 19 deletion. Seven patients had a partial response to E+B treatment, and one had a complete response. The 2-year survival rate was 62.5%. Three patients who were pre-treated with gefitinib had an E+B treatment duration of less than 1 year. At the time of this analysis, four patients had BM-related neurologic symptoms and multiple BMs, and were still receiving E+B with no evidence of treatment failure after more than 1 year. CONCLUSIONS: E+B can be used as first-line therapy for BM, even in patients with BM-related neurologic symptoms and multiple BMs.

Complete resection of an anterior mediastinal tumor by total arch replacement and pulmonary artery trunk plasty with a pericardial patch: A case report.

INTRODUCTION: Patients with undiagnosed anterior mediastinal tumors commonly undergo surgery for diagnosis and treatment. However, determining the optimal therapeutic strategy is difficult for tumors with substantial invasion, such as lesions touching the aortic arch (AA). CASE PRESENTATION: A 76-year-old man of Asian descent presented to our hospital because chest computed tomography (CT) revealed an anterior mediastinal tumor. This tumor surrounded the left subclavian vein and touched the AA. We suspected the tumor to be malignant. We therefore decided to resect the tumor with preparation for total arch replacement (TAR). The operation was performed in three steps. First, we performed a mediastinal sternotomy. However, the tumor had invaded the subclavian vein, so we resected this vein after adding a transmanubrial approach. However, because of invading the AA we needed next step. Second, we shifted the patient to the right lateral decubitus position. We performed partial resection of the left upper lobe and exfoliated the distal AA. Third, we shifted the patient to the dorsal position and implanted an artificial cardiopulmonary device, after which we performed TAR, and pulmonary artery (PA) trunk plasty with a pericardial patch. The operation was successful, with no major adverse events. Pathologically, the tumor was diagnosed as diffuse large B-cell lymphoma. DISCUSSION: If oncologically complete resection is preferable for tumors with substantial invasion, complete resection should be attempted even if the surgery is difficult. CONCLUSION: We performed complete resection of an anterior mediastinal tumor with TAR and PA trunk plasty using a pericardial patch.

Outcomes of patients undergoing surgery for thymic carcinoma: a single-center experience.

BACKGROUND: Thymic carcinoma is uncommon, presents locally at an advanced stage, and behaves aggressively. The optimum treatment for advanced thymic carcinoma is controversial. We retrospectively reviewed our institutional experience with patients with thymic carcinoma. METHODS: We analyzed the clinical data of six patients who underwent total thymectomy for thymic carcinoma at our institution from 2006 to 2016. Variables analyzed included sex, age, histological classification, Masaoka staging, postoperative treatment, and recurrence. RESULTS: The clinical characteristics of the six patients with thymic carcinoma (median age, 56 years; five men and one woman) were as follows: squamous cell carcinoma (n=5); sarcomatoid carcinoma (n=1); Masaoka stages II (n=1), III (n=2), IVa (n=1), and IVb (n=2). Four patients underwent combined pulmonary resection (66.7%) as a component of en bloc resection due to suspicion of pulmonary invasion. Four patients (66.7%) received postoperative therapy, and complete resection was achieved for four patients. There were no perioperative deaths. One patient experienced a recurrence. CONCLUSIONS: Complete resection for thymic cancer improved the prognosis of our patients, indicating that robust studies will be required to confirm our findings.

Virtual-assisted lung mapping (VAL-MAP) shortened surgical time of wedge resection.

BACKGROUND: The detection of extremely small lung tumors has increased with the development of computed tomography. Resection of such tumors by thoracoscopy is often hindered due to the unclear location of the tumor. Various methods of preoperative determination of such lesions have been attempted, but without marked success. Here we used virtual-assisted lung mapping (VAL-MAP) to perform surgical resection of small lung lesions. METHODS: We selected patients with pulmonary tumors that we anticipated to be difficult to identify during thoracoscopy and/or decide the resection line for sub-lobar lung resection. The wedge resections in the VAL-MAP group were compared to a group of patients who underwent wedge resection without VAL-MAP in 2013. RESULTS: Surgery duration was significantly shorter in the VAL-MAP group (average: 76.4 min) than in the 2013 group (average: 108.6 min; P=0.000451), although the VAL-MAP group (average major axis: 9.6 mm) had smaller tumors (P=0.000032) and more pure ground-glass opacities (GGOs) (P=0.0000919) than the 2013 group (average major axis: 16.6 mm). CONCLUSIONS: The findings of this study indicate that VAL-MAP is efficacious. In particular, VAL-MAP resulted in a shorter surgery duration and has expanded the indications of resectable lesions.

Capture of mesothelioma cells with 'universal' CTC-chip.

Malignant mesothelioma (MM) is a highly aggressive malignant tumor, predominantly associated with job-related exposure to asbestos. Development of effective and non-invasive modalities for diagnosis is an important issue in occupational medicine. Circulating tumor cells (CTCs), which are tumor cells that are shed from primary tumors and circulate in the peripheral blood, may be detected at an earlier stage than malignant tumors, and detection of CTCs may provide a novel insight into the diagnosis of MM. In a previous study evaluating clinical utility of CTCs, detected with a widely used system 'CellSearch', the authors indicated a significant however insufficient capability in the diagnosis of MM, suggesting need for a more sensitive system. Accordingly, the authors developed a novel microfluidic system to capture CTCs (CTC-chip), and demonstrated that the CTC-chip effectively captured MM cells (ACC-MESO-4) spiked in the blood by conjugating an anti-podoplanin antibody. The results of the present study demonstrated that the CTC-chip coated with the anti-podoplanin antibody captured another MM cell (ACC-MESO-1). However, the capture efficiencies were lower than those for ACC-MESO-4. In addition, an anti-mesothelin antibody was used to capture CTCs, however the CTC-chip coated with the anti-mesothelin antibody failed to effectively capture MM cells, possibly due to low mesothelin expression. Overall, the CTC-chip may capture specific types of CTCs by conjugating any antibody against an antigen expressed on CTCs, and may be a useful system for the diagnosis of malignant tumors, including MM.

Postoperative thoracic hemorrhage after right upper lobectomy with thoracic wall resection during rivaroxaban anticoagulant therapy for deep leg vein thrombosis: A case report.

INTRODUCTION: Postoperative pulmonary embolism (PE) is the one of the most important complications after thoracic surgery. This complicatin after the surgery is often treated by new anticoaglant drug, such as rivaroxaban, which dose not need to the monitoring of blood coaglation system. We experienced postoperative bleeding case during anticoaglant therapy using rivaroxaban. PRESENTATION OF CASE: The patient underwent a right upper lobectomy with lung and chest wall resection for lung cancer. On postoperative day (POD) 10, we started to use rivaroxaban to treat the deep vein thrombosis (DVT). Four days after starting the rivaroxaban treatment, severe surgical site hemorrhage occurred, which led to the need for the infusion of concentrated red cells (CRC). After stopping the rivaroxaban, the thoracic bleeding ceased. Because the event occurred so long after the surgery, and because the bleeding stopped after withdrawal of treatment, we believe that rivaroxaban induced the thoracic bleeding. CONCLUSION: Some reports in the field of orthopedics (Turpie et al., 2009) have noted that rivarxaban is effective to prevent postoperative DVT. However, there were few reports that invied the attention to postoperative bleeding be induced by rivarxaban. Thus, we describe this case in order to alert clinicians to the potential bleeding risks associated with the admistration of rivaroxaban postoperatively.

Mediastinal Tracheostoma for Treatment of Tracheostenosis after Tracheostomy in a Patient with Mucopolysaccharidosis-Induced Tracheomalacia.

BACKGROUND: Treatment of tracheostenosis after tracheostomy in pediatric patients is often difficult. Mucopolysaccharidosis is a lysosomal storage disease that may induce obstruction of the airways. CASE PRESENTATION: A 16-year-old male patient underwent long-term follow-up after postnatal diagnosis of type II mucopolysaccharidosis. At 11 years of age, tracheostomy was performed for mucopolysaccharidosis-induced laryngeal stenosis. One week prior to presentation, he was admitted to another hospital on an emergency basis for major dyspnea. He was diagnosed with tracheostenosis caused by granulation. The patient was then referred to our institution. The peripheral view of his airway was difficult because of mucopolysaccharidosis-induced tracheomalacia. For airway management, a mediastinal tracheostoma was created with extracorporeal membrane oxygenation. To maintain the blood flow, the skin incision for the mediastinal tracheal hole was sharply cut without an electrotome. The postoperative course was uneventful, and the patient was weaned from the ventilator on postoperative day 19. He was discharged 1.5 months postoperatively. Although he was referred to another institution because of respiratory failure caused by his primary disease 6 months postoperatively, his airway management remained successful for 1.5 years postoperatively. CONCLUSION: Mediastinal tracheostomy was useful for treatment of tracheostenosis caused by granulation tissue formation after a tracheostomy.

The major thoracic vascular invasion of lung cancer.

BACKGROUND: We actually investigated the surgical and pathological findings in cases which tumor invasion of the major thoracic vessels was suspected based on the preoperative Computed tomography (CT) findings. MATERIALS AND METHODS: We retrospectively reviewed our prospective database of all patients, who underwent lung resection for lung cancer from 2012 to 2014. 387 patients underwent lung cancer surgery. Among these patients, we analyzed 30 patients in whom pulmonary artery (PA) invasion was suspected and 11 patients in whom pulmonary vein (PV) or left atrium (LA) invasion was suspected based on the preoperative CT findings. RESULTS: Among the 30 patients with suspected PA invasion, there were 9 patients in whom the tumor could be peeled off the PA in actual thoracotomy. Pathological invasion of the PA was observed in 6 of these patients. The positive predictive value of the preoperative CT findings was 20%. Among the 11 patients with suspected PV or LA invasion, there were 2 patients in whom the tumor could be peeled off the PV or LA in actual thoracotomy. Pathological tumor invasion of the PV or LA was observed in 4 of these patients. The positive predictive value of the preoperative CT findings was 36%. CONCLUSION: The positive predictive value of the preoperative CT findings for tumor invasion of the thoracic vessels was low. Therefore, surgical opportunities that offer the chance of a cure shouldn't be missed in advanced lung cancer patients because the tumor is located near the major thoracic vessels on preoperative CT.