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A 72-year-old woman with advanced lung cancer had received systemic chemotherapy including atezolizumab. About three months after the initial administration of atezolizumab, her liver enzyme levels increased. The histopathological findings of the initial liver biopsy revealed acute inflammatory infiltrate, predominantly CD3+, CD4+ and CD8+ T lymphocytes, in the hepatic lobules. We diagnosed her with atezolizumab-induced immune-related acute hepatitis. Oral corticosteroid therapy successfully improved the elevation of serum aminotransferases. A sequential liver biopsy demonstrated the rapid progression of liver fibrosis. Because hepatocellular carcinoma occurs most often in advanced cases of chronic liver disease, we should pay close attention to immune-related acute hepatic injury when treating patients with advanced liver diseases using atezolizumab.

In patients with lung cancer invading the left atrium, performing complete resection is difficult. In many cases of complete resection, pneumonectomy is performed. We herein report two techniques in which complete resection with negative margins at the intrapericardial pulmonary vein and left atrium was achieved without pneumonectomy. In the first technique, the groove of the pericardium between the right and left atrium was dissected and an atrial cuff was made in a manner that elongated the intrapericardial pulmonary vein. In the second technique, traction was applied to the atrial cuff, and only the middle lobe vein of the elongated pulmonary vein was resected, to perform atrial cuff plasty. The upper lobe vein and inferior pulmonary vein could be preserved. These techniques of PV elongation and atrial cuff plasty are suitable for both achieving complete resection and lung preservation for lung cancer patients with invasion of the left atrium.

Pulmonary neuroendocrine tumors (NET), a subtype of lung cancer, comprises typical carcinoids (TCs), atypical carcinoids (ACs), large cell neuroendocrine carcinoma (LCNEC), and small cell lung carcinoma (SCLC). TCs and ACs are low-to-intermediate malignant tumors, on the other hand LCNEC and SCLC are high-grade carcinomas (1).

Background Fenestration is performed in patients with bronchopleural fistula to avoid a life-threatening situation. However, usually, this procedure is required 9-cm mean length of the incision with rib resection. Case presentation A 73-year-old man underwent right lower lobectomy with lymph node dissection (ND2a-2) for primary lung cancer (cT1cN2M0 Stage IIIA) with combined pulmonary fibrosis and emphysema. He developed a bronchopleural fistula on postoperative day 20, and we performed emergency fenestration without rib resection using a Lap-protector. The patient reported minimal pain postoperatively. As the rapid deterioration of the general condition due to the recurrence of the tumor was observed at the time of his 1-year postoperative follow-up, closing of the thoracic cavity was abandoned. However, using this fenestration, the control of infection in the thoracic cavity could be sufficiently performed without complications such as pain and pneumonia, and his routine activities were unaffected postoperatively. Conclusion Compared with conventional method, fenestration without rib resection using a Lap-protector is a more convenient and painless technique for postoperative bronchopleural fistula.

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.

Background: Pulmonary neuroendocrine tumor (NET) occurs with 20% of all lung cancers, and there are a limited number of literatures about the molecular aberrations, treatment and prognosis; especially in resected cases, as the operation indication for large cell neuroendocrine carcinoma (LCNEC) and small cell lung carcinoma (SCLC) is rare due to their aggressive behaviors. We investigated the relationship between postoperative survival and molecular expression patterns of pulmonary NET to establish a more effective treatment strategy. Methods: In the present study, the curative surgical resection of pulmonary NET was reviewed retrospectively. A total of 105 patients with pulmonary NET, who underwent complete resection between 1978 and 2016, were subjected to analysis with respect to histological characterization and clinical behaviors of pulmonary NET using immunohistochemistry (IHC) of neuroendocrine markers and programmed cell death-ligand 1 (PD-L1). Results: The pathological types included 67 SCLC, 18 LCNEC, 14 typical carcinoids (TCs) and 6 atypical carcinoids (ACs). The ACs had significantly worse prognosis than TCs. PD-L1 expression ratio in SCLC/LCNEC/TC/AC was 26.1%/50%/15.4%/20%, respectively. However, it was not significantly correlated with each prognosis. Therefore, the SCLC patients were analyzed, the overall 5-year survival of SCLC patients was found to be 47.3%. In the univariate analysis of the molecular expression of SCLC, neuroendocrine markers such as chromogranin-A (CGA) and synaptophysin (SYN) showed poor prognosis, albeit without significant differences. Conclusions: The neuroendocrine markers such as CGA and SYN might assist the prediction of prognosis and probably influence the decision for adjuvant chemotherapy or follow-up intervals after surgery in SCLC patients; however additional studies are essential.

Background Surgery for lung cancer invading the spine remains challenging associated with high morbidity and mortality. However, recent advances in surgical techniques as well as in perioperative care may improve outcomes of lung cancer surgery with vertebrectomy. We describe our surgical approach and assess the outcome lung cancer invading the spine. Methods We retrospectively reviewed our recent experiences of lung cancer with vertebral invasion, in which we have performed total or partial vertebrectomy from January 2011 through April 2015. Results We experienced eight patients who were treated with partial or total vertebrectomy for lung cancer. Vertebral invasion was evaluated by chest CT and MRI findings. All cases were no distant metastasis. N factors were all patients N0 revealed by chest CT and PET-CT. Two patients were treated preoperative induction therapy (CDDP + TS-1, Radiation 50 Gy). For the surgery, total vertebrectomy was performed two patients, hemi vertebrectomy was two patients, transverse-process resection was four patients. In all of eight cases, complete resection were perfomed with total or partial vertebrectomy. Morbidity was observed in six patients (75%); no mortality occurred. Six patients (75%) were survived after surgery (range: 12–62 months) and four patients (50%) were no recurrence. Five years overall survival rate was 71.4%. Conclusions In our experience, Lung cancer surgery combined with vertebrectomy is highly aggressive surgery associated with high morbidity. But, this procedure is a promising treatment option for selected patients, for example N0M0 disease with lung cancer invading the spine., Highlights • Surgery for lung cancer invading the spine remains challenging. • We describe our surgical approach and assess the outcome. • We experienced eight patients who were treated with partial or total vertebrectomy. • Five years overall survival rate was 71.4%.

Highlights • The treatment of patients for lung cancer with vertebral body invasion remains challenging. • We reported a case that total vertebrectomy (Th2) and dissection subclavian artery for lung cancer invading spine and subclavian artery. • We experienced complete resected one case that tumor location and invading was very complicated., Introduction Surgery for primary lung cancer invading the spine remains challenging. Here, we present a case of superior sulcus tumor (SST) with vertebral invasion, successfully resected with total vertebrectomy (Th2) and dissection of involved apical chest wall and the subclavian artery (SCA). Presentation of case A 62-year-old man was referred with the diagnosis of lung squamous cell carcinoma originating from left upper lobe (clinical stage IIIA/T4N0M0) involving the thoracic vertebrae (Th2) as well as the apical chest wall including three ribs (1st, 2nd and 3rd) and SCA. After induction concurrent chemo-radiotherapy, we achieved complete resection by three-step surgical procedures as follows: first, the anterior portion of involved chest wall including SCA was dissected through the trans-manubrial approach (TMA); next, the posterior portion of involved chest wall including ribs was dissected and left upper lobectomy with nodal dissection was performed through posterolateral thoracotomy; finally, total vertebrectomy (Th2) was performed through posterior mid-line approach. Discussion This tumor was existence of anterior and posterior position in pulmonary apex region. So that, it is very important for complete resecting this complicated tumor to work out operation’s strategy. Conclusion Surgery may be indicated for SST invading the spine, when complete resection is expected.

Background: Various anaplastic lymphoma kinase-tyrosine kinase inhibitors (ALK-TKIs) have been approved for use with patients with ALK-positive non–small cell lung cancer (NSCLC). However, little is known about the use of ALK-TKI in real-world clinical settings. Herein we present data from ALK-positive patients with NSCLC at our single institution. Methods: We retrospectively examined data from all patients who were administered ALK-TKIs for NSCLC from March 2012 until October 2018 at our institution. Results: Eleven patients received ALK-TKIs for NSCLC. The median age was 65 years (range, 45–85 years, mean 64 years), and all patients were diagnosed with adenocarcinoma. One patient had no treatment history, and the remaining 10 patients underwent surgery upon initiation of ALK-TKIs. Initial ALK-TKIs included crizotinib (n=2) and alectinib (n=9). The median follow-up was 21 months (range, 3.5–57 months). The 4-year overall survival (OS) rate was 71.4% for all patients. All patients achieved partial response or complete response. Two patients on crizotinib and one patient on alectinib experienced adverse events. Three patients received three types of ALK-TKIs; eight patients received only one ALK-TKI. One patient developed interstitial lung disease (ILD) and underwent salvage surgery after treatment with alectinib. ALK-TKIs affected brain metastases (BM) in four of five patients. Conclusions: Alectinib was associated with the best outcomes of available ALK-TKI medications. Alectinib is a key and approved drug. Alectinib should be administered as a first-line therapy for many patients.

Highlights • Surgical approach for locally advanced superior sulcus tumor is difficult. • We experienced a locally advanced superior sulcus tumor located from the anterior to posterior apex thoracic inlet. • Our surgical approach was effective and safe for treating a SST located from the anterior to posterior apex of the thoracic inlet., Introduction Superior sulcus tumors, frequently referred to as Pancoast tumors, are a wide range of tumors invading a section of the apical chest wall called the thoracic inlet. For this reason, a surgical approach and complete resection may be difficult to accomplish. We experienced a locally advanced superior sulcus tumor (SST) located from the anterior to posterior apex thoracic inlet and performed complete resection after definitive chemoradiation. Presentation of case A 71-year-old Japanese male presented at our hospital due to left back pain and an abnormal chest computed tomography (CT) scan showing 80 × 70 × 60-mm tumor located in the left middle apex thoracic inlet. This tumor was located near the subclavian artery, and the subclavian lymph nodes were swollen. The tumor was found to be an adenocarcinoma (clinical-T3N3M0 stage IIIB). Therefore, we performed definitive chemoradiation therapy. Slight reduction in the tumor size was noted after the treatment, and the subclavian lymph nodes were not swollen. We next performed surgical resection for this SST. Regarding the surgical approaches, the anterior approach was a transmanubrial approach, and the posterior approach was a Paulson’s thoracotomy. In this manner, we were able to perform complete en-bloc resection of this tumor. Discussion This surgical approach was effective and safe for treating a SST located from the anterior to posterior apex of the thoracic inlet. The patient remains healthy and recurrence-free at 2.5 years after the operation. Conclusion Surgical approach for SST is difficult. Therefore, this approach is effective and safety.

Background Pleomorphic lung cancer cells have been reported to produce cytokines, resulting in systemic reactions. Recently, the autonomous production of hematopoietic cytokines (granulocyte colony-stimulating factor [G-CSF], granulocyte-macrophage colony-stimulating factor [GM-CSF], and interleukin-6 [IL-6]) was observed in some of these patients. Case presentation We herein report a case of complete resection of right pleomorphic lung cancer producing IL-6. The patient had a high-grade fever before surgery, and a blood examination showed high IL-6 and CRP levels in the serum. After surgery, the patient no longer had a fever, and the elevated serum IL-6 levels had dropped to values less than those before the operation. Immunohistochemically, the carcinoma cells were faintly or focally positive for IL-6 and negative for G-CSF. Conclusions The symptoms in the present case were dramatically improved by surgery. In addition, an immunohistochemical examination showed that the cancer cells were positive for IL-6.

Intrapericardial vessel management is one of the necessary techniques for respiratory surgeons. We collected cases that had undergone intrapericardial vessel management for lung cancer, and herein discuss the practical performance and safety of this treatment method. We identified 23 (5.6%) of 413 patients who had undergone lung cancer surgery during the 30-month period from January 2011 to June 2013 at our institution. Twenty cases had large sized tumors near the hilum. Three cases demonstrated severe adhesion in the intrathoracic region due to a previous operation. The lung cancer staging was stage ⅠA in 1 case, stage ⅠB in 4 cases, stage ⅡB in 5 cases, stage ⅢA in 11 cases, stage ⅢB in 1 case, and stage Ⅳ in 1 case. We performed lobectomy in 11 cases, bilobectomy in 6 cases, and pneumonectomy in 6 cases. The average operation time was 366 minutes (137-965). Post operative complications were observed in five cases, including two cases of air-leakage and three cases of arrhythmia. All cases were able to walk on foot at discharge. It is important to clearly understand intrapericardial anatomy in order to carry out successful intrapericadial vessel management.

Background: Circulating tumor cells (CTCs) are tumor cells shed from primary tumor and circulate in the peripheral blood. CTCs, as a surrogate of distant metastasis, can be potentially useful in diagnosis and monitoring therapeutic effects in malignant tumors. Among a variety of systems for detection of CTCs, the “Cellsearch” is the only approved system for clinical use. However, EpCAM-negative tumor cells, such as those originating from non-epithelial cells and those undergoing epithelial-mesenchymal transition (EMT) cannot be captured with the “CellSearch” that is an EpCAM-based isolation system. Therefore, we have developed a novel polymeric microfluidic device (“Universal” CTC-chip) that can capture CTCs with or without EpCAM expression (AACR 2015). In the present study, we examined CTCs-detection performance of the CTC-chip in patients with thoracic malignant tumors (lung cancer [LC] as an “EpCAM-positive” tumor and malignant pleural mesothelioma [MPM] as an “EpCAM-negative” tumor) in comparison with that of the CellSearch. Methods: Peripheral blood sampled from each patient was divided and subjected to quantitative evaluation of CTCs with the CTC-chip as well as with the “CellSearch”. The CTC-chip, coated with an anti-EpCAM antibody, was used to capture CTCs in the blood samples (n=19) from lung cancer patients. To capture CTCs in the samples (n=11) from MPM patients, the CTC-chip was coated with an antibody against podoplanin that is expressed on the mesothelioma. After immuno-staining for cytokeratin and CD45 on the chip, a captured cell containing Hoechst-positive nucleus and cytokeratin-positive/ CD45-negative cytoplasm was judged as a CTC. The CTC-count for each sample was represented as the number per 7.5mL of the blood. Results: The median CTC-count detected with the CTC-chip in LC was 50 (range, 0-270), which was significantly higher than that (the median CTC-count, 0; range, 0-47) with the CellSearch (p Conclusion: The “universal” CTC-chip achieved higher performance in detection of CTCs of thoracic malignant tumors as compared with the CellSearch. The updated data will be presented at the AACR annual meeting 2017. Citation Format: Kazue Yoneda, Taiji Kuwata, Yasuhiro Chikaishi, Kenichi Kobayashi, Sakiko Yura, Hiroki Matsumiya, Masatoshi Kanayama, Akihiro Taira, Yusuke Nabe, Shinji Shinohara, Masaru Takenaka, Soichi Oka, Ayako Hirai, Yuko Tashima, Naoko Imanishi, Koji Kuroda, Fumihiro Tanaka. Detection of CTCs in thoracic malignant tumors with "universal" CTC-chip [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1721. doi:10.1158/1538-7445.AM2017-1721