Mikihiro Kohno

PD-L1 Is Upregulated by Simultaneous Amplification of the PD-L1 and JAK2 Genes in Non–Small Cell Lung Cancer

Objectives The programmed death ligand 1(PD‐L1)/programmed cell death protein 1 (PD‐1) pathway is one of the most important checkpoint pathways for mediating tumor‐induced immune suppression through T‐cell exhaustion. Recently, targeted therapies using monoclonal antibodies against components of this pathway have been shown to reduce tumor burden in patients with non–small cell lung cancer (NSCLC). However, the prognostic significance of PD‐L1 expression is controversial and the precise mechanisms of PD‐L1 gene activation in lung cancer have yet to be clarified. Methods We investigated copy number alterations (CNAs) in the PD‐L1 gene by real‐time PCR in 94 surgically resected lung cancer samples to find possible associations between PD‐L1 CNA and lung cancer biology. Janus kinase 2 gene (JAK2) CNA and its influence on the PD‐L1/PD‐1 pathway were also assessed. Results Five samples were shown to have PD‐L1 gene amplification, whereas 89 samples did not. The patients with PD‐L1 amplification had worse prognoses than did those without PD‐L1 amplification. Genetic amplification of the PD‐L1 gene was correlated with JAK2 gene amplification. The lung cancer cell line HCC4006 was found to harbor both JAK2 and PD‐L1 amplification. Flow cytometry analyses revealed the level of PD‐L1 protein expression to be higher in HCC4006 cells than in other NSCLC cell lines. Expression of the PD‐L1 protein was significantly reduced by the JAK2 inhibitor TG‐101348 and the signal transducer and activator of transcription 3 (STAT‐3) inhibitor BP‐1‐102, but not by the STAT1 inhibitor fludarabine. Conclusions Our data suggest that expression of PD‐L1 protein is upregulated by the simultaneous amplification of the PD‐L1 and JAK2 genes through JAK‐STAT signaling in NCSLC.

Granulocyte colony-stimulating-factor-producing hepatocellular carcinoma with extensive sarcomatous changes: report of a case

This report describes a rare case of hepatocellular carcinoma (HCC) producing granulocyte colony-stimulating factor (G-CSF). A 46-year-old male with chronic hepatitis B, who presented with fever, general malaise, loss of appetite, and weight loss, had a huge liver mass in the portal region. He had marked granulocytosis and his serum level of G-CSF was elevated. Complete tumor resection was performed, and the pathological assessment of the resected specimen revealed HCC with extensive sarcomatous changes and immunohistochemical staining for G-CSF and G-CSF receptor. Only a few cases of G-CSF-producing HCC have been reported, and this is the first case of G-CSF-producing HCC that also expressed G-CSF receptor.

The prognostic impact of the amount of tobacco smoking in non-small cell lung cancer—Differences between adenocarcinoma and squamous cell carcinoma

BACKGROUNDS The purpose of this study was to investigate the relationship between the level of tobacco smoking and the clinicopathological features of non-small cell lung cancer (NSCLC) patients, individually for adenocarcinoma (Ad) and squamous cell carcinoma (Sq). PATIENTS AND METHODS We retrospectively reviewed the clinical records of 1825 consecutive lung cancer patients who underwent surgery in our department. Among these, the data sets of 750 Ad patients and 364 Sq patients who received lobectomy or more extensive resection were available. RESULTS In Ad patients, those who had never smoked (never-smokers) (n=309) were more likely to be female, to have less advanced stage tumors, and to have a significantly better prognosis than those who had ever smoked (ever-smokers) (n=441) (5-year OS: never-smokers, 67.9%; ever-smokers, 53.7%, p<0.0001). In Sq patients, the never-smokers (n=15) were more likely to be female than the ever-smokers (n=349). Among ever-smokers, the light-smokers (PY≤30; n=56) were associated with more female patients, more advanced stage tumors, and significantly worse prognoses than were the heavy smokers (PY>30; n=292) (p=0.0003). The multivariate survival analysis showed that light smoking was related to a worse prognosis compared with heavy smoking (HR=2.06, 95% CI 1.43-2.98, p=0.0001). CONCLUSIONS The never-smokers had a significantly better prognosis than ever-smokers among Ad patients, whereas the light-smokers had a significantly worse prognosis than heavy smokers among Sq patients. There may be factors other than tobacco carcinogens that influence the development of Sq in never and/or light smokers.

Ground-glass opacity lesions on computed tomography during postoperative surveillance for primary non-small cell lung cancer

Improvement in chest high-resolution computed tomography (CT) has increased the detection of ground-glass opacity (GGO) lesions. However, there is no clear therapeutic consensus about concurrent GGO lesions detected during postoperative follow-up chest CT after treatment for primary lung cancer. This study retrospectively and prospectively investigated 21 patients in whom 53 GGO lesions were detected during postoperative follow-up CT of non-small cell lung cancer at Kyushu University Hospital from April 2009 to February 2010. We investigated clinicopathological factors, such as age, gender, lesion number, size, laterality, time of identification, and enlargement or emergence of the inner solid component. The malignancy rate of the concurrent GGO lesions was assessed by log-rank test in the Kaplan-Meier curves. Twenty percent of the 53 GGO lesions had malignant radiological findings during the 5-year follow-up after they were first identified by CT. The newly emerging GGO lesions at postoperative CT had significantly more malignant radiological findings (39.5%) than other GGO lesions (9.5%). Three potentially malignant GGO lesions were treated by surgical resection and three were treated by stereotactic radiotherapy. These six treated GGO lesions showed a good clinical course without recurrence after treatment. Special attention should be paid to newly emerging GGO lesions after resection of primary non-small cell lung cancer. It is necessary to select an appropriate treatment, taking account of various factors such as the laterality and number of GGO lesions or the pathological stage of the postoperative lung cancer.

Solitary pulmonary metastasis from malignant melanoma of the bulbar conjunctiva presenting as a pulmonary ground glass nodule: Report of a case.

We herein report a case of solitary pulmonary metastasis from malignant melanoma that presented as a pulmonary ground glass nodule. A 57‐year‐old man who had undergone resection of a malignant melanoma of the right bulbar conjunctiva at the age of 51 was referred to our hospital for management of ground glass opacity in his left lung. Because radiological examination suggested the nodule was an adenocarcinoma in situ, computed tomography (CT) follow‐up was planned. CT examination performed nine months later showed that the nodule had grown from 6 mm to 8 mm. Moreover, CT performed one and a half years after first detection revealed that the nodule had grown up to 10 mm. The patient, therefore, underwent partial resection of the lung for diagnosis and treatment. Pathological examination of the resected specimen revealed atypical cells with melanin granules proliferating in a lepidic‐like fashion. The cells were positive on S‐100 staining, indicating a pulmonary metastasis from malignant melanoma. Thus, metastatic tumors from malignant melanoma can present as ground glass opacities.

Treatment for recurrence after extrapleural pneumonectomy for malignant pleural mesothelioma: A single institution experience

Background:  Malignant pleural mesothelioma (MPM) is a relatively rare, aggressive neoplasm associated with asbestos exposure. Extrapleural pneumonectomy (EPP) is often performed for resectable MPM as part of a multidisciplinary treatment; however, available data on treatments for recurrence after EPP are limited.

Outcome of intravascular stent in superior vena cava syndrome

Background: Superior vena cava (SVC) syndrome is one of the oncologic emergency. The patients under life-threatening conditions require urgent treatment such as chemotherapy, radiation therapy and stent placement. It has been reported that stent placement provide a palliative benefit. However, indication for treatment of stenting are not well defined. Objective: The aim of this study was to evaluate the outcome of intravascular stent in SVCsyndrome. Methods: The subjects consisted of 11 patients who were undergone stent placement in Matsuyama Red Cross Hospital between June 2010 and April 2013. Contrast enhanced CT was made in all patients. Stent placement was made with self-expanding stent. Results: All patients had lung cancer (5 in adenocarcinoma, 4 in small cell carcinoma and 2 in non-small lung cancer). Seven patients previously had received chemotherapy and /or radiation therapy. In all patients, correct positioning of stents was achieved. Their symptoms completely disappeared within 6.8 hours. The median survival time was 133 days (range, 31 to 573 days). Major side effects were not observed. Conclusion: In our study, stent placement dramatically improved symptoms and quality of life. Stenting increased the survival benefit, especially in patients with improved performance status.

Localized biphasic type malignant mesothelioma arising in the peritoneum: Report of a case

This report describes a rare case of localized malignant biphasic (mixed epithelioid and sarcomatoid) mesothelioma arising in the peritoneum. A 69‐year‐old male with a history of asbestos exposure, complaining of a painful mass in the left chest wall, was found via computed tomography (CT) to have a tumor in the left peritoneum. The resected tumor was histologically and immunohistochemically consistent with a malignant mesothelioma with mixed epithelioid and sarcomatoid type and no distant metastasis. The diagnosis of localized malignant biphasic mesothelioma arising in the peritoneum was appropriate because there was no evidence of any other primary tumor.

A Rare Case of a Bronchial Anomaly Running in the Hilar Region from the Right Lower Lobe to the Middle Lobe

A 77-year-old male was referred to our department due to lung cancer (cT3N0M0) of the right lower lobe. During right lower lobectomy, a thin duct structure was recognized in the hilar region between the middle and lower lobes that was identified to be a supernumerary bronchus upon a review of the preoperative chest CT images. Although bronchial anomalies are rare, it is important to carefully view preoperative images for any such anomalies in order to more safely perform surgery.