Yoshiaki Furuhata

Telomerase Activity Significantly Correlates with Chromosome Alterations, Cell Differentiation, and Proliferation in Lung Adenocarcinomas

Telomerase activity was examined by the telomeric repeat amplification protocol assay in 25 cases of lung adenocarcinoma, in relation to cancer cell differentiation, proliferation, and chromosome alterations. Telomerase activity, chromosome alterations, and cell proliferation assessed by Ki-67 labeling were significantly lower (P < .001 to .05) in well-differentiated (10 cases) than in moderately differentiated (8 cases) or poorly differentiated (7 cases) lesions. Telomerase activity by semiquantitative analysis with scoring of 0 to 3 was significantly correlated with similarly graded chromosome alterations (P < .05) and Ki-67 labeling indices (P < .002). Telomerase activity and chromosome alteration (T-C) indices generated by multiplication of telomerase activity and chromosome alteration scores also showed a significant correlation with cell differentiation. The Clara cell subtype, confirmed by electron microscopic analysis, significantly predominated in the well-differentiated group, showing a low grade of telomerase activity and chromosome alterations and low Ki-67 labeling indices, suggesting clinical relevance. No significant association of telomerase activity was found with p53 protein accumulation or Bcl-2 protein expression. The good correlation of telomerase activity with chromosome alterations, cell differentiation, and Ki-67 labeling indices suggests that this parameter might have potential application in estimation of prognosis.

Transformation to small-cell lung cancer as a mechanism of acquired resistance to crizotinib and alectinib

A 56-year-old woman, a never-smoker, had postoperative recurrence of anaplastic lymphoma kinase rearranged lung cancer. She achieved a partial response to treatment with an anaplastic lymphoma kinase tyrosine kinase inhibitor, crizotinib. After the tumor regrowth, crizotinib was switched to alectinib; once again a partial response was observed. At the second recurrence, transbronchial needle aspiration of the right paratracheal node was performed, which revealed cytological findings of small-cell carcinoma. While treatment with cisplatin-irinotecan chemotherapy made reduction of some tumor shadows, including the biopsied mediastinal lymph nodes, new, small, nodular shadows, highly suggestive of pulmonary metastases, were detected in both lung fields. This case may show proof of the transformation to small-cell lung cancer as a mechanism of resistance to anaplastic lymphoma kinase tyrosine kinase inhibitors in anaplastic lymphoma kinase rearranged tumor. However, this transformation may also be only one part of the resistance mechanism of the heterogeneous tumor.

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.

An immunohistochemical study of the mesenchymal and epithelial components of pulmonary chondromatous hamartomas

Twenty‐five cases of solitary pulmonary chondromatous hamartomas (PCH) were examined by immunohistochemistry to evaluate the mesenchymal and epithelial components. PCH composed of predominantly mature cartilage were designated as C type, those predominantly composed of fibromyxoid tissue as FM type, and those predominantly composed of adipose tissue as A type. FM type PCH revealed various amounts of cartilage in various developmental stages, adipose tissue and fibromyxoid tissue, compared with a uniform pattern of cartilage tissue in C type. The cells of transitional form between spindle cells, stellate cells and chondrocytes were present in FM type. Epithelial components in PCH were bronchial, bronchiolar and cuboidal cells, mostly at the periphery of PCH. S‐100 protein consistently stained chondrocytes, stellate and spindle cells in the fibromyxoid tissue of solitary PCH. Fibroblast growth factor was immunolocalized to chondrocytes, spindle and stellate cells in the fibromyxoid tissue. The collagen type was associated with differentiation from primitive mesenchymal cells to chondrocytes (i.e. type I and III collagen appeared in fibromyxoid matrix and type II collagen in the cartilaginous matrix). Fibronectin coordinately appeared with type I and III collagens. The proliferating cell nuclear antigen labeling index of epithelial cells was comparable to those of neoplastic mesenchymal cells, but it was not significantly different between C type and FM type PCH. The primitive mesenchymal cells in the bronchial walls of the control premature neonates were also observed. This immunohistochemical study showed that the progenitor mesenchymal cells in the bronchial and bronchiolar walls may differentiate along chondrocytes, lipocytes, and smooth muscle cells in PCH and that epithelial proliferation is reactive and closely associated with neoplastic proliferation of the mesenchymal component.

Local Control and Cosmetic Outcome after Sector Resection with or without Radiation Therapy for Early Breast Cancer

Breast conserving surgery and radiation therapy (RT) can achieve a more favorable cosmetic outcome than mastectomy in patients with early breast cancer. However, it is widely recognized that RT is an impediment to improving the cosmetic outcome. Between 1985 and 1993, 113 patients were enrolled in a prospective randomized study to examine whether or not RT could be avoided following sector resection in patients with Stage I and II (UICC) invasive breast cancer. There was no significant difference in the 8 year local recurrence free survival rate between the RT and non-RT groups (92.3% versus 89.8% respectively). The characteristics of suitable patients would be negative nodes and microscopically negative resection margins. In conclusion, sector resection without RT is a reasonable option for some patients with early breast cancer.

Efficacy and safety of stereotactic body radiotherapy using CyberKnife in Stage I primary lung tumor

Background CyberKnife® (CK) is a new, advanced radiotherapy technique. This study aimed to evaluate its efficacy and toxicity in Japanese patients with early-stage primary lung tumor who were medically unfit and inoperable. Methods This retrospective study investigated patients who received CK treatment for medically inoperable Stage І primary lung tumor at the Japanese Red Cross Medical Center between June 2011 and September 2016. Each patient received a total of 36-48 Gy (median, 43 Gy) administered by CK in 4-5 fractions. Results Totally, 40 patients (T1a, n = 19; T1b, n = 15; T2a, n = 6) were included. Their median age was 86 (range, 56-95) years. Tracking required the use of fiducial markers in 28 patients and the Xsight Spine Tracking System in 12. The median follow-up was 14.5 (range, 1-51) months. Local recurrence occurred in seven (17.5%) patients. The local progression-free survival rates at 1 and 2 years were 83.9% and 74.0%, respectively. Distant recurrence occurred in regional lymph nodes (n = 5), the lung outside the radiation field (n = 3), and the bone (n = 1). Seven patients died. Overall survival rates at 1 and 2 years were 93.6% and 73.1%, respectively. Radiation pneumonitis was identified in 28 (70%) patients (Grade 1, n = 25; Grade 2, n = 2; Grade 5, n = 1). Conclusions CK showed good local control with limited toxicity and could be an alternative treatment modality in medically inoperable patients with Stage І primary lung tumor.

The combination of EBUS-TBNA and the PAB antibody led to a successful treatment for lung cancer in a patient with asymptomatic sarcoidosis mimicking nodal metastasis

Correct staging of lung cancer is important for the selection of the best therapy, but discriminating between lymphadenopathy from lung cancer and from sarcoidosis by imaging examinations is difficult. Additionally, distinguishing lymphadenopathy of sarcoidosis from sarcoid reactions which are sometimes caused by lung cancer is difficult on imaging and pathological findings. A 73-year-old woman was diagnosed as lung cancer clinical T1bN3M0 stage ШB based on false-positive 18F-fluoro-2-deoxyglucose positron emission tomography uptake. Because the effects of chemotherapy were different between the lymphadenopathy and the primary lesion, endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) was performed and revealed sarcoidosis as the cause of the lymphadenopathy with using a specific monoclonal antibody against Propionibacterium acnes (PAB antibody). Accordingly, the stage was changed to clinical T1bN0M0 stage ІA, for which radical operation was performed. EBUS-TBNA should be performed aggressively when the effect of chemotherapy is different between lymphadenopathies and other lesions, and the PAB antibody can help to discriminate between sarcoidosis and sarcoid reactions caused by lung cancer. The combination of EBUS-TBNA and the PAB antibody is expected to be valuable in the definitive diagnosis of a lymphadenopathy for the staging of lung cancer.

The Significant Antitumor Activity of Nivolumab in Lung Adenocarcinoma with Choriocarcinomatous Features

We report the case of a 60-year-old Japanese man with a metastatic brain tumor that caused ataxia. As a consequence of resection of a cerebellar tumor, the tumor was diagnosed as a poorly differentiated adenocarcinoma with choriocarcinomatous features. The patient underwent bronchoscopy, leading to a diagnosis of the same histology as the brain tumor. After the administration of first-line chemotherapy and maintenance therapy due to progressive disease, he was given nivolumab and obtained a partial response; however, 11-months later, computed tomography showed tumor progression. Our experience suggests that nivolumab has strong activity, even in patients with a rare form of lung cancer.

The Right Middle and the Inferior Pulmonary Vein Forming a Common Trunk

We herein report a rare surgical case of the right middle lobe vein draining into the inferior pulmonary vein. The anatomical abnormalities in pulmonary veins can have a serious impact on complications during pulmonary surgery. Surgeons must be aware of any variation in the pulmonary vessels, and preoperative assessment of pulmonary venous anomalies is important during pulmonary surgery.

Spontaneous esophageal rupture after gastrointestinal examination using barium

We experienced a case of spontaneous rupture of the esophagus after gastrointestinal examination using barium. A 48-year-old male experienced severe chest pain after vomiting following gastrointestinal examination. Chest X-ray revealed a right pneumothorax and pleural effusion by barium. We diagnosed spontaneous rupture of the esophagus and performed right thoracotomy 6 hours after onset of symptoms. At 10 cm above the diaphragm, there was a vertical perforation 3 cm in length. Following saline lavage, the ruptured esophageal wall was directly closed by the layer to layer method. The post operative course was uneventful and the patient was discharged 3 weeks after surgery. Cases of spontaneous rupture of the esophagus into the right thoracic cavity induced by gastrointestinal examination are extremely rare.