Hiroaki Tsunezuka

Bone mass increase specific to the female in a line of transgenic mice overexpressing human osteoblast stimulating factor-1

We have reported that transgenic mice overexpressing human osteoblast stimulating factor-1 (osf1) under the control of the human osteocalcin promoter have a significantly higher bone mineral content and density than nontransgenic littermates. Consequently, bone mass loss due to estrogen deficiency was compensated for in ovariectomized female mice. Here, we show that in this transgenic line, the bone mass increase was evident in female, but not male, mice, as evaluated using the ash assay, double-emission X-ray analysis, and calcein double-labeling to determine the bone formation rate. To elucidate a possible influence on gene expression, we analyzed genomic structures of the inserted transgene and its flanking regions in mouse chromosomes. The results revealed that the transgene was integrated in the mouse repetitive sequences, 234-bp-long Γ-satellite repeats, as inverted multiple (5 + 8) copies. Twelve copies at most seemed to be functional, but no direct evidence supporting female-specific mRNA synthesis of the transgene was obtained.

Intuitive Touch Panel Navigation System through Kyoto Digital Sosui Network

We have developed multi-touch panel robotic arm control system for thoracoscopic surgery. Our multi-touch panel navigation system consists of green laser guide maker, robotic arms with four spindles, multi-touch panel monitor, and PCs for control regulation. The multi-touch panel monitor recognized the finger-touch; thereby the tip of the robot arm is controlled just on the green maker. For estimation in remote control use, the PC for the robot control was placed in Kyoto Prefectural University of Medicine, which was connected through the Kyoto Digital Sosui Network, a gigabit Ethernet with layer-2 security. Another computer for the remote control of the PC for the robot control was placed in Yamashiro Public Hospital, 35 kilometers south of Kyoto city, through the same gigabit Ethernet. Using virtual network computing (VNC), which is a graphical desktop sharing system to control another computer, we demonstrated a remote control of the robot and collected the packets to examine the traffic bandwidth. The robot was successfully controlled in remote conditions. The throughput of the Ethernet was 16.4 ±3.6 Mbps in the remote control of the robot using VNC. The round-trip time was 19.9 ± 0.39 msec, while 8000 bytes data was sent by using ping command. We demonstrated an intuitive touch panel navigation system, which a surgical robot stopped an arterial bleeding in an animal model. The robot system was successfully controlled through a gigabit Ethernet between two distant hospitals.

Spontaneous Regression of Primary Pulmonary Synovial Sarcoma

We report a rare case of primary pulmonary synovial sarcoma that underwent spontaneous regression after a transbronchial biopsy. A 38-year-old woman with a well-demarcated solitary mass shadow on chest roentgenogram was referred to us. A transbronchial biopsy was performed, and immunohistochemical results as well as detection of SYT-SSX1 (SYnovial sarcoma Translocation-Synovial Sarcoma X chromosome breakpoint) transcripts resulted in a diagnosis of synovial sarcoma. A right lower lobectomy was performed during video-assisted thoracoscopic surgery. Pathologic examination revealed widespread coagulative necrosis with feeding arterioles occluded by organized thrombi. To our knowledge, this is the first report of a case of spontaneous regression of primary pulmonary synovial sarcoma.

Significance of PD-L1 expression in pulmonary metastases from head and neck squamous cell carcinoma

BACKGROUND The mechanism by which tumors escape the immune system has been actively investigated and is partly explained by the programmed death-1 (PD-1) and its ligand (PD-L1) pathway. This study is aimed at clarifying the prognostic significance of PD-L1 expression in patients with surgically resected pulmonary metastases of head and neck squamous cell carcinoma (HNSCC). PATIENTS AND METHODS A retrospective review was conducted of 26 HNSCC patients who underwent complete resection of pulmonary metastases. PD-L1 expression in both the primary and metastatic tumors was evaluated using immunohistochemistry (anti-PD-L1 antibody, clone SP263). High PD-L1 expression was defined as ≥50% of tumor cells with positive staining. Survival and prognostic impacts following pulmonary metastasectomy were analyzed based on the PD-L1 expression level. RESULTS The patients included 23 men and 3 women, with a median age of 65 years. Six (23%) of the pulmonary metastatic cases showed high PD-L1 expression, while their corresponding primary lesions had low PD-L1 expression. The 5-year overall survival rate after pulmonary metastasectomy was 57.6% in all cases. The 5-year overall survival rates were 72.5% and 16.7% in the low and high PD-L1 groups, respectively (p < 0.001). Multivariate analysis demonstrated that high PD-L1 expression and older age (>65 years) correlated independently with a shorter overall survival (p < 0.001). CONCLUSIONS High PD-L1 expression in pulmonary metastases could be an independent predictor of poor outcome in HNSCC patients undergoing pulmonary metastasectomy. This is the first report evaluating the prognostic implication of PD-L1 expression in metastatic HNSCC.

Successful treatment with afatinib for pancreatic metastasis of lung adenocarcinoma: a case report

Metastatic lung cancer of the pancreas is rare and optimal treatment protocols have not been determined. An asymptomatic 53-year-old man with primary lung cancer underwent a right lower lobectomy and was diagnosed with acinar adenocarcinoma, pT2bN2M0 stage IIIA. An epidermal growth factor receptor (EGFR) mutation (exon 19 deletion L747-A750insP) was detected in the primary tumor. Adjuvant platinum-based chemotherapy was administered. The patients serum carcinoembryonic antigen (CEA) level had increased to 38.6 ng/mL 32 months after surgery, and positron emission tomography-computed tomography (PET-CT) revealed a 2.5-cm, hypermetabolic nodule in the pancreatic body. Using endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA), the nodule was pathologically diagnosed as a pancreatic metastasis of lung adenocarcinoma. The EGFR status of the pancreatic metastasis was confirmed to be the same as that of the primary lung tumor. The patient started afatinib therapy and his serum CEA level immediately decreased and remained at approximately the reference limit. On a follow-up PET-CT scan after 10 months of treatment with afatinib, the metastatic nodule in the pancreas had disappeared and no accumulation of fluorine-18-deoxyglucose (FDG) was detected. To the best of our knowledge, this is the first reported case of a complete response of pancreatic metastatic lung adenocarcinoma to EGFR-tyrosine kinase inhibitors (TKIs).

Pulmonary atypical carcinoid in a patient with Cowden syndrome

Cowden syndrome is a phosphatase and tensin homologue on chromosome ten (PTEN) hamartoma tumour syndrome. The loss of function of the PTEN protein is associated with the risk of development and progression of several types of tumours, such as pulmonary neuroendocrine tumours and carcinoids. We present a 65-year old male non-smoker, who was diagnosed with Cowden syndrome and had a pulmonary tumour. He underwent wedge resection via video-assisted thoracoscopic surgery and was histopathologically diagnosed with an atypical carcinoid. To our knowledge, this is the first report on a pulmonary atypical carcinoid in a patient with Cowden syndrome. The present findings suggest a potential link between phosphoinositide-3 kinase/protein kinase B signalling in Cowden syndrome and the development of pulmonary neuroendocrine tumours, such as carcinoids.

Improvements in thoracic surgery outcomes: a multi-institutional collaboration study.

BackgroundTreatment protocols (including those for thoracic surgery) tend to be customized for individual hospitals. Procedural standardization is required to improve surgical tasks and patient outcomes. This study aimed to evaluate the effects of an initiative to standardize surgical tasks for efficient and safe performance.MethodsHospitals associated with the Division of Chest Surgery of the Kyoto Prefectural University of Medicine held joint meetings involving their thoracic surgeons and operating room nurses between February 2011 and November 2012 to standardize surgical tasks. Operation times and blood loss were compared before and after standardization.ResultsThe implementation rate of standardized surgical tasks was 97%. The pre-operative (from entry to the operating room until commencement of surgery) and post-operative (from conclusion of surgery until departure from the operating room) times were significantly decreased after the standardization. When compared according to operative group (all thoracic surgery, lung lobectomy, and partial lung resection), operation times were shorter for all three groups; in addition, the amount of blood loss was lower in all three groups after standardization. A post-standardization survey showed improved morale among the meeting participants.ConclusionsInterdisciplinary standardization of surgical tasks across institutions improved thoracic surgery tasks and surgical outcomes.

Three-dimensional kinematic analysis of active cervical spine motion by using a multifaceted marker device

Assessing cervical range of motion (CROM) is an important part of the clinical evaluation of patients with conditions such as whiplash syndrome. This study aimed to develop a convenient and accurate system involving multifaceted marker device (MMD)-based assessment of 3-dimensional (3D) dynamic coupled CROM and joint angular velocity. We used an infrared optical tracking system and our newly developed MMD that solved problems such as marker shielding and reflection angle associated with the optical tracking devices and enabled sequential and accurate analysis of the 3D dynamic movement of the polyaxial joint and other structurally complicated joints. The study included 30 asymptomatic young male volunteers (age, 22-27 years). The MMD consisted of 5 surfaces and 5 markers and was attached to the participants forehead. We measured active CROM (axial rotation, flexion/extension, and lateral bending) and joint angular velocity by the MMD. The MMD was easy to use, safe for patients and operators, could be constructed economically, and generated accurate data such as dynamic coupled CROM and angular velocity.