Masato Kanzaki

Functional closure of visceral pleural defects by autologous tissue engineered cell sheets

OBJECTIVE The occurrence of intraoperative air leaks is an unavoidable complication during pulmonary surgeries. However, current surgical methods are generally ineffective in closing these visceral pleural defects, resulting in a decreased quality of life for patients. Here, we examined novel tissue engineered cell sheets for the closure of pleural defects in a porcine model. METHODS Skin biopsies were harvested from juvenile swine and tissue sheets composed of dermal fibroblasts were created using ex vivo culture on temperature-responsive dishes. After creating a visceral pleural injury model, the tissue engineered autologous dermal fibroblast sheets were transplanted directly to the defects without the use of sutures or additional adhesive agents, such as fibrin glue. RESULTS The tissue engineered autologous dermal fibroblast sheets attached directly to the lung surface providing an immediate seal against up to 25 cm H2O of airway pressure. Four weeks after transplantation, the dermal fibroblast sheets remained present on the pleural surface, providing permanent closure. The dermal fibroblast sheets were also responsive to changes in lung volume due to mechanical ventilation. No recurrences of air leaks were observed throughout the follow-up period. CONCLUSIONS This study presents the development of an effective sealant for visceral pleural defects using autologous cells that have the flexibility to respond to expansion and contraction during respiration.

Thoracoscopic cell sheet transplantation with a novel device

Regenerative medicine with transplantable cell sheets fabricated on temperature‐responsive culture surfaces has been successfully achieved in clinical applications, including skin and cornea treatment. Previously, we reported that transplantation of fibroblast cell sheets to wounded lung had big advantages for sealing intraoperative air leaks compared with conventional materials. Here, we report a novel device for minimally invasive transplantation of cell sheets in endoscopic surgery, such as video‐assisted thoracoscopic surgery (VATS). The novel device was designed with a computer‐aided design (CAD) system, and the three‐dimensional (3D) data were transferred to a 3D printer. With this rapid prototyping system, the cell sheet transplantation device was fabricated using a commercially available photopolymer approved for clinical use. Square cell sheets (24 × 24 mm) were successfully transplanted onto wound sites of porcine lung placed in a human body model, with the device inserted through a 12 mm port. Such a device would enable less invasive transplantation of cell sheets onto a wide variety of internal organs. Copyright

Comparison of three software programs for three-dimensional graphic imaging as contrasted with operative findings,

OBJECTIVES Several types of practical three-dimensional (3D) imaging software programs are available, including those attached to computed tomographic devices. Three different software programs (Advantage Workstation Volume Share 4, OsiriX and CTTRY) were used to generate 3D images on the basis of imaging data obtained by 64-slice multidetector-row computed tomography in the same patient. METHODS Surgery was then performed referring to these 3D images in five patients. The characteristics, advantages, disadvantages and utility in the operative field of the images generated with each software program were compared with respect to actual operative findings. RESULTS There were no marked differences in vascular images at the segmental level among the software programs, and all three were considered useful for surgery. However, vascular images at the subsegmental level differed among the three programs. CONCLUSIONS The depiction of blood vessels at the subsegmental level lacked accuracy when compared with operative findings.

Presurgical Planning Using a Three-Dimensional Pulmonary Model of the Actual Anatomy of Patient with Primary Lung Cancer

OBJECTIVES Video-assisted thoracoscopic surgery (VATS) for both lobectomy and segmentectomy has been used widely for early stage nonsmall cell lung cancer (NSCLC). The objective of this study was to investigate the clinical feasibility of surgical planning using patients actual three-dimensional (3D) pulmonary model for the thoracoscopic surgical treatment of early stage NSCLC. METHODS We examined 57 patients with stage IA NSCLC ≤ 2 cm in diameter. Based on patients actual 3D pulmonary model created by using a homemade software program called CTTRY (Tokyo Womens Medical University, Tokyo, Japan), both the location of and extent of tumor invasion were assessed, and a suitable type of VATS lung resection for an individual was selected. RESULTS By the 3D models, tumors in 47 patients were localized within one segment, and other tumors (10 patients, 18%) were involved in multiple segments. VATS lung resections consisted of a single segmentectomy were performed in 25 patients; upper division resections, 9; lingulectomy, 5; extended segmentectomy, 7; single subsegmentectomy, 6; and multiple subsegmentectomy, 5. All 57 patients underwent successful VATS lung resection without massive bleeding. CONCLUSION Presurgical planning based on patients actual 3D pulmonary model is useful for patients with stage IA NSCLC ≤ 2 cm in diameter and for selecting an appropriate VATS lung resection for an individual.

Complete video-assisted thoracoscopic multi-subsegmentectomy based on patients' specific virtual 3-D pulmonary models

Video‐assisted thoracoscopic surgery is widely used for resecting early‐stage non‐small cell lung cancer. Segmentectomy and subsegmentectomy require a thorough knowledge of the 3‐D bronchovascular anatomy of the lung. Previously, our department reported using a 3‐D pulmonary model of a patient for thoracoscopic surgical treatment of non‐small cell lung cancer. This study investigates multi‐segmentectomy for patients with non‐small cell lung cancer.

Hypoglycemia Observed on Continuous Glucose Monitoring Associated With IGF-2-Producing Solitary Fibrous Tumor.

CONTEXT Tumors producing IGF-2 (IGF-2oma) are a major cause of spontaneous hypoglycemia. The treatment mainstay is surgical resection. Many case reports note resolution of hypoglycemia after IGF-2oma resection; however, outcomes are variable according to tumor type. We report a case of resolving hypoglycemia, observed on continuous glucose monitoring, after resection of an IGF-2-producing solitary fibrous tumor of pleura and review the current literature. CASE REPORT A 69-year-old woman presented with impaired consciousness because of hypoglycemia. An IGF-2oma was diagnosed as the cause for hypoglycemia because of decreased serum insulin and IGF-1, the presence of a pleural tumor, and a high-molecular-weight form of serum IGF-2 detected by Western immunoblot. Surgical resection was performed; pathological examination demonstrated a solitary fibrous tumor with low-grade malignancy. Continuous glucose monitoring showed reversal of hypoglycemia after tumor resection. Approximately 2 years after resection, the patient has no signs of tumor recurrence or hypoglycemia. CONCLUSIONS An IGF-2-producing solitary fibrous tumor of pleura in this case caused hypoglycemia. From a search of the literature of 2004-2014, 32 cases of IGF-2oma with hypoglycemia that underwent radical surgery were identified; in 19 (59%) patients, hypoglycemia was reversed, and there was no subsequent recurrence. The remaining 13 (41%) patients experienced tumor recurrence or metastasis an average of 43 months after initial tumor resection. The tumor of the present case was a low-grade malignancy. Regular follow-up with biomarker monitoring of glucose metabolism and assessment of hypoglycemic symptomatology, in conjunction with imaging tests, is important for detecting possible tumor recurrence and metastasis.

Controlled collagen crosslinking process in tissue-engineered fibroblast sheets for preventing scar contracture on the surface of lungs

For preventing the scar contracture of host tissue and adjusting the tensile strength of covering cell sheets, a controlled collagen crosslinking step process in the preparation of skin‐fibroblast sheets for repairing wound was investigated by using β‐aminopropionitrile (BAPN), a collagen crosslinking inhibitor, in the culture medium. Skin fibroblasts obtained from neonatal rats were cultured in medium with and without 0.25 mm BAPN for 7 days and seeded on temperature‐responsive culture dishes. After the confluent cells were non‐invasively harvested as a monolithic cell sheet, two cell sheets were transplanted to a lung‐injury site of athymic rats, which was closed by neither fibrin glue nor suturing. Four weeks after the transplantation the animals were sacrificed and the lungs with the transplanted cell sheets were examined. Although the control cell sheet‐transplanted lungs contracted the surrounding tissue, BAPN‐treated cell sheet‐transplanted lungs showed no contraction of the tissue. Collagen fibres of control cell sheets were more dense and thick than those of BAPN‐treated cell sheets, where the crosslinking of collagen fibres was clearly inhibited. Sodium dodecyl sulphate–polyacrylamide gel electrophoresis (SDS–PAGE) showed that BAPN‐treated cell sheets gave no β‐chain band, indicating that the collagen crosslinkings of the fibroblast sheets were able to be controlled by BAPN. BAPN‐treated fibroblast sheets promise to allow wound clefts to be repaired without scar contractures. Copyright

Acute exacerbation of idiopathic interstitial pneumonias after surgical resection of lung cancer

Idiopathic interstitial pneumonias (IIPs) are diffuse lung diseases of unknown cause. Morbidity and mortality are high in patients with IIPs who have undergone lung resection. Postoperative acute exacerbation (PAE) of IIPs is one of the fatal complications after lung resection. From January 2001 to October 2009, 758 consecutive patients with lung cancer who had undergone lung resection at Tokyo Womens Medical University Hospital were investigated retrospectively. Forty (5.3%) of 758 patients had IIPs. PAE of IIPs was developed in 12 of the patients with IIPs. There were no significant differences in the age, gender, operation methods, histology, and pathological stage in the patients with or without PAE of IIPs. Three patients died of uncontrollable PAE of IIPs in hospital. The 30-day mortality of patients with PAE of IIPs in the last nine-year period has clearly decreased compared with the 30-day mortality of patients with PAE of IIPs between January 1996 and December 2000. PAE of IIPs causes high mortality. It is very difficult to predict the occurrence of PAE of IIPs. More efforts are required to develop strategies to prevent PAE of IIPs.

Long-term survival in adult mediastinal neuroblastoma.

Neuroblastoma rarely occurs in adults, in whom prognosis is poor. Here we report on the effective use of multimodal therapy to achieve long-term survival in adult mediastinal neuroblastoma. In a 33-year-old male with severe pain radiating from the left hypochondrium to the back area, no abnormal shadow was detected on first examination; the shadow appeared in chest X-ray only 10 months later when the severe pain recurred. The patient was then referred to our department for further examination. Chest X-rays and chest CT scans revealed a posterior mediastinal mass beside the thoracic vertebrae. Diagnosis was confirmed after surgical resection, which was followed by outpatient adjuvant therapy through radiation and chemotherapy. The patient has survived 8 years and 8 months without recurrence or metastasis.

New findings on the three‐dimensional anatomical relations between the bronchi and pulmonary blood vessels at the pulmonary hilum

During the 1940s, considerable knowledge was acquired about the anatomy of pulmonary segments, and anatomical terms were proposed and have been widely accepted. In recent years, minimally invasive and thoracoscopic segmentectomy has been performed with a versatile sublobar resection approach on patients with early peripheral lung cancer, metastatic lung tumors, and undiagnosed nodules. The three‐dimensional (3D) anatomy of the bronchi and the pulmonary vessels has also been studied in individual patients. Three‐dimensional models of the bronchi and pulmonary vessels were prepared using homemade software from computed tomograms (CT) of the chests of patients scheduled to undergo surgical procedures. Using these models, the authors examined the 3D positional relationships of the segmental broncho‐arterial triangle (SBAT) created by three points defined by the origins and courses of the bronchi and the pulmonary arteries, which are located apart from each other at the pulmonary hilum, and the segmental pulmonary veins (SPV), which run near the SBAT. In the left and right upper lobes, many branches of the pulmonary arteries and parallel bronchi in subsegments were widely separated at the origin of the pulmonary hilum, creating a relatively large SBAT. However, as an exceptional case, an SPV passed through an SBAT in only one of 158 patients. To our knowledge, no similar findings have been documented previously. Our findings could help to determine resection surfaces for thoracoscopic segmentectomy in the future, and provide new insights into the 3D anatomy and development of the lung. Clin. Anat. 28:506–511, 2015.