Koyo Shirahashi

The importance of intraoperative fluid balance for the prevention of postoperative acute exacerbation of idiopathic pulmonary fibrosis after pulmonary resection for primary lung cancer.

OBJECTIVES Postoperative acute exacerbation (PAE) of idiopathic pulmonary fibrosis (IPF) is a serious complication that is hard to treat. Therefore, it is important to manage IPF patients in such a way as to avoid PAE. Conversely, the relationship between postoperative acute lung injury and perioperative fluid administration has been reported. Herein, we analyse the perioperative risk factors of PAE of IPF, including fluid management. METHODS Fifty-two patients diagnosed as having clinical IPF who underwent pulmonary resection (segmentectomy, lobectomy or bilobectomy) for primary lung cancer were analysed retrospectively. Preoperative predictive factors and perioperative management items, especially fluid management, were evaluated. RESULTS The incidence of PAE of IPF was 13.5% (7 of 52 patients). Six patients (85.7%) died of respiratory failure induced by uncontrollable PAE of IPF. Upon univariate analysis, the amount of the intraoperative fluid infused (ml/kg/h), the intraoperative fluid balance (ml/kg/h) and the preoperative C-reactive protein (CRP) level were found to be significantly higher in IPF patients who developed PAE than in those who did not. A multivariate logistic regression analysis showed that the intraoperative fluid balance and the preoperative CRP were prognostic factors for PAE of IPF [P = 0.026, odds ratio (OR) = 1.312 and P = 0.048, OR = 1.280, respectively]. CONCLUSIONS To prevent PAE of IPF, intraoperative management that minimizes intravenous fluid administration is essential. Moreover, caution is particularly important in patients with preoperative evidence of inflammation.

Skeletal muscle targeting in vivo electroporation-mediated HGF gene therapy of bleomycin-induced pulmonary fibrosis in mice

Lung fibrosis is a common feature of interstitial lung diseases, and apoptosis and fibrinogenesis play critical roles in its formation and progression. Hepatocyte growth factor (HGF) is one of the ideal therapeutic agents for prevention of lung fibrosis because of its antiapoptotic and fibrinolytic effects. The aim of this study is to establish nonviral HGF gene therapy of bleomycin-induced lung fibrosis avoiding the viral vector-related side effects. C57BL/6 mice were injected with 3.0 mg/kg body weight of bleomycin intratracheally. Following bleomycin injection, 50 μl of pUC-HGF (1 mg/ml) was injected into each of the quadriceps muscle. Immediately after plasmid injection, in vivo electroporation was performed with pulse generator. Skeletal muscle-targeting electroporation induced transgene expression on day 1 and persisted for 4 weeks, and human HGF was also detected in the lung. In mice transferred with HGF, pathological score (1.0±0.3 vs 3.2±0.6), TUNEL-positive cell index (4.5±1.1 vs 14.2±3.1), and hydroxyproline content (9.0±1.3 vs 14.4±5.1 μmol/g) were significantly reduced compared with the control. Furthermore, survival rate of HGF mice was significantly improved compared with the control. Our data indicate that HGF gene therapy with a single skeletal muscle-targeting electroporation has a therapeutic potential for bleomycin-induced lung fibrosis and this strategy can be applied as a practical gene therapy protocol for various organs.

Improvement of the survival rate after rat massive hepatectomy due to the reduction of apoptosis by caspase inhibitor

Background and Aim:  Acute liver failure after massive hepatectomy is caused by both necrosis and apoptosis in the remnant liver. We investigate the protective effect of the caspase inhibitor on apoptosis after massive hepatectomy in rats.

Pulmonary epithelioid hemangioendothelioma

We report two cases of pulmonary epithelioid hemangioendothelioma (PEH). Both patients presented with multiple bilateral pulmonary nodules, <10 mm diameter, on computed tomography (CT). Multiple pulmonary metastases were considered, but no primary malignant lesion was detected by other imaging modalities including 18F-fl uorodeoxyglucose positron emission tomography (18F-FDG-PET)/CT. Moreover, the nodules did not show increased uptake of 18F-FDG. We performed pulmonary wedge resections by video-assisted thoracoscopic surgery (VATS). Histological and immunohistochemical analysis revealed PEH in both. Positivity for the monoclonal antibody MIB-1 in the tumor cells was 5% in the fi rst case and 5%–10% in the second case. Slow tumor progression was detected with CT in the second case. Although 18F-FDG PET/CT is effective for screening other malignant lesions, it does not appear to be of direct use in the diagnosis and surgical planning of PEH. Pathological diagnosis by VATS is the most effective method. MIB-1 positivity should be analyzed as to whether it is a prognostic factor of PEH.

Effect of Postoperative Administration of Pregabalin for Post-thoracotomy Pain: A Randomized Study

OBJECTIVE The present study was performed to evaluate the effect of postoperative administration of pregabalin in patients who reported moderate-to-severe pain after epidural analgesia following thoracotomy. DESIGN An open-label, randomized, controlled, parallel-group study. SETTING A single center in Japan. PARTICIPANTS Consecutive patients (aged≥20 years) who reported moderate-to-severe pain after effectual 2-day epidural analgesia post-thoracotomy for lung cancer from February 2012 to March 2013. INTERVENTIONS Patients were assigned to 2 groups: control (control treatment: acetaminophen, 400 mg, and codeine phosphate powder, 20 mg) or pregabalin (pregabalin, 75 mg, plus control treatment). The 12-week study period included 2-week study treatment and 10-week follow-up. MEASUREMENTS AND MAIN RESULTS For efficacy, the primary endpoint was the visual analog scale (VAS) scores for pain at rest and with coughing at week 2, and secondary endpoints were the VAS scores for pain and the neuropathic pain questionnaire at week 12. Fifty patients were randomized (25 per group). At week 2, the VAS scores for pain at rest (mean [SD]) were 29.5 (21.9) in the control group and 16.3 (15) in the pregabalin group (p = 0.02); for pain with coughing, the scores were 45.2 (20.9) and 28.8 (25.9), respectively (p = 0.02). VAS scores improved more in the pregabalin group than in the control group over the 12 weeks. Patients free from possible neuropathic pain were 48% of the control group and 88% of the pregabalin group, respectively (p = 0.001). CONCLUSIONS Postoperative administration of pregabalin effectively reduced post-thoracotomy pain.

Unusual back pain caused by intervertebral disc degeneration associated with schmorl node at Th11/12 in a young athlete, successfully treated by anterior interbody fusion: a case report.

Study Design. A case report describing thoracic intervertebral disc degeneration and spondylolisthesis associated with a Schmorl node in a young athlete, which was successfully treated by anterior interbody fusion (AIF). Objective. To describe a rare pathologic condition with a clinical outcome of a surgical intervention. Summary of Background Data. Intervertebral degeneration and spondylolisthesis of the lower thoracic spine associated with a Schmorl node in a young athlete has not been reported. Methods. A 19-year-old male amateur soccer player presented with severe back pain during motion. This pain was associated with intervertebral disc degeneration, spondylolisthesis, and a Schmorl node at the Th11/12 level. He was surgically treated by AIF. Results. The AIF resulted in a solid fusion, an improvement in sagittal alignment, and amelioration of symptoms. Conclusion. The AIF procedure was effective for lower thoracic symptomatic intervertebral disc degeneration and spondylolisthesis associated with a Schmorl node.

Nonfunctional mediastinal parathyroid cyst: imaging findings in two cases

The authors describe the computed tomography (CT) and magnetic resonance (MR) imaging findings of a 69-year-old woman and a 69-year-old man with a nonfunctional mediastinal parathyroid cyst. In the described cases, unenhanced CT showed homogeneous areas of water density, and unenhanced MRI showed homogeneous areas that were isointense to cerebrospinal fluid, reflecting their serous fluid contents. Both cysts were located posterior to the left lower pole of the thyroid gland with an extension to the superior mediastinum, either anterior or posterior to the left brachiocephalic vein. CT and MR imaging findings of parathyroid cysts are nonspecific, and they are often difficult to differentiate from other cystic lesions located in the lower neck or in the superior mediastinum. However, a parathyroid cyst should be considered when radiologic images demonstrate its characteristic location, posterior to the thyroid gland, with an extension to the superior mediastinum.

Surgical technique of lung segmental resection with two intersegmental planes

Lung segmental resection is of two types: a simple type with resection of only one intersegmental plane, such as lingual or superior segmentectomy; and a complicated type with resection of two or more intersegmental planes, such as anterior segmentectomy. We present a method of identifying the intersegmental plane by physiological function. First, we cut the segmental pulmonary artery and vein. The entire lobe is then inflated with pure oxygen for 5 min. Immediately after oxygen inflation, the segmental bronchus is deflated and stapled. After a couple of minutes, the intersegmental plane is easily detected. In 117 patients who underwent segmentectomy, mean blood loss was 122 ± 193 ml and mean duration of drainage was 3.5 ± 4.8 days. Postoperative complications related to operative procedures occurred in 14 cases (12.0%). Our method of detecting intersegmental planes is convenient and useful for subsegmental resection, particularly for complicated-type cases.

Propensity score-matching analysis of hybrid video-assisted thoracoscopic surgery and thoracoscopic lobectomy for clinical stage I lung cancer

OBJECTIVES Video-assisted thoracoscopic surgery (VATS) lobectomy is classified into hybrid VATS (direct and video vision) and thoracoscopic VATS (video vision only). In this study, the outcomes of hybrid VATS and thoracoscopic VATS for clinical stage I lung cancer were compared using a propensity score-matching analysis. METHODS Hybrid and thoracoscopic VATS were performed in 178 and 76 patients, respectively. Propensity scores were calculated using logistic regression analysis and matched within a score of ±0.03 for age, sex, size of tumour, Charlson comorbidity index, preoperative therapy, percent vital capacity, forced expiratory volume in 1 s, clinical stage, pathological stage and histology. RESULTS In the non-matched analysis, the results for hybrid and thoracoscopic VATS, respectively, were as follows: mean age, 69 ± 9 and 66 ± 10 years (P = 0.04); tumour size, 24 ± 10 and 20 ± 7 mm (P < 0.01); 2-deoxy-2 [F-18]fluorodeoxyglucose positron emission tomography SUV, 5.6 ± 4.4 and 3.6 ± 3.2 (P < 0.01); clinical stage (IA/IB), 130/48 and 69/7 (P < 0.01); pathological stage (IA/IB/IIA and IIB/IIIA and IIIB), 89/56/15/18 and 57/14/2/3 (P < 0.01); postoperative complications, 66 (37.1%) and 16 (21.1%; P = 0.01); respiratory complications, 32 (18.0%) and 6 (7.9%; P = 0.04); 5-year overall survival (OS), 77.0 and 88.8% (log-rank P = 0.045); and 5-year disease-free survival (DFS), 67.2 and 81.1% (log-rank P = 0.02). In 66 matched cases, the results for hybrid and thoracoscopic VATS, respectively, were as follows: mean operative time, 245 ± 96 and 285 ± 85 min (P = 0.01); blood loss, 95 ± 100 and 86 ± 123 ml (P = 0.67); mean duration of drainage, 3.6 ± 2.7 and 3.2 ± 2.2 days (P = 0.37); postoperative complications, 21 (31.8%) and 14 (21.2%; P = 0.17); respiratory complications, 11 (16.7%) and 5 (7.6%; P = 0.11); 5-year OS, 72.5 and 86.0% (log-rank P = 0.25); and 5-year DFS, 68.4 and 77.2% (log-rank P = 0.17). CONCLUSIONS In this single-institution, propensity score-matched study, hybrid VATS showed a shorter operative time and similar outcomes compared with thoracoscopic lobectomy for clinical stage IA lung cancer.

Histologic Damage of Lung Allografts According to Magnitude of Acute Rejection in the Re-isotransplant Model

BACKGROUND Graft damage due to acute rejection has been reported as one of the risk factors in the chronic stage of cardiac and renal allografts. This study was designed to elucidate the histologic changes of grafts after ongoing acute allograft rejection was discontinued in models of lung re-isotransplantation. METHODS WKAH rat lungs were orthotopically transplanted into F344 recipients. Three days (3A group) and 5 days (5A group) after the first allotransplantation, the grafts were re-isotransplanted back into the WKAH rats (3RA and 5RA groups, respectively). Five days (5I group) after the first isotransplantation, the grafts were re-isotransplanted back into the WKAH rats (5RI group). The grafts were removed 30 and 60 days after re-isotransplantation and assessed histologically. RESULTS Typical acute allograft rejection developed in the 3A and 5A groups, and the changes were reduced after re-isotransplantation, although they remained significantly greater in the 5RA group than in the 3RA and 5RI groups. For intimal hyperplasia, the graft score 60 days after re-isotransplantation in the 5RA group was significantly higher than in the 5RI and 3RA groups. The changes in airway inflammation were significantly greater in the 5RA group than in the 3RA and 5RI groups at 60 days. Peribronchiolar fibrosis was significantly more frequent in the 5RA and 3RA groups than in the 5RI group. CONCLUSIONS Acute rejection and airway inflammation corresponded to the magnitude of rejection before retransplantation. Significant intimal hyperplasia developed in severe acute rejection, and peribronchiolar fibrosis occurred after the first acute rejection.