Akira Motohiro

Mechanisms involved in acute lung edema induced in dogs by oleic acid

We investigated mechanisms related to the development of acute lung edema, as induced by oleic acid in adult mongrel dogs. The intravenous injection of oleic acid (0.04 ml/kg) was considered to induce a permeability edema, as an enhancement of transvascular protein clearance was observed after the injection. The effects of oleic acid injection on systemic blood pressure (SBP), pulmonary arterial pressure (PAP), pulmonary arterial wedge pressure (PAWP), cardiac output (CO) and airway pressure (AWP) were measured. A significant decrease in CO and increase in AWP were evident after the injection, but there were no changes in SBP, PAP and PAWP. Treatment of the animals with prostaglandin I2 (PGI2) did not alter the induction of edema by oleic acid. However, the decrease in CO and increase in AWP were normalized by treatment with PGI2. Blood platelet count was not affected by oleic acid given in a dose of 0.04 ml/kg. To determine the direct effect of oleic acid on the vascular endothelium, the agent was injected through a catheter placed in the pulmonary artery. Electron microscopic examination revealed severe vacuolation on the endothelium of the pulmonary artery after only 1 min of exposure to oleic acid. Increased permeation of Evans blue into the subendothelial tissue was also observed with oleic acid treatment, compared with findings in the controls. These results indicate that the lung edema induced by oleic acid is due to an increased protein clearance, probably through a direct toxic effect on the vascular endothelium rather than an indirect toxic effect of chemical mediators released from the aggregated platelets.

Influence of chemotherapy on superoxide anion-generating activity of polymorphonuclear leukocytes in patients with lung cancer

The superoxide anion (O u20092− ) generating activity of polymorphonuclear leukocytes (PMN) in peripheral venous blood obtained from 15 patients with lung cancer was measured weekly after drug treatment. The amount of O u20092− generated by the cells before chemotherapy was 5.74 ± 0.42 nmol/minute/106 cells (mean ± SE). The value decreased gradually and reached a nadir of 1.98 ± 0.24 at 2 weeks after chemotherapy, at which time PMN count also reached a nadir of 1359 ± 251/μl (mean ± SE). The decreased O u20092− generating activity of the PMN recovered gradually thereafter and reached the level seen before the chemotherapy at 4 weeks. Expression of Fc receptors on the plasma membrane in PMN was measured after chemotherapy by the binding of iodine 125 (125I)‐immune complexes to the cells. Almost 40% decrease of the binding was observed in the cells obtained at 2 weeks after chemotherapy, compared with that in the cells before chemotherapy. These results indicate that PMN present in peripheral blood at 2 weeks after chemotherapy are not fully matured, in terms of O u20092− generating activity and the expression of Fc receptors.

Clinical Characterization of Node-Negative Lung Adenocarcinoma: Results of a Prospective Investigation

Objectives: In clinical stage IA lung adenocarcinoma, the clinical features of a truly node-negative population were prospectively investigated by means of a prospective investigational study. Methods: The clinical data and radiographic features of high-resolution computed tomography (HR-CT) were registered before operation in 169 clinical stage IA lung cancer patients who were scheduled to undergo a standard lobectomy and systemic mediastinal node dissection. The nodal metastasis was pathologically defined and the clinical factors associated with the presence of the nodal metastasis were evaluated. Results: In 114 assessable cases with adenocarcinomas, 15 (13.1%) were node-positive. The serum carcinoembryonic antigen (CEA), retraction sign, and intratumoral air-bronchogram on HR-CT were suggested to be predictive factors for lymph node metastasis, with hazard ratios of 12.44 (p = 0.0003), 6.53 (p = 0.0533), and 0.17 (p = 0.0073), respectively. In combination with the radiologic features and serum CEA, cases with elevated serum CEA or presence of retraction sign included 15.6% of node metastasis-positive, whereas all cases with normal CEA and absence of retraction sign showed no nodal metastasis. Cases with elevated serum CEA or absence of intratumoral air-bronchogram included 24.5% of node metastasis, whereas cases with normal CEA and presence of air-bronchogram showed 4.6% of node metastasis. The tumor size and the proportion of ground-glass attenuation were not associated with the incidence of nodal metastasis. Conclusions: The serum CEA and HR-CT features thus allowed us to identify node-negative lung adenocarcinomas measuring 3 cm or less in size.

Long-term surviving patient with inferior vena cava tumor thrombus and extrahepatic metastasis after spontaneous ruptured hepatocellular carcinoma.

We present a case of long-term survival in a patient with inferior vena cava tumor thrombus (IVCTT) and extrahepatic metastasis after resection for spontaneous ruptured hepatocellular carcinoma (HCC). The patient was a 73-year-old Japanese man previously diagnosed with chronic hepatitis B. He was referred to our emergency room and diagnosed with spontaneous ruptured HCC. The patient was immediately treated with transcatheter arterial embolization, and we then performed second-stage hepatic resection 50xa0days later. Although des-gamma-carboxy prothrombin was reduced to a normal level after hepatectomy, it gradually increased and computed tomography showed a disseminated tumor in the diaphragm near S2 of the liver with IVCTT and right atrium tumor thrombus. Recurrent HCC was treated with monthly transcatheter arterial infusion chemotherapy (TAI) and conformal radiotherapy (RT) of 40xa0Gy. After TAI and RT procedures, the disseminated tumor and IVCTT completely disappeared. Four years after TAI and RT procedures, the tumors were well controlled with no local recurrence. About 6−7xa0years after spontaneous ruptured HCC, lung metastasis and spleen metastasis were detected and resected, respectively. The patient is still alive and doing well over 7xa0years after spontaneous ruptured HCC.

Effect of free fatty acid on pulmonary transvascular fluid and protein exchange

SummaryWe demonstrated the effect of infusion of oleic acid, a common free fatty acid, on pulmonary vascular permeability in anesthetized dogs prepared with a lung lymph fistula. Infusion of oleic acid caused significant increases in lung lymph flow with no change in L/P protein ratio, resulting in significant increases in transvascular protein clearance. Pulmonary arterial and pulmonary arterial wedge pressures increased significantly from baseline but their elevation was slight. Cardiac output decreased significantly after oleic acid infusion. In contrast to the effects of oleic acid, left artrial hypertension caused increases in lung lymph flow that were associated with decreases in the L/P protein ratio. Lung water content was increased after oleic acid infusion, despite little effect on pulmonary vascular pressures. These findings indicate that oleic acid produced endothelial lung injury and increased pulmonary vascular permeability.

Pulmonary Resection for a Residual Tumor after Definitive Radiation in Locally Advanced Non-Small Cell Lung Cancer

Objective and Methods To clarify the benefits of surgery for a persistent tumor following definitive radiation in locally advanced non‐small cell lung cancer, five patients were retrospectively reviewed. Results All patients received definitive radiation, and three received concurrent chemotherapy followed by anatomical lung resection for a residual local tumor. The median time from the radiation to surgery was 8.2 weeks. There were no postoperative mortalities. Four patients developed distant metastasis with a mean recurrence‐free interval of 7.5 months. Conclusions Distant metastasis frequently occurred within a relatively short period after surgery. Further studies with a larger sample size are needed.

Video-assisted thoracoscopic esophagomyotomy for achalasia after pulmonary lobectomy

A 52-year-old man developed achalasia and a lung abscess due to aspiration pneumonia. We conducted a right upper lobectomy by thoracotomy for the abscess and, 2 weeks later, video-assisted thoracoscopic myotomy and fundoplication (modified Belsey Mark IV procedure) though the left thorax for achalasia. Three months after surgery, the patient was free of dysphasia and chest pain and had regained his original weight. Esophageal myotomy and fundoplication using video-assisted thoracoscopy appear to be feasible in treating achalasia involving impaired pulmonary function.