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Biomedical subjects

Motoyasu Sagawa

Publications and source records attributed to Motoyasu Sagawa.

At least 19 recordsLinked to original sources

A reanalysis of the Hitachi cohort study evaluating the effectiveness of low-dose CT screening for lung cancer.

The effectiveness of low-dose thoracic computed tomography (CT) screening for lung cancer for non-smokers or light smokers has been unclear. The results of the Hitachi cohort study performed by the conventional multivariable analysis suggested the reduction of lung cancer mortality by thoracic CT screening, but also revealed the lower all-cause mortality in the CT group, which indicated the existence of self-selection bias. Because the background of the subjects in the CT screening group and that in the X-ray screening group were very different, it is critical to adjust appropriately the confounding factors. In this brief report, we describe a re-evaluation of the results of the Hitachi Cohort Study performed by using more flexible methods, propensity score matching and inverse probability weighting.

epidemiology/public health↗

Fluorodeoxyglucose uptake correlates with the growth pattern of small peripheral pulmonary adenocarcinoma.

PURPOSE: Noguchi and colleagues reported that the growth pattern of small-sized adenocarcinoma was related to the vascular involvement and the prognosis of the patient. Noguchi's type A/B tumors had no lymph node metastasis, rare vascular involvement, and an excellent prognosis, which meant that Noguchi's type A/B tumors were preinvasive tumors of the peripheral type. Although Noguchi's classification was usually determined based on resected specimens, it would be useful to make a decision about the therapeutic strategy if the classification could be determined preoperatively based on the fluorodeoxyglucose (FDG) uptake. METHODS: The FDG uptake in 61 pulmonary adenocarcinomas measuring 3 cm or smaller in diameter was compared with the mediastinal uptake and was classified into five grades. The relationship between the FDG uptake and Noguchi's classification (A to F) was analyzed. RESULTS: The FDG uptake was significantly lower in Noguchi's type A/B tumors than in type C or in type D/E/F. Eleven of 12 tumors (92%) with no increased or a weak FDG uptake were classified as type A/B, whereas 32 of 33 tumors (97%) with a strong or very strong FDG uptake were classified as type C-F. CONCLUSIONS: The FDG uptake is helpful for making an accurate diagnosis of Noguchi's classification preoperatively in patients with pulmonary adenocarcinoma.

Adenocarcinoma↗

Stimulation of alveolar epithelial fluid clearance in human lungs by exogenous epinephrine.

OBJECTIVES: Because several experimental studies have demonstrated that cyclic adenosine monophosphate generation following beta-adrenoceptor activation can markedly stimulate alveolar fluid clearance, we determined whether the endogenous levels of catecholamines that occur in the pulmonary edema fluid and plasma of patients with acute lung injury are high enough to stimulate alveolar fluid clearance in the human lung. DESIGN: Observational clinical study. SETTING: Academic university hospital and laboratory. PATIENTS: Twenty-one patients with acute pulmonary edema plus ex vivo human lungs. INTERVENTIONS: Measurements of catecholamine levels in patient samples and controlled laboratory studies of the effects of these catecholamine levels on the rates of alveolar fluid clearance in ex vivo human lungs. MEASUREMENTS AND MAIN RESULTS: The concentrations of both epinephrine and norepinephrine in the pulmonary edema fluid and plasma were approximately 10 M (range of 1-8x10 M) in hydrostatic pulmonary edema (n=6) and acute lung injury patients (n=15). We therefore tested whether 10 M epinephrine or norepinephrine stimulated alveolar fluid clearance in isolated human lungs and found that these epinephrine or norepinephrine concentrations did not stimulate alveolar fluid clearance. However, higher concentrations of epinephrine (10 M), but not norepinephrine (10 M), significantly stimulated alveolar fluid clearance by 84% above control. Glibenclamide (10 M) and CFTRinh-172 (10 M), cystic fibrosis transmembrane conductance regulator inhibitors, completely inhibited the epinephrine-induced stimulation of alveolar fluid clearance. CONCLUSIONS: These results indicate that endogenous catecholamine concentrations in pulmonary edema fluid are probably not sufficient to stimulate alveolar fluid clearance. In contrast, administration of exogenous catecholamines into the distal airspaces can stimulate alveolar fluid clearance in the human lung, an effect that is mediated in part by cystic fibrosis transmembrane conductance regulator. Therefore, exogenous cyclic adenosine monophosphate-dependent stimulation will probably be required to accelerate the resolution of alveolar edema in the lungs of patients with pulmonary edema.

Adrenergic beta-Agonists↗

Denopamine stimulates alveolar fluid clearance via cystic fibrosis transmembrane conductance regulator in rat lungs.

OBJECTIVE: The objective of this study was to test the hypothesis that cystic fibrosis transmembrane conductance regulator (CFTR) plays a role in beta(1)-adrenergic agonist-stimulated alveolar fluid clearance. METHODS: Isotonic 5% albumin solutions containing different pharmacological agents were instilled into the alveolar spaces of the isolated rat lungs. The lungs were inflated with 100% oxygen at an airway pressure of 7 cm H(2)O and placed in a humidified incubator at 37 degrees C. Alveolar fluid clearance was estimated by the progressive increase in the albumin concentration over 1 h. To test the hypothesis, we determined whether CFTR Cl(-) channel inhibitors (glibenclamide and CFTR(inh)-172) inhibited the effect of denopamine, a beta(1)-adrenergic agonist, on stimulation of alveolar fluid clearance in the isolated rat lungs. RESULTS: Denopamine increased alveolar fluid clearance in a dose-dependent manner. Atenolol, a beta(1)-adrenergic antagonist, abolished the effects of denopamine on stimulation of alveolar fluid clearance. Although glibenclamide alone or CFTR(inh)-172 alone did not change basal alveolar fluid clearance, these CFTR inhibitors inhibited the effect of denopamine on alveolar fluid clearance. CONCLUSION: CFTR plays a role in beta(1)-adrenergic agonist-stimulated alveolar fluid clearance in rat lungs.

Adrenergic beta-Agonists↗

Localized bronchioloalveolar carcinoma with small foci of active fibroblastic proliferation. A report of 2 cases.

Localized bronchioloalveolar carcinoma (LBAC) without foci of active fibroblastic proliferation has been reported to be a pN0 disease. Predominantly, these tumors have not been associated with cancer relapse or death subsequent to surgery. Based on these observations, LBAC cases have been considered candidates for limited lung resection without lymph node dissection. However, this surgical option requires careful validation, and an accurate diagnosis is indispensable. The absence of foci of active fibroblastic proliferation must be confirmed by a thorough investigation. Nonetheless, these foci may escape detection, and even currently accepted diagnostic modalities may not be sufficient to accurately determine their absence. We illustrate this point by reporting 2 cases of LBAC with small but distinct foci of active fibroblastic proliferation.

Adenocarcinoma, Bronchiolo-Alveolar↗

Cytological characteristics of pulmonary large cell neuroendocrine carcinoma.

To establish cytological features of pulmonary large cell neuroendocrine carcinoma (LCNEC), we evaluated the cytological characteristics of LCNEC. Samples from 25 histologically confirmed LCNECs (14 touch imprint (TI) and 11 curettage) were analyzed. The findings were compared with those for seven small cell lung carcinomas. Cytological findings of TIs were as follows: Tumor cells were medium- to large-sized, round or polygonal, and nuclear polymorphism was observed. Some of the tumor cells had clearly identified cytoplasms, but naked nuclei were frequently observed. Nuclei were round, oval, or polygonal, and possessed thin and smooth nuclear membranes. The nuclear chromatin pattern was finely or coarsely granular. One or two nucleoli were observed in the nuclei, but were inconspicuous in some cases. Tumor cells appeared in clusters, and rosette formation was observed, but single cells were frequently observed also. Necrotic background and nuclear streaking were frequently observed. In brush or curettage specimens, the number of cells observed on a glass was small, but the findings were almost the same as those for the TI samples. TI samples have characteristic features, such as a neuroendocrine morphologic pattern, large cell size, abundant cytoplasm, finely or coarsely granular chromatin of the nucleus, and prominent nucleoli, and the diagnosis of LCNEC is possible. In brush or curettage specimen, the LCNEC diagnosis may be possible if a sufficient number of tumor cells are obtained.

Carcinoma, Neuroendocrine↗

Annual periodic increases in serum carcinoembryonic antigen concurrent with ground-glass opacity in the lung: report of a case.

A 63-year-old woman underwent a video-assisted thoracoscopic lobectomy for cancer of the right lung in 1999. The following year, a lesion with ground-glass opacity was found in the left lung, and pathological examination after a partial lung resection revealed atypical adenomatous hyperplasia with expression of carcinoembryonic antigen (CEA). During postoperative screening tests for tumor recurrence, there were periodic increases in the serum CEA level by twofold above the normal levels in 2002 and 2003. Clinical evaluations, including laboratory tests, radiographic imaging, and endoscopy examinations, showed no evidence of a CEA-producing tumor, except for a new ground-glass opacity in the left lung. To our knowledge, this is the first report of periodic increases in serum CEA levels in a patient with ground-glass opacity in the lung, not reflecting recurrence of the lung tumor.

Adenocarcinoma, Bronchiolo-Alveolar↗

Pulmonary T2N0 adenocarcinoma with metastasis to a lymph node in the thoracic wall.

We experienced a rare case of lung cancer without hilar/mediastinal nodal involvement or direct invasion to the thoracic wall, but with metastasis to a lymph node in the thoracic wall. A 72-year-old woman with lung cancer was admitted to our hospital for the surgical therapy. She had suffered from right pleuritis in her childhood. During the dissection of the pleural adhesion around the whole lung, one small black lymph node was found in the thoracic wall and resected. Then, right middle and lower lobectomy and systematic nodal dissection were performed. The postoperative pathological examination revealed that nodal involvement was not observed in all samples except in the lymph node in the thoracic wall. In lung cancer patients with broad pleural adhesion, we should pay attention to lymph nodes in the thoracic wall. If we find them, the nodes should be resected for accurate staging.

Adenocarcinoma↗

Computed tomographic images reflect the biologic behavior of small lung adenocarcinoma: they correlate with cell proliferation, microvascularization, cell adhesion, degradation of extracellular matrix, and K-ras mutation.

BACKGROUND: We previously reported that the computed tomographic M/L ratio (area of the tumor in the mediastinal computed tomographic image/area of the tumor in the lung computed tomographic image) of small peripheral lung adenocarcinoma is correlated with patient prognosis. METHODS: Immunostaining for p53, bcl-2, Ki-67, vascular endothelial growth factor, CD34, matrix metalloproteinase 2, matrix metalloproteinase 9, tissue inhibitor of matrix metalloproteinase 2, and mutation of K-ras was assessed in 131 surgically resected, primary peripheral lung adenocarcinomas of 30 mm or less in maximum diameter to clarify the relationship between computed tomographic findings and biologic activities. RESULTS: The numbers of patients with high labeling indexes of Ki-67 and high expression of vascular endothelial growth factor, CD34, matrix metalloproteinase 2, and matrix metalloproteinase 9 in the solid-type group (computed tomographic M/L ratio > or = 50%) were significantly higher than those in the faint density-type group (computed tomographic M/L ratio < 50%; P = .04 for Ki-67, P = .03 for vascular endothelial growth factor, P = .0009 for CD34, P = .001 for matrix metalloproteinase 2, and P = .00001 for matrix metalloproteinase 9). The number of patients with high levels of CD44v6 or tissue inhibitor of matrix metalloproteinase 2 staining in the faint density-type group was significantly higher than that in the solid-type group (P = .02 for CD44v6 and P = .01 for tissue inhibitor of matrix metalloproteinase 2). Independent variables capable of predicting computed tomographic M/L ratio included CD34, matrix metalloproteinase 2, matrix metalloproteinase 9, and tissue inhibitor of matrix metalloproteinase 2 (P = .0093, P = .0003, P = .0027, and P = .01, respectively; binary logistic regression analysis). CONCLUSIONS: Our results suggest that the computed tomographic image of small lung adenocarcinoma is correlated with biologic activities and thus provides possible prognostic information.

Adenocarcinoma↗

Uridine 5'-triphosphate stimulates alveolar fluid clearance in the isolated rat lungs.

Uridine 5'-triphosphate (UTP) increases chloride secretion followed by fluid movement into the proximal airspaces. However, little is known about whether UTP affects fluid movement in the distal airspaces. We studied the effect of UTP on basal and stimulated alveolar fluid clearance in the isolated rat lungs. Isosmotic 5% albumin solution was instilled into the alveolar spaces of isolated rat lungs, which were then inflated with 100% oxygen at an airway pressure of 7 cmH(2)O. Alveolar fluid clearance was measured by the progressive increase in albumin concentrations over 1 h. Although UTP (10(-9) - 10(-6) M) did not increase alveolar fluid clearance, UTP (10(-5) - 10(-3) M) and isoproterenol (10(-5) M), a beta-adrenergic agonist, increased alveolar fluid clearance by 40% and 120% of the basal values, respectively. A combined treatment of UTP (10(-4) M, 10(-3) M) and isoproterenol increased alveolar fluid clearance by 280% of the basal value. The effects of UTP in the presence and absence of isoproterenol were abolished by blockers of a P2 purinoceptor and chloride channels. These results indicate that UTP stimulates alveolar fluid clearance in the distal airspaces of rat lungs.

Adrenergic beta-Agonists↗

Malnutrition impairs alveolar fluid clearance in rat lungs.

Inadequate nutrition complicates the clinical course of critically ill patients, and many of these patients develop pulmonary edema. However, little is known about the effect of malnutrition on the mechanisms that resolve alveolar edema. Therefore, we studied the mechanisms responsible for the decrease in alveolar fluid clearance in rats exposed to malnutrition. Rats were allowed access to water, but not to food, for 120 h. Then, the left and right lungs were isolated for the measurement of lung water volume and alveolar fluid clearance, respectively. The rate of alveolar fluid clearance was measured by the progressive increase in the concentration of Evans blue dye that was instilled into the distal air spaces with an isosmolar 5% albumin solution over 1 h. Malnutrition decreased alveolar fluid clearance by 38% compared with controls. Amiloride (10(-3) M) abolished alveolar fluid clearance in malnourished rats. Either refeeding for 120 h following nutritional deprivation for 120 h or an oral supply of sodium glutamate during nutritional deprivation for 120 h restored alveolar fluid clearance to 91 and 86% of normal, respectively. Dibutyryl-cGMP, a cyclic nucleotide-gated cation channel agonist, increased alveolar fluid clearance in malnourished rats supplied with sodium glutamate. Terbutaline, a beta(2)-adrenergic agonist, increased alveolar fluid clearance in rats under all conditions (control, malnutrition, refeeding, and glutamate-treated). These results indicate that malnutrition impairs primarily amiloride-insensitive and dibutyryl-cGMP-sensitive alveolar fluid clearance, but this effect is partially reversible by refeeding, treatment with sodium glutamate, or beta-adrenergic agonist therapy.

Adenosine Triphosphate↗

A prostacyclin analogue, OP-41483alpha-CD, restores the ability of a beta2-adrenergic agonist to stimulate alveolar fluid clearance in rats.

PURPOSE: It is not yet known whether a prostacyclin analogue can affect alveolar fluid clearance. According to recent studies, high-dose (10(-3) M) terbutaline, a beta(2)-adrenergic agonist, failed to increase alveolar fluid clearance. Therefore, we examined the effects of OP-41483alpha-CD, a prostacyclin analogue, on alveolar fluid clearance in the presence of high-dose terbutaline in rats. METHODS: Albumin solution containing Evans blue dye and various drugs was instilled into the alveolar airspaces of isolated rat lungs, which were then inflated with 100% oxygen at an airway pressure of 8 cmH(2)O. Alveolar fluid clearance was measured by the progressive increase in dye concentrations over 1 h. RESULTS: Although 10(-5) and 10(-4) M terbutaline increased alveolar fluid clearance, 10(-3) M terbutaline did not. OP-41483alpha-CD restored the ability of 10(-3) M terbutaline to stimulate alveolar fluid clearance. The effect of OP-41483alpha-CD was consistent with the effect of atenolol, a beta(1)-adrenergic antagonist. The effect of OP-41483alpha-CD on alveolar fluid clearance was unchanged in lungs inflated with nitrogen. Prostaglandin E (PGE)(1) and PGE(2) analogues had similar effects to OP-41483alpha-CD on alveolar fluid clearance. CONCLUSION: These results indicate that a prostacyclin analogue restores the ability of high-dose terbutaline to stimulate alveolar fluid clearance.

Adrenergic beta-Agonists↗

Cavernoscopic removal of a fungus ball for pulmonary complex aspergilloma.

Lobectomy of the lung for aspergilloma is not always appropriate in elderly patients because of the high surgical risk. A 78-year-old male diagnosed with complex aspergilloma was referred to our hospital for recurrent hemoptysis. Because he refused lobectomy, we conducted a cavernoscopic removal of the fungus ball. The site of the skin incision was carefully designed preoperatively. After achieving access, the fungus ball was removed piece by piece under endoscopic view. Intraoperative blood loss equaled 30 mL. At 5 months postoperative follow-up, the patient had no evidence of recurrence. This procedure may be useful in some patients with complex aspergilloma.

Aged↗

Video-assisted thoracoscopic wedge resection for pulmonary sequestration.

A 60-year-old woman underwent a video-assisted thoracoscopic wedge resection of intralobar pulmonary sequestration instead of a lobotomy because the lesion was localized in the right basal segment. Preoperative 3-dimensional computed tomography was useful for identifying an aberrant artery arising from the thoracic aorta and distributing to the lesion. A successful outcome more than 4 years after the surgery indicates that a wedge resection under video-assisted thoracoscopy may prove to be a therapeutic option for localized pulmonary sequestration.

Aorta, Thoracic↗

Video-assisted bronchial stump reinforcement with an intercostal muscle flap.

For lobectomy patients at considerable risk of developing a postoperative bronchopleural fistula, the bronchial stump reinforcement with an intercostal muscle flap is sometimes performed. This procedure usually requires a standard thoracotomy, even if video-assisted thoracoscopic surgery (VATS) is better for the patient. Our patient was a 76-year-old male with lung cancer and severe diabetes mellitus. He underwent lobectomy and systematic nodal dissection combined with bronchial stump reinforcement using an intercostal muscle flap, performed as a VATS procedure. No postoperative complications were observed. This procedure is applicable to patients who are candidates for VATS lobectomy.

Aged↗