Biomedical subjects

Jun-ichi Ogawa

Publications and source records attributed to Jun-ichi Ogawa.

At least 19 recordsLinked to original sources

PubMed2006

Tumor-derived TGFbeta-1 induces dendritic cell apoptosis in the sentinel lymph node.

Lymphatic flux from a primary tumor initially flows into a tumor-draining lymph node (LN), the so-called sentinel LN (SLN). Carried by the lymph fluid are a variety of mediators produced by the tumor that can influence immune responses within the SLN, making it a good model with which to investigate tumor-related immunology. For instance, dendritic cell (DC) numbers are reduced in SLNs from melanoma and breast cancer patients. In the present study, we investigated the mechanism by which DC numbers were reduced within SLNs from patients with non-small cell lung cancer. We found that the incidence of apoptosis among DCs was higher in SLNs than in non-SLNs, as were levels of TGFbeta-1. In contrast, levels of TGFbeta-1 mRNA did not differ between SLNs and non-SLNs, but were 30 times higher in tumors than in either LN type. In vitro, incubation for 2 days with TGFbeta-1 induced apoptosis among both cultured DCs and DCs acutely isolated from normal thoracic LNs, effects that were blocked by the TGFbeta-1 inhibitor DAN/Fc chimera. Taken together, these results suggest that tumor-derived TGFbeta-1 induces immunosuppression within SLNs before the movement of tumor cells into the SLNs, thereby facilitating metastasis within those nodes.

Apoptosis↗

PubMed2006

Outcome and treatment strategy for mid- and lower-thoracic esophageal cancer recurring locally in the lymph nodes of the neck.

The aim of the present study was to assess the outcome of treatment for patients with recurrent mid- and lower-thoracic esophageal cancers in whom recurrence was localized to the lymph nodes of the neck, and to determine the best strategy for further treatment. Between 1989 and 2001, 270 patients with mid- and lower-thoracic esophageal cancer underwent curative esophagectomy; 90 of those patients had a cancer recurrence. Our focus was on lymph node recurrence, especially when the recurrent cancers were localized to the lymph nodes in the neck. The outcomes of those patients and the efficacy of the strategies used to treat the recurrent cancers were determined. In 43 patients (48%), recurrent cancer initially appeared in the lymph nodes. Among the 43 patients, 15 (35%) had localized neck recurrence. The time between tumor recurrence and death among the 15 patients with localized neck recurrence was significantly longer than among the 28 patients with other recurrence patterns. In addition, 15 patients underwent lymph node resection, while 28 patients were treated non-surgically. The time between tumor recurrence and death was significantly longer in patients treated surgically. Of the 15 patients in whom recurrence affected the neck lymph nodes only, 10 (67%) were treated surgically; their 2-year survival rate after recurrence was 45%. The outcomes of recurrent esophageal cancers localized to the lymph nodes of the neck were better than those seen with other recurrence patterns, and salvage resection followed by chemoradiation therapy would seem to be indicated for those patients.

Age Factors↗

PubMed2006

Treating gastric tube cancer with distal gastrectomy preserving the gastroepiploic artery.

Total resection of the gastric tube with lymphadenectomy is standard and reliable treatment for gastric tube cancer. However the risk associated with totally removing a gastric tube previously reconstructed through the posterior mediastinal route is significant, given the need to lyse a significant number of adhesions in order to reach the mediastinum. As a less invasive procedure, we used distal gastrectomy to treat superficial gastric tube cancer in 2 patients. The distal gastric tube was mobilized and resected with preservation of the right gastroepiploic artery, and the Roux-en-Y gastrojejunostomy was used for reconstruction. This procedure was curative with less surgical stress.

Aged↗

PubMed2006

Intraoperative sentinel lymph node mapping using a new sterilizable magnetometer in patients with nonsmall cell lung cancer.

PURPOSE: We recently developed a novel method for sentinel lymph node mapping using magnetic force. However, problems with the sterility and sensitivity of the magnetometer made intraoperative sentinel lymph node mapping impossible. The purpose of this study was to test the utility of a new, more sensitive, sterilizable magnetometer developed in our institute for in vivo sentinel lymph node mapping in patients with nonsmall cell lung cancer. DESCRIPTION: Ferumoxides (magnetite) served as the tracer. Twenty patients with nonsmall cell lung cancer participated in the study. Each received 5 mL of ferumoxides, which were injected around their tumor. Magnetic force was then measured intraoperatively using the new sterilizable magnetometer. EVALUATION: The in vivo sentinel lymph node detection rate was 80.0% (16 of 20). The accuracy, sensitivity, and false-negative rates were 100% (16 of 16), 100% (4 of 4) and 0% (0 of 12), respectively. Our preliminary study indicates that our new magnetometer enables in vivo sentinel lymph node mapping in patients with nonsmall cell lung cancer. CONCLUSIONS: This device safely and accurately detected sentinel lymph nodes in nonsmall cell lung cancer patients.

Aged↗

PubMed2005

Pulmonary reexpansion causes xanthine oxidase-induced apoptosis in rat lung.

The pathogenesis of reexpansion pulmonary edema is not yet fully understood. We therefore studied its mechanism in a rat model in which the left lung was collapsed by bronchial occlusion for 1 h and then reexpanded and ventilated for an additional 3 h. We then evaluated the production of reactive oxygen species in the lungs using fluorescent imaging and cerium deposition electron microscopic techniques and the incidence of apoptosis using the TdT-mediated dUTP-digoxigenin nick end labeling (TUNEL) method. We found that pulmonary reexpansion induced production of reactive oxygen species and then apoptosis, mainly in endothelial and alveolar type II epithelial cells. Endothelial cells and alveolar type I and II epithelial cells in the reexpanded lung were positive for TUNEL and cleaved caspase-3. DNA fragmentation was also observed in the reexpanded lung. In addition, wet-dry ratios obtained with reexpanded lungs were significantly higher than those obtained with control lungs, indicating increased fluid content. All of these effects were attenuated by pretreating rats with a specific xanthine oxidase inhibitor, sodium (-)-8-(3-methoxy-4-phenylsulfinylphenyl) pyrazolo[1,5-a]-1,3,5-triazine-4(1H)-one. It thus appears that pulmonary reexpansion activates xanthine oxidase in both endothelial and alveolar type II epithelial cells and that the reactive oxygen species produced by the enzyme induce apoptosis among the endothelial and alveolar type I and II epithelial cells that make up the pulmonary water-air barrier, leading to reexpansion pulmonary edema.

Animals↗

PubMed2005

Successful surgical treatment for diffuse esophageal spasm.

A 74-year-old man, who had previously received curative distal gastrectomy for gastric cancer, was admitted to our hospital with severe dysphagia and weight loss. Barium swallow examination revealed the esophagus to have the corkscrew appearance characteristic of diffuse esophageal spasm (DES). This diagnosis was confirmed by esophageal manometry, which revealed intermittent, simultaneous, high-amplitude (30-100 mmHg) contractions after 65% of wet swallows. The muscle layer was also found to be thickened throughout the spastic region. Long esophagomyotomy with fundoplication was performed after treatment with medication proved ineffective. Myotomy proceeded superiorly to the area under aortic arch and inferiorly 3 cm into the cardiac portion. Fluoroscopy of the esophagus after the operation showed the spastic changes to be absent, and the patient showed improved clinical signs. We therefore recommend long myotomy of the esophageal wall with antireflux surgery for DES with sever dysphagia that is resistant to conservative treatment.

Aged↗

PubMed2005

Magnetic resonance imaging for chylothorax after esophagectomy.

A 75-year-old man underwent esophagectomy for thoracic esophageal cancer. After the operation, the output fluid from the right chest drain increased, and laboratory analysis confirmed the fluid to be chyle. Magnetic resonance imaging (MRI) was then carried out to identify the leakage point and the size of the injury to the thoracic duct. The MRI clearly showed the leak point to be in the lower thoracic region. It thus appears that this non-invasive new approach using MRI is effective and suitable for diagnosis and establishment of an appropriate treatment plan for chylothorax after thoracic surgery.

Aged↗

PubMed2005

Intraoperative detection of lymph node micrometastasis with flow cytometry in non-small cell lung cancer.

OBJECTIVE: We sought to determine whether cytokeratin-positive cells can be detected as markers of lymph node metastasis by using flow cytometry within a time frame suitable for intraoperative decision making in non-small cell lung cancer. METHODS: Five lymph nodes from each of 20 patients with non-small cell lung cancer were randomly selected for study. Each node was divided longitudinally into 3 pieces: one piece for flow cytometry, one for immunohistochemical staining, and the last for conventional hematoxylin and eosin staining. In both flow cytometry and immunohistochemistry, cytokeratin-positive cells were detected with the fluorescein isothiocyanate-conjugated anti-cytokeratin antibody AE1/AE3. RESULTS: Cytokeratin-positive nodes were detected by means of flow cytometry within 40 minutes. Eight (8%) of the 100 lymph nodes from 4 (20%) of the 20 patients were deemed positive for metastasis on the basis of conventional histologic examination. By contrast, 33 (33%) lymph nodes from 13 (65%) patients were deemed positive on the basis of immunohistochemical cytokeratin staining, and 38 (38%) lymph nodes from 14 (70%) patients were deemed positive on the basis of flow cytometric cytokeratin-positive cell detection. All nodes deemed positive for metastasis on the basis of conventional and immunohistochemical methods were also positive on flow cytometry. CONCLUSIONS: Flow cytometry enables rapid intraoperative diagnosis of nodal metastasis in patients with non-small cell lung cancer. Flow cytometric detection of cytokeratin-positive cells within lymph nodes correlates with their immunohistochemical detection, and its level of sensitivity is greater than that of conventional histologic staining and about equal to that of immunohistochemical staining.

Biomarkers, Tumor↗

PubMed2005

The current status of sentinel lymph node mapping in non-small cell lung cancer.

Sentinel lymph node (SLN) mapping has become a common procedure in the treatment of breast cancer and malignant melanoma. Its primary benefit is that it enables surgeons to avoid nontherapeutic lymph node dissection and the complications that follow. There are also several studies of the use of SLN mapping in the treatment of non-small cell lung cancer (NSCLC) reported in the English literature, and all present evidence for the existence of SLNs in NSCLC. Nevertheless, SLN mapping is not widely used in the treatment of NSCLC for several reasons: first, special precautions are required to minimize exposure when radioisotopes are used as tracers; second, it is difficult to detect the blue dyes used as tracers within anthoracotic thoracic lymph nodes; and third, major complications comparable to the arm edema seen in breast cancer or the lymphedema and nerve injury seen in melanoma are not seen with mediastinal lymph node dissection (MLND). To address these issues, new techniques are being developed by groups at several institutes, including our own. We believe that SLN mapping will enable surgeons to more precisely stage NSCLC, after which more sensitive techniques can be employed on a limited amount of tissue to detect occult micrometastatic disease with less cost and effort. SLN mapping can also be applied to video-assisted thoracic surgery (VATS) for NSCLC, enabling surgeons to avoid nontherapeutic and technically difficult MLND often necessary with traditional open surgery. For all of these reasons, we think that SLN mapping will be useful in the treatment of NSCLC, and that further development aimed at making SLN mapping a practical surgical procedure is warranted.

Carcinoma, Non-Small-Cell Lung↗

PubMed2005

[Chemotherapy for an esophageal cancer patient undergoing continuous ambulatory peritoneal dialysis for chronic renal failure and measurement of plasma concentration of the drug].

We administered chemoradiotherapy consisting of 5-fluorouracil (5-FU) combined with cisplatin, radiation and sequential chemotherapy using nedaplatin for an esophageal cancer patient undergoing continuous ambulatory peritoneal dialysis (CAPD) for chronic renal failure. There are no reports in the literature of chemotherapy for a patient maintained on CAPD. The dosage of each drug was based on that for a patient undergoing hemodialysis, and the plasma concentration of each drug was examined. Chemotherapy consisted of 3-10 mg/body of cisplatin with 60-min infusion and 450 mg/body of 5-FU with continuous infusion over 5 days. There were no side effects and no increase in the concentration of either of the drugs. Subsequently, 50 mg/body of nedaplatin, which is half the dose for a patient with normal renal function, was administered. The area under the blood concentration time curve (AUC) of nedaplatin was 15.85 microg/ml, which was slightly low compared with that after infusion of 80 mg/m2 in patients with normal renal function. Grade 3 leukopenia and thrombocytopenia occurred. As a final result, a partial response was obtained, and the patient was able to eat solid food after treatment. Although chemotherapy consisting of low-doses of cisplatin and 5-FU and a half dose of nedaplatin was administered safely, further study is needed to determine the suitable regimens for a patient maintained on CAPD.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2004

Expression of tissue factor mRNA and invasion of blood vessels by tumor cells in non-small cell lung cancer.

PURPOSE: Tissue factor (TF), an initiator of the extrinsic coagulation cascade, is also expressed in a wide range of cancer cells and plays an important role in cancer progression and metastasis, as well as in processes independent of the blood coagulation pathway. For example, by acting as an adhesion molecule enabling tissue invasion, TF may play a key role in the metastatic process and angiogenesis in non-small cell lung cancer (NSCLC). METHODS: To further investigate the role of TF on tumor cell invasion in NSCLC, we measured the TF mRNA expression in the tumors of 42 NSCLC patients using real-time quantitative reverse transcription - polymerase chain reaction carried out in a LightCycler. We then compared the TF mRNA expression with histological evidence of invasion of blood and lymphatic vessels by tumor cells. RESULTS: Although there was no significant relationship between the TF mRNA expression and the invasion of lymphatic vessels, the TF mRNA expression was significantly higher in tumors that invaded blood vessels (Log(10) TF mRNA/GAPDH mRNA = 2.16 +/- 0.18) than in those that did not (1.59 +/- 0.16; P = 0.03). CONCLUSION: These results suggest that TF plays a major role in blood vessel invasion by tumor cells in NSCLC.

Adult↗

PubMed2004

Mediastinal neurofibroma originating from the left intrathoracic phrenic nerve: report of a case.

We report a case of mediastinal neurofibroma originating from the left phrenic nerve in a 42-year-old woman who was referred to us after a routine chest X-ray showed a smooth, round abnormal shadow in the left middle lung field adjacent to the heart. We resected a 25 x 20 x 20-mm tumor by video-assisted thoracic surgery. Histopathological examination confirmed that the lesion was a mediastinal neurofibroma originating from the left phrenic nerve without von Recklinghausen's disease. Neurogenic mediastinal tumors originating from the phrenic nerve are very rare, and to the best of our knowledge, no other case of a mediastinal neurofibroma originating from the phrenic nerve in a patient without von Recklinghausen's disease has ever been reported.

Adult↗

PubMed2004

Mesojejunal lymph node metastasis in esophageal cancer following total gastrectomy.

We report on a case of thoracic esophageal cancer following total gastrectomy (rho-Roux-en-Y reconstruction) with metastasis to the mesojejunal lymph nodes. Subtotal esophagectomy with reconstruction using pedicled colon and dissection of two lymph node fields was performed. During the operation, we found three lymph nodes showing metastasis at the rho-Roux loop of the mesentery, and resected the rho-Roux loop. The route of the lymphatic drainage to the abdomen from the thoracic tumor seemed to have been changed by the prior gastrectomy. Based on the pathological findings, the case was diagnosed with T2N4M0, Stage IVa. We did not confirm that the distant metastases skipped the mesojejunal lymph nodes preoperatively; the distant metastases were detected accidentally by lymphoscintigraphy using technetium-99m tin colloid. We believe this case highlights the need for detailed examinations in esophageal cancer patients who have had prior gastrectomy.

Aged↗

PubMed2004

Superior mediastinal and neck lymphatic mapping in mid- and lower-thoracic esophageal cancer as defined by ferumoxides-enhanced magnetic resonance imaging.

OBJECTIVE: The purpose of this study was to detect lymphatic drainage into the superior mediastinum and neck in thoracic esophageal cancer patients using ferumoxides-enhanced magnetic resonance imaging (MRI), and to have this information assist in determining the appropriate extent of lymphadenectomy. METHODS: Nine male patients with T2-T3 mid- and lower-thoracic esophageal cancer with lymph node metastasis were examined. The day before surgery, ferumoxides was endoscopically injected into the submucosal layer of the peritumoral lesion. Thereafter, lymph nodes in the superior mediastinum and neck, which were shown to be ferumoxides-enhanced on MRI, were harvested and evaluated; magnetic force from all harvested lymph nodes was measured ex vivo. RESULTS: MRI of the superior mediastinum and neck revealed 1(median) ferumoxides-enhanced lymph nodes in eight (89%) patients, and there was laterality in the lymphatic mapping in both areas. Of the 15 lymph nodes into which drainage was detected by enhanced MRI, 12 (80%) were magnetite-positive. In six patients (67%), magnetic resonance enhanced lymph nodes corresponded completely with the ex vivo magnetite examination, and in 3 patients (33%) there was partial agreement. In 3 (60%) of the 5 patients that showed paratracheal and/or supraclavicular lymph node metastases, all of the affected nodes were detected by MRI; in one patient some of the affected nodes were detected. CONCLUSION: Ferumoxides-enhanced MRI is useful for visualizing lymphatic drainage to the superior mediastinum and neck in thoracic esophageal cancer. It is an adequate procedure to form an estimate on the appropriate extent of lymphadenectomy.

Adult↗

PubMed2004

Hydrogen peroxide derived from intestine through the mesenteric lymph induces lung edema after surgical stress.

Compelling evidence indicates that the small intestine is the primary source of factors inducing lung injury after major surgery and that the lymphatic system is the major route by which these gut-derived factors reach the pulmonary circulation. This study investigated the mechanism of lung edema induced by surgical stress. After subjecting male, fasted, pathogen-free Sprague-Dawley rats to surgical stress (laparotomy and intestinal handling for 5 min), followed by ventilation for 5 h, we measured H2O2 production in the mucosa of small intestine and in the lung using 2',7'-dichlorofluorescein and intravital fluorescence microscopy. In addition, H2O2 in mesenteric lymph was measured using a quantitative assay; lung permeability was assessed as a function of extravasation of Evans blue dye; neutrophil accumulation was visualized by intravital fluorescence microscopy and assessed as a function of myeloperoxidase activity; and TNF-alpha levels were measured using a specific ELISA. The intensity of 2',7'-dichlorofluorescein fluorescence in the mucosa of small intestine, H2O2 levels of mesenteric lymph, and lung permeability were all significantly higher in rats subjected to surgical stress than in control animals. Moreover, all of these effects were blocked by pretreatment with a specific xanthine oxidase inhibitor. Surgical stress did not increase neutrophil accumulation or TNF-alpha production in the lung. In conclusion, surgical stress induces xanthine oxidase-dependent H2O2 production in the small intestine. The H2O2 then enters the mesenteric lymph and travels to the lung, where it increases capillary permeability and thus induces edema.

Animals↗

PubMed2003

Outcomes of active operation during intensive followup for second primary malignancy after esophagectomy for thoracic squamous cell esophageal carcinoma.

BACKGROUND: Recent advances in the treatment of thoracic esophageal cancer have afforded it a better prognosis. As a consequence, increasing attention is being paid to the outcomes with postoperative monitoring for second primary malignancies after esophagectomy, but no recent study has focused on the longterm followup and outcomes in these patients. STUDY DESIGN: In 1989, we began intensive prospective screening and surveillance designed to detect cancers of the head and neck, lung, stomach, residual esophagus, and colon/rectum after esophagectomy. Between 1989 and 2001, 365 patients underwent esophagectomy for thoracic squamous cell esophageal carcinoma in our department. Of those, 200 were followed up as part of this program. Excluded were patients in whom esophageal cancer recurred, patients with other prior or simultaneous malignancies, and patients who died within a year of operation. Clinicopathologic profiles and treatment outcomes were determined for 33 patients who developed a second primary malignancy after esophagectomy. RESULTS: The interval between the primary esophageal cancer and the secondary carcinoma was 49 +/- 40 months (median, 48 months). The second primary malignancies were located in the stomach (30%), head and neck (24%), lung (24%), colon/rectum (9%), liver (6%), pancreas (3%), and blood (6%). Twenty-one patients (64%) were classified as stage 0, I, or II; 10 (30%) were stage III or IV. Overall, the 2-year, 3-year, and 5-year survival rates following diagnosis of a second primary malignancy were 58.0%, 58.0%, and 48.6%, respectively. Of the 19 patients (58%) in whom second primary malignancies were detected before symptoms developed, the 5-year survival rate was 70.7%, which was significantly greater than that among patients whose secondary malignancies were discovered after symptoms developed (17.1%). CONCLUSIONS: Good outcomes in the treatment of second primary malignancies after esophagectomy for thoracic squamous cell esophageal carcinoma can be obtained with longterm, intensive followup and active surgical intervention for detected malignancies.

Aged↗

PubMed2003

Hydrogen peroxide-dependent declines in Bcl-2 induces apoptosis in hypoxic liver.

BACKGROUND: Low-flow hypoxia induces xanthine oxidase-dependent hydrogen peroxide production by hepatocytes in the midzone of blood-perfused rat livers and apoptosis in sinusoidal endothelial cells (SECs). As Bcl-2 is a potent inhibitor of apoptotic cell death and is localized mainly in the inner mitochondrial membrane and crista, the purpose of this study was to determine whether cell-specific changes in mitochondrial Bcl-2 levels could account for the hypoxia-induced apoptosis in SECs. MATERIALS AND METHODS: A low-flow hypoxia model was generated in isolated rat livers by reducing perfusate inflow pressure from 10 to 2.5 cmH2O for 2 h. Apoptosis was then evaluated using the TdT-mediated dUTP-digoxigenin nick end-labeling (TUNEL) method. Mitochondrial Bcl-2 protein levels were determined in hepatocytes and SECs using cryosectioning immunogold labeling electron microscopy.Results. TUNEL-positive nonparenchymal cells, identified as SECs, were observed predominantly in the midzone of low-flow hypoxic rat livers, whereas few parenchymal cells were stained. Mitochondrial Bcl-2 levels were higher in SECs than in hepatocytes under control conditions, but they declined significantly during hypoxia, though no morphological signs of apoptosis were apparent. In hepatocytes, by contrast, Bcl-2 levels were unaffected by hypoxia. Pretreatment with a specific xanthine oxidase inhibitor, sodium (-)-8-(3-methoxy-4-phenylsulfinylphenyl) pyrazolo [1,5-a]-1,3,5-triazine-4-olate monohydrate, which blocks production of hydrogen peroxide, also blocked both the hypoxia-induced apoptosis and the decline in mitochondrial Bcl-2 in SECs. CONCLUSION: Hydrogen peroxide-dependent declines in Bcl-2 induce apoptosis in SECs in the hypoxic rat liver.

Animals↗

PubMed2003

A novel method for sentinel lymph node mapping using magnetite in patients with non-small cell lung cancer.

OBJECTIVE: The detection rate of sentinel lymph nodes in patients with non-small cell lung cancer using isosulfan blue dye is too low for clinical use. Although exposure to radioactivity is reportedly minimal, special procedures are nonetheless required when a radioactive isotope is used as a tracer. Therefore, to eliminate the need for a radioactive tracer and to obtain a better detection rate than is obtained with isosulfan blue dye, we have developed a novel method that employs magnetite as the tracer. The aim of the present study was to test the feasibility of this technique. METHODS: The tracer employed was ferumoxides, a colloidal superparamagnetic iron oxide of nonstoichiometric magnetite. Thirty-eight non-small cell lung cancer patients participated in the study; each received 5 mL of ferumoxides, injected around the tumor intraoperatively. Fifteen minutes after injection, lung resection and lymph node dissection were carried out. The magnetic force within the lymph nodes was measured using a highly sensitive handheld magnetometer ex vivo. All lymph nodes were also subjected to conventional histological analysis. RESULTS: The rate of detection of sentinel lymph nodes was 81.6% (31/38). The accuracy, sensitivity, and false-negative rates were 96.8% (30/31), 85.7% (6/7), and 14.3% (1/7), respectively. CONCLUSION: Intraoperative sentinel lymph node mapping using ferumoxides and a highly sensitive magnetometer is a safe, accurate, and sensitive way to detect sentinel lymph nodes in non-small cell lung cancer patients.

Adult↗