Hiroshi Imano

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.

Survival Advantage of Using Autologous Blood Transfusion During Surgery for Esophageal Cancer

Abstract.Purpose: There is evidence that blood transfusion is associated with an increased rate of tumor recurrence. This study was conducted to assess the survival advantage of giving autologous blood instead of allogeneic blood during surgery for esophageal cancer. Methods: We retrospectively analyzed 62 patients who underwent esophagectomy for thoracic esophageal cancer between January 1991 and February 1995 and received allogeneic blood transfusion, and 61 patients operated on between March 1995 and February 1998, who received autologous blood transfusion. The clinicopathological factors and survival rates were compared between the two groups. Results: The clinicopathological factors that influenced prognosis were similar in the two groups; however, a definite survival advantage was evident in the autologous blood transfusion group. According to multivariate analyses, the transfusion of allogeneic blood was an independent prognostic factor (P = 0.0222), as was the presence of metastatic lymph nodes. Patients who received allogeneic blood transfusions perioperatively had more than a twofold greater risk (Hazard ration 2.406) of death over patients who received autologous blood transfusions. Conclusion: Autologous blood transfusion appears to be an independent prognostic factor for the survival of patients with esophageal cancer.

Visualization of lymphatic basin from the tumor using magnetic resonance lymphography with superparamagnetic iron oxide in patients with thoracic esophageal cancer.

Objective: To evaluate magnetic resonance (MR) lymphography with submucosal injection of superparamagnetic iron oxide (SPIO) for imaging lymphatic pathways from thoracic esophageal cancer. Methods: In 24 patients with esophageal cancer, SPIO was injected into the submucosal layer of the peritumoral region endoscopically and MR lymphography was conducted. In study 1, fast spoiled gradient-recalled acquisition using a steady-state (FSPGR) sequence was performed from the neck to the upper abdomen before and at 20, 40, and 60 minutes after injection in 10 patients. In study 2, FSPGR and spin echo T1-weighted images were obtained after injection in 14 patients. Areas scanned were the neck to the upper mediastinum and the upper abdomen. Results: In study 1, at 20 minutes after injection, the signal of each lymph node appeared attenuated when compared with precontrast images. The signal-to-noise ratio in lymph nodes exhibiting influx of SPIO was significantly lower than that found on precontrast images (P < 0.0005). In study 2, influx to the neck lymph nodes was detected in 8 patients (64.3%), whereas influx to the upper abdominal lymph nodes was detected in 13 (92.9%). Conclusions: Magnetic resonance lymphography with SPIO could visualize the lymphatic pathways draining from the injection site and the location of lymph nodes exhibiting influx of SPIO in patients with thoracic esophageal cancer.

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.

Methylprednisolone inhibits low-flow hypoxia-induced mitochondrial dysfunction in isolated perfused rat liver.

ObjectiveTo investigate the mechanism by which methylprednisolone protects the liver from hypoxia-induced injury. DesignProspective control study using the isolated rat liver. SettingAnimal research facility. SubjectsMale, fasted, pathogen-free Sprague-Dawley rats. InterventionsLow-flow hypoxia was produced by reducing afferent perfusate pressure from 10 to 2.5 cm H2O; isolated livers were portally perfused for 2 hrs. Measurements and Main ResultsWe measured mitochondrial membrane potential and hydrogen peroxide production by imaging rhodamine 123 and 2′-7′-dichlorofluorescein fluorescence, respectively. Leakage of mitochondrial enzymes was also monitored by assaying mitochondrial aspartate aminotransferase activity in the outflow perfusate, and the radical-scavenging effect of methylprednisolone was assessed by measuring luminol-dependent hydrogen peroxide chemiluminescence. Apoptosis in liver cells was determined by using terminal deoxynucleotidyl transferase–mediated dUTP-digoxigenin nick-end labeling. Rhodamine 123 fluorescence was significantly diminished in the hypoxic liver, especially in the region of the terminal hepatic venules, which is indicative of membrane depolarization in the mitochondria in those areas. Hypoxia-induced mitochondrial dysfunction was indicated by leakage of aspartate aminotransferase into the outflow perfusate, and increased 2′-7′-dichlorofluorescein fluorescence indicated increased hydrogen peroxide levels, particularly in the midzone. Pretreatment with 30, 10, or 3 mg/kg of methylprednisolone inhibited the hypoxia-induced mitochondrial membrane depolarization and enzyme leakage, although hydrogen peroxide levels and apoptosis in sinusoidal endothelial cells were unaffected. ConclusionsMethylprednisolone does not protect the liver from hypoxia-induced injury by suppressing hydrogen peroxide production. Instead, the beneficial effect of methylprednisolone seems to be related to its ability to protect against mitochondrial membrane depolarization under hypoxic conditions.

Simultaneous Esophagectomy and Coronary Artery Bypass Grafting Without Cardiopulmonary Bypass: Report of a Case

We successfully performed off-pump coronary artery bypass grafting (OPCAB) with concomitant esophagectomy in a 77-year-old man with esophageal cancer and severe stenosis of the anterior descending branch of the left coronary artery. Off-pump coronary artery bypass grafting was performed via median sternotomy and esophagectomy was done via the left thoracoabdominal approach. The patient was discharged with a patent graft 8 weeks after surgery. The benefits of OPCAB include that it is less invasive and heparinization can be avoided. This case report demonstrates that simultaneous OPCAB and esophagectomy is advantageous for a selected population with surgically correctable coronary artery disease and resectable esophageal cancer.

Case Report of Allergic Granulomatous Angitis Performed Enterectomy due to Mechanical Obstruction

症例は37歳の男性で, 腹痛と腹部膨満のため来院し, 腹部X線検査所見より腸閉塞の診断で入院した. 絶飲食, 補液で改善せずCTで機械的腸閉塞と診断し, 入院6日後に手術を施行した. トライツ靱帯から15cm肛門側の部位より50cmにわたり小腸壁の肥厚, 漿膜の発赤, 小腸間膜リンパ節の腫脹を認めた. 一部, 血流不良域もあり小腸を部分切除した. 病理組織学的検査所見で粘膜下層にフィブリノイド壊死を伴う小中動静脈の破綻と出血を認め, その周囲に好酸球浸潤を伴う肉芽組織形成を認めた. アレルギー性鼻炎の既往, 血管炎による発熱, 体重減少, 筋肉痛, および主要組織所見からアレルギー性肉芽腫性血管炎と診断した. 現在まで再発を認めていない. アレルギー性肉芽腫性血管炎による腸閉塞の本邦報告例は自験例を含め6例であり, 若干の文献的考察を加え報告する.

Soluble and cell-associated forms of some yet to be identified factor in transfused blood which promotes solid tumor growth in mice.

PurposeThe mechanism underlying the immunomodulation caused by blood transfusion has yet to be elucidated. The aim of the present study was to determine whether the transfusion of a soluble or insoluble factor present in stored blood can induce immunomodulation, which would thereby promote solid tumor growth.MethodsC57Bl/6J mice were subcutaneously inoculated with B16-CG melanoma cells, which secrete β-human chorionic gonadotropin (β-hCG). Following inoculation, each of three different products of allogeneic and syngeneic blood were transfused on days 0 and 1: fresh whole blood, stored whole blood, and supernatants from the stored blood. Tumor growth was then monitored by measuring urinary β-hCG. All mice were killed on day 15, and the tumor weight and volume were measured.ResultsTransfusion of all allogeneic blood products enhanced tumor growth, as did the stored syngeneic whole blood. Neither fresh syngeneic blood nor the supernatant from stored syngeneic blood promoted tumor growth. Although the tumors were not visually detectable until day 10 after inoculation, by day 7 the levels of urinary β-hCG were significantly higher in the mice that received allogeneic blood supernatant than in the mice that received saline.ConclusionsA soluble alloantigen enhances solid tumor growth, as does an insoluble factor present in stored syngeneic whole blood. The immunomodulation associated with this factor begins to enhance tumor growth within 7 days after transfusion.

A Case of Primary Malignant Esophageal Lymphoma Responding to Chemoradiation Therapy

症例は42歳の男性で, つかえ感を主訴に受診し, 上部消化管造影および内視鏡検査にて胸部中部食道に長径4cmの全周性狭窄を認めたが, 粘膜病変は見られなかった. CTで腫瘍は左主気管支, 下行大動脈に浸潤し, 悪性腫瘍が示唆された. 2度の消化管内視鏡下生検で確定診断をえられず, 胸腔鏡下腫瘍生検術を施行した. その結果, びまん性B細胞リンパ腫と診断された. 化学 (CHOP療法) および放射線 (40Gy) 療法を施行し, 完全寛解をえた. 治療後3年経過したが, 再発を認めていない. 確定病理診断の下, 化学放射線療法で3年の完全寛解をえた食道原発悪性リンパ腫の1例を報告した.