Yoshihisa Katayose

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.

Inhibition of heat shock protein 90 sensitizes melanoma cells to thermosensitive ferromagnetic particle-mediated hyperthermia with low Curie temperature

Heat shock protein (Hsp) 90 is a key regulator of a variety of oncogene products and cell‐signaling molecules, and the therapeutic benefit of its inhibition in combination with radiation or chemotherapy has been investigated. In addition, hyperthermia has been used for many years to treat various malignant tumors. We previously described a system in which hyperthermia was induced using thermosensitive ferromagnetic particles (FMP) with a Curie temperature (Tc = 43˚C) low enough to mediate automatic temperature control, and demonstrated its antitumor effect in a mouse melanoma model. In the present study, we examined the antitumor effects of combining a Hsp90 inhibitor (geldanamycin; GA) with FMP‐mediated hyperthermia. In cultured B16 melanoma cells, GA exerted an antitumor effect by increasing the cells’ susceptibility to hyperthermia and reducing expression of Akt. In an in vivo study, melanoma cells were subcutaneously injected into the backs of C57BL/6 mice. FMP were then injected into the resultant tumors, and the mice were divided into four groups: group I, no treatment (control); group II, one hyperthermia treatment; group III, GA alone; and group IV, GA with hyperthermia. When exposed to a magnetic field, the temperature of tissues containing FMP increased and stabilized at the Tc. In group IV, complete regression of tumors was observed in five of nine mice (56%), whereas no tumor regression was seen in groups I–III. Our findings suggest that inhibition of Hsp90 with hyperthermia increases its antitumor effect. Thus, the combination of FMP‐mediated, self‐regulating hyperthermia with Hsp90 inhibition has important implications for the treatment of cancer. (Cancer Sci 2009; 100: 558–564)

Radio-guided thoracoscopic surgery with 99mTc-methoxy-isobutylisonitrile for treating an ectopic mediastinal parathyroid adenoma in an adolescent girl

Here we report the case of a 17-year-old girl treated for an ectopic mediastinal parathyroid adenoma using 99mTc-methoxy-isobutyl-isonitrile (MIBI) and radio-guided thoracoscopic surgery. Her serum calcium and intact parathyroid hormone levels were elevated, and an anterior mediastinal tumor was noted on her chest computed tomography scan. At 2 h before surgery, the patient was given an injection of 370 MBq of 99mTc-MIBI. Because it was not possible visually to distinguish the tumor from the mature thymic tissue in which it was embedded, a search for the tumor was carried out using a gamma probe under thoracoscopy. Thereafter, the left thymus, including the radioactivity-positive tumor, was resected. We suggest that radio-guided thoracoscopic surgery with 99mTc-MIBI is an excellent procedure for treating ectopic mediastinal parathyroid adenomas embedded in the mature thymus of adolescents and young adults. This approach could be especially useful for young female patients, given its cosmetic advantage.

Estimation of pulmonary oxygen consumption in the early postoperative period after thoracic surgery

Lung injury, including pneumonia, can occur in the early postoperative period following thoracic surgery. Pulmonary oxygen consumption is thought to increase in patients with pulmonary infection. This study measured oxygen consumption in relationship to lung injury in the early postoperative period after thoracic surgery. Thirty‐five patients who underwent thoraco‐abdominal oesophagectomy for oesophageal cancer were studied. Measured oxygen‐consumption was obtained by indirect calorimetry and calculated oxygen‐consumption was simultaneously determined by the reverse Fick method. The difference in oxygen consumption was attributed to pulmonary oxygen consumption. The difference in oxygen consumption increased to 23.1 ml.min−1.m−2 on postoperative day 2. In patients with pneumonia the difference in oxygen consumption increased significantly to 39.0 ml.min−1.m−2 the day before clinical onset of pneumonia, and it increased further to 65.7 ml.min−1.m−2 on the day that pneumonia became clinically apparent. These findings suggest that the difference in oxygen consumption may be useful for estimating the extent of lung injury and for predicting pulmonary complications in the postoperative period.