Background. Hematogenous metastasis requires angiogenesis within the tumor. Previous studies have shown that microvessel counts in histologic sections of the primary tumor, which reflect angiogenesis, are correlated with metastasis in breast, prostate and Stage I nonsmall cell lung carcinoma. In this study, the authors investigated the association between angiogenesis, hematogenous metastasis and lymph node metastasis in all stages of lung adenocarcinoma. Methods. Microvessels were highlighted by immunostaining endothelial cells for factor VIII. We counted microvessels within the tumors of 42 patients who had surgical resection (25 with relapse and 11 without relapse more than 5 years after surgical resection). Without knowledge of patient outcome, microvessels were counted on a 200× field (0.723 mm2) in the most active areas of neovascularization. Results. The microvessel counts from patients with relapse after surgical resection (mean ± standard deviation, 75.4 ± 64.3) were significantly higher than those without relapse more than 5 years after surgical resection (42.6 ± 26.0) (P = 0.027). Analysis of regional lymph node metastases (factor N) revealed that the microvessel counts were 62.6 ± 35.1 for NO (no regional lymph node metastasis), 51.7 ± 22.2 for N1 (metastasis in ipsilateral, peribronchial and/or ipsilateral hilar lymph nodes, including direct extension), 75.4 ± 75.3 for N2 (metastasis in ipsilateral mediastinal and/or subcarinal lymph nodes), and 74.0 for N3 (metastasis in contralateral mediastinal, contralateral hilar, ipsilateral or contralateral scalene or supraclavicular lymph node[s]), and these values were not significantly different from each other. Conclusions. Angiogenesis assessed by microvessel counts, correlated positively with relapse after surgical resection and hematogenous metastasis in all stages of lung adenocarcinoma; there was no correlation with lymph node metastasis in lung adenocarcinoma.

SaryWe examined the relationship between the retention of thallium-201 (2"Tl) on a delayed scan and the metastatic potential of adenocarcinomas of the lung. We studied 43 patients with adenocarcinoma of the lung and divided them into two groups according to the presence or absence of lymph node metastasis. "Tl single photon emission computerised tomography (SPECT) was conducted twice: 15 min (early scan) and 120 min (delayed scan) after intravenous injection of 3 mCi of "'TI chloride. We calculated the retention index in order to evaluate the degree of 2D1T1 retention in the primary tumour. The retention indices were significantly higher in the group that was positive for lymph node metastasis than in the negtive group. In adenocarcinomas with high metastatic potential, I'l SPECT demonstrated slow washout or increased retention on the delayed scan. The retention index of 'Tl SPECT is a useful indicator of metastatic potential, thereby facilitating the prediction of prognosis, and provides insight into the relationship between "'TI uptake and malignancy. This is the first report demonstrating a significant relationship between the retention of uITl SPECT and lymph node metastasis.2"TI scintigraphy is used to diagnose myocardial infarction (Strauss et al., 1975), myocardial ischaemia (Strauss & Boucher, 1986) and thyroid tumour (Ochi et al., 1982; ElDesouki, 1991). Recently, -'OTI SPECT has been used for the detection of lung lesions (Tonami et al., 1989) and has been shown to be superior to gallium scintigraphy for lung cancer detection (Matsuno et al., 1991; Itoh et al., 1992). The uptake ratio of 2"TI SPECT for lung cancer differs according to the histological type (Togawa et al., 1985; Tonami et al., 1989). The accumulation patterns of 2"Tl on early and delayed scans differ between benign and malignant lung and thyroid tumours (Ochi et al., 1982; Tonami et al., 1989;El-Desouki, 1991). In benign tumours, '"Tl shows either no or reduced accumulation on the delayed scan, while malignant tumours accumulate 20'Tl on both the early and the delayed scans. Tonami et al. (1989) proposed the retention index as an indicator for the degree of '"Tl retention in the lesion. This index is useful in differentiating between malignant and benign lesions (Tonami et al., 1989;Suga et al., 1993). In a study of lung cancer Tonami et al. (1989) reported that this index was highest for small-cell lung carcinoma, the histological type in which lymph node metastasis occurs earliest. These observations prompted us to speculate that the retention index might represent the metastatic potential of lung cancers.Tumour size is not as good a predictive factor for adenocarcinomas as it is for squamous cell carcinomas. Even if adenocarcinomas of the lung are small in size, there may be extensive mediastinal lymph node metastases or distant metastases (Takise et al., 1988). Prediction of the metastatic potential of an adenocarcinoma would be the most valuable preoperative prognostic information.Given the existence of a variety of metastatic...

The authors calculated the uptake ratio to evaluate the degree of Tl-201 uptake in the primary tumor. This ratio was compared with survival time and other prognos-1 Department of Respiratory Medicine, Nikko tic factors. Memorial Hospital, Muroran, Japan. RESULTS.The authors studied 152 patients (125 men and 27 women). The group 2 Department of Nuclear Medicine, School of of patients with the low Tl-201 uptake ratio survived longer than the group of Medicine, Hokkaido University, Sapporo, Japan.patients with the high Tl-201 uptake ratio (median survival, 58 weeks vs. 33 weeks; P Å 0.0138 by the log rank test). The multivariate analysis confirmed that the Tl-3 Department of Medical Information Services, Nikko Memorial Hospital, Muroran, Japan.201 uptake ratio was an independent prognostic factor for survival. CONCLUSIONS. These results suggest that the Tl-201 uptake ratio provides indepen-4 First Department of Medicine, School of Medident and objective prognostic information for patients with lung carcinoma. Cancine, Hokkaido University, Sapporo, Japan.

Summary Thallium-201 single-photon emission computerized tomography (SPECT) was used to clarify the relationship between 201TI uptake and the response in chemotherapy to platinum compounds in 21 patients with small-cell lung cancer. 201TI-SPECT scans were obtained twice: at 15 min (early scan) and 120 min (delayed scan) after an intravenous injection of 111 MBq (3 mCi) of thallium-201 chloride. We obtained the uptake ratio from each scan and calculated the retention index:uptake ratio = region of interest uptake / contralateral normal lung uptake; retention index = (delayed ratio -early ratio)/early ratio. After 201TI scintigraphy, 12 patients received chemotherapy consisting of platinum compounds and nine were treated with chemoradiation. Among patients receiving only chemotherapy, the retention index correlated with the responses to chemotherapy. In an in vitro study, ouabain, an inhibitor of the Na,K-ATPase pump, reduced sensitivity to cisplatin and inhibited intracellular thallium uptake in the small-cell lung cancer cell line. These studies suggest that 201TI-SPECT is a useful indicator of response to chemotherapy with platinum compounds in small-cell lung cancer, and that Na,K-ATPase is commonly involved in transporting both thallium and platinum compounds into cancer cells.Keywords: 201TI-SPECT; chemotherapy; inductively coupled plasma mass spectrometry; cisplatin; Na,K-ATPase Cisplatin (CDDP) is a useful anti-cancer agent, particularly when used in the treatment of human ovarian, testicular, bladder and small-cell lung cancer (Loehrer et al, 1984;Ohmori et al, 1993). Many studies on cisplatin resistance mechanisms have revealed that the decline in intracellular accumulation of cisplatin is important in carcinoma cell lines (Hromas et al, 1987;Kraker and Moore, 1988;Andrews and Howell, 1990;Mann et al, 1990). Cisplatin accumulation in these cells is reported to be regulated by an alteration in their Na,K-ATPase levels (Kawai et al, 1987;Andrews et al, 1991;Ohmori et al, 1993). Thus, the response to chemotherapy with cisplatin might depend on alterations of Na,K-ATPase.Thallium-201 (201TI) scintigraphy is now used to diagnose myocardial infarction (Strauss et al, 1975), myocardial ischaemia (Strauss and Boucher, 1986) and thyroid tumour (Bleichrodt et al, 1987;Charkes et al, 1990). Recently, 207T1 single-photon emission computerized tomography (SPECT) was reported as being used to detect lung lesion (Tonami et al, 1989), and it is reportedly superior to gallium scintigraphy in detecting lung cancer (Itoh et al, 1992;Matsuno et al, 1992). Some studies demonstrated that TI accumulation in 201T1 scintigraphy is closely related to the Na,K-ATPase levels in malignant tumours (Britten and Blank, 1968;Muranaka, 1981;Kishida, 1987;Sehweil et al, 1989). And we reported that the delayed ratio is related to low levels of Na,K-ATPase activity (Takekawa et al, 1996). We hypothesized that the degree of TI uptake to tumour in 201Tl scintigraphy is associated with the response to chemotherapy with platinum compounds th...

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