著者

Yasuhiro Ito Akira Miyauchi Minoru Kihara Yuuki Takamura Kaoru Kobayashi Akihiro Miya

出版者

(社)日本内分泌学会

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

vol.59, no.5, pp.399-405, 2012 (Released:2012-05-31)

参考文献数

29

被引用文献数

10 41

---

Age is an important prognostic factor in papillary thyroid carcinoma (PTC). In this study, we investigated the difference in prognosis of 7 subsets of PTC patients without distant metastasis at presentation or a history of radiation exposure (20 years or younger, 21-30 years, 31-40 years, 41-50 years, 51-60 years, 61-70 years, and older than 70 years). The lymph node recurrence rate was high in patients 20 years or younger and those older than 60 years. Distant recurrence and carcinoma death rates significantly elevated in patients older than 60 years. The incidence of significant extrathyroid extension markedly increased with age, although that of large node metastasis or extranodal tumor extension did not differ much among the 7 subsets. With the Kaplan-Meier method, lymph node recurrence rate was poor in patients 20 years or younger and in those older than 60 years. Poor distant recurrence-free and cause specific survivals of patients older than 60 years were identified in the series of PTC patients with and without these aggressive features. It is therefore suggested that 1) Lymph node recurrence rate was high in patients 20 years or younger and those older than 60 years and 2) prognosis, including distant recurrence-free survival and cause-specific survival, of patients older than 60 years was poor regardless of clinicopathological features of PTC at initial surgery.

著者

Yasuhiro Ito Minoru Kihara Yuuki Takamura Kaoru Kobayashi Akihiro Miya Mitsuyoshi Hirokawa Akira Miyauchi

出版者

(社)日本内分泌学会

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

vol.59, no.7, pp.539-545, 2012 (Released:2012-07-31)

参考文献数

40

被引用文献数

10 32

---

Age is an important prognostic factor of papillary thyroid carcinoma (PTC). In this study, we investigated the prognosis and prognostic factors of PTC in patients younger than 20 years. We enrolled 110 patients who underwent initial surgery at Kuma Hospital between 1987 and 2008. Tumor size > 4 cm, metastatic node ≥ 3 cm, and significant extrathyroid extension were more frequently detected in 8 patients with distant metastasis at diagnosis than in 102 patients without distant metastasis. Ten- and 20-year lymph node recurrence-free survival (LN-RFS) and distant recurrence-free survival (DRFS) rates were 84 and 80%, and 95 and 89%, respectively. Metastatic node ≥ 3 cm, age ≤ 16 years, tumor size > 4 cm, and male gender affected LN-RFS, and the former two had an independent prognostic value in multivariate analysis. Metastastic node ≥ 3 cm, significant extrathyroid extension, age ≤ 16 years, tumor size > 4 cm, and a male gender predicted a poor DRFS, and the former two were independent prognostic factors. To date, only 2 patients have died of PTC. These findings suggest that, in the subset of PTC patients younger than 20 years, metastatic node ≥ 3 cm, significant extension, and age ≤ 16 were important signs of aggressiveness of carcinoma, and careful treatment is necessary for patients with these characteristics, although the cause-specific survival was excellent.

著者

Yasuhiro ITO Hiroshi YOSHIDA Rie MARUO Shinji MORITA Toru TAKANO Mitsuyoshi HIROKAWA Tomonori YABUTA Mitsuhiro FUKUSHIMA Hiroyuki INOUE Chisato TOMODA Minoru KIHARA Takashi URUNO Takuya HIGASHIYAMA Yuuki TAKAMURA Akihiro MIYA Kaoru KOBAYASHI Fumio MATSUZUKA Akira MIYAUCHI

出版者

(社)日本内分泌学会

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

vol.56, no.1, pp.89-97, 2009 (Released:2009-03-12)

参考文献数

49

被引用文献数

92 176

---

Recent studies have demonstrated that BRAFV600E mutation is a common event in papillary thyroid carcinoma and a majority of these lesions have shown a direct relationship between BRAFV600E mutation and aggressive characteristics, including a worse patient prognosis. However, there are no studies from Japan regarding this issue in a large series with adequate postoperative follow-up periods. We investigated BRAFV600E mutation in 631 patients with papillary carcinoma having median follow-up periods of 83 months. The prevalence of BRAFV600E mutation was 38.4%, and the rate was higher in carcinoma larger than 1.0 cm but did not successively increase with tumor size. Furthermore, the prevalence did not significantly increase in cases demonstrating high-risk biological features such as clinically apparent lymph node metastasis, massive extrathyroid extension, advanced age, distant metastasis at surgery, and advanced Stage. The disease-free survival of patients with BRAFV600E mutation did not differ from that of those without BRAFV600E mutation. These findings indicate that, although BRAFV600E mutation may play some roles in local carcinoma development, there is no evidence that BRAFV600E mutation significantly reflects the aggressive characteristics and poor prognosis of patients with papillary carcinoma in Japan.

著者

Yasuhiro Ito Takumi Kudo Minoru Kihara Yuuki Takamura Kaoru Kobayashi Akihiro Miya Akira Miyauchi

出版者

(社)日本内分泌学会

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

vol.59, no.10, pp.895-901, 2012 (Released:2012-10-31)

参考文献数

8

被引用文献数

3 11

---

In this study, we investigated the difference in lymph node-recurrence free survival (LN-RFS), distant recurrence-free survival (DRFS), and cause-specific survival (CSS) between patients with papillary thyroid carcinoma (PTC) in the entire group (Group I) and those with lymph node- and distant-recurrence-free survival (DFS) for 5 years after initial surgery (Group II). The LN-RFS of patients with all risk classifications in Group II was significantly better than that of those in Group I. The LN-RFS of intermediate-risk patients in Group II did not differ from that of low-risk patients in Group I, but LN-RFS of high-risk patients in Group II was significantly poorer than intermediate- and low-risk patients in Group I. DRFS and CSS of Group II patients did not significantly differ from those of Group I patients in the same risk classification. DRFS and CSS of high-risk patients in Group II were significantly poorer than those of intermediate- and low-risk patients in Group I, and those of intermediate-risk patients in Group II were also significantly poorer than those of low-risk patients in Group I. Taken together, the lymph node recurrence rate, but not distant recurrence and carcinoma death rates, of patients in all classifications significantly improved after DFS for 5 years. However, careful follow-up for lymph node recurrence of high-risk patients and for distant recurrence of intermediate- and high-risk patients is necessary thereafter.

著者

Hitomi Oda Akira Miyauchi Yasuhiro Ito Hisanori Sasai Hiroo Masuoka Tomonori Yabuta Mitsuhiro Fukushima Takuya Higashiyama Minoru Kihara Kaoru Kobayashi Akihiro Miya

出版者

(社)日本内分泌学会

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

pp.EJ16-0381, (Released:2016-09-22)

被引用文献数

92

---

The incidence of thyroid cancer is increasing rapidly in many countries, resulting in rising societal costs of the care of thyroid cancer. We reported that the active surveillance of low-risk papillary microcarcinoma had less unfavorable events than immediate surgery, while the oncological outcomes of these managements were similarly excellent. Here we calculated the medical costs of these two managements. We created a model of the flow of these managements, based on our previous study. The flow and costs include the step of diagnosis, surgery, prescription of medicine, recurrence, salvage surgery for recurrence, and care for 10 years after the diagnosis. The costs were calculated according to the typical clinical practices at Kuma Hospital performed under the Japanese Health Care Insurance System. If conversion surgeries were not considered, the ‘simple cost’ of active surveillance for 10 years was 167,780 yen/patient. If there were no recurrences, the ‘simple cost’ of immediate surgery was calculated as 794,770 yen/patient to 1,086,070 yen/patient, depending on the type of surgery and postoperative medication. The ‘simple cost’ of surgery was 4.7 to 6.5 times the ‘simple cost’ of surveillance. When conversion surgeries and recurrence were considered, the ‘total cost’ of active surveillance for 10 years became 225,695 yen/patient. When recurrence were considered, the ‘total cost’ of immediate surgery was 928,094 yen/patient, which was 4.1 times the ‘total cost’ of the active surveillance. At Kuma Hospital in Japan, the 10-year total cost of immediate surgery was 4.1 times expensive than active surveillance.

著者

Yasuhiro ITO Mitsuhiro FUKUSHIMA Chisato TOMODA Hiroyuki INOUE Minoru KIHARA Takuya HIGASHIYAMA Takashi URUNO Yuuki TAKAMURA Akihiro MIYA Kaoru KOBAYASHI Fumio MATSUZUKA Akira MIYAUCHI

出版者

The Japan Endocrine Society

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

pp.0905250282, (Released:2009-06-09)

被引用文献数

107 108

---

Lymph node metastasis is an important clinicopathological feature of papillary thyroid carcinoma (PTC). PTC having clinically apparent lateral node metastasis detectable on preoperative imaging studies (N1b) is known to show a dire prognosis. However, N1b cases include various levels of biological aggressiveness, depending on the size, number, laterality and invasiveness of metastatic nodes. We investigated differences in the prognoses of 621 N1b patients based on these features and compared their prognoses with those of 4297 patients without clinically apparent metastasis (N0) and 125 patients with clinically apparent central node metastasis only (N1a). Disease-free survival (DFS) and cause-specific survival (CSS) of N1b or N1a patients were significantly worse than those of N0 patients, but the prognosis of N1b patients did not differ from that of N1a patients. In the subset of N1b patients, metastatic nodes larger than 3cm, extranodal extension, or 5 or more clinically apparent metastatic nodes independently affected DFS and a combination of the former two features also showed an effect on CSS on multivariate analysis. Prognosis of N1b patients who had none of these features did not differ from that of N1a patients. It is therefore suggested that N1b patients having metastasis larger than 3cm, those showing extranodal extension, and those having 5 or more clinically apparent metastasis should regarded as high-risk, and that careful surgical treatment and postoperative follow-up are necessary.

著者

Yasuhiro Ito Akira Miyauchi Kaoru Kobayashi Minoru Kihara Akihiro Miya

出版者

(社)日本内分泌学会

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

pp.EJ14-0303, (Released:2014-08-07)

被引用文献数

1 19

---

The two types of prognostic factors of papillary thyroid carcinoma (PTC) are static and dynamic. The following static prognostic factors have been conventionally adopted: age, tumor size, extrathyroid extension, lymph node metastasis, and distant metastasis based on pre-, intra- and post-operative findings. These factors are useful to decide therapeutic strategies for PTC patients, including the extent of surgery and radioactive iodine (RAI) ablation. However, even the combination of these factors evaluated pathologically postoperatively is not good enough at predicting recurrence in clinical settings. The dynamic prognostic factors of changes in serum thyroglobulin (Tg) and thyroglobulin antibody (TgAb) values in patients who have undergone a total thyroidectomy are important to evaluate the progression of carcinoma recurrence and to predict patients’ cause-specific survival, regardless of their backgrounds and the clinicopathological features of their PTC. Dynamic prognostic factors are superior to static prognostic factors in terms of expressing the condition of recurrence on a real-time basis.

著者

Yasuhiro Ito Akira Miyauchi Kaoru Kobayashi Akihiro Miya

出版者

(社)日本内分泌学会

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

vol.61, no.3, pp.205-213, 2014 (Released:2014-03-30)

参考文献数

67

被引用文献数

17 30

---

In this review, we focused on the patient age as an indicator of tumor growth and prognostic significance in both clinical papillary thyroid carcinoma (PTC) and subclinical papillary microcarcinoma (PMC: PTC ≤ 1 cm). In clinical PTC, young age (< 30 years) and old age (≥ 60 years) significantly affected the disease-free survival of patients, and old age was a strong predictor of carcinoma death. In contrast, in subclinical PMC, growth activity significantly decreased with patient age, and young age (< 40 years) was an independent predictor of carcinoma growth, indicating that old patients with subclinical PMC are the best candidates for observation without immediate surgery. Taken together, our findings indicate that the role of patients’ age as an indicator of tumor growth differs significantly between clinical PTC and subclinical PMC.

著者

Yasuhiro ITO Takuya HIGASHIYAMA Mitsuyoshi HIROKAWA Mitsuhiro FUKUSHIMA Hiroyuki INOUE Tomonori YABUTA Chisato TOMODA Takashi URUNO Minoru KIHARA Yuuki TAKAMURA Akihiro MIYA Kaoru KOBAYASHI Fumio MATSUZUKA Akira MIYAUCHI

出版者

The Japan Endocrine Society

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

vol.55, no.6, pp.985-989, 2008 (Released:2008-12-27)

参考文献数

17

被引用文献数

4 20

---

Anaplastic carcinoma arises from differentiated carcinoma and generally shows a dire prognosis. Anaplastic transformation may occur not only in primary tumors but also in metastatic lymph nodes. We encountered 5 cases of papillary carcinoma showing anaplastic transformation in lymph nodes that were curatively resected. Patient ages ranged from 67 to 85 years. Two of these patients showed anaplastic transformation at the initial surgery and the remaining 3 showed anaplastic transformation after repeated recurrence to the lymph nodes. After resection of anaplastic lesions of the nodes, 2 patients underwent radiation therapy, whereas the remaining 3 did not receive any adjuvant therapy. One patient died of rapid growth of lung metastasis 5 months after the resection. One patient died of carcinoma 63 months after surgery. Two patients have survived to date, 6 and 85 months after resection, respectively. The remaining one patient died of heart failure 11 months after surgery. It is therefore suggested that long-term survival can be expected for patients with differentiated carcinoma showing anaplastic transformation in the lymph node if the lesions can be curatively resected.

著者

Yuuki TAKAMURA Keiichi NAKANO Takashi URUNO Yasuhiro ITO Akihiro MIYA Kaoru KOBAYASHI Tamotsu YOKOZAWA Fumio MATSUZUKA Kanji KUMA Akira MIYAUCHI

出版者

(社)日本内分泌学会

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

vol.50, no.5, pp.595-601, 2003 (Released:2003-11-12)

参考文献数

39

被引用文献数

15 30

---

TSH receptor antibodies (TRAb) are generally regarded as mediators of thyroid stimulation in Graves' disease. In addition, a high serum TRAb value during pregnancy is one of the risk factors for intrauterine death, prematurity, and fetal or neonatal hyperthyroidism. Recently, correlations between a high serum TRAb value and endocrine opthalmopathy were also suggested. Surgical resection of the thyroid is usually followed by a reduction of serum TRAb levels in variable degrees. The relation between the extent of the thyroidectomy and the degree of reduction is still controversial. In addition, the changes in the TRAb value after total thyroidectomy (TT) over a long period of time have never been studied. We studied the changes in serum TRAb values after TT and subtotal thyroidectomy (ST) for more than 7 years. Forty-one patients with Graves' disease underwent TT, and 99 patients underwent ST. The serum TRAb values and the ratio of the patients who achieved normal values among each group (normalization rates of TRAb) at 3 and 6 months, 1, 3, 5 and 7 years after surgery were compared between the TT group and ST group. The mean preoperative TRAb values were not significantly different between the TT and ST groups, and the mean TRAb values measured 3, 6 and 12 months after surgery were not significantly different between the groups. However, the TRAb values measured 3, 5 and 7 years after surgery were significantly (p

著者

Yasuhiro Ito Akira Miyauchi Minoru Kihara Kaoru Kobayashi Akihiro Miya

出版者

(社)日本内分泌学会

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

pp.EJ14-0138, (Released:2014-04-17)

被引用文献数

6 30

---

In papillary thyroid carcinoma (PTC), macroscopic extrathyroid extension (Ex) and clinical node metastasis (N) are prominent prognostic factors. Ex is divided into two grades in the UICC TNM classification: minimal and massive Ex. Massive Ex significantly affects patients’ prognoses, whereas minimal Ex has little prognostic value. N is also divided into two grades in the TNM classification: N1a and N1b, depending on the location of metastasis, with N1b graded higher than N1a. However, massive Ex and/or N-positive PTC includes patients with a wide range of biological characteristics and prognoses, depending on their degrees of Ex and N. Other clinicopathological features such as age, gender, and tumor size also influence the prognosis. In evaluations of the biological characteristics of PTC patients with Ex and/or N, we should consider the degrees and relationships of _Ex and N _ with other clinicopathological features.

著者

Yasuhiro Ito Akira Miyauchi Minoru Kihara Takuya Higashiyama Kaoru Kobayashi Akihiro Miya

出版者

(社)日本内分泌学会

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

vol.61, no.5, pp.491-497, 2014 (Released:2014-05-31)

参考文献数

12

被引用文献数

5 17

---

Among the several prognostic factors of papillary thyroid carcinoma (PTC), age is the most prominent. It is well known that elderly PTC patients have poorer prognoses. Here we investigated the prognostic impact of young age in univariate and multivariate analyses. We retrospectively analyzed 5,733 PTC patients without distant metastasis at presentation, who underwent initial surgery at Kuma Hospital. The median follow-up period was 150 months. We classified the patients into three groups: young (< 30 years), middle-aged (30−59), and older patients (≥ 60 years). The tumor size was larger and clinical node positivity was higher in the young patients, and significant extrathyroid extension was higher in the older patients compared to the other two groups. In the univariate analysis, the young patients showed poorer extrathyroidal locoregional and distant recurrence rates than the middle-aged patients, but not cause-specific survival rates. In the multivariate analysis, age < 30 years was an independent or marginal predictor of extrathyroidal locoregional and distant recurrence, but not of carcinoma-related death. Age ≥ 60 years independently affected PTC recurrence and death. Taken together, we should carefully treat young PTC patients because of the likeliness of extrathyroidal locoregional and distant recurrence, which may not be life-threatening.

著者

Kaoru KOBAYASHI Eri KAJIWARA Masayuki ISHIKAWA Hanaka MIMURA Hidenobu OKA Yoko EJIRI Masaya HOSODA Kan CHIBA

出版者

日本薬物動態学会 会長/日本薬物動態学会 DMPK編集委員長

雑誌

Drug Metabolism and Pharmacokinetics (ISSN:13474367)

巻号頁・発行日

vol.28, no.3, pp.265-268, 2013 (Released:2013-06-25)

参考文献数

18

被引用文献数

14

---

Treatment with benzbromarone (BBR), a potent uricosuric drug, can be associated with liver injury. Recently, we reported that culture of human hepatocellular carcinoma FLC-4 cells on micro-space cell culture plates could increase the functional expression of drug-metabolizing enzymes including CYP3A4 and CYP2C9, which are involved in 1′-hydroxylation and 6-hydroxylation of BBR, respectively. Therefore, we examined whether BBR and its two metabolites (1′-hydroxy BBR and 6-hydroxy BBR) have cytotoxic effects in FLC4 cells cultured on micro-space cell culture plates. The present study showed that BBR and 1′-hydroxy BBR, but not 6-hydroxy BBR, have cytotoxic effects in cells cultured on micro-space cell culture plates. BBR-induced cytotoxicity was decreased by CYP3A inhibitors (itraconazole and ketoconazole), an Nrf2 activator (tert-butylhydroquinone) and a GSH precursor (N-acetyl-L-cystein). In contrast, BBR-induced cytotoxicity was increased by a GSH biosynthesis inhibitor (buthionine sulfoximine) and an inhibitor of NAD(P)H quinone oxidoreductase 1 (dicoumarol). These results suggested that metabolic activation of 1′-hydroxy BBR via CYP3A, formation of quinone metabolites and the decrease in GSH levels were involved in the BBR-induced cytotoxicity observed in FLC4 cells cultured on micro-space cell culture plates.

著者

Yasuhiro ITO Mitsuhiro FUKUSHIMA Chisato TOMODA Hiroyuki INOUE Minoru KIHARA Takuya HIGASHIYAMA Takashi URUNO Yuuki TAKAMURA Akihiro MIYA Kaoru KOBAYASHI Fumio MATSUZUKA Akira MIYAUCHI

出版者

(社)日本内分泌学会

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

vol.56, no.6, pp.759-766, 2009 (Released:2009-09-25)

参考文献数

15

被引用文献数

55 108

---

Lymph node metastasis is an important clinicopathological feature of papillary thyroid carcinoma (PTC). PTC having clinically apparent lateral node metastasis detectable on preoperative imaging studies (N1b) is known to show a dire prognosis. However, N1b cases include various levels of biological aggressiveness, depending on the size, number, laterality and invasiveness of metastatic nodes. We investigated differences in the prognoses of 621 N1b patients based on these features and compared their prognoses with those of 4297 patients without clinically apparent metastasis (N0) and 125 patients with clinically apparent central node metastasis only (N1a). Disease-free survival (DFS) and cause-specific survival (CSS) of N1b or N1a patients were significantly worse than those of N0 patients, but the prognosis of N1b patients did not differ from that of N1a patients. In the subset of N1b patients, metastatic nodes larger than 3cm, extranodal extension, or 5 or more clinically apparent metastatic nodes independently affected DFS and a combination of the former two features also showed an effect on CSS on multivariate analysis. Prognosis of N1b patients who had none of these features did not differ from that of N1a patients. It is therefore suggested that N1b patients having metastasis larger than 3cm, those showing extranodal extension, and those having 5 or more clinically apparent metastasis should regarded as high-risk, and that careful surgical treatment and postoperative follow-up are necessary.

著者

Yasuhiro Ito Takumi Kudo Minoru Kihara Yuuki Takamura Kaoru Kobayashi Akihiro Miya Akira Miyauchi

出版者

(社)日本内分泌学会

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

vol.59, no.2, pp.119-125, 2012 (Released:2012-02-29)

参考文献数

13

被引用文献数

10 44

---

It is well-known that papillary thyroid carcinoma (PTC) has a generally indolent character and shows a favorable prognosis unless it has no high-risk features such as clinical lymph node metastasis, distant metastasis, and significant extrathyroid extension. In this study, we investigated the prognosis of 3,965 patients with PTC without these features. We classified these patients into 3 groups: T-1, tumor ≤ 2 cm (n = 2,591); T-2, tumor 2.1-4 cm (n = 1,123); T-3, tumor > 4 cm (n = 251). Ten-year recurrence rates of T-1, T-2, and T-3 patients were 0.3, 1.3, and 1.9% for the thyroid (in the subset of patients who underwent limited thyroidectomy), 1.9, 4.6, and 8.1% for lymph nodes, and 0.4, 1.6, and 3.4% for distant organs, respectively. A tumor size larger than 2 cm had an independent prognostic impact on all these recurrences also on multivariate analysis. These findings suggest that PTC larger than 2 cm exhibited more aggressive biological characteristics than that measuring 2 cm or less, even though it had no other high-risk features. However, the incidences of distant recurrence and carcinoma death were still low and it remains unclear whether extensive surgery is mandatory for otherwise low-risk PTC patients with large tumor.

著者

Kaoru KOBAYASHI Akane YOSHIDA Yoko EJIRI Sachiko TAKAGI Hanaka MIMURA Masaya HOSODA Tomokazu MATSUURA Kan CHIBA

出版者

日本薬物動態学会 会長/日本薬物動態学会 DMPK編集委員長

雑誌

Drug Metabolism and Pharmacokinetics (ISSN:13474367)

巻号頁・発行日

vol.27, no.5, pp.478-485, 2012 (Released:2012-10-26)

参考文献数

21

被引用文献数

18

---

Human hepatocellular carcinoma cell lines cultured in a monolayer show negligible activities of drug-metabolizing enzymes such as cytochrome P450s (CYPs) and UDP-glucuronosyltransferases (UGTs). Here, we show that culture of human hepatocellular carcinoma FLC-4 cells on 24-well plates arrayed with uniform micro-sized compartments on the bottom of the plates (micro-space cell culture plates) resulted in increased expression of drug-metabolizing enzymes (CYP1A2, CYP2C9, CYP3A4, UGT1A1, etc.) and nuclear receptors (pregnane X receptor, constitutive androstane receptor, etc.). When cells were treated with a typical CYP3A substrate (triazolam), CYP2C9 substrate (diclofenac) or UGT1A1 substrate (SN-38), large amounts of their metabolites were detected in the medium of cells cultured on micro-space cell culture plates. The formation of metabolites from triazolam, diclofenac and SN-38 was strongly inhibited by co-treatment with a CYP3A inhibitor (ketoconazole), CYP2C9 inhibitor (sulfaphenazole) and UGT1A1 inhibitor (ketoconazole), respectively. On the other hand, formation of metabolites was not observed in the medium of cells cultured in a monolayer. Finally, the cytotoxic effect of aflatoxin B1 was more potent in cells cultured on micro-space cell culture plates than in cells cultured in a monolayer. The results suggest that FLC-4 cells cultured on micro-space cell culture plates are useful for studying drug metabolism and drug-induced hepatotoxicity.