Eriko Takatori

Phase II clinical study of the combination chemotherapy regimen of irinotecan plus oral etoposide for the treatment of recurrent ovarian cancer (Tohoku Gynecologic Cancer Unit 101 Group Study).

Objective: To evaluate the efficacy and safety of the combination chemotherapy regimen of irinotecan plus oral etoposide for the treatment of patients with recurrent ovarian cancer after previous treatment with platinum and taxane agents. Patients and Methods: A total of 42 patients with recurrent ovarian cancer who had an evaluable lesion and provided informed consent for participation in the present study were analyzed. Irinotecan was administered intravenously at a dose of 60 mg/m2 on days 1 and 15. Etoposide was administered orally at a daily dose of 50 mg/body weight from days 1 to 21. A 28-day period comprised one cycle. The tumor response, adverse events, progression-free survival, and overall survival were examined. Tumor response was evaluated based on the Response Evaluation Criteria in Solid Tumors and the serum CA125 levels (Gynecologic Cancer Intergroup criteria). Adverse events were assessed according to the NCI-CTCAE (version 3.0). Results: Partial response was observed in 21 patients, stable disease in 14 patients, and progressive disease in 7 patients. The response rate was 50.0%, and the clinical benefit (partial response + stable disease) rate was 83.3%. Hematological toxicities of at least grade 3 severity included leukopenia in 21 patients (50.0%), neutropenia in 22 patients (52.4%), thrombocytopenia in 1 patient (2.4%), anemia in 9 patients (21.4%), and febrile neutropenia in 3 patients (7.1%). Nonhematological toxicities of at least grade 3 severity included queasy feeling in 5 patients (11.9%), vomiting in 3 patients (7.1%), and diarrhea in 2 patients (4.8%). Acute myeloid leukemia occurred in one patient (2.4%). Conclusions: It is suggested that combination chemotherapy with irinotecan plus oral etoposide offers significant clinical benefit to patients with recurrent ovarian cancer previously treated with platinum and taxane agents.

Tako-Tsubo Cardiomyopathy Caused Immediately following Cesarean Section Delivery of Triplets: A Case Report

The name ‘tako-tsubo’ cardiomyopathy was initially used to describe a unique ‘short-neck round-flask’-shaped form of left ventricular apical ballooning, resembling a Japanese tako-tsubo, a jar (tsubo) used for capturing octopus (tako). Tako-tsubo cardiomyopathy exhibits acute onset, transient left ventricular apical wall motion abnormalities with chest symptoms and minimal myocardial enzymatic release, mimicking acute myocardial infarction in patients without angiographic stenosis on coronary angiography. There have been few case reports on tako-tsubo cardiomyopathy, and this disorder is especially rare in pregnant women. A 30-year-old woman who was pregnant with triplets, and had been treated with ritodrine hydrochloride for 12 weeks for threatened premature delivery, underwent cesarean section with spinal anesthesia at 30 weeks’ gestation. Three hours later, she complained of acute chest pain, dyspnea and episodes of unconsciousness. She was transferred to the intensive care unit and intubated for ventilatory support. We diagnosed heart failure due to tako-tsubo cardiomyopathy based on heart ultrasonography, blood tests, chest X-ray, electrocardiogram and myocardial scintigraphy. She was extubated from the ventilator after 3 days of catecholamine, furosemide and carperitide administration. She was discharged from the hospital on day 53 without symptoms.

Case of peptide‐YY‐producing strumal carcinoid of the ovary: A case report and review

Ovarian carcinoid is a rare tumor accounting for approximately 0.1% of all ovarian malignancies. We describe a case of peptide‐YY‐producing strumal carcinoid of the ovary associated with severe constipation. A 48‐year‐old woman was found to have a pelvic mass on ultrasonography when she visited her primary doctor for a health check‐up. She was thus referred to our department. Magnetic resonance imaging revealed a solid right ovarian tumor 60 × 50 mm in size. The patient underwent a right adnexectomy and was histopathologically diagnosed as having strumal carcinoid of the ovary. On immunohistochemical examination, the tumor cells were positive for peptide YY. The patients constipation resolved rapidly after surgery. Based on her clinical course, her constipation was considered to have been caused by the strumal carcinoid of the ovary. The clinical course of this case supports the previously recognized correlation between peptide‐YY‐producing ovarian carcinoid and constipation.

Triple simultaneous primary invasive gynecological malignancies: a case report.

Double gynecologic cancer (primary cancers in two organs) is relatively rare. However, triple gynecologic cancer (primary cancers in three organs) is extremely rare. We experienced a case of triple cancer, with primary cervical, endometrial and ovarian cancers, each showing different histopathological features. A 50‐year‐old woman with a preoperative diagnosis of cervical cancer stage Ib1 with a pathological diagnosis of mucinous adenocarcinoma underwent radical hysterectomy. The pathological diagnoses of the extracted masses were endometrioid adenocarcinoma in the uterine corpus and serous adenocarcinoma in the left ovary. Consequently, triple cancer was diagnosed. After the operation, six cycles of a paclitaxel/carboplatin regimen were administered, and no relapse of the cancers has been observed to date. To our knowledge, this is only the second case report in the international literature of concurrent gynecologic triple cancers of epithelial origin; that is, invasive cervical, endometrial and ovarian cancers, each with different histopathological features.

Chemoradiotherapy with irinotecan (CPT-11) for adenoid cystic carcinoma of Bartholin's gland: A case report and review of the literature

► Adenoid cystic carcinoma of Bartholins gland is extremely rare, and only 80 cases have been reported in the international literature. ► We have presented a case in which a favorable outcome was achieved by chemoradiotherapy with CPT-11. ► This is the first report, to our knowledge, on chemoradiotherapy with CPT-11 for adenoid cystic carcinoma of Bartholins gland.

Neoadjuvant Chemotherapy Using Platinum-Based Regimens for Stage Ib2-II Squamous Cell Carcinoma and Non-Squamous Cell Carcinoma of the Cervix

The methods used for treating stage Ib2-IIb cervical cancers, with a bulky mass, differ between Japan and Western countries. In Western countries, concurrent chemoradiation (CCRT) has been recommended as a standard therapy for such tumors based on the results of multiple large-scale randomized trials and meta-analyses (Morris et al., 1999; Rose et al., 1999; Whitney et al., 1999; Pearcey et al., 2002; Eifel et al. 2004; Green et al. 2001; Lukka et al., 2002). In Japan, Korea, Italy and some other countries, the neoadjuvant chemotherapy (NAC) approach has been extensively introduced to clinical practice (Sugiyama et al., 1999). NAC is considered to be clinically significant in 2 respects: it is expected to improve the radicality and safety of surgery by reducing tumor size; and it is expected to exert systemic effects, i.e., effects on lymph node occult micrometastases, etc. A disadvantage of NAC is delayed initiation of the primary treatment, suggesting the necessity of completing NAC as an auxiliary therapy within a short period of time. Therefore, we may find that NAC is valuable if it can exert efficacy rapidly with high platinum dose intensity (DI), assuring that subsequent primary surgical therapy can be performed as soon as possible. At our facility, a platinum-based regimen has been used for NAC in patients with cervical cancer. Herein, we review the efficacy and safety data on NAC for squamous cell carcinoma of the uterine cervix. We previously reported our interim data and now present the results of an ongoing pilot study on the efficacy and safety of NAC for non-squamous cell carcinoma of the uterine cervix.

Are platinum agents, paclitaxel and irinotecan effective for clear cell carcinoma of the ovary? DNA damage detected with γH2AX induced by anticancer agents

ObjectivesDifferences in the incidences and types of DNA damage induced by antitumor agents for clear cell carcinoma (CCC) were determined in 2 ovarian CCC cell lines using γH2AX.Material and methodsThe antitumor activity of anticancer agents, CDDP, CBDCA, PTX and SN-38, was examined using ovarian clear cell carcinoma cultured cell lines (OVISE and RMG-I). After culture, each cell line was treated with each anticancer agent, the cells were collected, fixed, and then reacted with the anti-γH2AX antibody. γH2AX and nuclear DNA were then simultaneously detected by flow cytometry using FITC and propidium iodide, respectively, to determine γH2AX in each cell cycle phase.ResultsAfter administration of CDDP, DNA damage was frequent in S-phase cells, while cell-cycle arrest occurred in the G1 and G2/M phases and γH2AX did not increase in CDDP-resistant cells. Sensitivities to CDDP and CBDCA differed between the two cell lines. The antitumor effect of PTX is induced by G2/M arrest, and combination treatment with CBDCA, inducing DNA damage in G2/M-phase cells, might be effective.ConclusionsThis is the first study in Japan to evaluate the antitumor activity of anticancer agents by focusing on the relationship between the cell cycle and DNA damage using γH2AX as an indicator. The immunocytochemical method used in this study detects γH2AX, which indicates DNA damage even at very low concentrations and with high sensitivity. Therefore, a promising method of easily and rapidly identifying agents potentially effective against CCC.

Effective use of everolimus as salvage chemotherapy for ovarian clear cell carcinoma: a case report

A case study using mammalian target of rapamycin complex 1 in recurrent ovarian clear cell carcinoma (CCC) was recently conducted. We report our experience with a patient suffering from recurrent ovarian CCC who achieved long-term disease control with everolimus administration. The patient was a 53-year-old woman who was diagnosed with recurrent ovarian CCC with dissemination throughout the abdominal cavity. Previously, she had received three chemotherapy regimens, but the disease was progressive and she showed no response to treatment. Therefore, oral everolimus administration (everolimus 10 mg/day on days 1–28, a 28-day period comprised one cycle) was started. She was administered six cycles. The antitumor response was stable disease, and grade 3 anemia was observed. Chemotherapy was then switched to gemcitabine/docetaxel therapy. In the middle of the second cycle, a rapid increase in ascitic fluid and CA125 elevation were observed. Thereafter, the patient received best supportive care and died of the disease. Everolimus may inhibit malignant progression of ovarian CCC.

Clinical significance of atypical glandular cells in the Bethesda system 2001: a comparison with the histopathological diagnosis of surgically resected specimens.

Forty-one patients diagnosed with atypical glangular cells (AGC) underwent surgery, and the histopathological diagnosis results for the resected specimens and the clinical features were analyzed. Out of 41 patients, final pathological diagnosis was endometrial cancer in 13 patients, cervical adenocarcinoma in 8, AIS in 7, CIN3 in 6, others in 2, and no lesions in 5. In comparison with previous reports, malignant or premalignant lesions were detected more frequently in patients with AGC who underwent surgery. We believe that conization or hysterectomy aimed at diagnosis and treatment, as well as endometrial histodiagnosis, should be carried out aggressively in patients with AGC.

Investigation of the clinicopathological features of fallopian tube malignancy.

The present study investigated the clinico-pathological features of fallopian tube malignancy (FTM) and elucidated the biological behavior of this disorder. Data were compiled concerning FTM from 68 patients from 7 institutes. The patients included 60 cases with fallopian tube carcinoma and 8 cases with fallopian tube carcinosarcoma. The clinical stage was stage III or higher in 72% of the cases. A complete response or partial response was achieved in 56 and 10 of the 68 patients with FTM, respectively, indicating a response rate of 97.1%. The median observation period for FTM was 41 months (3 to 126 months). Three of the 19 patients with stage I/II disease (16%) and 31 of the 49 patients with stage III/IV disease (63%) experienced recurrence, with a median progression-free survival of 17.5 months, and a 3-year overall survival of 77.2%. Regarding the site of recurrence, local intraperitoneal recurrence (26.2%) and solitary recurrences in lymph nodes (19.0%) and in the liver (16.7%) were relatively frequent. Secondary debulking surgery (SDS) was performed in 15 patients (44%) out of the 34 recurrent FTMs. Conversely, recurrence was associated with ascites (carcinomatous peritonitis) in 4 of the 34 recurrent patients, but all 4 patients died. The median survival period after recurrence was 28 months: 7.5 and 30 months with and without ascites, respectively (P<0.001). A univariate analysis showed that prognosis was significantly correlated only with whether SDS could be performed. These results suggest that since FTM frequently results in solitary recurrence, aggressive recurrence treatment including SDS could improve prognosis.