Naotake Tanaka

Pelvic lymph node metastasis in endometrial cancer with no myometrial invasion

Objective To analyze the incidence of pelvic lymph node metastasis in endometrial carcinoma with no myometrial invasion. Methods Between 1971 and 1995, 684 women with stage I endometrial carcinoma underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, and pelvic lymphadenectomy. The incidence of pelvic lymph node metastases in 100 cases without myometrial invasion was examined. Results Histologic examination of the surgical specimens revealed a single pelvic lymph node metastasis in each of four cases. The incidence of pelvic lymph node metastasis was four of 83 in grade 1, zero of 13 in grade 2, and zero of four in grade 3 tumors. Conclusion Pelvic lymph node metastasis in endometrial cancer with no myometrial invasion is not rare, even with grade 1 tumors. Lymphadenectomies may be necessary in all patients with endometrial cancer, except when clinical or operative factors increase the procedures risk of morbidity.

Placental mesenchymal dysplasia initially diagnosed as partial mole.

Placental mesenchymal dysplasia is a rare condition of pregnancy that presents as macroscopic features of molar change in the placenta and normal karyotype fetus. These cases are often misdiagnosed as partial mole. We report a new case of mesenchymal dysplasia. A 27‐year‐old Japanese primigravida delivered an 820 g female baby (46XX karyotype) without congenital anomalies at 27 weeks gestation due to massive bleeding with placenta previa. The placenta had mimicking partial moles, grape‐like vesicles and normal villi that diffusely occupied the area on the maternal surface of the placenta. Pathologically, enlarged stem villi contained loose, moderately cellular connective tissue with focal cistern‐like formation, and peripherally located vessels. Abnormal trophoblastic proliferation and trophoblastic inclusions were not observed in any of the sections examined. Some villi contained chorioangiomatoid changes. The mother and child were followed up for more than 5 years and showed no sign of trophoblastic disease or Beckwith–Wiedemann syndrome features.

Diagnosis, clinicopathologic features, treatment, and prognosis of small cell carcinoma of the uterine cervix; Kansai Clinical Oncology Group/Intergroup study in Japan

OBJECTIVES This is a multicenter, collaborative study to accumulate cases of small cell carcinoma of the uterine cervix (SmCC), to clarify its clinical and clinicopathologic features and prognosis, and to obtain findings to establish future individualized treatment. METHODS At medical centers participating in the Kansai Clinical Oncology Group/Intergroup, patients diagnosed with SmCC between 1997 and 2007 were enrolled. Clinicopathologic features and prognosis were retrospectively evaluated in patients with SmCC diagnosed at a central pathologic review. RESULTS A total of 71 patients were registered at 25 medical centers in Japan. Of these, 52 patients (73%) were diagnosed with SmCC based on a pathological review. These 52 patients diagnosed with SmCC were analyzed. The median follow-up period was 57 months. The 4-year progression-free survival (PFS) was: IB1, 59%; IB2, 68%; IIB, 13%; and IIIB, 17%. The 4-year overall survival (OS) was: IB1, 63%; IB2, 67%; IIB, 30%; IIIB, 29%; and IVB, 25%. For postoperative adjuvant therapy, postoperative chemotherapy (a platinum drug in all cases) was compared to non-chemotherapy. The 4-year PFS was 65% and 14%, and the 4-year OS was 65% and 29%. PFS was significantly better (p=0.002), and the OS tended to be better (p=0.073) in the group with postoperative chemotherapy. CONCLUSION Even in patients with early stage SmCC, the prognosis is poor. However, in early stage patients, by adding postoperative chemotherapy, the prognosis may improve. Currently, various treatment protocols are used at each medical center, but in the future, a standardized treatment protocol for SmCC will hopefully be established.

Detection of epidermal growth factor receptor mRNA in peripheral blood of cervical cancer patients

OBJECTIVE Epidermal growth factor receptor (EGFR) has been reported to be expressed by immunohistochemistry in invasive cervical cancers. We evaluated the feasibility of detecting EGFR mRNA by EGFR-based reverse transcription polymerase chain reaction (RT-PCR) in peripheral blood of patients with cervical cancer. METHODS Expression of EGFR mRNA, cytokeratin (CK)-19 mRNA, and CK-20 mRNA was examined by RT-PCR in 12 human cervical cancer cell lines. All 12 cell lines expressed both EGFR mRNA and CK-19 mRNA, but only 4 of 12 (33.3%) cell lines expressed CK-20 mRNA. Peripheral blood samples from 20 healthy donors and 45 cervical cancer patients were also examined. RESULTS In peripheral blood from 20 healthy donors, neither EGFR mRNA nor CK-20 mRNA was expressed, but CK-19 mRNA was expressed in 13 of 20 (65%). In contrast, EGFR mRNA was expressed in 12 of 45 (26.7%) patients with cervical cancer (P = 0.0071, 2 test, patient vs control). On the other hand, expression of EGFR was observed in 98% of tumor tissues by immunohistochemistry. CK-19 mRNA and CK-20 mRNA were found in 35 of 45 (77.8%) and 0 of 45 (0%) patients, respectively (NS, chi(2) test, patient vs control). The rate of detection of EGFR mRNA in peripheral blood correlated with FIGO stage (P = 0.049). CONCLUSION Both CK-19 mRNA and CK-20 mRNA showed no diagnostic value as markers of circulating tumor cells in cervical cancers. However, EGFR mRNA in blood might be a useful marker of circulating tumor cells in cervical cancers.

Salvage combination chemotherapy with 5-fluorouracil and actinomycin D for patients with refractory, high-risk gestational trophoblastic tumors.

The objective of this study was to evaluate the efficacy and toxicity of a high‐dose 5‐fluorouracil and actinomycin D regimen (the FA regimen) as salvage chemotherapy for patients with high‐risk gestational trophoblastic tumors (GTTs).

Cytokeratin fragment 21-1 in gynecologic malignancy : comparison with cancer antigen 125 and squamous cell carcinoma-related antigen

We measured serum cytokeratin fragment 21-1 (CYFRA 21-1) levels by a solid-phase immunoradiometric assay in 102 healthy Japanese women, and set the reference value at 1.9 ng/ml (mean +2 SD of the serum levels based on a linear distribution). Pretreatment serum CYFRA 21-1 levels were also analyzed in 235 women with benign (n = 94) or malignant (n = 141) gynecologic disease, and were compared with the serum levels of CA 125 and SCC. The respective positivity rates for CYFRA 21-1 and CA 125 were 64.0 and 77.2% in ovarian malignancy, while they were 4.2 and 30.8% in benign ovarian masses. CYFRA 21-1 had an accuracy of 61.3% in diagnosing ovarian malignancy, which was higher than that of CA 125 (53.4%). The positive predictive value of CYFRA 21-1 for ovarian malignancy reached 94.1%, which was significantly (p < 0.005) higher than that of CA 125 (68.8%). These findings indicate the potential usefulness of CYFRA 21-1 as a tumor marker for ovarian malignancy. In addition, the positivity rates fo CYFRA 21-1 in cervical cancer (51.2%) and endometrial cancer (52.2%) were also similar to the respective rates for SCC and CA 125, which suggests that CYFRA 21-1 seems to be a general tumor marker for gynecologic malignancy.

Risk of abnormal pregnancy completing chemotherapy for gestational trophoblastic tumor

Abstract Objective This study analyzed the outcome of the first pregnancy following chemotherapy for gestational trophoblastic tumor (GTT). Methods A total of 387 patients with GTT (85 patients with high-risk GTT and 302 patients with low-risk GTT) underwent chemotherapy at Chiba University Hospital between 1974 and 2000. Of these patients, 130 women (18 with high-risk GTT and 112 with low-risk GTT), who achieved remission and had at least one conception following chemotherapy, were included in the study. Results The outcomes of all the first subsequent pregnancies in women treated with methotrexate, actinomycin-D, or etoposide (including those switched to other regimens), or combination therapy, were comparable to those in the Japanese general population. However, the incidence of abnormal pregnancies (spontaneous abortion, still birth, repeat mole) was significantly higher in women who conceived within 6 months of completing chemotherapy (4/15; 40%) than in those who conceived after the recommended waiting period of more than 12 months (10/95; 10.5%) ( P = 0.028). Conclusion Patients with GTT who achieved remission after chemotherapy with methotrexate, actinomycin-D, or etoposide, or combination therapy, may anticipate a normal future reproductive outcome. As pregnancies occurring within 6 months following remission are at risk of abnormalities, a waiting period of at least 6 months after chemotherapy for GTT is suggested.

Clinical Value of Tumor Markers for Early Detection of Recurrence in Patients with Cervical Adenocarcinoma and Adenosquamous Carcinoma

Objective: The clinical value of tumor markers for early detection of recurrence was investigated in 32 patients with cervical adenocarcinoma or adenosquamous carcinoma who had recurrent tumors. Methods: Serum levels of CA 125, CA 19-9, carcinoembryonic antigen (CEA), and squamous cell carcinoma antigen (SCC), in addition to clinical status at the time of recurrence were investigated. Results: Among the 32 patients, 26 had no symptoms at the time of recurrence. In 20 patients, elevated serum levels of tumor markers were the first sign of recurrence. In 21 patients with recurrent adenocarcinoma, the positive rates were 14% (CA 125), 62% (CA 19-9), 29% (CEA), and 5% (SCC). There were 71% of cases positive for CA 19-9 and/or CEA. In 11 patients with recurrent adenosquamous carcinoma, the corresponding positive rates were 37% (CA 125), 46% (CA 19-9), 64% (CEA), and 55% (SCC), with 100% positive for CA 19-9, CEA, and/or SCC. Conclusions: The combination of CA 19-9 and CEA is probably the most promising for detection of recurrent cervical adenocarcinoma. For adenosquamous carcinoma, the additional use of SCC is recommended.

Diagnostic accuracy of intraoperative imprint cytology in ovarian epithelial tumors.

Objective: To evaluate imprint cytology (IC) as the intraoperative pathological consultations for ovarian epithelial tumors (OET). Method: We reviewed ICs obtained from 354 consecutive surgical specimens of OET. Cytological specimens were classified into five categories. Final pathological diagnoses were made according to the WHO classification. We performed logistic regression analysis, calculated the limits among benign, borderline, and malignant lesions, and analyzed the diagnostic accuracy. We also made receiver operating characteristic (ROC) curves regarding IC. Results: The accuracies to differentiate benign and malignant lesions were 87.1 and 83.6%, respectively. In contrast, that of borderline lesions was 30.0%. The areas under ROC curves to diagnose benign, and malignant lesions were 0.888 (P<0.05) and 0.951 (P<0.05), respectively, that meant IC was significantly useful for diagnosis of malignancy. Conclusions: IC applied to OET was proved to be practically useful in establishing an intraoperative diagnosis by ROC curves.

Scalp metastasis of a serous ovarian cancer

Aggressive cytoreductive surgery and cisplatin-containing combination chemotherapy for ovarian cancer have certainly led to longer disease-free survival, while the incidence of distant metastasis is increasing (1,2). We report a case of serous ovarian cancer with FIGO Stage 2C, which suddenly recurred in the scalp without lung metastases and widespread intraperitoneal involvement at 29 months after primary surgery.