Successful surgical treatment and chemotherapy for ovarian cancer in a patient with idiopathic thrombocytopenic purpura.

Ovarian clear cell adenocarcinoma (OCCA) is known to have a worse prognosis than ovarian serous adenocarcinoma due to its poor response to conventional platinum-based chemotherapy. Idiopathic thrombocytopenic purpura (ITP), which usually reveals severe thrombocytopenia, is a common autoimmune disorder. However, to date very few cases of ovarian cancer associated with ITP have been reported in the literature. We report a case of a 57-year-old woman who developed OCCA 14 years after the diagnosis of ITP. The patient presented with abdominal distention and mild tenderness. We performed the operation with high-dose immunoglobulin therapy preoperatively, and diagnosed OCCA. Postoperatively, six cycles of cytotoxic chemotherapy with irinotecan hydrochloride plus cisplatin were performed every 4-5 weeks without thrombocytopenia. We conclude that combination chemotherapy with irinotecan hydrochloride plus cisplatin is useful for a case of OCCA associated with ITP.

Combined phospho-Akt and PTEN expressions associated with post-treatment hysterectomy after conservative progestin therapy in complex atypical hyperplasia and stage Ia, G1 adenocarcinoma of the endometrium.

Young patients with complex atypical hyperplasia (CAH) or stage Ia, G1 adenocarcinoma (IaG1) of the endometrium, who desire to preserve fertility, can select the conservative therapy by oral progestin, medroxyprogesterone acetate (MPA). However, conservative treatments involve potential risks of progression and recurrence. In an attempt to find out molecular markers for sensitivity to MPA, we performed immunohistochemical analysis of PTEN, phospho-Akt, p53, ER and PgR in MPA-treated 31 cases with CAH or IaG1. Eleven of 12 cases (92%) with CAH and 15 of 19 cases (79%) with IaG1 demonstrated an initial complete response, while five patients underwent hysterectomy due to no response. Four of 11 responders (36%) with CAH and five of 15 responders (33%) with IaG1 later developed relapse. Five of nine patients (56%) with CAH and three of 11 patients (27%) with IaG1 became pregnant after infertility treatment. Immunohistochemical analysis revealed that phospho-Akt expression was significantly decreased by MPA administration (p=0.002). Furthermore, combination of two factors, weak phosho-Akt or PTEN-null expression, was found to be significantly associated with receiving hysterectomy (p=0.04), while each factor showed a trend without statistical significance (p=0.07 and 0.2, respectively). Strong expression of both ER and PgR significantly correlated with successful pregnancy after infertility treatment following complete response to MPA (p=0.02). Our observations in vivo suggest that anti-tumor action of MPA may be mediated by dephosphorylation of Akt, and that immunohistochemical evaluation of phospho-Akt and PTEN may be able to predict the outcome of MPA therapy.

Cytodiagnostic problems in uterine sarcoma. Analysis according to a novel classification of tumor growth types.

OBJECTIVE: To clarify the cytologic diagnostic problems of uterine sarcomas and the differential properties between pure sarcomas and carcinosarcomas. STUDY DESIGN: Four leiomyosarcomas and 21 carcinosarcomas (homologous and heterologous) treated at the Saitama Cancer Center from 1991 to 2000 were analyzed macroscopically and microscopically. RESULTS: Of 4 leiomyosarcomas, 3 were intramuscular, localized type, with a negative diagnosis for sarcoma. Of 21 carcinosarcomas, 7 were exophytic type with little necrosis (B-1), 5 were exophytic type with marked necrosis (B-2), 6 were exophytic type with a small sarcomatous component (B-3), and 3 were endophytic type (B-4). All endometrial smears were positive for sarcoma in B-1, whereas 5 of 14 (36%) were positive in the latter 3 types (B-2, 3 and 4). CONCLUSION: In pure leiomyosarcomas, the sarcomatous portions are usually covered with normal endometrium. In carcinosarcomas, sarcomatous component is relatively limited in some cases and frequently covered with marked necrosis or carcinomatous tissue. These pathologically specific findings should make cytologic diagnosis difficult in uterine sarcomas.

Safety and immunogenicity of a peptide containing the cross-neutralization epitope of HPV16 L2 administered nasally in healthy volunteers.

Amino acid (aa) 108-120 of L2 protein of human papillomavirus (HPV) type 16 contains a cross-neutralization epitope against genital HPV. We designed a placebo-controlled trial in healthy adults to evaluate the safety and immunogenicity of a synthetic peptide consisting of the aa 108-120 of HPV16 L2 (L2-108/120) region. A total of 13 volunteers were given nasal inoculations with 0.1 (n=5) or 0.5mg (n=5) doses of the peptides or placebo (n=3) without adjuvant at weeks 0, 4, and 12. Sera were collected before inoculation and at 6, 16 and 36 weeks. The inoculation caused no serious local and systemic complications. The inoculation generated anti-L2 antibodies binding to both HPV16 and 52 L1/L2-capsids in four of the five recipients in the 0.5mg group. Sera of the four recipients showed neutralizing activities against HPV16 and 52. Serological responses to the peptides were not found in the 0.1mg group and the placebo group recipients. This study suggests the L2-108/120 peptide is tolerable in humans and has the potential as a broad-spectrum prophylactic vaccine against genital HPV.