Ling-Chui Wong

p73 expression is associated with the cellular radiosensitivity in cervical cancer after radiotherapy.

Apoptosis is one of the causes of cell death in cervical cancer following radiotherapy (S. S. Liu et al., Eur. J. Cancer, 37: 1104–1110, 2001). By studying the gene expression profile with cDNA apoptotic array, the p73 gene was found overexpressed in radiosensitive cervical cancers when compared with radioresistant ones. To investigate the role of the p73 gene in relation to clinical assessment of radiosensitivity in cervical cancer based on the findings of residual tumor cells in cervical biopsies after completion of radiotherapy, we studied the protein expression of p73 in 59 cervical cancers after radiotherapy and 68 normal cervices using immunohistochemistry. The expression of p73 was found to be significantly increased in cancer samples and, more importantly, in those samples sensitive to radiotherapy (P < 0.001). The overexpression of p73 actually predicted a better prognosis in cervical cancer patients (P < 0.001). To investigate the possible involvement of p73 downstream genes, the protein expressions of p21 and Bax were studied. The expression of p21, but not Bax, was found to be positively correlated with the expression of p73 (P = 0.001). Furthermore, the epigenetic regulation of p73 expression via DNA methylation was also investigated in 103 cervical cancers and 124 normals. Hypermethylation of p73 gene was observed in 38.8% of cervical cancers, and it was significantly associated with reduced or absent p73 expression (P < 0.001). Reactivation of p73 expression in two cervical cancer cell lines by demethylation treatment supported the role of methylation in the regulation of p73 expression. Our findings suggested that p73 expression was related to the radiosensitivity of cervical cancer cells and may play an important role in the regulation of cellular radiosensitivity.

Wide local excision (WLE) for vaginal intraepithelial neoplasia (VAIN).

BACKGROUNDnTo assess the use of wide local excision in the treatment of VAIN.nnnMETHODSnA retrospective review on 40 WLE procedures for VAIN.nnnRESULTSnThe mean age was 60 years. Thirty-six (90%) patients had previous treatment for genital tract cancer or pre-cancer. The median duration and blood loss during operation was 45 minutes and 50 mls respectively. Fifteen complications affected 11 patients. Only one of five patients with vaginal cancer was diagnosed prior to WLE. Of the 35 patients treated for VAIN 3, 12 (34%) developed abnormal cytology during follow up three had residual VAIN 3, five had recurrent VAIN 3 and four had invasive cancer diagnosed. The remaining 23 (66%) patients were disease free at a median follow up of 44 months.nnnCONCLUSIONSnAblative therapy for VAIN 3 is unsafe as occult invasive foci can be missed by biopsy. WLE is efficacious in treating high grade VAIN 3. Long term surveillance of the lower genital tract is needed to diagnose metachronous lesions.

4-epidoxorubicin in recurrent cervical cancer

Thirty‐eight patients with histologically proven recurrent cervical cancer were treated with epirubicin, an analogue of anthracycline. There were eight complete responders and ten partial responders. The overall response rate was 47.8%. The survival duration of the responders was significantly longer than that of the nonresponders. The optimal dose of epirubicin has yet to be determined. The dosage of 120 mg/m2 was well tolerated. The role of epirubicin as an adjuvant chemotherapeutic agent in the treatment of cervical cancer was discussed.

Clinical Trial of Bleomycin in the Treatment of Gestational Trophoblastic Disease

Abstract Five patients with gestational trophoblastic disease were treated with intramuscular injections of Bleomycin. Three patients showed complete response. Two needed additional methotrexate. The place of Bleomycin in combination therapy for gestational trophoblastic disease is discussed.

Mitomycin chemotherapeutic pleurodesis to palliate malignant pleural effusions secondary to gynecological cancer

BACKGROUNDnTo assess the efficacy of mitomycin pleurodesis in women with end stage malignant effusion.nnnMETHODSnRetrospective analysis.nnnRESULTSnOf the 13 patients treated six had ovarian, six had endometrial and one had cervical adenocarcinoma. The median time of onset of effusion from diagnosis of primary disease was 12 months (range 1-75). Ten patients were evaluable for response. The median age of the patients was 59 years (range 42 to 74). Ten (77%) of them had repeated thoracocentesis prior to mitomycin pleurodesis. The median duration and volume of drainage was 4 days (range 2-11) and 3.1 liters (range 1.2-10.2) respectively. One of two patients developed a pneumothorax and required the insertion of an additional chest drain. Overall, seven patients (70%) responded - one completely (CR) and six partially (PR), while three did not respond. Four of five patients with ovarian cancer had a partial response, two of four patients with endometrial cancer (one CR and one PR) responded. The only patient with cervical cancer had a partial response. Nine patients (69%) had enough symptomatic improvement to be discharged home. The drug cost of bleomycin 60 units (US

Hyperglycosylated hCG in the management of quiescent and chemorefractory gestational trophoblastic diseases

191), another commonly used agent, was more than twice as expensive as mitomycin 30 mg (US

Hepatic Arteriogram for Gestational Trophoblastic Tumor: Is It Useful?

84).nnnCONCLUSIONSnMitomycin pleurodesis can palliate 70% of patients for at least 1 month. It offers cheap and effective palliation. There is a suggestion that patients quality of life is improved.

Loss of imprinting of the IGF-II and H19 genes in epithelial ovarian cancer.

We read with interest the paper of LA Cole and CY Muller (ref. Gynecol. Oncol. 2010 Jan, 116(1): 3–9, epub. 2009 Oct 12) on the use of hCG-H in the management of quiescent and chemorefractory gestational trophoblastic disease (GTD). The primary author is a very well respected clinical chemist who has contributed much to the field of hCG and its role in gestational trophoblastic neoplasia (GTN). However, we wish to voice our concern over the role of hCG-H in managing GTN, as experience with using this is still very limited and has not been prospectively validated. Moreover, the quality of the clinical data provided in the study is inadequate and, therefore, the conclusions made are unreliable. Crucially, none of us has seen the described clinical Letters to the Editor

Mitochondrial DNA variant 16189T>C is associated with susceptibility to endometrial cancer.

The presence of liver metastasis will be staged as IV in the FIGO 1992 Gestational Trophoblastic Tumor (GTT) staging. This study was to determine the role of hepatic arteriogram (HAG) in the management of GTT. It is a retrospective analysis of 309 patients treated from 1981 to 2001. Patients were restaged according to the FIGO 1992 classification with or without taking into account the HAG result. Outcome measures including mortality, drug resistance and recurrence of disease, as well as treatment with and without the HAG result were compared. Eighty-one (26.2 percent) patients had HAG and 11 (3.6 percent) also had ultrasound (USG) features of liver metastasis. Interval between diagnosis and treatment were significantly different between USG and HAG positive groups (Mann-Whitney U test, P < 0.05). Seventeen (5.5 percent) of the 309 patients died of the disease and 7 (41.2 percent) of them had liver metastasis. Three (27.3 percent) of the 11 patients who had USG features of liver metastasis died of the disease; mortality is significantly higher than those without USG features of metastasis (Chi-square test, P < 0.05). Patients classified as medium to high risk with or without taking HAG as a feature of liver metastasis were associated with higher mortality and recurrent rate (Chi-square test, P < 0.05). On the other hand, the chance of drug resistance was higher in the medium to high risk group after reclassifying all HAG positive patients as negative for liver metastasis (Chi-square test, P < 0.05). HAG evidence of liver metastasis did not correlate with patient mortality. HAG was not an appropriate investigation in the management of GTT.