One-year follow-up of single-visit approach to cervical cancer prevention based on visual inspection with acetic acid wash and immediate cryotherapy in rural Thailand.

The aim is to evaluate 1) the visibility of cervical squamocolumnar junction (SCJ) after cryotherapy treatment and 2) to evaluate the effectiveness of cryotherapy treatment originally performed as part of a safety, acceptability, and feasibility (SAFE) demonstration project evaluating the SAFE of visual inspection with acetic acid (VIA) followed by immediate offer of cryotherapy among those who were tested positive and eligible for treatment. A total of 704 women presented at 1-year follow-up exam during which VIA was performed again by nurses. Six hundred and forty eight (92.0%) women received colposcopy and any kind of biopsy, if indicated, by trained physician colposcopists at a referral hospital. At 1 year, VIA nurses assessed 42 of 648 referred women (6.5%) as abnormal (test positive or suspected cancer). The SCJ was visible to the colposcopists in 91.7% (594/648) of the women. Among 42 women assessed as abnormal by the nurses, colposcopic findings were abnormal in 83.3% (35/42), with one low-grade squamous intraepithelial lesion, two high-grade squamous intraepithelial lesion (HSIL), and one adenocarcinoma confirmed later by biopsy. Among 606 VIA negative women, colposcopy was abnormal in only 23.4% (142/606), with two cases of HSIL confirmed later. Given that the SCJ was visible in the vast majority of women (91.7%) after cryotherapy, VIA could be used to provide follow-up for women previously treated. The disease negative rate after cryotherapy (no human papillomavirus infection, no cervical intraepithelial neoplasia, and no cancer) at 1 year after treatment was 85.5% (554/648).

Flow cytometric analysis of DNA ploidy and S-phase fraction of Stage IIIB cervical carcinoma.

OBJECTIVES: To evaluate the role of flow cytometry-measured DNA ploidy and S-phase fraction as survival prognostic indicators in women with FIGO Stage IIIB squamous cell carcinoma of cervix. METHODS: We retrospectively reviewed the medical and pathological records of women with Stage IIIB squamous cell cervical carcinoma treated between 1993 and 1996. Flow cytometric analysis of DNA ploidy and S-phase fraction was performed by the modified Hedley technique using paraffin-embedded tissue. Survival was calculated using the Kaplan-Meier life-table analysis. RESULTS: Of the 75 cases, 66 were analyzable. Diploid tumors were found in 73%. The mean S-phase fraction was 14% (SD = 5.4). The overall 5-year survival rate was 60%. The survival of patients with aneuploidy tumors was significantly worse than that of the diploid tumors (p = 0.001). The survival of the patients who had S-phase fraction > 12% was significantly worse than those who had S-phase fraction < or =12% (p = 0.04). CONCLUSIONS: In this homogeneous study population, we found that aneuploidy and S-phase fraction >12% correlated with poor survival. Identifying this poor prognostic group would be of benefit in considering additional treatment for a better outcome.

Phase I clinical trial of chemoimmunotherapy in combination with radiotherapy in stage IIIB cervical cancer patients.

To determine the feasibility and toxicity of a chemoimmunotherapy regimen in combination with radiotherapy in stage IIIB cervical cancer patients, cisplatin 10-20 mg/m(2) intravenous (iv) weekly, 5-fluorouracil (5FU) 500 mg/m(2) (24-h infusion) weekly, interferon alpha-2a 3 MU subcutaneously 3 days a week, and 13-cis-retinoic acid 0.5 mg/kg/day orally were given in concurrence with 8-week period of radiotherapy and continued for another 4 weeks after finishing radiotherapy. The dose of cisplatin was escalated from 10 mg/m2 in the first group of three patients (level 1) to 15 mg/m(2) in the second group of three patients (level 2) and to 20 mg/m(2) in the third group of two patients (level 3) if the former groups could tolerate the drugs well. Patients in levels 1 and 2 had tolerable toxicities. Two patients in level 3 experienced grade 4 leukopenia, so chemoimmunotherapy was discontinued after 2 and 3 cycles orderly. After recovery from toxicities, they continued with radiotherapy. In conclusion, cisplatin 15 mg/m2, 5-FU 500 mg/m(2) weekly, interferon alpha-2a 3 MU subcutaneously 3 days a week, and 13-cis-retinoic acid 0.5 mg/kg/day orally in combination with radiotherapy in stage IIIB cervical cancer patients is tolerable. Leukopenia is the dose-limiting toxicity.

Phase II study of high-dose megestrol acetate in platinum-refractory epithelial ovarian cancer.

Our objective was to determine the efficacy of megestrol acetate in the treatment of platinum-refractory epithelial ovarian cancer (EOC), and to evaluate the toxicities and quality of life (QOL) associated with this therapy. Patients with platinum-resistant epithelial ovarian cancer were treated with megestrol acetate (800 mg/day) orally for 28 days and then 400 mg/day for a minimum of 28 days before being assessed ready for evaluation of response to therapy. Patients who demonstrated a complete response (CR), partial response (PR) or stable disease were continued in the study until there was objective evidence of disease progression. All patients who went off study were followed up at regular intervals, every 2 months, to assess overall survival. Thirty-six patients were enrolled. Response was observed in seven of 36 patients (three CR and four PR). The response rate was 19.4% (95% CI 9-36). Four of the responders had the endometrioid cell type, while two were clear cell carcinoma and one was serouscystadenocarcinoma. All three CR patients had the histology of endometrioid carcinoma with the tumors located in the pelvis. Median survival of the study population was 5.8 months. Median survival in the responders was 12 months, while median survival in the non-responders was 5.5 months. Median progression-free survival in the responders was 8.3 months, while median progression-free survival in the non-responders was only 2 months. The majority of patients gained weight and had a fair quality of life score during treatment. The only toxicity observed was alopecia (grade 1) in four patients. We conclude that megestrol acetate has modest but definite activity in patients with platinum-refractory EOC, particularly in a small subset of the endometrioid subtype with limited disease in the pelvis. Only minimal toxicity was observed and the patients had a fair QOL score during the treatment.

Advanced epithelial ovarian carcinoma in Thai women: should we continue to offer second-look laparotomy?

OBJECTIVE: To determine survival among patients with epithelial ovarian carcinoma (EOC) who underwent a second-look laparotomy (SLL) and those refusing the procedure. Also to analyze factor(s) influencing the survival of the patients. METHOD AND MATERIAL: Medical records were reviewed of patients with advanced EOC who were clinically free of disease after primary surgery and platinum-based chemotherapy between January 1, 1992, and December 31, 1998. All of them were offered SLL. Measurement outcomes include patient survival and disease-free survival. RESULTS: There were 50 patients with clinically complete remission after chemotherapy. Sixteen patients underwent SLL, and thirty-four patients refused the procedure (NSLL). Seven patients (43.8%) were reported to have positive SLL. After the median follow-up time of 35 months, 12 patients had died, and 5 patients were lost to follow-up. The median survival time for patients with SLL was about 60 months. Five-year survival rates of patients in the SLL, and NSLL groups were 37 per cent (95%CI = 7%-69%), and 88 per cent (95%CI = 65%-96%) respectively (P<0.001). The median time to relapse was about 25 months for patients with negative SLL. Five-year disease-free survival rates of patients in the negative SLL, and NSLL groups were 28 per cent (95%CI = 4%-59%), and 54 per cent (95%CI = 34%-70%) respectively (P=0.251). By Cox regression analysis, tumor grade was the only significant prognostic factor influencing patients' survival (HR = 6, 95%CI of HR = 1.2-34.2). CONCLUSION: The second-look laparotomy doesn't have a favorable impact on overall and disease-free survival. Tumor grade is the only independent prognostic variable for survival of the patients.

The efficacy of chemically-stabilized chlorite-matrix (TCDO) in the management of late postradiation cystitis.

Carcinoma of the uterine cervix is the most common cancer of women in Thailand. The most frequent complication after pelvic radiation for uterine cancer is radiation cystitis. The management of severe late postradiation cystis is far from satisfactory. The objective of this study was to evaluate the efficacy of chemically-stabilized chlorite-matrix (TCDO) in patients with severe radiation cystitis. This study was conducted at the Department of Obstetrics and Gynecology, Ramathibodi Hospital and the Department of Radiology, Siriraj Hospital between September 1997 and September 1998. Twenty patients with grade 3 radiation cystitis after radiotherapy were enrolled into this study. TCDO was administered at a dose of 0.5 ml/kg body weight per day on 5 consecutive days as intravenous infusion over 4 hours. The response rate after the first cycle was 80 per cent with 30 per cent of the patients showing complete response. The follow-up time (13 patients) ranging from 1-9 months revealed no recurrent bleeding. There were no side effects from TCDO therapy. The result suggests good efficacy of TCDO in the treatment of postradiation cystitis.

Recent management of malignant ovarian germ cell tumors: a study of 34 cases.

OBJECTIVE: To review the outcome of the treatment in patients with malignant ovarian Germ cell tumors with respect to survival and surgical management at a single institution during 1990-1996. METHODS: Thirty-four patients with malignant ovarian Germ cell tumors were studied retrospectively for their surgical management. Fourteen patients had pure dysgerminoma, 11 endodermal sinus tumor, 6 immature teratoma, and 3 mixed Germ cell tumors. Nine patients had stage IA, 8 stage IC, 2 stage IIC, 8 stage III, 3 stage IV, and 4 referred patients with recurrent diseases. RESULTS: Nineteen patients underwent primary conservative surgery, 11 had primary nonconservative surgery. Twenty-two patients were treated with chemotherapy (BEP or EP or PVB regimen). Five patients with pure dysgerminoma received adjuvant radiotherapy. Persistent remission was achieved in 26 patients. Two patients (7.4%) had recurrence after remission. Seven patients had died of the diseases. Patients with complete clinical remission did not undergo second-look surgery. The overall survival was 78.8%, 100% for immature teratoma, 84.6% for pure dysgerminoma, 72.8% for endodermal sinus tumor, and 33.3% for mixed Germ cell tumors, with median follow-up time 31 (3-93) months. CONCLUSION: Patients with limited diseases regardless of histologic types can be safely managed by unilateral salpingo-oophorectomy followed by, if indicated, 3-4 courses of cisplatin-based chemotherapy. For advanced diseases, conservative surgery is advisable in patients with endodermal sinus tumor.

Epithelial ovarian cancer treated by platinum or platinum analogue with cyclophosphamide: experience in Ramathibodi Hospital.

This study presented the outcome of 92 EOC patients treated by platinum or platinum analogue with cyclophosphamide from January 1, 1993 to December 31, 1995. There were 77 evaluable patients. The follow-up ranged from 4-42 months (median 14 months). The over all 3-year survival was 64 per cent and the median progression-free interval was 16 months for the whole group. There was no significant difference in survival between patients who received cisplatin and those who received carboplatin (P = 0.093). Patients who underwent optimal debulking surgery had significantly longer progression-free interval (P = 0.001) than those who had sub-optimal surgery. Fifty four per cent of patients with clear cell carcinoma died of the disease. Patients who received cisplatin had a drop out rate while on therapy more often (24% vs 5.3%) than that of carboplatin. Toxicities from chemotherapy were moderate but manageable.

A randomized study comparing suture with non-suture cold-knife conization.

OBJECTIVE: To compare the short-term outcome of cold-knife conization between suture and non-suture (with Monsel's solution pack) methods. METHODS: Between February, 1990 and March, 1992, 142 patients underwent cold-knife conization were randomly allocated into 2 groups. The hemostasis was done by suture in one group and by Monsel's solution pack without suture in the other group. The patients' and cone specimens' characteristics as well as short-term outcome were recorded and compared using Chi-square test, Fisher exact test and t-test where appropriate. RESULTS: The patients' characteristics, cone size, and histologic diagnosis of both groups were comparable. The non-suture group had shorter operative time (10.69 +/- 7.86 vs. 20.04 +/- 6.99 minutes) and lesser late hemorrhage (2.9 vs. 15.9%) than the suture group (p < 0.05). There was no statistical difference in the operative blood loss. CONCLUSION: The non-suture method of conization should replace the traditional suture method.

Virilization associated with choriocarcinoma.

We demonstrate here two autopsy-proven cases of virilization associated with choriocarcinoma. The first patient was a 27-year-old woman with a 7-year history of metastatic choriocarcinoma who presented with left hemiparesis and virilization. Serum testosterone concentration was 18 nmol/l, free testosterone 471 pmol/l, dehydroepiandrosterone sulphate (DHEA-sulphate) 1.7 mumol/l, sex hormone binding globulin 12.3 nmol/l, estradiol (E2) 1,843 pmol/l, and hCG 1.6 x 10(5) IU/l. The second patient was a 21-year-old virilized woman with metastatic choriocarcinoma who presented in semicomatose state. Limited endocrine investigation revealed serum testosterone 27 nmol/l and hCG 2.7 x 10(5) IU/l. Both patients died despite chemotherapy and radiation therapy. Autopsy findings revealed choriocarcinoma with brain and multiple organ metastasis in both. Pathology of the ovaries of both patients demonstrated hyperplasia of luteinized theca cells and lutein cells. We postulate that an association of virilization and choriocarcinoma resulted from long-standing stimulation of ovary by hCG causing theca cell hyperplasia with subsequent hypertestosteronemia and virilization.

Combined radiotherapy and hysterectomy in the treatment of high risk stage II invasive carcinoma of the uterine cervix.

This is a prospective non-randomized study of 127 patients with stage IIB carcinoma of the cervix treated with irradiation and followed by surgery at Ramathibodi Hospital between 1980 and 1989. The criteria for combined treatment were an enlarged cervical mass of over 5 cm, including a barrel-shaped cervix, inadequate or improper radium insertion due to obliterated cervical os, and endometrial extension. The 5-year survival rate was 84.37%. The incidence of pelvic failure was 10.2% and extrapelvic failure was 6.3%. Those revealing residual disease in hysterectomy specimens had a worse prognosis. The increase in the survival rate in this study as compared to other reports may have been due to the use of higher dosages of irradiation. It is concluded that combined treatment was effective in dealing with poor prognosis groups of carcinoma of the cervix. It improved the pelvic and extrapelvic control as well as the survival rate with acceptable complications.

Prognostic factors associated with recurrence in stage IB cervical carcinoma after radical hysterectomy and pelvic lymphadenectomy.

Radical hysterectomy with pelvic lymphadenectomy is the treatment of choice for stage IB cervical carcinoma. Recurrence of disease usually results in poor prognosis. The prognostic factors associated with recurrence were analyzed in 182 patients with stage IB cervical carcinoma treated with radical hysterectomy with pelvic lymphadenectomy at Department of Obstetrics and Gynaecology, Ramathibodi Hospital from May 1969 to December 1988. Twenty-one patients (11.5%) developed recurrent cervical cancer. Factors which were found to have statistical significance associated with recurrence were positive lymph node, positive surgical margin and cervical lesion size of 3 cm or more. The application of these factors was discussed.

The experience in using whole pelvic irradiation in management of massive bleeding from carcinoma of the uterine cervix.

At the Radiation Therapy Section, Ramathibodi Hospital, from June 1, 1981 to May 31, 1991, there were 35 out of 1,683 new cases of carcinoma of the uterine cervix which presented with massive bleeding per vagina. All were treated via cobalt-60 teletherapy covering the whole pelvic region by 12 x 12 cm2 or 16 x 16 cm2 field sizes. Eighteen cases received a radiation dose of 300 cGy/fraction while 16 cases received 400 cGy and one case received 600 cGy. All had bleeding controlled within 2-6 fractions, twenty-two cases (62.9%) within 3 fractions and 34 cases (97.1%) within 5 fractions. There was no severe acute complication in all patients. In 10 patients who were followed up to the range of 3-70 months, median 16.5 showed no severe late complications.

Results of treatment in stage IIB squamous cell carcinoma of the uterine cervix: comparison between two and one intracavitary insertion.

To compare the results of treatment in stage IIB squamous cell carcinoma of the uterine cervix of two treatment regimens, two radium insertions vs one insertion, a prospective randomized study was carried out at Ramathibodi Hospital from 1 January 1983 to 31 December 1986, and the results were evaluated at the end of March 1991. The patients in treatment I (90 cases) received 40-41.4 Gy whole pelvic external irradiation and two intracavitary radium insertions, while patients in treatment II (53 cases) received 50.0-50.4 Gy and one intracavitary insertion. Both groups received the same total dose at point A, about 85-90 Gy. At 4 and 5 years, by the Kaplan-Meier survival curve, the disease-free survivals were 76 and 76% vs 79 and 79%, respectively, in treatment I and treatment II, which showed no significant difference by the log-rank test. Both groups had comparable serious complication rates, 0% vs 1.9%, respectively. However, grade I complications in treatment II, 35.8%, were higher than those in treatment I, 17.8% (P less than 0.01). Therefore, we concluded that treatment II provided the same disease-free survival and a very low rate of serious complications. To replace treatment I, the dose at the rectum and urinary bladder should be maintained with caution.

Uterine sarcomas at Ramathibodi Hospital (1969-1986).

Uterine sarcoma is a rare gynecological malignancy. This retrospective study covered a period of 18 years and during that time 15 cases of uterine sarcoma were treated in Ramathibodi Hospital. It represented an incidence of 6 per 10,000 gynecological admissions. There were 9 leiomyosarcomas, 3 endometrial stromal sarcomas, 2 mixed mullerian sarcomas, and one rhabdomyosarcoma. The average age of the patients was 45.67 years, 3 under 40 and five after menopause. The mean parity was 4. The most common presenting symptoms were vaginal bleeding and abdominal mass. The diagnostic curettage was positive in only 2 out of 7 cases. All were treated by hysterectomy and bilateral salpingo-oophorectomy. Two out of 4 cases who received adjuvant radiotherapy or chemotherapy were still-alive at 1 and 3 year follow-up. The crude survival rate was 40 per cent.

Pattern of treatment failure among patients who died of invasive carcinoma of the uterine cervix.

During January 1979 to December 1982, 78 cases of invasive carcinoma of the uterine cervix (stage IB-IV) whose causes of death were established have been reviewed. The major causes of death were either pelvic failure, extrapelvic failure and the combination of both pelvic and extrapelvic failure, which were 47.5, 32.0 and 17.9 per cent respectively. Most of the patients died within 3 years after the established diagnosis of residual or recurrence or metastases of disease, more than half were dead within 12 months. To improve survival rate of the patients, ways must be found to overcome pelvic as well as extrapelvic failures.

Cervical cancer survival at Ramathibodi Hospital 1979-1983.

Carcinoma of the cervix is the most common malignant neoplasm among the female population. The treatment is surgery for stage IB and radiotherapy for all stages of disease. In a developing country like Thailand, the percentage of lost to follow-up after complete treatment is usually high. The purpose of this study is to present the follow-up and survival rate of patients with carcinoma of the cervix at Ramathibodi Hospital. From 1979 to 1983 there were 323 patients with carcinoma of the cervix who had been treated at Ramathibodi Hospital. The majority of patients (51.9%) were in stage II. The 5-year follow-up rate was 87.73 per cent which is better than the previous reports from Thailand. The 5-year survival rate was 93.75 per cent for stage I, 63.12 per cent for stage II and 42.22 per cent for stage III with an overall survival rate of 61.65 per cent. The 5-year survival rate in this study is not different from other reports.

Combined radiotherapy and hysterectomy in the treatment of high risk stage II invasive carcinoma of the uterine cervix: a preliminary report.

From January 1979 to December 1983, 187 cases of stage II, invasive carcinoma of the uterine cervix were studied prospectively to evaluate survival rate and treatment sequelae. Forty-one cases with any of these conditions; (a) partial response or inadequate radium insertion from obliterated cervical os; (b) endometrial extension; (c) enlarged cervical mass over 5 cm or barrel-shaped; and (d) with pelvic mass, were treated by the combination of radiotherapy and simple abdominal hysterectomy with bilateral salpingoophorectomy (group I), while the rest of 146 cases (group II) were treated by definitive radiotherapy alone. The 5-year follow-up rates were 87.8 per cent in group I and 70.6 per cent group II, respectively. The recurrence free survival rates at 5 years were 80.6 per cent in group I and 63.1 per cent in group II. The immediate and late sequelae were the same in both groups. We concluded that combined treatment was more effective than radiation alone in cases with a poorer prognosis.

The risk factors in the development of persistent trophoblastic disease following hydatidiform mole.

Hydatidiform mole (HM) is not uncommon in our country. Its dangerous sequalae is the fatal persistent trophoblastic disease (PTD). The prognostic risk factors for the development of PTD were analyzed in 108 cases of HM treated in Ramathibodi Hospital from 1978 to 1986. Statistical univariate analysis was by calculation of relative risk (RR) and chi-square test. The incidence of PTD was 27.8 per cent. The significant risk factors were the presence of theca-lutein cyst, gestational age of less than 16 weeks, "large for date" uterus, and patients' age of 40 years or more. Their RR were 4.25, 3.11, 3.00 and 2.68 respectively. These findings were comparable with previous reports. The use of prophylactic chemotherapy in patients with these risk factors was suggested.