Combined chemotherapy regimen of carboplatin and paclitaxel as adjuvant treatment for papillary serous and clear cell endometrial cancer.

OBJECTIVE: Uterine papillary serous carcinoma (UPSC) and uterine clear cell carcinoma (UCCC) are highly aggressive variants of endometrial cancer. The optimal adjuvant regimen for these uterine malignant types has not yet been defined. The objective of this study was to evaluate the efficacy and toxicity of a combined chemotherapy regimen of carboplatin and paclitaxel as adjuvant treatment for patients with UPSC and UCCC variants. METHODS: A retrospective analysis of results of adjuvant chemotherapy that was based on 6 cycles of carboplatin (area under the curve, 5-6) and paclitaxel (175 mg/m2) q3 weeks. RESULTS: Twenty-one patients were eligible for analysis. All patients in this group underwent surgery before chemotherapy, with reported optimal debulking in 90% (n = 19). Fourteen patients (66%) had advanced stage (International Federation of Gynecology and Obstetrics stages III-IV) at the time of diagnosis. Five patients (24%) were treated with pelvic radiotherapy after the chemotherapy regimen. Clinical no-evidence-of-disease status was recorded in 19 patients (90%) at the end of the planned chemotherapy schedule. With a median follow-up of 25 months (8-61 months), 11 patients (58%) had recurrence and all have died of disease. Median progression-free interval was 13 months with a median survival of 27 months. Grade 3 toxicity was recorded in 7 patients (33%). Neutropenia developed in 3 patients (14%), neuropathy in 3 (14%), anaphylaxis in 1 (4.6%), and anemia in 1 (4.6%). Dose reduction was needed in 6 patients (29%), treatment delay in 6 (29%), and treatment cessation in 2 patients (10%). CONCLUSIONS: The regimen of carboplatin and paclitaxel is active in patients with UPSC and UCCC with an acceptable toxicity profile.

Successful carboplatin desensitization in patients with proven carboplatin allergy.

BACKGROUND: Carboplatin is one of the most useful and well tolerated cytotoxic drugs for gynecologic malignancies. Hypersensitivity to carboplatin is not rare among patients receiving multiple recurrent treatments with this drug. The aim of the current study was to offer a safe and convenient carboplatin desensitization strategy to patients with a proven allergic reaction to this drug. METHODS: Patients with an immediate objective allergic reaction to carboplatin were skin tested with the drug. A 6-hour carboplatin desensitization protocol was administered to the patients with a carboplatin-positive skin test on each of the following treatment courses. RESULTS: Twenty-three patients with an allergic reaction to carboplatin and a positive skin test were included in the current study. Twenty patients (86.9%) were desensitized. One patient developed a mild urticarial rash. Nineteen patients tolerated 80 desensitization courses uneventfully. CONCLUSIONS: The data presented a successful desensitization protocol for individuals with a proven allergic reaction to carboplatin. The protocol was safe and convenient and offered an effective therapeutic strategy to patients who required this drug.

A comparison between different postoperative treatment modalities of uterine carcinosarcoma.

OBJECTIVE: Uterine carcinosarcomas are highly aggressive neoplasms with no established effective adjuvant therapy. The aim of the present study was to compare between the outcome in three medical institutions in each of which a different postoperative treatment modality was preferred, namely, chemotherapy in one, whole pelvic irradiation (WPI) in another, and sequential treatment (i.e., chemotherapy followed by WPI) in the third. METHODS: The hospital records of all 49 uterine carcinosarcoma patients diagnosed and operated from 1995 to 2003 in the three institutions were reviewed. Non-parametric test was used to compare the median age between the treatment groups. Survival was calculated using the Kaplan-Meier method and compared by the log-rank test. Cox proportional hazard regression model was used to assess the effect of treatment type on survival after adjustment for stage. RESULTS: Only about half of the patients (51%) had stage I at diagnosis and the majority of the patients (83.7%) had postoperative adjuvant treatment. The overall 5-year survival of the 41 patients that had postoperative treatment was 49.6%. The highest median survival and 5-year survival rate was observed in the sequential treatment group. Controlling for stage, this treatment modality was associated with a significant decrease in mortality of about 80% when compared to postoperative chemotherapy alone, and a non-significant decrease in mortality of about 50% when compared to WPI alone (HR = 0.20; 95% CI 0.04-0.99, P = 0.049 and HR = 0.50; 95% CI 0.1-2.32, P = 0.4, respectively). CONCLUSIONS: The improved outcome in patients who received postoperative sequential treatment seems to indicate that further exploration of this treatment modality is justified.

Uterine sarcomas versus leiomyomas: gray-scale and Doppler sonographic findings.

PURPOSE: The aim of the study was to evaluate the contribution of gray-scale sonography and Doppler flow studies in differentiating between uterine sarcomas of different histologic types and leiomyomas. PATIENTS AND METHODS: The study included 111 patients, divided retrospectively into 2 groups: 98 patients with leiomyomas and 13 with postoperative diagnosis of uterine sarcoma. This latter group was further divided into a group of 6 patients with uterine leiomyosarcoma and 7 with malignant mixed mesodermal tumor. The gray-scale sonograms and Doppler parameters in the 3 groups were compared. RESULTS: The patients with leiomyomas were younger than those with sarcomas (52 years +/- 11 versus 65 years +/- 15, p < 0.05). No differences were noted between the 3 groups regarding gravidity, parity, symptoms upon admission, or findings during physical examination. The sonographic appearances of the leiomyomas were similar to those of the leiomyosarcomas, but in 6/7 cases, they were different from those of the malignant mixed mesodermal tumors. There was a significant difference between the mean resistance index in arterioles of the leiomyomas (0.59 +/- 0.01) and that of the malignant mixed mesodermal tumors (0.41 +/- 0.06) (P < 0.001) but not between those of the leiomyomas and the leiomyosarcomas (0.49 +/- 0.18). CONCLUSIONS: Doppler flow studies may assist in differentiating between leiomyomas and malignant mixed mesodermal tumors but not between leiomyomas and leiomyosarcomas.

Combination of endometrial thickness and time since menopause in predicting endometrial cancer in women with postmenopausal bleeding.

PURPOSE: This study was conducted to assess the combination of endometrial thickness, as measured by transvaginal sonography, and time since menopause, in predicting the presence of endometrial cancer in women with postmenopausal bleeding. METHODS: The study group consisted of 95 women with postmenopausal bleeding who underwent sonographic measurement of endometrial thickness followed by endometrial biopsy. No patient had ever received hormone replacement therapy. RESULTS: The mean endometrial thickness was significantly lower in the absence of endometrial carcinoma (6.9 +/- 4.3 mm) than in its presence (13.5 +/- 7.7 mm) (p < 0.005). The incidence of endometrial carcinoma increased with increases in endometrial thickness and the number of years since menopause. No patient had carcinoma when the endometrium was less than 5 mm thick, but 18.5% did when the thickness exceeded 9 mm. The incidence of cancer was 2.6% in women who had undergone menopause less than 5 years earlier but was 21.4% in women who had undergone menopause more than 15 years prior. Multiple logistic regression analysis showed that time since menopause and endometrial thickness were statistically significant predictors of endometrial carcinoma. CONCLUSIONS: Time since menopause and endometrial thickness together define cutoff points for the diagnostic biopsy of tissue samples for endometrial carcinoma; that is, within a particular time interval, sampling should not be performed if the thickness is below a given value. When using cutoff points of 6 mm of endometrial thickness for women experiencing menopause 5-15 years prior and 5 mm in those going through menopause 15 or more years prior, approximately 60% of invasive procedures may be avoided. In addition, models derived by multiple logistic regression can be used to calculate a patient's risk of cancer based on her age and endometrial thickness.

Inflammatory skin metastases from ovarian carcinoma--a case report and review of the literature.

BACKGROUND: Skin metastases from ovarian carcinoma are rarely reported. Most cases present as cutaneous nodules, generally as periumbilical Sister Joseph's nodules. An uncommon presentation of cutaneous metastases from ovarian epithelial carcinoma is the inflammatory pattern, which mimics herpetiform lesions to the skin. CASE: A 48-year-old patient with refractory ovarian carcinoma, complicated by groin lymph node metastatic disease developed edema, in the form of "Peau d'orange," over the lower abdominal skin, the upper aspects of the lower extremities, and the gluteal skin. Large areas of multiple erythematous vesicular appearance that resembled herpes zoster lesions were noted. Biopsy of the skin lesions revealed ovarian skin metastases. CONCLUSIONS: The diagnosis of ovarian skin metastases is uncommon. It mimics inflammatory viral infection as herpes zoster lesions. Supportive care is needed due to painful presentation.

Age contrasts in clinical characteristics and pattern of care in patients with epithelial ovarian cancer.

OBJECTIVE: The objective of this study was to document and highlight aspects of ovarian cancer treatment that pertain, especially, to elderly women. METHODS: Data were collected retrospectively from all epithelial ovarian cancer patients who were diagnosed in the Gynecologic Oncology Unit at Meir Hospital, Kfar-Saba, Israel, from January 1994 to December 1998. RESULTS: The study group comprised 143 patients (<70 years n = 97, > or =70 years n = 46). Both groups presented with the same distribution of stages. The elderly group had fewer primary debulking surgical interventions (54.3%) than the younger group (84.5%) (P = 0.001)). Age was not a limiting factor in achieving optimal debulking in those patients who did undergo surgery (older 53%, younger 54%). Almost 92% of the younger patients entered a first-line chemotherapy regimen compared to 65.2% of the older patients (P = 0.001). The elderly patients were more likely to receive neoadjuvant chemotherapy (43.3.3% vs 13.4%, P < 0.01) and hematological toxicity was significantly more common (75% vs 36.3%; P = 0.001), although no significant difference was noted between the groups in Grade 3-4 patients (> or =70 years, 62.5% vs <70 years, 45.5%; P = 0.2). The elderly patients were more likely to have dose reductions and treatment delays compared to the younger patients (60% vs 22.4%; P < 0.001, and 46.6% vs 19.1%; P = 0.004, respectively) and they had similar overall response rates (RR) and complete response (80% vs 87.6% and 60% vs 71.9%, respectively). CONCLUSIONS: Older women who present with the same distribution of stages as their younger counterparts are likely to be treated more conservatively than younger ovarian cancer patients. In this study, however, when surgery was performed, the optimal tumor debulking rates were similar in each group. Although high morbidity, most often hematological toxicity, occurs in elderly patients following chemotherapy, the overall RR compared favorably with that of younger patients.

Detection of tumor circulating cells by cytokeratin-20 in the blood of patients with granulosa cell tumors.

OBJECTIVE: Cytokeratins (CKs) are constituents of the intermediate filaments of epithelial cells which are expressed in various combinations, depending on the epithelial type and the degree of differentiation. Using the reverse transcriptase-polymerase chain reaction (RT-PCR) technique, we recently demonstrated that cytokeratin-20 (CK-20), the most recently discovered cytokeratin, is expressed in endometrial carcinoma tumors, in blood, and in lymph nodes with micrometastases of patients treated for endometrial carcinomas. However, CK-20 expression could not be demonstrated in the endometrium of patients with benign diseases, in peripheral blood, in lymph nodes of healthy subjects, or in normal blood cells. The aim of this study was to examine whether CK-20 expression in blood can be used as a biomarker for the detection of the dissemination of malignant cells in patients treated for granulosa cell tumors (GCTs). METHODS: In this study, we used RT-PCR to determine the expression of CK-20 in the following groups: (i) blood of patients (n = 14) treated for GCTs, (ii) GCT samples (n = 4); (iii) lymph nodes (n = 2) of patients treated for GCTs; (iv) blood from subjects with benign sex-cord-stromal tumors (n = 2); (v) normal ovaries of two menstruating women (n = 4); (vi) tumor specimens of epithelial ovarian carcinomas (EOCs) (n = 14); and (vii) blood samples (n = 18) and lymph nodes (n = 11) of healthy women. RESULTS: In Group I, CK-20 was positive in the blood in 86% (12/14) of the patients. In Group II, CK-20 was positive in 100% (4/4) of the GCT samples. In Group III, CK-20 was positive in 100% (2/2) of the lymph nodes examined. In Groups IV and V, CK-20 was negative in 100% (2/2) of the blood samples and in the normal ovarian specimens (4/4) that were examined. In Group VI, CK-20 was positive in 14% (2/14) of nonmucinous EOCs. In Group VII, CK-20 was negative in 100% (18/18) of blood and in (11/11) lymph node specimens (specificity 100%). CONCLUSIONS: These results indicate that RT-PCR of CK-20, because of its high sensitivity and specificity, is a potential biomarker for detecting metastases in blood and in micrometastases in lymph nodes of patients treated for GCTs.

Papillary serous carcinoma of the peritoneum coexisting with or after endometrial carcinoma.

OBJECTIVE: Papillary serous carcinoma of the peritoneum (PSCP) coexisting with, or after, endometrial carcinoma (EC) is an extremely rare condition with no documented patient series. The aim of this investigation was to describe our experience in treating five patients diagnosed with PSCP synchronously with EC and two others who developed PSCP metachronously after EC. METHODS: In this retrospective study, we reviewed and analyzed the clinical and pathological data of seven patients diagnosed and managed over a 10-year period. The diagnosis of PSCP was mostly based on the inclusionary criteria of the Gynecologic Oncology Group [1]. Disease stages were determined using the FIGO criteria for epithelial ovarian cancer (EOC) and endometrial carcinomas [2]. The treatment for PSCP was similar to that for advanced EOC and immunohistochemical studies were performed using archival material for PSCP and EC in order to determine p53, Bcl-2, HER2, and estrogen and progesterone receptor (ER, PR) status. Germline mutation analyses were performed for the two most common mutations pertaining to BRCA1 and the one most common mutation pertaining to BRCA2 genes only. RESULTS: Five patients with PSCP and synchronous EC initially underwent surgical treatment. The remaining two underwent surgery originally for EC and, thereafter, for metachronous PSCP. All seven patients had advanced stages (III or IV) of PSCP and stage I only EC. At the time of analysis, four patients were alive. p53, Bcl-2, ER, and PR were found to have been expressed in various rates in both or one of the neoplasms. However, no HER2 was found to have been expressed, either in PSCP or in EC. All germline mutation analyses were negative. CONCLUSIONS: The results obtained in this study show that PSCP can occur either synchronously or metachronously with lower stage EC that is associated with advanced disease stages. We suggest that this clinical form of PSCP with synchronous or metachronous EC is a very aggressive and lethal clinical form and differs markedly from the vast majority of multiple gynecologic neoplasms of the upper genital canal diagnosed in the ovarian-endometrial group, of which EOC are mostly diagnosed as stage I diseases with high-rate cures.