Management of squamous cell vulvar cancer: a review.

Squamous cell vulvar cancer is a rare gynecologic malignancy. Standard treatment for early stage disease consists of wide radical excision of the primary tumor with inguinal-femoral lymphadenectomy or sentinel lymph node mapping/biopsy. Because of the general paucity of patients with advanced vulvar cancer, there is no standard therapy for advanced disease and therefore treatment should be individualized. Intergroup trials are needed to clarify the value of chemoradiation, neoadjuvant chemotherapy and targeted therapy in patients with advanced squamous cell cancer of the vulva to identify modalities with the best therapeutic index and lowest morbidity.

Chemotherapy of vulvar cancer: a review.

Squamous cell carcinoma of the vulva is a rare disease with good prognosis if diagnosed early. The standard primary therapy is surgery. Neoadjuvant radiation or chemotherapy has been used to achieve resectability of the tumor and to decrease the radicality of the surgery. Chemotherapy with platinum compounds, paclitaxel and targeted therapy (erlotinib) has shown activity. International collaborative trials are needed to identify the best therapeutic strategy for patients with squamous cell cancer of the vulva who are not candidates for primary surgery or concomitant chemoradiation. We review the various treatment options available to patients with advanced or recurrent squamous cell cancer of the vulva.

Platinum-based combination chemotherapy for the treatment of advanced-stage squamous cell carcinoma of the vulva.

BACKGROUND: Chemoradiation is an alternative to radical vulvectomy with en bloc node dissection for advanced vulvar cancer. We report a case of complete clinical and pathologic response with chemotherapy alone in a patient with advanced vulvar cancer. CASE: A middle-aged woman known to have had human immunodeficiency virus (HIV) for 10 years was newly diagnosed with advanced-stage squamous carcinoma of the vulva. She was treated with a total of nine cycles of platinum-based combination chemotherapy, with complete clinical and pathologic response. She remains in complete clinical remission without evidence of recurrent disease by noninvasive testing in the absence of any further therapy 24 months after her last chemotherapy treatment. CONCLUSION: Platinum-based combination chemotherapy may be used successfully for patients with advanced-stage squamous carcinoma of the vulva.

Merkel cell carcinoma in a patient with noninvasive vulvar Paget's disease.

We present the first case of inguinal Merkel cell carcinoma of unknown primary origin in a patient with vulvar Paget's disease. Correlation with immune suppression of both entities warrants further investigation. Additionally, this case highlights the value of ultrasound scanning in the detection of inguinal metastasis.

Stage III uterine carcinosarcoma: 2009 International Federation of Gynecology and Obstetrics Staging System and Prognostic Determinants.

OBJECTIVES: (1) To determine the significance of positive peritoneal cytology and pelvic versus para-aortic lymph node involvement in uterine carcinosarcoma. (2) To evaluate the impact of isolated retroperitoneal lymph node involvement (IIIC-N) versus retroperitoneal lymph node involvement plus other evidence of extrauterine disease spread (IIIC-N+) on survival in patients with stage IIIC uterine carcinosarcoma. METHODS: Data were extracted from the Surveillance, Epidemiology, and End Results database between 1988 and 2005. Statistical analysis used χ, Kaplan-Meier method, and Cox proportional hazards model. RESULTS: A total of 690 women were identified. When comparing overall survival between patients with disease spread to uterine serosa and/or adnexa and those with positive peritoneal cytology, there was no significant difference (25.4% vs 15.5%, P = 0.2). However, although the 5-year overall survival was comparable between patients with positive pelvic lymph nodes and those with positive para-aortic lymph nodes (22.1% vs 25.4%, P = 1.0), it was significantly worse in stage IIIC-N(+) compared to stage IIIC-N patients (15.0% vs 33.4%, P < 0.001). Only patient's age (P < 0.001), race (P = 0.03), stage (P < 0.03), and lymphadenectomy (P < 0.001) were independent predictors of survival after adjusting for other contributing factors. In addition, the results of unadjusted analysis concerning the survival difference between different stage groups were confirmed on multivariate analysis. CONCLUSIONS: Positive peritoneal cytology is associated with poor prognosis in uterine carcinosarcoma, comparable to current International Federation of Gynecology and Obstetrics stage IIIA classification of disease. Although there does not seem to be a significant survival difference between patients with positive pelvic versus those with para-aortic lymph nodes, the prognosis seems to be much worse in patients with stage IIIC uterine carcinosarcoma with other evidence of extrauterine disease spread, suggesting the need for more aggressive therapy.

Stage IIA1 versus stage IIA2 cervical cancer: does the new staging criteria predict survival?

OBJECTIVE: (1) To determine the correlation of 2008 International Federation of Gynecology and Obstetrics staging system with survival in patients with stage IIA cervical cancer, (2) to elucidate the treatment patterns in stage IIA1 and stage IIA2 cervical cancer, and (3) to investigate whether radical hysterectomy or radiation influenced overall survival. METHODS: Data were extracted from the Surveillance, Epidemiology and End Results database between 1988 and 2005. Statistical analysis used χ test, Kaplan-Meier method, Cox regression, and logistic regression. RESULTS: Of the 560 women, 271 (48.4%) had stage IIA1, and 289 (51.6%) had stage IIA2 cervical cancer. Stage IIA2 patients were younger than stage IIA1 patients (mean age, 49 years vs 54 years; P = 0.01). Stage IIA1, compared with stage IIA2, differed significantly regarding the administration of primary radiation (47.2% vs 64.7%, P < 0.001) and adjuvant radiation (60.5% vs 77.5%, P = 0.006). The following variables were significantly associated with the performance of radical hysterectomy: patient age, 65 years or younger, tumor size, ≤ 2 cm or lesser, high tumor grade, and nonsquamous tumor histology. The incidence of adjuvant radiation after radical hysterectomy was high (48% [tumor size, ≤ 2 cm] to 86% [tumor size, >6 cm]). The 5-year overall survival was not significantly different between stages IIA1 and IIA2 (65.8% vs 59.5%, P = 0.2). Only patient age (P = 0.01), tumor size (P = 0.02), and lymph node status (P = 0.002) were independent predictors of survival. When controlled for other contributing factors, there was no significant difference in survival between patients treated by radical hysterectomy and primary radiation. CONCLUSIONS: The 2008 International Federation of Gynecology and Obstetrics staging criteria is not an independent predictor of survival in stage IIA cervical cancer. Given the equivalent efficacy of radical hysterectomy and radiation, attention should be paid to the high risk of adjuvant radiation in these patients.

Feasibility of extension of platinum-free interval with weekly bolus topotecan and subsequent platinum retreatment outcomes in recurrent ovarian cancer.

PURPOSE: The goal of this study was to evaluate the outcomes and response in a cohort of patients with presumed platinum-sensitive disease who were subsequently retreated with platinum after receiving weekly bolus topotecan at the time of initial recurrence. METHODS: A retrospective review of our institutional databases identified a cohort of platinum-sensitive women with recurrent ovarian and peritoneal carcinoma. Antitumor responses and toxicities were assessed for patients retreated with platinum-based chemotherapy following weekly bolus topotecan (4 mg/m²). RESULTS: Twenty-six patients (median age 63 years, range 45-80 years) were identified. Advanced stage (III/IV) ovarian carcinoma was most common (96%). Residual disease after primary cytoreductive surgery was less than 1 cm in 65% of the cohort. Platinum retreatment was well tolerated. Grade 3 neutropenia occurred most commonly (8%) without any episodes of grade 4 myelotoxicity. Fatigue (12%) and hypersensitivity reaction (15%) were the most common non-hematologic toxicities during platinum retreatment. Of the 26 patients, 5 (19%) had a complete response, 5 (19%) had a partial response, 10 (39%) had stable disease, and 6 (23%) had progressive disease. Thirty-nine percent of patients with stable or progressive disease during weekly bolus topotecan responded to subsequent platinum retreatment. Response to platinum retreatment, treatment-free interval, and platinum-free interval was significant prognosticators for survival (P < 0.05). CONCLUSION(S): The results of this retrospective analysis suggest that weekly bolus topotecan, as intervening non-platinum, may result in acceptable toxicities and response rates during platinum retreatment in platinum-sensitive relapsed ovarian or peritoneal carcinoma.

Life-threatening clostridial sepsis in a postmenopausal patient with degenerating uterine leiomyoma.

Clostridium perfringens is a fulminant infection that affects patients with a high rate of morbidity and mortality. Fortunately, C. perfringens-associated sepsis and death in the gynecologic patient is rarely encountered. We report a case of intrauterine C. perfringens presenting as life-threatening sepsis in a postmenopausal patient.

Racial disparities in survival among patients with germ cell tumors of the ovary--United States.

OBJECTIVE(S): To compare the survival of African American (AA) and white (W) patients with malignant germ cell tumors of the ovary (OGCT). METHODS: Patients with a diagnosis of OGCT were identified from Surveillance, Epidemiology, and End Results Program (SEER) from 1988 to 2004, and were divided into African American (AA) and white (W) subgroups. Only surgically treated patients were included. Histology was grouped into dysgerminoma (D), malignant teratoma (MT), and mixed germ cell tumors with pure non-dysgerminoma cell tumors (MGCT/PNDCT). Statistical analysis using Chi-square, Fisher's Exact Test, Kaplan-Meier survival methods, and Cox regression proportional hazards were performed. RESULTS: In 1110 patients with OGCT, 970 (87.4%) were W and 140 (12.6%) were AA. MGCT/PNDCT histology was equally represented in AA and W. However, W were twice as likely to present with D (W 34% vs. AA 16%, p<0.01) and 1.5 times less likely to present with MT (W 41% vs. AA 59%, p<0.01). The majority (W 64%, AA 64%) of OGCT were stage I. Advanced stage (FIGO III and IV) tumors were more prominent in AA (24% vs. 18%, p>0.05). Complete surgical staging effort was utilized more frequently in W (49%) as compared to AA (38%; p=0.001). Overall 5-year survival was 92% for W and 86% for AA (p=0.02). In multivariate analysis race was not an independent predictor of survival when histology, stage and surgical staging were controlled. CONCLUSION(S): In our study, a higher prevalence of complete surgical staging and a favorable distribution of low risk histologic types may explain the improved survival observed in white patients with OGCT. However, race was not an independent predictor of survival.

Image-guided percutaneous cryotherapy for the management of gynecologic cancer metastases.

OBJECTIVE: To report the clinical response to image-guided percutaneous cryotherapy (IPC) for the palliative management of localized metastases in patients with gynecologic malignancies. METHODS: Institutional review board approval and patient consent were obtained. Gynecologic oncology patients were identified from our institution's cryotherapy database from August 2003 to August 2007. Cryotherapy was performed with 2.4 mm diameter probes (Endocare, Irvine, CA) with ultrasound or computerized tomography (CT) guidance under conscious sedation and local anesthesia. Follow-up was conducted by imaging studies and clinical encounters, using Response Evaluation Criteria in Solid Tumors (RECIST criteria). RESULTS: Twenty-eight ablation sessions were performed for 41 metastatic foci in 15 patients with gynecologic malignancies. Twelve patients had prior chemotherapy and 5 patients had prior radiation. Median follow-up was 317.5 days (range 95-1189). Median post-procedure pain score: 3/10 (range 0-5). Mean initial tumor size was 2.6 cm in maximal diameter. Median reduction in tumor diameter at 1 month was 21.4% (range 2-67.4%), at 3 months was 43.6% (range 16-80.4%), at 6 months was 54.7% (range (16.6-88.9%) and at 9 months was 58.2% (range 32-88.9%). Ten patients received concurrent chemotherapy, 8 had progression of disease at other sites and 2 had stable disease, while the cryotherapy site improved. One of 5 patients who had cryotherapy in the previously irradiated zone had recurrence. A liver capsule hematoma developed as an immediate complication in one patient and an enterocutaneous fistula developed in another. CONCLUSION: IPC is a well-tolerated, effective tool for local control of isolated metastatic foci as a single-modality treatment and for local control of symptomatic metastases in select patients undergoing systemic therapy for the management of gynecologic malignancies.

A population-based analysis of 788 cases of yolk sac tumors: A comparison of males and females.

Yolk sac tumors (YST) are a rare and aggressive germ cell tumor. The objective of this study is to compare the patient characteristics and survival of YST in males and females. Demographic and clinicopathologic information were obtained from the Surveillance, Epidemiology, and End Results Program from 1973 to 2003. Statistical analysis was performed using Independent-sample t-test, chi(2) test, Kaplan-Meier methods and Cox proportional hazards regression. Seven hundred eighty-eight patients were identified, 451 (57%) were males and 337 (43%) were females. The mean age at diagnosis was similar in males and females. The age at diagnosis showed a bimodal distribution with an increased incidence in the first 4 years of life and during the 2nd to 4th decade of life. The most common site of the primary tumor was gonadal, namely testis 336 (42.6%) and ovary 257 (32.6%). Among the extragonadal sites, tumor site of origin differed in males and females. The 5-year survival of extragonadal YST (66%) was worse than gonadal YST (86%) (p < 0.05). The overall median survival for the cohort was 87 months. This was similar in males (81 months) and females (91 months) (p > 0.05). As the year of diagnosis progressed from 1973 to 2003, survival of both males and females with YST consistently improved. The bimodal age distribution of YST generates the hypothesis that sex steroids may play a role in selected YST. Although the overall survival in all YST patients has improved over the past few decades, the primary sites of origin differ in males and females and impact prognosis.

Long-term follow-up of a randomized trial comparing concurrent single agent cisplatin, cisplatin-based combination chemotherapy, or hydroxyurea during pelvic irradiation for locally advanced cervical cancer: a Gynecologic Oncology Group Study.

PURPOSE: We report the long-term survival and toxicity of a randomized phase III study comparing cisplatin alone with cisplatin, flurouracil, and hydroxyurea versus hydroxyurea concurrent with pelvic irradiation for patients with locally advanced cervical cancer with pathologically negative para-aortic nodes. PATIENTS AND METHODS: Comparisons of progression-free (PFS) and overall survival (OS) between treatment arms utilized Kaplan-Meier and log-rank statistics. Relative risk estimates adjusting for prognostic factors were determined using the Cox proportional hazards regression model. Pearson's 2 test was used to assess differences in adverse events. RESULTS: The analysis included 526 patients. The median follow-up among surviving patients was 106 months. Consistent with the original report, improvement in PFS and OS was evident for both cisplatin-containing arms compared with hydroxyurea (P < .001). Analogous results were seen for stage IIB and for stage III disease (each P < .025). The relative risk of progression of disease or death was 0.57 (95% CI, 0.43 to 0.75) with cisplatin and 0.51 (95% CI, 0.38 to 0.67) with cisplatin-based combination chemotherapy compared with hydroxyurea. Among 518 patients who received radiation, acute (grade 3 or 4) gastrointestinal or urologic toxicities occurred in 66 with cisplatin (19.1%) and 29 with hydroxyurea (16.8%). Delayed radiation toxicity occurred in six patients who received cisplatin (1.7%) and two who received hydroxyurea (1.2%; P = .680). CONCLUSION: Cisplatin-based chemotherapy during pelvic radiation therapy improves long-term PFS and OS among locally advanced cervical cancer patients collectively and for stage IIB and III disease, individually. There was no observed increase in late toxicity with cisplatin-based chemoradiotherapy.

Ultrasonography-guided transvaginal endometrial biopsy: a useful technique in patients with cervical stenosis.

BACKGROUND: In patients with failed dilatation and curettage due to stenotic cervix, options for endometrial sampling are limited. We propose the ultrasonography-guided transvaginal endometrial biopsy. CASES: Two postmenopausal women presented with bleeding and failed dilatation and curettage due to a stenotic cervix. Under direct transvaginal ultrasound guidance, a 20-gauge needle was inserted through the vaginal vault and anterior uterine wall into the endometrium. The endometrium was aspirated, and specimen was submitted to cytology. One patient had endometrial adenocarcinoma and underwent a staging procedure. The other patient had a benign cytology and was followed up clinically. CONCLUSION: The ultrasonography-guided endometrial biopsy is a viable option for endometrial sampling in the presence of stenotic cervix.

Hypoxia up-regulates the effects of prostaglandin E2 on tumor angiogenesis in ovarian cancer cells.

OBJECTIVE: Emerging evidence supports a role for prostaglandins (PG) and their synthesizing enzyme, cyclooxygenase (COX), in tumor angiogenesis. The objective of this study was to investigate the effects of prostaglandin E(2) (PGE(2)) on the expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible transcription factor-1 alpha (HIF-1alpha) genes in epithelial ovarian cancer (EOC) cells. METHODS: Two human EOC cell lines, MDAH-2774 and SKOV-3, were treated with exogenous dimethyl prostaglandin E(2) (dmPGE(2)) at two doses of 10 and 50 microg/ml and cultured for 24 h under both normoxic and hypoxic conditions. Total RNA was extracted from EOC cells with the use of a monophasic solution of phenol and GITC/Trizol method. The levels of COX-2, VEGF, and HIF-1alpha mRNA were measured by quantitative reverse transcription PCR (RT-PCR). RESULTS: Under normoxic conditions, treatment of both ovarian cancer cell lines with dmPGE(2) resulted in a significant increase in VEGF expression but had no effect on HIF-1alpha. Culturing the cells under hypoxic conditions resulted in an increase in HIF-1alpha and VEGF mRNAs. The combination of hypoxia and dmPGE(2) treatment resulted in the highest levels of VEGF and HIF-1alpha when compared to either individual treatment. CONCLUSION: PGE(2) is a potent stimulator of VEGF expression in ovarian cancer cells. This effect of PG is further potentiated under hypoxic conditions where it is also associated with a significant increase in HIF-1alpha expression.

Radiation therapy with or without chemotherapy for cervical cancer with periaortic lymph node metastasis.

The purpose of this article is to evaluate the efficacy of chemoradiation therapy (CRT) and radiation therapy (RT) alone for cervical cancer with periaortic nodal metastasis (PANM). Twenty-one patients with cervical cancer with PANM were identified. Eleven patients received concomitant CRT with cisplatin-based chemotherapy and 10 received RT alone. The median age was 44 years. Ten, 5, and 6 patients had International Federation of Gynecology and Obstetrics stages IB, IIB, and IIIB disease. The RT doses to point A and the periaortic region were 80 to 85 Gy (low dose rate equivalent) and 45 Gy. The median follow-up was 26 months (range 3 to 141 months). The 1- and 3-year disease-specific survival were 81.8% and 81.8%, and 70% and 30%, respectively, for the CRT and RT groups, (P = 0.11). The 1- and 3-year pelvic and periaortic control rates (PPC) were 100% and 100% (CRT), and 56.3% and 42.2% (RT) (P = 0.03). The 1- and 3-year free-from-distant metastasis (DM) rates were 81.8% and 81.8% (CRT), and 78.7% and 49.2% (RT) (P = 0.54). All patients who developed DM died of their disease. CRT is a feasible treatment option to improve the PPC for these patients. Because of the high rate of distant metastasis despite PPC, more effective systemic therapy should be explored.

Upper extremity deep vein thrombosis associated with indwelling peripheral venous catheters in gynecology oncology patients.

OBJECTIVE: The goal of this study was to review the clinical presentation, management, and outcome of upper extremity deep vein thrombosis (UEDVT) in women with gynecologic malignancies who had indwelling peripheral venous access catheters. METHODS: From a retrospective review of medical records, we identified 13 patients with various gynecologic malignancies who were diagnosed with UEDVT during their disease course. We obtained tumor data, detailed information regarding the indwelling catheters used, and the diagnosis and management of UEDVT. RESULTS: Two hundred sixty-four women with gynecologic malignancies underwent insertion of an indwelling peripheral catheter by interventional radiology over a 5-year period. A total of 325 catheters were placed in these patients. Thirteen patients developed UEDVTs, and all had a catheter in situ at the time of DVT diagnosis. Eleven of thirteen patients had Peripheral Access System (PAS) Ports and two had peripheral indwelling central catheters (PICCs). The mean age of the patients was 53 years (range, 32-70). At the time of UEDVT diagnosis patients had the following: progressive cancer (n = 8), stable disease (n = 1), no evaluable disease (n = 4), and actively receiving chemotherapy (n = 7). Clinical signs/symptoms at the time of diagnosis included: catheter occlusion (n = 2), arm swelling and pain (n = 10), and superior vena cava syndrome (n = 1). Diagnosis of thrombosis was confirmed using Doppler ultrasound (n = 4), venography (n = 5), and both modalities (n = 4). Management of UEDVT consisted of anticoagulation with warfarin (2-6 months) (n = 9), urokinase infusion (n = 2), intravenous antibiotics for 21 days and heparin for 10 days (n = 1), arm elevation only (n = 1), Lovenox for 60 days (n = 1), and no therapy (n = 1). There were no complications associated with anticoagulation. No patient had a pulmonary embolism. The incidence of UEDVT among our patients with indwelling venous catheters was 5.7%. CONCLUSION: Symptomatic UEDVT is an uncommon complication of indwelling peripheral venous catheters in women with gynecologic malignancies. The risk of pulmonary embolism is low in this patient population.