Smooth muscle neoplasms of the vulva masquerading as Bartholin gland duct cysts.

Smooth muscle neoplasms of the vulva can be mistaken for Bartholin duct cysts, which can lead to a delay in diagnosis. We present a case of vulvar leiomyoma and a case of leiomyosarcoma that clinically mimicked Bartholin duct cysts. Identification of leiomyosarcomas in this region is particularly important; due to the risk of recurrence, patients may need radiation and/or chemotherapy in addition to adequate surgical treatment and appropriate follow up. Prior series have shown that risk of recurrence is related to inadequate resection and not to the size or grade of tumor. It is critical that pathologists recognize smooth muscle tumors of the vulva and communicate to clinicians the importance of clear margins and wide local excision in cases of malignancy.

Ritonavir-Mediated Induction of Apoptosis in Pancreatic Cancer Occurs via the RB/E2F-1 and AKT Pathways.

Recent observations suggest a lower incidence of malignancies in patients infected with HIV during treatment with Highly Active Anti-Retroviral Therapy (HAART) utilizing protease inhibitors. We investigated the effects of ritonavir, a FDA approved HIV protease inhibitor, on proliferation of pancreatic ductal adeno-carcinoma (PDAC) cell lines. Human PDAC cell lines BxPC-3, MIA PaCa-2, and PANC-1 were propagated under standard conditions and treated with serial dilutions of ritonavir. Ritonavir inhibited cell growth in a dose-dependent manner as well as activated the intrinsic apoptotic pathway in human pancreatic ductal adenocarcinoma (PDAC) cell lines. We observed down-modulation of cell-cycle promoting and up-regulation of cell-cycle inhibitory genes; enhanced interaction of retinoblastoma protein (RB) with E2F-1 transcription factor; inhibition of phosphorylation of RB, resulting in sequestration of E2F-1 and subsequent down-regulation of S phase genes; decreased interaction of E2F-1 with its consensus binding sites; inhibition of cell motility and invasiveness; and inhibition of the AKT pathway. Our results demonstrate a potential use of ritonavir as part of combination chemotherapy for PDAC. Since ritonavir is FDA approved for HIV, drug repositioning for PDAC would limit the costs and reduce risks.

MicroRNA-101 inhibits growth of epithelial ovarian cancer by relieving chromatin-mediated transcriptional repression of p21(waf¹/cip¹).

PURPOSE: MicroRNA-101 (miR-101) expression is negatively associated with tumor growth and proliferation in several solid epithelial cancers. Enhancer of zeste homolog 2 (EzH2) appears to be a functional target of miR-101. We explore the role of miR-101 and its interaction with EzH2 in epithelial ovarian carcinoma (EOC). METHODS: In situ hybridization (ISH) for miR-101 was performed on EOC patient tissues and normal controls. EOC cell lines were transfected with miR-101 and subjected to growth analysis and clonogenic assays. Cell motility was assessed by Boyden chamber and wound-healing assays. P21(waf1/cip1) and EzH2 interaction was assessed by Chromatin Immunoprecipitation (ChIP) assay in MDAH-2774 cells. SCID mice were assessed for tumor burden after injection with miR-101 or control vector-treated MDAH-2774 cells. RESULTS: ISH analysis revealed a decrease in miR-101 expression in EOC compared with normal tissue. MiR-101 re-expression in EOC cell lines resulted in increased apoptosis, decreased cellular proliferation, invasiveness, and reduced growth of tumor xenografts. CHIP assays revealed that re-expression of miR-101 inhibited the interaction of EzH2 with p21(waf1/cip1) promoter. CONCLUSIONS: MiR-101 re-expression appears to have antitumor effects, providing a better understanding of the role of miR-101 in EOC.

Intra-operative detection of nodal metastasis in early stage cervical cancer: a survey of the practice patterns of SGO members.

OBJECTIVES: To determine the practice patterns of members of Society of Gynecologic Oncologists (SGO) in different clinical situations involving the intra-operative detection of nodal metastasis in early stage cervical cancer. METHODS: A study questionnaire was mailed to the current members of SGO (n=874). Data were collected using an internet survey database. Frequency distributions were determined, and non parametric tests were performed. RESULTS: Thirty percent SGO members responded (n=274). Only 38.6% routinely performed an intra-operative frozen section evaluation of the lymph nodes. Of these; most (79%) did not abort the radical hysterectomy (RH) for an isolated microscopically positive pelvic lymph node. The likelihood of aborting RH for microscopic nodal involvement increased however with number of positive pelvic lymph nodes (21% with 1, 40% with 2-3, and 61% with >3 positive pelvic lymph nodes), involvement of para-aortic lymph nodes (61%), or bilaterally positive lymph nodes (54%). Similarly, a large number did not complete the RH due to gross involvement of pelvic (45%) or para-aortic lymph node/s (69%). Most (90%) completed the lymphadenectomy before aborting RH. When completing RH, the majority tailored its extent to perform a less radical resection. Variables significantly associated with the likelihood of completing RH in different clinical situations included: location of current practice (West), practice type (private), years in practice (>15 years), and number of cases seen per year (>10/month). CONCLUSION: Practice patterns of SGO members are considerably diverse, which is reflective of the conflicting evidence available in the literature. Well designed studies are required to determine the best overall approach.

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.

Anticancer activity of a broccoli derivative, sulforaphane, in barrett adenocarcinoma: potential use in chemoprevention and as adjuvant in chemotherapy.

INTRODUCTION: The incidence of Barrett esophageal adenocarcinoma (BEAC) has been increasing at an alarming rate in western countries. In this study, we have evaluated the therapeutic potential of sulforaphane (SFN), an antioxidant derived from broccoli, in BEAC. METHODS: BEAC cells were treated with SFN, alone or in combination with chemotherapeutic, paclitaxel, or telomerase-inhibiting agents (MST-312, GRN163L), and live cell number determined at various time points. The effect on drug resistance/chemosensitivity was evaluated by rhodamine efflux assay. Apoptosis was detected by annexin V labeling and Western blot analysis of poly(ADP-ribose) polymerase cleavage. Effects on genes implicated in cell cycle and apoptosis were determined by Western blot analyses. To evaluate the efficacy in vivo, BEAC cells were injected subcutaneously in severe combined immunodeficient mice, and after the appearance of palpable tumors, mice were treated with SFN. RESULTS: SFN induced both time- and dose-dependent decline in cell survival, cell cycle arrest, and apoptosis. The treatment with SFN also suppressed the expression of multidrug resistance protein, reduced drug efflux, and increased anticancer activity of other antiproliferative agents including paclitaxel. A significant reduction in tumor volume was also observed by SFN in a subcutaneous tumor model of BEAC. Anticancer activity could be attributed to the induction of caspase 8 and p21 and down-regulation of hsp90, a molecular chaperon required for activity of several proliferation-associated proteins. CONCLUSIONS: These data indicate that a natural product with antioxidant properties from broccoli has great potential to be used in chemoprevention and treatment of BEAC.

Validation of tumor size as staging variable in the revised International Federation of Gynecology and Obstetrics stage I leiomyosarcoma: a population-based study.

INTRODUCTION: Tumor size has been introduced as a staging variable in the 2008 International Federation of Gynecology and Obstetrics (FIGO) staging system for stage I leiomyosarcoma. In the prior 1988 FIGO staging system, leiomyosarcoma used the same staging criteria as endometrial cancer including cervical involvement. In this large population-based study, we validate the use of tumor size for purposes of risk stratification among stage I leiomyosarcoma patients. METHODS: Data were extracted from the Surveillance, Epidemiology, and End Results database between 1988 and 2005. Kaplan-Meier log rank and Cox proportional hazards models were used for survival analysis and to identify possible predictors for survival. RESULTS: The identified cohort included 819 women: 158 (19.3%), 2008 FIGO stage IA and 661 (80.7%), 2008 FIGO stage IB leiomyosarcoma. The 5-year overall survival rate was better in stage IA than in stage IB leiomyosarcoma (76.6% vs 48.4%, P < 0.001). Similarly, the 5-year overall survival rates were significantly different (P < 0.001) among women with different tumor size categories: 5 cm or smaller, 5.1 to 10 cm, and larger than 10 cm (76.6%, 52.9%, and 41.9%, respectively). The difference in 5-year overall survival rates between women with and without cervical involvement was significant (28.5% vs 55.3%, P = 0.014). Although age (P < 0.001), cervical involvement (P = 0.014), tumor grade (P < 0.001), tumor size (P < 0.001), performance of salpingo-oophorectomy (P = 0.001), and stage (P < 0.001) were all significant prognostic factors on univariate analysis, only age (P = 0.007), tumor size (P < 0.001), tumor grade (P < 0.001), and performance of salpingo-oophorectomy (P = 0.02) were significant predictors on multivariate analysis. Variables not found significant on univariate analysis (hence excluded from the Cox model) included lymphadenectomy, radiation, and race. CONCLUSIONS: The new staging system using tumor size is better for risk stratification in stage I leiomyosarcoma compared with the 1988 FIGO staging system of endometrial cancer.

Ovarian and uterine carcinosarcomas: a comparative analysis of prognostic variables and survival outcomes.

INTRODUCTION: Carcinosarcomas (malignant mixed Mullerian tumor) of the female genital tract are rare tumors associated with poor outcome. The objective of this study was to identify site-specific differences by comparing carcinosarcomas originating in the uterus and the ovaries. METHODS: Data on patients with uterine and ovarian carcinosarcomas were extracted from the Surveillance, Epidemiology, and End Results database between 1988 and 2005. Kaplan-Meier log rank and Cox proportional hazards models were used for survival analysis and for identification of possible predictors for survival. RESULTS: The identified cohort included 3683 women of whom 2759 (75%) have uterine carcinosarcoma and 924 (25%) have ovarian carcinosarcomas. The patients with uterine carcinosarcoma were older than the patients with ovarian carcinosarcoma (median age, 67 vs 65 years; P < 0.001). The women with uterine carcinosarcoma compared with those with ovarian carcinosarcoma were more often African American (17.3% vs 6%; P < 0.001) and presented more often with localized disease (47% vs 10.8%; P < 0.001). Uterine carcinosarcoma compared with ovarian carcinosarcoma differed significantly with regard to the performance of lymphadenectomy (62.6% vs 41.2%; P < 0.001) and the administration of radiotherapy (38.2% vs 4.8%; P < 0.001). When controlled for the extent of disease spread, uterine carcinosarcoma had a more aggressive clinical course and shorter survival compared with ovarian carcinosarcoma. Although age (P < 0.001), race (P = 0.01), stage (P < 0.001), lymphadenectomy (P < 0.001), and radiation (P < 0.001) were all significant prognostic factors in uterine carcinosarcoma, only age (P < 0.001), stage (P < 0.001), and lymphadenectomy (P < 0.001) were significant predictors in ovarian carcinosarcoma. CONCLUSION: Although uterine carcinosarcoma presents at an earlier stage than ovarian carcinosarcoma, it has a worse prognosis compared with ovarian carcinosarcoma, with a similar extent of disease spread. Improved survival observed in lymphadenectomy group lends support to its routine performance in patients with uterine and ovarian carcinosarcomas.

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.

Sulforaphane induces cell cycle arrest by protecting RB-E2F-1 complex in epithelial ovarian cancer cells.

BACKGROUND: Sulforaphane (SFN), an isothiocyanate phytochemical present predominantly in cruciferous vegetables such as brussels sprout and broccoli, is considered a promising chemo-preventive agent against cancer. In-vitro exposure to SFN appears to result in the induction of apoptosis and cell-cycle arrest in a variety of tumor types. However, the molecular mechanisms leading to the inhibition of cell cycle progression by SFN are poorly understood in epithelial ovarian cancer cells (EOC). The aim of this study is to understand the signaling mechanisms through which SFN influences the cell growth and proliferation in EOC. RESULTS: SFN at concentrations of 5-20 microM induced a dose-dependent suppression of growth in cell lines MDAH 2774 and SkOV-3 with an IC50 of ~8 microM after a 3 day exposure. Combination treatment with chemotherapeutic agent, paclitaxel, resulted in additive growth suppression. SFN at ~8 microM decreased growth by 40% and 20% on day 1 in MDAH 2774 and SkOV-3, respectively. Cells treated with cytotoxic concentrations of SFN have reduced cell migration and increased apoptotic cell death via an increase in Bak/Bcl-2 ratio and cleavage of procaspase-9 and poly (ADP-ribose)-polymerase (PARP). Gene expression profile analysis of cell cycle regulated proteins demonstrated increased levels of tumor suppressor retinoblastoma protein (RB) and decreased levels of E2F-1 transcription factor. SFN treatment resulted in G1 cell cycle arrest through down modulation of RB phosphorylation and by protecting the RB-E2F-1 complex. CONCLUSIONS: SFN induces growth arrest and apoptosis in EOC cells. Inhibition of retinoblastoma (RB) phosphorylation and reduction in levels of free E2F-1 appear to play an important role in EOC growth arrest.

Reduction of hypoxia-induced angiogenesis in ovarian cancer cells by inhibition of HIF-1 alpha gene expression.

PURPOSE: The goal of this study was to investigate the effects of silencing HIF-1 alpha gene expression with specific small interfering RNA (siRNA) on VEGF production and angiogenesis in epithelial ovarian cancer (EOC) cells. METHODS: Two EOC cell lines, MDAH-2774 and SKOV-3, were cultured under normoxic (20% O(2)) and hypoxic (2% O(2)) conditions using standard techniques. After EOC cells were transfected with siRNA, HIF-1 alpha and VEGF mRNA levels were measured by real-time RT-PCR. Angiogenesis was evaluated utilizing an in vitro assay model consisting of human umbilical vein endothelial cells (HUVEC) and polymerized ECM Matrix. RESULTS: Both EOC cell lines evaluated constitutively expressed HIF-1 alpha and VEGF mRNA. HIF-1 alpha and VEGF mRNA levels were significantly increased in response to hypoxia (P < 0.05). Under hypoxic conditions, inhibition of HIF-1 alpha gene expression by a specific siRNA resulted in a significant reduction in HIF-1 alpha and VEGF mRNA levels (P < 0.05). In the in vitro angiogenesis model, supernatant from the hypoxic EOC cells induced the HUVEC to form a complex tubular network, a hallmark of angiogenesis. Semi-quantitative analysis of the angiogenesis assay revealed a significant reduction in tube formation when supernatant from HIF-1 alpha siRNA-treated hypoxic EOC cell was used (P < 0.05). CONCLUSION: Inhibition of HIF-1 alpha expression by specific siRNA resulted in a significant decrease in VEGF production and angiogenesis. Further investigation of HIF-1 alpha inhibition for anti-tumor activity is warranted and may potentially prove HIF-1 alpha as a therapeutic target in the management ovarian cancer.

Analysis of the expression of human tumor antigens in ovarian cancer tissues.

Biomarkers for early detection of cancer have great clinical diagnostic potential. Numerous reports have documented the generation of humoral immune responses that are triggered in response to changes in protein expression patterns in tumor tissues and these biomarkers are referred to as tumor associated antigens (TAAs). Using a high-throughput technology, we previously identified 65 proteins as diagnostically useful TAAs by profiling the humoral immune responses in ovarian cancer (OVCA) patients. Here we determined the expression status of some of those TAAs in tissues from OVCA patients. The protein expression patterns of 4 of those 65 antigens, namely NASP, RCAS1, Nijmegen breakage syndrome1 (NBS1) and eIF5A, along with p53 and Her2 (known molecular prognosticators) and two proteins that interact with NBS1, MRE11 and RAD50, were assessed by immunohistochemistry (IHC). NASP and RCAS1 proteins were more frequently expressed in ovarian cancer tissues than with normal ovarian tissue and serous cystadenomas and MRE11 was less frequently expressed. When evaluated simultaneously, only NASP and MRE11 remained statistically significant with sensitivity of 66% and specificity of 89%. None of these proteins' expression levels were prognostic for survival. Together, our results indicate that occurrence of humoral immune responses against some of these TAAs in OVCA patients is triggered by antigen protein overexpression.

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.

Ritonavir blocks AKT signaling, activates apoptosis and inhibits migration and invasion in ovarian cancer cells.

BACKGROUND: Ovarian cancer is the leading cause of mortality from gynecological malignancies, often undetectable in early stages. The difficulty of detecting the disease in its early stages and the propensity of ovarian cancer cells to develop resistance to known chemotherapeutic treatments dramatically decreases the 5-year survival rate. Chemotherapy with paclitaxel after surgery increases median survival only by 2 to 3 years in stage IV disease highlights the need for more effective drugs. The human immunodeficiency virus (HIV) infection is characterized by increased risk of several solid tumors due to its inherent nature of weakening of immune system. Recent observations point to a lower incidence of some cancers in patients treated with protease inhibitor (PI) cocktail treatment known as HAART (Highly Active Anti-Retroviral Therapy). RESULTS: Here we show that ritonavir, a HIV protease inhibitor effectively induced cell cycle arrest and apoptosis in ovarian cell lines MDH-2774 and SKOV-3 in a dose dependent manner. Over a 3 day period with 20 muM ritonavir resulted in the cell death of over 60% for MDAH-2774 compared with 55% in case of SKOV-3 cell line. Ritonavir caused G1 cell cycle arrest of the ovarian cancer cells, mediated by down modulating levels of RB phosphorylation and depleting the G1 cyclins, cyclin-dependent kinase and increasing their inhibitors as determined by gene profile analysis. Interestingly, the treatment of ritonavir decreased the amount of phosphorylated AKT in a dose-dependent manner. Furthermore, inhibition of AKT by specific siRNA synergistically increased the efficacy of the ritonavir-induced apoptosis. These results indicate that the addition of the AKT inhibitor may increase the therapeutic efficacy of ritonavir. CONCLUSION: Our results demonstrate a potential use of ritonavir for ovarian cancer with additive effects in conjunction with conventional chemotherapeutic regimens. Since ritonavir is clinically approved for human use for HIV, drug repositioning for ovarian cancer could accelerate the process of traditional drug development. This would reduce risks, limit the costs and decrease the time needed to bring the drug from bench to bedside.

Successful pregnancy after fertility-sparing surgery for peritoneal psammocarcinoma: a case report.

BACKGROUND: Psammocarcinoma is a rare form of low grade serous carcinoma of the ovary or peritoneum. Although limited to case reports and small series, psammocarcinoma appears to have an indolent course. CASE: A 27-year-old, nulliparous female presented with an adnexal mass. Following fertility-sparing surgery and adjuvant chemotherapy, she was able to achieve a successful pregnancy. Fifteen years after initial conservative treatment, she remains without pathologic evidence of cancer. CONCLUSION: Psammocarcinoma are rare neoplasms that appear to have an indolent clinical course. Pregnancy after the diagnosis and treatment of psammocarcinoma may not alter the clinical course of the disease.

Second neoplasms in survivors of endometrial cancer: impact of radiation therapy.

OBJECTIVE: To evaluate the association of radiotherapy to subsequent second cancers in endometrial carcinoma survivors. METHODS: Subjects with endometrial cancer as their first malignancy were identified from the Surveillance, Epidemiology and End Results (SEER) database from 1973 to 2004 and were divided into radiation (R) and No Radiation (NR) groups. Person years at risk (PYR), observed (O) and expected (E) counts and SIR (standardized incidence ratio) were determined. (%) increase in relative risk (RR) for R vs. NR group was calculated using Poisson regression. Absolute Excess Risk (AER) was 'O' minus 'E' per 10,000 PYRs. RESULTS: Of 90,502 subjects 31,643 (34.9%) were in R and 52,182 (57.6%) in NR. The radiation status of 6677 (7.3%) was unknown. In the R group 4203 developed second cancers vs. 5563 in NR group; relative risk for R group-1.25 (95% CI 1.20 to 1.29). A total of 17.11 excess tumors were observed in R group (AER). The relative risk increased with latency of exposure and peaked at (>10 years), being 40% (p<0.001). The statistically significant (%) increase in RR for individual organs was as follows: urinary bladder (124%), vagina (88%), vulva (83%), sarcoma (70%), colon and rectum (43%) and lung (29%). CONCLUSION: In the largest study reporting on association of radiotherapy to subsequent second neoplasms in endometrial cancer survivors, the increased risk of second cancers was most pronounced in the field of exposure and was affected by latency since exposure.

Radiation-associated endometrial cancer.

OBJECTIVE: To compare prognostic variables and survival of radiation-associated endometrial cancers with sporadic second endometrial cancers. METHODS: Patients with primary cancers of pelvic organs (urinary system, colorectal, cervix, vulva, and vagina) were identified from the Surveillance, Epidemiology, and End Results (SEER) database between 1973 and 2005. Among these patients, those who received pelvic radiation and subsequently developed endometrial cancer formed the radiation-associated endometrial cancers cohort (cases), whereas those who did not receive pelvic radiation but subsequently developed endometrial cancer formed the sporadic second endometrial cancers cohort (controls). Comparisons between radiation-associated endometrial cancers and sporadic second endometrial cancers used chi, t tests, Kaplan-Meier, and cox proportional hazards analysis. RESULTS: In 205 radiation-associated endometrial cancer patients and 1,001 sporadic second endometrial cancer patients, the mean age of diagnosis was 65 years and 68 years, respectively (P<.001). The mean latency between primary pelvic organ cancer and second endometrial cancer was 110 months for the radiation-associated endometrial cancers and 77 months for the sporadic second endometrial cancers (P=.03). The lesions in the radiation-associated endometrial cancers cohort (compared with sporadic second endometrial cancers) were far more likely to be nonendometrioid histology (76.2% compared with 51%, P<.001), poorly differentiated (58% compared with 28%, P<.001), and advanced stage (International Federation of Gynecology and Obstetrics III and IV [corrected] combined) (43% compared with 16%, P<.001). The 5-year survival rate for radiation-associated endometrial cancers and sporadic second endometrial cancers was 27.1% and 57.1%, respectively (P<.001). In multivariable analysis, after controlling for age, race, histology, stage, grade, and treatment, the hazard ratio for death of radiation-associated [corrected] endometrial cancers was 1.4 (95% ((CI)) [corrected] 1.2-3.6; P=.002). CONCLUSION: The radiation-associated endometrial cancers carry a grave prognosis because they are more likely to be nonendometrioid, poorly differentiated advanced stage cancers. The longer latency and extensive spread at diagnosis among radiation-associated endometrial cancers may suggest a possible delay in clinical presentation and diagnosis. LEVEL OF EVIDENCE: II.

Carboplatin and paclitaxel adjuvant chemotherapy in primitive neuroectodermal tumor of the uterine corpus.

Primitive neuroectodermal tumor of the uterine corpus (PNET) is rare and appears to have an aggressive clinical course. We report on a postmenopausal woman with optimal surgically cytoreduced advanced-stage PNET in which adjuvant combination chemotherapy with platinum and taxane agents was unsuccessful in extending her disease-free survival.

A comparison of younger vs older women with vulvar cancer in the United States.

OBJECTIVE: The purpose of this study was to compare the prognostic variables and survival of younger (< 50 years) to that of older (> or = 50 years) women with vulvar cancer. STUDY DESIGN: Subjects with invasive squamous cell carcinoma of the vulva were identified from the limited use Surveillance, Epidemiology, and End Results (SEER) Program 1988-2005. Comparisons between younger and older women were accomplished with chi(2) and t-tests. Survival analysis was accomplished with Kaplan-Meier for univariate analysis and Cox proportional hazards model for multivariate analysis. RESULTS: A total of 6965 patients met inclusion criteria, of whom 1345 patients (19.3%) were younger and 5620 patients (80.7%) were older. The 5-year survival was 87.5% for younger women and 52.5% for older women (P < .001). After data were controlled for race, stage, grade, and surgical treatment, older patients had a hazard ratio of 3.9 (95% CI, 3.2-4.7) for death. CONCLUSION: A striking survival difference exists between younger and older women with squamous cell vulvar cancer, which supports the view that etiopathogenesis of this disease may vary between age groups.

Prognostic significance of keratinization in squamous cell cancer of uterine cervix: a population based study.

PURPOSE: To determine the influence of keratinization on prognosis in squamous cell cancer (SCC) of the uterine cervix. METHODS: Patients with keratinized squamous cell carcinoma (KSCC) and non-keratinized squamous cell carcinoma (NKSCC) of the cervix were identified from the Limited Use SEER database from 1988 to 2004. A subgroup of patients who did not have radiation or surgery formed the basis to study the natural history of the disease. Data were analyzed using Pearson Chi-square, Student's T tests. Kaplan-Meier and Cox Regression Proportional Hazards survival analysis was conducted in SPSS and SEER-Stat software. RESULTS: The KSCC group had 3,102 and the NKSCC had 3,751 patients with mean age being 51 and 49 years, respectively (P = 0.001). In general, patients with KSCC were more likely to have advanced stage (FIGO III and IV) disease while patients with NKSCC were more likely to have poorly differentiated neoplasms (P < 0.001). The prevalence of lymph node metastasis remained similar in both histology types (P > 0.05). Overall, the 5-year survival in KSCC was 63.4% as compared to 65.3% in the NKSCC group (P = 0.04). Patients treated by surgery had no difference in survival; however, patients treated by radiation had a median survival in KSCC of 33 months (n = 928, 95% CI 27.7-38.3) as compared to 38 months (n = 1,140, 95% CI 32.1-43.8) in NKSCC (P = 0.03). A total of 165 KSCC and 147 NKSCC patients did not receive treatment. Within this subgroup, the median survival was 10 months (95% CI 5.93-14.07) as compared to 28 months (95% CI 17.9-38.0; P = 0.001) respectively for the two cohorts. In multivariate analysis stage, treatment status, nodal metastasis and keratinization were independent predictors of survival (P < 0.05). CONCLUSION: This is the largest study reporting on the prognostic importance of keratinization in SCC. KSCC may be less radiosensitive and associated with shorter overall survival. Also, in the natural history of the SCC, keratinization signifies striking reduction in survival.