Angiosarcoma following MammoSite partial breast irradiation.

Angiosarcoma is a rare tumor of endothelial origin which commonly arises in small blood or lymphatic vessels. Its development in the treated breast following adjuvant external beam radiation is also rare. To our knowledge, there are no reported cases in the literature or MammoSite registry which describe the occurrence of angiosarcoma in the treated breast following MammoSite brachytherapy. This is a case report of a 74 year old female who developed angiosarcoma 4 years after receiving MammoSite balloon brachytherapy following surgical resection of a T1mic N0 M0 infiltrating ductal carcinoma.

Health-related quality of life outcomes associated with four cisplatin-based doublet chemotherapy regimens for stage IVB recurrent or persistent cervical cancer: a Gynecologic Oncology Group study.

PURPOSE: To assess the differences in health-related quality of life (HRQL) of 4 cisplatin containing doublet chemotherapy combinations in women with advanced/recurrent cervical carcinoma. METHODS: Patients were randomized to three-week cycles of paclitaxel + cisplatin (PC); vinorelbine + C (VC); gemcitabine + C (GC); or topotecan + C (TC). We report HRQL results from data available on 434 eligible patients enrolled into this 513 patient trial. HRQL was assessed with the Functional Assessment of Cancer Therapy-Cervix (FACT-Cx) the FACT/Gynecologic Oncology Group (FACT/GOG) four-item neurotoxicity scale, and the 0-10 "worst pain" item from the Brief Pain Inventory, at baseline (pre-treatment), prior to beginning cycle 2, prior to beginning cycle 5, and at 9 months after enrollment. As reported by Monk et al. (2009) [13] VC, GC and TC were found not to be superior to PC with regard to progression-free survival or overall survival. RESULTS: The trial was terminated early due to planned interim futility analysis, reducing power for HRQL analysis from 85% to 55%. Patients receiving VC, GC and TC doublets did not report significantly different HRQL, neuropathy, or pain from those who received the PC (control) doublet. Patients receiving PC tended to report worse neuropathy during treatment than patients who received other doublets (especially GC and TC), but the differences were not statistically significant. CONCLUSION: None of the 3 experimental doublets was different from PC in terms of HRQL during treatment. Long-term toxicity data are inconclusive. Except where patients may wish to reduce their risk of worsening pre-treatment neuropathy, PC remains the standard of care for this disease.

Langerhans' cell histiocytosis of the vulva: the Iowa experience.

BACKGROUND: Vulvar presentation of Langerhans' cell histiocytosis (histiocytosis X) is rare. Symptoms and signs at the time of presentation can include pruritus, pain, dyspareunia, burning, discharge and presence of a discrete lesion and/or generalized ulceration. Once a diagnosis of Langerhans' cell histiocytosis is made, there is no formal treatment protocol. This report highlights 2 clinical cases diagnosed and treated at a tertiary care center. CASES: We report the case histories of 2 women who presented to the Vulva/Vaginal Disease Clinic at the University of Iowa. The first patient, a 76-year-old woman, had a 1-year history of vulvar pruritus. The second patient, a 39-year-old woman, had a 3-month history of a clitoral growth. CONCLUSION: Presentation of Langerhans' cell histiocytosis as a vulvar primary condition is rare and probably underdiagnosed as its clinical presentation can vary. Such patients often have been treated for recurrent yeast or presumed herpes simplex virus infections. Langerhans' cell histiocytosis should be considered as a differential diagnosis in females who present with chronic pruritus, pain, ulcerations or intermittent rashes.

Characterizing short-term release and neovascularization potential of multi-protein growth supplement delivered via alginate hollow fiber devices.

Multi-protein (10-250 kDa) endothelial cell growth supplement (ECGS) contains growth factors of varying sizes resulting in advanced release rates from diffusion-based drug delivery devices. As a result, the biochemical stimulus provided by ECGS for neovascularization in the critical initial stages of cell transplantation in artificial organs may differ from that for single growth factor delivery. In this study, both in vitro and in vivo studies were conducted with ECGS to correlate in vitro release of multiple angiogenic growth factors to vascularization potential in vivo. The short-term release of ECGS from calcium alginate gels supported in the lumen of polypropylene (PP) hollow fibers was investigated in vitro for up to 142 h. The overall time constant increased from 2, 2.2 and 6.3 h as the alginate concentration was increased from 1.5%, 2% and 3%, respectively. However, time constants for individual species ranged from 1.5 to 77 h. The in vivo bioactivity of released ECGS was assessed for up to 21 days using a Lewis rat model implanted with 1.5% calcium alginate gels supported in PP and polysulfone hollow fibers. For the ECGS-releasing PP hollow fiber system, a two-fold increase in neovascularization with respect to the control was observed for the period between 7 and 17 days post-implantation at the device-tissue interface (p<0.05).

Randomized phase III trial of cisplatin with or without topotecan in carcinoma of the uterine cervix: a Gynecologic Oncology Group Study.

PURPOSE: On the basis of reported activity of methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) or topotecan plus cisplatin in advanced cervix cancer, we undertook a randomized trial comparing these combinations versus cisplatin alone, to determine whether survival is improved with either combination compared with cisplatin alone, and to compare toxicities and quality of life (QOL) among the regimens. PATIENTS AND METHODS: Eligible patients were randomly allocated to receive cisplatin 50 mg/m(2) every 3 weeks (CPT); cisplatin 50 mg/m(2) day 1 plus topotecan 0.75 mg/m(2) days 1 to 3 every 3 weeks (CT); or methotrexate 30 mg/m(2) days 1, 15, and 22, vinblastine 3 mg/m(2) days 2, 15, and 22, doxorubicin 30 mg/m(2) day 2, and cisplatin 70 mg/m(2) day 2 every 4 weeks (MVAC). Survival was the primary end point; response rate and progression-free survival (PFS) were secondary end points. QOL data are reported separately. RESULTS: The MVAC arm was closed by the Data Safety Monitoring Board after four treatment-related deaths occurred among 63 patients, and is not included in this analysis. Two hundred ninety-four patients enrolled onto the remaining regimens: 146 to CPT and 147 to CT. Grade 3 to 4 hematologic toxicity was more common with CT. Patients receiving CT had statistically superior outcomes to those receiving CPT, with median overall survival of 9.4 and 6.5 months (P = .017), median PFS of 4.6 and 2.9 months (P = .014), and response rates of 27% and 13%, respectively. CONCLUSION: This is the first randomized phase III trial to demonstrate a survival advantage for combination chemotherapy over cisplatin alone in advanced cervix cancer.

Randomized trial of cisplatin and ifosfamide with or without bleomycin in squamous carcinoma of the cervix: a gynecologic oncology group study.

PURPOSE: Phase II trial reports have suggested that the addition of bleomycin to the combination of cisplatin and ifosfamide may improve response rates and possible survival in squamous carcinoma of the cervix. This study prospectively evaluates the combination of bleomycin to this regimen in women with histologically proven advanced recurrent or persistent squamous cell carcinoma of the cervix. PATIENTS AND METHODS: Eligible women were randomized to receive either cisplatin (50 mg/m(2)), ifosfamide (5 g/m(2) over 24 hours), and mesna (6 g/m(2) during ifosfamide infusion and the following 12 hours) (CI) versus bleomycin 30 units over 24 hours on day 1 followed by cisplatin (50 mg/m(2)), ifosfamide (5 g/m(2) over 24 hours), and mesna (6 g/m(2) during ifosfamide infusion and the following 12 hours) (CIB). Three hundred three women were enrolled onto this trial, of which 287 were assessable. RESULTS: There were no significant differences between CI and CIB with regard to response rates (32% v 31.2%, respectively), progression-free survival (PFS), or overall survival. PFS and survival were associated with initial performance status (PS). Patients with a PS of 0 experienced a lower rate of failure (P =.013) and a lower risk of death (P =.009) compared with patients with PS of 2. The most frequent grade 3/4 toxicities were leukopenia, neutropenia, anemia, thrombocytopenia, and nausea and vomiting. Neither regimen was associated with a significant increase in incidence of these toxicities. CONCLUSION: The CI regimen was virtually identical to CIB with regard to response rate, PFS, survival, and toxicity profile. Thus, the addition of bleomycin in the dose-schedule employed to cisplatin and ifosfamide did not improve outcome in patients with advanced cervical cancer.

Intraperitoneal radioactive phosphorus (32P) versus observation after negative second-look laparotomy for stage III ovarian carcinoma: a randomized trial of the Gynecologic Oncology Group.

PURPOSE: The objectives of this prospective randomized study of consolidation therapy were to evaluate recurrence-free survival (RFS), overall survival (OS), and the morbidity of intraperitoneal (IP) chromic phosphate suspension (32P) therapy in patients with stage III epithelial ovarian carcinoma who have no detectable evidence of disease at the second-look laparotomy (SLL) procedure after primary chemotherapy. PATIENTS AND METHODS: In a multi-institution clinical cooperative trial, 202 eligible patients with a negative SLL were randomly selected to receive either 15 mCi IP 32P (n = 104) or no further therapy (NFT; n = 98). RESULTS: With a median follow-up of 63 months in living patients, 68 patients in the IP 32P group (65%) and 63 patients in the NFT group (64%) have developed tumor recurrence. The relative risk of recurrence is 0.90 (IP 32P to NFT) (90% confidence interval [CI], 0.68 to 1.19). The 5-year RFS rate is 42% and 36% for the IP 32P and NFT groups, respectively; the difference is not statistically significant (log-rank test, P =.27). There was no statistically significant difference in OS (P =.19). The relative risk of death is 0.85 (IP 32P to NFT) (90% CI, 0.62 to 1.16). Sixteen patients (8%) experienced grade 3 or 4 adverse effects, with eight in each respective group. CONCLUSION: Intraperitoneal chromic phosphate did not decrease the risk of relapse or improve survival for patients with stage III epithelial ovarian cancer after a negative SLL. Despite complete pathologic remission at SLL after initial surgery and platinum-based chemotherapy, 61% of stage III ovarian cancer patients had tumor recurrence within 5 years of negative SLL. This indicates a need for more effective initial therapy and further studies of consolidation therapy.

Phase III study of cisplatin with or without paclitaxel in stage IVB, recurrent, or persistent squamous cell carcinoma of the cervix: a gynecologic oncology group study.

PURPOSE: To determine whether cisplatin plus paclitaxel (C+P) improved response rate, progression-free survival (PFS), or survival compared with cisplatin alone in patients with stage IVB, recurrent, or persistent squamous cell carcinoma of the cervix. PATIENTS AND METHODS Eligible: patients with measurable disease, performance status (PS) 0 to 2, and adequate hematologic, hepatic, and renal function received either cisplatin 50 mg/m2 or C+P (cisplatin 50 mg/m2 plus paclitaxel 135 mg/m2) every 3 weeks for six cycles. Tumor measurements and quality-of-life (QOL) assessments were obtained before each treatment cycle. RESULTS: Of 280 patients entered, 6% were ineligible. Among 264 eligible patients, 134 received cisplatin and 130 received C+P. Groups were well matched with respect to age, ethnicity, PS, tumor grade, disease site, and number of cycles received. The majority of all patients had prior radiation therapy (cisplatin, 92%; C+P, 91%). Objective responses occurred in 19% (6% complete plus 13% partial) of patients receiving cisplatin versus 36% (15% complete plus 21% partial) receiving C+P (P = .002). The median PFS was 2.8 and 4.8 months, respectively, for cisplatin versus C+P (P < .001). There was no difference in median survival (8.8 months v 9.7 months). Grade 3 to 4 anemia and neutropenia were more common in the combination arm. There was no significant difference in QOL scores, although a disproportionate number of patients (cisplatin, n = 50; C+P, n = 33) dropped out of the QOL component, presumably because of increasing disease, deteriorating health status, or early death. CONCLUSION C+P is superior to cisplatin alone with respect to response rate and PFS with sustained QOL.

Vulvar cellular angiofibroma: a case report.

Cellular angiofibroma is a benign growth initially described in 1997, with few reports to date. A 31-year-old woman presented with a 3-year history of a small left labial mass, which had recently increased in size to 5 cm, and was clinically thought to be a lipoma. A simple excision was performed. Histologically, the mass was consistent with a cellular angiofibroma. Ten months later, the growth has not recurred. Cellular angiofibroma is a rare, benign mesenchymal lesion typically occurring on the vulva, and should be considered in the differential diagnosis of a painless, soft, vulvar mass.

Stockpiling of transitional and classic primary follicles in ovaries of women with polycystic ovary syndrome.

Recently, we proposed an oocyte-growth differentiation factor-9 hypothesis that predicts alterations in the initial stages of folliculogenesis in polycystic ovary syndrome (PCOS) ovaries. Here, we test this hypothesis by scoring the composition of follicles in normal and PCOS ovaries. Follicles were classified as primordial, transitional primary, classic primary, secondary, and Graafian. A total of 2274 follicles were scored. The total number of growing follicles was significantly greater in PCOS ovaries than normal, but the number of nongrowing primordial follicles did not differ. Consequently, the increase in growing follicles in PCOS cannot be explained by increased primordial follicle recruitment. Differential counts showed that the number of growing follicles at each stage of development was significantly greater: PCOS had 2.7-fold more primary, 1.8-fold more secondary, and 2-fold more Graafian follicles than normal. The greatest effect was on the classic primary follicles where the number was almost 5-fold greater in PCOS ovaries. The absence of apoptosis in normal and PCOS preantral follicles argues that the increase in growing follicles in PCOS cannot be explained by changes in atresia. We conclude, therefore, that primary follicle growth is abnormally slow in PCOS and the dynamics are reflected in a stockpiling of classic primary follicles.

Phase III trial of four cisplatin-containing doublet combinations in stage IVB, recurrent, or persistent cervical carcinoma: a Gynecologic Oncology Group study.

PURPOSE: Assess toxicity and efficacy of cisplatin (Cis) doublet combinations in advanced and recurrent cervical carcinoma. PATIENTS AND METHODS: Patients were randomly assigned to paclitaxel 135 mg/m(2) over 24 hours plus Cis 50 mg/m(2) day 2 every 3 weeks (PC, reference arm); vinorelbine 30 mg/m(2) days 1 and 8 plus Cis 50 mg/m(2) day 1 every 3 weeks (VC); gemcitabine 1,000 mg/m(2) day 1 and 8 plus Cis 50 mg/m(2) day 1 every 3 weeks (GC); or topotecan 0.75 mg/m(2) days 1, 2, and 3 plus Cis 50 mg/m(2) day 1 every 3 weeks (TC). Survival was the primary end point with a 33% improvement relative to PC considered important (85% power, alpha = 5%). Quality-of-life data were prospectively collected. RESULTS: A total of 513 patients were enrolled when a planned interim analysis recommended early closure for futility. The experimental-to-PC hazard ratios of death were 1.15 (95% CI, 0.79 to 1.67) for VC, 1.32 (95% CI, 0.91 to 1.92) for GC, and 1.26 (95% CI, 0.86 to 1.82) for TC. The hazard ratios for progression-free survival (PFS) were 1.36 (95% CI, 0.97 to 1.90) for VC, 1.39 (95% CI, 0.99 to 1.96) for GC, and 1.27 (95% CI, 0.90 to 1.78) for TC. Response rates (RRs) for PC, VC, GC, and TC were 29.1%, 25.9%, 22.3%, and 23.4%, respectively. The arms were comparable with respect to toxicity except for leucopenia, neutropenia, infection, and alopecia. CONCLUSION: VC, GC, and TC are not superior to PC in terms of overall survival (OS). However, the trend in RR, PFS, and OS favors PC. Differences in chemotherapy scheduling, pre-existing morbidity, and toxicity are important in individualizing therapy.

Subinvolution of the placental site as an anatomic cause of postpartum uterine bleeding: a review.

CONTEXT: Subinvolution of the placental site is an anatomic cause of delayed postpartum uterine bleeding that may be underrecognized by general surgical pathologists. OBJECTIVE: To review the physiology of uteroplacental arterial development and normal postpartum involution, and to present the characteristic clinical and histopathologic features of subinvolution. DATA SOURCES: Literature review (MEDLINE via PubMed and Ovid) regarding the pathology and pathophysiology of placental site subinvolution. Review of the clinical and pathologic characteristics of our own institution's previously diagnosed cases of subinvolution from hysterectomy and endomyometrial curettage specimens. CONCLUSIONS: Surgical pathologists must be aware of the cardinal histopathologic findings of subinvolution, and this diagnosis must be considered in every postpartum curettage or hysterectomy specimen presented to the surgical pathologist. Subinvolution of the placental site is an important diagnosis, as this process implies an idiopathic cause, rather than an iatrogenic cause, of postpartum uterine bleeding. The etiology of placental site subinvolution remains poorly characterized.

Randomized phase III trial of whole-abdominal irradiation versus doxorubicin and cisplatin chemotherapy in advanced endometrial carcinoma: a Gynecologic Oncology Group Study.

PURPOSE: To compare whole-abdominal irradiation (WAI) and doxorubicin-cisplatin (AP) chemotherapy in women with stage III or IV endometrial carcinoma having a maximum of 2 cm of postoperative residual disease. PATIENTS AND METHODS: Four hundred twenty-two patients were entered onto this trial. Of 396 assessable patients, 202 were randomly allocated to receive WAI, and 194 were allocated to receive AP. Irradiation dosage was 30 Gy in 20 fractions, with a 15-Gy boost. Chemotherapy consisted of doxorubicin 60 mg/m2 and cisplatin 50 mg/m2 every 3 weeks for seven cycles, followed by one cycle of cisplatin. RESULTS: Most patient and tumor characteristics were well balanced. The median patient age was 63 years; 50% had endometrioid tumors. Median follow-up time was 74 months. The hazard ratio for progression adjusted for stage was 0.71 favoring AP (95% CI, 0.55 to 0.91; P < .01). At 60 months, 50% of patients receiving AP were predicted to be alive and disease free when adjusting for stage compared with 38% of patients receiving WAI. The stage-adjusted death hazard ratio was 0.68 (95% CI, 0.52 to 0.89; P < .01) favoring AP. Moreover, at 60 months and adjusting for stage, 55% of AP patients were predicted to be alive compared with 42% of WAI patients. Greater acute toxicity was seen with AP. Treatment probably contributed to the deaths of eight patients (4%) on the AP arm and five patients (2%) on the WAI arm. CONCLUSION: Chemotherapy with AP significantly improved progression-free and overall survival compared with WAI. Nevertheless, further advances in efficacy and reduction in toxicity are clearly needed.

Septuplet placenta: a case report.

OBJECTIVE: On November 19, 1997, 7 liveborn infants (4 boys and 3 girls) were delivered by cesarean delivery at 30.5 weeks gestational age. The pregnancy was the result of artificial induction of ovulation. STUDY DESIGN: The septuplet placenta was evaluated with a standard and systematic procedure for placentas of multiple births that revealed a septamnionic, septchorionic architecture with 5 fused and 2 unfused placentas. RESULTS: Each of the 7 umbilical cords contained 3 vessels. Two cords were velamentous; the remaining 5 cords were inserted eccentrically. The ratio of combined birth weights of the 7 infants to total placental weight (7.52:1) correlated with normograms of singleton and twin gestations. CONCLUSION: This ratio and additional calculations were used for comparison and for additional clinicopathologic correlations.

Sinonasal adenocarcinoma: immunohistochemical marking and expression of oncoproteins.

BACKGROUND: Relatively little is known concerning the immunohistochemical marking of sinonasal adenocarcinoma (SNA). The most clinically problematic tumors are those that seem histologically identical to colonic adenocarcinoma, a neoplasm that may metastasize to the sinonasal region. To determine whether differentiated immunohistochemical expression of keratins could differentiate primary from metastatic tumors and to understand the biology of these tumors, differentiated keratin and oncoprotein expression was investigated. METHODS: Eleven patients with sinonasal adenocarcinoma were investigated for expression of cytokeratins 7 and 20 (CK7, CK20), AE 1/3, CAM 5.2, smooth muscle-specific actin, muscle-specific actin, desmin, S-100, carcinoembryonic antigen (CEA), p53, and HER-2/neu. RESULTS: All sinonasal adenocarcinomas of intestinal type were cytokeratin 7 positive. None of the tumors showed myoepithelial differentiation. Strong HER-2/neu staining was seen in some tumors. CONCLUSIONS: Strong HER-2/neu staining in some cases suggests this oncogene may be involved in the genesis of SNA. Immunohistochemical staining with cytokeratin 7 may be potentially useful in differentiating primary from metastatic disease in sinonasal adenocarcinomas of the intestinal subtype.

Ovarian mixed germ cell tumor with predominance of polyembryoma: a case report with literature review.

An ovarian mixed germ cell tumor in a 34-year-old woman contained a predominant component of polyembryoma as well as foci of choriocarcinoma, yolk sac tumor, and immature teratoma. No previous cases of identical composition have been found in the literature.

Phase II trial of danazol in advanced, recurrent, or persistent endometrial cancer: a Gynecologic Oncology Group study.

OBJECTIVES: To evaluate the activity and toxicity of danazol in advanced, recurrent, or persistent endometrial carcinoma. METHODS: Eligible patients with advanced, recurrent, or persistent endometrial carcinoma not amenable to curative therapy were treated with danazol at a dose of 100 mg four times per day until disease progression or toxicity necessitated discontinuation. Eligibility criteria included the presence of measurable disease and no prior chemotherapy. Immunohistochemical analysis of metastatic tumor tissue for estrogen and progesterone receptors was required. RESULTS: Twenty-five patients were enrolled and 3 were excluded. Six patients had tumors staining positive for both estrogen and progesterone receptors. There were no responders among 22 eligible patients. Six patients (27%) demonstrated stable disease as their best response. The median progression-free survival and overall survival were 1.9 and 14.4 months, respectively. A median total dose of 21.7 (range: 1.4 to 67.2) of danazol was administered. Therapy was discontinued in 5 eligible patients due to toxicity. Four of these patients experienced hepatic toxicity. CONCLUSIONS: Danazol has minimal activity in advanced, recurrent, or persistent endometrial carcinoma.