Ultrasound and Histopathologic Correlation of Ovarian Cystadenofibromas: Diagnostic Value of the "Shadow Sign".

OBJECTIVES: Cystadenofibromas (CAFs) are rare benign ovarian tumors without a widely accepted ultrasound (US) pattern. They are usually described by as thin-walled, unilocular or multilocular, and at times septated cysts with scant blood flow and no solid components. We describe a unique US feature, the "shadow sign," seen in prospectively diagnosed benign CAFs. We also provide the histopathologic basis for this typical US appearance. METHODS: Ultrasound (US) examinations were performed in our obstetric and gynecologic US unit. Pathologic examinations were performed by a dedicated gynecologic pathology team. The US and pathology department's database was searched for the diagnosis of a CAF between 2010 and 2017. RESULTS: We identified 20 patients who underwent transvaginal US examinations with a sole US diagnosis of a CAF, and the tumors were surgically removed. The common US feature across the 20 cases was the presence of hyperechoic avascular shadowing nodules. The correlating histologic features were unilocular or multilocular cysts with a smooth internal wall surface lined by a simple epithelium and occasional robust polypoid fibrous stroma. CONCLUSIONS: This US marker helps in differentiating CAFs from borderline ovarian tumors, which do not show this US feature. We hope that recognizing the suggested shadow sign as an additional descriptor of CAFs will lead to minimizing their unnecessary removal and eliminating additional and unnecessary imaging by computed tomography and magnetic resonance imaging.

Ovarian cancer in BRCA mutation carriers: improved outcome after intraperitoneal (IP) cisplatin.

BACKGROUND: Ovarian cancer arising in women with BRCA mutations is known to have a more favorable outcome and to be more responsive to platinum-based regimens than in those without a hereditary background. We analyze our previously published intraperitoneal (IP) studies in relation to BRCA mutation status and update their outcomes. METHODS: Among 62 patients with ovarian cancer enrolled in IP platinum doublet studies in clinical trials (with etoposide (n = 18), with floxuridine (n = 30), and with topotecan (n = 14)), a deleterious BRCA mutation was eventually identified in 10 patients. The outcomes in these BRCA mutation carriers are described and compared with survival of others in respective trials. RESULTS: Ten patients that were confirmed to have BRCA mutations-all with high-grade and stages IIC to IV disease-survived a median of 10 years (range: 4-18+) after receiving IP cisplatin-based regimens. Two continue with no evidence of disease since their IP treatment, while four others remain alive with recurrences after 8, 9, 10, and 11 years, respectively. CONCLUSIONS: This experience suggests that IP cisplatin leads to favorable long term outcomes in advanced ovarian cancer in women with defective homologous recombination (i.e., with deleterious BRCA mutations). Whether such cisplatin dose-intensification from IP relative to (intravenous) IV drug administration leads to superior results in these mutation carriers requires further study.

Phase 1/pharmacology study of intraperitoneal topotecan alone and with cisplatin: potential for consolidation in ovarian cancer.

PURPOSE: Most ovarian cancers recur after first-line treatment. We studied the pharmacology, tolerability, and therapeutic potential of intraperitoneal (IP) topotecan, alone and with IP cisplatin. METHODS: Patients received IP topotecan 1.5 mg (flat dose) daily on days 1-5 (level 0) via IP catheter. Subsequent cohorts received IP cisplatin 50 mg/m(2) on day 1 added to topotecan 1.5 mg on days 1-3 (level I), topotecan 1.25 mg on days 1-3 (level II), or topotecan 1.25 mg on days 1-5 (level III). Plasma and IP concentrations of total and lactone (E-ring closed) topotecan were measured on days 1 and 2 in cycles 1 and 2. RESULTS: Sixteen patients (15 tubo-ovarian, 1 gastric cancers) were entered at levels 0 (3), I (4), II (4), or III (5). Dose-limiting neutropenias occurred in seven patients at dose levels I and III; grade 3 thrombocytopenia occurred in two at level III. Other toxicities included grade 1 hives in two, serum creatinine elevations in two, and Staphylococcus epidermidis and chemical peritonitis (one each). A median progression-free survival of 13 months was recorded among ovarian cancer patients who had minimal (6) or no residuum (3) after platinum-based induction; 5 are alive at 4 years. Topotecan's AUC IP/AUC plasma ratios ranged from 13 to 119. CONCLUSION: Topotecan IP for 3-5 days is tolerable; occasionally, myelosuppression is dose-limiting. Topotecan 1.25 mg (days 1-3) with IP cisplatin 50 mg/m(2) (day 1) is a regimen suitable for consolidation in phase 3 trials.

Upper limb nerve entrapment syndromes in veterans with lower limb amputations.

OBJECTIVE: To examine the prevalence and severity of upper limb entrapment syndromes in a sample of veterans with lower limb amputations. DESIGN: A descriptive survey, pilot study. SETTING: 2008 National Disabled Veterans Winter Sports Clinic. PARTICIPANTS: Twenty participants with various lower limb amputations. METHODS: All study participants completed a questionnaire that included symptoms of both upper limbs, medical history, time since amputation, medication history, use of assistive technology, and wheelchair characteristics. A physical examination and electrodiagnostic testing were then performed on each participant. The physical examination included an assessment of bilateral upper limb weakness or sensory abnormalities, thenar/hypothenar atrophy, deep tendon reflexes, Tinel test of the wrist and elbow, and the Phalen maneuver. All nerve conduction studies were performed by an American Board of Electrodiagnostic Medicine-certified physiatrist. OUTCOME MEASURES: Correlation between symptoms, examination findings, and electrodiagnostic findings with the participant's demographic data in the questionnaire. RESULTS: Twenty participants (19 men and 1 woman) were enrolled in the study, with a total of 38 upper limbs evaluated. The mean age of the study population was 59 +/- 13 years, with an average of 23 years since the amputation. Sixteen (80%) of 20 participants had electrodiagnostic findings consistent with median neuropathy across the wrist (26/38 affected limbs, 6 participants with unilateral and 10 with bilateral findings), and 14 (70%) of 20 participants had ulnar entrapment neuropathy across the elbow (22/38 affected limbs, 6 participants with unilateral and 8 with bilateral findings). Several participants (6 of 20, 30%) were found to have electrodiagnostic evidence of ulnar entrapment neuropathy across the wrist (10 of 38 affected limbs, 2 participants unilateral and 4 bilateral findings). CONCLUSION: A high number of veterans with lower limb amputations presented with upper limb nerve entrapment syndromes. Careful attention to these nerve entrapment syndromes in lower limb amputees is necessary because the symptoms may be confounded by other chronic pain-related disorders.

Origin, frequency and clinical significance of glandular cells in liquid-based pap tests from patients posthysterectomy.

OBJECTIVE: To quantify the frequency and significance of glandular cells in posthysterectomy liquid-based (SurePath, TriPath Imaging, Burlington, North Carolina, U.S.A.) vaginal Pap tests. STUDY DESIGN: The presence of benign glandular cells in vaginal Pap tests from posthysterectomy patients represents a diagnostic challenge and may pose management issues. We investigated the presence, frequency and significance of glandular cells in 52 liquid-based (SurePath) vaginal Pap tests from posthysterectomy patients by combining cytomorphologic findings with adjunctive immunohistochemistry and mucin stains performed on cell block preparations and correlated the findings with clinical data. RESULTS: After performing these special studies, the frequency of reporting glandular cells in posthysterectomy Pap tests decreased from 3.5% to 1.2% of all vaginal Pap tests performed in a 6-month period. CONCLUSION: A strong association of the presence of benign appearing glandular cells and a previous history of gynecological malignancy (71%) and chemotherapy/radiation (59%) were noted, likely representing a regenerative process in response to injury or therapy.

Prolonged topotecan infusion with cisplatin in the first-line treatment of ovarian cancer: an NYGOG and ECOG study.

OBJECTIVE: To determine the toxicity and efficacy of combined therapy with cisplatin and prolonged infusion topotecan as front line therapy in women with epithelial ovarian cancer. PATIENTS AND METHODS: Women with previously untreated, measurable and non-measurable epithelial ovarian cancer, stages Ic-IV were eligible. Patients were treated with cisplatin 75 mg/m(2) on day 1, followed by topotecan 0.3 to 0.4 mg/m(2)/day given as a continuous infusion over 14-21 days, every 28 days. Dose levels and duration of infusion were adjusted for toxicity as appropriate. Patients were evaluated for response to treatment and treatment toxicity by standard NYGOG criteria. RESULTS: Sixty patients were enrolled. Among the 20 patients with post-surgical residual disease >2 cm, 80% [95% CI (56.3%, 94.3%)] demonstrated an objective response to therapy. The median progression-free survival for all 60 patients enrolled was 19.3 months with a median overall survival of 45.6 months given the median follow-up of 55 months (range 6-81 months). Five year survival is estimated to be 41%. Toxicity was observed in the first four patients treated with topotecan (0.4 mg/m(2)/day x 21 days) and dosing was continued at 0.3 mg/m(2)/day x 14 days thereafter. Of the 56 patients treated at the amended dose level, marrow suppression continued to be dose-limiting, with 86% of patients experiencing grade 3 or 4 neutropenia, 55% experiencing grade 3 or 4 thrombocytopenia and 50% of patients experiencing grade 3 or 4 anemia. Nonetheless, only 11/245 cycles administered were associated with febrile neutropenia and/or infection (8 port-related). Other non-hematologic toxicity was as expected. There were no treatment-related deaths. CONCLUSION: This large, multicenter phase II study of prolonged infusion topotecan in combination with cisplatin demonstrated similar response, time to progression and survival compared with reported results of taxane and platinum combinations. Hematologic toxicity was greater but tolerated. Further studies investigating topotecan in combination with platinum therapy as a first line agent are warranted.

Biweekly 72-hour 9-aminocamptothecin infusion as second-line therapy for ovarian carcinoma: phase II study of the New York Gynecologic Oncology Group and the Eastern Cooperative Oncology Group.

PURPOSE: To determine the antitumor activity of the novel topoisomerase I inhibitor 9-aminocamptothecin (9-AC) given over 72 hours every 2 weeks in patients with ovarian carcinoma previously treated with one platinum-containing regimen. PATIENTS AND METHODS: Patients with ovarian carcinoma who received one prior platinum-containing regimen were eligible. Patients were stratified based on whether their disease was measurable, or nonmeasurable but assessable. 9-AC 35 microg/m(2)/h was administered by continuous infusion for 72 hours every 2 weeks via ambulatory pump. RESULTS: Sixty patients were entered, 32 with measurable and 28 with nonmeasurable but assessable disease. Ten (16.7%) of 60 patients responded (95% CI, 7.2% to 26.1%), with four complete responses and six partial remissions. The response rate for patients with measurable and nonmeasurable but assessable disease was 22% (95% CI, 7.6% to 36.2%) and 10.7% (95% CI, 2.3% to 28.2%), respectively. None of the responders were platinum-resistant. Nineteen patients (32%) had stable disease. The major toxicities were hematologic, with 25% of patients having grade 3 and 35% having grade 4 neutropenia, including five episodes of febrile neutropenia, 17% having grade 3 to 4 thrombocytopenia, and 27% having grade 3 to 4 anemia. Nonhematologic toxicity included grade 3 to 4 nausea (27%) and grade 3 to 4 vomiting (12%). CONCLUSION: This phase II multicenter trial of biweekly 72 hour 9-AC infusion as second-line therapy for ovarian cancer demonstrates comparable activity to standard approved agents in patients with both measurable and nonmeasurable but assessable disease. Toxicity consists mainly of moderate but controllable myelosuppression. Further studies combining 9-AC with other agents active in ovarian cancer for use as second-line therapy are warranted.