Procurement and cytological features of human fallopian tube fimbrial cells by ex vivo imprinting and washing.

INTRODUCTION: Fallopian tube intraepithelial cancer is a postulated precursor of epithelial ovarian carcinomas. As research continues on epithelial ovarian carcinomas' developmental pathways, representative tubal tissue must be procured for diagnostic, biological, and molecular studies without compromising pathological diagnosis. MATERIALS AND METHODS: Fallopian tube fimbrial epithelia were harvested from postmenopausal women undergoing surgery for non-neoplastic gynecologic lesions (n = 16) and epithelial ovarian carcinomas (n = 6). Cytological imprints and washings were obtained from each fimbria and stained by Diff-Quik and rapid Papanicolaou for general cytomorphology; by Trypan blue for cell viability; and by rapid immunohistochemistry for evaluation of low molecular weight cytokeratin, MIB-1, p53, and high-mobility group A (HMGA2) expression. RESULTS: Benign and malignant tubal imprints harvests yielded means of 3.5 × 105 and 1.2 × 106 cells/fimbria, respectively, with viabilities higher than 85%. A mean of 2.5 × 105 cells/fimbria was obtained from fimbrial washings. The mean DNA, RNA, and protein contents of benign imprints were 2.4, 1.5, and 67 µg/fimbria, respectively. Benign cell populations contained nearly 97% cytokeratin-positive and p53/HMGA2-negative cells, which were dispersed within a watery to proteinaceous material and rare microcalcifications. Fimbrial imprints from serous carcinomas involving the fimbriae exhibited abnormal p53 and HMGA2 expression, high proliferation, and diagnostic criteria of malignancy, including prominent nucleoli and cell crowding. CONCLUSIONS: Ex vivo harvest from operative specimens allows for collection of cell populations representative of native fimbrial epithelium and free of significant contaminants. Tubal harvest facilitates triaging of cellular material for basic, clinical, and translational studies on cancer pathobiology and also represents a potential diagnostic adjunct to emerging in vivo high-resolution optical technologies.

Measurement of phospholipids may improve diagnostic accuracy in ovarian cancer.

BACKGROUND: More than two-thirds of women who undergo surgery for suspected ovarian neoplasm do not have cancer. Our previous results suggest phospholipids as potential biomarkers of ovarian cancer. In this study, we measured the serum levels of multiple phospholipids among women undergoing surgery for suspected ovarian cancer to identify biomarkers that better predict whether an ovarian mass is malignant. METHODOLOGY/PRINCIPAL FINDINGS: We obtained serum samples preoperatively from women with suspected ovarian cancer enrolled through a prospective, population-based rapid ascertainment system. Samples were analyzed from all women in whom a diagnosis of epithelial ovarian cancer (EOC) was confirmed and from benign disease cases randomly selected from the remaining (non-EOC) samples. We measured biologically relevant phospholipids using liquid chromatography/electrospray ionization mass spectrometry. We applied a powerful statistical and machine learning approach, Hybrid huberized support vector machine (HH-SVM) to prioritize phospholipids to enter the biomarker models, and used cross-validation to obtain conservative estimates of classification error rates. RESULTS: The HH-SVM model using the measurements of specific combinations of phospholipids supplements clinical CA125 measurement and improves diagnostic accuracy. Specifically, the measurement of phospholipids improved sensitivity (identification of cases with preoperative CA125 levels below 35) among two types of cases in which CA125 performance is historically poor - early stage cases and those of mucinous histology. Measurement of phospholipids improved the identification of early stage cases from 65% (based on CA125) to 82%, and mucinous cases from 44% to 88%. CONCLUSIONS/SIGNIFICANCE: Levels of specific serum phospholipids differ between women with ovarian cancer and those with benign conditions. If validated by independent studies in the future, these biomarkers may serve as an adjunct at the time of clinical presentation, to distinguish between women with ovarian cancer and those with benign conditions with shared symptoms and features.

Salvage spiral sling techniques: alternatives to manage disabling recurrent urinary incontinence in females.

PURPOSE: Females with recurrent stress urinary incontinence after anti-incontinence surgery represent a therapeutic challenge. In our experience and that of others standard sling procedures have occasionally failed to correct these problems. We determined the effectiveness of various spiral sling techniques used in these cases to manage pipe stem urethras in which conventional slings had failed. MATERIALS AND METHODS: Between January 2007 and July 2008 we evaluated 30 female patients with persistent stress urinary incontinence after multiple failed anti-incontinence procedures. Preoperative and postoperative evaluation consisted of history, physical examination, number of pads, Stamey score and quality of life questionnaires. RESULTS: We followed 28 patients a minimum of 15 months (range 15 to 18). Mean patient age was 60 years (range 36 to 84). At presentation patients had undergone a mean of 3.5 prior vaginal procedures (range 1 to 6) and used a mean of 7 pads daily (range 3 to 12). Of the patients 21 received a synthetic spiral sling, 5 received an autologous spiral sling (rectus fascia in 3 and fascia lata in 2) and 3 received a lateral spiral sling. Mean pad use decreased to 0.9 daily (range 0 to 2, p<0.05). Postoperative mean Stamey score decreased from 2.6 to 0.3 (p<0.05). Complications included unilateral vesical perforation in 3 patients with a contralateral lateral spiral sling. The overall success rate was 72%. CONCLUSIONS: Salvage spiral sling techniques are a satisfactory alternative treatment for refractory stress urinary incontinence. When synthetic material cannot be used, autologous tissue can provide similar results. When the bladder is perforated unilaterally, a lateral spiral sling can be used on the contralateral side.

Disabling complications with slings for managing female stress urinary incontinence.

OBJECTIVE: To report an increase in the referral of patients with disabling complications after the failure of conservative therapy, their presentation, final surgical management and clinical outcome, following the use of non-autologous slings (NAS), currently the primary surgical procedure for managing stress urinary incontinence (SUI) in women. PATIENT AND METHODS: Thirty-eight patients (mean age 64 years) required surgical management for disabling complications after placing a NAS for SUI. Sling types were synthetic (25), xenografts (six) and allografts (four). Twenty (53%) patients presented with bladder outlet obstruction, 13 (34%) with sling erosion, three (8%) with worsened SUI, and two (5%) with unobstructive severe urgency and frequency. RESULTS: The sling was dissected and incised with no complication in 19 of 20 patients. One had a posterior urethral defect during sling dissection. Twelve patients (60%) acquired normal voiding and were continent. Among the 13 patients who had the sling dismantled and urethrolysis, two had recurrent or persistent SUI, two de-novo urgency/frequency and one developed osteitis pubis. Three patients with disabling SUI received a pubovaginal sling placed proximal to the bladder neck, and had an overall improvement in their urinary control with no retention. Two unobstructed patients with urgency and frequency did not improve with anticholinergic medication and pelvic floor therapy, and are now candidates for botulinum toxin injection or neurostimulation. CONCLUSIONS: The complication rate with periurethral NAS for managing SUI in females is substantial. Patients with refractory urgency/frequency after the sling need a complete evaluation with cystoscopy and video-urodynamics. Obstruction and erosion are the commonest problems and require surgical correction.

BRCA1 and BRCA2 mutations account for a large proportion of ovarian carcinoma cases.

BACKGROUND: It is believed that BRCA1 and BRCA2 germline mutations account for the majority of hereditary ovarian carcinomas; however, to the authors' knowledge, there are scant data on the prevalence and spectrum of mutations, genotype/phenotype correlations, tumor histology, and family history characteristics. To address this gap, the authors conducted a population-based study of 232 incident epithelial ovarian carcinomas in the Tampa Bay area. METHODS: Genetic testing for the BRCA1 and BRCA2 genes was performed through full sequencing and BRCA1 rearrangement testing. RESULTS: Of 209 women with invasive ovarian carcinoma, 32 women (15.3%) had mutations in BRCA1 or BRCA2, including 20 BRCA1 mutations and 12 BRCA2 mutations. Of the BRCA2 mutations, 58% were outside the "ovarian cancer cluster region" (OCCR). Variants of uncertain significance were detected in 8.2% of women with invasive ovarian carcinoma. No mutations were identified in women with borderline or invasive mucinous tumors. Among the BRCA mutation-positive women, 63% had serous tumors. A family history of breast and/or ovarian carcinoma was reported in 65%, 75%, and 43.5% of relatives of BRCA1 carriers, BRCA2 carriers, and non-BRCA1/BRCA2 carriers, respectively. CONCLUSIONS: The data from this study suggested that 1) previous studies may have underestimated the frequency of BRCA1 and BRCA2 mutations in ovarian carcinomas, especially outside the OCCR; 2) it may be reasonable to offer genetic counseling to any woman with an invasive, nonmucinous epithelial ovarian tumor; and 3) among patients with invasive ovarian carcinoma, family history is not sufficiently accurate to predict mutation status.

Lysophospholipids are potential biomarkers of ovarian cancer.

OBJECTIVE: To determine whether lysophosphatidic acid (LPA) and other lysophospholipids (LPL) are useful markers for diagnosis and/or prognosis of ovarian cancer in a controlled setting. METHOD: Plasma samples were collected from ovarian cancer patients and healthy control women in Hillsborough and Pinellas counties, Florida, and processed at the University of South Florida H. Lee Moffitt Cancer Center and Research Institute (Moffitt). Case patients with epithelial ovarian cancer (n = 117) and healthy control subjects (n = 27) participated in the study. Blinded LPL analysis, including 23 individual LPL species, was performed at the Cleveland Clinic Foundation using an electrospray ionization mass spectrometry-based method. LPL levels were transmitted to Moffitt, where clinical data were reviewed and statistical analyses were performed. RESULTS: There were statistically significant differences between preoperative case samples (n = 45) and control samples (n = 27) in the mean levels of total LPA, total lysophosphatidylinositol (LPI), sphingosine-1-phosphate (S1P), and individual LPA species as well as the combination of several LPL species. The combination of 16:0-LPA and 20:4-LPA yielded the best discrimination between preoperative case samples and control samples, with 93.1% correct classification, 91.1% sensitivity, and 96.3% specificity. In 22 cases with both preoperative and postoperative samples, the postoperative levels of several LPL, including S1P, total LPA, and lysophosphatidylcholine (LPC) levels and some individual species of LPA and LPC, were significantly different from preoperative levels. CONCLUSION: LPA, LPI, LPC, and S1P appear useful as diagnostic and prognostic biomarkers of ovarian cancer.

Superior vena cava syndrome during chemotherapy for stage 3c fallopian tube adenocarcinoma.

BACKGROUND: Superior vena cava syndrome is most often encountered in patients with malignancies. The diagnosis constitutes an oncologic emergency with prompt treatment indicated to manage the acute symptoms. There are few reports describing the syndrome in patients with gynecologic malignancies and central venous catheters. Management has included treatment of the metastatic disease and anticoagulation/thrombolysis with catheter removal early in therapy. CASE REPORT: The case described is the first report of a patient with fallopian tube carcinoma complicated by SVC syndrome. The complication was attributed to an implanted venous access port being utilized to give adjuvant combination chemotherapy. CONCLUSIONS: Superior vena cava syndrome is rarely encountered in gynecologic oncology patients and constitutes a medical emergency. When encountered in the setting of an implanted catheter, thrombolysis and anticoagulation is an alternative to catheter removal in selected patients.

Continent colonic urinary reservoir (Florida pouch): long-term surgical complications (greater than 11 years).

PURPOSE: We analyzed the long-term results (greater than 10 years) of a continent cutaneous colonic urinary reservoir (Florida pouch), focusing primarily on the incidence of significant complications. MATERIALS AND METHODS: Between January 1986 and October 1991, 179 patients underwent continent cutaneous colonic urinary reservoir construction. Of these patients 105 died of primary disease or were lost to followup, leaving 38 males and 36 females with a mean followup of 133 months with adequate data for analysis who are the subject of this report. The surgical technique has been previously reported. Briefly, a detubularized right colonic segment forms the reservoir, a tapered external limb reinforced at the ileocecal valve level allows continent catheterization and the ureters are directly anastomosed to the pouch. The diseases that prompted urinary diversion included bladder cancer in 28 cases, conversion from another diversion in 12, neurogenic bladder in 11, interstitial cystitis in 10, crippling incontinence in 4, radiation cystitis in 6, hemorrhagic cystitis in 1, exstrophy in 1 and colon cancer in 1. A total of 146 direct ureterocolonic reimplantations were performed. RESULTS: Complications were grouped by etiology and the number of patients, including abdominal wall (peristomal hernia in 3 patients or 4%), external limb (incontinence in 5 or 6.7%, stomal stenosis in 3 or 4% and difficult catheterization in 1 or 1.4%), reservoir stones (4 or 5.4%), ureteral obstruction (primary reimplantation in 7 of 108 or 6.3%, repeat reimplantation in 4 of 24 or 16.4% and radiated ureters in 4 of 14 or 28.4%) and metabolic (persistent diarrhea in 2 or 2.7%, renal failure in 2 or 2.7% and low vitamin B12 in 3 or 4%). Severe acidosis developed in 4 individuals (5.5%). Of the 12 patients who underwent conversion from another type of diversion 7 (58%) experienced metabolic alterations. CONCLUSIONS: In the long term continent colonic reservoirs have an acceptable complication rate. The most common problem is ureteral obstruction, especially in patients who have previously undergone irradiation (28.4% versus 6.3%, Fisher's test p = 0.02). Patients in whom longer bowel segments were resected, such as those with conversion from another type of diversions, experienced a greater number of complications, especially ureteral obstruction associated with repeat reimplantation (16.4% versus 6.3%, Fisher's test p = 0.23) and metabolic derangements (58% versus 6.4%, Fisher's test p = 0.0001).