Hector Arango

Aspirin effects on endometrial cancer cell growth

Objective To find whether aspirin (acetylsalicylic acid, ASA) inhibits the growth of endometrial cancer cells in vitro in a way similar to that in colorectal cancer cells and to investigate the mechanisms by which aspirin might lead to growth inhibition. Methods Ishikawa human endometrial tumor cells were grown in the presence of ASA (1–5 mM) for 96 hours. Controls were treated with vehicle (absolute ethanol). Cell proliferation was assessed by 3-(4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide assay. Apoptosis was determined by terminal deoxynucleotidyl transferase–mediated dUTP nick-end labeling assay. Analysis of cell-cycle distribution and bcl-2 expression was assessed by flow cytometry. Results Acetylsalicylic acid induced a dose-dependent inhibition of Ishikawa cells in vitro. The percentage of growth inhibition was 21–88% at concentrations of 1–5 mM. It also induced apoptosis and reduced bcl-2 expression in Ishikawa cells in a dose-dependent manner. Control cells and cells treated with the lowest concentration of ASA exhibited 2% apoptosis and more than 60% of the population expressed bcl-2. Apoptosis levels increased as levels of ASA increased from 2 to 5 mM (7–58%) with a concommitant decrease in bcl-2 expression from 46% at 2 mM to 2% at 5 mM. Acetylsalicylic acid concentrations of 3 mM or greater induced a shift from the resting phase (G0/G1) to S phase of the cell cycle. Conclusion Acetylsalicylic acid inhibited Ishikawa cell growth in vitro in a dose-dependent manner. Apoptosis is one of the mechanisms involved in the response, which can be mediated in part by downregulation of bcl-2.

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.

ANTERIOR ENTEROCELE FOLLOWING CYSTECTOMY FOR INTRACTABLE INTERSTITIAL CYSTITIS

PURPOSE We clinically define the development of an anterior vaginal wall hernia following cystectomy for the management of intractable interstitial cystitis and establish surgical technique for its correction. MATERIALS AND METHODS Of 27 women who underwent simple cystectomy and urethrectomy for intractable interstitial cystitis an anterior vaginal wall hernia developed in 3 (71, 56 and 61 years old) at 8, 14 and 16 months, respectively, postoperatively. Clinical appearance was similar to a midline cystocele but it contained bowel contents in the form of an anterior enterocele. Anterior enterocele was associated with vaginal vault prolapse in 1 patient who was treated with transvaginal sacro-spinous colpopexy. Patients with isolated anterior enterocele required a transabdominal approach with mobilization of the intestinal hernia contents and obliteration of the intervaginal abdominal wall space. RESULTS At 12, 19 and 33 months following reconstruction prolapse has not recurred, and sexual function was restored in 1 patient. CONCLUSIONS These cases suggest that an extended simple cystectomy performed on women with intractable interstitial cystitis may result in a weakening of the anterior vaginal wall with resultant anterior enterocele formation. When it is associated with vaginal vault prolapse a transvaginal technique may be considered but we prefer a transabdominal approach for an isolated anterior enterocele. Prevention of this entity may be warranted at the time of cystectomy.

The Failed Anti-Incontinence Mechanism: A Flap Valve or Cecal Wrap for Surgical Reconstruction

PURPOSE On a long-term basis patients with continent urinary diversions may have an acceptable number of complications, such as urinary incontinence. We report on a new surgical technique for treatment of the incompetent anti-incontinence segment. MATERIALS AND METHODS Seven patients presented with a large capacity, low pressure reservoir and an incompetent anti-incontinence mechanism. The original anti-incontinence mechanism consisted of an intussuscepted reimplanted appendix (Mitrofanoff) in 2 patients, tapered ileum and reinforced ileocecal valve in 3, and tapered and reimplanted ileal segment in 2. Surgical reconstruction involved 2 stages: stage 1 - lengthening and tubularizing the cecum with the anti-incontinence segment and stage 2 - creation of the flap valve mechanism. Stage 2 required intraoperative modification when abundant peri-reservoir fibrosis, a thin-walled reservoir (cecal wrap) or an excessive thickened mesentery was encountered. RESULTS After a mean followup of 7 months 6 of 7 patients performed catheterization every 4 hours and were continent. Several patients required a concomitant procedure with the incontinence revision. CONCLUSIONS We describe a 2-stage technique for correction of a variety of untoward anatomical conditions related to a failed anti-incontinence segment with continent urinary reservoirs. Concomitant repair of other coexisting structural abnormalities related to the continent reservoir may also be necessary.

Vibroacoustic Stimulation and Auditory Acuity in Preterm Infants

Vibroacoustic stimulation (VAS) is widely accepted as a simple and inexpensive adjunctive antenatal test for fetal well-being. However, possible adverse effects of VAS on auditory acuity are not completely known and are of concern, especially for infants delivered prematurely. The purpose of our study was to evaluate neonatal hearing with the brain stem auditory evoked response (BAER) in 33 preterm neonates exposed to acoustic stimulation in utero and to compare the results with those of 33 preterm neonates who were not exposed to acoustic stimulation. Of the 33 exposed neonates, four had abnormal BAER results, indicating an apparent hearing loss. In three of four cases, an infectious etiology was found, suggesting a lack of association between antenatal VAS and hearing loss. By comparison, of the 33 preterm infants not exposed to VAS antenatally (control group), one infant had an abnormal BAER result and was subsequently diagnosed to have suffered a congenital hearing loss.Thus, the risk of acoustic trau...

A Pilot Study Utilizing Intraoperative Lymphoscintigraphy for Identification of the Sentinel Lymph Nodes in Vulvar Cancer

OBJECTIVE To identify sentinel lymph nodes using intraoperative lymphoscintigraphy. METHODS Technetium-99-labeled sulfur colloid was injected at the site of primary vulvar carcinoma. An intraoperative gamma counter was used to identify one or more sentinel lymph nodes. RESULTS Ten patients underwent bilateral inguinal and femoral lymphadenectomy. The clinical stages are as follows: T1 in 6, T2 in 2, and T3 in 2. A total of four groins (3 patients) were positive for metastases. In one patient only the sentinel node was positive for disease. In a second patient, two unilateral nodes were positive for disease and both were identified with the gamma counter as sentinel nodes. In the third patient, a single sentinel node was positive for malignancy in each groin. Multiple nonsentinel lymph nodes were positive in each groin in this patient. In no case was the sentinel node negative when other nonsentinel nodes were positive. CONCLUSION Intraoperative lymphoscintigraphy quantitatively identifies one or more sentinel lymph nodes. Since sentinel lymph nodes can be localized transcutaneously, this technique may be useful for selective lymphadenectomy. Larger patient accrual is necessary to verify this technique.