Cervical ectopy: associations with sexually transmitted infections and HIV. A cross-sectional study of high school students in rural South Africa.

OBJECTIVES: It has been hypothesised that ectopy may be associated with increased susceptibility to sexually transmitted infections (STIs). In this cross-sectional study, we wanted to explore the association between STIs (including HIV) and cervical ectopy. METHODS: We included 700 sexually active young women attending randomly selected high schools in a rural district in KwaZulu-Natal, South Africa. The district is endemic of HIV and has a high prevalence of STIs. We did computer-assisted measurements of the ectocervical area covered by columnar epithelium (ectopy) in colposcopic images and STI analyses on cervicovaginal lavage and serum samples. All participating women answered a questionnaire about sexual behaviour and use of contraceptives. RESULTS: The mean age was 19.1 years. Ectopy was found in 27.2%, HIV in 27.8%, chlamydia in 25.3% and gonorrhoea in 15.6%. We found that age, parity, chlamydia and gonorrhoea, years since menarche, years since sexual debut and number of sexual partners were associated with ectopy. In multivariate analysis with chlamydia infection as the dependent variable, women with ectopy had increased odds of having chlamydia infection (adjusted OR 1.78, p=0.033). In women under 19 years of age, we found twofold higher odds of being HIV-positive for those with ectopy (OR 2.19, p=0.014). CONCLUSIONS: In conclusion, cervical ectopy is associated with Chlamydia trachomatis infection and HIV in the youngest women.

Photodynamic therapy of cervical intraepithelial neoplasia 1-3 and human papilloma virus (HMV) infection with methylaminolevulinate and hexaminolevulinate--a double-blind, dose-finding study.

INTRODUCTION: Cervical intraepithelial neoplasia (CIN) 1-3 is the precursor of invasive cervical cancer and associated with human papillomavirus infection. Standard treatment is surgical and may be associated with subsequent pregnancy complications. Photodynamic therapy (PDT) of CIN may be an interesting alternative. MATERIAL AND METHODS: Patients were treated by PDT using hexaminolevulinate (HAL) and methylaminolevulinate in six dose and light groups and two incubation periods in a double-blind setting. Follow-up examinations were performed after 3, 6, and 12 months with histology, cytology, and HPV testing. RESULTS: We included eight patients with CIN1, 23 with CIN2, and 36 with CIN3. Treatment was well tolerated. HAL 40 mM with 3-hour application turned out to be the most-effective group with 67% (10/15) complete response rate. The combined complete and partial response for patients with CIN2 was 83% (20/24). CONCLUSION: PDT with CIN may be a safe and effective procedure for CIN treatment.

Surgical outcome of obstetric fistula: a retrospective analysis of 595 patients.

OBJECTIVE: The aim of the study was to investigate obstetric fistula in terms of patient demographics, fistula characteristics and predictors of surgical outcome. DESIGN: Retrospective cross-sectional study. SETTING: Fistula referral hospital in eastern Democratic Republic of Congo. Population. Five hundred and ninety-five women receiving fistula repair from November 2005 to November 2007. METHODS: Review of patient records for information on patient demographics, obstetric history, clinical data for index pregnancy, fistula characteristics and surgical information. Cross-tabulations and multivariate logistic regression models were used to predict surgical outcome. MAIN OUTCOME MEASURES: Fistula closure and incontinence despite fistula closure. Results. 82.9% had developed fistula following obstructed labor, 17.1% after medical interventions of which 71.1% involved cesarean section or peripartum hysterectomy. Median age at fistula development was 23 years; 40.8% were primiparous and 43.2% were parity three or more. Women took a median of two years to seek treatment. Closure rate was 87.1%, with 15.6% remaining incontinent. Failure to close the fistula was significantly associated with previous repairs, amount of fibrosis and fistula size. Compared with primary repairs, the odds ratio of failure was almost five times greater for three or more repairs (odds ratio 4.7, 95% confidence interval 2.2-10.0). Incontinence was significantly associated with previous repairs, amount of fibrosis and fistula location. Compared with fistulas with a high location, the odds ratio of incontinence for low, circumferential fistulas was 6.3 (95% confidence interval 2.5-16.4). CONCLUSIONS: Fistula in Democratic Republic of Congo was found in both primiparous and multiparous women, indicating a need for increased access to obstetric care for all pregnant women. Fistulas repaired for the first time, with no fibrosis and size <2 cm, had the best surgical outcome.

Assessment of endoglin and calprotectin as potential biomarkers in ovarian carcinoma and borderline tumors of the ovary.

OBJECTIVE: The objective of the study was to analyze circulating endoglin concentration in ovarian carcinoma and evaluate a prognostic role for calprotectin and endoglin in effusions in advanced-stage disease. STUDY DESIGN: Preoperative plasma concentration of endoglin from women with benign ovarian tumors (n = 71), borderline ovarian tumors (BOT, n = 39), and ovarian carcinomas (n = 89) was analyzed with an enzyme-linked immunosorbent assay, as were endoglin and calprotectin concentrations in effusions from 164 women with advanced-stage ovarian carcinoma. RESULTS: Median endoglin plasma concentration was higher in the BOT group as compared with both control and invasive carcinoma groups (4.9 vs 4.5 and 4.3 ng/mL, P = .04 and P = .02), whereas the difference between the control and invasive group was not statistically significant (4.5 vs 4.3 ng/mL, P = .08). Endoglin and calprotectin effusion concentrations did not correlate with survival. CONCLUSION: Circulating endoglin is not elevated in advanced ovarian carcinoma. This is in contrast to the situation in breast and gastric cancer.

Circulating calprotectin in ovarian carcinomas and borderline tumors of the ovary.

OBJECTIVE: Recent studies indicate that circulating calprotectin may serve as a biomarker in some cancers. We investigated whether this is the case for ovarian neoplasms. STUDY DESIGN: Calprotectin was analyzed with an enzyme-linked immunosorbent assay in EDTA-plasma collected prior to surgery from women with ovarian carcinomas (n = 89), borderline ovarian tumors (BOT, n = 39), and benign ovarian tumors (n = 71). Serum CA 125 was analyzed in the same study population. RESULTS: Median plasma calprotectin concentration was elevated in ovarian carcinoma, compared with controls, as well as compared with BOT (both P < .001). A positive correlation was found between CA 125 and calprotectin concentrations in ovarian carcinoma. Receiver operating characteristic curves demonstrated a larger area under the curve for CA 125 (0.85) as compared with calprotectin (0.70). CONCLUSION: Plasma calprotectin is elevated in invasive ovarian cancer, but when used as a tumor marker, it is inferior to CA 125.

Complete destruction of urethra and bladder neck following symphysiotomy and results of attempted corrective surgery.

Four (0.8%) out of 526 obstetric fistulas were related to a preceding symphysiotomy procedure. Complete destruction of the urethra and bladder neck with retropubic fibrosis was found. Faulty technique is the most probable cause. All women had stillborn babies before the symphysiotomy delivery, and tissue damage due to obstructed labor could have been a predisposing factor. A neo-urethra was successfully constructed in three of the four women, but continence in standing position was not obtained.

Sexual violence-related fistulas in the Democratic Republic of Congo.

OBJECTIVE: To determine the magnitude of traumatic gynecologic fistulas caused by sexual violence in the Democratic Republic of Congo. METHODS: A retrospective analysis of hospital records from 604 consecutive patients who received treatment for gynecologic fistulas at Panzi Hospital between November 2005 and November 2007. RESULTS: Of the 604 patients, 24 (4%) reported that their fistulas had been caused by sexual violence; of these, 5 (0.8%) had developed fistulas as a direct result of forced penetration with foreign objects and/or gang rapes. Of the remaining patients, 6 had a fistula before they were raped, 9 developed iatrogenic fistulas following inappropriate instrumentation to manage rape-induced spontaneous abortion or stillbirth, or after abdominal hysterectomy, and 4 developed fistulas after prolonged and obstructed labor. CONCLUSION: Traumatic fistulas are rare compared to obstetric fistulas. Fistulas indirectly related to sexual violence are likely to be more common than those directly related. All fistulas resulting from sexual violence, whether direct or indirect, should be considered traumatic and special care should be given to these women.

The activated nerve growth factor receptor p-TrkA is selectively expressed in advanced-stage ovarian carcinoma.

The objective of this study was to compare the expression of the nerve growth factor (NGF) receptors TrkA and p75 in ovarian borderline tumors, International Federation of Gynecology and Obstetrics (FIGO) stage I carcinomas and advanced-stage (FIGO stage III-IV) carcinomas, and to assess a possible association between NGF receptor expression and mitogen-activated protein kinase (MAPK) activation in borderline tumors and FIGO stage I carcinomas. Sections from 119 borderline tumors, 57 FIGO stage I invasive ovarian carcinomas, and 56 advanced-stage carcinomas were evaluated for expression of activated phospho-TrkA (p-TrkA) and p75 using immunohistochemistry. MAPK activation was analyzed in stage I carcinomas and borderline tumors using phospho-specific antibodies against the extracellular-regulated kinase (p-ERK), the high osmolarity glycerol response kinase (p-p38), and the c-jun amino-terminal kinase (p-JNK). p-TrkA membrane expression was significantly more frequent in advanced-stage carcinomas compared with both borderline and stage I carcinomas (P < .001). p75 membrane expression was comparable in the 3 groups (P > .05). p-ERK and p-p38 expression was comparable in borderline and stage I carcinomas, whereas p-JNK was more frequently expressed in stage I ovarian carcinomas (P < .001). NGF receptor expression showed no association with MAPK activation in borderline and stage I carcinomas. In conclusion, expression of biologically active p-TrkA receptor at the cell membrane is up-regulated along tumor progression in ovarian carcinoma, whereas p75 expression remains unaltered. These data provide further evidence regarding the clinical role of p-TrkA in ovarian carcinoma. NGF receptors probably signal via MAPK-independent pathways in ovarian carcinoma.

Characteristics of Blood Vessels in Female Genital Schistosomiasis: Paving the Way for Objective Diagnostics at the Point of Care.

BACKGROUND: The mucosal changes associated with female genital schistosomiasis (FGS) encompass abnormal blood vessels. These have been described as circular, reticular, branched, convoluted and having uneven calibre. However, these characteristics are subjective descriptions and it has not been explored which of them are specific to FGS. METHODS: In colposcopic images of young women from a schistosomiasis endemic area, we performed computerised morphologic analyses of the cervical vasculature appearing on the mucosal surface. Study participants where the cervix was classified as normal served as negative controls, women with clinically diagnosed FGS and presence of typical abnormal blood vessels visible on the cervical surface served as positive cases. We also included women with cervical inflammatory conditions for reasons other than schistosomiasis. By automating morphological analyses, we explored circular configurations, vascular density, fractal dimensions and fractal lacunarity as parameters of interest. RESULTS: We found that the blood vessels typical of FGS are characterised by the presence of circular configurations (p < 0.001), increased vascular density (p = 0.015) and increased local connected fractal dimensions (p = 0.071). Using these features, we were able to correctly classify 78% of the FGS-positive cases with an accuracy of 80%. CONCLUSIONS: The blood vessels typical of FGS have circular configurations, increased vascular density and increased local connected fractal dimensions. These specific morphological features could be used diagnostically. Combined with colourimetric analyses, this represents a step towards making a diagnostic tool for FGS based on computerised image analysis.

[Primary treatment of ovarian cancer]. / Primaerbehandling av ovarialcancer.

BACKGROUND: Patients with epithelial ovarian cancer are often diagnosed with advanced disease; hence they have a generally poor survival rate. The main objective was to assess the clinical effectiveness of the four main treatment options in the primary treatment of epithelial ovarian cancer: i) adjuvant chemotherapy and/or adjuvant radiotherapy, ii) cytoreductive surgery, iii) neoadjuvant chemotherapy in advanced disease, and iv) postoperative chemotherapy in advanced disease. MATERIAL AND METHODS: The scientific literature was identified by searches in Medline, Embase and Cochrane CCTR and by additional manual searches. Using criteria defined by protocol, two reviewers assessed each study according to relevance, quality and validity. Among 2227 publications identified, 635 were read as full-text articles, and 90 studies were critically assessed as relevant publications. All included studies were systematised in three subgroups according to the quality of the study design in question and the validity of the results: high, moderate, or low. A total of 45 studies of high or moderate quality form the documentary basis for this review. RESULTS: Current data are inconclusive regarding the effect of adjuvant chemotherapy. Retrospective data show a survival advantage for patients who have had maximum cytoreductive surgery. The effect of neoadjuvant chemotherapy is uncertain. Several questions remain unanswered despite wide acceptance of paclitaxel-carboplatin as the current standard in first-line treatment. INTERPRETATION: This systematic review demonstrates the need for more clinical studies.

Schistosoma haematobium infection and CD4+ T-cell levels: a cross-sectional study of young South African women.

Schistosoma (S.) haematobium causes urogenital schistosomiasis and has been hypothesized to adversely impact HIV transmission and progression. On the other hand it has been hypothesized that HIV could influence the manifestations of schistosomiasis. In this cross-sectional study, we explored the association between urogenital S. haematobium infection and CD4 cell counts in 792 female high-school students from randomly selected schools in rural KwaZulu-Natal, South Africa. We also investigated the association between low CD4 cell counts in HIV positive women and the number of excreted schistosome eggs in urine. Sixteen percent were HIV positive and 31% had signs of urogenital schistosomiasis (as determined by genital sandy patches and / or abnormal blood vessels on ectocervix / vagina by colposcopy or presence of eggs in urine). After stratifying for HIV status, participants with and without urogenital schistosomiasis had similar CD4 cell counts. Furthermore, there was no significant difference in prevalence of urogenital schistosomiasis in HIV positive women with low and high CD4 cell counts. There was no significant difference in the number of eggs excreted in urine when comparing HIV positive and HIV negative women. Our findings indicate that urogenital schistosomiasis do not influence the number of circulating CD4 cells.

Colourimetric image analysis as a diagnostic tool in female genital schistosomiasis.

Female genital schistosomiasis (FGS) is a highly prevalent waterborne disease in some of the poorest areas of sub-Saharan Africa. Reliable and affordable diagnostics are unavailable. We explored colourimetric image analysis to identify the characteristic, yellow lesions caused by FGS. We found that the method may yield a sensitivity of 83% and a specificity of 73% in colposcopic images. The accuracy was also explored in images of simulated inferior quality, to assess the possibility of implementing such a method in simple, electronic devices. This represents the first step towards developing a safe and affordable aid in clinical diagnosis, allowing for a point-of-care approach.

The first step toward diagnosing female genital schistosomiasis by computer image analysis.

Schistosoma haematobium causes female genital schistosomiasis (FGS), which is a poverty-related disease in sub-Saharan Africa. Furthermore, it is co-endemic with human immunodeficiency virus (HIV), and biopsies from genital lesions may expose the individual to increased risk of HIV infection. However, microscopy of urine and hematuria are nonspecific and insensitive predictors of FGS and gynecological investigation requires extensive training. Safe and affordable diagnostic methods are needed. We explore a novel method of diagnosing FGS using computer color analysis of colposcopic images. In a cross-sectional study on young women in an endemic area, we found strong associations between the output from the computer color analysis and both clinical diagnosis (odds ratio [OR] = 5.97, P < 0.001) and urine microscopy for schistosomiasis (OR = 3.52, P = 0.004). Finally, using latent class statistics, we estimate that the computer color analysis yields a sensitivity of 80.5% and a specificity of 66.2% for the diagnosis of FGS.

Genital schistosomiasis and its unacknowledged role on HIV transmission in the STD intervention studies.

Treatment of sexually transmitted infections (STIs) has been hypothesised to decrease HIV transmission. Although observational studies show an association between STIs and HIV, only one prospective randomised controlled trial (RCT) has confirmed this. Female genital schistosomiasis can cause genital lesions, accompanied by bloody discharge, ulcers or malodorous discharge. Genital schistosomiasis is common, starts before puberty and symptoms can be mistaken for STIs. Three observational studies have found an association between schistosomiasis and HIV. Genital lesions that develop in childhood are chronic. This paper sought to explore the possible effects of schistosomiasis on the RCTs of STI treatment for HIV prevention. In the study sites, schistosomiasis was a likely cause of genital lesions. The studies recruited women that may have had genital schistosomal lesions established in childhood. Schistosomiasis endemic areas with different prevalence levels may have influenced HIV incidence in intervention and control sites differently, and some control group interventions may have influenced the impact of schistosomiasis on the study results. Schistosomiasis is a neglected cause of genital tract disease. It may have been an independent cause of HIV incidence in the RCTs of STI treatment for HIV prevention and may have obscured the findings of these trials.

The colposcopic atlas of schistosomiasis in the lower female genital tract based on studies in Malawi, Zimbabwe, Madagascar and South Africa.

BACKGROUND: Schistosoma (S.) haematobium is a neglected tropical disease which may affect any part of the genital tract in women. Female genital schistosomiasis (FGS) may cause abnormal vaginal discharge, contact bleeding, genital tumours, ectopic pregnancies and increased susceptibility to HIV. Symptoms may mimic those typical of sexually transmitted infections (STIs) and women with genital schistosomiasis may be incorrectly diagnosed. An expert consensus meeting suggested that the following findings by visual inspection should serve as proxy indicators for the diagnosis of schistosomiasis of the lower genital tract in women from S. haematobium endemic areas: sandy patches appearing as (1) single or clustered grains or (2) sandy patches appearing as homogenous, yellow areas, or (3) rubbery papules. In this atlas we aim to provide an overview of the genital mucosal manifestations of schistosomiasis in women. METHODOLOGY/PRINCIPAL FINDINGS: Photocolposcopic images were captured from women, between 1994 and 2012 in four different study sites endemic for S. haematobium in Malawi, Zimbabwe, South Africa and Madagascar. Images and specimens were sampled from sexually active women between 15 and 49 years of age. Colposcopic images of other diseases are included for differential diagnostic purposes. SIGNIFICANCE: This is the first atlas to present the clinical manifestations of schistosomiasis in the lower female genital tract. It will be freely available for online use, downloadable as a presentation and for print. It could be used for training purposes, further research, and in clinical practice.

Effect of female genital schistosomiasis and anti-schistosomal treatment on monocytes, CD4+ T-cells and CCR5 expression in the female genital tract.

BACKGROUND: Schistosoma haematobium is a waterborne parasite that may cause female genital schistosomiasis (FGS), characterized by genital mucosal lesions. There is clinical and epidemiological evidence for a relationship between FGS and HIV. We investigated the impact of FGS on HIV target cell density and expression of the HIV co-receptor CCR5 in blood and cervical cytobrush samples. Furthermore we evaluated the effect of anti-schistosomal treatment on these cell populations. DESIGN: The study followed a case-control design with post treatment follow-up, nested in an on-going field study on FGS. METHODS: Blood and cervical cytobrush samples were collected from FGS negative and positive women for flow cytometry analyses. Urine samples were investigated for schistosome ova by microscopy and polymerase chain reaction (PCR). RESULTS: FGS was associated with a higher frequency of CD14+ cells (monocytes) in blood (11.5% in FGS+ vs. 2.2% in FGS-, p = 0.042). Frequencies of CD4+ cells expressing CCR5 were higher in blood samples from FGS+ than from FGS- women (4.7% vs. 1.5%, p = 0.018). The CD14+ cell population decreased significantly in both compartments after anti-schistosomal treatment (p = 0.043). Although the frequency of CD4+ cells did not change after treatment, frequencies of CCR5 expression by CD4+ cells decreased significantly in both compartments (from 3.4% to 0.5% in blood, p = 0.036; and from 42.4% to 5.6% in genital samples, p = 0.025). CONCLUSIONS: The results support the hypothesis that FGS may increase the risk of HIV acquisition, not only through damage of the mucosal epithelial barrier, but also by affecting HIV target cell populations, and that anti-schistosomal treatment can modify this.

Long-term outcomes after pelvic radiation for early-stage endometrial cancer.

PURPOSE: This follow-up of a randomized study was conducted to assess the long-term effects of external beam radiation therapy (EBRT) in the adjuvant treatment of early-stage endometrial cancer. PATIENTS AND METHODS: Between 1968 and 1974, 568 patients with stage I endometrial cancer were included. After primary surgery, patients were randomly assigned to either vaginal radium brachytherapy followed by EBRT (n = 288) or brachytherapy alone (n = 280). Overall survival was analyzed by using the Kaplan-Meier method. A Cox proportional hazards model was used to estimate hazard ratios (HRs) with 95% CIs. We also conducted analyses stratified by age groups. RESULTS: After median 20.5 years (range, 0 to 43.4 years) of follow-up, no statistically significant difference was revealed in overall survival (P = .186) between treatment groups. However, women younger than age 60 years had significantly higher mortality rates after EBRT (HR, 1.36; 95% CI, 1.06 to 1.76) than the control group. The risk of secondary cancer increased after EBRT, especially in women younger than age 60 years (HR, 2.02; 95% CI, 1.30 to 3.15). CONCLUSION: We observed no survival benefit of external pelvic radiation in early-stage endometrial carcinoma. In women younger than age 60 years, pelvic radiation decreased survival and increased the risk of secondary cancer. Adjuvant EBRT should be used with caution, especially in women with a long life expectancy.

Cesarean delivery-related fistulae in the Democratic Republic of Congo.

OBJECTIVE: To compare the characteristics of urogenital fistulae after cesarean delivery with those after spontaneous vaginal delivery. METHODS: A retrospective analysis of hospital records of 597 consecutive patients with a urogenital fistula who received treatment at Panzi Hospital, Bukavu, Democratic Republic of Congo, during 2005-2007. RESULTS: Of 576 women with an obstetric fistula, 229 (40%) had had a cesarean delivery; 55 (24%) of the 229 fistulae were considered to be iatrogenic. The distribution of risk factors (age, stature, parity, and labor duration) was similar to that among 226 women with a spontaneous vaginal delivery, but the odds ratios for having a ureterovaginal or a vesicouterine fistula were 11.9 (95% confidence interval [CI] 2.8-51.2) and 9.5 (95% CI 2.8-31.9), respectively. Vesicovaginal fistulae with cervical involvement were also significantly more frequent in the cesarean delivery group. The fistulae in this group had less surrounding fibrosis and there was less treatment delay. Stillbirth rates were 87% (cesarean delivery) and 95% (spontaneous vaginal delivery). CONCLUSION: The data indicate that cesarean delivery-related fistulae are a separate clinical entity. Focus on this condition is important for fistula prevention and provision of adequate obstetric care, particularly for training in surgery and alternative delivery methods.

POLD2 and KSP37 (FGFBP2) correlate strongly with histology, stage and outcome in ovarian carcinomas.

BACKGROUND: Epithelial ovarian cancer (EOC) constitutes more than 90% of ovarian cancers and is associated with high mortality. EOC comprises a heterogeneous group of tumours, and the causes and molecular pathology are essentially unknown. Improved insight into the molecular characteristics of the different subgroups of EOC is urgently needed, and should eventually lead to earlier diagnosis as well as more individualized and effective treatments. Previously, we reported a limited number of mRNAs strongly upregulated in human osteosarcomas and other malignancies, and six were selected to be tested for a possible association with three subgroups of ovarian carcinomas and clinical parameters. METHODOLOGY/PRINCIPAL FINDINGS: The six selected mRNAs were quantified by RT-qPCR in biopsies from eleven poorly differentiated serous carcinomas (PDSC, stage III-IV), twelve moderately differentiated serous carcinomas (MDSC, stage III-IV) and eight clear cell carcinomas (CCC, stage I-IV) of the ovary. Superficial scrapings from six normal ovaries (SNO), as well as biopsies from three normal ovaries (BNO) and three benign ovarian cysts (BBOC) were analyzed for comparison. The gene expression level was related to the histological and clinical parameters of human ovarian carcinoma samples. One of the mRNAs, DNA polymerase delta 2 small subunit (POLD2), was increased in average 2.5- to almost 20-fold in MDSC and PDSC, respectively, paralleling the degree of dedifferentiation and concordant with a poor prognosis. Except for POLD2, the serous carcinomas showed a similar transcription profile, being clearly different from CCC. Another mRNA, Killer-specific secretory protein of 37 kDa (KSP37) showed six- to eight-fold higher levels in CCC stage I compared with the more advanced staged carcinomas, and correlated positively with an improved clinical outcome. CONCLUSIONS/SIGNIFICANCE: We have identified two biomarkers which are markedly upregulated in two subgroups of ovarian carcinomas and are also associated with stage and outcome. The results suggest that POLD2 and KSP37 might be potential prognostic biomarkers.