[Symphysiotomy to relieve shoulder dystocia]. / Symfysiotomie voor het opheffen van schouderdystocie.

Symphysiotomy to manage shoulder dystocia is seldom used in the western world. For this reason, in well-resourced countries knowledge of its recuperation rate and the management of physical discomfort in the post-partum period is scarce. We describe two cases of symphysiotomy for shoulder dystocia. Both babies did very well in the postpartum period. The short-term 6-week and 6-month follow-up of both mothers is described. Short-term maternal complications were minor and based on prolonged immobilization. In accordance with the international literature, the short-term and long-term follow-up after symphysiotomy for shoulder dystocia was good and there were no major maternal or neonatal complications. We therefore wish to advocate symphysiotomy as a good and safe option to deliver a baby in cases of severe shoulder dystocia, when all other manoeuvres fail.

Straylight values after refractive surgery: screening for ocular fitness in demanding professions.

PURPOSE: To study straylight testing as a screening method for ocular fitness after refractive surgery in demanding professions and to determine the distribution of elevations in straylight as a result of refractive surgery in a non-research setting in contrast with earlier reports in research settings. DESIGN: Cross-sectional study. PARTICIPANTS AND CONTROLS: The refractive surgery population consisted of 373 eyes in 198 subjects with a history of refractive surgery. The reference population consisted of 402 eyes in 214 young individuals without a history of refractive surgery. METHODS: Data were collected as part of routine testing at The Queen Astrid Military Hospital (Belgium), an independent military institution responsible for medical fitness examinations. Intraocular straylight was measured with the commercially available C-Quant instrument (Oculus Optikgeräte GmbH, Wetzlar, Germany), using the psychophysical compensation comparison (CC) method. Fellow eyes were compared to evaluate methodological aspects. The prevalence of impairment was evaluated for 2 age-independent cutoff criteria, a 2.0-fold and 3.2-fold increase, and an age-dependent cutoff criterion corresponding to an increase of 0.20 log units. MAIN OUTCOME MEASURES: Methodological aspects such as repeatability, systematic differences, and distance to impaired scores, and prevalence of impaired straylight values after refractive surgery using proposed cutoff criteria. RESULTS: The CC method exhibited good repeatability, and the chance of impaired scores due to variability in measurement was small. The prevalence of impaired straylight values was minimal in the reference population. In the refractive population, 9% (33/373) of values were above the factor 2.0 criterion, 2% (7/373) were above the factor 3.2 criterion, and 12% (45/373) were 0.20 log units above the age reference. CONCLUSIONS: Straylight testing is a viable screening method for ocular fitness after refractive surgery. Patients from the general population who have undergone refractive surgery have significant elevations more frequently than surgery populations from high-quality research centers.

Differentiated vulvar intraepithelial neoplasia is often found in lesions, previously diagnosed as lichen sclerosus, which have progressed to vulvar squamous cell carcinoma.

Lichen sclerosus is considered to be the precursor lesion of vulvar squamous cell carcinoma, of which only 2-5% progress to squamous cell carcinoma. Differentiated vulvar intraepithelial neoplasia (VIN) has been proposed to be the direct precursor lesion, but this is a recently recognized, and a difficult to diagnose, entity, which may easily be mistaken for a benign dermatosis. The aim of this study was to test the hypothesis that of all lesions that have been diagnosed as lichen sclerosus in the past, a part might currently be diagnosed as differentiated VIN, and to identify histopathological differences between lichen sclerosus lesions with and without progression to vulvar squamous cell carcinoma. All lichen sclerosus slides were revised by two expert gynecopathologists and histopathological characteristics were documented. After revision of lichen sclerosus biopsies without progression (n = 61), 58 were reclassified as lichen sclerosus. Revision of lichen sclerosus biopsies with progression yielded concordant diagnoses in 18 of 60 cases (30%). Of 60 lesions, 25 (42%) were reclassified as differentiated VIN. The median time from differentiated VIN to vulvar squamous cell carcinoma was shorter (28 months) than that from lichen sclerosus to vulvar squamous cell carcinoma (84 months) (P < 0.001). Lichen sclerosus that progressed to squamous cell carcinoma, but did not meet the criteria for differentiated VIN, more often showed parakeratosis (P = 0.004), dyskeratosis (P < 0.001), hyperplasia (P = 0.048) and basal cellular atypia (P = 0.009) compared with lichen sclerosus without progression. In conclusion, differentiated VIN diagnosis has been frequently missed and is associated with rapid progression to squamous cell carcinoma. Patients with lichen sclerosus with dyskeratosis and parakeratosis, hyperplasia and/or basal cellular atypia should be kept under close surveillance as these lesions also tend to progress to squamous cell carcinoma.

Hemoglobin level predicts outcome for vulvar cancer patients independent of GLUT-1 and CA-IX expression in tumor tissue.

Intratumoral hypoxia has been associated with poor prognosis in several solid tumors. The aim of this study was to determine whether the hypoxia-associated markers glucose transporter (GLUT)-1 and carbonic anhydrase (CA)-IX expression and preoperative hemoglobin (Hb) levels correlate with presence of inguinofemoral or distant metastases, and disease-free survival (DSS) in vulvar squamous cell carcinoma (SCC) patients. Vulvar SCC (n=103) were reviewed for histopathological characteristics by an expert gynecopathologist and stained for GLUT-1 and CA-IX. Clinical data and preoperative Hb levels were obtained from medical records. No significant correlations were observed between GLUT-1 or CA-IX expression patterns and preoperative Hb levels, presence of inguinofemoral or distant metastases and DSS. However, anemic patients (Hb<11.2 g/dL) had significantly more inguinofemoral metastases and lower Hb level was an independent prognostic factor for a worse DSS (p<0.001). The number of comorbidic conditions was inversely correlated with preoperative Hb level. Preoperative Hb levels are associated with poor DSS for vulvar SCC patients, whereas tumor hypoxia reflected by GLUT-1 and CA-IX expression does not have a predictive value. Because preoperative Hb levels inversely correlated with the number of comorbidic conditions and not with GLUT-1 or CA-IX expression, it is most likely that preoperative Hb levels represent overall physical condition.

The effect of vulvar lichen sclerosus on quality of life and sexual functioning.

Lichen sclerosus (LS) is a chronic skin disorder mostly seen on the female anogenital skin. The aim of this study was to evaluate the quality of life (QoL) and sexuality in female patients with LS and to compare their scores with healthy controls. In addition, we wanted to find factors associated with impaired sexual functioning in patients with LS. Members of the Dutch LS foundation and support group were asked to fill in three questionnaires: the Dermatology Quality of Life Index, Female Sexual Function Index (FSFI) and Female Sexual Distress Scale (FSDS). 215 of 368 patients returned their questionnaire (58.4%). Their scores were compared to a control group which consisted of 61 women of similar age (p = 0.472) without a skin disorder. Of all domains of QoL, LS interfered most with sexual functioning. Patients significantly scored lower on all subscales of the FSFI (desire (p = 0.016), arousal (p < 0.001), lubrication (p < 0.001), orgasm (p < 0.001), satisfaction (p < 0.001) and pain (p < 0.001), indicating worse sexual functioning. These problems with sexual functioning brought about significant sexual distress (p < 0.001). Patients who experienced more influence on their QoL had more sexual difficulties, leading to more sexual distress independent of their age.

Specific intraepithelial localization of mast cells in differentiated vulvar intraepithelial neoplasia and its possible contribution to vulvar squamous cell carcinoma development.

AIMS: The aetiology of vulvar squamous cell carcinomas (SCC) that are not causally associated with high-risk human papillomavirus remains largely elusive. The aim of this study was to analyse the inflammatory response in its presumed precursor lesions, lichen sclerosus (LS) and differentiated vulvar intraepithelial neoplasia (dVIN), and provide evidence that dVIN is a likely precursor of vulvar SCC. METHODS AND RESULTS: Immunohistochemical analyses for CD4+, CD8+, CD20+, CD68+, S100+ and tryptase-positive immune cells were performed and quantified in LS (n = 7), dVIN (n = 19), SCC (n = 11), and normal vulvar tissue (n = 8). The subepithelial inflammatory response in dVIN and SCC was comparable, but absent in LS. Abundant intraepithelial mast cells were observed in dVIN only, and confirmed by electron microscopy, toluidine blue staining and cKIT expression. Adjacent keratinocytes displayed increased proliferation as determined by MIB-1 positivity. Electron microscopy revealed intraepithelial mast cell degranulation. Intraepithelial mast cells were not or infrequently observed in vulvar hyperplasia (n = 13), condylomata acuminata (n = 5), keratinocytic intraepidermal neoplasia of sun-exposed skin (n = 15), epidermal hyperplasia of head and neck (n = 12), and psoriasis (n = 3). CONCLUSIONS: These data indicate that dVIN can be recognized by intraepithelial mast cells and that they might promote the progression of dVIN to SCC.

High levels of p53 expression correlate with DNA aneuploidy in (pre)malignancies of the vulva.

The molecular pathogenesis of human papilloma virus-unrelated vulvar squamous cell carcinoma is not well known. Whether malignant progression of lichen sclerosus and differentiated vulvar intraepithelial neoplasia to vulvar squamous cell carcinoma could be accompanied by altered DNA content has not been studied extensively. DNA content in isolated nuclei of microdissected normal vulvar epithelium (n = 2), lichen sclerosus (n = 9), differentiated vulvar intraepithelial neoplasia (n = 13), and squamous cell carcinoma (n = 17) from 22 patients was measured via DNA image cytometry. For additional analysis, 6 differentiated vulvar intraepithelial neoplasia lesions were selected, bringing the number of patients to 28. p53 expression was determined by immunohistochemistry on consecutive tissue sections. Thirty-eight percent (5/13) of differentiated vulvar intraepithelial neoplasia lesions and 65% (11/17) of squamous cell carcinomas were DNA aneuploid or tetraploid. In lesions that contained differentiated vulvar intraepithelial neoplasia and adjacent squamous cell carcinoma, the ploidy status of differentiated vulvar intraepithelial neoplasia did not exceed that of squamous cell carcinoma. We observed a strong correlation between high p53 expression and DNA aneuploidy. This relation was also present at the level of a single nucleus, measured by sequential image cytometry of p53 immunohistochemistry followed by DNA image cytometry on formalin-fixed tissue sections. Similarly, we found p53-positive nonproliferating cells with increased DNA content in the superficial compartment of 6 additional solitary differentiated vulvar intraepithelial neoplasia lesions that were not associated with squamous cell carcinoma, indicating ascending aneuploid cells from the basal compartment. DNA ploidy measurements suggest that differentiated vulvar intraepithelial neoplasia has a higher malignant potential than lichen sclerosus and thus is a more likely precursor of squamous cell carcinoma. Furthermore, high p53 expression correlates with increased DNA content and aneuploidy; but it requires further research to unveil a possible causal relation.

How to design magneto-based total analysis systems for biomedical applications.

This article reviews recent developments on magnetoresistive detection of magnetic beads or nanoparticles by nanoscale sized sensors. Sensors are analyzed from an experimental and a numerical point of view in respect to their capability to either localize the position of a single magnetic particle or to detect the number of particles in a certain range. Guidelines are shown up on how to extend single sensors to sensor arrays with very high spatial resolution and how to modify the sensor shape in order to provide long distance measurements. Further, sensors in biological lab-on-a-chip environments are discussed. The magnetic ratchet and a gravitation based microfluidic component are reviewed as important tools to position and, therefore, detect biological components in continuous-flow devices.

A patient with lichen sclerosus, Langerhans cell histiocytosis, and invasive squamous cell carcinoma of the vulva.

We report a patient with vulvar lichen sclerosus, Langerhans cell histiocytosis (LCH), and later vulvar cancer. In LCH, high amounts of non functional Langerhans cells are present in the affected tissue, making it possible that LCH may have contributed to vulvar cancer development in this patient.

The prognostic value of blood and lymph vessel parameters in lichen sclerosus for vulvar squamous cell carcinoma development: an immunohistochemical and electron microscopy study.

OBJECTIVE: The objective of the study was to quantify vessel type and density in lichen sclerosus (LS) to find a marker for its malignant potential. STUDY DESIGN: Quantitative analysis was performed on paraffin-embedded tissue samples of 28 patients with LS (7 adjacent to vulvar squamous cell carcinoma, 21 solitary) and immunohistochemical staining for CD34 (vascular and lymphangiogenic lymph endothelial cells), D2-40 (lymphatic-specific marker), and alpha-SMA (pericyte marker). Electron microscopy was performed on fresh tissue. RESULTS: No significant differences in vessel density or other vessel parameters could be demonstrated between the 2 groups. In hyalinized lesions, vessel diameter, and alpha-SMA positivity was reduced compared with nonhyalinized lesions. Electron microscopy revealed detachment of pericytes from vascular endothelial cells and increased thickening of basement membrane, whereas endothelial cell function did not appear strongly impaired. CONCLUSION: Malignant potential of LS cannot be predicted by vessel characteristics. Hyalinization in LS is associated with pericyte detachment from the basal lamina of vascular endothelial cells.

Update on the sentinel lymph node procedure in vulvar cancer.

Currently, standard treatment for early-stage vulvar cancer typically includes wide local excision of the primary tumor and inguinofemoral lymphadenectomy. The morbidity of this treatment is high. The sentinel lymph node (SLN) procedure provides us with a technique for determining the status of the regional lymph nodes with less treatment-related morbidity. Recently, a large multicenter observational study provided level 3 evidence indicating that it appears safe to omit inguinofemoral lymphadenectomy in case of a negative SLN. This review focuses on the different aspects of the SLN procedure in vulvar cancer.

Never forget medication as a cause: vaginal ulceration caused by nicorandil.

A patient was referred to our vulvar outpatient clinic because of a vaginal ulceration that persisted for 3 years and that had been unresponsive to any prescribed therapy. After a possible association was found with nicorandil therapy, this medication was stopped. Thereafter, the ulceration fully healed within 6 months.

The etiologic role of HPV in vulvar squamous cell carcinoma fine tuned.

PURPOSE: High-risk human papilloma virus (HPV) plays a role in the development of a subset of vulvar squamous cell carcinomas. Uncertainty exists about the true impact of HPV in this tumor type because conflicting reports have been published with diverging prevalence rates. This study was done to fine tune the role of high-risk HPV infection in vulvar squamous cell carcinoma development in relation to clinical prognosis. EXPERIMENTAL DESIGN: 130 vulvar squamous cell carcinomas of patients with known survival data were analyzed for histology of the adjacent lesion (differentiated or HPV-associated usual vulvar intraepithelial neoplasia), in relation to p16(INK4A) expression as marker of HPV activity, and presence and integration of high-risk HPV DNA. RESULTS: Usual vulvar intraepithelial neoplasia was present adjacent to vulvar squamous cell carcinoma in 25 of 130 cases. Usual vulvar intraepithelial neoplasia-associated squamous cell carcinomas had high p16(INK4A) expression, and 24 of 25 squamous cell carcinomas contained integrated high-risk HPV DNA. Differentiated vulvar intraepithelial neoplasia was found adjacent to 105 of 130 vulvar squamous cell carcinomas. High-risk HPV was detected in 11 (10.5%) differentiated vulvar intraepithelial neoplasia-associated vulvar squamous cell carcinoma but correlated with high p16(INK4A) expression in only one case. Integration of viral DNA was never observed in differentiated vulvar intraepithelial neoplasia-associated squamous cell carcinomas, which suggests that a causal relationship of high-risk HPV in differentiated vulvar intraepithelial neoplasia-associated tumors is highly unlikely. The disease-specific survival of the differentiated vulvar intraepithelial neoplasia-associated vulvar squamous cell carcinoma patients was significantly worse compared with patients with a usual vulvar intraepithelial neoplasia-associated tumor. CONCLUSIONS: High-risk HPV is causally associated with the development of usual vulvar intraepithelial neoplasia associated squamous cell carcinomas, which comprise 19% of all vulvar squamous cell carcinomas, but not with differentiated vulvar intraepithelial neoplasia-associated vulvar squamous cell carcinomas. Differentiated vulvar intraepithelial neoplasia-associated vulvar squamous cell carcinomas have a significantly worse prognosis.

The role of sentinel node biopsy in gynecological cancer: a review.

PURPOSE OF REVIEW: In early-stage vulvar, cervical and endometrial cancer, lymph node status is the most important prognostic factor. Surgical treatment is aimed at removing the primary tumor and adequately staging the regional lymph nodes. As morbidity of regional lymphadenectomy is high, sentinel node biopsy is a technique with potential for adequate staging with less treatment-related morbidity. This manuscript reviews its current role in vulvar, cervical and endometrial cancer. RECENT FINDINGS: In early-stage vulvar cancer, level 3 evidence indicates that it appears to be safe to omit inguinofemoral lymphadenectomy in case of a negative sentinel node. However, false-negative results with fatal consequences do occur and are often attributable to procedural failures. For early-stage cervical cancer, level 3 evidence points to an acceptable false-negative rate of a negative sentinel node; clinical utility and safety remain to be established. The optimal technique of the sentinel node biopsy in endometrial cancer is currently unclear. SUMMARY: In early-stage vulvar cancer, data suggest that sentinel node biopsy could be offered as a treatment option instead of routine inguinofemoral lymphadenectomy. However, more (long-term follow-up) data are needed to further appreciate real clinical benefits. It is emphasized that the procedure should be performed by a skilled multidisciplinary team, centralized in oncology centers and preferably within the protection of clinical trials. For cervical cancer, data are promising, but routine application cannot be recommended due to lack of data on clinical utility and safety. For endometrial cancer, studies on the sentinel node biopsy are still in feasibility stage.

Vulvar squamous cell carcinoma development after diagnosis of VIN increases with age.

OBJECTIVE: The purpose of the present study is to investigate the trends in incidence of both usual (u) and differentiated (d) vulvar intraepithelial neoplasia (VIN) separately, their malignant potential and the relation with other HPV related anogenital lesions in the Netherlands during a 14-year-period. METHODS: The incidences of both types of VIN and vulvar SCC were retrieved from the Nationwide Netherlands Database of Histo- and Cytopathology. Population data were retrieved from the Database of Statistics Netherlands. RESULTS: In the study period, the incidence of uVIN and dVIN increased, while the incidence of vulvar SCC remained stable. The overall percentage of uVIN patients that were later diagnosed with vulvar SCC was 5.7%, which was significantly lower than the percentage for dVIN patients (32.8%). In addition to this 5.6-fold increased conversion rate, the time of progression from dVIN to SCC development was significantly shorter than that of uVIN (p=0.005). Percentage of uVIN patients that were later diagnosed with SCC significantly increased with age (p=0.005), whereas the time to SCC significantly shortened with age (p=0.05). Forty-one percent of uVIN patients had a past, concomitant or future HPV-associated lesion of the lower genital tract, which is in contrast to the 3% for dVIN patients. CONCLUSIONS: An increase in diagnoses of both uVIN and dVIN has not led to an increase in vulvar SCC incidence. The malignant potential of dVIN is higher than that for uVIN. For uVIN the malignant potential increases with age.

Does experience in colposcopy improve identification of high grade abnormalities?

OBJECTIVE: This study investigates whether experience in colposcopy improves identification of high grade abnormalities. The sensitivity and positive predictive value (PPV) of colposcopy in identifying high grade intra-epithelial lesions (HSIL) performed by relatively inexperienced as compared to experienced colposcopists are evaluated. STUDY DESIGN: Of 18,421 colposcopies performed at the Royal Women's Hospital, Melbourne, Australia, between 1999 and 2004 by 5 senior and 11 junior colposcopists, the colposcopic impression was correlated with the histopathology result of the biopsy taken at 6020 colposcopies, with respect to the experience of the colposcopist. RESULTS: Colposcopy had a 60% sensitivity and 60% PPV in identifying HSIL in this study. In case of a high-grade referral smear the sensitivity and PPV in identifying HSIL were, respectively 76% and 73%, compared with 26% and 48% in case of a low-grade referral smear, no difference in overall colposcopic performance between experienced and inexperienced colposcopists was observed. However, the sensitivity of identifying HSIL was significantly higher with inexperienced colposcopists, and the PPV was significantly higher with experienced colposcopists. CONCLUSION: In this study experience did not improve colposcopic performance, but differences in colposcopic strategy between the two groups were noted. The rather low overall sensitivity and PPV of colposcopy in identifying HSIL, especially in case of a low-grade referral smear, indicate that the role of colposcopy in the detection and treatment of cervical abnormalities is to assess size, site, and extent of an abnormality, rather than to assess the severity of this abnormality. Histology must remain the gold standard for treatment.