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(See the major article by Howell-Jones et al on pages 1397–403.) The human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine (Cervarix®; GlaxoSmithKline Vaccines) has been demonstrated to have high efficacy against infection and both low- and high-grade cervical intraepithelial neoplasia (CIN; caused by oncogenic HPV types 16 and 18, with substantial cross protection against other high-risk HPV types 31, 33, 45, and 51 [1, 2]. Low-risk HPV types are found in approximately 12% of low-grade CIN, although there is likely to be coinfection with high-risk types [3]. While immunogenicity has been demonstrated in boys [4], the HPV-16/18 AS04-adjuvanted vaccine is not currently licensed for use in boys. Genital warts (GWs) are the most common viral sexually transmitted infection in the Western world, and a 30% increase in new diagnoses was seen in the United Kingdom between 2000 and 2009 [5]. Treatment has a significant morbidity and can be frustrating, and recurrences are common. This causes psychosocial distress to patients and results in substantial financial costs [6, 7]. GWs result from persistent infection with low-risk HPV genotypes, predominantly 6 and 11, although other low-risk types were not evaluated in the former study [8, 9]. It has been suggested that a small proportion of GWs may be caused by HPV types 16 and 18; [10, 11] if true, limited efficacy against warts could occur with a vaccine directed against these types [10, 11]. The HPV-16/18 AS04-adjuvanted vaccine was chosen for the UK national vaccination program, which commenced in September 2008 and has achieved >84% uptake in 12- to 15-year-old girls for all 3 doses. A catch-up program to the age of 18 years achieved between 50% and 70% uptake for all 3 doses [12]. Public Health England (formerly the Health Protection Agency), which monitors rates of sexually transmitted infections in England, has reported a decrease in new diagnoses of GWs in genitourinary medicine clinics among young women since 2008 [13]. By 2011, the overall reduction was 13.3% among 16- to 19-year-olds, with the greatest decline (20.8%) in 17-year-olds, for whom HPV-16/18 AS04-adjuvanted vaccine coverage in 2011 was estimated at 64%. By contrast, rates in the older age groups were generally either static or increasing [14]. Among the potential reasons for this decrease, as discussed by Howell-Jones et al [14], is the possibility of an effect of the HPV-16/18 ASO4-adjuvanted vaccine on low-risk HPV types. A post hoc analysis of the PATRICIA (PApilloma TRIal against Cancer In young Adults) trial was therefore performed to ascertain whether any protection against low-risk HPV types was apparent.

Background Acute gastric dilatation is a rare but severe complication of anorexia nervosa. Gastric dilatation causing abdominal compartment syndrome with lower-limb ischemia is even less common. This case report illustrates the importance of a holistic clinical approach of every patient presenting to the emergency department (ED), even when the reason for admittance is organ specific. Case Report We report the case of a young female patient presenting to the ED with a painful white left leg. Clinical examination revealed acute lower-limb ischemia, abdominal distention, and shock. Diagnostic work-up, including an abdominal computed tomography scan, showed compression of the aorta, inferior vena cava, and both iliac arteries, as well as hypoperfusion of the right kidney and left liver lobe, all due to compression by a massive gastric dilatation. Gastroscopy revealed a massively dilated stomach containing > 6 L of fluid and gastric wall ischemia. After decompression, the circulation to the lower limbs recovered immediately. The day after admission the patient developed an acute abdomen leading to a semi-urgent laparoscopy during which a sleeve gastrectomy was performed for the treatment of partial gastric necrosis. Clinical evolution afterward was favorable and the patient recovered completely. Conclusions This case report underscores the importance of a thorough clinical examination in every patient admitted to the ED. Early diagnosis and treatment are mandatory in preventing fatal complications.

Leydig cell hyperplasia and Leydig cell tumours of the ovary are rare. We present two cases in which patients had increased blood levels of testosterone and frank hirsutism. Imaging showed minimal abnormalities. After adrenal disease had been ruled out, they underwent a bilateral oophorectomy. One case showed a Leydig cell hyperplasia, the other a Leydig cell tumour. An androgen producing tumour should be excluded in every woman with evidence of hirsutism or frank virilization and markedly elevated testosterone levels. Adrenal disease with androgen hypersecretion can be suspected by detailed clinical, laboratory and radiologic imaging. Although DHEAS has a good sensitivity in the detection of adrenal origin of hyperandrogenism (and hence a good negative predictive value) it is not specific (specificity ranging from 85 to 98%). Imaging of the ovaries can be helpful but does not rule out ovarian disease if normal. Indeed, diffuse stromal Leydig cell hyperplasia and Leydig cell tumours (usually small) may escape imaging and in some cases diagnosis can only be made on pathology. As these clinical entities represent a diagnostic and therapeutic challenge, oophorectomy should be considered in postmenopausal women with hirsutism and elevated testosterone levels, after the exclusion of adrenal causes. The procedure is relatively safe and effective. Follow-up remains indicated.

Boerhaave's syndrome is a rare but potentially fatal condition characterised by a transmural tear of the distal oesophagus induced by a sudden increase in pressure. Diagnosis is challenging as the classic triad of vomiting, abdominal or chest pain, and subcutaneous emphysema is absent in many patients. Management is multidisciplinary and relies on rapid, distinct, and repeated imaging. Treatment has not been standardised and may be conservative, endoscopic, or surgical. We present a typical case which illustrates possible diagnostic pitfalls and the therapeutic conundrum surrounding management of the syndrome. Based on time of presentation and eventual presence of sepsis, a therapeutic algorithm is proposed.

Dabigatran etexilate is emerging as an alternative for vitamin K antagonists, but evidence-based guidelines for management of intracerebral hemorrhage and acute ischemic stroke in patients taking this drug are nonexistent. This review summarizes current knowledge on key pharmacological features and the assessment of dabigatran activity. Pragmatic approaches are provided for individualized decision taking with regard to hemostatic therapy and reperfusion strategies in acute stroke patients.

Background. Lymphoedema of the operated and irradiated breast is a common complication following early breast cancer treatment. There is no consensus on objective diagnostic criteria and standard measurement tools. This study investigates the use of ultrasound elastography as an objective quantitative measurement tool for the diagnosis of parenchymal breast oedema. Patients and methods. The elasticity ratio of the subcutis, measured with ultrasound elastography, was compared with high-frequency ultrasound parameters and subjective symptoms in twenty patients, bilaterally, prior to and following breast conserving surgery and breast irradiation. Results. Elasticity ratio of the subcutis of the operated breast following radiation therapy increased in 88.9% of patients, was significantly higher than prior to surgery, unlike the non operated breast and significantly higher than the non operated breast, unlike preoperative results. These results were significantly correlated with visibility of the echogenic line, measured with high-frequency ultrasound. Big preoperative bra cup size was a significant risk factor for the development of breast oedema. Conclusions. Ultrasound elastography is an objective quantitative measurement tool for the diagnosis of parenchymal breast oedema, in combination with other objective diagnostic criteria. Further research with longer follow-up and more patients is necessary to confirm our findings.

Objective: Bacterial vaginosis (BV), the most common vaginal disorder among women of reproductive age, has been suggested as co-factor in the development of cervical cancer. Previous studies examining the relationship between BV and cervical intra-epithelial neoplasia (CIN) provided inconsistent and conflicting results. The aim of this study is to clarify the association between these two conditions. Methods: A systematic review and meta-analysis were conducted to summarize published literature on the association between BV and cervical pre-cancerous lesions. An extensive search of electronic databases Medline (Pubmed) and Web of Science was performed. The key words 'bacterial vaginosis' and 'bacterial infections and vaginitis' were used in combination with 'cervical intraepithelial neoplasia', 'squamous intraepithelial lesions', 'cervical lesions', 'cervical dysplasia', and 'cervical screening'. Eligible studies required a clear description of diagnostic methods used for detecting both BV and cervical precancerous lesions. Publications were included if they either reported odds ratios (OR) and corresponding 95% confidence intervals (CI) representing the magnitude of association between these two conditions, or presented data that allowed calculation of the OR. Results: Out of 329 articles, 17 cross-sectional and 2 incidence studies were selected. In addition, two studies conducted in The Netherlands, using the national KOPAC system, were retained. After testing for heterogeneity and publication bias, meta-analysis and meta-regression were performed, using a random effects model. Although heterogeneity among studies was high (chi(2) = 164.7, p < 0.01, I-2 = 88.5), a positive association between BV and cervical pre-cancerous lesions was found, with an overall estimated odds ratio of 1.51 (95% CI, 1.24-1.83). Meta-regression analysis could not detect a significant difference between studies based on BV diagnosis, CIN diagnosis or study population. Conclusions: Although most studies were cross-sectional and heterogeneity was high, this meta-analysis confirms a connection between BV and CIN.

Summary Background Cervical intraepithelial neoplasia grade 2 or greater (CIN2+) is the surrogate endpoint used in licensure trials of human papillomavirus (HPV) vaccines. Vaccine efficacy against CIN3+, the immediate precursor to invasive cervical cancer, is more difficult to measure because of its lower incidence, but provides the most stringent evidence of potential cancer prevention. We report vaccine efficacy against CIN3+ and adenocarcinoma in situ (AIS) in the end-of-study analysis of PATRICIA (PApilloma TRIal against Cancer In young Adults). Methods Healthy women aged 15–25 years with no more than six lifetime sexual partners were included in PATRICIA, irrespective of their baseline HPV DNA status, HPV-16 or HPV-18 serostatus, or cytology. Women were randomly assigned (1:1) to receive an HPV-16/18 AS04-adjuvanted vaccine or a control hepatitis A vaccine via an internet-based central randomisation system using a minimisation algorithm to account for age ranges and study sites. The patients and study investigators were masked to allocated vaccine. The primary endpoint of PATRICIA has been reported previously. In the present end-of-study analysis, we focus on CIN3+ and AIS in the populations of most clinical interest, the total vaccinated cohort (TVC) and the TVC-naive. The TVC comprised all women who received at least one vaccine dose, approximating catch-up populations and including sexually active women (vaccine n=9319; control=9325). The TVC-naive comprised women with no evidence of oncogenic HPV infection at baseline, approximating early adolescent HPV exposure (vaccine n=5824; control=5820). This study is registered with ClinicalTrials.gov, number NCT00122681. Findings Vaccine efficacy against CIN3+ associated with HPV-16/18 was 100% (95% CI 85·5–100) in the TVC-naive and 45·7% (22·9–62·2) in the TVC. Vaccine efficacy against all CIN3+ (irrespective of HPV type in the lesion and including lesions with no HPV DNA detected) was 93·2% (78·9–98·7) in the TVC-naive and 45·6% (28·8–58·7) in the TVC. In the TVC-naive, vaccine efficacy against all CIN3+ was higher than 90% in all age groups. In the TVC, vaccine efficacy against all CIN3+ and CIN3+ associated with HPV-16/18 was highest in the 15–17 year age group and progressively decreased in the 18–20 year and 21–25 year age groups. Vaccine efficacy against all AIS was 100% (31·0–100) and 76·9% (16·0–95·8) in the TVC-naive and TVC, respectively. Serious adverse events occurred in 835 (9·0%) and 829 (8·9%) women in the vaccine and control groups, respectively; only ten events (0·1%) and five events (0·1%), respectively, were considered to be related to vaccination. Interpretation PATRICIA end-of-study results show excellent vaccine efficacy against CIN3+ and AIS irrespective of HPV DNA in the lesion. Population-based vaccination that incorporates the HPV-16/18 vaccine and high coverage of early adolescents might have the potential to substantially reduce the incidence of cervical cancer. Funding GlaxoSmithKline Biologicals.

Neuroblastoma is an aggressive embryonal tumor that accounts for similar to 15% of childhood cancer deaths. Hitherto, despite the availability of comprehensive genomic data on DNA copy number changes in neuroblastoma, relatively little is known about the genes driving neuroblastoma tumorigenesis. In this study, high resolution array comparative genome hybridization (CGH) was performed on 188 primary neuroblastoma tumors and 33 neuroblastoma cell lines to search for previously undetected recurrent DNA copy number gains and losses. A new recurrent distal chromosome 1q deletion (del(1)(q42.2qter)) was detected in seven cases. Further analysis of available array CGH datasets revealed 13 additional similar distal 1q deletions. The majority of all detected 1q deletions was found in high risk 11q deleted tumors without MYCN amplification (Fisher exact test p = 5.61 x 10-5). Using ultra-high resolution (similar to 115 bp resolution) custom arrays covering the breakpoints on 1q for 11 samples, clustering of nine breakpoints was observed within a 12.5-kb region, of which eight were found in a 7-kb copy number variable region, whereas the remaining two breakpoints were colocated 1.4-Mb proximal. The commonly deleted region contains one miRNA (hsa-mir-1537), four transcribed ultra conserved region elements (uc.43-uc.46) and 130 protein coding genes including at least two bona fide tumor suppressor genes, EGLN1 (or PHD2) and FH. This finding further contributes to the delineation of the genomic profile of aggressive neuroblastoma, offers perspectives for the identification of genes contributing to the disease phenotype and may be relevant in the light of assessment of response to new molecular treatments

Background Bacterial vaginosis (BV), an alteration of vaginal flora involving a decrease in Lactobacilli and predominance of anaerobic bacteria, is among the most common cause of vaginal complaints for women of childbearing age. It is well known that BV has an influence in acquisition of certain genital infections. However, association between BV and cervical human papillomavirus (HPV) infection has been inconsistent among studies. The objective of this meta-analysis of published studies is to clarify and summarize published literature on the extent to which BV is associated with cervical HPV infection. Methods Medline and Web of Science were systematically searched for eligible publications until December 2009. Articles were selected based on inclusion and exclusion criteria. After testing heterogeneity of studies, meta-analysis was performed using random effect model. Results Twelve eligible studies were selected to review the association between BV and HPV, including a total of 6,372 women. The pooled prevalence of BV was 32%. The overall estimated odds ratio (OR) showed a positive association between BV and cervical HPV infection (OR, 1.43; 95% confidence interval, 1.11-1.84). Conclusion This meta-analysis of available literature resulted in a positive association between BV and uterine cervical HPV infection.

Introduction The spinal cord is a target for many neurosurgical procedures used to treat chronic severe pain. Neuromodulation and neuroablation are surgical techniques based on well-known specific anatomical structures. However, anatomical and electrophysical changes related to the tethered spinal cord make it more difficult to use these procedures. Case presentation We report the case of a 37-year-old Caucasian woman who had several surgical interventions for tethered cord syndrome. These interventions resulted in severe neuropathic pain in her lower back and right leg. This pain was treated by spinal cord stimulation using intra-operative sensory mapping, which allowed the cord's optimal placement in a more caudal position. Conclusion The low-voltage and more caudally placed electrodes are specific features of this treatment of tethered cord syndrome.

(2010). The new RBSS Platform for Internet Based Scientific Studies. Acta Chirurgica Belgica: Vol. 110, No. 1, pp. 9-9.

The effectiveness of the dendritic cell (DC) vaccination protocols that are currently in use could be improved by providing the DCs with a more potent maturation signal. We therefore investigated whether the T-cell stimulatory capacity of human monocyte-derived DCs could be increased by co-electroporation with different combinations of CD40L, CD70, and constitutively active toll-like receptor 4 (caTLR4) encoding mRNA. We show that immature DCs electroporated with CD40L and/or caTLR4 mRNA, but not those electroporated with CD70 mRNA, acquire a mature phenotype along with an enhanced secretion of several cytokines/chemokines. Moreover, these DCs are very potent in inducing naive CD4(+) T cells to differentiate into interferon-gamma (IFN-gamma)-secreting type 1 T helper (Th1) cells. Further, we assessed the capacity of the electroporated DCs to activate naive HLA-A2-restricted MelanA-specific CD8(+) T cells without the addition of any exogenous cytokines. When all three molecules were combined, a >500-fold increase in MelanA-specific CD8(+) T cells was observed when compared with immature DCs, and a >200-fold increase when compared with cytokine cocktail-matured DCs. In correlation, we found a marked increase in cytolytic and IFN-gamma/tumor necrosis factor-alpha (TNF-alpha) secreting CD8(+) T cells. Our data indicate that immature DCs genetically modified to express stimulating molecules can induce tumor antigen-specific T cells in vitro and could prove to be a significant improvement over DCs matured with the methods currently in use.

Background: Myxopapillary ependymoma commonly affects the filum terminale. They are usually well-circumscribed lesions; making complete removal is possible in most cases. Subarachnoidal seeding has been reported months or years after partial or subtotal resection, and more rarely infratentorial metastases. We report an exceptional case presenting with diffuse metastases along the spinal and intracranial subarachnoidal space from the sacral level up to the lateral sulci. Methods: This 25-year-old Caucasian male presented with a 2.5-month history of severe back pain when lying and dysesthesia in both legs. Neurological examination showed only some fasciculations in both quadriceps muscles and was further normal. MR imaging revealed numerous enhancing nodular lesions, varying from 1 to 3 cm in size, scattered throughout the whole spinal cord, around the brainstem and in the Sylvian sulci.We performed a dorsal laminectomy at D4 level because of severe spinal cord compression. Pathological examination demonstrated a myxopapillary ependymoma. Oral chemotherapy was started to avoid radiotherapy regarding the important tumour extent. Despite stable MR imaging, the patient complained of increased back pain and bilateral leg dysesthesia after 2 cycles of Temozolamide and was subsequently treated by radiation therapy. Discussion: Myxopillary ependymoma is considered to be a benign tumour (WHO grade I) arising from the medullar conus and filum terminale involving the whole CNS. The tumour tends to grow slowly, without infiltration of the surrounding neural tissue with seldom metastasis. Intracranial seeding has been reported several months or years after subtotal or partial removal, but spontaneously intracranial seeding at diagnosis is extremely rare.

Background: Glioblastoma (GBM) is the most common primary malignant brain tumour in adults with a median survival of about 1 year.Amplification of the epidermal growth factor receptor (EGFR) gene is found in 30 to 50% of GBM. So far no clear influence of EGFR amplification status on prognosis has been shown. The objective of this multicentre retrospective study was to assess the prognostic value of EGFR gene amplification on overall survival in GBM patients. Methods: 72 patients with newly diagnosed GBM were included between January 2003 and December 2005. Histological diagnosis was made by the same neuropathologist according to the WHO criteria. EGFR gene amplification status for all tumours was assessed with fluorescence in situ hybridisation (FISH). Results: Themedian age of the patients was 64 years (range: 23-84), 51% of men and 49% of women. The prognostic relevance of age at diagnosis on survival was shown in this study: younger glioblastoma patients ((pwhereas 51% showed no amplification. 10% of the GBMs showed an increased EGFR gene copy number with aneusomy of chromosome- 7.There was no statistical significant difference in survival between EGFR gene amplified and non-amplified tumours (p=0.293). Conclusion: The results of our study show that the EGFR gene amplification status has no significant prognostic value in GBM patients.As expected younger patients have a better prognosis than older patients.

BACKGROUND: 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and some related environmental contaminants are aryl hydrocarbon receptor (AhR) ligands that exert reproductive and developmental toxicity in laboratory animals. In humans, fertility-related effects are less documented. OBJECTIVE: The aim of this study was to investigate the relationship between dioxin-like biological activity in serum and parameters of reproductive status in men from the general population 5 months after a polychlorinated biphenyl and dioxin food-contamination episode in Belgium. DESIGN: In the framework of the cross-sectional Flemish Environment and Health Study (FLEHS), we recruited 101 men 20-40 years of age and evaluated sperm parameters, measured sex hormones, and gathered information on a number of lifestyle factors. In addition, we determined the AhR-mediated enzymatic response elicited by individual serum samples and expressed it as TCDD equivalent concentrations (CALUX-TEQs) using an established transactivation assay. RESULTS: Age (p = 0.04) and the frequency of fish (p = 0.02) and egg (p = 0.001) consumption were independent positive determinants of serum dioxin-like activity. After correcting for possible confounders, we found that a 2-fold increase in CALUX-TEQ > 16 pg/L was associated with a 7.1% and 6.8% (both p = 0.04) decrease in total and free testosterone, respectively. We also observed a more pronounced drop in semen volume of 16.0% (p = 0.03), whereas sperm concentration rose by 25.2% (p = 0.07). No relationship was found with total sperm count or sperm morphology. CONCLUSIONS: These data suggest an interaction of dioxin-like compounds with the secretory function of the seminal vesicles or prostate, possibly indirectly through an effect on testosterone secretion, at levels not affecting spermatogenesis as such. ispartof: Environ Health Perspect vol:114 issue:11 pages:1670-1676 ispartof: location:United States status: published

Surgical bullectomy is the treatment of choice for giant emphysematous bulla. We report a case of successful nonsurgical treatment with bronchoscopic placement of one-way endobronchial valves that are currently under investigation for the treatment of end-stage emphysema. In patients who are poor surgical candidates, this noninvasive bronchoscopic treatment may represent a valuable alternative.

Various mesenchymal lesions, some of which have only recently been characterized, may affect the vulva. Because of their apparently shared origin from vulvovaginal mesenchyme, these lesions can resemble one another superficially and can be challenging diagnostically. Clinically, benign lesions and tumor-like conditions may mimic a malignant process because of hypercellularity, mitotic activity, and rapid growth. We report on a 84-year-old diabetic and hypertensive woman who had previously undergone skinning vulvectomy for lichen planus and an embolectomy of the left femoral artery. The patient presented with a rapidly growing vulvar mass. The biopsy showed spindle cell proliferation in a loose myxoid stroma with granulation tissue and a mixed inflammatory infiltrate. Based on histology and immunohistochemistry, the initial diagnosis was that of a benign lesion. In view of the persistent recurrence of the lesion and the absence of metastatic spread, we conclude that the lesion has a low-grade malignant potential and suggest the diagnosis of florid cellular reactive pseudosarcomatous myofibroblastic proliferation.

Paediatric breast disorders represent a varied set of abnormalities. The bulk of breast pathology in children and adolescents consists of congenital and developmental anomalies, infections and tumours of which most are benign. As breast development represents an important, early manifestation of female sexuality, inadequate development often constitutes a major worry for the adolescent and her parents. We briefly discuss the normal embryologic and physiologic aspects of breast development, which will serve as an introduction to the congenital and developmental problems seen in young girls and adolescents.

The aim of this study was to examine the inflammatory reaction occurring in the pleural space of patients suffering from primary spontaneous pneumothorax (PSP) using pleural lavage, which was performed in patients with PSP and in healthy control subjects (essential hyperhidrosis patients undergoing thoracoscopy for sympathicolysis treatment). Cellular and solute composition of lavage fluid, peripheral blood and parietal pleural biopsies were analysed. PSP lavage fluid showed an increase in all differentiated leucocytes, but most strikingly eosinophils and neutrophils. In the blood of patients with PSP, the total number of leucocytes and the absolute number of eosinophils, neutrophils and monocytes were also significantly increased. The time in which air was present in the pleural space was positively correlated with the increase of eosinophils in lavage fluid, parietal pleura and blood. Eosinophilic cationic protein was elevated after PSP and strongly correlated with the absolute number of lavage eosinophils. Chemo and cytokine analysis in lavage fluid showed differences in concentrations of interleukin (IL)-5, IL-6, IL-8, IL-12p40, tumour necrosis factor-alpha and RANTES, but not of eotaxin. Surprisingly, high levels of lipopolysaccharide binding protein were also measured. Primary spontaneous pnumothorax is associated with a substantial pleural inflammatory reaction. The authors hypothesise that mechanical stretch factors, lipopolysaccharide binding protein/lipopolysaccharide complexes or other environmental components trigger pleural inflammation after primary spontaneous pnumothorax.

Inflammatory pseudotumors are rare benign lung tumors. Two cases of inflammatory pseudotumors with different clinical presentations (one intrapulmonary, one endobronchial) are described. Diagnostic and therapeutic options are reviewed. Cryotherapy is proposed as a possible treatment of endobronchial inflammatory pseudotumors.

BACKGROUND: Sperm extracted from testicular biopsies of azoospermic men can successfully be used for ICSI. The concern exists that testicular sperm from azoospermic men suffering from severe testicular failure may have a higher frequency of aneuploidy, which may lead to an increased risk for chromosomally abnormal offspring. METHODS: Testicular sperm from patients showing spermatogenic failure (n = 17) and from patients with normal spermatogenesis (n = 26) were analysed by fluorescence in-situ hybridization (FISH). Numerical chromosomal abnormalities for chromosomes X, Y and 18 were evaluated by FISH in a total of 1697 testicular sperm derived from 43 azoospermic patients. RESULTS: No difference was observed between the frequency of chromosomal abnormalities in testicular sperm from patients with normal spermatogenesis (5.6%) and from patients with spermatogenic failure (8.2%). However, the frequency of aneuploidy for chromosome 18 was higher in the group of azoospermic patients with spermatogenic failure than in the group with normal spermatogenesis (3.2 versus 1.3%). Within the obstructive group, sex chromosome aneuploidy (4.5%) occurred more frequently than chromosome 18 aneuploidy (1.3%; P < 0.001). Among testicular sperm derived from patients with spermatogenic failure, sex chromosomal aneuploidy (5.8%) was similar to that for chromosome 18 (3.2%). CONCLUSIONS: So far, no difference in the total frequency of chromosomal abnormalities has been observed between patients with normal spermatogenesis and patients with severe testicular failure. However, aneuploidy for chromosome 18 was higher in the group with spermatogenic failure.

BACKGROUND: This study investigated the donor concept of children who were born by means of donor insemination (DI), and their lesbian parents. METHODS: A total of 41 children aged between 7 and 17 years, and 45 parents, took part in the follow-up study. In-depth topic interviews were used to reconstruct how DI children and their mothers perceived the donor. Data were collected about the birth story, about children’s conversations with their mothers concerning donor characteristics and about children’s and parents’ attitudes towards the status of the donor. RESULTS: 54% of these children preferred donor anonymity at this point in their life, whereas 46% wanted to know more about the donor. The majority of the latter group would have liked to know the donor’s identity, with boys outnumbering girls. The remaining children of this group were content with non-identifying information. Children wanted to know more about the donors whereas the majority of the mothers preferred the donor to remain anonymous. CONCLUSIONS: Our results suggest that among DI children in general and among members of the same family, unit opinions differ on the status of the donor. A flexible system offering different types of donors seems to be necessary in order to meet the needs of each family.

Erosion of and protrusion into the tracheobronchial tree by esophageal stents is a rare complication; until now, only 3 cases of bronchial erosion in patients with underlying bronchial carcinoma and esophageal tumoral involvement have been published. This is the first report of penetration

Neuroblastoma is an embryonic tumor arising from immature sympathetic nervous system cells. Recurrent genomic alterations include MYCN and ALK amplification as well as recurrent patterns of gains and losses of whole or large partial chromosome segments. A recent whole genome sequencing effort yielded no frequently recurring mutations in genes other than those affecting ALK. However, the study further stresses the importance of DNA copy number alterations in this disease, in particular for genes implicated in neuritogenesis. Here we provide additional evidence for the importance of focal DNA copy number gains and losses, which are predominantly observed in MYCN amplified tumors. A focal 5 kb gain encompassing the MYCN regulated miR-17~92 cluster as sole gene was detected in a neuroblastoma cell line and further analyses of the array CGH data set demonstrated enrichment for other MYCN target genes in focal gains and amplifications. Next we applied an integrated genomics analysis to prioritize MYCN down regulated genes mediated by MYCN driven miRNAs within regions of focal heterozygous or homozygous deletion. We identified RGS5, a negative regulator of G-protein signaling implicated in vascular normalization, invasion and metastasis, targeted by a focal homozygous deletion, as a new MYCN target gene, down regulated through MYCN activated miRNAs. In addition, we expand the miR-17~92 regulatory network controlling TGFß signaling in neuroblastoma with the ring finger protein 11 encoding gene RNF11, which was previously shown to be targeted by the miR-17~92 member miR-19b. Taken together, our data indicate that focal DNA copy number imbalances in neuroblastoma (1) target genes that are implicated in MYCN signaling, possibly selected to reinforce MYCN oncogene addiction and (2) serve as a resource for identifying new molecular targets for treatment. © 2013 Kumps et al., SCOPUS: ar.j, info:eu-repo/semantics/published

Objective To report a novel fertility preservation strategy in a woman with recurrent serous borderline ovarian tumor in the conserved ovary involving ex-vivo retrieval of in vivo matured oocytes and subsequent embryo cryopreservation. Design Case report. Setting Tertiary infertility care unit. Patient(s) A 27-year-old woman presented for follow-up visit with a history of borderline serous adenocarcinoma treated conservatively with left oophorectomy and fertility-sparing laparoscopic staging. Ultrasound scan revealed a recurrent disease in the right ovary. Intervention(s) Ex-vivo retrieval of mature oocytes after ovarian stimulation. Main Outcome Measure(s) Fertility preservation. Result(s) The patient underwent ovarian stimulation followed by a laparotomy and oophorectomy on the day of oocyte retrieval. A puncture of the follicles was performed in the operating theatre with a maximum ischemia time of 14 minutes. Eleven mature oocytes were aspirating, resulting in seven zygotes for cryopreservation. Conclusion(s) Mature oocytes can be successfully retrieved ex-vivo from the oophorectomy specimen after a controlled ovarian hyperstimulation (COH) protocol. This method provides a possible strategy for fertility preservation in patients with recurrent ovarian cancer without the risk of cancer cells spillage associated with the standard transvaginal oocyte retrieval.

(2010). The RBSS Patronage of local scientific surgical meetings. Acta Chirurgica Belgica: Vol. 110, No. 1, pp. 1-1.

Back ground Systematic reviews have concluded that hrHPV DNA testing using target-amplification tests is as accurate on vaginal self-samples as on clinician-taken specimens for the detection of cervical precancer. However, insufficient evidence is available for specific HPV assay/self-sample device combinations.ObjectivesThe VALHUDES protocol is designed as a diagnostic test accuracy study that aims to compare the clinical sensitivity and specificity of particular hrHPV assay(s) on vaginal self-samples and first-void-urine, collected in agreement with standardized protocols, with hrHPV testing on matched clinician-taken samples.Study designFive hundred enrolled women referred to a colposcopy clinic are invited to collect a first-void urine sample and one or more vaginal self-samples with particular devices before collection of a cervical sample by a clinician. Sample sets are subsequently analysed in a laboratory accredited for HPV testing. Disease verification for all enrolled patients is provided by colposcopy combined with histological assessment of biopsies.ResultsA first VALHUDES study has started in Belgium in December 2017 with enrolment from four colposcopy centres. The following assays are foreseen to be evaluated: RealTime High Risk HPV assay (Abbott), cobas-4800 and -6800 (Roche), Onclarity (BD), Xpert HPV (Cepheid) and Anyplex II HPV HR (Seegene).ConclusionGiven empirical evidence that the relative accuracy of HPV-testing on self- vs clinician-samples is robust across clinical settings, the VALHUDES protocol offers a framework for validation of HPV assay/self-sample device combinations that can be translated to a primary screening setting.

Florence Talrich,1,2 Astrid Van Damme,1,2 Hilde LA Bastiaens,3 Jochen Bergs,4 Marlies EB Rijnders,5 Katrien Beeckman1,2,6 1Department of Public Health, Vrije Universiteit Brussel (VUB), Jette, Belgium; 2Departement of Nursing and Midwifery Research Group (NUMID), Universitair Ziekenhuis Brussel (UZ Brussel), Jette, Belgium; 3Department Family Medicine and Population Health, Universiteit Antwerpen, Antwerp, Belgium; 4Department of Healthcare, Universiteit Hasselt, Hasselt, Belgium; 5Department of Child Health, TNO, Leiden, the Netherlands; 6Department Nursing and Midwifery, Universiteit Antwerpen, Antwerp, BelgiumCorrespondence: Florence Talrich, Laarbeeklaan 103, Brussel, Jette, 1090, Belgium, Tel +324749853, Email florence.talrich@vub.beIntroduction: Group Antenatal Care (GANC) is an alternative for traditional antenatal care. Despite the model is well accepted among participants and is associated with positive effects on pregnancy outcomes, recruitment of participants can be an ongoing challenge, depending on the structure and financing of the wider health system. This is especially the case for primary care organizations offering GANC, which depend on other health care providers to refer potential participants. The main objective of this study is to understand what determinants are at play for health care providers to refer to GANC facilitators in primary care organizations. Accordingly, we make recommendations for strategies in order to increase the influx of women in GANC.Methods: Qualitative findings were obtained from 31 interviews with healthcare providers responsible for the referral of women to the GANC facilitators working in primary care organizations, GANC facilitators and stakeholders indirectly involved in the referral. The domains of the Consolidated Framework for Implementation Research (CFIR) and the Theoretical Domains Framework (TDF) helped to develop interview questions and raise awareness of important elements during interviews and thematic analyses.Results: The findings show that before health care providers decide to refer women, they undergo a complex process that is influenced by characteristics of the potential referrer, GANC facilitator, woman, professional relationship between the potential referrer and the GANC facilitator, organization and broader context.Discussion: Based on these findings and current literature, we recommend that the GANC team implements strategies that anticipate relevant determinants: identify and select potential referrers based on their likelihood to refer, select champions, invest in communication, concretise the collaboration, provide practical tools, involve in policymaking.Keywords: antenatal care, CenteringPregnancy, group-based care, recruitment, primary healthcare

▸ In this study we propose an innovative treatment strategy in patients with cathecolaminergic polymorphic ventricular tachycardia. ▸ These patients often suffer from inappropriate ICD shocks. ▸ Left cardiac symphatethic denervation could represent a solution in patients in whom arrhythmic episodes are refractory to betablockers or antiarrhythmic drugs.

The immunostimulatory capacity of dendritic cells is improved by co-electroporation with mRNA encoding CD40 ligand, constitutively active toll-like receptor 4, and CD70 (TriMix-DC). This pilot clinical trial evaluated the feasibility, safety, and immunogenicity of a therapeutic vaccination containing autologous TriMix-DC co-electroporated with mRNA encoding a human leukocyte antigen class II-targeting signal linked to 1 of 4 melanoma-associated antigens (MAGE-A3, MAGE-C2, tyrosinase, and gp100) in patients with advanced melanoma. Thirty-five American Joint Committee on Cancer stage III/IV melanoma patients received autologous TriMix-DC (4 administrations 2 weeks apart). Immune monitoring was performed by evaluating skin biopsies of delayed type IV hypersensitivity (DTH) reactions for presence of vaccinal antigen-specific DTH-infiltrating lymphocytes (DIL). Thereafter, patients could receive interferon-alpha-2b (IFN-alpha-2b) 5 MU subcutaneously 3 times weekly and additional TriMix-DC every 8 weeks. TriMix-DC-related adverse events comprised grade 2 local injection site reactions (all patients), and grade 2 fever and lethargy (2 patients). Vaccinal antigen-specific DIL were found in 0/6 patients tested at vaccine initiation and in 12/21 (57.1%) assessed after the fourth vaccine. A positive postvaccination DTH test correlated with IL-12p70 secretion capacity of TriMix-DC. No objective responses to TriMix-DC alone were seen according to RECIST. Twenty-nine patients received IFN-?-2b after the fourth vaccine without unexpected adverse events. During TriMix-DC/IFN-alpha-2b combination therapy, 1 partial response and 5 stable disease (disease control of >6 months with regression of metastases) were observed in 17 patients with evaluable disease at baseline. In conclusion, this study demonstrated that therapeutic vaccination with autologous TriMix-DC is feasible, safe, and immunogenic and can be combined with sequential IFN-alpha-2b.

Letter to the editor Dear Editor, Intravenous recombinant tissue plasminogen activator (IV rtPA) is the only approved therapy for acute ischemic stroke. International guidelines stipulate that anticoagulant use is a (relative) contraindication for treatment with IV rtPA. Rivaroxaban is an oral direct factor Xa inhibitor that is increasingly being used in routine clinical practice for primary prevention and treatment of venous thromboembolism, stroke prevention in nonvalvular atrial fibrillation and only in Europe as secondary prevention in acute coronary syndromes. It is therefore expected that clinicians will be increasingly confronted with the question how to treat acute ischemic stroke in these patients. Data on the bleeding risk in patients treated with IV rtPA while taking rivaroxaban are lacking. Various commercial assays have been developed to measure the drug concentration, but as these are not yet widely available bedside [4], the prothrombin time (PT) is suggested as a limited alternative to assess the presence of anticoagulant effect, especially in urgent situations. We report the case of an 80 year old male right-handed patient presenting with a global aphasia, conjugated eye deviation and head rotation to the left, complete right hemianopsia, severe right hemicorporal sensory loss and paralysis (National Institutes of Health Stroke Scale score, NIHSS, 19). The patient was taking rivaroxaban 20 mg once daily since several weeks for paroxysmal atrial fibrillation and recent pulmonary emboli. The last drug intake was 24 h before presentation. The non-contrast computed tomography (CT) scan showed the presence of a left insular ribbon sign (Fig. 1A) and a 'dot sign' in the M2 segment of the left middle cerebral artery; the latter could be confirmed by reconstruction images of the perfusion acquisition. Perfusion-CT demonstrated an important hypoperfusion of the territory of the left middle cerebral artery, mainly consisting of a large area of ischemic penumbra (prolonged Tmax) and a relatively small ischemic core (decreased CBV). The platelet count was 364 × 109/L (normal: 158-450 × 109/L), PT was 44% (normal: >70%), the International Normalized Ratio was 1.8 (normal: 0.8-1.3), fibrinogen was 359 mg/dL (normal: 180-400 mg/dL) and the activated partial thromboplastin time was 29.4 s (normal: 22.2-34.4 s). Renal function was within normal limits. Treatment with intravenous thrombolysis was initiated 135 min after stroke onset after informed consent was obtained by proxy. Except for mild and self-limiting hematuria, no complications occurred. The patient gradually improved after administration of IV rtPA (NIHSS at 24 h after symptom onset: 8), with persisting motor aphasia. Control CT scan of the brain showed an infarction confined to the left subinsular region with hemorrhagic transformation compatible with the ischemic core lesion on perfusion images. Transcranial ultrasound 2 days after stroke demonstrated reperfusion of the left middle cerebral artery. This case underlines the need for further studies on the safety of intravenous thrombolysis in patients taking rivaroxaban. Prospective registration of similar cases in an (international) database is of highly added value.

Postpneumectomy syndrome is a rare condition, occurring most often after right-sided pneumectomy. Treatment usually consists of restoring the disturbed anatomy using invasive surgical techniques. We present 4 patients with postpneumectomy syndrome and 3 patients with postlobectomy syndrome, treated successfully with less invasive endobronchial stent placement.

In 1994 a 44-yr-old male was admitted for surgical resection of a hard, not painful, nodule which was believed to originate from the isthmus of the thyroid gland. He was known to have mild asthma, treated with inhaled corticosteroids and short-acting β2-agonists. His medical record revealed a smoking history of 20 pack-yrs. The patient denied any other symptoms, except the presence of the nodule. On physical examination a hard nodule was felt anteriorly to the trachea. A clear separation with the thyroid gland could not be made. A preoperative computed tomography (CT) scan of the neck revealed a calcified nodule on the midline, adjacent to the trachea (fig. 1⇓). Laboratory studies demonstrated a euthyroid status. Fig. 1.— Chest computed tomography scan. Internal scale bar=5 cm. During surgery, the nodule could not be separated from the tracheal cartilaginous ring and a left hemithyroidectomy, with resection of part of the affected cartilaginous ring, was carried out (histology of the nodule in fig. 2a⇓). The tracheal defect was closed with a muscle flap. The patient continued to do well on follow-up examinations ≤5 yrs postoperatively, without complaints. …