Joseph de Nanassy

Oocyte donation pregnancies and the risk of preeclampsia or gestational hypertension: a systematic review and metaanalysis

The purpose of this study was to determine whether pregnancies that were achieved via oocyte donation, compared with pregnancies achieved via other assisted reproductive technology methods or natural conception, demonstrate increased risk of preeclampsia or gestational hypertension. Comparative studies of pregnancies that were achieved with oocyte donation vs other methods of assisted reproductive technology or natural conception with preeclampsia or gestational hypertension were included as 1 of the measured outcomes. Abstracts and unpublished studies were excluded. Two reviewers independently selected studies, which were assessed for quality with the use of methodological index for non-randomized studies, and extracted the data. Statistical analysis was conducted. Of the 523 studies that were reviewed initially, 19 comparative studies met the predefined inclusion and exclusion criteria and were included in the metaanalysis, which allowed for analysis of a total of 86,515 pregnancies. Our pooled data demonstrated that the risk of preeclampsia is higher in oocyte-donation pregnancies compared with other methods of assisted reproductive technology (odds ratio, 2.54; 95% confidence interval, 1.98-3.24; P < .0001) or natural conception (odds ratio, 4.34; 95% confidence interval, 3.10-6.06; P < .0001). The risk of gestational hypertension was also increased significantly in oocyte donation pregnancies in comparison with other methods of assisted reproductive technology (odds ratio, 3.00; 95% confidence interval, 2.44-3.70; P < .0001) or natural conception (odds ratio, 7.94; 95% confidence interval, 1.73-36.36; P = .008). Subgroup analysis that was conducted for singleton and multiple gestations demonstrated a similar risk for preeclampsia and gestational hypertension in both singleton and multiple gestations. This metaanalysis provides further evidence that supports that egg donation increases the risk of preeclampsia and gestational hypertension compared with other assisted reproductive technology methods or natural conception.

Langerhans cell histiocytosis: a comprehensive review.

Summary Langerhans cell histiocytosis (LCH) is currently regarded as a myeloid neoplasm, with remarkably broad clinical spectrum, ranging from isolated skin or bone lesions to a disseminated disease that can involve nearly any organ. LCH is generally regarded as a sporadic disease that occurs predominantly in the paediatric population. The diagnosis of LCH is confirmed by immunohistochemistry (IHC) by demonstrating the presence of dendritic cell markers such as S100 protein, in addition to CD1a and langerin. Contrary to previous beliefs, recent literature reveals that the pathogenesis of LCH might involve a clonal process implicating BRAF c.1799T>A (p.Val600Glu) and other mutations [(600DLAT) B-RAF and (T599A) B-RAF, somatic MAP2K1 mutations]. Through this review article, we have summarised the latest understanding of the biological and salient histological characteristics of LCH and its potential morphological mimics.

Mullerian Adenosarcoma of the Cervix in a 10-Year-Old Girl: Case Report and Review of the Literature

UNLABELLED Müllerian adenosarcoma is a rare neoplasm usually found in postmenopausal women. It usually presents as a polypoid mass within the endometrium. It is a biphasic tumor, composed of a benign epithelial component and a malignant stromal component. To date, this neoplasm has been reported in only 16 adolescent girls. We present a case of a 10-year-old girl who was diagnosed with müllerian adenosarcoma arising from the endocervix, the youngest female ever reported. CASE REPORT A 10-year-old previously healthy girl presented to the Emergency Department at the Childrens Hospital of Eastern Ontario with a painless mass protruding from her vagina. She had experienced mild vaginal bleeding for two weeks prior to her presentation. On physical examination, her vital signs were stable, and pubertal development was Tanner III breast and Tanner II pubic development. Rectoabdominal examination was negative. Two polypoid lesions were seen protruding past the hymenal ring and were removed in the emergency department. On gross examination, they were a dark tan color and had a fleshy appearance with a gelatinous consistency. They measured 5.5 x 1.5 x 1.0 cm and 3.5 x 1.5 x 1.5 cm. The final pathology revealed müllerian adenosarcoma, favoring an endocervical origin. Further investigations, including an abdominal/pelvic ultrasound and MRI and chest radiography, were negative. The patient subsequently underwent examination under anesthesia, vaginoscopy, hysteroscopy, polypectomy, and dilatation and curettage. The vagina appeared normal. At the level of the cervix, there were 3 polypoid gelatinous structures arising from the endocervix and extruding past the exocervix. They measured 0.8 x 0.5 x 0.2 cm up to 1.1 x 0.7 x 0.5 cm. The lesions were removed. Hysteroscopic inspection of the uterine cavity did not find any abnormalities. An endometrial curettage was performed. Pathology confirmed a diagnosis of müllerian adenosarcoma originating from the endocervix. Uterine curettings were negative for malignancy. After a thorough evaluation of the available literature, review with the Regional Tumor Board and extensive discussions with the family, a decision was made to perform a radical hysterectomy, bilateral salpingectomy, bilateral pelvic lymph node dissection, upper vaginectomy and preservation of ovaries. The procedure was uncomplicated. Clinically, there was no evidence of residual disease. The final pathology was negative for malignancy. CONCLUSION Müllerian adenosarcoma of the endocervix is a very rare pediatric tumor. Due to the rarity of this tumor in this age group, optimal therapy is uncertain. Most experts recommend hysterectomy. The review of literature reveals a high recurrence rate following conservative surgical management. Chemotherapy and radiation have not been used in the absence of extensive pelvic and/or residual disease. Poor prognostic factors include depth of invasion, sarcomatous overgrowth and high-grade malignant features in the stromal component. If recurrence occurs, it tends to be local and following prior conservative treatments such as cone biopsy or trachelectomy. Recurrences may occur late and thus long term follow-up of these patients is recommended.

Manuka honey: histological effect on respiratory mucosa.

Background Chronic rhinosinusitis (CRS) is an inflammatory disease in which bacteria are commonly implicated often in the form of a biofilm. Manuka honey has been shown in vitro to be an effective treatment against two common CRS pathogens both in the planktonic and in the biofilm forms. The purpose of this study was to determine if the application of manuka honey to respiratory epithelium would result in histological evidence of epithelial injury. Methods Using a rabbit animal model, a nonrandomized controlled trial of four treatment regimes was performed with two rabbits in each group. The left nasal cavity was irrigated with a 1.5-mL manuka honey solution once daily and the right nasal cavity was not treated. Groups 1–3 were treated for 3, 7, and 14 consecutive days, respectively, and killed the morning after the last treatment. Group 4 was treated for 14 consecutive days followed by a 14-day washout period and then killed the following morning. The nasal respiratory mucosa was immediately harvested after death. The mucosa was examined by light microscopy for histological change in comparison with the control side. Results Cilia were not measured quantitatively but were equally present on the treated and untreated mucosa. There was no histological evidence of inflammation, epithelial injury, or significant morphological changes. Conclusion The application of a manuka honey solution to rabbit nasal respiratory mucosa over different treatment intervals did not show evidence of histological epithelial injury.

Juvenile Granulosa and Theca Cell Tumor of the Ovary as a Rare Cause of Precocious Puberty: Case Report and Review of Literature

BACKGROUND The differential diagnosis for precocious puberty in a young female includes peripheral causes. This case documents a rare cause of peripheral precocious puberty--a juvenile granulosa and theca cell ovarian tumor--and a brief review of the literature for this tumor type. CASE A 7-year-old girl presented with rapid onset of pubertal development and elevated estradiol levels. Menarche occurred 5 months after thelarche. A thorough workup revealed a large multicystic left ovary. Other causes of precocious puberty were excluded. She underwent an exploratory laparotomy and left salpingo-oophorectomy. Pathology reported a juvenile granulosa and theca cell tumor of the ovary, FIGO stage 1A. Postoperatively, she experienced a cessation of vaginal bleeding and estradiol levels normalized. A literature review found that early stage disease has an excellent prognosis and that adjuvant chemotherapy is not indicated in this setting. SUMMARY AND CONCLUSION Juvenile granulosa and theca cell tumor of the ovary is a rare cause of peripheral precocious puberty, even more so than juvenile granulosa cell tumor, due to the theca component. Treatment is surgical and an excellent prognosis is possible for early stage disease.

Update on molecular findings in rhabdomyosarcoma

Rhabdomyosarcoma (RMS) is the most common malignant soft tissue tumour in children and adolescents. Histologically RMS resembles developing fetal striated skeletal muscle. RMS is stratified into different histological subtypes which appear to influence management plans and patient outcome. Importantly, molecular classification of RMS seems to more accurately capture the true biology and clinical course and prognosis of RMS to guide therapeutic decisions. The identification of PAX-FOXO1 fusion status in RMS is one of the most important updates in the risk stratification of RMS. There are several genes close to PAX that are frequently altered including the RAS family, FGFR4, PIK3CA, CTNNB1, FBXW7, and BCOR. As with most paediatric blue round cell tumours and sarcomas, chemotherapy is the key regimen for RMS therapy. Currently there are no direct inhibitors against PAX-FOXO1 fusion oncoproteins and targeting epigenetic cofactors is limited to clinical trials. Failure of therapy in RMS is usually related to drug resistance and metastatic disease. Through this review we have highlighted most of the molecular aspects in RMS and have attempted to correlate with RMS classification, treatment and prognosis.

Congenital mesoblastic nephroma: a study of 19 cases using immunohistochemistry and ETV6-NTRK3 fusion gene rearrangement

Mesoblastic nephroma (MN) is the most common renal tumour in the first 3 months of life and accounts for 3-5% of all paediatric renal neoplasms. To further understand the morphological variants of MN, we identified 19 cases of MN (five classic, eight cellular and six mixed) and examined each case for markers known to be important in urogenital embryological development (PAX8, WT1 and RCC), stem cell associated markers (Oct 4, CD34 and c-kit), muscle/myofibroblastic markers (muscle specific actin, calponin and h-caldesmon), aberrant transcription factors, cell cycle regulation and other oncogenic proteins (p16, cyclin D1 and beta-catenin). Fluorescence in situ hybridisation (FISH) testing for ETV6-NTRK3 gene fusion/rearrangement revealed further differentiation between the subtypes with ETV6-NTRK3 gene fusion detected in 0/5 of the classic MN, 8/8 of the cellular MN and 5/6 of the mixed MN cohorts, respectively. Our results conclude that cyclin D1 and beta-catenin may be useful markers for differentiating between cellular MN and classic MN when the histology is not conclusive. The absence of expression of stem cell markers and markers involved in urogenital development suggests that MN is not a nephroma and most likely represents a soft tissue tumour, with congenital infantile fibrosarcoma representing cellular MN with a predilection to arise in the kidney. In addition, the immunophenotype and genetic fingerprint of mixed MN most likely represents a heterogenous group of tumours that are mostly cellular type, with areas that are phenotypically less cellular.

Analysis of the Clinical Significance and Cost Associated With the Routine Pathological Analysis of Pediatric Inguinal Hernia Sacs

PURPOSE Pediatric inguinal and scrotal surgeries for inguinal hernia, cryptorchidism and hydrocele are common and usually involve the excision of a hernia sac. Groups at many centers send hernia sacs for pathological analysis to identify occult disease as well as structures that may have been erroneously resected. We hypothesized that, since the incidence of significant findings is low and the associated health care costs are significant, the routine pathological analysis of inguinal hernia sacs is unnecessary. MATERIALS AND METHODS After receiving institutional review board approval we retrospectively reviewed pathology reports at our institution of patients who underwent surgery with an inguinal hernia sac sent for pathological analysis from January 2000 to September 2009. The primary outcome was to determine the incidence of clinically significant structures in hernia sac specimens. The secondary outcome was to evaluate the costs associated with analyzing these specimens. RESULTS A total of 2,287 boys and 441 girls underwent some form of inguinal or scrotal surgery during the study. In the 2,287 boys a total of 2,657 hernia sac specimens were analyzed, of which 2 (0.08%) contained clusters of epididymal-like tubules. Most unexpected findings were likely clinically insignificant, including mesothelial proliferation in 5.6% of cases, genital duct remnants in 0.8%, lipoma in 0.23% and adrenocortical rests in 0.04%. The average cost of analyzing hernia sac specimens at our institution was approximately

Histologic analysis of eosinophils and mast cells of the gastrointestinal tract in healthy Canadian children.

7,100 Canadian annually. CONCLUSIONS Routine analysis of inguinal hernia sacs is unnecessary and costly, and should be reserved for cases in which resection of important structures such as the vas deferens is suspected.

Pediatric Blastic Plasmacytoid Dendritic Cell Neoplasm: A Systematic Literature Review

Many gastrointestinal (GI) disorders, including GI eosinophilia and inflammatory bowel disease, can be characterized by increased mucosal eosinophils (EOs) or mast cells (MCs). Normal mucosal cellular counts along the GI tract in healthy children have not been established for a Canadian pediatric population. To establish a benchmark reference, we quantified EO and MC from 356 mucosal biopsies of the GI tract obtained during upper and lower endoscopic biopsies of 38 pediatric patients in eastern Ontario. Mean total counts of EO varied for the 11 tissues we examined, from a low of 7.6±6.5/high-power field (HPF) (×40 [×400, 0.55mm(2)]) in the body of the stomach to a high of 50.3±17.4/HPF in the cecum. The lower GI tract (ileum, cecum, colon, sigmoid, and rectum) generally had higher total EO counts than the upper GI tract (antrum and body of stomach, duodenum, and duodenal cap) (combined average of 32.1±20.6 versus 19.3±15.8, respectively). Similarly, the number of mucosal MC was different in the various regions of the GI tract ranging from 0.04±0.2/HPF in the duodenal cap to 0.9±2.6/HPF in the ileum. Total counts for EO and MC in the lamina propria were not significantly different between sexes when adjusted for multiple testing. EO polarity was absent in many cases, irrespective of the GI region. These numeration and localization of EO and MC will provide normative data for upper and lower endoscopic GI biopsies in the pediatric population of Eastern Ontario.