Higher estradiol levels are associated with lower neonatal birthweight after fresh and frozen embryo transfers. A cohort study of 3631 singleton IVF pregnancies.

AIM: To assess the birthweight of neonates conceived after fresh and frozen embryo transfers (FET) and, if different, to investigate whether estradiol levels during the late follicular phase were associated with the observed difference. METHODS: Singleton pregnancies from fresh and FET transfers between January 1990 and December 2013 were compared retrospectively. A total of 2885 singleton pregnancies after fresh embryo transfer and 746 after FET were analyzed. Obstetric and neonatal outcomes were compared between fresh and FET cycles. RESULTS: The singletons born after FET were found to have a significantly higher birth weight (3313 g), compared to those born after fresh embryo transfer (3143 g); p < .001. The main predictor of this difference was found to be estradiol levels at the end of the follicular phase. The difference in birthweight was inversely correlated to estradiol levels considering all cycles together but also considering fresh and frozen cycles separately. CONCLUSIONS: Our study demonstrates a link between high estradiol levels and low birth weight of singletons after IVF both in fresh and frozen-thawed embryo transfer cycles. It provides additional support to the involvement of hyperestrogenemia in the process of implantation and on the subsequent fetal development.

Pathological response of colorectal liver metastases treated after induction treatment.

BACKGROUND: Mortality for colorectal cancer is mainly due to liver metastases, surgical resection remains the curative treatment and use of neoadjuvant therapy improves resectability of metastases. Pathological response is an important prognostic factor. AIM: To evaluate tumor response by Tumor regression grade (TRG) according Rubbia-Brandt et al and correlation with survival. To establish chemotherapy-related liver injury. METHODS: Thrity-eight patients resected for colorectal cancer liver metastases after neoadjuvant chemotherapy were enrolled in this study. Tumor regression grade (TRG) according to Gradding Rubbia-Brandt et al. was evaluated. RESULTS: Sex ratio was 1.5 with an average age of was 55 years. Twenty-five patients were in stage IV (65.7% of patients with synchronous liver metastases). Overall survival was 62% at 12 months, 42% at 24 months and 21% at 36 months. Thirty-four patients (89.5%) received Oxaliplatin and nine (23.7%) irinotecan. Twenty patients (52.6%) had no histologic response (TRG 4 and 5), nine (23.7%) had a major response (TRG 1 and 2) and nine had a partial response (TRG3). Survival was more important with major pathologic response than with partial response or no response. No statistically significant relation was found between survival and the different types of response. Chemotherapy-related liver injury were present in 21 patients (55.2%).  Conclusions: Scoring system with three grades are currently recommanded to evaluate pathological response and new histopathological data are proposed. Larger studies are required to validate these items and their utility for therapeutic decisions.

NDM-5 carbapenemase-encoding gene in multidrug-resistant clinical isolates of Escherichia coli from Algeria.

Here, we report the first autochthonous cases of infections caused by blaNDM-5 New Delhi metallo-ß-lactamase-producing Escherichia coli strains recovered from urine and blood specimens of three patients from Algeria between January 2012 and February 2013. The three isolates belong to sequence type 2659 and they coexpress blaCTX-M-15 with the blaTEM-1 and blaaadA2 genes.

Cadmium exposure affects the expression of genes involved in skeletogenesis and stress response in gilthead sea bream larvae.

Gilthead sea bream larvae (Sparus aurata) aged 47 days post hatching (dph) (11.6-12.8 mg in wet weight) were exposed to several sublethal concentrations of Cd(2+) (0.1, 5 and 10 mg/L) during 6 days in order to investigate the effects of this heavy metal on the expression of selected genes involved in detoxification (metallothionein-mt, glutathione peroxidase 1-gpx1), stress response (heat shock protein 70-hsp70, tumour necrosis factor α-tnfα) and ossification (osteocalcin-oc) processes. For this purpose, specimens of 47 dph were exposed first for 72 h from 0.1 to 20 mg/L of Cd(2+) in order to evaluate the median lethal concentration (LC(50)) for this metal, which was determined at 15.32 mg/L. Considering the results regarding the relative transcript levels of gpx1 and hsp70, Cd(2+) at any of the tested levels (0.1, 5 and 10 mg/L) did not induce oxidative stress in gilthead sea bream larvae, whereas relative transcript levels of mt were increased at 5 and 10 mg/L of Cd(2+) probably to detoxify this metal excess. Relative transcript levels of tnfα were not level dependent and were down-regulated in larvae exposed to 5 and 10 mg/L of Cd(2+). At those concentrations, transcript levels of oc were down-regulated suggesting a disruption in bone mineralization. Results from this study provided insights in some molecular mechanisms underlying Cd(2+)-induced toxicity in fish at early stages of development. This is the first study to show that cadmium contamination can depress oc expression in teleosts.

Conservative treatment of glassy cell cervical cancer: A case report.

Glassy cell carcinoma (GCC) constitutes a rare yet histologically aggressive subtype of cervical cancer known for its rapid proliferation and high risk of recurrence and metastasis. Due to its low prevalence, the medical literature lacks large retrospective and prospective studies, and thus, no standardized management has been defined. The recommended treatment for GCC is radical hysterectomy with bilateral pelvic lymphadenectomy; however, since it mainly affects young women of reproductive age, data in the literature suggest conservative management, such as radical trachelectomy. The present report describes the cases of 2 young patients treated conservatively with pelvic lymphadenectomy and radical trachelectomy for early-stage GCC of the cervix. The first patient was a 37-year-old patient who presented a 15-mm GCC tumor [International Federation of Gynecology and Obstetrics (FIGO) stage IB1], and the second patient was a 23-year-old patient who presented a 14-mm GCC tumor (FIGO stage IB1). The first patient presented early vaginal recurrence 3 months postoperatively, which was treated with concomitant pelvic chemoradiation (45 Gy) followed by vaginal and uterine brachytherapy (15 Gy). The second patient presented internal iliac nodal recurrence 1 year after treatment, which was treated by carboplatin-paclitaxel-Avastin-based chemotherapy, followed by laparoscopic paraaortic lymph node dissection and pelvic chemoradiation (45 Gy). Both patients were tumor-free after 5 and 6 years, respectively. Due to the aggressiveness of GCC of the cervix and its high risk of recurrence, conservative treatment should be considered cautiously and should not be the standard of care.

Compound heterozygous null mutations of NOBOX in sisters with delayed puberty and primary amenorrhea.

BACKGROUND: Premature ovarian insufficiency (POI) is a heterogeneous clinical syndrome defined by a premature loss of ovarian function that associates menstrual disturbances and hypergonatropic hypogonadism. POI is a major cause of female infertility affecting 1% of women before the age of 40 and up to 0.01% before the age of 20. The etiology of POI may be iatrogenic, auto-immune or genetic but remains however undetermined in a large majority of cases. An underlying genetic etiology has to be searched in idiopathic cases, particularly in the context of a family history of POI. METHODS: Whole exome sequencing (WES) was performed in trio in a Belgian patient presenting POI and in her two parents. The patient presented delayed puberty and primary amenorrhea with hypergonadotropic hypogonadism. RESULTS: WES identified two novel compound heterozygous truncating mutations in the Newborn oogenesis homeobox (NOBOX) gene, c.826C>T (p.(Arg276Ter)) and c.1421del (p.(Gly474AlafsTer76)). Both mutations were confirmed by Sanger sequencing in the proband's sister who presented the same phenotype. Both variants were pathogenic and very likely responsible for the severe POI in this family. CONCLUSION: We report here for the first time compound heterozygous truncating mutations of NOBOX in outbred patients, generalizing biallelic NOBOX null mutations as a cause of severe POI with primary amenorrhea. In addition, our findings also suggest that NOBOX haploinsufficiency is tolerated.

Influence of high temperature on cadmium-induced skeletal deformities in juvenile mosquitofish (Gambusia affinis).

The aim of this study was to assess the effect of high temperature on cadmium (Cd)-induced skeletal deformities in juvenile Mosquitofish, Gambusia affinis. For this purpose, 188 juveniles (1 day old) were equally divided into the control group, which was maintained in Cd-free water at 24 degrees C, and three treated groups exposed either to Cd (0.4 mg/l as Cd Cl(2)) at 24 degrees C, to high temperature (32 degrees C), or to Cd at 32 degrees C for 30 days. The results showed that Cd exposure at 24 degrees C significantly increased the Cd accumulation (P < 0.0001) in the whole tissues of juveniles as well as the incidence of skeletal deformities (P < 0.01) compared with control animals. Exposure to high temperature also led to a significant increase in the incidence of skeletal deformities (P < 0.01) with respect to the control group. Interestingly, our results showed that the combined exposure to Cd and high temperature led to a more significant increase in Cd accumulation and in the frequency of spinal deformities than exposure to Cd or high temperature alone. These results confirm that temperature increases Cd toxicity and needs to be taken into account for the accurate prediction and assessment of Cd-induced spinal deformities in fish.

Novel inactivating follicle-stimulating hormone receptor mutations in a patient with premature ovarian insufficiency identified by next-generation sequencing gene panel analysis.

OBJECTIVE: To find the genetic etiology of premature ovarian insufficiency (POI) in a patient with primary amenorrhea and hypergonadotropic hypogonadism. DESIGN: Case report. SETTING: University hospital. PATIENTS: A Belgian woman aged 32 years with POI at the age of 17, her parents, and her sister whose POI was diagnosed at age 29. INTERVENTIONS: Analysis of a panel of 31 genes implicated in POI (POIGP) using next-generation sequencing (NGS), Sanger sequencing, and in vitro functional study. MAIN OUTCOME MEASURES: Gene variants, family mutational segregation, and in vitro functional impact of the mutant proteins. RESULTS: The analysis of the gene panel using NGS identified the presence of two novel follicle-stimulating hormone receptor (FSHR) missense mutations at a compound heterozygous state in the affected patient: c.646 G>A, p.Gly216Arg, and c.1313C>T, p.Thr438Ile. Sanger sequencing showed the presence of each mutation at heterozygous state in the patient's parents and at heterozygous compound state in the affected sister. Both substituted amino acids (Gly216 and Thr438) were conserved in FSHR of several vertebrate species as well as in other glycoproteins receptors (TSHR and LHCGHR), suggesting a potentially important role in glycoprotein receptor function. An in vitro functional study showed similar results for both variants with more than 90% reduction of their cell surface expression and a 55% reduction of their FSH-induced cyclic adenosine 3':5' monophosphate (cAMP) production compared with the wild-type FSHR. CONCLUSIONS: The analysis of a gene panel of 31 genes implicated in POI allowed us to identify two novel partially inactivating mutations of FSHR that are likely responsible for the POI phenotype of the proband and of her affected sister.

Primary neuroendocrine tumour of the common hepatic duct: An unexpected Klatskin-like lesion.

The biliary system is an uncommon location for neuroendocrine tumours (NETs), and within this system, the common hepatic duct is an even more rare site for NETs. Clinical and radiological presentations are challenging because these tumours may be preoperatively confused with Klatskin-like lesions. Here we report a well-differentiated grade 2 NET arising from the common hepatic duct in a 64-year-old female. Curative surgery was performed, and no evidence of recurrent disease was observed at the 2-months follow-up.

[Unexpected discovery of isolated osteochondroma in the pubic symphysis]. / Ostéochondrome solitaire de la symphyse pubienne de découverte fortuite.

Osteochondroma is the most common benign bone tumor. It usually affects the metaphyses of the long bones, in particular around the knee and the proximal humerus. It very rarely affects the pubic symphysis, usually with an atypical symptomatology. We here report the case of a 35-year old man in whom osteochondroma in the pubic symphysis encroaching on the iliopubic branch was fortuitously discovered. Radiological examinations as well as macroscopic and histological examination confirmed the diagnosis and the absence of signs of malignancy.

A disconcerting false gastric diverticulum mimicking malignancy.

Gastric diverticula are the most uncommon form of gastrointestinal diverticula. They can either be of true or false type with different pathogenesis. They may be very challenging to diagnose as symptoms are nonspecific and imaging can simulate a malignant lesion. We report an unusual case of pre-pyloric diverticulum in a 69-year-old man, leading to severe gastric obstruction with a poor general condition. As subsequent endoscopy and imaging were alarming and couldn't exclude malignancy, the patient underwent an antrectomy. The final diagnosis was made on pathological examination. We discuss, through this case, the clinical and pathological features of gastric diverticula with an emphasis on the pathogenesis of this rare entity and the risk of a malignant transformation.

Accuracy of fine-needle aspiration cytology of head and neck masses.

BACKGROUND: Head and neck masses are a common presentation in daily practice and can be challenging to both clinicians and cytopathologists. Fine needle aspiration cytology (FNAC) is a widely used method for the diagnosis of head and neck masses. The aim of the study was to assess our institutional experience of the accuracy of FNAC in the diagnosis of head and neck masses. METHODS: A total of 1262 FNACs were conducted from January 2013 to December 2016 and subdivided into benign and malignant categories. The thyroid and salivary glands FNACs were classified according to the Bethesda System for Reporting Thyroid cytopathology and to the Milan System for Reporting Salivary Gland Cytopathology respectively. The measures of diagnostic accuracy of FNAC were determined taking histology as a gold standard. RESULTS: A total of 7 false negative (FN) and 6 false positive (FP) FNACs were identified. Overall sensitivity and specificity of FNAC for a malignant diagnosis were 92% and 94.4%, respectively. Accuracy of FNACs of head and neck masses was 93.5% for all sites. The salivary gland group had the highest rate of FN (2.8%). All FP were reported in the thyroid group. These cases were cytologically classified suspicious for malignancy (n = 3) and papillary carcinoma (n = 3) and proved to be lymphocytic thyroiditis on final histology. Among the most common locations, cytology of lymph nodes provided the best sensitivity (98.2%). Salivary glands as well as lymph nodes had the best specificity (100%). CONCLUSION: FNAC of head and neck masses has a high accuracy allowing a correct therapeutic management. However, this accuracy depends on the anatomic location of the mass.

Colorectal cancer in young adults: a retrospective study of 32 tunisian patients.

Young people under the age of 40 with colorectal cancer represent a distinct subgroup with a more aggressive disease behaviour compared to older patients. This study aim to provide an updated overview on clinicopathological features, treatment and outcome of colorectal cancer in young adults under the age of 40. In our retrospective study, we reviewed 32 cases of colorectal cancer in young adults aged less than 40 years that were diagnosed at the pathology department of Mongi Slim hospital over a fifteen-year period (April 2000 - November 2014). Our study group included 13 male and 19 female patients (sex-ratio M/F = 0,68) between 17 and 39 years of age (mean = 31,25 years). The presenting clinical symptoms were dominated by altered bowel habits (n=17), followed by bleeding per rectum (n=16). Histopathological examination of the surgical and biopsy specimens established the diagnosis of mucinous adenocarcinoma in nine cases, well-differentiated adenocarcinoma in 11 cases, moderately differentiated adenocarcinoma in six cases, poorly differentiated adenocarcinoma in four cases and signet ring cell carcinoma in two cases. The tumours were classified after surgery as stage I (n = 2) (6%), stage IIA (n = 7) (22%), stage IIB (n=4) (13%), stage IIC (n=1) (3%), stage IIIB (n=8) (25%), stage IIIC (n= 4) (12%), stage IVA (n=4) (13%) and stage IVB (n=2) (6%). During the follow-up period which ranged between one month and 9 years, local recurrence of the tumour occurred in six cases, seven patients had hepatic metastases and seven patients died after a mean follow-up period of seven months. Molecular genetic studies are increasing the understanding of the pathobiology of colorectal cancer and may ultimately allow at-risk patients to be identified at an earlier stage.

Efficacy of Fine-Needle Aspiration Cytology in the Diagnosis of Tuberculous Cervical Lymphadenitis.

OBJECTIVE: This study assesses the role of fine-needle aspiration cytology (FNAC) in the diagnosis of tuberculous lymphadenitis (TL) in comparison with histology and bacteriology findings. STUDY DESIGN: We undertook a descriptive retrospective study of 937 FNAC specimens from 851 patients with cervical lymph nodes. The FNAC findings were then compared to histopathology and bacteriology. RESULTS: Of the 937 aspirates, the cytopathological diagnoses consisted of 426 (55.9%) TL, 185 (24.3%) reactive lymphoid hyperplasia, 18 (2.3%) suppurative inflammation, 78 (10.2%) malignant metastatic tumor, and 54 (7%) lymphoma. Of the 426 TL cases, 171 were diagnosed by FNAC combined with bacteriological examination. In this group, 22 cases were found to be positive on Ziehl-Neelsen stain and 16 by culture. A histopathology report was available for 62 cases. Compared to histopathology, the overall diagnostic sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of FNAC in the diagnosis of cervical TL were, respectively, 96.77, 100, 100, and 96.67%. When comparing bacteriology to histopathology, these values were 97.44, 100, 100, and 91.67%. CONCLUSION: Our study shows that FNAC is a sensitive and specific tool for the diagnosis of cervical TL.

Routine histopathological study of cholecystectomy specimens. Useful? A retrospective study of 1960 cases.

BACKGROUND AND AIMS: Traditionally, a gallbladder removed for presumed benign disease is sent for histopathological examination, but this practice has been the subject of controversy. AIM: The aim of this study was to assess the usefulness of routine histopathological examination of cholecystectomy specimens and its impact on the management of patients. PATIENTS AND METHODS: The histopathological reports of 1960 patients who underwent cholecystectomy from January 2011 to November 2016 were retrospectively reviewed. Results : There were 519 men and 1441 women (sex-ratio M/F = 0,36) aged between 8 and 96 years (mean = 51,23 years). All patients underwent cholecystectomy (either open or laparoscopic). Histological examination of the surgical specimens showed chronic cholecystitis (n = 1319) (67,29%), acute cholecystitis (n = 117) (5,96%), cholestrolosis (n = 255) (13%), follicular cholecystitis (n = 230) (11,73%), xanthogranulomatous cholecystitis (n = 6) (0,30%), cholesterol polyps (n = 5) (0,255), tubular adenoma (n = 3) (0,15%), mucocele (n = 2) (0,10%), pancreatic heterotopia (n = 2 ) (0,10%), hyperplastic Luschka ducts (n = 2) (0,10%), adenomyoma (n = 2) (0,10%), porcelain calcification (n = 2) (0,10%) and biliary-type adenocarcinoma (n = 9) (0,46%). In 9 cases (0,46%), the gallbladder was histologically normal. CONCLUSION: Our study shows that the incidence of pre-malignant and malignant lesions of the gallbladder is very low. We therefore recommend selective histopathological examination of cholecystectomy specimens with abnormal macroscopic findings.

[Colon adenocarcinoma and synchronous type 1 papillary renal cell carcinoma: a unique association]. / Adénocarcinome colique et carcinome à cellules rénales papillaire de type 1 synchrones: une association exceptionnelle.

The detection of primary tumors synchronous with colorectal cancer has been the subject of multiple publications. This association can occur sporadically or fall under the framework of well defined clinical syndromes such as Lynch syndrome. Synchronous association of colorectal cancer (CRC) and renal cell carcinoma is rare. It is even more rare when renal cell carcinoma is of papillary origin, with only 2 cases reported in the literature. The association between CRC and renal cell carcinoma does not seem to be related to mismatch repair proteins (MMR) abnormality and does not include, up to now, any clinical syndrome. We report the case of a 69-year old woman with colorectal cancer associated with synchronous type 1 papillary renal cell carcinoma unexpectedly detected during screening for CRC. We here discuss the pathogenesis as well as the prognosis of this rarely described entity.

Crohn's disease and schistosomiasis: a rare association.

Schistosomiasis is a chronic enteropathogenic disease caused by blood flukes of the genus Schistosoma. Coexistence of schistosomiasis with Crohn's disease is very rare. To the best of our knowledge, this association has been described in literature only once. A 20-year-old male patient with a past medical history of appendectomy and ileocecal Crohn's disease, presented with abdominal pain and vomiting. Ileocolonoscopy showed an ulcerated and congested appearance of the upper rectum and sigmoid. Computed tomography scan revealed a circumferential thickening of the terminal ileum with luminal stenosis. Histopathological examination of the biopsy specimens revealed a focally ulcerated colonic epithelium. The lamina propria was fibrous harbouring a polymorphic inflammatory infiltrate including lymphocytes and plasma cells organized in lymphoid follicles admixed with eosinophils and neutrophils. In the submucosa, there were two well-preserved schistosoma eggs surrounded by a thick shell with a barely visible terminal spine. The final pathological diagnosis was colonic schistosomiasis associated with Crohn's disease. The patient underwent an ileocecal resection for stenosis of the terminal ileum complicated with enterocutaneous fistula. The postoperative course was uneventful. A stool examination and serology tests were planned for this patient who was lost to follow-up.

[Solitary necrotic nodule of the liver: about two cases]. / Le nodule nécrotique solitaire du foie: à propos de deux cas.

Nodular liver lesions mainly consist of tumors. Solitary necrotic nodule of the liver is rare. Preoperative diagnosis is difficult. We report the case of a 43-year old woman undergoing surgery for the treatment of a rectal adenocarcinoma metastatized to the liver. Abdominal CT scan showed liver nodule mimicking liver metastasis. The second case is that of a 56 year-old man undergoing cholecystectomy in whom a liver nodule was detected intraoperatively. In both cases, liver nodule was subcapsular and was resected. Anatomopathological examination allowed the diagnosis of solitary necrotic nodule of the liver. Nonspecific necrotic nodule of the liver should be suspected in liver lesions, even in neoplastic context. Characterization using imaging studies and puncture biopsy of liver lesions can be useful.