Cleft palate lateral synechia syndrome in two patients and literature review.

Cleft palate lateral synechia (CPLS) syndrome is an extremely rare congenital malformation syndrome of unknown origin, characterized by the association of cleft palate and one or more intraoral lateral synechiae (OMIM # 119550). Fewer than 20 cases have been described to date. The clinical and histological findings and results of genetic investigations for two additional cases of CPLS are presented herein, in order to better delineate this syndrome, within the context of the relevant literature. The first case presented with a U-shaped cleft palate, bilateral synechiae, and Pierre Robin sequence, requiring early sectioning of the synechiae because of severe feeding problems. The second case presented with a V-shaped cleft palate and a single synechia, running from the left border of the cleft to the floor of the mouth, and was without feeding difficulties. In both cases, histopathological examination of the synechiae revealed an aspect of mucous membranes macroscopically, while staining of sections indicated lymphocyte infiltrates and parakeratosis with stratified squamous epithelium, associated with vessel and connective tissue abnormalities. Sequencing of candidate genes did not identify a genetic cause. Accurate clinical descriptions, histopathological diagnosis, and genetic investigations of patients with synechiae are lacking in the literature. Better characterization of future cases of CPLS will give new insights into its developmental causes.

Systems Pharmacology Modeling of Prostate-Specific Antigen in Patients With Prostate Cancer Treated With an Androgen Receptor Antagonist and Down-Regulator.

First-in-human (FIH) studies with AZD3514, a selective androgen receptor (AR) down-regulator, showed decreases of >30% in the prostate-specific antigen (PSA) in some patients. A modeling approach was adopted to understand these observations and define the optimum clinical use hypothesis for AZD3514 for clinical testing. Initial empirical modeling showed that only baseline PSA correlated significantly with this biological response, whereas drug concentration did not. To identify the mechanistic cause of this observation, a mechanism-based model was first developed, which described the effects of AZD3514 on AR protein and PSA mRNA levels in LNCaP cells with and without dihydrotestosterone (DHT). Second, the mechanism-based model was linked to a population pharmacokinetic (PK) model; PSA effects of clinical doses were subsequently simulated under different clinical conditions. This model was used to adjust the design of the ongoing clinical FIH study and direct the backup program.

Training and practice of cytotechnologists: a discussion forum focused on Europe.

OBJECTIVES: To discuss the role and training of cytotechnologists (CTs) in Europe, to identify areas of good practice and to provide an informed opinion to those providing guidelines for training and practice in Europe. METHODS: All members of the Editorial Advisory Board of Cytopathology were invited to take part in a 'discussion forum' for which six topics were circulated in advance concerning the roles of CTs with regard to: (1) pre-screening slides; (2) 'signing out' reports; (3) carrying out ancillary techniques; (4) supervising laboratory staff; (5) taking part in rapid on-site evaluation (ROSE) of fine needle aspirates (FNAs); and (6) whether CTs were trained specifically in cytopathology or in general histopathology. Notes of the meeting were circulated by email and a final report was agreed by 22 participants from 17 predominantly European countries. RESULTS: Training for CTs throughout Europe was variable, especially for non-gynaecological cytology, which was inconsistent with the range of activities required. The participants recommended graduate entry, preliminary training in general laboratory technology, and subsequent training to take account of the probability and, in some centres, the reality of primary cervical cancer screening changing from cytology to human papillomavirus (HPV) testing. They further recommended that CTs should perform HPV tests and take part in ROSE for FNAs, and they supported the European Federation of Cytology Societies developing guidelines for training and practice. CONCLUSION: With CT training added to a university-based education in laboratory or biomedical science, a career in cytotechnology should be an attractive option involving a diverse range of laboratory and clinically based activities.

Fibrolamellar variant of hepatocellular carcinoma does not have a better survival than conventional hepatocellular carcinoma--results and treatment recommendations from the Childhood Liver Tumour Strategy Group (SIOPEL) experience.

PURPOSE: Fibrolamellar hepatocellular carcinoma (FL-HCC) and conventional hepatocellular carcinoma (HCC) cases in two consecutive paediatric HCC trials were analysed to compare outcome and derive treatment implications. PATIENTS AND METHODS: Data of 24 FL-HCC (24% PRETEXT IV) and 38 HCC (42% PRETEXT IV) cases from SIOPEL-2 and -3 (1995-1998, 1998-2006) were analysed. Patients were treated according to SIOPEL-2 and -3 high-risk protocol (carboplatin+doxorubicin alternating with cisplatin; seven preoperative, three postoperative cycles) or with primary surgery followed by chemotherapy as indicated. RESULTS: Thirteen of 24 FL-HCC (54%) and 32/38 HCC (84%) were initially treated with chemotherapy. Eight FL-HCC (33%) and five HCC patients (13%) had primary surgery. Partial response was observed in 31% of FL-HCC versus 53% of HCC patients (p=0.17). Complete resection was achieved in ten FL-HCC and seven HCC patients (p=0.08). Three-year event free survival (EFS) was 22% for FL-HCC versus 28% for HCC. Overall survival (OS) was not significantly different at 3 years follow up (42% for FL-HCC versus 33% for HCC, p=0.24). EFS/OS Kaplan-Meier curves did not differ significantly, with median follow up of 43 (FL-HCC) and 60 (HCC) months. No significant correlation was found between potential prognostic factors and OS. In the entire cohort nine out of 23 (39%) patients with complete resection or orthotopic liver transplantation versus 34/39 (87%) without successful surgical treatment, died. CONCLUSIONS: Long-term OS in FL-HCC and HCC is similar. With low response rates, complete resection remains the treatment of choice.

Intestinal infection with Trichinella spiralis induces distinct, regional immune responses.

The aim of this study was to evaluate differences between the small and large intestines (SI and LI) with regard to colonization and immunity during infection with Trichinella spiralis. In orally infected C57BL/6 mice, the gender ratios of worms differed among the SI, cecum, and LI. Mucosal mastocytosis developed in the SI but not in the LI, consistent with reduced IL-9 and IL-13 production by explants from the LI. Despite these differences, worms were cleared at the same rate from both sites. Furthermore, IL-10 production was reduced in the LI, yet it was instrumental in limiting local inflammation. Finally, passive immunization of rat pups with tyvelose-specific antibodies effectively cleared fist-stage larvae from all intestinal regions. We conclude that despite regional differences in immune responsiveness and colonization, immune mechanisms that clear T. spiralis operate effectively throughout the intestinal tract.

Pancreatic resections for solid or cystic pancreatic masses in children.

OBJECTIVES: The aim of the study was to assess the diagnosis and management of solid pancreatic neoplasm in children and the type of surgical treatment, focusing on short- and long-term outcomes. METHODS: We retrospectively reviewed the charts of all children who had undergone pancreatic resection for suspicion of pancreatic tumor in Kremlin Bicêtre Hospital, Paris, between 1986 and 2008. We studied the symptoms at diagnosis, the type of surgery, and the short- and long-term morbidity and mortality. RESULTS: Of 18 patients identified, there were 7 pseudopapillary tumors, 3 neuroblastomas, 2 rhabdomyosarcomas, 1 acinar cell carcinoma, 1 endocrine cell carcinoma, 1 renal angiomyolipoma, and 3 pancreatic cysts. Symptoms at diagnosis were abdominal trauma, abdominal mass, and jaundice. Operative procedures were duodenopancreatectomy (11), mid-pancreatic resections (2), splenopancreatectomy (2), distal pancreatectomy (1), and tumorectomy (2). There were no deaths related to surgery. The postoperative morbidity rate was 45%, including 2 cases of fistula (11%) occurring after a mid-pancreatic resection and a pancreaticoduodenectomy. The median follow-up was 4.2 years (range 2-11). There was no diabetes mellitus, but there was 1 case of fat diet intolerance requiring pancreatic enzyme substitution. All of the children had a growth curve within normal limits. CONCLUSIONS: In this experience, pancreatic resections have proven to be a safe and efficient procedure, with low long-term morbidity, for the treatment of tumoral and selected nontumoral pancreatic masses.

[Evaluation of the Fluo-RAL (RAL) kit for the identification of mycobacteria by fluorescence microscopy]. / Évaluation du kit Fluo-RAL (RAL) pour la recherche de mycobactéries en microscopie à fluorescence.

AIM OF THE STUDY: This study has examined the sensitivity of a commercially available fluorochrome stain, the Fluo-RAL kit (RAL), in comparison to the Degommier's stain as gold standard. MATERIALS AND METHODS: Hundred and thirty-three twin smears, made directly from samples or after their decontamination with N-acetyl-L-cysteine NaOH, were stained, the first slide with the Degommier's method and the second with the Fluo-RAL kit. The samples were 58 sputums, 31 broncho-aspirations, nine gastric lavages, 11 bronchoalveolar lavages, six pleural fluids, two cerebro-spinal fluids, 11 biopsies, two blood cultures and two deep pus. They were examined with 400 × objective under standard fluorescence UV filter by two laboratory technicians independently. The results were expressed with semi-quantitative mean from 0 to 4+. RESULTS: Hundred and thirty-two results were agreed in grading between the two methods: 73 negative smears, nine quantified as rare (1+), 11 as few (2+), 32 as moderate (3+) and seven as numerous (4+). The only discrepant result had concerned a positive smear quantified as 1+ with the Degommier's stain and as 2+ with the Fluo-RAL kit. This discrepancy was confirmed after a second examination. CONCLUSION: After this study, the Fluo-RAL kit was considered as agreed for its daily use in our laboratory. It improves the standardisation of fluorescence microscopy without additional cost or waste of time and reduces the chemical risk in the laboratory. This test, associated with reading using light-emitting diodes, could allow the development of fluorescence microscopy, the higher sensitive method for direct diagnosis of tuberculosis, in poor-resource countries where tuberculosis is a public health problem.

[Glycopeptide-resistant enterococci carriage: Are actual isolation and identification techniques sufficient?]. / Portage d'entérocoques résistants aux glycopeptides : les techniques d'isolement et d'identification actuelles sont-elles suffisantes ?

UNLABELLED: The monitoring of infection by glycopeptide-resistant enterococci (GRE) is one of the main elements of hospital hygiene policy. It involves systematic rectal swabs in clinics at risk (asymptomatic carriage). AIM: We compare two GRE screening methods and evaluate a new kit associating multiplex PCR and hybridization (Génotype(®) Enterococcus, Hain Lifescience) on a panel of 448 samples collected over a 4-month period. PATIENTS AND METHODS: The first method is based on direct inoculation of the sample; the second one involves a preliminary enrichment phase followed by molecular diagnosis allowing the identification of species of enterococci as well as glycopeptide resistance genes. RESULTS: All the resistant strains were isolated using the enrichment technique. The incidence of GRE (VanA) carriage was 0,55% (two out of 362 patients, two out of 448 isolates) with two Enterococcus faecium VanA. Six Enterococcus gallinarum VanC1 and two Enterococcus casseliflavus VanC2/C3 were also isolated and identified. The main clinics concerned are intensive care and hematology. The two patients with E. faecium VanA had been previously given glycopeptides for 10 days. For three strains, the molecular method allowed to correct prior erroneous results based on rapid identification (RapidID32Strep V2.0). CONCLUSION: The method using direct samples inoculation underestimates real incidence of GRE carriage. The performances of Génotype(®) Enterococcus molecular method, evaluated for other parameters using reference strains and DNA sequencing, offer new possibilities applicable to routine laboratory.

Wnt signaling and hepatocarcinogenesis: the hepatoblastoma model.

The Wnt/ß-catenin pathway plays a key role in liver development, regeneration and tumorigenesis. Among human cancers tightly linked to abnormal Wnt/ß-catenin signaling, hepatoblastoma (HB) presents with the highest rate (50-90%) of ß-catenin mutations. HB is the most common malignant tumor of the liver in childhood. This embryonic tumor differs from hepatocellular carcinoma by the absence of viral etiology and underlying liver disease, and by distinctive morphological patterns evoking hepatoblasts, the bipotent precursors of hepatocytes and cholangiocytes. Recent studies of the molecular pathogenesis of hepatoblastoma have led to identify two major tumor subclasses resembling early and late phases of prenatal liver development and presenting distinctive chromosomal alterations. It has been shown that the molecular signature of Wnt/ß-catenin signaling in hepatoblastoma is mainly imposed by liver context, but differs according to developmental stage. Finally, the differentiation stage of tumor cells strongly influences their invasive and metastatic properties, therefore affecting clinical behavior.

Evaluation of FibroTest-ActiTest in children with chronic hepatitis C virus infection.

FibroTest-ActiTest (FT-AT) has been validated in adults with chronic hepatitis C virus (HCV) infection as a noninvasive alternative to liver biopsy (LB), but there are few data of its use in children. The objective of the present study was to evaluate FT-AT in children with HCV infection and to compare FT-AT analysis with liver histology. A total of 43 serum samples from 38 children with chronic HCV infection were analyzed retrospectively. Histological evaluation was performed according to the METAVIR scoring system. In 16 of the children, 21 serum samples were tested with FT-AT and compared to 21 LB (serum/LB pairs) in nontransplanted and liver-transplanted children. FT-AT was also measured in 22 infected children without LB and in 50 healthy controls. FT-AT values in controls were comparable to those of healthy adults, validating the adult FT-AT parameters in children. In most infected children (74%), the FT-AT score was

Professionals' and laypersons' appreciation of various options for Class III surgical correction.

SUMMARY: The objectives of this study were to evaluate the assessments of maxillofacial surgeons, orthodontists, and laypersons on the predicted aesthetic outcome of various surgical options in Class III correction and the associations between certain initial cephalometric values and the judges' preferred option. Pre-surgical lateral headfilms and coloured profile photographs of 18 skeletal Class III Caucasian adult patients (10 males and 8 females) with a mean age of 24.5 years were used. The headfilms were hand traced and digitized. Conventional cephalometric analysis was performed. Computerized predictions of three surgical options, mandibular setback, Le Fort I advancement, and bimaxillary surgery, were made. For each case, the pre-surgical profile photograph with the three predictions was presented on a printed page. The questionnaire was sent to 51 maxillofacial surgeons (response rate 45.1 per cent), 78 orthodontists (response rate 71.8 per cent), and 61 laypersons (response rate 100 per cent) to aesthetically evaluate the pre-surgical photographs and the surgical predictions by placing a mark along a 10-graded visual analogue scale (VAS) using a standard profile for calibration. Confidence interval was calculated for each patient. An independent samples t-test was used to detect initial cephalometric values associated with the judges' preferred option and analysis of variance/Tukey's honestly significant differences to evaluate differences between judges. Intra-observer reliability was assessed with a paired t-test. All treatment predictions led to improved scoring of facial aesthetics with the exception of the setback option for three patients. For 14 patients, general agreement for the preferred option existed between the three groups of judges. Laypersons tended to give lower improvement scores than professionals. Overjet, nasofacial, and nasomental angles were important in decision making between the mandibular setback and Le Fort I options (the more negative the overjet, the larger the nasofacial angle, the smaller the nasomental angle, the greater the preference for the Le Fort I option). Wits appraisal seemed to be important in decision making between the mandibular setback and bimaxillary options (the more negative the Wits appraisal, the greater the preference for the latter option).

[Children born with a cleft: treatment at the CHUV in Lausanne]. / Prise en charge des fentes labio-maxillo-palatines au CHUV.

A cleft can be labial, labial-maxillary, unilateral or bilateral labial-maxillary-palatal, or isolated palatal. A multidisciplinary team includes several specialists who will handle the diverse problems of children born with a cleft. This team will follow the child through each developmental stage and assemble an optimal treatment plan, thus reducing the onus on the family. Depending on the type of cleft and the age of the child, feeding, speech, ORL, dental, orthodontic, esthetic and possibly also psychological problems will be taken care of. This is why cleft treatment starts at the time it is diagnosed, before or after birth, and ends when the child is fully grown. It requires a complete interdisciplinary team and the collaboration with obstetricians and geneticians.

[Management of antenatal fetal abdominal tumors. Clues for the diagnosis of a congenital mesoblastic nephroma]. / Conduite à tenir obstétricopédiatrique devant la découverte anténatale d'une masse hyperéchogène rétropéritonéale. Arguments en faveur d'un néphrome mésoblastique congénital.

The prenatal diagnosis of abdominal mass poses the problem of its origin. Renal tumors are rarer than neuroblastoma but they are most often congenital mesoblastic nephroma. The congenital mesoblastic nephroma has a good forecast in spite of a sonographic impressive aspect. MRI can help to locate tumor but cannot tell difference between the different kinds of renal tumor. Prenatal forecast is especially linked with hydramnios and hydrops fetalis. Histolological study of the tumor is important for the prognosis. Two morphological subtypes are currently distinguished: the classic type with a good forecast and the atypical or cellular type. Distant metastases have been related only to the cellular form but especially in infants aged more than 3 months and never in the newborns. The diagnosis of the tumor does not change the mode of delivery except in case of an important volume. Complications are searched during the first days of life: hypertension, hypercalcemia, vomiting, hyperreninemia. Radical nephrectomy is performed after the end of the first week. In case of a classic form, the healing is always obtained. In case of cellular form, distant metastases are searched. In any rate, the follow-up is recommended until the end of the growth.

Orthodontists' and laypersons' aesthetic assessment of Class III subjects referred for orthognathic surgery.

This study was undertaken to compare laypersons' and professionals' perception of soft tissue profiles of Class III adults, and to evaluate which cephalometric variables are likely to influence the profile assessment score (PAS). Lateral headfilms and coloured profile photographs of 18 skeletal Class III Caucasian adult patients (10 males, 8 females with a mean age of 24.5 years) prior to surgery, and nine adult Caucasian patients (four males, five females with a mean age of 27.4 years) with a dental Class I occlusion and no major skeletal discrepancy were included in the study. The headfilms were hand traced and digitized. Various cephalometric variables were calculated by computer software. Each printed profile photograph was evaluated aesthetically by 18 laypersons and 18 orthodontists using a 10-graded visual analogue scale (VAS) and a standard profile for calibration. Intra-observer reliability was tested and no significant error was found. Paired and unpaired t-tests were used to compare the scores. The association between various cephalometric variables and the PAS was tested. In general, compared with orthodontists, laypersons were less critical in their evaluation of the Class III profiles (+0.3 grade on the VAS) as well as the reference profiles (+0.7). The reference profiles were found to be more attractive than the Class III profiles by both laypersons and orthodontists (+2.3 grades). The degree of facial concavity had a negatively predictive value for the orthodontists' and laypersons' evaluations. The degree of facial concavity together with the steepness of the mandibular plane were negatively predictive factors for the PAS given by the orthodontists.

Mycobacterium avium-intracellulare contamination of mammalian cell cultures.

Mycobacterium avium contamination has been described as a putative contaminant of nonphagocytic mammalian cells. Screening of numerous cultured nonphagocytic mammalian cell lines revealed the presence of intracellular bacteria that were identified as M. avium-intracellulare. An extensive and critical analysis of the origin of infection, of cure protocols, and of biological manifestations in M. avium-infected cells is presented. As no tremendous visible alteration of turbidity or pH of cell culture media, and no morphological change occurred in most M. avium-infected cell cultures, detection of an infection by these bacteria is rather difficult. Recommendations are given for treatment of irreplaceable cultures and prevention of mycobacterial contamination in a tissue culture facility.

Deep-seated rectal/anal basaloid carcinoma: useful immunocytochemistry in rare squamous cell carcinoma variants.

OBJECTIVES: To report the cytological aspects of ano-rectal basaloid carcinoma (BC) variant in endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) conventional and liquid-based cytology (LBC), in a series of 10 cases of deep-seated squamous cell carcinomas (SCC), and to discuss the diagnostic difficulties in interpreting the morphology and immunocytochemical findings. METHODS: Ten cases of EUS-FNA smears and LBC specimens of deep-seated pelvic masses were retrospectively collected from January 2001 to November 2006. RESULTS: Ten EUS-FNA specimen cases were SCC, eight corresponding to usual SCC and two to BC-variant. Of these two cases, only one was correctly diagnosed by EUS-FNA specimen, whereas in the second case, the initial cytological diagnosis was poorly differentiated adenocarcinoma and the final diagnosis of basaloid carcinoma variant was established on surgical resection. Immunocytochemistry (ICC) using CK7, CK20 and CK34betae12 on FNA specimens confirmed the diagnosis retrospectively. CONCLUSION: The diagnosis of basaloid variant of SCC in a rectal location can be very difficult, both on account of the uncommon location and because of the low specificity of morphological aspects on EUS-FNA smears. The immunocytochemical technique, including a limited spectrum of keratins (CK7, CK20, CK34betae12, and p63) is necessary to avoid this diagnostic pitfall.

[Adenomatous hyperplasia of the conjunctiva]. / Hyperplasie adénomateuse de la conjonctive.

We report a case of adenomatous hyperplasia of the conjunctiva. A 42-year-old man was referred for a left conjunctival lesion involving the caruncle; the histopathological patterns revealed benign adenomatous hyperplasia, a disease that may originate in the conjunctiva. Adenomatous hyperplasia of the conjunctiva is a benign condition. The absence of cytonuclear anomalies and mitotic activity distinguishes adenomatous hyperplasia from adenocarcinoma and mucoepidermoid carcinoma.

Transcription factors involved in pancreas development are expressed in paediatric solid pseudopapillary tumours.

AIMS: Solid pseudopapillary tumours (SPT) are rare pancreatic tumours, especially in children. The origin of this benign tumour remains unknown. Mutations of beta-catenin, a gene essential for pancreatic development, are constantly found, leading to delocalization of immunohistochemical signals from the cytoplasm to the nuclei of tumour cells. The aim was to report clinical and histological data of eight children with SPT and explore the immunohistochemical expression of pancreatic duodenal homeobox (PDX) 1 and Sox9, known to be crucial for pancreatic development and linked to the beta-catenin cascade. METHODS AND RESULTS: Eight children with features suggestive of SPT underwent surgical resection. Tumours displayed typical histological appearances. One was incompletely resected and recurred. Immunolabelling revealed nuclear location of beta-catenin in all cases and strong cytoplasmic but no nuclear expression of PDX1 or Sox9 in all but one case. CONCLUSIONS: The clinical behaviour of SPT in the paediatric population is similar to its adult counterpart. Complete surgical resection is essential. PDX1 and Sox9 proteins are exclusively expressed in the cytoplasmic compartment in SPT, suggesting overexpression of the corresponding genes linked to beta-catenin mutations. These findings favour the hypothesis that SPT originates from transformation of normally quiescent pancreatic stem cells.