ABHD6 suppression promotes anti-inflammatory polarization of adipose tissue macrophages via 2-monoacylglycerol/PPAR signaling in obese mice.

OBJECTIVE: Pro-inflammatory polarization of adipose tissue macrophages (ATMs) plays a critical role in the pathogenesis of obesity-associated chronic inflammation. However, little is known about the role of lipids in the regulation of ATMs polarity and inflammation in response to metabolic stress. Deletion of α/ß-hydrolase domain-containing 6 (ABHD6), a monoacylglycerol (MAG) hydrolase, has been shown to protect against diet-induced obesity and insulin resistance. METHODS: Here we investigated the immunometabolic role of macrophage ABHD6 in response to nutrient excess using whole-body ABHD6-KO mice and human and murine macrophage cell-lines treated with KT203, a selective and potent pharmacological ABHD6 inhibitor. RESULTS: KO mice on high-fat diet showed lower susceptibility to systemic diet-induced inflammation. Moreover, in the setting of overnutrition, stromal vascular cells from gonadal fat of KO vs. control mice contained lower number of M1 macrophages and exhibited enhanced levels of metabolically activated macrophages (MMe) and M2 markers, oxygen consumption, and interleukin-6 (IL-6) release. Likewise, under in vitro nutri-stress condition, inhibition of ABHD6 in MMe-polarized macrophages attenuated the expression and release of pro-inflammatory cytokines and M1 markers and induced the upregulation of lipid metabolism genes. ABHD6-inhibited MMe macrophages showed elevated levels of peroxisome proliferator-activated receptors (PPARs) and 2-MAG species. Notably, among different MAG species, only 2-MAG treatment led to increased levels of PPAR target genes in MMe macrophages. CONCLUSIONS: Collectively, our findings identify ABHD6 as a key component of pro-inflammatory macrophage activation in response to excess nutrition and implicate an endogenous macrophage lipolysis/ABHD6/2-MAG/PPARs cascade, as a lipid signaling and immunometabolic pathway, which favors the anti-inflammatory polarization of ATMs in obesity.

Immune checkpoint inhibitor-induced neurotoxicity is not associated with seroprevalence of neurotropic infections.

BACKGROUND: Immune checkpoint inhibitors (ICI) substantially improve outcome for patients with cancer. However, the majority of patients develops immune-related adverse events (irAEs), which can be persistent and significantly reduce quality of life. Neurological irAEs occur in 1-5% of patients and can induce severe, permanent sequelae or even be fatal. In order to improve the diagnosis and treatment of neurological irAEs and to better understand their pathogenesis, we assessed whether previous neurotropic infections are associated with neurological irAEs. METHODS: Neurotropic infections that might predispose to ICI-induced neurological irAEs were analyzed in 61 melanoma patients from 3 countries, the Netherlands, Australia and Germany, including 24 patients with neurotoxicity and 37 control patients. In total, 14 viral, 6 bacterial, and 1 protozoal infections previously reported to trigger neurological pathologies were assessed using routine serology testing. The Dutch and Australian cohorts (NL) included pre-treatment plasma samples of patients treated with neoadjuvant ICI therapy (OpACIN-neo and PRADO trials; NCT02977052). In the Dutch/Australian cohort a total of 11 patients with neurological irAEs were compared to 27 control patients (patients without neurological irAEs). The German cohort (LMU) consisted of serum samples of 13 patients with neurological irAE and 10 control patients without any documented irAE under ICI therapy. RESULTS: The association of neurological irAEs with 21 possible preceding infections was assessed by measuring specific antibodies against investigated agents. The seroprevalence of all the tested viral (cytomegalovirus, Epstein-Barr-Virus, varicella-zoster virus, measles, rubella, influenza A and B, human herpes virus 6 and 7, herpes simplex virus 1 and 2, parvovirus B19, hepatitis A and E and human T-lymphotropic virus type 1 and 2), bacterial (Borrelia burgdorferi sensu lato, Campylobacter jejuni, Mycoplasma pneumoniae, Coxiella burnetti, Helicobacter pylori, Yersinia enterocolitica and Y. pseudotuberculosis) and protozoal (Toxoplasma gondii) infections was similar for patients who developed neurological irAEs as compared to control patients. Thus, the analysis provided no evidence for an association of described agents tested for seroprevalence with ICI induced neurotoxicity. CONCLUSION: Previous viral, bacterial and protozoal neurotropic infections appear not to be associated with the development of neurological irAEs in melanoma patients who underwent therapy with ICI across 3 countries. Further efforts are needed to unravel the factors underlying neurological irAEs in order to identify risk factors for these toxicities, especially with the increasing use of ICI in earlier stage disease.

[Adverse effects of licorice consumed as food: An update]. / Toxicités de l'exposition alimentaire à la réglisse : mise au point.

The word "licorice" refers to the plant, its root, and its aromatic extract. From a commercial point of view, Glycyrrhiza glabra is the most important species with a wide range of uses (herbal medicine, tobacco industry, cosmetics, food and pharmaceutical). Glycyrrhizin is one of the main constituents of licorice. Glycyrrhizin is hydrolyzed in the intestinal lumen by bacterial ß-glucuronidases to 3ß-monoglucuronyl-18ß-glycyrrhetinic acid (3MGA) and 18ß-glycyrrhetinic acid (GA), which are metabolized in the liver. Plasma clearance is slow due to enterohepatic cycling. 3MGA and GA can bind to mineralocorticoid receptors with very low affinity, and 3MGA induces apparent mineralocorticoid excess syndrome through dose-dependent inhibition of 11ß-hydroxysteroid dehydrogenase type 2 in renal tissue. The cases of apparent mineralocorticoid excess syndrome reported in the literature are numerous and sometimes severe, even fatal, most often in cases of chronic high dose consumption. Glycyrrhizin poisonings are characterized by hypertension, fluid retention, and hypokalemia with metabolic alkalosis and increased kaliuresis. Toxicity depends on the dose, the type of product consumed, the mode of consumption (acute or chronic) and a very large inter-individual variability. The diagnosis of glycyrrhizin-induced apparent mineralocorticoid excess syndrome is based on the history, clinical examination, and biochemical analysis. Management is primarily based on symptomatic care and stopping licorice consumption.

Term newborns at risk for early-onset neonatal sepsis: Clinical surveillance versus systematic paraclinical test.

INTRODUCTION: Early-onset neonatal sepsis is a rare but potentially lethal infection that is very often suspected in daily practice. Previous national guidelines recommended the use of systematic paraclinical tests for healthy term newborns with suspected infection. These guidelines were updated in 2017 by the French Health Authority (Haute Autorité de santé), and promote initial clinical monitoring taking into account the infectious risk level for term and near-term born infants. OBJECTIVES: To assess the impact of the new recommendations on antibiotic therapy prescription and invasive tests, and on the outcomes of infants born from 36weeks' gestation. MATERIALS AND METHODS: This study compared the management and the outcome of neonates born from 36weeks' gestation at the level III University Hospital of Nancy, according to their infectious risk level during two periods, before and after the update of national recommendations: from July 1 to December 31, 2017, versus July 1 to December 31, 2018. Data were retrospectively collected from the infants' files. This study compared the number and length of antibiotic treatment and the number of invasive tests, the number of documented infections, the number and length of hospitalization, and mortality between the two periods. RESULTS: During the first period, among 1248 eligible newborns, 643 presented an infectious risk factor, versus 1152 newborns with 343 having an infectious risk factor during the second period. Antibiotic treatment was initiated for 18 newborns during the first period (1.4%) and for nine during the second (0.8%) (P=0.13). The mean (SD) duration of the antibiotic treatment was longer in the first than in the second period: 6.3±2days vs. 3.1±2.3days (P=0.003). There was no death related to neonatal infection. A total of 1052 blood samples were collected during the first period versus 51 during the second (P<0.01). There was no documented infection. In the first period, there were 18 newborns (1.4%) hospitalized for suspected infection versus nine (0.8%) in the second period (P=0.13). The duration of hospitalization was 5.7±1.7days in the first period versus 5.2±3days in the second (P=0.33). CONCLUSION: In this study, the application of the new guidelines enabled a reduction of antibiotic exposure and a reduction of invasive tests without additional risk.

The German CPU registry: Comparison of smokers and nonsmokers.

BACKGROUND: Chest pain is a major reason for admission to an internal emergency department, and smoking is a well-known risk factor for coronary artery disease (CAD) and acute coronary syndrome (ACS). The aim of this analysis is to illustrate the differences between smokers and nonsmokers presenting to German chest pain units (CPU) in regard to patient characteristics, CAD manifestation, treatment strategy, and prognosis. METHODS: From December 2008 to March 2014, 13,902 patients who had a complete 3­month follow-up were enrolled in the German CPU registry. The analysis comprised 5796 patients with ACS and documented smoking status. RESULTS: Of all the patients in the CPU registry, 35.2% were smokers. Compared with nonsmokers, they were 13.5 years younger (58.2 vs. 71.7 years, p < 0.001), predominantly men (77.1% vs. 65.2%, p < 0.001), and were more frequently diagnosed with single-vessel disease (32.1% vs. 25.2%) as well as ST-elevation myocardial infarction (STEMI; 23.8% vs. 15.5%, p < 0.001). Although the Global Registry of Acute Coronary Events (GRACE) Risk Score for hospital mortality was lower in the group of smokers (106.1 vs. 123.3, p < 0.001), we did not observe any differences in CPU death (0.4% vs. 0.4%, p = 0.69) and CPU major adverse cardiac event (MACE) rates (3.8% vs 2.9%, p = 0.073) between the groups. In the 3­month follow-up, we documented higher mortality rates in the nonsmoker group (1.9% vs. 2.9%, p = 0.035) in correlation with the GRACE Risk Score (80.3 vs. 105.2, p < 0.001). MACE rates were similar during the follow-up (3.1% vs. 4.1%, p = 0.065). CONCLUSION: Observations from the German CPU registry demonstrate that smoking is a strong predictor of acute CAD manifestation early in life, especially STEMI. In spite of a lower GRACE Risk Score and fewer comorbidities, smokers had a rate of hospital mortality similar to the older group of nonsmokers.

Management of anticoagulated patients in dentoalveolar surgery: a clinical comparative study.

OBJECTIVES: This prospective, comparative, clinical study analyzed the postoperative bleeding risk of patients on anticoagulation therapy (AT) who were undergoing tooth extractions and osteotomies. MATERIALS AND METHODS: Patients with the following ATs were included (test groups): (1.) platelet aggregation inhibitors (PAIs), (2.) vitamin K inhibitors, (3.) low molecular weight heparin (LMWH), and (4.) direct oral anticoagulants (DOACs). Patients in the control group were not on any AT (non-AT group). Patients were subdivided into the following treatment groups: (1.) single tooth extraction, (2.) serial extraction (≥ 2 adjacent teeth), and (3.) tooth osteotomy. Pre-, intra-, and postoperative data concerning the treatment, extent of the surgery, and bleeding were recorded and statistically evaluated. RESULTS: There were 15 postoperative bleeding events in 838 patients (1.7%): four (0.7%) in the non-AT group (n = 603 patients) and 11 (4.7%) in the AT group (n = 235 patients). The surgical procedure had no statistically significant effect on postoperative bleeding frequencies. Patients taking vitamin K inhibitors had a significantly higher risk of postoperative bleeding compared with patients without AT (p < 0.00001). Four patients were hospitalized due to the severity of the bleeding (vitamin K inhibitor group). Postoperative bleeding events were all controlled with local hemostatic measures. CONCLUSIONS: The postoperative bleeding risk after tooth extractions and osteotomies in patients continuing AT is low, and bleeding can be controlled with local hemostatic measures. CLINICAL RELEVANCE: AT should be continued in patients undergoing tooth removal procedures under the provision that local hemostatic measures are applied.

Comparative Lipid Peroxidation and Apoptosis in Embryo-Larval Zebrafish Exposed to 3 Azole Fungicides, Tebuconazole, Propiconazole, and Myclobutanil, at Environmentally Relevant Concentrations.

Azole fungicides have entered the aquatic environment through agricultural and residential runoff. In the present study, we compared the off-target toxicity of tebuconazole, propiconazole, and myclobutanil using embryo-larval zebrafish as a model. The aim of the present study was to investigate the relative toxicity of tebuconazole, propiconazole, and myclobutanil using multiple-level endpoints such as behavioral endpoints and enzymatic and molecular biomarkers associated with their mode of action. Zebrafish embryos were exposed to azoles at environmentally relevant and high concentrations, 0.3, 1.0, and 1000 µg/L, starting at 5 h postfertilization (hpf) up to 48 hpf, as well as 5 d postfertilization (dpf). Relative mRNA expressions of cytochrome P450 family 51 lanosterol-14α-demethylase, glutathione S-transferase, caspase 9, phosphoprotein p53, and BCL2-associated X protein were measured to assess toxicity attributable to fungicides at the mRNA level, whereas caspase 3/7 (apoptosis) and 3,4-methylene​dioxy​amphetamine (lipid peroxidation) levels were measured at the enzymatic level. Furthermore, mitochondrial dysfunction was measure through the Mito Stress test using the Seahorse XFe24 at 48 hpf. In addition, light to dark movement behavior was monitored at 5 dpf using Danio Vision® to understand adverse effects at the organismal level. There was no significant difference in the light to dark behavior with exposure to azoles compared to controls. The molecular biomarkers indicated that propiconazole and myclobutanil induced lipid peroxidation, oxidative stress, and potentially apoptosis at environmentally relevant concentrations (0.3 and 1 µg/L). The results from the mitochondrial respiration assay indicated a slight decrease in spare respiratory capacity with an acute exposure (48 hpf) to all 3 azoles at 1000 µg/L. Based on the present results, propiconazole and myclobutanil are acutely toxic compared to tebuconazole in aquatic organisms at environmentally relevant concentrations. Environ Toxicol Chem 2019;38:1455-1466. © 2019 SETAC.

[Sonographic diagnostics in operative intensive care medicine : Pericardial hematoma after cardiac surgery]. / Sonographische Diagnostik in der operativen Intensivmedizin : Perikardhämatom nach kardiochirurgischen Eingriffen.

These two case reports describe the use of transthoracic echocardiography in cardiac surgery patients during postoperative intensive care, when a pericardial hematoma developed. A focused echocardiographic examination was performed, which in both cases led to the correct diagnosis and revealed the cause for hemodynamic instability. Following additional computed tomography (CT) scans, cardiac surgery was performed on one patient, while in the other, bedside sonography was used for controlled pleural puncture and drainage of the pericardial hematoma. The case reports demonstrate that intrathoracic bleeding after cardiac surgery may develop with a latency of days to weeks, which can become hemodynamically relevant and require an intervention. Bedside point of care echocardiography opens the way for securing the diagnosis by means of CT or magnetic resonance imaging (MRI) if the circulatory state of the patient allows this prior to hematoma drainage or evacuation.

Effectiveness of antibacterial prophylaxis in children with acute leukemia: A report from a single institution over a 20-year period.

BACKGROUND: Infection is the major cause of treatment-related mortality in childhood acute leukemia, mainly due to bacterial translocation across the intestinal mucosa. Only a few studies have reported the impact of different antibacterial prophylaxis treatments on digestive tract flora and infection-related mortality. PROCEDURES: We performed a retrospective analysis of two different digestive tract decontamination modalities (selective or total digestive decontamination) in a large single-center series of 323 children during the induction treatment of acute leukemia between January 1995 and December 2014. We examined the impact of antibiotic prophylaxis and food regimen (sterile or selected) on the digestive tract flora during the period of antibacterial prophylaxis, on the frequency of bacteremia, and on antibiotic sensitivity. RESULTS: Only one Gram-negative (Klebsiella pneumonia) translocation occurred in the SDD group. No infection-related death occurred. Extended-spectrum beta-lactamase (ESBL) bacteria were observed in seven of 170 (4%) patients in the SDD group. The faecal-flora total suppression and faecal-flora Gram-negative bacilli suppression was 67 and 77%, respectively, in the TDD group with sterile food, 0 and 58%, respectively, in the SDD group with sterile food, and 6 and 63%, respectively, in the SDD group with selective food. CONCLUSIONS: This study gives a rationale not to use antibacterial prophylaxis systematically in children who receive induction treatment for acute leukemia; additionally, antibiotics should only be used in case of stool contamination by highly pathogenic bacteria with a high potential of translocation.

EGR2 mutations define a new clinically aggressive subgroup of chronic lymphocytic leukemia.

Recurrent mutations within EGR2 were recently reported in advanced-stage chronic lymphocytic leukemia (CLL) patients and associated with a worse outcome. To study their prognostic impact, 2403 CLL patients were examined for mutations in the EGR2 hotspot region including a screening (n=1283) and two validation cohorts (UK CLL4 trial patients, n=366; CLL Research Consortium (CRC) patients, n=490). Targeted deep-sequencing of 27 known/postulated CLL driver genes was also performed in 38 EGR2-mutated patients to assess concurrent mutations. EGR2 mutations were detected in 91/2403 (3.8%) investigated cases, and associated with younger age at diagnosis, advanced clinical stage, high CD38 expression and unmutated IGHV genes. EGR2-mutated patients frequently carried ATM lesions (42%), TP53 aberrations (18%) and NOTCH1/FBXW7 mutations (16%). EGR2 mutations independently predicted shorter time-to-first-treatment (TTFT) and overall survival (OS) in the screening cohort; they were confirmed associated with reduced TTFT and OS in the CRC cohort and independently predicted short OS from randomization in the UK CLL4 cohort. A particularly dismal outcome was observed among EGR2-mutated patients who also carried TP53 aberrations. In summary, EGR2 mutations were independently associated with an unfavorable prognosis, comparable to CLL patients carrying TP53 aberrations, suggesting that EGR2-mutated patients represent a new patient subgroup with very poor outcome.

Combined therapy in children and adolescents with classical Hodgkin's lymphoma: A report from the SFCE on MDH-03 national guidelines.

Hodgkin's lymphoma (HL) in children and adolescents is highly curable, but children are at risk of long-term toxicity. The MDH-03 guidelines were established in order to decrease the burden of treatment in good-responder patients, and this report should be considered a step toward further optimization of treatment within large collaborative trials. We report the therapy and long-term outcomes of 417 children and adolescents treated according to the national guidelines, which were applied between 2003 and 2007 in France. The patients were stratified into three groups according to disease extension. Chemotherapy consisted of four cycles of VBVP (vinblastine, bleomycin, VP16, prednisone) in localized stages (G1/95 pts/23%), four cycles of COPP/ABV (cyclophosphamide, vincristine, procarbazine, prednisone, adriamycin, bleomycin, vinblastine) cycles in intermediate stages (G2/184 pts/44%) and three cycles of OPPA (vincristine, procarbazine, prednisone, adriamycin) plus three cycles of COPP in advanced stages (G3/138 pts/33%). Radiation therapy of the involved field was given to 97% of the patients, with the dose limited to 20 Gy in good responders (88%). With a median follow-up of 6.6 years, the 5-year event-free survival (EFS) and overall survival (OS) were 86.7% (83.1-89.7%) and 97% (94.5-98.1%), respectively. EFS and OS for G1, G2, and G3 were 98% and 100%, 81% and 97%, and 87% and 95%, respectively. Low-risk patients treated without alkylating agents and anthracycline had excellent outcomes and a low expected incidence of late effects. Intensification with a third OPPA cycle in high-risk group patients, including stage IV patients, allowed for very good outcomes, without increased toxicity.

Diagnosis and Treatment of Nasopharyngeal Carcinoma in Children and Adolescents - Recommendations of the GPOH-NPC Study Group.

Nasopharyngeal carcinoma (NPC) is a rare malignant tumor arising from epithelial cells of the nasopharynx. Its incidence is highest in Southeast Asia. Age distribution of NPC is bimodal, with one peak in young adolescents and another in patients 55-59 years of age. EBV appears to be the primary etiologic agent in the pathogenesis, environmental factors such as nitrosamines and genetic factors are contributory. NPC is most commonly diagnosed in locally advanced stages, with lymph node metastases occurring in up to 90% of patients. About 5-10% of patients present with distant metastases. Diagnosis of NPC is made histologically, supported by an abnormal anti-EBV-VCA IgA titer and elevated plasma EBV-DNA load. Superior results in children and adolescents with advanced locoregional NPC, with overall and event-free survival rates>90%, have been achieved by neoadjuvant chemotherapy with 5-fluoruracil and cisplatin, followed by synchronous radiochemotherapy and subsequent maintenance therapy with interferon-ß as demonstrated by the 2 prospective studies GPOH-NPC-91 and -2003. Response to therapy can be assessed by PET-imaging and in patients with complete remission after neoadjuvant chemotherapy, the radiation dose to the primary tumor can be safely reduced from 59.4 to 54.4 Gy. Since the majority of long term sequalae such as xerostomia, skin and tissue fibrosis are caused by high radiation dosages, radiotherapy modalities such as intensity-modulated radiotherapy should be used to efficiently spare non-tumorous tissue. For patients with metastatic disease and relapse, survival chances are low. New treatment strategies, such as the application of EBV-specific T-lymphocytes should be considered for these patients.

First protein and peptide characterization of the tarsal adhesive secretions in the desert locust, Schistocerca gregaria, and the Madagascar hissing cockroach, Gromphadorhina portentosa.

Peptides and proteins have been largely neglected in the analysis of insect tarsal adhesives. After extraction of the protein fraction of the tarsal secretion of the desert locust, Schistocerca gregaria, and Madagascar hissing cockroach, Gromphadorhina portentosa, we combined Fourier transform infrared spectroscopy (FTIR), sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and matrix-assisted laser desorption/ionization mass spectrometry (MALDI-TOF MS) analyses for protein mass detection. In both these insects, SDS-PAGE analysis revealed several protein bands ranging from 8-190 kDa in both the tarsal secretion and the tibia control sample. Two (S. gregaria) and one (G. portentosa) protein bands exclusively occurred in the tarsal secretion and can be considered to belong to peptides and proteins specific to this secretion. MALDI-TOF analyses revealed 83 different proteins/peptides of 1-7 kDa in S. gregaria, and 48 of 1-11 kDa in G. portentosa. 59 (S. gregaria) and 27 (G. portentosa) proteins exclusively occurred in the tarsal secretion. In G. portentosa, a characteristic series of signal peaks occurred in the range of c. 10-12 kDa, each peak being approximately 160 Da apart. Such a pattern is indicative of proteins modified by glycosylation. Our approach demonstrates that extensive sampling involving considerable time and manpower to sample the adhesive fluid directly from the tarsi opens up a perspective for extracting peptides and proteins in sufficient quantities. This makes them accessible to the field of proteomics and thus to elucidate their possible function in the adhesive process.

Management of anticoagulated patients in implant therapy: a clinical comparative study.

OBJECTIVES: This prospective clinical comparative study aimed to analyze the postoperative bleeding risk of patients continuing their anticoagulation therapy (AT) and undergoing implant surgery and bone grafting procedures. MATERIALS AND METHODS: The treatments ranged from the insertion of single or multiple dental implants over implant exposures to sinus floor augmentation and vertical and/or lateral bone grafting with autologous bone grafts. The patients of the test groups (AT groups) were treated with platelet aggregation inhibitors (PAIs), Vitamin-K inhibitors, Vitamin-K inhibitor withdrawal bridged with heparin (LMWH), or new/direct oral anticoagulants (NOACs/DOACs). Patients of the control group were non-anticoagulated (non-AT group). Surgical procedures were performed in the same manner in all groups. Pre, intra, and postoperative data concerning the treatment, extent of the surgery and bleedings was recorded and statistically evaluated. RESULTS: There were seven postoperative bleedings in 564 patients (1.2%), four in the AT groups (3.4%), and three in the non-AT group (0.6%). No thromboembolic complication occurred in the whole observation period. The invasiveness of the surgical procedure had no statistically significant effect on bleeding frequencies. Patients taking Vitamin-K inhibitors had a significantly higher risk of a postoperative bleeding compared to patients without any AT (P = 0.038). Two patients were hospitalized due to the severity of the bleeding as a precautionary measure (one in the non-AT and one in the PAI group). All bleedings were easily controllable with local hemostatic measures. There was no postoperative bleeding recorded for patients taking DOACs. CONCLUSIONS: Anticoagulation therapy should be continued in patients undergoing implant surgery and bone grafting procedures avoiding thromboembolic complications. Surgeons should always apply the most minimally invasive approach to reduce postoperative risks and be able to apply local hemostatic measures in terms of a bleeding complication.

[Axillary lymph node metastases with an occult breast: About 16 cases from a cohort of 7770 patients]. / Envahissement ganglionnaire axillaire sans tumeur primitive mammaire retrouvée : à propos de 16cas issus d'une cohorte de 7770patientes.

OBJECTIVES: Isolated axillary lymph node metastases is an unusual clinical presentation of breast carcinoma. We studied its different issues. METHODS: This study is a follow-up study of 16patients, treated between 1996 and 2012, presenting with axillary metastases with an occult breast carcinoma, which could not be identified by physical examination nor by a conventional imaging or a breast MRI. Clinical characteristics, histological analysis, treatment, monitoring and five-year survival rate were studied. RESULTS: The incidence of this kind of breast cancer was 0.20%. A breast MRI was performed in 75% of the patients. The histology of these tumors showed a rate of hormono-sensibility of 50% and an HER2 overexpression of 44%. Sixty-nine percent of the patients had no breast surgery or radiotherapy; global five-year survival rate for these women was 77.4%±11.5. CONCLUSION: The survival rates of this study should lead the practitioner to choose a less aggressive breast therapy. Moreover, the histological characteristics explain the high metastatic potential of these tumors, and relate them to the HER2+ subclass of gene expression patterns of breast carcinomas.

Implementation of a non-lethal biopsy punch monitoring program for mercury in smallmouth bass, Micropterus dolomieu Lacepède, from the Eleven Point River, Missouri.

A non-lethal biopsy method for monitoring mercury (Hg) concentrations in smallmouth bass (Micropterus dolomieu; smallmouth) from the Eleven Point River in southern Missouri USA was evaluated. A biopsy punch was used to remove a muscle tissue plug from the area immediately below the anterior dorsal fin of 31 smallmouth. An additional 35 smallmouth (controls) were held identically except that no tissue plug was removed. After sampling, all fish were held in a concrete hatchery raceway for 6 weeks. Mean survival at the end of the holding period was 97 % for both groups. Smallmouth length, weight and Fulton's condition factor at the end of the holding period were also similar between plugged and non-plugged controls, indicating that the biopsy procedure had minimal impact on growth under these conditions. Tissue plug Hg concentrations were similar to smallmouth Hg data obtained in previous years by removing the entire fillet for analysis.

Efficiency of 5-ALA mediated photodynamic therapy on hypoxic prostate cancer: a preclinical study on the Dunning R3327-AT2 rat tumor model.

OBJECTIVES: To evaluate photodynamic therapy (PDT) using 5-ALA-induced protoporphyrin IX (PPIX) in an in vivo hypoxic tumor model and its monitoring using MRI. MATERIAL AND METHODS: Dunning R3327-AT2 tumors were grafted in the neck of Copenhagen rats. PDT using 150 mg 5-ALA/kg i.v. was performed by focal interstitial illumination of the photosensitized tumor (λ=633 nm; fluence=100 J/cm(2)). MRI at baseline and 2 days after treatment (T1, T2 and dynamic gadolinium enhanced sequences) were performed. Necrosis volumes were determined on post-procedure MRI. Tumors were resected 2 days post-PDT and obtained necrosis was determined histopathologically. Intra-tumoral PPIX distribution was evaluated using confocal microscopy and tissue porphyrin quantification. RESULTS: Twenty rats were treated divided into three groups: continuous (n=7), fractionated illumination (n=7), and a control group receiving only light or only ALA or neither (n=6). Baseline MRI confirmed the hypoxic character of tumors. Necrosis volumes determined on posttreatment MRI were not reproducible and presented with important geometric and volumetric variability. Average necrosis volumes of 0.39 cc (0-0.874 cc) in the continuous group, 0.24 cc (0.107-0.436 cc) in the fractionated group and 0.012 cc (0-0.071 cc) in the control group were observed. Intra-tumoral PPIX distribution was heterogeneous and PPIX quantification revealed low intra-tumoral concentration. CONCLUSION: Necrosis volumes induced by 5-ALA-mediated PDT were highly variable and non reproducible, probably because of lack of intra-tissular oxygen. Photosensitizer was poorly represented inside the tumor and its distribution was heterogeneous. Our study suggests that 5-ALA-mediated PDT might not be the best management option for hypoxic prostatic adenocarcinoma.

Risk of gestational trophoblastic neoplasia after hCG normalisation according to hydatidiform mole type.

OBJECTIVE: The risk of gestational trophoblastic neoplasia (GTN) after a hydatidiform mole (HM) is well known. However, the risk of GTN after normalisation of hCG in HM is poorly reported. The aim of this study was to evaluate the risk of GTN after normalisation of hCG according to HM types. METHODS: This prospective cohort study carried out between 2000 and 2010 used the database of the French Trophoblastic Disease Centre (FTDC). A total of 2008 registered patients with ascertained types of HM were analysed. Cases of GTN occurring after normalisation of hCG were analysed. RESULTS: A GTN developed in 239 out of 1980 HMs (12.1%) and 6 out of these 239 post-molar GTN (2.5%) were diagnosed after normalisation of hCG. The risk of GTN after normalisation of hCG was 0.34% (6/1747) following a HM, 0% (0/593) after a partial HM (PHM), 0.36% (4/1122) after a complete HM (CHM), and 9.5% (2/21) after a multiple pregnancy with HM. CONCLUSIONS: The risk of post-molar GTN justifies hCG monitoring in all women with HM. However, after normalisation of hCG, monitoring of PHM can be stopped safely while it should be maintained for CHM and more importantly for multiple pregnancies with HM.