Survival of patients managed in France for duodenal neuroendocrine tumors (D-NET): a 20-year multicenter cohort study from the GTE group: a cohort study.

INTRODUCTION: Duodenal neuroendocrine tumours (D-NETs) have a low incidence; however, their diagnosis has been increasing. Features such as tumour location, size, type, histological grade, and stage were used to adapt the treatment to either endoscopic (ER) or surgical (SR) resections. There is no consensus regarding the definitive treatment. The authors' study aimed to describe the management of non-metastatic, well-differentiated D-NETs in France and its impact on patient survival. METHODS: A registry-based multicenter study using prospectively collected data between 2000 and 2019, including all patients managed for non-metastatic G1 and G2 D-NETs, was conducted in the GTE group. RESULTS: A total of 153 patients were included. Fifty-eight benefited from an ER, and 95 had an SR. No difference in recurrence-free survival (RFS) was observed regardless of treatment type. There was no significant difference between the two groups (ER vs. SR) in terms of location, size, grade, or lymphadenopathy, regardless of the type of incomplete resection performed or regarding the pre-therapeutic assessment of lymph node invasion in imaging. The surgery allowed for significantly more complete resection (patients with R1 resection in the SR group: 9 vs. 14 in the ER group, P<0.001). Among the 51 patients with positive lymph node dissection after SR, tumour size was less than or equal to 1 cm in 25 cases. Surgical complications were more numerous (P=0.001). In the sub-group analysis of G1-G2 D-NETs between 11 and 19 mm, there was no significant difference in grade (P=0.977) and location (P=0.617) between the two groups (ER vs. SR). No significant difference was found in both morphological and functional imaging, focusing on the pre-therapeutic assessment of lymph node invasion (P=0.387). CONCLUSION: Regardless of the resection type (ER or SR) of G1-G2 non-metastatic D-NETs, as well as the type of management of incomplete resection, which was greater in the ER group, long-term survival results were similar between ER and SR. Organ preservation seems to be the best choice owing to the slow evolution of these tumours.

Discordance between immunochemistry of mismatch repair proteins and molecular testing of microsatellite instability in colorectal cancer.

BACKGROUND: DNA mismatch repair system deficiency (dMMR) is found in 15% of colorectal cancers (CRCs). Two methods are used to determine dMMR, immunohistochemistry (IHC) of MMR proteins and molecular testing of microsatellite instability (MSI). Only studies with a low number of patients have reported rates of discordance between these two methods, ranging from 1% to 10%. MATERIALS AND METHODS: Overall, 3228 consecutive patients with CRCs from two centers were included. Molecular testing was carried out using the Pentaplex panel and IHC evaluated four (MLH1, MSH2, MSH6, and PMS2; cohort 1; n = 1085) or two MMR proteins (MLH1 and MSH2; cohort 2; n = 2143). The primary endpoint was the rate of discordance between MSI and MMR IHC tests. RESULTS: Fifty-one discordant cases (1.6%) were initially observed. Twenty-nine out of 51 discordant cases were related to IHC misclassifications. In cohort 1, after re-reading IHC and/or carrying out new IHC, 16 discordant cases were reclassified as nondiscordant. In cohort 2, after the addition of MSH6/PMS2 IHC and re-examination, 13 were reclassified as nondiscordant. In addition, 10 misclassifications of molecular tests were identified. Finally, only 12 discordant cases (0.4%) remained: 5 were proficient MMR/MSI and 7 were dMMR/microsatellite stable. CONCLUSIONS: Our study confirmed the high degree of concordance between MSI and MMR IHC tests. Discordant cases must be reviewed, and if needed, tests must be repeated and analyzed by an expert team.

[Overview of feelings and practices of gynecologists and obstetricians for the noninvasive prenatal testing in France]. / État des lieux du ressenti et des pratiques des gynécologues-obstétriciens face au dépistage prénatal non invasif en France.

OBJECTIVES: To evaluate the feelings and practices of French obstetrician-gynecologists in prescribing the noninvasive prenatal testing (NIPT) before the release of the French High Authority of Health recommendations. METHODS: Descriptive, declarative and transversal study, analyzing the feelings and practices of obstetrician-gynecologists, members of the French College of Gynecologists and Obstetricians (CNGOF) between February and May 2017 using an online questionnaire. Practitioners' feedback was self-assessed for several clinical situations using a numerical scale ranging from 1 to 10. This experience was rated as "good" (grades 6 to 10) or "bad" (grades 1-5). RESULTS: Overall, 529 practitioners (29.2%) of 1812 CNGOF members, answered the online questionnaire. A "good" feeling was found for more than 65% of the practitioners audited. Feelings were significantly better for obstetricians, sonographers (P<0.05) and CPDPN members (P=0.003) compared to other practitioners. Situations where the DPNI was proposed "systematically" were risks greater than 1/250 (70.9%), between 1/250 and 1/500 (59.4%), greater than 1/250 associated with history of spontaneous miscarriages and/or fetal death in utero (66%), greater than 1/250 associated with pregnancy resulting from PMA (68.3%), history of fetal aneuploidy (54%) and a parent carrying a Robertsonian translocation (51.6%). CONCLUSION: This study highlights a good overall feeling of the practitioners with the NIPT.

Use of Tenax® films to demonstrate the migration of chemical contaminants from cardboard into dry food.

Contaminants in food packaging are a challenge of our time since the packaging material itself has been found to represent a source of food contamination through the migration of substances from it. Before first use, packaging materials destined for the packaging of dry foods can be evaluated by performing migration experiments with the simulant for dry foods, Tenax®. This simulant is commercially available as a powder that is more difficult to handle during the migration experiments. This paper reports the development of a Tenax film. The film can be applied to the cardboard surface to conduct the migration test. After the migration is completed, the film can be easily extracted to determine the concentration of the contaminants in the film. Finally, the performance of the Tenax film was compared with the conventional Tenax powder for the evaluation of 15 model migrants.

Evaluation of the migration of 15 photo-initiators from cardboard packaging into Tenax(®) using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS).

Photo-initiators are widely used to cure ink on packaging materials used in food applications such as plastic films or cartonboards. In migration studies, food simulants are very often used to simulate food, like Tenax(®), which is the simulant for dry foodstuffs. In this paper a fast and reliable confirmation method for the determination of the following photo-initiators in Tenax(®) is described: benzophenone (BP), 4,4'-bis(diethylamino)benzophenone (DEAB), 2-chloro-9H-thioxanthen-9-one (CTX), 1-chloro-4-propoxy-9H-thioxanthen-9-one (CPTX), 2,4-diethyl-9H-thioxanthen-9-one (DETX), 2,2-dimethoxy-2-phenyl acetophenone (DMPA), 4-(dimethylamino)benzophenone (DMBP), 2-ethylanthraquinone (EA), ethyl-4-dimethylaminobenzoate (EDMAB), 1-hydroxylcyclohexyl phenyl ketone (HCPK), 2-hydroxy-4'-(2-hydroxyethoxy)-2-methylpropiophenone (HMMP), 2-isopropyl-9H-thioxanthen-9-one (ITX), 4-methylbenzophenone (MBP), Michler's ketone (MK), and 4-phenylbenzophenone (PBZ). After the migration study was completed, the simulant Tenax(®) was extracted using acetonitrile, followed by analysis on ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Quantification was carried out using benzophenone-d10 (BP-d10) as internal standard. The presented method is validated in terms of matrix effect, specificity, linearity, recovery, precision and sensitivity, showing the method can detect all photo-initiators at very low concentrations (LOD < 0.125 µg g(-1) for all substances). Finally, the procedure was applied to real samples, proving the capabilities of the presented method.

Subcellular localization of neural-specific NPDC-1 protein.

NPDC-1 is a gene specifically expressed in neural cells when they stop to divide and begin to differentiate. Immunocytochemical study analysis of differentiated PC12 cells transfected with NPDC-tag vectors showed that NPDC-1 is transported in vesicles from the Golgi apparatus to the cell membrane and is then likely internalized into endosomes. The protein colocalized, at least partially, with synaptic vesicle proteins: synaptophysin, synaptobrevin 2, and Rab3 GEP (Rab3 GTP/GDP exchange protein). Moreover, subcellular fractionation of rat brain showed that crude synaptic membrane and crude synaptic vesicle fractions were enriched in NPDC-1. Although NPDC-1 bound Rab3 GEP in vitro, it seems unlikely to be involved in Ca2+-dependent exocytosis and, thus, in synaptic vesicle trafficking.

Functional analysis of the NPDC-1 gene.

Mouse NPDC-1 (Neural Proliferation Differentiation and Control-1) is specifically expressed in neural cells when they stop dividing and start to differentiate. The NPDC-1 protein has been shown to interact with the E2F1 transcription factor, D-type cyclins and Cdk2. Immunocytochemical studies and subcellular fractionation of rat brains disclosed a partial colocalization of NPDC-1 with synaptic vesicle proteins, suggesting additional functional interactions. Here, we report the characterization of the mouse and human genes that were found to display very similar structures. We mapped the human gene to chromosome 9q34.3. No obvious pathological defect has been previously linked to this region. In order to gain further insights into its function(s), we generated null mice for the NPDC-1 gene. We did not detect any macroscopic phenotypical defect. Analysis of the upstream sequence of the mouse NPDC-1 gene delineated two regions involved in its negative and positive transcriptional regulation. Evidence for the regulation of NPDC-1 by Krox family transcription factors is presented.

A twinned monoclinic crystal form of human peroxiredoxin 5 with eight molecules in the asymmetric unit.

The monoclinic crystal form of human peroxiredoxin 5 with eight molecules in the asymmetric unit was obtained under exactly the same conditions as the tetragonal form with one molecule in the asymmetric unit, except that the latter was briefly cryosoaked with halide for derivatization. A merohedral twinning was observed, which is rather unusual in the monoclinic system and only possible with particular unit-cell dimensions. After detwinning the native and a mercury derivative, the structure was solved by the SIR method with the help of the non-crystallographic symmetry. The packing of the monoclinic and tetragonal forms are compared, with special attention to the role of bromide ions in the change of space group after crystallization. The availability of nine (eight monoclinic plus one tetragonal) independent molecules allows an analysis of the mobility. The two Cys residues implicated in the peroxide-reduction mechanism are located in rigid regions but are covered by mobile loops.

Crystal structure of human peroxiredoxin 5, a novel type of mammalian peroxiredoxin at 1.5 A resolution.

The peroxiredoxins define an emerging family of peroxidases able to reduce hydrogen peroxide and alkyl hydroperoxides with the use of reducing equivalents derived from thiol-containing donor molecules such as thioredoxin, glutathione, trypanothione and AhpF. Peroxiredoxins have been identified in prokaryotes as well as in eukaryotes. Peroxiredoxin 5 (PRDX5) is a novel type of mammalian thioredoxin peroxidase widely expressed in tissues and located cellularly to mitochondria, peroxisomes and cytosol. Functionally, PRDX5 has been implicated in antioxidant protective mechanisms as well as in signal transduction in cells. We report here the 1.5 A resolution crystal structure of human PRDX5 in its reduced form. The crystal structure reveals that PRDX5 presents a thioredoxin-like domain. Interestingly, the crystal structure shows also that PRDX5 does not form a dimer like other mammalian members of the peroxiredoxin family. In the reduced form of PRDX5, Cys47 and Cys151 are distant of 13.8 A although these two cysteine residues are thought to be involved in peroxide reductase activity by forming an intramolecular disulfide intermediate in the oxidized enzyme. These data suggest that the enzyme would necessitate a conformational change to form a disulfide bond between catalytic Cys47 and Cys151 upon oxidation according to proposed peroxide reduction mechanisms. Moreover, the presence of a benzoate ion, a hydroxyl radical scavenger, was noted close to the active-site pocket. The possible role of benzoate in the antioxidant activity of PRDX5 is discussed.

[HBME-1 immunostaining in thyroid pathology]. / Intérêt de l'HBME-1 en pathologie thyroïdienne.

The aim of this study was to evaluate wether HBME-1 immunohistochemical analysis can reliably differentiate benign thyroid lesions from thyroid carcinomas. Fifty benign and 87 malignant lesions were analyzed. All papillary carcinomas (67/67) were HBME-1 positive, as well as 14 of 20 follicular well-differentiated carcinomas and 13 of 29 atypical follicular adenomas and 4 out of 21 goiters were weakly and focally positive. HBME-1 highlighted micronests of papillary carcinomas. The reactivity of HBME-1 in the tall-cell variant of papillary carcinomas was apical and stronger than in classical papillary carcinomas. Positive HBME-1 immunostaining is in support of the diagnosis of the follicular variant of papillary carcinoma and highlights micropapillary carcinomas. HBME-1 may be of additional value in the diagnosis of thyroid malignancy.

NPDC-1, a regulator of neural cell proliferation and differentiation, interacts with E2F-1, reduces its binding to DNA and modulates its transcriptional activity.

We have previously identified NPDC-1, a neural factor involved in the control of proliferation and differentiation, and we have shown that the stable introduction of NPDC-1 into transformed cells down-regulates cell proliferation both by increasing the generation time and by suppressing transformed properties. The data presented here indicate that, in vitro, NPDC-1 is able to interact with the transcription factor E2F-1 and some cell cycle proteins, such as D-cyclins and cdk2. In addition, two-hybrid experiments in mammalian cells show that the interaction between NPDC-1 and E2F-1 can also occur in vivo. This interaction reduces the binding of E2F-1 to DNA and its transcriptional activity. Taken together, the data suggest that NPDC-1 could influence cell cycle progression and neural differentiation through its association with E2F-1.

Bronchial stump aspergillosis.

Two cases of bronchial stump aspergillosis were diagnosed 5 and 6 years after pneumonectomy for lung cancer. In each case, the fungal mass was endoscopically removed using standard forceps. A recurrence of the fungal mass persisted until all visible protruding nylon threads in the airway lumen were destroyed with a Nd:YAG laser. Removal of the visible suture is necessary for eliminating the infection. No additional local or systemic antifungal therapy is needed.

Volume changes of isolated human K562 leukemia cells induced by electric field pulses.

Electropermeabilization of immobilized human leukemia K562 cells was studied by measuring changes in cell volume. Such changes reflect mass transfer between the cell and external medium. Electropermeabilization was carried out in an isosmotic water-sorbitol medium with a range of electric field strengths from 500 to 800 V. cm(-1), corresponding to low-energy levels. Electroporation of the K562 cell membrane was found to provoke an inflow of sorbitol and a corresponding osmotic inflow of water and/or an outflow of intracellular solutes due to Fick diffusion. Such flows were found to involve the shrinkage, swelling, or rupture of K562 cells, depending on the characteristics of the electric field and of the physiological state of cells. The behavior of immobilized cells was observed during their exposure to the electric field. The response in immobilized cell volume corresponded with the theoretical pore size and pore opening time, permitting an explanation of the behavior of cell suspensions subject to electrical fields.

Histidine modification and mutagenesis point to the involvement of a large conformational change in the mechanism of action of phage lambda lysozyme.

Phage lambda lysozyme (lambdaL) is structurally related to other known lysozymes but its mechanism of action is different from the classical lysozyme mechanism, acting as a transglycosidase rather than a hydrolase. As two conformations have been revealed by the crystal structure, we investigated the effect of mutating and modifying a histidine located near to or far from the active site in the respective closed and open conformations. Whereas its asparagine mutation has little or no effect on activity, its N-carbethoxylation inactivates the enzyme. This provide further evidence for the involvement of the closed conformation and for the need of conformational mobility in lambdaL function.

Crystal structure of the EF-hand parvalbumin at atomic resolution (0.91 A) and at low temperature (100 K). Evidence for conformational multistates within the hydrophobic core.

Several crystal structures of parvalbumin (Parv), a typical EF-hand protein, have been reported so far for different species with the best resolution achieving 1.5 A. Using a crystal grown under microgravity conditions, cryotechniques (100 K), and synchrotron radiation, it has now been possible to determine the crystal structure of the fully Ca2+-loaded form of pike (component pI 4.10) Parv.Ca2 at atomic resolution (0.91 A). The availability of such a high quality structure offers the opportunity to contribute to the definition of the validation tools useful for the refinement of protein crystal structures determined to lower resolution. Besides a better definition of most of the elements in the protein three-dimensional structure than in previous studies, the high accuracy thus achieved allows the detection of well-defined alternate conformations, which are observed for 16 residues out of 107 in total. Among them, six occupy an internal position within the hydrophobic core and converge toward two small buried cavities with a total volume of about 60 A3. There is no indication of any water molecule present in these cavities. It is probable that at temperatures of physiological conditions there is a dynamic interconversion between these alternate conformations in an energy-barrier dependent manner. Such motions for which the amplitudes are provided by the present study will be associated with a time-dependent remodeling of the void internal space as part of a slow dynamics regime (millisecond timescales) of the parvalbumin molecule. The relevance of such internal dynamics to function is discussed.

Andrews thoracoplasty as a treatment of post-pneumonectomy empyema: experience in 23 cases.

BACKGROUND: Andrew's thoracopleuroplasty has been described for treating tuberculous empyemas with bronchopleural fistulas. We report on its utilization for treating postpneumonectomy empyemas. METHODS: During a 25 year period, 23 patients underwent thoracopleuroplasty for treating postpneumonectomy empyemas, after a period of drainage-irrigation of the cavity. Seven patients presented with persistent bronchial fistula at operation. After resection of the costal arches surrounding the infected cavity, the cavity was cleaned, and the external parietal plane was sutured to the mediastinal plane. Only drainage of the subscapular space was left in place. RESULTS: Postoperative mortality was 4.3%. Postoperative recovery was simple in 17 cases, whereas a superficial abscess was evacuated in 3 cases. The procedure failed in 3 cases, which were treated by open thoracostomy (2), and by reenlargment of the thoracopleuroplasty (1). The sequelae were mainly a diminution of the shoulder mobility, especially when the first rib was resected. CONCLUSIONS: Thoracopleuroplasty may safely treat postpneumonectomy empyemas, even those with bronchial fistulas. Most patients are definitively and rapidly cured with limited sequelae.

Scimitar syndrome with pulmonary arteriovenous fistulas.

Right abnormal pulmonary venous return into the inferior vena cava associated with abnormal fissure, dextrocardia, and systemic arterial supply of a variable degree, are the characteristics of the scimitar syndrome. We report on a patient in whom this rare syndrome was associated with pulmonary arteriovenous fistulas within the involved lung.

Desmoid fibromatosis of the shoulder and of the upper chest wall following a clavicular fracture.

A desmoid tumor of the shoulder girdle infiltrating the upper chest wall and weighing 1500 g was almost completely removed in an 18-year-old man, 27 months after a bifocal fracture of the clavicule. Thirteen years later, the patient was free of recurrence. The interval time between trauma and diagnosis, as the particular characteristics of aggressive fibromatosis, strongly support a major causal role of the clavicular fracture in the occurrence of this tumor.

[Pleural mesotheliomas. Current knowledge]. / Les mésothéliomes pleuraux. Revue d'actualité.

Pleural mesotheliomas are rare primary tumors of the pleura. Three groups are classified under the term mesothelioma: 1) benign pleural mesothelioma for which complete surgical treatment is curative with a good prognosis; 2) localized malignant mesothelioma which is a fibrosarcoma, best treated by wide en-bloc resection; 3) diffuse malignant mesothelioma which is mainly of epithelial type. The prognosis is poor in spite of all therapeutic approaches using irradiation, chemotherapy and surgery, alone or in combination, and long-term survivals are uncommon. Two surgical approaches are currently available for patients with diffuse mesothelioma: radical extrapleural pneumonectomy and pleurectomy/decortication. Rigorous combinations of multimodality therapy are needed to improve local control and survival.

[Pleural fibromas: a review based on 12 cases]. / Les fibromes pleuraux: mise au point à partir de douze observations.

The authors report 12 cases of pleural fibroma, which is a rare benign tumor, usually discovered incidentally. However, these tumors are sometimes associated with a paraneoplastic syndrome, or may lead to compressive symptoms related to their large size. Radical resection is mandatory because recurrence may occur, sometimes several years later with a malignant behavior. Long-term follow-up is therefore necessary to detect any recurrence, particularly when certain prognostic factors are initially present.