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Pathogenic variants (PVs) in BRCA1/2 genes account for ∼6% of breast and 20% of ovarian cancers. Most breast tumors developed by BRCA1 carriers are triple negative. BRCA2 tumors have similar rates of estrogen receptor positivity as sporadic controls but are less likely to be human epidermal growth factor receptor 2 (HER2)-positive. Prevalence of HER2 positivity among breast cancers (BCs) in BRCA1/2 mutation carriers is poorly and variably described, ranging from 0% to 10% and 0% to 13% in BRCA1 and BRCA2 carriers, respectively.We assessed the prevalence of HER2 positivity among a single institutional cohort of 398 BCs developed in carriers of BRCA1/2 PVs (240 BRCA1, 158 BRCA2). Subsequently, a systematic review of the literature and pooled analysis was carried out.In our series we found a 7% HER2 positivity rate among all first BRCA1/2 BCs overall. In BRCA1 carriers, 5.4% of BCs were HER2-positive compared with 9.5% in BRCA2-mutated patients. Among bilateral BCs, HER2-positive cases were 15.2% in the BRCA1 group and 23.1% in the BRCA2 group. Notably, six BRCA1 and eight BRCA2 carriers showed discordant HER2 status between BC and bilateral BC (23.7%, 14/59). The systematic review included 21 083 BRCA1/2 patients from 73 eligible studies. The pooled rate of BRCAmut/HER2-positive BCs is 9.1% (95% confidence interval 7.3% to 11.2%). BRCA1 and BRCA2 when reported as separate data ranged from 0% to 33.3% (mean 8.3%) and from 0% to 86% (mean 10.3%), respectively.As compared with sporadic cases, BCs occurring in BRCA1 and/or BRCA2 PVs carriers are less frequently HER2-positive. Prevalence of HER2 positivity in our series was consistent with pooled analysis and did not exceed 10%. Although not common, co-existence of BRCA mutations and HER2 overexpression and/or gene amplification should be acknowledged. More research is needed to better characterize this subgroup of patients who should not be excluded a priori from clinical trials of targeted therapy for BRCA1/2-driven cancers.

Introduction/ Background Loss of phosphatase and tensin homolog (PTEN) expression and alterations in mismatch repair (MMR) genes are regarded as early oncogenic events in breast cancer. It has recently been hypothesized that the polyadenosine tract in PTEN might be a target for mutation in MMR-deficient endometrial tumors. However, the frequency and significance of MMR alterations in breast cancer is debated, and their relationship with PTEN status has not been investigated in the breast. Aims In this study, we sought to explore the relationships between PTEN expression and MMR alterations and to define whether PTEN immunohistochemistry is a predictor of MMR status in breast cancer. Methods 309 cases, including 261 invasive ductal carcinomas, no special type, 32 invasive lobular carcinomas, and 16 invasive ductal carcinomas, mixed types, carefully characterized from clinical and pathological standpoints, were reviewed and used to construct 11 tissue microarrays (TMAs). For each case, a mean of 4.5 tumor tissue cores (range 3 to 6 cores) was sampled, incorporating distinct topographic areas of the tumor, as well as matched non-neoplastic breast tissue, and, when present, associated in situ carcinoma. Taken together, 1381 spots were generated. Each TMA was subjected to immunohistochemical analysis of PTEN and the DNA MMR proteins MLH1, MSH2, MSH6 and PMS2. In order to allow a quick navigation within each TMA, and to minimize human-related biases, each stained slide was digitalized and blindly analyzed by two pathologists using a dedicated software able to segment TMA cores. The pattern of expression was therefore annotated manually on a digital database using a specific add-on module. Results According to clinicopathologic surrogate definition of intrinsic subtypes, PTEN protein loss was more frequent in luminal A-like and triple negative groups compared to luminal B-like carcinomas, as recently observed in other studies. MMR status in Luminal B-like tumors did not differ significantly between PTEN-retained and PTEN-loss groups, regardless HER2 amplification. In particular, retained PTEN expression was a predictor of MMR proficiency in approximately 35% of cases for this group. However, in luminal A-like and triple negative breast cancer groups, retained positive expression of MMR proteins was observed in 100% of cases showing PTEN wild-type immunohistochemical expression. Discussion: The present study is the first to investigate PTEN protein loss in a large set of breast carcinomas based on DNA MMR status by immunohistochemistry. Our findings broaden the understanding of the biology underpinning breast cancer, suggesting that MMR alterations are likely to be independent of PTEN status in the majority of luminal B-like breast cancers and that, in a way akin to endometrial carcinoma, MMR deficiency could play a part in the development of PTEN alterations in luminal A-like and triple negative breast cancers. The integration of traditional pathology with cutting-edge digital tools allowed a rapid quantification of immunohistochemistry and effective data organization in this wide cohort multi-variable study. Conclusion: PTEN immunohistochemistry is a useful adjunct in the clinical evaluation of breast cancer patients, being able to capture all MMR-proficient luminal A-like and triple negative tumors., Diagnostic Pathology, Vol 1 No 8 (2016): 13. European Congress on Digital Pathology

The aim of our research is to study respiratory and dermatologic diseases (irritative and allergic) in a cohort of workers exposed to vegetal esters based metal cutting fluids of the latest generation. A cohort of 81 workers (mean age 34.5 years, seniority 17.4 years), with mean exposure to vegetal esters based metal cutting fluids of 2.8 years, has been subjected to clinical evaluations. The investigation did not reveal any disease or disorder of the respiratory system, any folluculitis or any allergic contact dermatitis caused by sensitization to vegetal esters based metal cutting fluids. On the contrary we documented 5 cases of irritant contact dermatitis, even if favored by an improper use of protection devices. According to early results, the introduction of vegetal esters based metal cutting fluids seems to reduce the risk to the worker's health. A longitudinal surveillance is still needed to confirm that even in the medium and long-term sensitizations will not occur.

Fold-thrust belts are commonly interpreted as ''thin-skinned'' structures, developed above a detachment, with the underlying basement remaining undeformed. However, inmany areas, particularlywhere compressional tectonismwas preceded by rifting, models of basement fault reactivation may be more appropriate. The contrasts between thin-skinned and deep-rooting, inversion-dominated deformation in building fold-thrust complexes are investigated using a case history from the Italian Apennines. Three sectors were chosen to represent the marked lateral variations in structural style evident in the thrust belt. The outer portion of the Marche (in the north) is contrasted with a section through the Lucanian Apennines in the south and with the Molise district of the Central Apennines. The Marche structures are readily explained in terms of inversion, a model that is consistent with new deep seismic data onshore and conventional seismic from the nearby Adriatic Sea. The displacements implicit for the inversion model are a factor of five less than for existing thin-skinned interpretations. However, these styles are not applicable throughout the Apennines. Well data in the Southern Apennines of Lucania demonstrate large-scale thin-skinned thrusting, with 57 km of horizontal displacement since earliest Pliocene time. This includes 14 km of shortening that ramps up through the buried Apulian Platformcarbonates. These deeper structures may be restored using ramp-dominated thrust geometries. The Molise sector shows broadly the same structural style as for Lucania: allochthonous shallow-water carbonates and pelagic basin units overlie the carbonates of the Apulian Platform, with the major difference being that here, the pelagic basin units are detached at the level of the Oligocene-lower Miocene Argille Varicolori. In this setting, the Apulian carbonates may be restored using only 5 km of displacement. The overlying allochthon probably has accommodated about 45 km of displacement since the earliest Pliocene. Therefore, the Apennines show differing structural styles with differing displacements along their length. Thick-skinned thrusting models may be applied to the Marche and to structures in the buried Apulian units.

Fetal DNA in maternal plasma may represent a source of genetic material for prenatal noninvasive diagnosis of genetic diseases. We evaluated a cohort of physiological pregnancies to determine if fetal DNA can be retrieved at any gestational week in sufficient quantity to be analyzed with advanced mutation detection technologies. We performed fetal DNA quantification by real-time polymerase chain reaction (PCR) on the SRY gene in 356 women sampled from 6 to 40 gestational weeks. Fetal DNA was retrieved at any week. All female fetuses were correctly identified. In 5 of 188 (2.6%) male-bearing pregnancies, no amplification was obtained. For noninvasive testing, complete clearance of fetal DNA after delivery is mandatory. Long-term persistence was not detected in women with previous sons or abortions. These findings confirm that maternal plasma may represent the optimal source of fetal genetic material. For noninvasive diagnosis of genetic diseases, we evaluated microchip technology. The detection limit for a minority allele determined by diluting a mutated DNA into a wild-type plasma sample was 5 genome equivalents, indicating that the test might be applied to the identification of paternally inherited fetal alleles in maternal plasma. The addition of peptide nucleic acids (PNAs) to either the PCR reaction or the chip hybridization mixture allowed approximately 50% inhibition of wild-type allele signals.

The authors report the gynaecological pathology of surgical interest occurring in an Emergency Department in the first half of 2000 and occasionally found during an operation in women who presented a pelvic mass or abdominal pain.Six women, average age of 50 years, reached the Emergency Department: five of them were operated with an emergency procedure.Of the 6 cases, 1 patient was affected by uterine mass, 1 by uterine-ovarian mass and 3 by ovarian mass; in one patient, affected by ovarian tumour, another intervention was necessary for intestinal metastasis.The authors have considered the clinical aspect of the abdominal masses, the age of the patients, the diagnostic laboratory and instrumental implications, the surgical approach and the histological result, referring to literature. Their contribution is related to the need for an appropriate surgical approach in emergency where it may, sometimes, solve or, at least, stabilize an uncertain clinical case, thanks to the implicit basic knowledge of multidisciplinary surgical technique.

Report the experience of the Marseille's anti-poison center with lead poisoning adults.Between 1993 and 2000, 45 adults patients consulted the poison Centre of Marseille for a history of lead exposure (9 women, 36 men, average age 44 YO, between 22 an 76 YO). The lead sources were mostly occupational (welding, heavy metal industries...), but some were environmental (shooting as a hobby, hunting,...).Ninety-one percent of the patients presented with a clinical feature of possible lead intoxication (asthenia, abdominal pain, anaemia, seizures,...). For 22 patients, calcitetracemate provocation test was negative. 6 patients with a positive test refused to be treated. 16 patients with a positive test were treated with chelation therapy (average lead blood level 566 micrograms/l--mini 320 micrograms/l, maxi 943 micrograms/l--and average lead urine elimination 3,011 micrograms/24 H--mini 789 micrograms/24 H, maxi 7,229 micrograms/24 H. 58 cures were done (1 to 12 cures for each patient). The average quantities of lead eliminated in the urine during the chelation therapy was 30,912 micrograms +/- 29,059 micrograms by case. For 12 patients who stopped the lead exposure after the diagnosis of lead poisoning, the chelaion therapy permitted to decrease the lead blood level of 69%. For 4 patients still exposed during the treatment, the lead blood level decrease of 7% only. For the 16 treated patiEnts, a clinical improvement was noted, and no adverse effects of chelation therapy was observed during the 58 cures.

The urinary bladder occupies the deep pelvic cavity and is well protected from the bacin: this is the reason why it can rarely be traumatized. Anyway it could suffer traumas, which can cause extraperitoneal and intraperitoneal ruptures. A classification of traumas that can injure the urinary bladder and the treatments of these lesions are presented. A clinical case personal observed regarding a 78 year-old female patient is described. An accidental fall and direct trauma in the hypogastrium caused a rupture of her urinary bladder. In this case, the patient was anuric, though the macrohematuria and microhematuria can be present in the 85% of the urinary bladder lesions. This is an interesting case since it deals with a urinary bladder wall rupture, due to a trivial trauma on the bladder.

Restenosis is the main limitation of percutaneous angioplasty, especially in vessels of small diameters such as the coronary arteries, the femoro-popliteal and tibial-peroneal arteries and the arterio-venous dialysis grafts. The extensive use of tents has not entirely prevented its occurrence, whereas treating in-stent restenosis gives even more uncertain results. Endovascular radiotherapy has emerged over the past few years as a promising approach to both prevent and cure it. The analogy between the tumour-like cellular proliferations observed in post-angioplasty restenosis and tumour processes prompted pioneering works to study the effect of ionizing radiations in animal models of arterial restenosis. The demonstrated feasibility, tolerance and efficacy of this approach lead to test this strategy in humans. The results of 3 recently presented randomized double-blind trials in the treatment of coronary in-stent restenosis have been so promising that endovascular brachytherapy might now be considered the treatment of choice in this indication. Other randomized trials are currently carried out to test whether endovascular brachytherapy may prevent restenosis in coronary and femoro-popliteal arteries as well as in hemodialysis shunts. In the present review, we describe the basics of the biological effects of ionizing radiations, the technical modalities to deliver endovascular radiations, our current knowledge about their effects on the vascular wall and the restenosis mechanisms, and the results of the first clinical studies. Finally, we address the remaining problems in the use of endovascular curietherapy and question the promises and challenges of its clinical application.

During CT scanning, a pancreatic lipoma was diagnosed in a 70 year-old woman presenting with abdominal pain, elevated amylase and abnormal liver function tests. The patient underwent surgical excision of the lipoma located in the head of the pancreas. The postoperative course was uneventful. This is the third case of pancreatic lipoma described in the literature. It is a very rare neoplasm that should be included in the category of "non-ductal" tumors of the pancreas. The role of different diagnostic tools for the differential diagnosis of ductal pancreatic adenocarcinoma is discussed.

The antigenic structures recognized by anti-endothelial cell antibodies (AECA) in sera from 10 Wegener's granulomatosis (WG) and 12 systemic lupus erythematosus (SLE) patients with signs of vasculitis were characterized by immunoprecipitation of selectively radiolabeled surface membrane proteins from human umbilical vein endothelial cells. Electrophoretic analysis of the immunoprecipitated proteins revealed reactivities against endothelial antigens ranging in size from 200 to 25 kDa. AECA antigens were not cell specific, since the same sera also reacted, at least in part, with radiolabeled human fibroblast surface proteins. The majority of WG patients displayed a constant precipitation pattern of five proteins (180, 155, 125, 68, and 25 kDa). On the contrary, AECA from SLE sera reacted with a more heterogeneous series of endothelial proteins. A group of four proteins, however, was also found in the majority of SLE sera: 200, 180, 155, and 25 kDa. In addition, some endothelial antigens were immunoprecipitated only by WG (125 kDa) or by SLE sera (200 kDa), suggesting a different endothelial reactivity in different vasculitic processes. The reaction did not involve intracellular proteins as demonstrated by the lack of reactivity of SLE sera negative for AECA but positive for anti-cytoplasmic or anti-nuclear antibodies. These data confirming that AECA recognize surface endothelial determinants further support a potential pathogenetic role for these antibodies in autoimmune vasculitis.

We analyzed the role of the Marseille pharmacovigilance center (working in collaboration with the local poison treatment center) in informing the general public on medicinal drugs. Over a 9-month period, the center received 115 requests from members of the public for information. 82.6% of callers were not members of the health professions and wanted information for themselves (61.7%, 67.6% women) or their children (26.08%). The questions mainly involved drug interactions (28.7%), side-effects (26%) and precautions for use in particular circumstances (20%). 178 proprietary drugs (47 of which had been bought over the counter) were mentioned. The main therapeutic classes were neuropsychiatric drugs (n = 41), cardiovascular drugs (n = 17) and analgesics (n = 16). A number of communication difficulties and problems of a deontological nature were encountered. Full information was provided in every case, together with advice on prevention to about half the callers.

Selective intracoronary injection of microspheres labelled with radioactive substances which emit gamma rays with different energy levels (Indium 113 m and Technetium 99 m) allows us to explore by scintigraphic methods the areas of distribution of the two coronary arteries. Having been carefully calibrated, the particles are injected in limited numbers, and block the precapillary arterioles, where they gradually diminish in number. Scintigraphic examination is carried out in various projections (anteroposterior, left anterior oblique and right anterior oblique) immediately after coronary arteriography. Coronary scintigraphy allows us to establish the integrity of the distribution network of a coronary trunk which appears normal on coronary arteriography, to visualise the diminution of flow caused by a stenosed but patent trunk, and to visualise the extent of the collateral circulation and the quality of revascularisation achieved by an aorto-coronary bypass operation.

Comparison between the effective systemic ejection fraction defined by radiocardiography and cardiac chambers scanning, and the whole left ventricular ejection fraction calculated by cineangiocardiography allows an accurate assessment of mitral and aortic regurgitation extent. In case of both mitral and aortic insufficiency, each regurgitation can be quantitatively dissociated by means of the aortic isotopic dilution curve recorded at the same time as the radiocardiogram.

The comparison in 36 patients of two-dimensional echocardiography and scintigraphy of the cardiac cavities in the steady state with left cineventriculography selective for the evaluation of anomalies in left ventricular contraction post infarction shows good agreement between these techniques for the detection of major segmental anomalies, a higher sensitivity being found for echocardiography in dyskinesis. The overall rejection fraction calculated by two-dimensional echocardiography is correlated with the ejection fraction calculated in left cineventriculography (r = 0.57; p less than 0.001). The same is true of the overall ejection fraction obtained by cavitary scintigraphy (r = 0.62; p less than 0.01). The indices of residual myocardium in the anterior wall (IRM ant) and the posterior wall (IRM post) calculated in apical echographic section for the two cavities and in left cineventriculography (oblique anterior right) are also well correlated (IRM ant: r = 0.70 and p less than 0.001; IRM post: r = 0.46 and p less than 0.01). The determination of these parameters as well as the percentage of shortening of the left ventricular small axis measured by echocardiography TM, to the smallest value, permits a valid assessment of ventricular function and makes it possible to avoid coronaroventriculography when this function is too impaired.

The hyperemic response induced by the tri-iodinated contrast agent injection for coronarography assesses functional value of the arteriolar areas of coronary distribution. The intracoronary injection of two kinds of micropheres labeled with gamma emitter radionuclides of different levels of energy (99m-Technetium and 113m-Indium) provides comparison of the studied areas-scintigraphies at rest and during hyperemia.

Advantage may be taken of the hyperaemic response to the iodine contained in the contrast medium injected during coronary angiography to assess the functional value of the coronary tree using radioactive microspheres. This series comprises 73 selective coronary scans performed in the resting state (113 m In marked microspheres) and during the hyperaemic phase (99 m TC marked microspheres) in 70 patients. A positive hyperaemic response distal to severe truncular stenosis indicates a good distal arteriolar bed and collateral circulation for aorto-coronary bypass grafting. After aorto-coronary bypass (23 cases), the hyperaemic response gives an indication of the functional value of the revascularised myocardium. In 71% cases, the results correlate well with the measurement of the peroperative blood flow through the graft. It is usually positive when the bypass graft is implanted with good distal arterial run off.

To evaluate the extra-cellular space, we measure the impedance (or resistance) of the extra-cellular electrolyte compartment with an alternating current at a fixed frequency of 5 kHz that can't pass through the cellular membrane. Total water is measured by the impedance to a current of 1 MHz which is conducted by extra and intra cellular hydro-electrolytic space. There is a good correlation between electrical impedance measurements and distribution of isotopic markers. The extra-cellular compartment was evaluated by diffusion of D.T.P.A. marked with 99mTc or with 111In and the total water by the diffusion of Antipyrin marked with 1,311 or 1,231. The findings indicate that there is not a significant difference between the results of the size of extra-cellular water measured by electrical impedance and D.T.P.A. diffusion (r = 0.75). Comparable results have been obtained in the determination of total water by electrical impedance measure and diffusion of Antipyrin (r = 0.90). We have also studied by method of electric impedance:--The state of hydratation in head injured patients and after pituitary surgery.--The lean body mass and hydro-electrolyte compartments in pregnancy. Electrical impedance measure seems to be a simple and reliable method to assess the hydric state of patients.

AECA represent a new family of autoantibodies detectable in systemic autoimmune diseases. Different findings support their poten-tial importance both from a diagnostic and a prognostic point of view: 1. AECA do not seem to be a mere epiphenomenon; 2. Are not related to a polyclonal B-cell activation; 3. React with surface endothelial antigens; 4. Correlate with disease activity; 5. In some cases behave as an indirect marker of in vivo endothelial damage; 6. Correlate with disease activity; and 7. In vitro experiments support a possible pathogenetic role in sus-taining autoimmune vasculitis.