Stimulated Raman histology: one to one comparison with standard hematoxylin and eosin staining

International audienceWe present for the first time one-to-one correspondence between standard hema-toxylin/eosin (H&E) stained tissue sections and stimulated Raman histology (SRH)-a label-free technique in which stimulated Raman scattering (SRS) and second harmonic generation (SHG) are combined to generate virtual H&E images. Experiments were performed on both human thin cryogenic slides from the gastrointestinal tract (GI) and thick freshly excised biopsies from endoscopic surgery. Results on cryogenic slides evidenced an excellent agreement between SRH and H&E images while the ones on biopsies established the relevance of SRH for rapid intraoperative histology to assist in surgical decision making

Miniprobe confocal endomicroscopy for biliary stenosis: which place in 2012?

"L’endomicroscopie confocale est une technique émergeante qui permet la réalisation de véritables biopsies optiques au niveau du tractus digestif. Le diagnostic histologique pré-opératoire du cholangiocarcinome reste toujours très difficile avec une fiabilité très basse. Pour essayer d’améliorer cette situation, certaines équipes ont évalué la microscopie confocale pour la détection in vivo du cholangiocarcinome. Récemment des mini-sondes de microscopie confocale ont été développées permettant d’obtenir une histologie in vivo. Les images sont obtenues après injection de fluoroscéine qui permet une meilleure visualisation des vaisseaux sanguins. Etant donné que la néoangiogénèse est un des premiers évènements de la cancérogenèse, la mise en évidence d’une néo-vascularisation anarchique serait fortement évocatrice d’une transformation maligne. Cet article va essayer de faire le point sur les données de la littérature concernant cette nouvelle technique appliquée aux sténoses biliaires d’origine indéterminée. Des critères de la malignité ont déjà été établis en 2009 et publiés en 2011 sous le nom des critères de Miami. Depuis, deux études comparatives (Confocal I vs Brossage et biopsies biliaires per CPRE) ont montré la supériorité de la microscopie confocale avec une fiabilité de 83 à 86 % pour le diagnostic de malignité versus 50 à 53 % pour l’histologie standard. L’endomicroscopie confocale biliaire représente un progrès incontestable dans le diagnostic de malignité des sténoses biliaires indéterminées ; néanmoins, d’autres études restent nécessaires notamment pour définir les critères de sténoses inflammatoires afin de pouvoir différencier cholangite sclérosante primitive et cholangiocarcinome. "Confocal endomicroscopy is an emergent technique allowing for real optical biopsies in the GI tract. The preoperative diagnosis of cholangiocarcinoma is associated with a low sensitivity. To overcome this limitation, a new imaging modality was evaluated to detect neoplasia in vivo in the biliary tract. Recently, confocal miniprobes have been introduced, enabling in vivo histopathology.Images can be acquired after intravenous application of fluorescein. This approach has the further benefit to make blood vessels clearly visible. Because angiogenesis has been mentioned as an essential step in the development of cancers, documentation of blood flow, vessel density, and configuration might be relevant. This paper refers to the literature data regarding this new diagnostic technique for undetermined biliary strictures. Malignancy criteria were described during a meeting in Miami in 2009 and published on the same year as Miami’s criteria. Two studies reported the superiority of confocal microscopy versus the conventional brush cytology orERCP guided biopsies with an accuracy of 83 to 86% vs. 50-53%. The last study has reported a high negative predictive value of the confocal microscopy around 93%.Intraductal confocal microscopy represents a huge progress in the diagnostic of undetermined biliary strictures, but a better definition of benign criteria will be necessary to differentiate cholangiocarcinoma from primary sclerosing cholangitis

Impact of radiotherapy in the management of locally advanced extrahepatic cholangiocarcinoma

BACKGROUND: Optimal therapy for patients with unresectable locally advanced extrahepatic cholangiocarcinoma (ULAC) remains controversial. We analysed the role of radiotherapy in the management of such tumors. METHODS: We retrospectively reviewed the charts of patients treated in our institution with conformal-3D external-beam-radiotherapy (EBRT) with or without concurrent chemotherapy. RESULTS: Thirty patients were included: 24 with a primary tumor (group 1) and 6 with a local relapse (group 2). Toxicity was low. Among 25 patients assessable for EBRT response, we observed 9 complete responses, 4 partial responses, 10 stabilisations, and 2 progressions. The median follow-up was 12 months. Twenty out of 30 patients (66%) experienced a relapse, which was metastatic in 75% of cases in the whole series, 87% in group 1, 60% in group 2 (p = 0.25). Twenty-eight patients (93%) died of relapse or disease complications. Median overall survivals in the whole group and in group 1 or 2 were respectively 12, 11 and 21 months (p = 0.11). The 1-year and 3-year progression-free survivals were respectively 38% and 16% in the whole series; 31% and 11% in group 1, 67% and 33% in group 2 (p = 0.35). CONCLUSION: EBRT seems efficient to treat ULAC, with acceptable toxicity. For primary disease, the high rate of metastatic relapse suggests to limit EBRT to non-progressive patients after induction chemotherapy

Anti-proliferative and anti-secretory effects of everolimus on human pancreatic neuroendocrine tumors primary cultures: is there any benefit from combination with somatostatin analogs?

Therapeutic management of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) is challenging. The mammalian target of rapamycin (mTOR) inhibitor everolimus recently obtained approval from the Food and Drug Administration for the treatment of patients with advanced pancreatic neuroendocrine tumors (pNETs). Despite its promising antitumor efficacy observed in cell lines, clinical benefit for patients is unsatisfactory. The limited therapeutic potential of everolimus in cancer cells has been attributed to Akt activation due to feedback loops relief following mTOR inhibition. Combined inhibition of Akt might then improve everolimus antitumoral effect. In this regard, the somatostatin analog (SSA) octreotide has been shown to repress the PI3K/Akt pathway in some tumor cell lines. Moreover, SSAs are well tolerated and routinely used to reduce symptoms caused by peptide release in patients carrying functional GEP-NETs. We have recently established and characterized primary cultures of human pNETs and demonstrated the anti-proliferative effects of both octreotide and pasireotide. In this study, we aim at determining the antitumor efficacy of everolimus alone or in combination with the SSAs octreotide and pasireotide in primary cultures of pNETs. Everolimus reduced both Chromogranin A secretion and cell viability and upregulated Akt activity in single treatment. Its anti-proliferative and anti-secretory efficacy was not improved combined with the SSAs. Both SSAs did not overcome everolimus-induced Akt upregulation. Furthermore, caspase-dependent apoptosis induced by SSAs was lost in combined treatments. These molecular events provide the first evidence supporting the lack of marked benefit in patients co-treated with everolimus and SSA

Gene expression profiling of patient‐derived pancreatic cancer xenografts predicts sensitivity to the BET bromodomain inhibitor JQ1: implications for individualized medicine efforts

Abstract c‐MYC controls more than 15% of genes responsible for proliferation, differentiation, and cellular metabolism in pancreatic as well as other cancers making this transcription factor a prime target for treating patients. The transcriptome of 55 patient‐derived xenografts show that 30% of them share an exacerbated expression profile of MYC transcriptional targets (MYC‐high). This cohort is characterized by a high level of Ki67 staining, a lower differentiation state, and a shorter survival time compared to the MYC‐low subgroup. To define classifier expression signature, we selected a group of 10 MYC target transcripts which expression is increased in the MYC‐high group and six transcripts increased in the MYC‐low group. We validated the ability of these markers panel to identify MYC‐high patient‐derived xenografts from both: discovery and validation cohorts as well as primary cell cultures from the same patients. We then showed that cells from MYC‐high patients are more sensitive to JQ1 treatment compared to MYC‐low cells, in monolayer, 3D cultured spheroids and in vivo xenografted tumors, due to cell cycle arrest followed by apoptosis. Therefore, these results provide new markers and potentially novel therapeutic modalities for distinct subgroups of pancreatic tumors and may find application to the future management of these patients within the setting of individualized medicine clinics

Agreement on endoscopic ultrasonography-guided tissue specimens: Comparing a 20-G fine-needle biopsy to a 25-G fine-needle aspiration needle among academic and non-academic pathologists

Background and Aim: A recently carried out randomized controlled trial showed the benefit of a novel 20-G fine-needle biopsy (FNB) over a 25-G fine-needle aspiration (FNA) needle. The current study evaluated the reproducibility of these findings among expert academic and non-academic pathologists. Methods: This study was a side-study of the ASPRO (ASpiration versus PROcore) study. Five centers retrieved 74 (59%) consecutive FNB and 51 (41%) FNA samples from the ASPRO study according to randomization; 64 (51%) pancreatic and 61 (49%) lymph node specimens. Samples were re-reviewed by five expert academic and five non-academic pathologists and rated in terms of sample quality and diagnosis. Ratings were compared between needles, expert academic and

Anapath instantané en per-opératoire : a technologie SRH

International audienc

Anapath instantané en per-opératoire : a technologie SRH

International audienc

Adénocarcinomes nasosinusiens (étude clinique, histologique et phénotypique de 41 patients)

MONTPELLIER-BU Médecine UPM (341722108) / SudocPARIS-BIUM (751062103) / SudocMONTPELLIER-BU Médecine (341722104) / SudocSudocFranceF