G Monges’s research while affiliated with Institut Paoli Calmettes and other places

Background and objectives: Subepithelial lesions (SELs) of the upper part of the digestive tract are rare, and it can be difficult to characterize them. Recently, contrast-enhanced endosonography (EUS) and elastometry have been reported as useful adjuncts to EUS and EUS-guided fine needle aspiration (EUS-FNA) in cases of pancreatic mass and lymph node involvement. The aim of this retrospective analysis was to evaluate whether contrast-enhanced EUS can discriminate benign submucosal lesions from malignant ones. We describe our retrospective experience using the contrast agent SonoVue® (Bracco Imaging, Milan, Italy) in an attempt to increase the diagnostic yield. Patients and methods: Between May 2011 and September 2014, 14 patients (5 men, 9 women; median age 64 years, range 31-80 years) with SELs of the stomach or esophagus underwent EUS with SonoVue® (low mechanical index). There were 3 esophageal lesions and 11 gastric lesions. Mean size of the lesions was 30 mm (range 11-50 mm). They were discovered after anemia (n = 5), dysphagia (n = 1), and pain (n = 4) and during follow-up for resected gastrointestinal stromal tumors (GISTs) (n = 1) and a standard upper gastrointestinal endoscopy (n = 3). On endoscopic sonograms, 10 of these lesions were hypoechoic and located in the fourth layer (muscularis), and 4 were in the second or third layer (mucosa and submucosa). Contrast enhancement was assessed in the early phase (after several seconds) and late phase (>30 seconds); a final diagnosis was made based on the findings of EUS-FNA using a 19-gauge ProCore (Cook Medical, Bloomington, IN) (n = 9) or 22-gauge FNA system (Cook Medical) (n = 1), the resected specimen (n = 3), or deep biopsy (n = 1). Different immunostaining was used in the pathologic studies (RNA was analyzed later using the C-kit, CD-117, CD-34, desmin, DOG-1, α-smooth actin, caldesmon, PS-100, and Ki-67 antibodies). Results: Final diagnoses were leiomyoma (n = 4), GIST (n = 5), schwannoma (n = 1), inflammatory tumor of Helvig (n = 1), pancreas rest (n = 2), and fibrosis (n = 1). No complications occurred. All 5 GISTs showed enhancement in the early and late phases, whereas the 8 remaining lesions did not show any enhancement. Only 1 leiomyoma showed heterogeneous enhancement. Limitations: The monocentric and retrospective study design and small number of patients. Conclusions: In cases of SELs of the stomach or esophagus, SonoVue® could be a complementary tool to endosonography to differentiate GISTs (early and clear enhancement) from other SELs (few or no enhancement), such as leiomyomas or pancreatic rest. These results are similar to those of the few, small studies published on this topic, but more studies with a larger number of patients are needed to confirm these findings.

Background and aim: Scanty data about inter-observer agreement (IOA) among pathologists in the evaluation of pancreatic samples acquired with EUS histology needle are available. The aim of this study was to determine IOA on adequacy of pancreatic histology specimens obtained with a 22G needle by a panel of experienced pathologist, in comparison with the 19G needle. Methods: This multicentre prospective study involved 73 pancreatic specimens prepared using histology needles of different calibres. Five pathologists independently reviewed all the samples, assessing the presence of a core, specimen adequacy and the possibility to perform additional analyses. IOA determined by Fleiss' Kappa statistic was used as the primary outcome measure. Secondary outcome was to compare 22G versus 19G needle results. Results: A core was present in 57% of pancreatic specimens obtained by 22G needle. The specimens were considered adequate in 72% of cases, with poor agreement among pathologists (p = 0.02, Fleiss' κ = 0.26). The possibility to perform further analyses was rated as 'positive' in 66% of cases without significant difference among observers (p = 0.80). When comparing the results, the presence of a core and the adequacy of tissue slides were significantly better for the 19G needle (57% vs. 84% p = 0.002; 72% vs. 83% p = 0.004, respectively). Reproducibility in the assessment of pancreatic sample adequacy was significantly better with the 19G needle (κ = 0.26 for 22G samples vs. κ = 0.81 for 19G samples). Conclusions: Our results suggest that histology sampling of pancreatic masses should be performed with a 19G histology needle, since is able to provide a core in the majority of cases, with 83% of adequate specimens and excellent results in term of reproducibility among pathologists.

Trial registration: ClinicalTrials.gov (NCT01563133).

Human epidermal growth factor receptor 2 (HER2) dysregulation is associated with tumorigenesis in gastric/gastroesophageal junction cancer; however, the number of patients with HER2-positive disease is unclear, possibly due to differing scoring criteria/assays. Data are also lacking for early disease. We aimed to assess the HER2-positivity rate using approved testing criteria in a large, real-life multinational population. HER2-positivity was defined as an immunohistochemistry staining score of 3+, or immunohistochemistry 2+ and HER2 amplification detected by in situ hybridization. A total of 4949 patients were enrolled and results showed that 14.2% of 4920 samples with immunohistochemistry results were HER2-positive. HER2-positivity was significantly higher in males (16.1% vs. 9.6% in females), in gastroesophageal versus stomach tumors (22.1% vs. 12.9%), in biopsy versus surgical samples (18.3% vs. 13.0%), in intestinal tumor subtypes versus diffuse (21.5% vs. 4.8%) and mixed types (21.5% vs. 8.5%) (P<0.001), in mixed versus diffuse types (8.5% vs. 4.8%), and in "other" versus diffuse types (11.7% vs. 4.8%; P=0.002). There were no significant differences between stages. Patients in the youngest age percentile had significantly lower HER2-positivity rates than patients in the remaining percentiles (9.2% vs. 15.9%, 15.7%, and 15.1%; P<0.001). HER2-positivity was highest in France (20.2%) and lowest in Hong Kong (10.4%). In conclusion, HER-EAGLE, the first study of its kind to be conducted in a large, multinational population of almost 5000 patients, gives valuable insights into the real-world HER2-positivity rate in a gastric/gastroesophageal junction cancer patient population not selected for disease stage or histology.

Introduction: Many changes have recently occurred in the practice of NET pathology. We therefore aimed to evaluating how pathologists have adapted their daily practice to the most recent international guidelines for diagnostic and prognostic evaluation. Procedures: A 12-month prospective study (PRONET) was carried out among French pathologists between August 2010 and July 2011. Data were collected using an anonymous electronic case report form. Observations: 500 laboratories were invited, 149 accepted to participate, 80 were active and 59 provided eligible cases. 1,340 cases were collected. The primary tumour was gastroenteropancreatic in 58.1% of cases and thoracic in 18.1%; it was from another site in 9.7%; 12.3% of cases were metastases of unknown origin. Pathological diagnosis was made from the examination of surgical samples in 58.1% of cases, biopsy specimens in 33.5%, endoscopic resections in 3.1% and cytological preparations in 4.2%. For the demonstration of the neuroendocrine nature of the tumor, chromogranin A and synaptophysin were tested in, respectively, 97.1% and 82.8% of cases. Differentiation status was definitely provided in 95.7% of cases. Mitotic count was attempted in 80.1% of cases and Ki67 index in 80.7%. In GEP-NETs, histological grading was available in 95.9% of the cases. WHO classification was available or feasible in 94.1% of GEP-NETs and 93.8% of thoracic NETs. TNM staging was performed according to UICC in 74.8% of GEP-NETs and according to ENETS in 55.6%. Conclusions: PRONET study shows that the current recommendations and diagnostic procedures are satisfactorily respected by most pathologists in daily practice.

Background and aims The differential diagnosis of solitary pancreatic cystic lesions is sometimes difficult. Needle-based confocal laser endomicroscopy (nCLE) performed during endoscopic ultrasound–fine-needle aspiration (EUS-FNA) enables real-time imaging of the internal structure of such cysts. Criteria have already been described for serous cystadenoma and intraductal papillary mucinous neoplasm (IPMN). The aims of the study were to determine new nCLE criteria for the diagnosis of pancreatic cystic lesions, to propose a comprehensive nCLE classification for the characterization of those lesions, and to carry out a first external retrospective validation . Methods Thirty-three patients with a lone pancreatic cystic lesion were included (CONTACT 1 study). EUS-FNA was combined with nCLE. Diagnosis was based on either pathology result (Group 1, n = 20) or an adjudication committee consensus (Group 2, n = 13). Six investigators, unblinded, studied cases from Group 1 and identified nCLE criteria for mucinous cystic neoplasm (MCN), pseudocyst (PC), and cystic neuroendocrine neoplasm (NEN). Four external reviewers assessed, blinded, the yield and interobserver agreement for the newly identified (MCN, PC) and previously described (IPMN, SC) criteria in a subset of 31 cases. Results New nCLE criteria were described for MCN (thick gray line), PC (field of bright particles), and cystic NEN (black neoplastic cells clusters with white fibrous areas). These criteria correlated with the histological features of the corresponding lesions. In the retrospective validation, a conclusive nCLE result was obtained for 74 % of the cases (87 % “true” and 13 % “false” with respect to the final diagnosis). On this limited case series, the nCLE criteria showed a trend for high diagnostic specificity (>90 % for mucinous cysts, 100 % for non-mucinous cysts). Conclusions Based on this newly completed atlas of interpretation criteria, nCLE could facilitate the diagnosis of pancreatic cystic lesion types.

The ductal adenocarcinoma of the pancreas is a tumor with a very poor prognosis. Complete histological resection remains the only potential curative treatment for patients with pancreatic adenocarcinoma. The pathological report leads to the diagnosis and provides information about the prognosis factor. In 2015, at the time of the quality assurance, it should be concise and specifies for maximum completeness. This report aimed to describe the pathological workup and proposed standardized items for pathological reports of pancreatic adenocarcinoma.

Introduction: Endoscopic ultrasonography (EUS)-guided fine-needle aspiration (FNA) have a better accuracy for the detection of pancreatic tumors compared with others images modalities. We assessed if the image criteria of elastography and contrast harmonic echo-endoscopic ultrasound could help in choosing the appropriate FNA-needle in the evaluation of focal pancreatic mass in other to maximize the diagnostic yield. This study prospectively included all new patients with focal pancreatic masses referred to be examined by EUS from October to December/2013. A total of 21 patients performed EUS with sequentially elastography and intravenous injection of a second-generation contrast agent (2.4 mL of SonoVue, Braco International, The Netherlands). The lesions which appear hipovascular were assessed with 22 gauge or 25 gauge FNA-needles. The hipervascular masses were biopsied with 19 gauge needles. Results: The topography of the lesions varied on 13 at the head, 4 at the body and 1 on the tail. The finding of a hypoenhanced mass was found in 57% (12/21 patients). Hyperenhanced was detected in 28% (6/21 patients). There were 14% (three patients) which the data were not recorded. The cytological diagnosis was achieved in 81% (17/21 patients) on the first biopsy. The others four patients have reached the diagnosis on the second examination. Of those four patients, in one was used the ProCore 25 gauge (lesion on the uncinatus process), and another one was used both 22 gauge and 25 gauge in the first examination. Conclusion: A characterization of the pancreatic lesions with elastography and contrast agents might be useful for clinical decision of which needle is better to improve biopsy quality and minimize EUS-FNA negatives results.