Concordance, intra- and inter-observer agreements between light microscopy and whole slide imaging for samples acquired by EUS in pancreatic solid lesions.

BACKGROUND: No study has compared the performance of light microscopy (LM) and whole slide imaging (WSI) for endoscopic ultrasound (EUS) histological acquired tissue samples from pancreatic solid lesions (PSLs). We evaluated the concordance between LM and WSI and the inter- and intra-observer agreements among pathologists on PSLs EUS acquired samples. METHODS: LM and WSI from 60 patients with PSLs were evaluated by five expert pathologists to define: diagnostic classification, presence of a core, number and percentage of lesional cells. Washout period between evaluations was 3 months. Time of the procedures was also assessed. RESULTS: Forty-eight cell-block and 12 biopsy samples were evaluated. A high concordance between LM and WSI was found. Inter- and intra-observer agreements for diagnostic classification were substantial and complete, respectively. For all the other parameters, the inter-observer agreement was usually higher for LM. For the intra-observer, a substantial agreement was reached regarding the presence of tissue core and the number and the percentage of malignant cells. Median time for performing LM was significantly shorter than for WSI (p < 0.0001). CONCLUSIONS: LM and WSI of cell-block and biopsy samples acquired by EUS in PSLs were highly concordant, with a substantial inter-observer and a complete intra-observer agreements regarding diagnostic classification.

Good performance of platinum-based chemotherapy for high-grade gastroenteropancreatic and unknown primary neuroendocrine neoplasms.

To evaluate efficacy and safety of platinum and etoposide combination in the treatment of advanced gastroenteropancreatic (GEP) and unknown primary (CUP) neuroendocrine carcinomas (NEC), we analysed the records of 21 consecutive patients treated with this regimen from 1999 to 2012. Objective responses were obtained in 11 patients (52%) and disease stability (DS) in 5 (24%). Median progression-free survival (PFS) was 7 months (95% CI, 5.33-8.66). Median overall survival (OS) was 16 months (95% CI, 14.97-17.03). Patients with limited liver disease had a significantly (p = 0.002) better PFS than patients with extrahepatic disease at diagnosis with 9 months (95% CI, 7.14-10.85) vs. 4 months (95% CI, 1.60-6.40). Two patients experienced durable complete response (30 and 90 months). The most common grade 3-4 toxicities were neutropenia (61%), anaemia (50%), nausea and vomiting (27%) and fatigue (22%). The platinum plus etoposide regimen has an acceptable toxicity profile and is effective in patients with GEP and CUP-NECs.

Matricellular proteins and survival in patients with pancreatic cancer: A systematic review.

Extracellular matrix (ECM) plays a fundamental role in tissue architecture and homeostasis and modulates cell functions through a complex interaction between cell surface receptors, hormones, several bioeffector molecules, and structural proteins like collagen. These components are secreted into ECM and all together contribute to regulate several cellular activities including differentiation, apoptosis, proliferation, and migration. The so-called "matricellular" proteins (MPs) have recently emerged as important regulators of ECM functions. The aim of our review is to consider all different types of MPs family assessing the potential relationship between MPs and survival in patients with pancreatic ductal adenocarcinoma (PDAC). A systematic computer-based search of published articles, according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) Statement issued in 2009 was conducted through Ovid interface, and literature review was performed in May 2017. The search text words were identified by means of controlled vocabulary, such as the National Library of Medicine's MESH (Medical Subject Headings) and Keywords. Collected data showed an important role of MPs in carcinogenesis and in PDAC prognosis even though the underlying mechanisms are still largely unknown and data are not univocal. Therefore, a better understanding of MPs role in regulation of ECM homeostasis and remodeling of specific organ niches may suggest potential novel extracellular targets for the development of efficacious therapeutic strategies.

Stromal and epithelial transcriptional map of initiation progression and metastatic potential of human prostate cancer.

While progression from normal prostatic epithelium to invasive cancer is driven by molecular alterations, tumor cells and cells in the cancer microenvironment are co-dependent and co-evolve. Few human studies to date have focused on stroma. Here, we performed gene expression profiling of laser capture microdissected normal non-neoplastic prostate epithelial tissue and compared it to non-transformed and neoplastic low-grade and high-grade prostate epithelial tissue from radical prostatectomies, each with its immediately surrounding stroma. Whereas benign epithelium in prostates with and without tumor were similar in gene expression space, stroma away from tumor was significantly different from that in prostates without cancer. A stromal gene signature reflecting bone remodeling and immune-related pathways was upregulated in high compared to low-Gleason grade cases. In validation data, the signature discriminated cases that developed metastasis from those that did not. These data suggest that the microenvironment may influence prostate cancer initiation, maintenance, and metastatic progression.Stromal cells contribute to tumor development but the mechanisms regulating this process are still unclear. Here the authors analyze gene expression profiles in the prostate and show that stromal gene signature changes ahead of the epithelial gene signature as prostate cancer initiates and progresses.

MicroRNAs as possible biomarkers for diagnosis and prognosis of hepatitis B- and C-related-hepatocellular-carcinoma.

Aim of the present review is to summarize the current knowledge about the potential relationship between miRNAs and hepatitis B virus (HBV)-hepatitis C virus (HCV) related liver diseases. A systematic computer-based search of published articles, according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis Statement, was performed to identify relevant studies on usefulness of serum/plasma/urine miRNAs, as noninvasive biomarkers for early detection of HBV and HCV-induced hepatocellular carcinoma (HCC) development, as well as for its prognostic evaluation. The used Medical Subject Headings terms and keywords were: "HBV", "HCV", "hepatocellular carcinoma", "microRNAs", "miRNAs", "diagnosis", "prognosis", "therapy", "treatment". Some serum/plasma miRNAs, including miR-21, miR-122, mi-125a/b, miR-199a/b, miR-221, miR-222, miR-223, miR-224 might serve as biomarkers for early diagnosis/prognosis of HCC, but, to date, not definitive results or well-defined panels of miRNAs have been obtained. More well-designed studies, focusing on populations of different geographical areas and involving larger series of patients, should be carried out to improve our knowledge on the potential role of miRNAs for HCC early detection and prognosis.

Possible association between hepatitis C virus and malignancies different from hepatocellular carcinoma: A systematic review.

AIM: To summarize the current knowledge about the potential relationship between hepatitis C virus (HCV) infection and the risk of several extra-liver cancers. METHODS: We performed a systematic review of the literature, according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) Statement. We extracted the pertinent articles, published in MEDLINE and the Cochrane Library, using the following search terms: neoplasm/cancer/malignancy/tumor/carcinoma/adeno-carcinoma and non-Hodgkin lymphomas, kidney/renal-, cholangio-, pancreatic-, thyroid-, breast-,oral-, skin-, prostate-, lung-, colon-, stomach-, haematologic. Case series, case-series with control-group, case-control, cohort-studies as well as meta-analyses, written in English were collected. Some of the main characteristics of retrieved trials, which were designed to investigate the prevalence of HCV infection in each type of the above-mentioned human malignancies were summarised. A main table was defined and included a short description in the text for each of these tumours, whether at least five studies about a specific neoplasm, meeting inclusion criteria, were available in literature. According to these criteria, we created the following sections and the corresponding tables and we indicated the number of included or excluded articles, as well as of meta-analyses and reviews: (1) HCV and haematopoietic malignancies; (2) HCV and cholangiocarcinoma; (3) HCV and pancreatic cancer; (4) HCV and breast cancer; (5) HCV and kidney cancer; (6) HCV and skin or oral cancer; and (7) HCV and thyroid cancer. RESULTS: According to available data, a clear correlation between regions of HCV prevalence and risk of extra-liver cancers has emerged only for a very small group of types and histological subtypes of malignancies. In particular, HCV infection has been associated with: (1) a higher incidence of some B-cell Non-Hodgkin-Lymphoma types, in countries, where an elevated prevalence of this pathogen is detectable, accounting to a percentage of about 10%; (2) an increased risk of intra-hepatic cholangiocarcinoma; and (3) a correlation between HCV prevalence and pancreatic cancer (PAC) incidence. CONCLUSION: To date no definitive conclusions may be obtained from the analysis of relationship between HCV and extra-hepatic cancers. Further studies, recruiting an adequate number of patients are required to confirm or deny this association.

Tensegrity model hypothesis: may this paradigm be useful to explain hepatic and pancreatic carcinogenesis in patients with persistent hepatitis B or hepatitis C virus infection?

CONTEXT: Hepatitis B (HBV) and hepatitis C virus (HCV) possess well-known oncogenic properties and may promote carcinogenesis in liver. However antigens and replicative sequences of HBV/HCV have been also detected in different extra-hepatic tissues, including the pancreas. Although epidemiological studies and meta-analyses have recently suggested that HBV/HCV may be also risk factors for pancreatic cancer and several researches have investigated the possible mechanisms and intra-/extra-cellular paths involved in pancreatic and hepatic carcinogenesis, to date, these complex processes remain largely unexplained. OBJECTIVES: In our paper, we aimed to propose a comprehensive and qualitative hypothetical model, describing how HBV/HCV may exert their oncogenic role. METHODS: We performed a systematic research of scientific literature, by searching MEDLINE, the Cochrane Library and EMBASE databases. The used keywords were: "chronic HBV/HCV", "pancreatic cancer", "liver carcinoma", "carcinogenesis mechanisms", "tensional integrity", "cytoskeleton", and "extracellular matrix". RESULTS: Taking advantage from available studies, we suggest an unifying hypothesis based on results and data, obtained from different areas of research. In particular we considered the well-defined model of tensional integrity and correlated it to changes induced by HBV/HCV in viscoelastic properties/stiffness of cellular/extracellular microenvironments. These events perturb the tightly-regulated feedback loop, which usually couples the intracellular-generated forces to substrate rigidity of extracellular compartments. Therefore, such a change strongly affects intracellular functions and cellular fate, by promoting a substantial deregulation of critical intracellular biochemical activities and genome expression. CONCLUSIONS: Our hypothesis might provide for the first time a reliable system, which correlates tensional integrity model with intra-/extra-cellular modifications, occurring in liver and pancreas during HBV/HCV-induced carcinogenesis. This approach might improve our understanding of pathogenetic mechanisms involved in the development of pancreatic and hepatic carcinogenesis , enhancing the possibility of their treatment. Furthermore, should the usefulness of this model be definitively confirmed, it might be also helpful to extend its field of application to other viruses-related cancers.

Synchronous association of two neuroendocrine gastroenteropancreatic tumors, an adenocarcinoma of the cecum, and a Meckel's diverticulum: a case report.

Neuroendocrine gastroenteropancreatic tumors constitute a heterogeneous group of neoplasms, with the primary tumors being located in the gastric mucosa, pancreas, and small and large intestine. The development of a second primary malignancy in patients with these tumors is a well-described phenomenon, and the reported incidence ranges from 12% to 46%. The most common site of associated noncarcinoid malignancies is the gastrointestinal tract, which involves from 30% to 60% of the tumors. We report a case of concurrent colon carcinoma and two neuroendocrine tumors of the duodenum.

Rapid on-site evaluation of transbronchial aspirates in the diagnosis of hilar and mediastinal adenopathy: a randomized trial.

BACKGROUND: Rapid on-site evaluation (ROSE) of transbronchial needle aspirates has long been used during flexible bronchoscopy, but its usefulness in the diagnosis of hilar and mediastinal adenopathy is controversial. The aim of the present study was to evaluate the extent to which ROSE can be valuable in patients undergoing transbronchial needle aspiration (TBNA) for the diagnosis of hilar and mediastinal adenopathy. METHODS: A total of 168 consecutive patients with enlarged lymph nodes were randomized to undergo TBNA with or without ROSE. The primary outcome measure of the study was the diagnostic yield of TBNA on a per-patient basis. Secondary outcome measures included the percentage of adequate specimens on a per-lymph node basis, the number of biopsy sites on a per-patient basis, and the complication rate of bronchoscopy on a per-patient basis. RESULTS: We found no significant difference between the TBNA group and the ROSE group in terms of diagnostic yield (75.3% vs 78.3%, respectively; P = .64), and percentage of adequate specimens (86.5% vs 78.4%, respectively; P = .11). The median (interquartile range) number of biopsy sites was significantly lower in the ROSE group (1 [1-2] vs 2 [1-2], respectively; P = .0005). The complication rate of bronchoscopy was significantly lower in patients undergoing on-site review (6% vs 20%; P = .01), whereas the complication rate of TBNA was similar among the study groups. CONCLUSIONS: ROSE of transbronchial aspirates from hilar and mediastinal nodes enables avoidance of additional biopsy without loss in diagnostic yield and reduces the complication rate of bronchoscopy. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00915330; URL: www.clinicaltrials.gov

Virtual microscopy and digital cytology: state of the art.

The paper approaches a new technological scenario relevant for the introduction of the digital cytology (D-CYT) in the health service. A detailed analysis of the state of the art on the status of the introduction of D-CYT in the hospital and more in general in the dispersed territory has been conducted. The analysis was conducted in a form of review and was arranged into two parts: the first part focused on the technological tools needed to carry out a successful service (client server architectures, e-learning, quality assurance issues); the second part focused on issues oriented to help the introduction and evaluation of the technology (specific training in D-CYT, health technology assessment in-routine application, data format standards and picture archiving computerized systems (PACS) implementation, image quality assessment, strategies of navigation, 3D-virtual-reality potentialities). The work enlightens future scenarios of actions relevant for the introduction of the technology.

The virtual slide in the promotion of cytologic and hystologic quality in oncologic screenings.

A regional experience environment in virtual microscopy and digital pathology comprehending the digital cytology is presented. The project has been conducted in Emilia-Romagna and it has been planned for the promotion and the quality assessment in screening cytology and histology for the prevention of the tumors of uterine cervix, breast and colon-rectum cancers. During the project it has been envisaged the design of a dedicated picture archive and communication system (PACS) for cooperative diagnosis, didactics and training, teleconsulting, documentation of rare cases and pilot experiences; furthermore selected cases are catalogued in the PACS with the aim of the check of the diagnostic concordance in the oncologic screening.

Intrahepatic cholangiocarcinoma resembling a thyroid follicular neoplasm.

The first case of well-differentiated intrahepatic cholangiocarcinoma with remarkable follicular architecture resembling a follicular neoplasm of thyroid is described in a 52-year-old man. The follicles contained homogenous eosinophilic material akin to colloid and were lined by benign-looking cuboidal cells. Immunohistochemically, thyroid transcription factor-1 (TTF-1) and thyroglobulin were negative and the patient had no evidence of a previous or concomitant thyroid tumour. This case can be added to the list of extrathyroid primary tumours that resemble thyroid neoplasms.