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Inflammatory pseudotumor of the liver (IPTL) is a rare benign lesion that can mimic hepatic malignant neoplasms. A 79-year-old woman, in follow-up care for a left breast cancer, was referred to our Ultrasound Diagnostic Centre for a hepatic mass of unknown nature, displayed on PET-CT, CT and Abdominal Ultrasonography (US). The patient presented with abdominal pain and low-grade fever, increased values of C-Reactive Protein (CRP) and gamma-glutamyl transpeptidase (γGT). Abdominal US confirmed the presence of a heterogeneous polycyclic mass 4.0 × 3.7 cm in size, sub-capsular, localized in the segment VI, isoechoic in arterial phase and hypoechoic in portal and late phase on contrast-enhanced ultrasound (CEUS). A liver biopsy revealed the presence of chronic inflammatory cells without evidence of malignancy. As the patient did not respond to medical therapy, she underwent hepatic segmentectomy and cholecystectomy. At histology, the specimen showed acute and chronic inflammation with xanthogranulomatous features.

Pancreatic adenocarcinoma (PDAC) is the most frequent histological type of malignancy in the pancreas. Extracellular matrix (ECM), plays a critical role during the process of human carcinogenesis and the possible diversity in matricellular proteins composition of ECM may have a significant impact on the clinical course of PDAC. Aim of this paper was to evaluate the expression of three matricellular proteins, including Periostin (POSTN), Tenascin (TNS) and Osteopontin (OPN), in PDAC from long-survival (LS) and non-long survival (NLS) patients. A total of 30 PDAC were analyzed, 15 from patients that survived more than 60 months after surgery (LS) and 15 that died from the disease within 24 (NLS). RNA was extracted and OPN, TNS and POSTN mRNA levels were evaluated by qRT-PCR.LS and NLS samples showed the same type of POSTN and TN isoforms. On the contrary, OPN seems to be preferentially expressed in NLS PDAC. Moreover, OPNb and OPNc isoforms were expressed exclusively in NLS samples. In conclusion, Our data led to hypothesize a possible relationship between the expression of different isoforms of each of these proteins and the clinical outcome of patients with PDAC.

Carcinoma of the ampulla of Vater is an uncommon neoplasm and represents 0.5% of all gastrointestinal malignancies, being less common than carcinoma of the pancreas and bile ducts. The most common ampullary tumor is the adenocarcinoma with tubular growth pattern. Signet ring cell carcinoma is extremely rare. In this article, we report a case of signet ring cell carcinoma of the ampulla of Vater showing focal neuroendocrine amphicrine differentiation and intestinal phenotype, which occurred in a 49-year-old male who is still alive 7 years after surgery, without evidence of recurrence. This long-term survival might be attributed not only to the early stage of the disease but also to the neuroendocrine differentiation and the absence of genetic alterations.

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 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.

Context.—Integration of the analysis of genetic markers with endoscopic ultrasound–guided fine-needle aspiration and cytologic evaluation has increased the accuracy of the preoperative diagnosis of pancreatic lesions. The application of high-throughput gene panel analysis using next-generation sequencing platforms is now offering a great opportunity for further improvements.Objective.—To review the application of next-generation sequencing to the preoperative diagnosis of pancreatic lesions.Data Sources.—For data acquisition, a PubMed search using the terms next-generation sequencing, pancreas, pancreatic lesions, pancreatic tumors, and EUS-FNA was performed covering the years 2000–2017.Conclusions.—KRAS remains the gene most widely studied for preoperative single-gene tests. Next-generation sequencing reliably allows analysis of multiple gene markers starting from limited amounts of DNA. The study of multigene panels has become a very attractive option for the management and preoperative risk stratification of patients with pancreatic cancer.

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.

Background Pancreatic adenocarcinoma (PDAC) is one of the deadliest human malignancies. Although surgery is currently the only effective treatment for PDAC, most patients survive less than 20 months after tumor resection. Objective The primary goal was to investigate alterations in KRAS, TP53, SMAD4 and CDKN2A/p16 in tumors from patients with exceptionally long survival after surgery. Methods Tumors from 15 patients with PDAC that survived more than 55 months after surgery ("LS") were analyzed for KRAS, TP53, IDH1, NRAS and BRAF using next-generation sequencing. SMAD4 and CDKN2A/p16 was tested using immunohistochemistry. MGMT promoter methylation was investigated. Results Tumors from "LS" have a lower prevalence of KRAS and TP53 mutations and had more frequently SMAD4 retained expression, if compared with that of patients died within 24 months from surgery. The survival of patients with wild-type KRAS and TP53 tumors was more than twice longer than that of patients bearing KRAS and TP53 mutations (90.2 vs. 41.1 months). Patients with KRAS wild-type tumors and that retained SMAD4 expression had a survival twice longer than cases with alterations in both genes (83.8 vs. 36.7 months). Eleven tumors (39.3%) showed MGMT methylation. Conclusions Our data indicate that absence of KRAS, TP53 and SMAD4 genetic alterations may identify a subset of pancreatic carcinomas with better outcome.

Background: Rapid on-site evaluation (ROSE) improves the adequacy and accuracy of EUS-guided tissue acquisition, although it is not routinely widely available. Evidence suggested that core needles might overcome the absence of ROSE. The aim of this study was to evaluate the influence of ROSE on the adequacy and accuracy of EUS-guided tissue acquisition with core needles in patients with pancreatic solid lesions. Methods: Patients who underwent EUS-guided tissue acquisition of pancreatic mass lesions were retrospectively identified at three tertiary referral centers and those performed with the core needle were included. Adequacy, defined as the rate of cases in which a tissue specimen for proper examination was achieved, with and without ROSE was the primary outcome measure. The diagnostic accuracy and tissue core acquisition were the secondary outcome measures. Results: A total of 333 patients with pancreatic solid mass lesions were included in the study; 140 cases sampled with ROSE and 193 cases without ROSE. The adequacy was 92.1 % in the group sampled with ROSE and 88.1 % in the group without ROSE (p = 0.227). In the ROSE group sensitivity, specificity, and accuracy were 90.7, 100 and 92.1 %, respectively. In the group without ROSE, sensitivity, specificity, and accuracy were 87.2, 100, and 88.1 %, respectively. No difference for all these figures was observed between the two groups. The tissue core was available in 61.4 and 53.4 % of cases with and without ROSE, respectively (p = 0.143). Conclusion: In the absence of ROSE, EUS-based tissue acquisition with Core needle should be considered since it achieves comparable tissue sampling adequacy and accuracy.

Pancreatic ductal adenocarcinoma (PDAC) is expected to become the second leading cause of cancer-associated death in the next decade or so. It is widely accepted that tumorigenesis is linked to specific alterations in key genes and pancreatic neoplasms are some of the best characterized at the genomic level. Recent whole-exome and whole-genome sequencing analyses confirmed that PDAC is frequently characterized by mutations in a set of four genes among others: KRAS, TP53, CDKN2A/p16, and SMAD4. Sequencing, for example, is the preferable technique available for detecting KRAS mutations, whereas in situ immunochemistry is the main approach for detecting TP53 gene alteration. Nevertheless, the diagnosis of PDAC is still a clinical challenge, involving adequate acquisition of endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) and specific pathological assessment from tissue architecture to specific biomolecular tests. The aim of the present review is to provide a complete overview of the current knowledge of the biology of pancreatic cancer as detected by the latest biomolecular techniques and, moreover, to propose a paradigm for strict teamwork collaboration in order to improve the correct use of diagnostic sources.

Background Cytologic diagnosis by endoscopic ultrasound-guided fine needle aspiration is associated with low sensitivity and adequacy. A newly designed endoscopic ultrasound-guided fine needle biopsy device, endowed with a side fenestration, is now available. Aims We carried out a study with the aim of evaluating the feasibility, safety, and diagnostic yield of the 22-gauge needle with side fenestration for endoscopic ultrasound fine needle aspiration and biopsy of pancreatic cystic lesions. Methods 58 patients with 60 pancreatic cystic lesions consecutively referred for endoscopic ultrasound guided-fine needle aspiration were enrolled in a prospective, dual centre study, and underwent fine needle aspiration and biopsy with the 22-gauge needle with side fenestration. Results Fine needle aspiration and biopsy was technically feasible in all cases. In 39/60 (65%) pancreatic cystic lesions, the specimens were adequate for cyto-histologic assessment. In lesions with solid components, and in malignant lesions, adequacy was 94.4% ( p = 0.0149) and 100% ( p = 0.0069), respectively. Samples were adequate for histologic evaluation in 18/39 (46.1%) cases. There were only 2 (3.3%) mild complications. Conclusions Fine needle aspiration and biopsy with the 22-gauge needle with side fenestration is feasible, and superior to conventional endoscopic ultrasound-guided fine needle aspiration cytology from cystic fluid, particularly in pancreatic cystic lesions with solid component or malignancy, with a higher diagnostic yield and with no increase in complication rate.

Background and Aims The recent development of microforceps for EUS through-the-needle biopsy (TTNB) sampling of the wall of pancreatic cystic lesions (PCLs) allows the collection of histologic specimens never handled and evaluated before by pathologists. We aimed to estimate the interobserver agreement among pathologists in evaluating such samples. Methods TTNB specimen slides from 40 PCLs with worrisome features were retrieved and independently evaluated for specimen adequacy, presence of lining epithelium, grade of epithelial dysplasia, presence of ovarian type stroma, and specific diagnosis by 6 expert pathologists from 6 different tertiary care centers. The Gwet's AC1 was used to assess interobserver agreement. Results An almost perfect agreement was observed for specimen adequacy (AC1, .82; 95% confidence interval [CI], .79-.98), presence of lesional epithelium (AC1, .90; 95% CI, .86-.92), epithelial dysplasia (AC1, .97; 95% CI, .95-.99), and ovarian-like stroma (AC1, .90; 95% CI, .86-.93). When considering all diagnoses separately, a moderate to substantial agreement was observed (AC1, .62; 95% CI, .57-.67), similarly to mucinous cysts versus serous adenoma versus other diagnoses (AC1, .65; 95% CI, .59-.70) and for mucinous cysts versus all other diagnoses (AC1,.74; 95% CI, .68-.84). The agreement for diagnosis of mucinous cystic neoplasm versus intraductal mucinous papillary neoplasm was almost perfect (AC1, .88; 95% CI, .81-.95). Conclusions Interobserver agreement between expert pathologists in the evaluation of TTNB samples from PCLs with worrisome features was close to perfection for all evaluated parameters, except definitive diagnosis. When mucinous cystic lesions were compared versus all other diagnoses, the agreement became substantial, thus indicating that TTNB specimens can provide important information for PCL management decisions.

Objectives: PEComas (perivascular epithelioid cell tumors) are a family of neoplastic lesions that share overlapping ultrastructure and morphological and immunohistochemical appearance and include angiomyolipoma, lymphangioleiomyomatosis, and clear cell “sugar” tumor of the lung, as well as similar tumors that occur in a variety of visceral, cutaneous, and soft tissue sites throughout the body. Methods: A 40-year-old woman came to medical attention because of epistaxis and because of unilateral nasal obstruction of 3 months' duration. Endoscopic examination revealed a well-demarcated exophytic lesion attached to the anterior portion of the middle turbinate. Results: The lesion was superficially located, and therefore amenable to complete surgical excision. Seven years after surgery, the patient is alive and well, without evidence of local recurrence or metastastic disease. Based on morphological and immunohistochemical appearance, a diagnosis of PEComa with worrisome histologic features was rendered. Conclusions: In the present study, we describe a PEComa that occurred in the nasal cavity and discuss the behavior of this entity. The importance of recognizing this disease will ensure its consideration in the differential diagnosis of tumors of the head that have similar morphological features. The histogenesis of PEComa still remains elusive, and collection of additional cases with a prolonged follow-up will be important in accurately determining the behavior of these distinctive tumors.

The use of endoscopic ultrasonography has allowed for improved detection and pathologic analysis of fine needle aspirate material for pancreatic lesion diagnosis. The molecular analysis of KRAS has further improved the clinical sensitivity of preoperative analysis. For this reason, the use of highly analytical sensitive and specific molecular tests in the analysis of material from fine needle aspirate specimens has become of great importance. In the present study, 60 specimens from endoscopic ultrasonography fine needle aspirate were analyzed for KRAS exon 2 and exon 3 mutations, using three different techniques: Sanger sequencing, allele specific locked nucleic acid PCR and Next Generation sequencing (454 GS-Junior, Roche). Moreover, KRAS was also tested in wild-type samples, starting from DNA obtained from cytological smears after pathological evaluation. Sanger sequencing showed a clinical sensitivity for the detection of the KRAS mutation of 42.1%, allele specific locked nucleic acid of 52.8% and Next Generation of 73.7%. In two wild-type cases the re-sequencing starting from selected material allowed to detect a KRAS mutation, increasing the clinical sensitivity of next generation sequencing to 78.95%. The present study demonstrated that the performance of molecular analysis could be improved by using highly analytical sensitive techniques. The Next Generation Sequencing allowed to increase the clinical sensitivity of the test without decreasing the specificity of the analysis. Moreover we observed that it could be useful to repeat the analysis starting from selectable material, such as cytological smears to avoid false negative results.

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.

Five cases of mucoepidermoid carcinoma (MEC) of the breast are reported. All patients were women ranging in age from 29 years to 80 years. As histological grading is one of the most important prognostic factors in breast invasive carcinomas, MEC was graded using the Auclair et al. [1] grading system specific for MEC of salivary glands and the Elston and Ellis [4] grading method, a widely employed grading system in breast cancer. It was found that the two different grading systems appear to be interchangeable in assessing the grade of MEC of the breast. Accordingly, three cases were regarded low grade (G. 1), one intermediate (G. 2) and one high grade (G. 3). The cases were studied with immunohistochemistry and were found to have the same keratin pattern shown by their salivary gland counterpart. It was found that there are more similarities than differences between MEC of the breast and of salivary glands.

Background Pancreatic mucinous cystic lesions might develop malignancy if untreated, or could harbor malignancy at the time of the diagnosis. Many reports stated that cyst fluid carcinoembryonic antigen is an accurate diagnostic marker of pancreatic mucinous cysts. Methods A man with a incidental pancretic cystic lesion of 35 mm in diameter was admitted to our Department. CT and EUS did not reveal solid components, main duct was not dilated and cyst fluid CEA was very high (1445 ng/ml). Results The patient underwent a pancreatoduodenectomy and the surgical specimen showed a pseudocyst with columnar mucinous epithelium, consistent with low-grade PanIN. Conclusions Is it possible that the mucinous epithelium of panIN was responsible for the unexpectedly high CEA value?Clinicians should be aware of the usefulness of the CEA level in cystic fluid but even a very high CEA value should not be considered by itself to be evidence of a mucinous lesion.

Early detection of small pancreatic cancer is important because expected survival is markedly better for tumors ≤2 cm. A new endoscopic ultrasound-(EUS) guided biopsy needle with side fenestration has been recently developed to enable fine-needle biopsy (FNB) under EUS guidance. The aim of this study was to evaluate the outcome of EUS–FNB using a 22-gauge ProCore needle in solid pancreatic lesions ≤2 cm, in terms of diagnostic accuracy and yield. From January 2011 to December 2012, all consecutive EUS-guided tissue sampling of small pancreatic lesions (≤2 cm) were performed using 22-gauge ProCore needles; the data of these patients were analyzed retrospectively. Sixty-eight patients with a mean age of 65.7 years were included. The mean lesion size was 16.5 mm (range 5–20). None of the patients developed complications. On pathological examination, the tissue retrieved was judged adequate in 58 out of 68 cases (85.3 %) and the presence of a tissue core was recorded in 36 out of 68 cases (52.9 %). The overall sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 80, 100, 100, 40, and 82 %, respectively. Our results suggested that EUS–FNB of small pancreatic lesions using a 22-gauge ProCore needle is effective and safe, and supports our hypothesis that EUS–FNB is highly useful in establishing the nature of small pancreatic lesions.

The Ki-67 labeling index has been found to bear prognostic significance in gastrointestinal neuroendocrine tumors (NETs), and it was recently incorporated in NET histological grading. Nevertheless, a reliable preoperative determination of NET grading could be useful in clinical practice. The aim of this study is to compare the results of Ki-67 labeling index, as measured on cytological samples and on surgical specimens of patients with pancreatic NETs (P-NETs). We also investigated whether concordance might be improved, using a 5 % (instead of 2 %) cutoff value for defining G2 tumors. We retrospectively identified 48 consecutive patients with 53 P-NETs, from our five institutions, and we measured Ki-67 labeling index on their cytological samples and surgical specimens. The traditional 2 % and the alternative 5 % cutoff values were used to classify G2 tumors. The concordance rate between cytological and histological grading was 46/53 (86.8 %; weighted κ statistic 0.77; 95 % confidence interval (95 % CI) 0.60-0.94). No cases of cytological G1-G2 NETs were upgraded to G3 neuroendocrine carcinoma (NEC) at histological grading. Cytology was found to be highly specific in the diagnosis of both G2 (94.1 %; 95 % CI 80.3-99.3) and G3 tumors (100.0 %; 95 % CI 92.8-100), but the sensitivity was poor for G2 NETs (66.7 %; 95 % CI 38.4-88.2) and high for the prediction of G3 NECs (100 %; 95 % CI 39.8-100.0). When the 5 % cutoff value was adopted, concordance rate was 49/53 (92.4 %; weighted κ 0.82; 95 % CI 0.64-1.00). In conclusion, Ki-67 cytological expression can distinguish well-differentiated (both G1 and G2) from poorly differentiated P-NETs, and it may be useful for their preoperative classification. © 2014 Springer-Verlag.

Merkel cell carcinoma of the parotid gland associated with Warthin tumour: report of two cases Aims: Two cases of Merkel cell carcinoma occurring simultaneously and in close association with a Warthin tumour of the parotid gland are reported Methods and results: The patients were a 65-year-old man and a 70-year-old man, respectively. The Merkel cell carcinoma component was immunoreactive for chromogranin and keratin 20 and contained neuroendocrine-type granules at the ultrastructural level. Conclusions: The histogenesis of this heretofore undescribed combination is discussed.

A case of uterine leiomyoma with skeletal muscle differentiation is described. The patient is a 40-year-old woman who underwent abdominal hysterectomy and left salpingo-oophorectomy for fibroids. Evidence of skeletal muscle differentiation was evident at light and electron microscopy in one out of three "ordinary" leiomyomas. This was also shown by positive immunoreactions with antiskeletal muscle actin and myoglobin antisera. To our knowledge, this is the second case reported of the occurrence of skeletal muscle differentiation within a uterine leiomyoma and highlights the divergent differentiating potential of smooth muscle cells.

A case of extra-abdominal fibromatosis (EF) of the orbit is described in a 35-year-old man presenting with progressive exophthalmos, right ptosis and diplopia. MRI showed an orbital mass of intermediate signal in T1-weighted images (WI) and low signal in T2WI, which enhanced non-homogeneously after contrast injection. The histological diagnosis of EF was made and the lesion was surgically removed. No recurrence occurred in 40 months of follow-up.

Background A solid pseudopapillary tumour of the pancreas (SPTP) is a rare neoplasm. Aim We herein present five cases of SPTP diagnosed using endoscopic ultrasound (EUS) guided fine-needle biopsy (FNB) using a needle with side fenestration (ProCore-needle). Methods From January 2011 to June 2012 in five patients with SPTP tissue acquisition was carried out with a 19-gauge (4 patients) or a 22-gauge (one patient) needle. Results The mean age of the patients was 30.8 years, the mean lesion size was 49 mm and the most common location was the tail of the pancreas (3 cases). When the samples were evaluated macroscopically, small core fragments were observed in all cases. A preoperative diagnosis of SPTP was made in all patients on the basis of the histocytological and characteristic immunophenotypic patterns and was confirmed at final surgical histology. Conclusions In our experience, EUS-FNB is an effective and secure method for a preoperative diagnosis of SPTP.

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.

Background The difference in the diagnostic accuracy of 22- versus 25-gauge needles in EUS-FNA is not clear. Aims To compare the rates of technical success, diagnostic accuracy and complications of EUS-FNA performed with 22-gauge and 25-gauge needles on the same solid pancreatic mass. Methods All patients with solid pancreatic masses evaluated from September 2007 to December 2008 were enrolled and underwent EUS-FNA with both 22- and 25-gauge needles with randomisation of needle sequence. The accuracy of the EUS-FNA was determined by comparing the cytological results with the final surgical pathological diagnoses or with the results of a clinical follow-up. A cytological score with different qualitative parameters was created, and a comparison between these parameters was carried out for each needle. Results Fifty patients with 50 pancreatic masses were recruited. Technical success was 100% and no complications occurred. Diagnostic accuracy was 94% and 86% for the 25- and 22-gauge needles, respectively. Analysis of the cytological score showed a tendency towards the 25-gauge needle, although the difference was not statistically significant. Conclusions EUS-FNA performed with 22- or 25-gauge needles had the same diagnostic accuracy. Our study results confirm a significant trend towards a better cytological diagnosis for the 25-gauge needle.

none 21 Pancreatic adenocarcinoma (PAC) is a very aggressive cancer with a poor prognosis. To date, the causes and pathogenetic mechanisms involved in the development of this malignancy remain largely unknown. Therefore, additional studies are required to improve our knowledge of the events that occur during the process of pancreatic carcinogenesis. The purpose of this article is to describe the most recent evidence, concerning the possible risk factors and mechanisms that may contribute to determine the development of PAC, as well as models, such as the tensegrity model, that may explain this complex process. Available studies suggest that approximately 15-20% of human malignancies are somehow associated with chronic infection. Some epidemiological research has shown that some infectious agents represent risk factors for PAC. In particular, several reports showed that the infection caused by some micro-organisms, including helicobacter pylori and some bacterial species of oral microbiota, as well as by viral agents, such as human immunodeficiency virus (HIV), and hepatitis B (HBV) and C (HCV) viruses, is associated with an increased probability of developing PAC. For the first time, observational studies and meta-analyses have suggested that HBV and HCV, two hepatotropic viruses with oncogenic properties, may be also risk factors for PAC. However, the small number of available reports, nearly all performed in Asian populations, limits their validity to these ethnic groups. Therefore, additional studies focusing on populations of different geographical areas and enrolling larger series of patients are required to confirm this association. Furthermore, an accurate description and a better understanding of the events and of the pathogenetic mechanisms involved in the process of pancreatic carcinogenesis, as proposed by the tensegrity model, might be a useful approach to effectively deal with this pathology. Sirio Fiorino;Letizia Bacchi-Reggiani;Laura Pontoriero;Claudio Gallo;Elisabetta Chili;Michele Masetti;Nicola Zanini;Anna Grondona;Tania Silvestri;Gaia Deleonardi;Elisabetta Magrini;Roberto Motta;Adele Fornelli;Arrigo Bondi;Dario De Biase;Paola Baccarini;Giovanni Tallini;Antonio Tropeano;Andrea Cuppini;Gastone Castellani;Elio Jovine Sirio Fiorino;Letizia Bacchi-Reggiani;Laura Pontoriero;Claudio Gallo;Elisabetta Chili;Michele Masetti;Nicola Zanini;Anna Grondona;Tania Silvestri;Gaia Deleonardi;Elisabetta Magrini;Roberto Motta;Adele Fornelli;Arrigo Bondi;Dario De Biase;Paola Baccarini;Giovanni Tallini;Antonio Tropeano;Andrea Cuppini;Gastone Castellani;Elio Jovine

EUS to exclude, detect and stage ampullary lesions and perform biopsy or FNA. EUS excluded suspected malignant disease in 43% of cases. Mo1477 FISH Analysis of Aspirates Increases the Sensitivity of EUS-Guided FNA for the Diagnosis of Pancreatic Adenocarcinoma Jose-Guillermo De La Mora-Levy*, Juan O. Campuzano, Judith Cruz-Velazquez, Octavio Alonso, Julio Sanchez Del Monte, Sergio R. Sobrino-Cossio, Angelica Hernandez-Guerrero Gastroenterology, National Cancer Institute, Mexico City, Mexico; Cytogenetics, National Cancer Institute, Mexico City, Mexico Background: The sensitivity of EUS-guided cytology for the diagnosis of pancreatic adenocarcinoma is between 70 & O90%; among the identified factors that predict a positive result, the presence of a cytopathologist, number and passes and posible the type of needle have been identified as helpful. Aim: To study if the addition of FISH to cytology increases the sensitivity of EUS-guided FNA. Material & Methods: Consecutive patients with a pancreatic mass, sent for EUS-guided FNA to our Unit. An Olympus GF-UCT 160 echoendoscope and 22 gauge needles (EchoTip , Cook Medical), were used. Between 1-4 passes (median: 2) were performed for preparation of slides and cell block; 1 random slide was used for FISH analysis, which was performed using a commercially available kit (Urovision ). NO cytopathologist was present during the procedure. A total of 112 patients was calculated as the number needed to demonstrate at least a 10% increase in sensitivity, assuming an average of 80% sensitivity. A positive result was considered when either cytopathology or FISH alone or both were positive. Diagnostic values were calculated for Cytology, FISH and the combination; increase in sensitivity was the main variable. Inadequate specimens were purposely not included. The gold standard was considered to be: the surgical specimen, or a combination of CA 19-9 values, appropriate clinical and imaging picture plus compatible outcome on follow-up (FU). The study was approved by the IRB of our Institution. Results: A total of 105 patients were included; 16 were excluded for various reasons and analysis was performed on 89 patients. 49 were female, with a median age of 58 years (37-84); median FU was 4 months (1-12). Diagnostic values are shown in Table 1: A 13% increase in sensitivity was found, even when the calculated number was not reached. Conclusion: The addition of FISH analysis to EUS-guided FNA increases the sensitivity and positive results in patients with pancreatic adenocarcinoma. FISH could be used routinely, specially in settings without an onsite cytopathologist and with relatively few needle passes.

s / Pancreatology 13 (2013) S2–S98 S81 OR body mass index OR lean tissue loss OR fat free mass). Relevant Abstracts were read, eligible articles retrieved and a manual search of the bibliographies performed. The «related article» function in PubMed was used to identify missed studies. English language relevant clinical studies of any level of evidence were included. Unpublished data, Abstract or duplicate publications were excluded. Results: Two articles were found of 343 articles and related research. Two retrospective trials included 152 patients with inoperable pancreatic adenocarcinoma. The prevalence of sarcopenia was 62(56%) and 26(63%) patients. All had advanced cancer and underwent chemotherapy/chemoradiation. Sarcopenia was assessed by means of CT-scan skeletal muscle calculation. Sarcopenia alone was not significantly associated with poor survival. In multivariate analysis sarcopenic obesity but not sarcopenia alone was associated with significantly lower survival. Conclusion: The systematic review showed the lack of data about sarcopenia impact on survival in patients with pancreatic cancer. It justifies the need of further research. PII-96 Abstract id: 85. Liver resection for metastatic periampullary cancer: Is it (sometimes) worthwile? Nicola Zanini , Raffaele Lombardi , Luca Valeriani , Dario de Biase , Francesco Cinquantini , Adele Fornelli , Michele Masetti , Elio Jovine . Dept of Surgery, Maggiore Hospital, Bologna, Italy Dept of Clinical Nutrition, Maggiore Hospital, Bologna, Italy University of Bologna, Bologna, Italy Dept of Radiology, Maggiore Hospital, Bologna, Italy Dept of Pathology, Maggiore Hospital, Bologna, Italy Introduction: Surgery is generally not indicated for metastatic periampullary adenocarcinoma because it does not appear to improve survival. Aims: Is metastastic periampullary cancer an absolute contraindication to surgery? Could someone benefit from liver resection? Patients & methods: Our prospectively collected database (20032012) lists 21 patients who underwent liver resection for metastases from periampullary adenocarcinoma. Resection was offered to young patients who were fit for surgery and had few synchronous or metachronous metastases. Potential prognostic factors were taken into consideration to design a score that was applied to the study population to predict survival. Results: Ductal carcinoma was the primary tumor in 15 patients; the remaining patients had ampullary carcinoma or distal bile duct carcinoma. One right hepatectomy, 2 bisegmentectomies and 18 atypical resections were performed. Simultaneous liver and pancreatic resection did not significantly improve postoperative morbidity and mortality compared to standard pancreatic resection. The median overall survival from liver resection (OS) of patients with synchronous and metachronous disease was 11.4 months (95% CI: 6.0-16.9) and 28.5 months (95% CI: 1.7-55.2), respectively (p1⁄40.12). The proposed score was able to divide the subjects into three classes of prognosis, inwhich the estimated OS was significantly different. Conclusion: Surgery for liver metastases from periampullary tumors is controversial. It is not suggested for most patients, and death may occur even earlier compared to palliative cure. However, a small group of highly select patients could benefit from surgery. PII-97 Abstract id: 109. MMP9 and S100A9 expression in peripheral blood mononuclear cells (PBMC) are correlated with PDAC and with PDAC-associated diabetes mellitus Stefania Moz , Dania Bozzato , Carlo Federico Zambon , Paola Fogar , Michela Pelloso , Anna Caterina Milanetto , Andrea Padoan , Filippo Navaglia , Eliana Greco , Claudio Pasquali , Mario Plebani , Daniela Basso . Department of Medicine DIMED,University of Padova., Italy Department of Surgical, Oncological and Gastroenterological Sciences DISCOG; University of Padova, Italy Introduction: Tumor-stroma-endocrine interactions favour pancreatic adenocarcinoma (PDAC) growth/progression and PDAC-associated diabetes mellitus (DM). S100A8/A9 and the matrix methalloproteinases (MMPs) 8 and 9 are overexpressed in PDAC stroma. Aims: To verify whether S100A8, S100A9, MMP8 and MMP9 mRNA in PBMC is useful for diagnosing and staging PDAC and/or for detecting PDACassociated DM. To study the impact of S100A8/A9 and of PDAC-associated growth factors and cytokines on MMPs expression. Patients & methods: S100A8, S100A9, MMP8 e MMP9 mRNA were quantified by qRT-PCR in 62 PDAC, 37 chronic pancreatitis, 23 pancreatobiliary tract tumors (PBT) and 30 healthy controls (HC). PBMC (blood donors) were treated with insulin, EGF, TGFb1, S100A8/A9 before MMP8 and MMP9 mRNA analysis. Results:MMP8 andMMP9 were higher in PDAC and in PBT than in HC (Kruskal-Wallis Test: p

Thirty cases of ductal carcinoma in situ (DCIS) of the breast, showing histological microcalcifications, were studied to clarify their mechanism of formation. Undecalcified sections revealed three types of calcium precipitates: type I and II granular calcifications (GCs) and laminar calcifications (LCs). In type I GCs the core on which the calcium had deposited was constituted mainly by nuclear debris. Type II GCs were predominantly composed by mucosubstances. LCs were the result of calcium deposits on mucoid or proteinaceous material, arranged in concentric lamellae. LCs and type II GCs were mainly present in well and intermediately differentiated DCIS. Type I GCs were observed in only DCIS with necrosis, frequently being present in intermediately and poorly differentiated DCIS.

In the recent World Health Organization (WHO) classification of lung and pleural tumours [4], bronchioloalveolar carcinoma (BAC) was considered a variant of pulmonary adenocarcinoma characterised by an exclusive growth upon the wall of pre-existing alveoli (“lepidic growth”), without stromal infiltration. When these strict criteria are applied, BAC becomes a rare neoplasm. Traditionally, it is subdivided into two types: mucinous and non-mucinous, the latter being composed of type-II pneumocytes and/or Clara cells [1, 2]. We describe a nonmucinous BAC with peculiar foci of nodular growth, an apparently unreported finding in such a tumour. The patient was a 51-year-old woman, non-smoker, presenting with dry cough and malaise. A chest X-ray revealed a diffuse opacity in the lower lobe of the left lung, which did not resolve with antibiotic therapy. A total body computed tomography (CT) scan was negative for extrapulmonary lesions. An explorative thoracotomy was performed, followed by a left pneumonectomy. Two years after surgery, the patient presented with multiple opacities in the controlateral lung, not biopsied and clinically interpreted as neoplastic recurrences. Chemotherapy was therefore administered, but the patient died of disease progression 6 years after surgery. No autopsy was performed. Macroscopically, the lower lobe and the lingula showed an ill-defined area of parenchymal consolidation, 10 cm in diameter. Histologically, most of the lesion was composed of moderately atypical columnar cells, with overlapping nuclei, abundant eosinophilic cytoplasm and frequent apical snouting, growing along the alveolar wall (Fig. 1). In the material examined (ten blocks from the tumour), the underlying pulmonary architecture was always preserved, and no foci of stromal infiltration were present. Occasionally, multiple small intra-alveolar neoplastic nodules were observed, composed of cells morphologically identical to those lining the alveoli (Fig. 1). The nodules had a squamoid appearance, bearing some resemblance to the morules seen in endometrioid adenocarcinoma of the uterus or in well-differentiated foetal adenocarcinomas of the lung [3]: however, no obvious squamous differentiation was seen. The other lung parenchyma, the bronchial margin and the hilar lymph nodes were unremarkable. Immunohistochemically, cytokeratin AE1/AE3, cytokeratin 7 and thyroid transcription factor (TTF)-1 were strongly expressed in the lepidic and in the nodular component of the tumour (Fig. 1), whereas chromogranin and synaptophysin were negative. Collagen IV and laminin confirmed the endo-alveolar location of the nodules (Fig. 1). This lesion fulfils the morphologic criteria for nonmucinous BAC, being composed of neoplastic cells with an exclusive “lepidic” growth, in the absence of stromal invasion [4]. The peculiar feature of our case consists in the multiple foci of nodular growth, a finding which, to the best of our knowledge, has not been previously described in BAC. In our opinion, these foci should be considered non-invasive, based on the absence of both architectural complexity and stromal desmoplasia. It seems likely that this phenomenon represents just a A. Fornelli · A. Cancellieri Department of Pathology, Ospedale Maggiore, Bologna, Italy

thymic masses by indium-111-DTPA-D-pentetreotide scintigraphy. J Nucl Med. 1998;39:634-9. 22. Reisiene T, Bell GI. Molecular biology of somatostatin receptors. Endocr Rev. 1995;16:427-42. 23. Patel YC, Srikant CB. Subtype selectivity of peptide analogs for all five cloned human somatostatin receptors (hsstr 1-5). Endocrinolgy. 1994;135:2814-7. 24. Filosso PL, Ruffini E, Oliaro A, Papalia E, Donati G, Rena O. Long-term survival of atypical bronchial carcinoids with liver metastases, treated with octreotide. Eur J Cardiothorac Surg. 2002;21: 913-7.