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Multifocal fibrosing thyroiditis (MFT) is an enigmatic entity, characterized by multiple fibrotic scar-like lesions with a paucicellular fibrotic center surrounded by a cellular peripheral area with reactive-appearing follicular cell atypia and variable chronic inflammation. Although poorly recognized and likely underreported in surgical pathology, the entity is considered rare with only 65 cases to date–including the current one reported to expand on the preoperative findings of this under-recognized entity. The average age of the patients is 46.8 years (range 15–71 years), 94% are female, with female to male ratio of 15:1. Individual MFT lesions typically have a superficial location. The average number of fibrotic lesions is 15.4 (range 2–51 per MFT case). Their average size is 3.1 mm (range 0.4–15.1). MFT is a disorder of diseased thyroids, typically found postoperatively in glands removed for other reasons, such as chronic lymphocytic/Hashimoto thyroiditis (32.3%), follicular nodular disease (nodular hyperplasia) (30.1%), hyperthyroidism/diffuse hyperplasia (Graves disease) (9.2%). Intriguing is the association with papillary thyroid carcinoma–present in 38.5% of MFT cases, and particularly with sub-centimetric and multifocal papillary thyroid carcinoma, with which MFT can be confused. Cases where MFT is the only thyroid pathology (7.7%) can be preoperatively mistaken for papillary thyroid carcinoma, due to worrisome ultrasound (US) and cytologic features, both of which are here documented for the first time as a component of this article. Wider recognition of MFT and of its cytologic and ultrasound features at preoperative evaluation may reduce unnecessary thyroidectomies.

Peritoneal carcinomatosis (PC) is defined as a metastatic involvement of the peritoneum by several other primary sites and it is characterized by a marked worsening of prognosis, with limited treatment opportunities. Subsequently, PC should be ruled out before any invasive treatment is administered. A new through-the-needle micro-biopsy forceps (MF) was recently introduced that permits micro-histology cores. In this case series, we evaluated the feasibility of MF in the assessment of PC to complete patient diagnostic work-ups. Five consecutive patients referred for endoscopic ultrasound staging were sampled using MF. Sampling was feasible in all patients with a technical success of 100%. No adverse events were reported in any cases. This technique was feasible and safe with a technical success rate of 100%. It permitted sampling of peritoneal irregularity, obtained high-quality tissue fragments in all cases, and enabled an additional assessment, i.e., immunohistochemical staining.

Endoscopic ultrasound-guided tissue acquisition (EUS-TA) of solid pancreatic tumors shows optimal specificity despite fair sensitivity, with an overall suboptimal diagnostic yield. We aim to quantify the adequacy and accuracy of EUS-TA and assess predictive factors for success, focusing on the presence and degree of specimen fibrosis. All consecutive EUS-TA procedures were retrieved, and the specimens were graded for sample adequacy and fibrosis. The results were evaluated according to patients’ and tumor characteristics and the EUS-TA technique. In total, 407 patients (59% male, 70 [63–77] year old) were included; sample adequacy and diagnostic accuracy were 90.2% and 94.7%, respectively. Fibrosis was significantly more represented in tumors located in the head/uncinate process (p = 0.001). Tumor location in the head/uncinate (OR 0.37 [0.14–0.99]), number of needle passes ≥ 3 (OR 4.53 [2.22–9.28]), and the use of cell block (OR 8.82 [3.23–23.8]) were independently related to adequacy. Severe fibrosis was independently related to false negative results (OR 8.37 [2.33–30.0]). Pancreatic tumors located in the head/uncinate process showed higher fibrosis, resulting in EUS-TA with lower sample adequacy and diagnostic accuracy. We maintain that three or more needle passes and cell block should be done to increase the diagnostic yield.

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 and Objective: A new 20-gauge (G) biopsy needle with a core-trap technology has been developed with a large core size and enhanced flexibility. The aim of this multicenter study was to determine the feasibility, efficacy, and safety of EUS-guided fine-needle biopsy (EUS-FNB) with the new 20G needle in diagnosing subepithelial lesions (SELs). Materials and Methods: Retrospectively collected data from consecutive patients with SELs undergoing EUS-FNB with the 20G needle at five centers were analyzed. Results: A total of 50 SELs were included. The mean lesion size was 43.1 ± 17.5 mm. The lesion locations were esophagus (n = 1), stomach (n = 37), distal duodenum (n = 5), rectum (n = 6), and colon (n = 1). The procedure was technically feasible in all patients. Definitive diagnosis with full histological assessment including immunohistochemistry was obtained in 88% (44/50) of the patients. Considering malignant versus benign lesions, the sensitivity, specificity, positive predictive value, and negative predictive value were 85% (95% confidence interval [CI] 70.2–94.3), 100% (95% CI 58.7%–100%), 100% (95% CI 85.1%–100%), and 62.5 (95% CI 27.7–84.8), respectively. No major complications requiring additional care have been observed. Conclusions: In this multicenter study, we found that EUS-FNB with the new 20G core needle is an effective and safe method for the diagnosis of SELs with a high rate of producing adequate histological material and high diagnostic accuracy even from difficult-to-approach anatomical locations.

Background and Objective: EUS-guided fine-needle biopsy has become the standard for tissue sampling. A new 20G ProCore™ (PC) needle has been developed to overcome the limitations of tissue acquisition of the smaller needles (22G, 25G) and the rigidity of the larger one (19G). The aim of this study is to assess the performance of the 20G PC needle. Materials and Methods: Patients who underwent EUS-guided tissue acquisition with the 20G PC needle of pancreatic and extra-pancreatic mass lesions were retrospectively identified at three Italian centers (Bologna, Fermo, and Palermo). Diagnostic adequacy, accuracy, and tissue core acquisition were the outcome measures. All the cases were performed without rapid on-site evaluation. Results: A total of 384 patients with pancreatic (62.2%) and extra-pancreatic lesions were included in the study. For pancreatic lesions, adequacy, accuracy, sensitivity, and specificity were 92.4%, 91.5%, 90.8%, and 100%, respectively, with a number needed to misdiagnose (NNM) of 11.8. The tissue core was obtained in 72% of cases. Transduodenal approach was performed in 150 pancreatic lesions; adequacy, accuracy, and tissue core acquisition were 88.7%, 90%, and 66%, respectively (NNM 10). For extrapancreatic lesions, adequacy, accuracy, sensitivity, specificity, and tissue core sampling were 95.3%, 95.3%, 92.6%, 100%, and 84.5% (NNM 21.3). Conclusions: The 20G PC needle showed high diagnostic adequacy and accuracy, regardless the access route.

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.

Background A hallmark of pancreatic ductal adenocarcinoma is the desmoplastic reaction, but its impact on the tumor behavior remains controversial. Our aim was to introduce a computer -aided method to precisely quantify the amount of pancreatic collagenic extra-cellular matrix, its spatial distribution pattern, and the degradation process. Methods A series of normal, inflammatory and neoplastic pancreatic ductal adenocarcinoma formalin-fixed and paraffin-embedded Sirius red stained sections were automatically digitized and analyzed using a computer-aided method. Results We found a progressive increase of pancreatic collagenic extra-cellular matrix from normal to the inflammatory and pancreatic ductal adenocarcinoma. The two-dimensional fractal dimension showed a significant difference in the collagenic extra-cellular matrix spatial complexity between normal versus inflammatory and pancreatic ductal adenocarcinoma. A significant difference when comparing the number of cycles necessary to degrade the pancreatic collagenic extra-cellular matrix in normal versus inflammatory and pancreatic ductal adenocarcinoma was also found. The difference between inflammatory and pancreatic ductal adenocarcinoma was also significant. Furthermore, the mean velocity of collagenic extra-cellular matrix degradation was found to be faster in inflammatory and pancreatic ductal adenocarcinoma than in normal. Conclusion These findings demonstrate that inflammatory and pancreatic ductal adenocarcinomas are characterized by an increased amount of pancreatic collagenic extra-cellular matrix and by changes in their spatial complexity and degradation. Our study defines new features about the pancreatic collagenic extra-cellular matrix, and represents a basis for further investigations into the clinical behavior of pancreatic ductal adenocarcinoma and the development of therapeutic strategies.

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.

RECOMMENDATIONSFor routine EUS-guided sampling of solid masses and lymph nodes (LNs) ESGE recommends 25G or 22G needles (high quality evidence, strong recommendation); fine needle aspiration (FNA) and fine needle biopsy (FNB) needles are equally recommended (high quality evidence, strong recommendation).When the primary aim of sampling is to obtain a core tissue specimen, ESGE suggests using 19G FNA or FNB needles or 22G FNB needles (low quality evidence, weak recommendation).ESGE recommends using 10-mL syringe suction for EUS-guided sampling of solid masses and LNs with 25G or 22G FNA needles (high quality evidence, strong recommendation) and other types of needles (low quality evidence, weak recommendation). ESGE suggests neutralizing residual negative pressure in the needle before withdrawing the needle from the target lesion (moderate quality evidence, weak recommendation).ESGE does not recommend for or against using the needle stylet for EUS-guided sampling of solid masses and LNs with FNA needles (high quality evidence, strong recommendation) and suggests using the needle stylet for EUS-guided sampling with FNB needles (low quality evidence, weak recommendation).ESGE suggests fanning the needle throughout the lesion when sampling solid masses and LNs (moderate quality evidence, weak recommendation).ESGE equally recommends EUS-guided sampling with or without on-site cytologic evaluation (moderate quality evidence, strong recommendation). When on-site cytologic evaluation is unavailable, ESGE suggests performance of three to four needle passes with an FNA needle or two to three passes with an FNB needle (low quality evidence, weak recommendation).For diagnostic sampling of pancreatic cystic lesions without a solid component, ESGE suggests emptying the cyst with a single pass of a 22G or 19G needle (low quality evidence, weak recommendation). For pancreatic cystic lesions with a solid component, ESGE suggests sampling of the solid component using the same technique as in the case of other solid lesions (low quality evidence, weak recommendation).ESGE does not recommend antibiotic prophylaxis for EUS-guided sampling of solid masses or LNs (low quality evidence, strong recommendation), and suggests antibiotic prophylaxis with fluoroquinolones or beta-lactam antibiotics for EUS-guided sampling of cystic lesions (low quality evidence, weak recommendation). ESGE suggests that evaluation of tissue obtained by EUS-guided sampling should include histologic preparations (e. g., cell blocks and/or formalin-fixed and paraffin-embedded tissue fragments) and should not be limited to smear cytology (low quality evidence, weak recommendation).

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.

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.

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.Image: Signaling pathways (Figure 1), JOP. Journal of the Pancreas, Vol 15, No 2 (2014): March - p. 84-218

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.

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

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