Publications by authors named "Erminia Manfrin"

70 Publications

EUS-GUIDED FINE-NEEDLE BIOPSY WITH OR WITHOUT RAPID ON-SITE EVALUATION FOR DIAGNOSIS OF SOLID PANCREATIC LESIONS: A RANDOMIZED CONTROLLED NON-INFERIORITY TRIAL.

Gastroenterology 2021 Jun 8. Epub 2021 Jun 8.

Second Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan.

Background And Aims: Benefit of rapid on-site evaluation (ROSE) on diagnostic accuracy of endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) has never been evaluated in a randomized study. This trial aimed to test the hypothesis that in solid pancreatic lesions (SPLs), diagnostic accuracy of EUS-FNB without ROSE was not inferior to that of EUS-FNB with ROSE.

Methods: Non-inferiority study (non-inferiority margin 5%) conducted at 14 centers in eight countries. Patients with SPLs requiring tissue sampling were randomly assigned (1:1) to undergo EUS-FNB with or without ROSE, using new generation FNB needles. The touch imprint cytology technique was used to perform ROSE. Primary endpoint was diagnostic accuracy. Secondary endpoints included safety, tissue core procurement, specimen quality, and sampling procedural time.

Results: Eight hundred patients were randomized over an 18-month period, and 771 analyzed (385 with ROSE and 386 without). Comparable diagnostic accuracies were obtained in both arms (96.4% with ROSE and 97.4% without ROSE, p=0.396). Non-inferiority of EUS-FNB without ROSE was confirmed with an absolute risk difference of 1.0% (two-sided 90% CI: -1.1% to 3.1%, p<0.001). Safety and sample quality of histological specimens were similar in both groups. A significantly higher tissue core rate was obtained by EUS-FNB without ROSE (70.7% vs. 78.0%, p=0.021), with a significantly shorter mean sampling procedural time (17.9 ± 8.8 vs. 11.7 ± 6.0 minutes, p<0.0001).

Conclusion: EUS-FNB demonstrated high diagnostic accuracy to evaluate SPLs independently on execution of ROSE. When new generation FNB needles are used, ROSE should not be routinely recommended. ClinicalTrial.gov, number NCT03322592.
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http://dx.doi.org/10.1053/j.gastro.2021.06.005DOI Listing
June 2021

CT Simplified Radiomic Approach to Assess the Metastatic Ductal Adenocarcinoma of the Pancreas.

Cancers (Basel) 2021 Apr 13;13(8). Epub 2021 Apr 13.

Unit of General and Pancreatic Surgery, The Pancreas Institute, Policlinico GB Rossi, University of Verona, 37129 Verona, Italy.

The aim of this study was to perform a simplified radiomic analysis of pancreatic ductal adenocarcinoma based on qualitative and quantitative tumor features and to compare the results between metastatic and non-metastatic patients. A search of our radiological, surgical, and pathological databases identified 1218 patients with a newly diagnosed pancreatic ductal adenocarcinoma who were referred to our Institution between January 2014 and December 2018. Computed Tomography (CT) examinations were reviewed analyzing qualitative and quantitative features. Two hundred eighty-eight patients fulfilled the inclusion criteria and were included in this study. Overall, metastases were present at diagnosis in 86/288 patients, while no metastases were identified in 202/288 patients. Ill-defined margins and a hypodense appearance on portal-phase images were significantly more common among patients with metastases compared to non-metastatic patients ( < 0.05). Metastatic tumors showed a significantly larger size and significantly lower arterial index, perfusion index, and permeability index compared to non-metastatic tumors ( < 0.05). In the management of pancreatic ductal adenocarcinoma, early detection and correct staging are key elements. The study of computerized tomography characteristics of pancreatic ductal adenocarcinoma showed substantial differences, both qualitative and quantitative, between metastatic and non-metastatic disease.
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http://dx.doi.org/10.3390/cancers13081843DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069159PMC
April 2021

Molecular and Clinical Insights in Malignant Brenner Tumor of the Testis With Liver Metastases:A Case Report.

Front Oncol 2021 12;11:663489. Epub 2021 Apr 12.

Unit of Medical Oncology and Biomolecular Therapy, Polilinico Riuniti, Foggia, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy.

Malignant Brenner Tumor (mBT) is extremely rare. Although BT are almost exclusive ovarian neoplasms, they may constitute a highly unusual tumor of the testis; in fact, only seven fully documented cases have been reported to date. Because of their rarity, the pathogenesis of these tumors has not been clarified and there is no standard therapeutic approach. We report the first case of epididymal mBT with synchronous, multiple, liver metastases and a very dramatic clinical course. Both primary tumor and metastasis were subjected to mutational analysis of 20 cancer associated genes. Primary tumor showed Tyr375Cys and His1047Arg missense mutations. Both mutations are reported as pathogenic in ClinVar database. The same mutation was present in liver metastasis. Based on these results we believe that the FGFR pathway could be an ideal candidate for personalized treatment, offering hope to a subset of patients with mBT. Personalized approach, including mutational analysis and molecular testing should be required in patients with rare tumors in order to clarify diagnosis and improve therapeutic strategies.
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http://dx.doi.org/10.3389/fonc.2021.663489DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072450PMC
April 2021

Endoscopic Ultrasound Through-the-Needle Biopsy for the Diagnosis of an Abdominal Bronchogenic Cyst.

Clin Endosc 2021 Feb 17. Epub 2021 Feb 17.

Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, Unit of General and Hepatobiliary Surgery, University of Verona Hospital Trust, University of Verona, Verona, Italy.

A 57-year-old woman with epigastric pain was diagnosed with a 6-cm abdominal cystic lesion of unclear origin on cross-sectional imaging. Endoscopic ultrasound (EUS) demonstrated a unilocular cyst located between the pancreas, gastric wall, and left adrenal gland, with a regular wall filled with dense fluid with multiple hyperechoic floating spots. A 19-G needle was used to puncture the cyst, but no fluid could be aspirated. Therefore, EUS-guided through-the-needle biopsy (EUS-TTNB) was performed. Histological analysis of the retrieved fragments revealed a fibrous wall lined by "respiratory-type" epithelium with ciliated columnar cells, consistent with the diagnosis of a bronchogenic cyst. Laparoscopic excision was performed, and the diagnosis was confirmed based on the findings of the surgical specimen. Abdominal bronchogenic cysts are extremely uncommon, and a definitive diagnosis is commonly obtained after the examination of surgical specimens due to the lack of pathognomonic findings on cross-sectional imaging and poor cellularity on EUS-guided fine-needle aspiration cytology. EUS-TTNB is useful for establishing a preoperative histological diagnosis, thus supporting the decision-making process.
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http://dx.doi.org/10.5946/ce.2020.195DOI Listing
February 2021

Dual-tracer (68Ga-DOTATOC and 18F-FDG-)-PET/CT scan and G1-G2 non-functioning pancreatic neuroendocrine tumors: A single-center retrospective evaluation of 124 non-metastatic resected cases.

Neuroendocrinology 2021 Jan 28. Epub 2021 Jan 28.

Introduction: The combined use of 68Gallium [68GA]-DOTA-peptides and 18Fluorine-fluoro-2-deoxyglucose [18F-FDG] PET/TC scans in the work-up of pancreatic neuroendocrine tumors (PanNETs) is controversial. This study aimed at assessing both tracers' capability to identify tumors and to assess its association with pathological predictors of recurrence.

Methods: Prospectively collected, preoperative, dual-tracer PET/CT scan data of G1-G2, non-metastatic, PanNETs that underwent surgery between January 2013 and October 2019 were retrospectively analyzed.

Results: The final cohort consisted of 124 cases. There was an approximately equal distribution of males and females(50.8%/49.2%), and G1 and G2 tumors(49.2%/50.8%). The disease was detected in 122(98.4%) and 64(51.6%) cases by 68Ga-DOTATOC and by 18F-FDG PET/CT scans, respectively, with a combined sensitivity of 99.2%. 18F-FDG-positive examinations found G2 tumors more often than G1 (59.4% versus 40.6%;p = 0.036), and 18F-FDG-positive PanNETs were larger than negative ones (median tumor size 32 mm, IQR 21 versus 26 mm, IQR 20;p = 0.019). The median Ki67 for 18F-FDG-positive and -negative examinations was 3(IQR 4) and 2(IQR 4), respectively, (p = 0.029). At least one pathologic predictor of recurrence was present in 74.6% of 18F-FDG-positive cases (versus 56.7%;p = 0.039), whereas this was not found when dichotomizing the PanNETs by their dimensions (≤/> 20 mm). None of the two tracers predicted nodal metastasis. ROC curve analysis showed that 18F-FDG uptake higher than 4.2 had a sensitivity of 49.2%, and specificity of 73.3% for differentiating G1 from G2 (AUC=0.624, p=0.009).

Conclusion: The complementary adoption of 68Ga-DOTATOC and 18F-FDG tracers may be valuable in the diagnostic work-up of PanNETs despite not being a game-changer for the management of PanNETs ≤ 20 mm.
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http://dx.doi.org/10.1159/000514809DOI Listing
January 2021

Comparison between EUS-guided fine-needle aspiration cytology and EUS-guided fine-needle biopsy histology for the evaluation of pancreatic neuroendocrine tumors.

Pancreatology 2021 Mar 24;21(2):443-450. Epub 2020 Dec 24.

Department of Diagnostics and Public Health, G.B. Rossi University Hospital, Verona, Italy.

Background/objectives: Studies comparing EUS-guided fine-needle aspiration (EUS-FNA) with EUS-guided fine-needle biopsy (EUS-FNB) for the evaluation of pancreatic neuroendocrine tumors (pNETs) are lacking. We aimed at comparing EUS-FNA with EUS-FNB in terms of Ki-67 proliferative index (PI) estimation capability, cellularity of the samples, and reliability of Ki-67 PI/tumor grading compared with surgical specimens.

Methods: Patients diagnosed with pNETs on EUS and/or surgical specimens were retrospectively identified. Specimens were re-evaluated to assess Ki-67 PI feasibility, sample cellularity by manual counting, and determination of Ki-67 PI value. Outcomes in the EUS-FNA and EUS-FNB groups were compared. Kendall rank test was used for Ki-67 PI correlation between EUS and surgical specimens. Subgroup analysis including small (≤20 mm), non-functioning pNETs was performed.

Results: Three-hundred samples from 292 lesions were evaluated: 69 EUS-FNA cytology and 231 EUS-FNB histology. Ki-67 PI feasibility was similar for EUS-FNA and EUS-FNB (91.3% vs. 95.7%, p = 0.15), while EUS-FNB performed significantly better in the subgroup of 179 small pNETs (88.2% vs. 96.1%, p = 0.04). Rate of poor cellulated (<500 cells) specimens was equal between EUS-FNA and EUS-FNB. A significant correlation for Ki-67 PI values between EUS and 92 correspondent surgical specimens was found in both groups, but it was stronger with EUS-FNB (tau = 0.626, p < 0.0001 vs. tau = 0.452, p = 0.031). Correct grading estimation was comparable between the two groups (p = 0.482).

Conclusion: Our study showed stronger correlation for Ki-67 values between EUS-FNB and surgical specimens, and that EUS-FNB outperformed EUS-FNA in the evaluation of small pNETs. EUS-FNB should become standard of care for grading assessment of suspected pNETs.
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http://dx.doi.org/10.1016/j.pan.2020.12.015DOI Listing
March 2021

Time to standardize through-the-needle biopsy specimen handling.

Gastrointest Endosc 2020 10;92(4):981-983

Department of Diagnostics and Public Health, G.B. Rossi University Hospital, Verona, Italy.

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http://dx.doi.org/10.1016/j.gie.2020.05.009DOI Listing
October 2020

Diagnostic yield of endoscopic ultrasound-guided tissue acquisition of solid pancreatic lesions after inconclusive percutaneous ultrasound-guided tissue acquisition.

Scand J Gastroenterol 2020 Sep 20;55(9):1108-1113. Epub 2020 Jul 20.

Digestive Endoscopy Unit, The Pancreas Institute, G.B. Rossi University Hospital, Verona, Italy.

Introduction: After a failed percutaneous ultrasound (US)-guided sampling, it is recommended that endoscopic ultrasound (EUS)-guided tissue acquisition (TA) be performed for non-resectable solid pancreatic lesions according to the European Federation of Societies for Ultrasound in Medicine and Biology. However, the diagnostic performance of EUS-guided TA in this setting is unknown.

Methods: We retrospectively analyzed the performance and safety of EUS-guided TA in patients with a previous failed percutaneous biopsy. We also evaluated the diagnostic delays between the percutaneous approach and EUS diagnosis.

Results: Over a period of 2 years, 49 patients were identified (29 males, mean age 65 years). The reasons for failure of percutaneous sampling were inadequate samples in 25 (52.1%) cases and lesions that were not visible or targetable in 24 (47.9%) cases. In one case, EUS-guided TA was not performed because of the interposition of a metallic biliary stent. No adverse events were recorded for both the percutaneous and EUS approaches. The median diagnostic delay was 12 days. Overall, the sensitivity and accuracy of EUS-guided TA were 92.7 and 93.7%, respectively. A subgroup analysis examined cases with inadequate samples obtained with the percutaneous approach, and the sensitivity and accuracy of EUS-guided TA were 85.7 and 88%, respectively.

Conclusion: EUS-guided TA is safe and accurate for the diagnosis of pancreatic lesions after a previous inconclusive percutaneous approach.
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http://dx.doi.org/10.1080/00365521.2020.1794021DOI Listing
September 2020

Response.

Gastrointest Endosc 2020 07;92(1):236-237

Department of Diagnostics and Public Health, G.B. Rossi University Hospital, Verona, Italy.

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http://dx.doi.org/10.1016/j.gie.2020.03.010DOI Listing
July 2020

Primary pancreatic lymphoma: Clinical presentation, diagnosis, treatment, and outcome.

Eur J Haematol 2020 Oct 2;105(4):468-475. Epub 2020 Jul 2.

Hematology Unit, Department of Medicine, University of Verona, Verona, Italy.

Primary pancreatic lymphoma (PPL) is a rare disease representing 0.1% of malignant lymphomas, which lacks well-defined diagnostic and therapeutic protocols.

Objectives: To describe PPL clinical, diagnostic and histological characteristics, together with therapy and outcome, in a relatively large series of patients.

Methods: The study includes 39 PPL patients, aged ≥15 years, observed from January 2005 to December 2018, in 8 Italian Institutions.

Results: The main symptoms were abdominal pain (58%) and jaundice (47%). Lactate dehydrogenase serum levels were elevated in 43% of patients. Histological specimens were mostly obtained by percutaneous (41%) or endoscopic (36%) biopsy, with diffuse large B-cell lymphoma being the most frequent (69%) histological diagnosis. Chemotherapy was administered alone in 65% of patients, with radiotherapy in 17%, or after surgery in 9%. The 2-year overall survival (OS) was 62%, the 2-year progression-free survival (PFS) 44%. Debulking surgery (with or without chemotherapy) was associated with a significant worse OS. Three (9.4%) of 32 high-grade patients experienced a central nervous system (CNS) relapse.

Conclusions: PPL is rare, often high-grade, with symptoms and localization similar to other pancreatic malignancies. Biopsy should be the preferred diagnostic method. High-grade PPL should undergo CNS prophylaxis.
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http://dx.doi.org/10.1111/ejh.13468DOI Listing
October 2020

Endoscopic ultrasound-guided fine-needle aspiration for the diagnosis and grading of pancreatic neuroendocrine tumors: a retrospective analysis of 110 cases.

Endoscopy 2020 11 4;52(11):988-994. Epub 2020 Jun 4.

General and Pancreatic Surgery Unit, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy.

Background: Data on the reliability of the Ki-67 index and grading calculations from endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of pancreatic neuroendocrine tumors (PanNETs) are controversial. We aimed to assess the accuracy of these data compared with histology.

Methods: Cytological analysis from EUS-FNA in patients with suspected PanNETs (n = 110) were compared with resection samples at a single institution. A minimum of 2000 cells were considered to be adequate for grading. Correlation and agreement between cytology and histology in grading and Ki-67 values, respectively, were investigated. Secondary outcomes included the diagnostic performance of EUS-FNA.

Results: EUS-FNA samples were adequate for PanNET diagnosis and PanNET grading in 98/110 (89.1 %) and 77/110 (70.0 %) patients, respectively; thus, 77 samples were adequate for comparing cytology vs. histology. There were 67 (62.0 %), 40 (36.4 %), and 1 (0.9 %) patients with a final diagnosis of G1, G2, and G3 tumors, respectively. EUS-FNA grading was concordant with surgical pathology in 81.8 % of patients; under- and overgrading occurred in 15.6 % and 2.6 %, respectively. The overall level of agreement for grading was moderate (Cohen's κ = 0.59, 95 % confidence interval [CI] 0.34 - 0.78). Spearman's rho for Ki-67 in tumors ≤ 20 mm and > 20 mm was strong and moderate, respectively (rho = 0.68, 95 %CI 0.47 - 0.83; rho = 0.59, 95 %CI 0.35 - 0.75). The Bland - Altman plot showed that the Ki-67 values were comparable and reproducible between the two measurements.

Conclusions: Although they were not available for a significant number of patients, grading and Ki-67 values from cytology correlated with histology moderately to strongly.
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http://dx.doi.org/10.1055/a-1180-8614DOI Listing
November 2020

Randomized trial comparing fork-tip and side-fenestrated needles for EUS-guided fine-needle biopsy of solid pancreatic lesions.

Gastrointest Endosc 2020 Sep 17;92(3):648-658.e2. Epub 2020 May 17.

Gastroenterology and Digestive Endoscopy Unit, The Pancreas Institute, Department of Medicine, G.B. Rossi University Hospital, Verona, Italy.

Background And Aims: The aim of this study was to compare the performance of EUS-guided fine-needle biopsy using fork-tip or side-fenestrated needles in patients with solid pancreatic lesions.

Methods: A randomized controlled study was conducted in a single academic center on patients who underwent sampling with fork-tip or side-fenestrated 22-gauge or 25-gauge needles. Three passes were performed, each independently evaluated by a blinded pathologist and by endosonographers for macroscopic on-site evaluation (MOSE). The primary outcome was histologic yield; secondary aims were safety, diagnostic yield, sample quality, number of needle passes required to establish a diagnosis, and reliability of MOSE.

Results: One hundred ninety-two patients were enrolled. Both 22-gauge and 25-gauge fork-tip needles retrieved significantly higher rates of histologic samples than side-fenestrated needles (P < .013). Safety and diagnostic accuracy were comparable in the 2 arms, whereas sample quality (tissue integrity and blood contamination) was significantly better in the fork-tip group (P < .0001). The median number of diagnostic passes was lower using fork-tip needles (P = .054). The agreement between MOSE and pathologic evaluation was almost perfect in the fork-tip group and fair in the side-fenestrated group.

Conclusions: Both needles showed equivalent safety and diagnostic accuracy. However, fork-tip needles provided a higher rate of extremely good-quality histologic samples and required fewer needle passes to reach a diagnosis. MOSE is a highly reliable tool when fork-tip needles are used compared with side-fenestrated needles. (Clinical trial registration number: NCT03622229.).
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http://dx.doi.org/10.1016/j.gie.2020.05.016DOI Listing
September 2020

Targeted next-generation sequencing identifies genomic abnormalities potentially driving the prognosis of early-stage invasive lobular breast carcinoma patients stratified according to a validated clinico-pathological model.

Breast 2020 Apr 27;50:56-63. Epub 2020 Jan 27.

Oncologia Medica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica Del Sacro Cuore, Roma, Italy. Electronic address:

Introduction: The clinico-pathological and molecular factors that drive the prognosis of invasive lobular breast carcinoma (ILC) are not entirely explored. In this regard, the development and validation of a prognostic model for ILC and the investigation of the distribution of molecular abnormalities (focusing on CDK4/6 alterations) according to prognosis were the aims of this study.

Patients And Methods: Two clinico-pathological multi-center data-sets of early-stage ILC patients (Training/Validation Set, TS/VS) were gathered. A 3-class model was developed according to the multivariate analysis for disease-free-survival (DFS) and externally validated. Mutational, copy number variation and transcriptomic analyses by targeted next generation sequencing (NGS) were performed (and validated with quantitative PCR) in an explorative cohort of patients with poor and good prognosis.

Results: Data from overall 773 patients (TS/VS: 491/282) were gathered. The developed model significantly discriminated low/intermediate/high risk in the TS (10-years DFS: 76.3%/67.6%/39.8%, respectively, p<0.0001) and in the VS (p<0.0001). In the explorative cohort for molecular analysis (34 patients), CDK4 gain was present exclusively in the poor prognosis group (35.0%, p = 0.03; OR 7.98, 95%CI 1.51-42.1, p = 0.014). Moreover, CDK4 and 6 overexpression showed a trend toward an association with poor prognosis (OR 2.7, 95%CI 0.4-18.1, p = 0.3; OR 3.29, 95%CI 0.56-19.25, p = 0.18).

Conclusions: A risk stratification model, able to accurately separate early-stage ILC patients' prognosis into different risk classes according to clinico-pathological variables, allowed to investigate potential biomarkers of prognosis with targeted NGS. CDK4 gain is suggested for future validation as a prognostic biomarker and a potential therapeutic opportunity in ILC patients.
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http://dx.doi.org/10.1016/j.breast.2020.01.034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7375560PMC
April 2020

Endoscopic Ultrasound Features Associated with Malignancy and Aggressiveness of Nonhypovascular Solid Pancreatic Lesions: Results from a Prospective Observational Study.

Ultraschall Med 2021 Apr 9;42(2):167-177. Epub 2019 Oct 9.

Gastroenterology and Digestive Endoscopy Unit, The Pancreas-Institute, Integrated University-Hospital of Verona, Italy.

Background And Study Aims:  On contrast-enhanced imaging studies, nonhypovascular (i. e., isovascular and hypervascular) patterns can be observed in solid pancreatic lesions (SPLs) of different nature, prognosis, and management. We aimed to identify endoscopic ultrasound (EUS) features of nonhypovascular SPLs associated with malignancy/aggressiveness. The secondary aims were EUS tissue acquisition (EUS-TA) outcome and safety in this setting of patients.

Patients And Methods:  This prospective observational study included patients with nonhypovascular SPLs detected on cross-sectional imaging and referred for EUS-TA. Lesion features (size, site, margins, echotexture, vascular pattern, and upstream dilation of the main pancreatic duct) were recorded. Malignancy/aggressiveness was determined by evidence of carcinoma at biopsy/surgical pathology, signs of aggressiveness (perineural invasion, lymphovascular invasion, and/or microscopic tumor extension/infiltration or evidence of metastatic lymph nodes) in the surgical specimen, radiologic detection of lymph nodes or distant metastases, and/or tumor growth > 5 mm/6 months. Uni- and multivariate analyses were performed to assess the primary aim.

Results:  A total of 154 patients with 161 SPLs were enrolled. 40 (24.8 %) lesions were defined as malignant/aggressive. Irregular margins and size > 20 mm were independent factors associated with malignancy/aggressiveness (p < 0.001, OR = 5.2 and p = 0.003, OR = 2.1, respectively). However, size > 20 mm was not significant in the subgroup of other-than-neuroendocrine tumor (NET) lesions. The EUS-TA accuracy was 92 %, and the rate of adverse events was 4 %.

Conclusion:  Irregular margins on EUS are associated with malignancy/aggressiveness of nonhypovascular SPLs. Size > 20 mm should be considered a malignancy-related feature only in NET patients. EUS-TA is safe and highly accurate for differential diagnosis in this group of patients.
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http://dx.doi.org/10.1055/a-1014-2766DOI Listing
April 2021

Interobserver agreement among expert pathologists on through-the-needle microforceps biopsy samples for evaluation of pancreatic cystic lesions.

Gastrointest Endosc 2019 11 16;90(5):784-792.e4. Epub 2019 Jul 16.

Pathology Unit, Azienda USL Città di Bologna, Ospedale Maggiore, Bologna, Italy.

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.
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http://dx.doi.org/10.1016/j.gie.2019.07.011DOI Listing
November 2019

Association between macroscopically visible tissue samples and diagnostic accuracy of EUS-guided through-the-needle microforceps biopsy sampling of pancreatic cystic lesions.

Gastrointest Endosc 2019 12 14;90(6):933-943. Epub 2019 May 14.

Department of Diagnostics and Public Health, G.B. Rossi University Hospital, Verona, Italy.

Background And Aims: EUS-guided through-the-needle biopsy (TTNB) sampling has been reported to improve diagnostic yield compared with cytology for the evaluation of pancreatic cystic lesions (PCLs). The number of macroscopically visible tissue samples needed to reach an adequate diagnosis is still unknown.

Methods: This is a retrospective, single-center study on consecutive patients with PCLs with risk features (cyst >3 cm, thickened wall, cyst growth during follow-up, and mural nodules) who underwent TTNB sampling. The capability of differentiating mucinous versus nonmucinous cysts, ability to obtain a cyst-lining epithelium, definition of the grade of dysplasia, and specific diagnosis of cyst histotype were evaluated for 1, 2, or 3 TTNB macroscopically visible specimens.

Results: Sixty-one patients were evaluated. A 100% histologic adequacy was reached by 2 samples (P = .05 versus 1). Compared with cytology, 1 TTNB specimen improved the possibility of defining cyst histotype (P < .0001), whereas 2 specimens increased all 4 diagnostic categories (P < .003). Two specimens also increased diagnostic yield compared with 1 sample (P < .085). The collection of a third sample did not improve the value of any diagnostic categories. A specific diagnosis was reached in 74% of patients with 2 histologic samples. The diagnostic reliability of TTNB sampling compared with surgical histology was 90%, with a 22.9% rate of adverse events.

Conclusions: Two TTNB macroscopically visible specimens reached 100% histologic adequacy and a specific diagnosis in 74% of patients. The collection of a third specimen did not add any additional information and should be avoided to possibly decrease the risk of adverse events.
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http://dx.doi.org/10.1016/j.gie.2019.05.009DOI Listing
December 2019

EUS-guided core biopsies of pancreatic solid masses using a new fork-tip needle: A multicenter prospective study.

Dig Liver Dis 2019 09 20;51(9):1275-1280. Epub 2019 Apr 20.

Digestive Endoscopy Unit, Division of Gastroenterology, Humanitas Research Hospital, Milan, Italy. Electronic address:

Background And Aim: Endoscopic ultrasound-guided sampling (EUS sampling) is a safe and effective technique. The study aim was to evaluate the presence of a histological core from pancreatic lesions using a new 25G fork-tip needle.

Methods: Observational multicenter prospective and analytical study, including consecutive patients with solid pancreatic masses referred for EUS-guided sampling. At each needle pass, the endoscopist performed macroscopic on-site evaluation (MOSE). The primary outcome was the histological core procurement rates. Secondary outcomes were the evaluation of interobserver agreement between endoscopists and pathologists, adequacy of EUS samples for the diagnosis and post-procedure adverse events.

Results: 100 patients were enrolled in 3 centers. The mean size of the lesions was 28.5 mm (SD 11.7). Final diagnoses were adenocarcinoma (68%), neuroendocrine tumor (21%), inflammatory mass/benign lesions (8.0%), and pancreatic metastasis (3.0%). The pathologists described the presence of a core in 67 samples (67.0% of patients), with poor agreement with MOSE (kappa, 0. 12; 95% CI: 0.03-0.28). The diagnostic accuracy was 93%. We observed 6% of mild adverse events.

Conclusion: The new 25-gauge core needle showed good overall adequacy and a good rate of histological specimens during EUS sampling of solid pancreatic masses, with a minimum number of passes and no major complications. Clinicaltrial.gov number, NCT02946840.
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http://dx.doi.org/10.1016/j.dld.2019.03.025DOI Listing
September 2019

Pseudo solid-appearing pancreatic serous microcystic adenomas: Histologic diagnosis with the EUS core biopsy fork-tip needle.

Endosc Ultrasound 2019 Sep-Oct;8(5):334-341

Unit of Digestive Endoscopy, The Pancreas Institute, University of Verona, Verona, Italy.

Background And Objectives: Despite rarely, serous cystic adenoma (SCA) can assume a pseudo-solid aspect mimicking other pancreatic neoplasm as neuroendocrine tumor. EUS-FNA cytology has low diagnostic accuracy due to the scant cellularity of the collected samples. Histological diagnosis is usually made after resection. Recently, end-cutting needles for EUS-fine-needle biopsy (EUS-FNB), which obtain tissue cores by penetrating the lesions, have been developed. We aimed to assess the capability of EUS-FNB with SharkCore™ needles in the preoperative diagnosis of serous cystic adenoma pseudo-solid-appearing on imaging (Sa-SCA).

Materials And Methods: Between January 2016 and January 2018, data from consecutive adult patients, who were referred for EUS-FNB of a solid pancreatic lesion and were diagnosed with having SCA, were retrieved from a single-center institutional database.

Results: Two patients were excluded because of microcystic aspect at EUS. Histological diagnosis of SCA was made by EUS-FNB in the remaining 7 patients (5 females; mean age of 62.5 years). Lesions (mean size of 19.8 mm) were hypervascular on cross-sectional imaging, slightly hyperdense magnetic resonance imaging with T2-weighted images can, and negative at Ga-somatostatin receptor positron emission tomography and fluoro-deoxyglucose positron emission tomography. EUS-FNB samples were judged adequate for a definitive diagnosis in all cases, achieving specimens suitable for histological evaluation and several ancillary stains. Histochemical positivity for periodic acid-Schiff (PAS) and PAS with diastase digestion was observed in 7/7 cases. Immunohistochemical positivity for α-inhibin (7/7), GLUT1 (6/6), MUC6 (5/5), and negativity for synaptophysin (7/7) and chromogranin A (2/2) favored SCA diagnosis.

Conclusions: In the case of preoperative workup suspected for Sa-SCA, a "forward acquiring" needle could improve the rate of preoperative histological diagnosis.
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http://dx.doi.org/10.4103/eus.eus_11_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6791108PMC
March 2019

Keratocystoma of the parotid gland is rare and requires an integrated multidisciplinary approach: Report of a case and a literature review.

Diagn Cytopathol 2019 Jun 22;47(6):614-616. Epub 2019 Feb 22.

Pathology Unit, Department of Pathology and Diagnostics, University and Hospital Trust of Verona, Verona, Italy.

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http://dx.doi.org/10.1002/dc.24161DOI Listing
June 2019

Histologic retrieval rate of a newly designed side-bevelled 20G needle for EUS-guided tissue acquisition of solid pancreatic lesions.

United European Gastroenterol J 2019 02 30;7(1):96-104. Epub 2018 Sep 30.

Gastroenterology and Digestive Endoscopy Unit, The Pancreas Institute, G.B. Rossi University Hospital, Verona, Italy.

Background: Innovative approaches to improve diagnostic yield of endoscopic ultrasound-guided tissue acquisition (EUS-TA) have focused on needle design with development of fine-needle biopsy (FNB) needles with microcore-acquisition technology. Recently, a 20-gauge (20G) antegrade-cutting-side-bevelled biopsy needle (ProCore®) was developed for EUS-TA, but data about its diagnostic performance and histological capability are scant.

Objectives: We assessed the diagnostic performance and histologic retrieval rate of a new 20G antegrade-cutting-side-bevelled biopsy needle compared with a 22G reverse-side-bevelled needle for EUS sampling of solid pancreatic lesions.

Patients And Methods: A retrospective analysis of 238 consecutively collected patients who underwent EUS-TA using a 20G or a 22G ProCore® needle, without rapid on-site evaluation (ROSE), was conducted at two centres.Sensitivity, specificity, positive predictive value and negative predictive value were calculated. Histologic tissue retrieval was evaluated applying a scoring system for each case.

Results: Sensitivity and specificity were estimated as 98.4-100% in the 20G-, and 94.9-100% in the 22G-needle groups, respectively ( > 0.99). The 20G procured more histologic-grade tissues (92.6% vs 49.5%,  < 0.0001) achieved by a lower number of passes (2.64 vs 3.44,  < 0.0001) compared to the 22G.

Conclusions: Both side-bevelled FNB needles achieved a high diagnostic sensitivity. The 20G-side-bevelled needle obtained a significantly higher microcore retrieval rate.
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http://dx.doi.org/10.1177/2050640618804443DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6374840PMC
February 2019

A Pancreatic Lymphoepithelial Cyst With Floating Balls.

Clin Gastroenterol Hepatol 2020 04 30;18(4):A32. Epub 2019 Jan 30.

Department of Diagnostics and Public Health, G.B. Rossi University Hospital, Verona, Italy.

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http://dx.doi.org/10.1016/j.cgh.2019.01.029DOI Listing
April 2020

JAK/Stat5-mediated subtype-specific lymphocyte antigen 6 complex, locus G6D (LY6G6D) expression drives mismatch repair proficient colorectal cancer.

J Exp Clin Cancer Res 2019 Jan 22;38(1):28. Epub 2019 Jan 22.

Department of Sciences and Technologies, University of Sannio, Via Port'Arsa, 1182100, Benevento, Italy.

Background: Human microsatellite-stable (MSS) colorectal cancers (CRCs) are immunologically "cold" tumour subtypes characterized by reduced immune cytotoxicity. The molecular linkages between immune-resistance and human MSS CRC is not clear.

Methods: We used transcriptome profiling, in silico analysis, immunohistochemistry, western blot, RT-qPCR and immunofluorescence staining to characterize novel CRC immune biomarkers. The effects of selective antagonists were tested by in vitro assays of long term viability and analysis of kinase active forms using anti-phospho antibodies.

Results: We identified the lymphocyte antigen 6 complex, locus G6D (LY6G6D) as significantly overexpressed (around 15-fold) in CRC when compared with its relatively low expression in other human solid tumours. LY6G6D up-regulation was predominant in MSS CRCs characterized by an enrichment of immune suppressive regulatory T-cells and a limited repertoire of PD-1/PD-L1 immune checkpoint receptors. Coexpression of LY6G6D and CD15 increases the risk of metastatic relapse in response to therapy. Both JAK-STAT5 and RAS-MEK-ERK cascades act in concert as key regulators of LY6G6D and Fucosyltransferase 4 (FUT4), which direct CD15-mediated immune-resistance. Momelotinib, an inhibitor of JAK1/JAK2, consistently abrogated the STAT5/LY6G6D axis in vitro, sensitizing MSS cancer cells with an intact JAK-STAT signaling, to efficiently respond to trametinib, a MEK inhibitor used in clinical setting. Notably, colon cancer cells can evade JAK2/JAK1-targeted therapy by a reversible shift of the RAS-MEK-ERK pathway activity, which explains the treatment failure of JAK1/2 inhibitors in refractory CRC.

Conclusions: Combined targeting of STAT5 and MAPK pathways has superior therapeutic effects on immune resistance. In addition, the new identified LY6G6D antigen is a promising molecular target for human MSS CRC.
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http://dx.doi.org/10.1186/s13046-018-1019-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6343337PMC
January 2019

Urothelial bladder carcinoma metastasizing to the eye: A systematic review and case report.

Oncol Lett 2019 Jan 15;17(1):462-467. Epub 2018 Oct 15.

Department of Diagnostics and Public Health-Section of Pathology, University and Hospital Trust of Verona, I-37134 Verona, Italy.

The eye is a rare site for disseminated malignancies; nevertheless, several tumors may metastasize to ocular structures. Few cases of urothelial and bladder cancer with eye involvement have been described in the literature thus far. The rarity of metastatic ocular localization implies an accurate differential diagnosis among the possible primary tumor sites. However, a specific diagnostic algorithm is not currently available, nor a defined therapeutic approach. Eye metastases are associated with advanced disease and poor prognosis. Physicians should be made aware of the possibility of eye involvement in patients with a past medical history of urothelial bladder cancer associated with ocular symptoms. The present case reports discusses the first documented case, to the best of our knowledge, of an urothelial bladder cancer metastasizing to the retro bulbar region that infiltrates the lacrimal gland. Furthermore, the report provides a systematic qualitative review of the current literature on eye metastases from urothelial bladder cancer using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses.
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http://dx.doi.org/10.3892/ol.2018.9579DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6313172PMC
January 2019

Diagnostic management of occult nodal lymphangioleiomyomatosis detected during pelvic cancer staging. Localized finding or systemic disease?

Sarcoidosis Vasc Diffuse Lung Dis 2019 1;36(1):33-38. Epub 2019 May 1.

Pneumology Unit, Hospital "Mater Salutis", ULSS9 Scaligera, Legnago (VR), Italy.

Background: Lymphangioleiomyomatosis (LAM) is a neoplastic disease that generally arises in the lung (pLAM) and may be associated with "Tuberous sclerosis complex" (TSC). Occasionally, LAM can arise at the extrapulmonary sites (eLAM), such as the mediastinum, the retroperitoneum or the lymph nodes. 25-30% of the patients affected by pLAM develop eLAM. In asymptomatic patients, the presence of mediastinal and retroperitoneal eLAM preceded that of pLAM by usually 1-2 years. Nevertheless, some authors reported that the nodal eLAM, detected during pelvic cancer staging, arise in patents without pLAM and/or TSC. In this paper we review the Literature of this rare condition suggesting its diagnostic management.

Results: To date, it has been reported 30 cases. The mean age at diagnosis is 55 years and around 30% of patients are postmenopausal. In only 2 cases was diagnosed a following p-LAM. One patient with endometrioid carcinoma and pelvic nodal eLAM reported germiline mutation. None case was associated with both p-LAM and TSC.

Conclusions: The retrospective probability to have p-LAM in patients with staging pelvic nodal e-LAM is 6,6% (4/30) lower than the probability to have e-LAM in patients affected by p-LAM (25-30%). In both this association is more probable sporadically than associated with TSC. The association between cancer staging pelvic nodal e-LAM and TSC is low (3%; 1/30). The p-LAM developed are asymptomatic with a behavior, regardless of hormonal status, similar to lesions diagnosed in postmenopausal although further studies are mandatory to confirm it.
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http://dx.doi.org/10.36141/svdld.v36i1.7110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7247108PMC
June 2020

Colonic Ewing Sarcoma/PNET associated with liver metastases: A systematic review and case report.

Pathol Res Pract 2019 Feb 29;215(2):387-391. Epub 2018 Nov 29.

Mater Salutis" Hospital, ULSS9, 37045 Legnago, Verona, Italy. Electronic address:

Ewing Sarcoma is a highly lethal undifferentiated tumor of bone. ES is a small round cell tumor with etiological and characteristic chromosomal translocations between TET/FET (TLS/FUS, EWSR1, and TAF15) and ETS (E26 transformation-specific) family genes. Generally, therapeutic approach for metastatic Ewing Sarcoma includes both local (surgery and radiotherapy) and systemic (chemotherapy) disease control with an overall cure rate of 20%. For extra-osseous tumors, the most common primary sites of disease are trunk, extremities, head and neck, retroperitoneum. Among other sites, Ewing Sarcoma/PNET may also rarely arise in colon and rectum. Even if colonic Ewing Sarcoma/PNET have been previously reported in 5 cases, none of those reports came from right side of the colon. In this article, we report the first case of right-sided Ewing Sarcoma with synchronous liver metastases completely responding to first line chemotherapy. Furthermore, we provide a systematic qualitative review of the current literature on adult colorectal Ewing Sarcoma using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).
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http://dx.doi.org/10.1016/j.prp.2018.11.021DOI Listing
February 2019

Touch imprint cytology on endoscopic ultrasound fine-needle biopsy provides comparable sample quality and diagnostic yield to standard endoscopic ultrasound fine-needle aspiration specimens in the evaluation of solid pancreatic lesions.

Cytopathology 2019 03 21;30(2):179-186. Epub 2018 Dec 21.

Department of Diagnostics and Public Health, G.B. Rossi University Hospital, Verona, Italy.

Objectives: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is the gold standard for the diagnosis of solid pancreatic lesions (SPLs). Cytological samples can also be obtained using touch imprint cytology (TIC) on EUS fine-needle biopsy (FNB) specimens. We aimed to compare sample quality and diagnostic yield of EUS-FNA-standard cytology (EUS-FNA-SC) to that of EUS-FNB-TIC in a series of patients with SPLs.

Methods: Thirty-two consecutive patients referred for EUS-tissue acquisition of SPLs who underwent rapid on-site evaluation of both EUS-FNA-SC and paired EUS-FNB-TIC during the same endoscopic session were retrospectively identified. Sample quality (evaluated in terms of blood contamination, presence of clots, tissue casts, cellularity, and necrosis) and diagnostic yield were compared between the techniques.

Results: The mean number of passes to reach diagnosis at rapid on-site evaluation was similar between EUS-FNA-SC and EUS-FNB-TIC (1.09 ± 0.3 vs 1.13 ± 0.34, P = .711). EUS-FNA-SC scores of sample quality were comparable to those of EUS-FNB-TIC (blood contamination, 2.47 ± 1.11 vs 2.25 ± 1.14, P = .109; clots, 1.25 ± 0.76 vs 1.19 ± 0.69, P = .624; tissue casts, 3.56 ± 0.88 vs 3.59 ± 1.09, P = .872; cellularity, 2.84 ± 1.11 vs 3.09 ± 1.09, P = .244; necrosis, 2.25 ± 1.08 vs 2.53 ± 1.02 P = .059; total score, 12.38 ± 2.88 vs 17.66 ± 2.38, P = .536). Adequacy, sensitivity and diagnostic accuracy of the two sampling techniques were equal (93.7%, 90.6% and 90.6%, respectively).

Conclusions: EUS-FNB-TIC provides comparable samples to those of EUS-FNA-SC and combines the benefits of cytology and histology for the evaluation of SPLs by employing a single needle during the same endoscopic procedure.
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http://dx.doi.org/10.1111/cyt.12662DOI Listing
March 2019

Patterns of Recurrence after Resection for Pancreatic Neuroendocrine Tumors: Who, When, and Where?

Neuroendocrinology 2019 27;108(3):161-171. Epub 2018 Nov 27.

Department of General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy.

Background/aims: Pancreatic neuroendocrine tumors (pan-NENs) represent an increasingly common indication for pancreatic resection, but there are few data regarding possible recurrence after surgery. The aim of the study was to describe the frequency, timing, and patterns of recurrence after resection for pan-NENs with consequent implications for postoperative follow-up.

Methods: We performed a retrospective analysis of pan-NENs resected between 1990 and 2015 at The Pancreas Institute, University of Verona Hospital Trust. Predictors of recurrence were assessed. Survival analysis was conducted using the Kaplan-Meier and conditional survival (CS) methods.

Results: The cohort consisted of 487 patients with a median follow-up of 71 months. Recurrence developed in 12.3%: 54 (11.1%) liver metastases, 11 (2.3%) local recurrence, 10 (2.1%) nodal recurrence, and 8 (1.6%) metastases in other organs. Thirty-one (6.4%) died due to disease recurrence. Size > 21 mm, G3 grade, nodal metastasis, and vascular infiltration were independent predictors of overall recurrence. Recurrence occurred either during the first year of follow-up (n = 9), or after 10 years (n = 4). CS analysis revealed that nonfunctioning G1 pan-NEN ≤20 mm without nodal metastasis or vascular invasion had a negligible risk of developing recurrence. In the present series, after 5 years of follow-up without developing recurrence, tumor recurrence occurred only in the form of liver metastases.

Conclusions: Recurrence of pan-NENs is rare and is predicted by tumor size, nodal metastasis, grading, and vascular invasion. Patients with G1 pan-NEN without nodal metastasis and vascular invasion may be considered cured by surgery. After 5 years without recurrence, follow-up should focus on excluding the development of liver metastases.
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http://dx.doi.org/10.1159/000495774DOI Listing
December 2019

Improvement of maternal and fetal outcomes in women with sickle cell disease treated with early prophylactic erythrocytapheresis.

Transfusion 2018 09 8;58(9):2192-2201. Epub 2018 Jul 8.

Department of Medicine, University of Verona and AOUI-Verona, Policlinico GB Rossi, Verona, Italy.

Background: The desire for pregnancy in sickle cell disease (SCD) women has become a true challenge for hematologists, requiring a multidisciplinary approach. Erythrocytapheresis (ECP) is an important therapeutic tool in SCD, but only limited data on starting time and the effects of ECP during pregnancy are available.

Study Design And Methods: This is a double-center retrospective cross-sectional study on a total of 46 single pregnancies in SCD women from January 2008 to June 2017. ECP was started at 10.7 ± 5.2 weeks of gestation, and prophylactic enoxaparin (4,000 U daily) was introduced due to the reported high prevalence of thromboembolic events in pregnant SCD women.

Results: The alloimmunization ratio was 2.1 per 1,000 and the alloimmunization rate was 5.6%. In early ECP-treated SCD women, no severe vaso-occlusive crisis, sepsis or severe infection, or preeclampsia or eclampsia were observed. We found normal umbilical arterial impedance during pregnancy, suggesting an optimal uteroplacental function in early ECP-treated SCD women. This was also supported by the improvement in newborn birthweights compared to previous studies. In our cohort, three SCD women were started later on ECP (20-25 weeks), and gestation ended with late fetal loss. Placenta pathology documented SCD-related damage and erythroblasts in placental vessels, indicating fetal hypoxia.

Conclusions: Collectively, our data generate a rationale to support a larger clinical trial of early ECP program in SCD pregnancy.
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http://dx.doi.org/10.1111/trf.14767DOI Listing
September 2018

Beyond Pancreatic Cyst Epithelium: Evidence of Ovarian-Like Stroma in EUS-Guided Through-the-Needle Micro-Forceps Biopsy Specimens.

Am J Gastroenterol 2018 07 14;113(7):1059-1060. Epub 2018 Jun 14.

Gastroenterology and Digestive Endoscopy Unit, The Pancreas Institute, Policlinico G.B. Rossi, University Hospital, Verona, Italy. Department of Diagnostics and Public Health, Policlinico G.B. Rossi, University Hospital, Verona, Italy. Unit of General and Pancreatic Surgery, The Pancreas Institute, Policlinico G.B. Rossi, University Hospital, Verona, Italy. ARC-Net Research Centre, Policlinico G.B. Rossi, University Hospital, Verona, Italy.

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http://dx.doi.org/10.1038/s41395-018-0124-6DOI Listing
July 2018

Endoscopic ultrasound-through-the-needle biopsy in pancreatic cystic lesions: A multicenter study.

Dig Endosc 2018 Nov 5;30(6):760-770. Epub 2018 Jul 5.

Digestive Endoscopy Unit, Catholic University, Rome, Italy.

Background And Aim: Tissue acquisition in pancreatic cystic lesions (PCL) is the ideal method for diagnosis and risk stratification for malignancy of these lesions. Direct sampling from the walls of PCL with different devices has shown better results than cytology from cystic fluid. We carried out a retrospective, multicenter study to evaluate the feasibility, safety, and diagnostic yield of a micro-forceps, specifically designed to be used through a 19-gauge needle after endoscopic ultrasonography (EUS)-guided puncture of PCL.

Methods: We retrospectively collected data from patients who underwent EUS-through-the-needle biopsy (EUS-TTNB) in PCL at six referral centers.

Results: The sampling procedure was carried out in 56 patients (mean age 57.5 ± 13.1 years, M:F 17:39), and was technically successful in all of them (100%; 95% confidence interval [CI], 94-100%). Adverse events occurred in 9/56 (16.1%; 95% CI, 8-28%) patients, with self-limited intracystic hemorrhage the most common (7/56, 12.5%; 95% CI, 5-24%). All adverse events were mild, and resolved without any specific intervention. Specimens were considered adequate for histological diagnosis in 47/56 (83.9%; 95% CI, 72-92%). In two of these patients, despite the histological adequacy, a diagnosis could not be reached. In two other cases, a specimen sufficient for a cytological diagnosis was obtained. Overall diagnostic yield by combining cytological and histological samples was 47/56 (83.9%; 95% CI, 72-92%).

Conclusion: EUS-TTNB with micro-forceps in PCL is feasible, safe, and has a high diagnostic yield. Future prospective studies are needed to better assess the clinical impact of EUS-TTNB on the management of PCL.
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http://dx.doi.org/10.1111/den.13197DOI Listing
November 2018