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Mirko D'Onofrio

Publications and source records attributed to Mirko D'Onofrio.

At least 19 recordsLinked to original sources
PubMed2026

Intraductal Papillary Squamous Neoplasm (IPSN) of the Pancreas: Histological and Molecular Characterization of a Novel and Distinct Intraductal Cancer Precursor.

We report 6 intraductal papillary squamous neoplasms (IPSNs) of the pancreas, a rare but distinctive tumor whose biological features remain largely unknown. Five cases were investigated using an integrated approach combining histomorphological evaluation, immunohistochemistry, and multiregional molecular profiling through whole-exome DNA sequencing and whole-transcriptome RNA sequencing. Only targeted DNA sequencing was available on a sixth recently diagnosed case. Histologically, the intraductal lesions were characterized by large, confluent papillae with fibrovascular cores lined by multilayered epithelial cells with diffuse squamous differentiation. All cases harbored a concomitant invasive carcinoma. The associated invasive carcinomas consistently included a pancreatic tubular/ductal adenocarcinoma; in 5 cases, a poorly differentiated squamous cell carcinoma was also present, the proportion/features of which met the diagnostic criteria of adenosquamous carcinoma in 2 of them. Genomic analyses revealed that IPSNs and their matched invasive carcinomas shared the majority of somatic alterations, supporting a shared clonal origin for the 2 components. Activating KRAS mutations and biallelic inactivation of CDKN2A were detected in all cases. Recurrent mutations involved members of the SWI/SNF chromatin-remodeling complex and KMT2D. Additionally, FGFR1 and MYC amplifications were identified in 2 distinct cases (1 case each). Molecular alterations restricted to the invasive component involved mediators of the transforming growth factor-β signaling pathway. Transcriptomic profiling demonstrated a basal-like expression pattern in all IPSNs and squamous cell carcinomas, although in 2 cases, the matched pancreatic tubular/ductal adenocarcinoma shifted toward a classical transcriptomic subtype. In conclusion, through integrated histological assessment and multiregional molecular sequencing, we demonstrate that IPSN represents a bona fide precursor of invasive pancreatic cancer, a new addition to the intraductal neoplasms category. This study challenges the current paradigm that pancreatic squamous epithelium plays no role in the initiation of pancreatic carcinogenesis, providing the first evidence of its involvement in early tumorigenic processes and yielding immediate implications for pancreatic tumor classification and biological understanding.

Humans↗
PubMed2007

Standardize and compare contrast-enhanced ultrasonographic digital images obtained with different technologies: how to overcome the subjectivity.

OBJECTIVE: This study was conducted to compare digital images obtained with cadence contrast pulse sequencing (CPS) and coherent contrast imaging (CCI) technologies for contrast-enhanced ultrasonography (CEUS). METHODS: A CEUS study on 17 focal liver lesions was performed using CPS and CCI technologies with a second-generation contrast media. The lesion/liver ratio and conspicuity index were then calculated and compared with Adobe Photoshop 6.0. RESULTS: Lesion/liver ratio and conspicuity index using CCI ranged from 1.3 to 7.1 (mean value, 3) and 19 to 127 (mean value, 58), respectively; by using CPS, we obtained results ranging from 2 to 19.1 (mean value, 8.9) and 57 to 164 (mean value, 109.2). Lesion/liver ratio and the conspicuity index for the lesions using CPS showed significantly (p < 0.0001) superior results than those obtained using CCI. CONCLUSION: The computed analysis with standardization allows an objective evaluation of digital images of CEUS. CPS technology resulted in better lesion conspicuity compared to CCI during CEUS study on focal liver lesions.

Contrast Media↗
PubMed2006

Mass-forming pancreatitis: value of contrast-enhanced ultrasonography.

AIM: To assess the utility of contrast-enhanced ultrasonography (CEUS) with a second-generation contrast medium in the differential diagnosis between mass-forming pancreatitis and pancreatic carcinoma. METHODS: From our radio-pathology database, we retrieved all the patients affected by mass-forming pancreatitis or pancreatic carcinoma who underwent CEUS. We evaluated the results of CEUS in the study of the 173 pancreatic masses considering the possibilities of a differential diagnosis between mass-forming pancreatitis and pancreatic tumor by identifying the "parenchymographic" enhancement during the dynamic phase of CEUS, which was considered diagnostic for mass-forming pancreatitis. RESULTS: At CEUS, 94% of the mass-forming pancreatitis showed intralesional parenchymography. CEUS allowed diagnosis of mass-forming pancreatitis with sensitivity of 88.6%, specificity of 97.8%, positive predictive value of 91.2%, negative predictive value of 97.1%, and overall accuracy of 96%. CEUS significantly increased the diagnostic confidence in the differential diagnosis between mass-forming pancreatitis and pancreatic carcinoma, with receiver operating characteristic curve areas from 0.557 (P = 0.1608) for baseline US to 0.956 (P < 0.0001) for CEUS. CONCLUSION: CEUS allowed diagnosis of mass-forming pancreatitis with diagnostic accuracy of 96%. CEUS significantly increases the diagnostic confidence with respect to basal US in discerning mass-forming pancreatitis from pancreatic neoplasm.

Contrast Media↗
PubMed2006

Comparison of contrast-enhanced ultrasonography versus baseline ultrasound and contrast-enhanced computed tomography in metastatic disease of the liver: diagnostic performance and confidence.

AIM: The aim of this study was to compare contrast-enhanced ultrasonography (CEUS) to baseline US and contrast-enhanced computed tomography (CT) in metastatic disease of the liver diagnosed or suspected by US during presurgical staging or postsurgical follow-up for primary malignancies. MATERIALS AND METHODS: Two hundred-fifty-three patients considered suitable for US due to the complete explorability of the liver and with one to five proven or suspected liver metastases at baseline US were included. All patients underwent US before and after microbubble injection, and multiphase contrast-enhanced CT. Independent panels of readers reviewed US and CT scans and recorded liver metastases according to a 5-grade scale of diagnostic confidence. Sensitivity, specificity (diagnostic performance) and area under the receiver operating characteristics (ROC) curve (diagnostic confidence) were calculated. RESULTS: Reference standards revealed no metastases in 57/253, more than five in 59/253, and one to five in 137/253 patients. In patients with one to five metastases, CEUS versus baseline US revealed more metastases in 64/137 and the same number in 73/137 patients while CEUS versus CT revealed more metastases in 10/137, the same number in 99/137, and lower number in 28/137. Sensitivity, specificity, and area under ROC curve of CEUS (83%, 84%, 0.929, respectively) differed from baseline US (40%, 63%, 0.579, respectively; P<0.01) while did not differ from CT (89%, 89%, 0.945, respectively; P>0.05). CONCLUSION: CEUS improved liver metastases diagnosis in comparison with baseline US while it revealed similar diagnostic performance and confidence to contrast-enhanced CT in patients considered suitable for US and with proven or suspected liver metastases at baseline US.

Aged↗
PubMed2005

Contrast-enhanced ultrasonography better identifies pancreatic tumor vascularization than helical CT.

BACKGROUND: Contrast-enhanced ultrasonography (CEUS) is a recently introduced field of ultrasonography (US). To assess the ability of CEUS to identify the vascularization of solid pancreatic tumors in comparison to helical CT. METHODS: Forty-two resected pancreatic tumors, found at US, were studied with CEUS and helical CT. The tumor enhancement at CEUS was scored in comparison to the baseline aspect of the lesion and/or the extralesional pancreatic parenchyma together with the adjacent vessels during the dynamic study. All the lesions underwent pathological examination using H&E stains and CD34 markers with an evaluation of the microvessel density (MVD). The correlation of CEUS and helical CT with the MVD of the lesions was established with Spearman's test. RESULTS: The correlation of CEUS with the MVD of the lesions was significantly superior (Rs = 0.914; p < 0.0001) to that of helical CT (Rs = 0.635; p < 0.0001). CONCLUSIONS: CEUS is better than helical CT in the identification of the vascularization of solid pancreatic tumors. CEUS, when the pancreatic gland is optimally visualized, should be therefore considered a complementary imaging modality in the characterization of pancreatic tumors. CEUS can be a valid onco-imaging modality for quantifying tumoral vascularization in a noninvasive and accurate way.

Adenocarcinoma↗
PubMed2005

Hypoechoic focal liver lesions: characterization with contrast enhanced ultrasonography.

PURPOSE: To evaluate the late sinusoidal phase of contrast enhancement with a 2nd-generation ultrasound contrast enhanced medium in the characterization of hypoechoic focal liver lesions. METHODS: We studied 88 hypoechoic liver lesions (diameter range, 1-18 cm; with 18 lesions 2 cm or less) found on conventional grayscale sonography (US) with contrast-enhanced ultrasonography (CEUS). Final diagnosis was made using contrast enhanced helical CT, contrast enhanced MR, angiography (DSA), and/or histopathic confirmation or clinical imaging follow-up. RESULTS: There were 37/88 benign lesions demonstrated: 17 cavernous hemangiomas, 3 capillary hemangiomas, 11 focal nodular hyperplasias (FNH), 3 focal areas of sparing in hepatic steatosis, 2 adenomas, and 1 intrahepatic necrotic area. Malignant lesions demonstrated included 51/88: 27 hepatocellular carcinomas (HCC) in cirrhosis, 11 metastatic carcinomas, 10 metastatic endocrine tumors, 2 cholangiocellular carcinomas (CCC) and 1 non-Hodgkin's lymphoma (NHL). CEUS characterized 30/37 (81%) benign lesions and 45/51 (88%) malignant lesions. On the basis of the results obtained during the sinusoidal contrast enhanced phase of CEUS, diagnosis of benignancy was possible in 35/37 (95%) of benign liver lesions and diagnosis of malignancy in 49/51 (96%) of malignant liver lesions. The enhancement pattern of 13 small (< or = 2 cm in diameter) hypervascular liver lesions (3 capillary hemangiomas, 2 FNHs, 4 HCCs, 4 metastatic endocrine tumors) was better demonstrated on CEUS than on helical CT. In these cases the hyper vascularization of the lesions shown on CEUS was not confirmed on CT. CONCLUSIONS: CEUS distinguished malignant from benign hypoechoic liver lesions with an accuracy of 95%.

Angiography, Digital Subtraction↗
PubMed2005

Tumor vessel compression hinders perfusion of ultrasonographic contrast agents.

Contrast-enhanced ultrasound (CEUS) is an advanced approach to in vivo assessment of tumor vascularity and is being increasingly adopted in clinical oncology. It is based on 1- to 10 microm-sized gas microbubbles, which can cross the capillary beds of the lungs and are effective echo enhancers. It is known that high cell density, high transendothelial fluid exchange, and poorly functioning lymphatic circulation all provoke solid stress, which compresses vessels and drastically reduces tumor blood flow. Given their size, we supposed that the perfusion of microbubbles is affected by anatomic features of tumor vessels more than are contrast agents traditionally used in dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Here, we compared dynamic information obtained from CEUS and DCE-MRI on two experimental tumor models exhibiting notable differences in vessel anatomy. We found that tumors with small, flattened vessels show a much higher resistance to microbubble perfusion than to MRI contrast agents, and appear scarcely vascularized at CEUS examination, despite vessel volume adequate for normal function. Thus, whereas CEUS alone could induce incorrect diagnosis when tumors have small or collapsed vessels, integrated analysis using CEUS and DCE-MRI allows in vivo identification of tumors with a vascular profile frequently associated with malignant phenotypes.

Albumins↗
PubMed2005

Contrast-enhanced ultrasonography of small solid pseudopapillary tumors of the pancreas: enhancement pattern and pathologic correlation of 2 cases.

OBJECTIVE: The purpose of this series is to describe the value of contrast-enhanced ultrasonography (CEUS) in the characterization of small pseudopapillary tumors (SPTs) of the pancreas. METHODS: Two cases of SPTs found on conventional ultrasonography, both located at the pancreatic body, were studied with spiral computed tomography, magnetic resonance imaging, and CEUS. A final diagnosis was obtained with histologic analysis after distal pancreatectomy. Immunohistochemical analysis of the tumors with the CD34 antigen was performed. RESULTS: At CEUS, the 2 SPTs had a slight peripheral rim enhancement in the early dynamic phases. The presence of this enhancement pattern at CEUS, not clear at spiral computed tomography or at magnetic resonance imaging, suggested the diagnosis of SPTs with a peripheral pseudocapsule deriving from the compression of the pancreatic parenchyma. The presence of a perilesional pseudocapsule was proved at immunohistochemical analysis of the tumors with the CD34 antigen. CONCLUSIONS: Contrast-enhanced ultrasonography can improve the characterization of SPTs by showing the typical rim enhancement of these pancreatic tumors.

Adolescent↗
PubMed2005

Accuracy of ultrasound in the detection of liver fibrosis in chronic viral hepatitis.

PURPOSE: To assess the accuracy of ultrasonography (US) in the identification and grading of hepatic fibrosis in patients afflicted with chronic viral liver disease, compared to histological examination as a gold standard. MATERIALS AND METHODS: We prospectively studied 105 patients (32 F, 73 M) affected by chronic viral liver disease in 36 months. Patients were studied with B-mode US and then underwent US-guided liver biopsy. All the patients were studied with conventional US with a Sequoia 512, 6.0 (Acuson, Mountain View CA, USA). We evaluated the following US parameters: liver margins, parenchymal echotexture, portal vein caliber and spleen diameter. The four B-mode US parameters were used for the US grading (from 0 to 4). Scheuer's grading (from 0 to 4) was used for the histological score. Grades 3 and 4 were considered as positive for fibrosis. Sensitivity, specificity, positive and negative predictive values and accuracy were calculated in the case of absence, positivity of one or all the US parameters. The correlation between US and histological scores was evaluated with Spearman's test. RESULTS: At histology seventy-seven patients (73%) had absent grade 0 (1 patient; 1%), low-moderate grade 1 (35 patients; 33%) or grade 2 (41 patients; 39%) liver fibrosis. Twenty-eight patients (27%) had severe grade 3 (16 patients; 15%) or grade 4 (12 patients; 11%) fibrosis. In the case of absence of US parameters sensitivity was 32%, specificity 32%, positive predictive value 15%, negative predictive value 57% and accuracy 32%. In the case of positivity of at least one of the US parameters the values were 68%, 68%, 43%, 84% and 69%. In the case of presence of all the US signs the results were 25%, 100%, 100%, 79% and 80%. None of the 77 patients with a healthy liver or with low-grade fibrosis was positive for all the US parameters. All the patients positive for all of the ultrasonographic parameters had high-grade fibrosis or cirrhosis at liver biopsy. Correlation between B-mode and histological scores was not statistically significant (Rs=0.45; p=0.0001). CONCLUSIONS: US identification of liver fibrosis in chronic liver disease is possible with 25% sensitivity, 100% specificity, 100% positive predictive value and 79% negative predictive value, with an 80% diagnostic accuracy.

Biopsy, Needle↗
PubMed2004

In vivo mapping of spontaneous mammary tumors in transgenic mice using MRI and ultrasonography.

PURPOSE: To compare T1- or T2-weighted magnetic resonance imaging (MRI) and ultrasonography (US) as tools for in vivo mapping of different tissue components in spontaneous tumors of transgenic mice. MATERIALS AND METHODS: Human-like mammary adenocarcinomas from FVB/neuT transgenic mice were analyzed by T2-weighted and T1-weighted MRI at 4.7 Tesla and US and then, after excision, were paraffin-embedded for histologic analysis. The histologic samples were prepared taking care to obtain sections that spatially matched the MRI and US images as precisely as possible. RESULTS: US can obtain basic information such as the size of developing tumors in experimental animals and can identify necrotic areas. T2-weighted MRI, especially if compared to T1-weighted MRI and/or US, allows advanced analysis of morphologic aspects, with high resolution in the differentiation of details of necrotic areas such as coagulation, liquefaction, biphasic splitting of cysts, and fibrotic and lipidic infiltration. CONCLUSION: Of the three methods, T2-weighted MRI provides the most information about the anatomy of tumors. However, when distinctions between the different types of necrosis are not needed, US analysis is to be preferred for its practicality.

Animals↗
PubMed2004

Contrast-enhanced US of hepatocellular carcinoma.

PURPOSE: To evaluate the capabilities of contrast-enhanced ultrasound (CEUS) in the characterization of hepatocarcinoma (HCC) in terms of accuracy as compared to spiral CT and diagnostic gain as compared to conventional and Doppler US. MATERIALS AND METHODS: Forty-three patients with viral hepatopathy or cirrhosis diagnosed with HCC (6 histologically and 37 cytologically proven) were retrospectively studied. Between January 2002 and May 2003, all patients were evaluated with CEUS after detection of at least one suspicious nodule on US. CEUS features of HCCs were retrospectively compared with those on conventional and Doppler US, and spiral CT. RESULTS: HCCs varied between 1.2 cm and 18 cm in diameter; 14/43 were small' (< or = 2 cm). In 18/43 patients, HCC was multifocal. Doppler US revealed 24/43 hypervascular nodules. On CEUS, 37/43 (86%) showed contrast enhancement in the arterial phase, 13/37 (35%) with negative colour and power Doppler US examination; in 6/37 (16%) contrast enhancement in the arterial phase was not visible on spiral CT. On CEUS, 6/43 hypovascular HCCs were characterized as malignant in the sinusoidal phase. On CEUS, the sinusoidal phase revealed additional nodules not visible on baseline US in 3/18 multifocal HCCs. CONCLUSIONS: CEUS diagnosis of HCC in cirrhotic liver is possible with a combination of the arterial phase, which shows tumoral hypervascularity in the microcirculation, and the sinusoidal phase, which allows to confirm the malignancy of the nodule.

Aged↗
PubMed2003

Interventional radiology in the treatment of high-flow renal arteriovenous fistulas. Report of two cases.

PURPOSE: To describe the morphological and haemodynamic characteristics of high-flow idiopathic renal arteriovenous fistulas and the radiological treatment techniques. MATERIALS AND METHODS: Two cases of idiopathic renal arteriovenous fistula were treated with transcatheter embolization. In the first case, the anomalous arteriovenous communication was embolized with acrylic glue through the afferent artery while the efferent vein was temporarily occluded with a balloon catheter using the "stop flow" technique. In the second case, the fistula was occluded from the arterial side using Gianturco coils and the "free flow" technique. RESULTS: In both cases post-procedural angiography demonstrated occlusion of the fistula. A color-Doppler US examination 6 months later showed the regularization of flow parameters in the renal artery and vein. Angiographic follow-up showed occlusion of the arteriovenous fistula, regularization of the renal artery calibre and normal renal parenchymal flow. CONCLUSIONS: Embolization is the best treatment for rare, high-flow, renal arteriovenous fistulas. The "stop flow" technique with acrylic glue is fast and economical. The "free flow" technique with coils is more expensive and complex, but just as effective.

Adult↗
PubMed2002

Non-traumatic abdominal emergencies: imaging and intervention in acute pancreatic conditions.

Pancreatic emergency, unrelated to traumatic events, can occur as a consequence of the more significant pancreatic pathologies (acute and chronic pancreatitis, tumors) or of the interventional or surgical treatment carried out as therapy for the above-mentioned lesions. Acute pancreatic conditions are represented by pancreatic infections, the involvement of organs, structures, and adjacent spaces within the pancreatic disease, and, lastly, vascular complications. Acute pancreatic conditions are common in pancreatic diseases and can be catastrophic; even if there is a gamut in the severity of clinical presentation, each can be potentially life threatening. Immediate radiological detection of the lesions together with a correct therapeutic percutaneous radiological approach whenever an interventional procedure is preferable to surgery or, when performed before surgery, whenever it can optimize its results, is of fundamental importance in the management of these patients. This article focuses on the essential role of radiology and the integration of imaging and intervention in acute pancreatic conditions.

Acute Disease↗
PubMed2002

Gastroduodenal artery stump haemorrhage following pylorus-sparing Whipple procedure: treatment with covered stents.

BACKGROUND/AIMS: To report a case of bleeding after pancreatoduodenectomy in a patient with pancreatic leak and portal thrombosis who was successfully treated with an endovascular approach. METHODS: A 58-year-old male, suffering from neoplasm of the distal bile duct, underwent a pylorus-preserving Whipple procedure. On the 18th day, following a sudden drop in pressure and low haematocrit values, the patient underwent surgery. The source of the bleeding was not found. Six days later, following the appearance of bleeding from the abdominal drainage and haematemesis with shock, the patient had an immediate angiography. Bleeding from the gastroduodenal artery stump was evident, the portography showed no portal flow. With respect to the shortness of the stump, safe embolisation with coils, while preserving the common hepatic artery patency, was difficult to obtain. RESULTS: By transcatheter placement of covered stents into the hepatic artery and thereby occluding the origin of the gastroduodenal artery, the bleeding was stopped. After 2 months, CT angiography showed patency of both the common and proper hepatic arteries. Nine months after the procedure the patient is in good health. CONCLUSIONS: Percutaneous placement of covered stents can be the solution in cases where transcatheter embolisation is not recommendable because of portal vein thrombosis.

Angiography↗