G Zamboni

Ultrasonography of the pancreas. 4. Contrast-enhanced imaging

The introduction of contrast-enhanced ultrasonography (CEUS) has lead to great developments in the diagnostic capabilities of ultrasound. Second generation contrast media, characterized by harmonic responses at low mechanical index of the ultrasound beam, have already proven usefulness in the study of the liver but other abdominal organs can take advantage from the dynamic study during continuous ultrasonographic scans. The dynamic observation of the enhancement allows the perfect evaluation of the abdominal organs perfusion. The perfusion of the pancreas is well correlated to the semeiology of the gland parenchymography at CEUS. The study of the pancreas is a new and promising application of CEUS. CEUS can be used to better identify pancreatic lesions respect to conventional Ultrasound (US) or to characterize pancreatic lesions already visible at US. Moreover the staging of some pancreatic lesions can be improved by the use of contrast media. This article will review the clinical application of CEUS in the different pancreatic pathologies.

Histopathological diagnosis of pancreatic intraepithelial neoplasia and intraductal papillary-mucinous neoplasms: interobserver agreement.

Objectives: The goal of this study was to evaluate the consistency of distinction between pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary-mucinous neoplasms (IPMN) and the hypothesis that guidelines for their distinction might be inadequate. Methods: A group of 93 pancreas specimens from surgical resections or autopsies that contained lesions consistent with histopathological diagnoses of PanIN-1A, PanIN-1B, PanIN-2, or IPMN (adenoma or borderline) was collected. The classification of these neoplasms by 6 pathologists, 2 from Europe, 2 from Japan, and 2 from the United States, was compared. The pathologists initially used guidelines current in their practice and then reviewed 47 of the 93 specimens a second time using new consensus definitions and guidelines for PanIN and IPMN that were developed in 2003. Results: The initial comparison showed frequent disagreement regarding both category and grade of the lesions. Agreement was greater for category than grade. In the second review, agreement among the 6 reviewers improved, remaining higher for category, although disagreements persisted for both category and grade. Conclusions: We conclude that the new definitions of PanIN and IPMN improve the consistency in classifying these lesions, but additional work is needed to further improve the reproducibility of their classification.

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.

Pancreatic multicenter ultrasound study (PAMUS)

AIM To describe the typical CEUS pattern of pancreatic lesions and to evaluate the diagnostic accuracy of Contrast-enhanced ultrasound (CEUS) in their characterization. MATERIALS AND METHODS All US and CEUS examinations of focal pancreatic masses performed in six centers during a period of five years were reviewed. Inclusion criteria were: focal pancreatic mass pathologically proved, visible at ultrasound (US) and studied with CEUS. All lesions were then evaluated for size, aspect and enhancement pattern. Sensitivity, specificity, positive and negative predictive values with 95% CIs were calculated to define diagnostic accuracy of CEUS in respect to pathology. Diagnostic confidence of US and CEUS, discerning between benign and malignant lesions, were represented by using ROC (receiver operating characteristics) curves. Agreement was evaluated by means of k statistics. RESULTS 1439 pancreatic lesions were included. At CEUS the lesions were divided into solid (89%) and cystic (12%) masses and classified into six and eight categories, respectively. Among the solid lesions, adenocarcinomas were characterized with an accuracy of 87.8%. Among the cystic lesions, cystic tumors were diagnosed with an accuracy of 97.1%. ROC curve area increased from 0.637 for US to 0.877 for CEUS (p<0.0001). Inter-observer agreement was slightly higher for solid (k=0.78) than cystic (k=0.62) lesions. In none of the centers side effects were reported. CONCLUSION CEUS is accurate in the characterization of pancreatic lesions. CEUS should be considered as a complementary imaging method for pancreatic lesions characterization.

Contrast-enhanced sonography of nonfunctioning pancreatic neuroendocrine tumors.

OBJECTIVE Diagnosis of malignancy and prognostic assessment continue to be problems in the management of nonfunctioning pancreatic endocrine tumors. Histologic examination is the reference standard. The aim of our study was to compare B-mode and contrast-enhanced sonographic findings regarding nonfunctioning pancreatic endocrine tumors. Signs of malignancy, such as Ki67 index and presence of hepatic metastasis, were considered. MATERIALS AND METHODS We retrospectively reviewed the cases of 38 consecutively registered patients with nonfunctioning pancreatic endocrine tumors evaluated with B-mode and contrast-enhanced sonography and resected. At contrast-enhanced sonography all lesions were divided into hypovascular lesions and isovascular or hypervascular lesions. On the basis of homogeneity of enhancement, lesions were classified as homogeneous and inhomogeneous. During the late phase of contrast enhancement, all solid focal hypoechoic liver lesions detected at contrast-enhanced sonography were considered hepatic metastatic lesions. Among pathologic data, grading, mitotic index, and Ki67 index were evaluated. Spearmans test was used to compare contrast-enhanced sonographic enhancement pattern with pathologic grade. RESULTS In the arterial phase, 24 of 38 nonfunctioning pancreatic endocrine tumors (63.1%) were hypervascular, seven (18.4%) were isovascular, and seven (18.4%) were hypovascular. Positive correlation was found between contrast-enhanced sonographic findings and Ki67 index (r(s) = 0.62; p < 0.0001). The difference between contrast-enhanced and B-mode sonography in the diagnosis of nonfunctioning pancreatic endocrine tumors was statistically significant (p < 0.05). Use of contrast-enhanced sonography increased diagnostic confidence in the detection of hepatic metastasis. The areas under the receiver operating characteristic curves were 0.916 for B-mode sonography and 1.000 for contrast-enhanced sonography (p < 0.05). There was moderate positive correlation between contrast-enhanced sonographic enhancement pattern and the presence of hepatic metastasis at diagnosis (r(s) = 0.46; p = 0.004) and between Ki67 index and the presence of hepatic metastasis (r(s) = 0.48; p = 0.0022). CONCLUSION The contrast-enhanced sonographic enhancement pattern of nonfunctioning pancreatic endocrine tumors has a positive correlation with Ki67 index, which is considered the most reliable independent predictor of the presence of malignancy.

Branch duct IPMTs: value of cross-sectional imaging in the assessment of biological behavior and follow-up.

Branch duct intraductal papillary mucinous tumors (IPMTs) are increasingly being described and represent a challenge for the physician. Recent imaging modalities, especially computed tomography and magnetic resonance, allow for a correct diagnosis, but IPMTs can manifest with different degrees of cellular atypia so it is very important to be able to establish the biological behavior of the lesion. Sixty-five patients were included in this study: 29 of them underwent surgery, and the other 36 were followed with cross-sectional imaging. Among patients who underwent surgery, 11 had benign lesions and 18 had malignant lesions. Overall sensitivity, specificity, and accuracy in the diagnosis of malignancy for all the cross-sectional imaging techniques were 61%, 81%, and 69%, respectively. Among patients who were followed and had a magnetic resonance cholangiopancreatographic diagnosis of branch duct IPMT with imaging features indicative of benignity, only two showed modifications over the follow-up period. Even considering some important biases (small number of patients and relatively short follow-up), interesting conclusions can be drawn: the imaging diagnosis of malignancy can be trusted, whereas that of benignity cannot be relied upon, but if the signs of malignancy are absent, the slow growth of the lesions justifies watchful follow-up in the correct clinical setting.

Predictors of Ectopic Fat Accumulation in Liver and Pancreas in Obese Men and Women

The aim of the present study was to determine the relationship between body fat distribution, adipocytokines, inflammatory markers, fat intake and ectopic fat content of liver and pancreas in obese men and women. A total of 12 lean subjects (mean age 47.25 ± 14.88 years and mean BMI 22.85 ± 2), 38 obese subjects (18 men and 20 women) with mean age 49.1 ± 13.0 years and mean BMI 34.96 ± 4.21 kg/m2 were studied. Measurements: weight, height, BMI, waist circumference, as well as glucose, insulin, HOMA (homeostasis model assessment of insulin resistance), cholesterol, triglycerides, high‐density lipoprotein cholesterol, high sensitivity C‐reactive protein, daily energy intake, leptin, and adiponectin. Magnetic resonance was used to evaluate visceral, subcutaneous adipose tissue (SCAT) as well as liver and pancreas lipid content using in‐phase and out‐of‐phase magnetic resonance imaging (MRI) sequence. Obese subjects had significantly higher weight, waist circumference, SCAT, deep SCAT, visceral adipose tissue (VAT), liver and pancreatic lipid content than lean subjects. Obese women had significantly lower VAT, liver and pancreas lipid content regardless of same BMI. In multiple regression analyses, the variance of liver lipid content explained by gender and VAT was 46%. When HOMA was added into a multiple regression, a small increase in the proportion of variance explained was observed. A 59.2% of the variance of pancreas lipid content was explained by gender and VAT. In conclusion, obese men show higher VAT and ectopic fat deposition in liver and pancreas than obese women despite same BMI. Independent of overall adiposity, insulin resistance, adiponectin and fat intake, VAT, measured with MRI, is the main predictor of ectopic fat deposition in both liver and pancreas.

Focal liver lesions: sinusoidal phase of CEUS

Ultrasound examination is the first imaging modality for hepatic study in neoplastic and chronic liver diseases. Focal liver lesions frequently cause diagnostic problems in terms of characterization, especially when small and hypoechoic to the rest of the parenchyma. Contrast- enhanced ultrasonography (CEUS) has shown its value in the characterization of focal liver lesions. This study assessed the value of the sinusoidal phase of CEUS with a second-generation contrast agent in the characterization of focal liver lesions to distinguish benign from malignant. Two hundred hepatic lesions with suspicious features at baseline ultrasound were prospectively studied with CEUS. Sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy of the sinusoidal phase in the characterization of benign versus malignant liver lesions were evaluated. Hypoechogenicity of the focal liver lesion, during the sinusoidal phase of CEUS, allowed the diagnosis of malignancy with a sensitivity of 85%, specificity of 88%, positive predictive value of 92%, negative predictive value of 77%, and diagnostic accuracy of 86%. The diagnostic confidence in the diagnosis of malignancy significantly increased, with receiver operating characteristic curve areas from 0.536 for baseline ultrasound to 0.902 for the sinusoidal phase of CEUS.

Intrahepatic peripheral cholangiocarcinoma (IPCC): comparison between perfusion ultrasound and CT imaging

PurposeThis study was done to compare the perfusion patterns of intrahepatic peripheral cholangiocarcinoma (IPCC) on contrast-enhanced ultrasound (CEUS) and dynamic computed tomography (CT).Materials and methodsWe retrospectively reviewed 23 histologically proven cases of IPCC. All lesions were studied by CEUS with sulfur hexafluoride-filled microbubbles coated with a phospholipid capsule, and by dynamic CT. Contrast-enhancement patterns were evaluated in the arterial phase (CEUS 10–20 s after the injection; CT 25–30 s after the injection) and in the delayed phase (CEUS 120 s after the injection; CT>2–3 min after the injection).ResultsLesions were single in 18/23 cases (78%), single with nearby satellite lesions in 1/23 (4%) cases and multifocal with distant secondary lesions in 4/23 (17%) cases. Lesion diameter was 2–5 cm in 7/23 cases (30%), 5–7 cm in 13/23 cases (57%) and >7 cm in 3/23 (13%) cases. On CEUS, lesions were hypervascular in 16/23 cases (70%). On delayed-phase CEUS, 22/23 lesions (96%) were markedly hypoechoic. CT showed that the lesions were hypovascular in the arterial phase in 15/23 cases (66%) and hypervascular in 7/23 (30%) cases; one lesion (1/23; 4%) was isovascular. On delayed-phase CT, lesions were hyperdense in 17/23 cases (74%), hypodense in 5/23 (22%) cases and isodense in 1/23 (43%) cases.ConclusionsEnhancement discrepancy between delayed-phase CEUS (hypoechogenicity) and CT (hyperdensity) is common semiological findings in the study of IPCC.RiassuntoObiettivoConfrontare le caratteristiche perfusionali del colangiocarcinoma intra-epatico periferico (IPCC) in ecografia con mdc (CEUS) e TC dinamica.Materiali e metodiAnalisi retrospettiva di 23 casi di colangiocarcinoma periferico istologicamente accertati. Tutte le lesioni sono state studiate con CEUS utilizzando microbolle a base di esaflururo di zolfo ricoperte da una capsula di fosfolipidi quale mezzo di contrasto e con TC dinamica. Sono state valutate le caratteristiche della impregnazione lesionale nelle fasi arteriosa (CEUS: 10–20 s dopo l’iniezione; TC: 25–30 s dopo l’iniezione) e tardiva (CEUS: 120 s dopo l’iniezione; TC>2–3 min dopo l’iniezione).RisultatiIn 18/23 (78%) la lesione era singola, in 1/23 (4%) singola con lesioni satelliti a ridosso della lesione principale e in 4/23 (17%) multifocale con lesioni a distanza rispetto alla lesione prinicipale. Le dimensioni delle lesioni erano comprese tra 2 e 5 cm di diametro in 7/23 (30%), tra 5 e 7 cm in 13/23 (57%) e superiori a 7 cm in 3/23 (13%). La CEUS ha evidenziato ipervascolarizzazione delle lesioni in 16/23 (70%). Ventidue su 23 lesioni (96%) in fase tardiva CEUS, sono risultate marcatamente ipoecogene. La TC ha evidenziato ipovascolarizzazione delle lesioni in fase arteriosa in 15/23 (66%) ed ipervascolarizzazione in 7/23 (30%); una lesione (1/23; 4%) era isovascolarizzata. In fase tardiva TC la lesione era iperdensa in 17/23 (74%) casi, ipodensa in 5/23 (22%) e isodensa in 1/23 (43%) casi.ConclusioniIl riscontro di una discordanza di enhancement in fase tardiva tra CEUS (ipoecogenicità) e TC (iperdensità) rappresenta frequente rilievo semeiologico nello studio del colangiocarcinoma intraepatico periferico.

Resectable Pancreatic Adenocarcinoma: Is the Enhancement Pattern at Contrast-Enhanced Ultrasonography a Pre-Operative Prognostic Factor?

The aim of our study was to determine whether the enhancement pattern of pancreatic adenocarcinoma at contrast-enhanced ultrasonography (CEUS) is related to patient prognosis after resection. CEUS of 42 resected adenocarcinomas were retrospectively reviewed. Tumors were divided into two groups: group A=poorly vascularized (presence of avascular areas) or group B=well vascularized (absence of avascular areas). All lesions were resected and underwent pathological examination assessing tumor differentiation as: undifferentiated (poorly differentiated) or differentiated (moderately and well differentiated). Mean vascular density (MVD) was also evaluated. CEUS enhancement and pathology were correlated (Spearmans test). Survival was analyzed with the Kaplan-Meier method. Multivariate analysis was performed with the Cox regression model. There were 30 differentiated and 12 undifferentiated adenocarcinomas at pathology. At CEUS, 10 lesions were poorly vascularized, whereas 32 lesions were well vascularized. Positive correlation was observed between CEUS groups and tumoral differentiation (rs=0.51; p=0.001) and between CEUS and MVD (rs=0.74; p<0.0001). Median survival in patients with group A vascularization at CEUS was significantly lower than in group B (p=0.015). Cox proportional hazard model revealed the presence of poorly vascularized tumor at CEUS (p=0.0001) as a predictor of higher mortality. In conclusion, CEUS enables accurate depiction of the vascularization of adenocarcinoma, with positive correlation to histology grade and MVD.