Imaging of combined hepatocellular-cholangiocarcinoma in cirrhosis and risk of false diagnosis of hepatocellular carcinoma.

Background: Diagnosis of hepatocellular carcinoma can be achieved by imaging in cirrhotic patients. Combined hepatocellular-cholangiocarcinoma is a primary liver tumor and its imaging patterns have been poorly investigated. Misdiagnosis for either hepatocellular carcinoma or benign lesions can occur. We aimed to evaluate the enhancement pattern of combined hepatocellular-cholangiocarcinoma in cirrhosis with imaging techniques and to estimate the risk of misdiagnosis for hepatocellular carcinoma. Methods: All histology-confirmed combined hepatocellular-cholangiocarcinoma in cirrhosis seen in two Italian centers between 2003 and 2016, in which at least one imaging technique had been performed, was retrospectively collected. The enhancement pattern was analyzed for all available imaging modalities. Results: A total of 37 combined hepatocellular-cholangiocarcinoma nodules were identified. Contrast-enhanced ultrasound, computed tomography, and magnetic resonance imaging had been performed in 27, 34, and 17 nodules, respectively. Contrast-enhanced ultrasound was at higher risk of misdiagnosis for pure hepatocellular carcinoma than computed tomography (p = 0.005) or magnetic resonance imaging (p = 0.040). Only six of 24 combined hepatocellular-cholangiocarcinoma lesions submitted to both contrast-enhanced ultrasound and computed tomography showed coincident patterns; contrast-enhanced ultrasound correctly suggested a condition of malignancy in a higher number of cases than computed tomography (p < 0.001) and magnetic resonance imaging (p = 0.002). Conclusions: Contrast-enhanced ultrasound misdiagnosed a higher number of combined hepatocellular-cholangiocarcinoma as hepatocellular carcinoma than computed tomography and magnetic resonance imaging. However, the latter techniques were able to identify features of malignancy less often.

Widen NomoGram for multinomial logistic regression: an application to staging liver fibrosis in chronic hepatitis C patients.

The interpretation of regression models results can often benefit from the generation of nomograms, 'user friendly' graphical devices especially useful for assisting the decision-making processes. However, in the case of multinomial regression models, whenever categorical responses with more than two classes are involved, nomograms cannot be drawn in the conventional way. Such a difficulty in managing and interpreting the outcome could often result in a limitation of the use of multinomial regression in decision-making support. In the present paper, we illustrate the derivation of a non-conventional nomogram for multinomial regression models, intended to overcome this issue. Although it may appear less straightforward at first sight, the proposed methodology allows an easy interpretation of the results of multinomial regression models and makes them more accessible for clinicians and general practitioners too. Development of prediction model based on multinomial logistic regression and of the pertinent graphical tool is illustrated by means of an example involving the prediction of the extent of liver fibrosis in hepatitis C patients by routinely available markers.

Fournier's gangrene: Clinical case and review of the literature.

Fournier's gangrene is a life-threatening acute necrotizing fasciitis of perianal,genitourinary and perineal areas. Nowadays, is well known that Fournier gangrene is almost never an idiopathic disease. In this article we report a case of a 70-year-old patient that initially was not treated properly. The gold standard therapy of the Fournier's gangrene remains today a complete, early and extended surgical debridement.

Ex vivo pulmonary nodule detection with miniaturized ultrasound convex probes.

BACKGROUND: The intraoperative localization of small and deep pulmonary nodules is often difficult during minimally invasive thoracic surgery. We compared the performance of three miniaturized ultrasound (US) convex probes, one of which is currently used for thoracic endoscopic diagnostic procedures, for the detection of lung nodules in an ex vivo lung perfusion model. METHODS: Three porcine cardiopulmonary blocks were perfused, preserved at 4°C for 6 h and reconditioned. Lungs were randomly seeded with different patterns of echogenicity target nodules (9 water balls, 10 fat, and 11 muscles; total n = 30). Three micro-convex US probes were assessed in an open setting on the pleural surface: PROBE 1, endobronchial US 5-10 MHz; PROBE 2, laparoscopic 4-13 MHz; PROBE 3, fingertip micro-convex probe 5-10 MHz. US probes were evaluated regarding the number of nodules localized/not localized, the correlation between US and open specimen measurements, and imaging quality. RESULTS: For detecting target nodules, the sensitivity was 100% for PROBE 1, 86.6% for PROBE 2, and 78.1% for PROBE 3. A closer correlation between US and open specimen measurements of target diameter (r = 0.87; P = 0.0001) and intrapulmonary depth (r = 0.97; P = 0.0001) was calculated for PROBE 1 than for PROBES 2 and 3. The imaging quality was significantly higher for PROBE 1 than for PROBES 2 and 3 (P < 0.04). CONCLUSIONS: US examination with micro-convex probes to detect pulmonary nodules is feasible in an ex vivo lung perfusion model. PROBE 1 achieved the best performance. Clinical research with the endobronchial US micro-convex probe during minimally invasive thoracic surgery is advisable.

Contrast-enhanced ultrasonography to diagnose complicated acute cholecystitis.

Gangrenous cholecystitis and perforation are severe complications of acute cholecystitis, which have a challenging preoperative diagnosis. Early identification allows better surgical management. Contrast-enhanced computed tomography (ceCT) is the current diagnostic gold standard. Contrast-enhanced ultrasonography (CEUS) is a promising tool for the diagnosis of gallbladder perforation, but data from the literature concerning efficacy are sparse. The aim of the study was to evaluate CEUS findings in pathologically proven complicated cholecystitis (gangrenous, perforated gallbladder, pericholecystic abscess). A total of 8 patients submitted to preoperative CEUS, and with subsequent proven acute complicated cholecystitis at surgical inspection and pathological analysis, were retrospectively identified. The final diagnosis was gangrenous/phlegmonous cholecystitis (n. 2), phlegmonous/ulcerative changes plus pericholecystic abscess (n. 2), perforated plus pericholecystic abscess (n. 3), or perforated plus pericholecystic biliary collection (n. 1). Conventional US findings revealed irregularly thickened gallbladder walls in all 8 patients, with vaguely defined walls in 7 patients, four of whom also had striated wall thickening. CEUS revealed irregular enhancing gallbladder walls in all patients. A distinct wall defect was seen in six patients, confirmed as gangrenous/phlegmonous cholecystitis at pathology in all six, and in four as perforation at macroscopic surgical inspection. CEUS is a non-invasive easily repeatable technique that can be performed at the bedside, and is able to accurately diagnose complicated/perforated cholecystitis. Despite the limited sample size in the present case series, CEUS appears as a promising tool for the management of patients with the clinical possibility of having an acute complicated cholecystitis.

Development and validation of a nomogram based on clinical factors and standard laboratory tests for prediction of clinically significant liver fibrosis in chronic hepatitis C virus infection.

OBJECTIVES: Staging liver fibrosis in chronic viral hepatitis C (HCV) patients is essential for prompting surveillance and treatment. The aim of this study was to develop a nomogram, on the basis of simple clinical and laboratory variables, to predict three clinically significant stages of fibrosis (nil-mild, moderate, advanced/cirrhosis), using histology as reference, and to compare its performance with that of FibroTest, a widely used noninvasive fibrosis score. MATERIALS AND METHODS: Nomograms are graphical representations of a mathematical formula, used as predictive tools. The study retrospectively recruited 406 HCV patients undergoing liver biopsy. Nomogram was developed in a training set of 252 patients and tested in a validation set of 154 patients. Histology was staged according to the Metavir system. Fibrosis stages were subgrouped as follows: advanced fibrosis/cirrhosis (F3/F4, 24%), nil-mild (F0/F1, 36%), and moderate (F2, 40%). Age at biopsy, aspartate aminotransferase, γ-glutamyl transpeptidase, albumin, platelet count, and prothrombin activity formed the basis for the so-called Fibro-Nomogram, which, in one graphical representation, estimates probability for different stages of fibrosis. RESULTS: Areas under the receiver-operating characteristic curves for advanced fibrosis/cirrhosis were similar for training (0.86) and validation sets (0.87). For nil-mild fibrosis, area under the receiver-operating characteristics were 0.81 and 0.79. Compared with FibroTest, Fibro-Nomogram performed slightly better at predicting severe fibrosis (F3/F4) with positive likelihood ratio (LR+) 5.07 (95% confidence interval 3.08-8.37) versus LR+ 3.82 (95% confidence interval 2.56-5.71) for FibroTest. For nil-mild fibrosis, the two tests showed limited but comparable performances. CONCLUSION: In HCV patients, Fibro-Nomogram, an inexpensive and readily available predictive tool, could enable clinicians to interpret patients' profile, concurrently stratifying patients into three clinically relevant probability categories with good overall performance.

Quantification of enhancement of focal liver lesions during contrast-enhanced ultrasound (CEUS). Analysis of ten selected frames is more simple but as reliable as the analysis of the entire loop for most parameters.

The aim of the study was to evaluate the reliability of the analysis of only 10 frames rather than of a whole clip in performing quantitative assessment of tumor enhancement of focal liver lesions (FLLs) following ultrasound contrast injection. Contrast-enhanced ultrasonography (CEUS) examinations of 31 FLLs (median diameter: 30mm) were performed. All clips were analyzed and quantified with an early prototype of the SonoLiver software (TomTec GmbH, Munich and Bracco Research SA, Geneva), first evaluating the entire clip then selecting only 10 frames at different time intervals. Enhancement measurements obtained from the analysis of the entire clip or of only 10 frames were closely correlated (r=0.931 and p<0.0001 for Area Under the Curve; r=0.944 and p<0.0001 for Perfusion Index). In conclusion, enhancement quantification of FLLs can be reliably obtained from only 10 frames, rather than the entire clip, at least for most parameters, making such procedure easier for potential routine use.

Criteria for diagnosing benign portal vein thrombosis in the assessment of patients with cirrhosis and hepatocellular carcinoma for liver transplantation.

Malignant portal vein thrombosis is a contraindication for liver transplantation. Patients with cirrhosis and early hepatocellular carcinoma (HCC) may have either malignant or benign (fibrin clot) portal vein thrombosis. The aim of this study was to assess prospectively whether well-defined diagnostic criteria would enable the nature of portal vein thrombosis to be established in patients with HCC under consideration for liver transplantation. Benign portal vein thrombosis was diagnosed by the application of the following criteria: lack of vascularization of the thrombus on contrast-enhanced ultrasound and on computed tomography or magnetic resonance imaging, absence of mass-forming features of the thrombus, absence of disruption of the walls of veins, and, if uncertainty persisted, biopsy of the thrombus for histological examination. Patients who did not fulfill the criteria for benign thrombosis were not placed on the transplantation list. In this study, all patients evaluated at our center during 2001-2007 with a diagnosis of HCC in whom portal vein thrombosis was concurrently or subsequently diagnosed were discussed by a multidisciplinary group to determine their suitability for liver transplantation. The outcomes for 33 patients who met the entry criteria of the study were as follows: in 14 patients who were placed on the transplantation list and underwent liver transplantation, no malignant thrombosis was detected when liver explants were examined histologically; 5 patients who were placed on the transplantation list either remained on the list or died from causes unrelated to HCC; in 9 patients, liver transplantation was contraindicated on account of a strong suspicion, or confirmation, of the presence of malignant portal vein thrombosis; and 5 patients who were initially placed on the transplantation list were subsequently removed from it on account of progression of HCC in the absence of evidence of neoplastic involvement of thrombosis. In conclusion, for a patient with HCC and portal vein thrombosis, appropriate investigations can establish whether the thrombosis is benign; patients with HCC and benign portal vein thrombosis are candidates for liver transplantation.

Characterization of focal liver lesions with contrast-enhanced ultrasound.

The introduction of second generation microbubble ultrasound (US) contrast agents, such as SonoVue (Bracco, Milan, Italy), has considerably improved the diagnostic yield of US imaging for the evaluation of focal hepatic lesions in recent years because of its ability to very sensitively depict tumoral vascularity. In addition, contrast-enhanced US (CEUS) has the advantage of the absence of ionizing radiation, the widespread availability, even at the bedside, and the possibility to characterize a lesion as soon as detected on conventional B-mode US, commonly used as the first technique for exploration of the liver. The present review focuses on the basic principles of the technique and the various patterns of benign and malignant hepatic lesions at CEUS, contributing to their characterization. Understanding of these enhancement features at CEUS according to the type of tumors enables to make more accurate characterization of focal liver lesions as well as give better advice to oncologists, hepatologists or other clinicians in case of suspected liver tumors.

Malignancies in primary biliary cirrhosis.

(Table is included in full-text article.)PBC in the advanced stage, corresponding to PBC stage IV, was shown in the past to be associated with an increased incidence of hepatocellular carcinoma (HCC). There is currently a debate, about the increase in incidence of extrahepatic malignancies, as some, but not all studies reported these neoplasms to be more common, especially breast cancer, irrespective of the PBC disease stage. In this issue of the journal a case series is reported on the incidence of various malignancies in a cohort of 212 patients with PBC from Greece. Considering as reference the cancer registries of another Mediterranean Country, like Italy, we could suggest that the incidence of extrahepatic malignancy, breast included, is not increased in PBC patients. Indeed, a more accurate analysis of the literature, shows that higher incidence of breast cancer were reported only for PBC patients evaluated in the 1970s and early 1980s, for whom a contribution of immunosuppressive agents, largely under investigation at that time, could be speculated. PBC patients do not need, therefore, to be submitted to stricter surveillance programs for extrahepatic cancer than the general population. As far as the development of HCC is concerned, instead, PBC patients should undergo the usual surveillance reserved to other categories of cirrhotic patients, according to published guidelines for the management of HCC. Such surveillance should start only when PBC patients have reached disease stage IV (frank cirrhosis).