Ipilimumab and immune-mediated adverse events: a case report of anti-CTLA4 induced ileitis.

BACKGROUND: Ipilimumab is a fully human monoclonal antibody directed against cytotoxic T-lymphocyte antigen-4 , a key negative regulator of T-cell activation approved by the Food and Drug Administration as of March 2011 for the treatment of metastatic melanoma. As a result of the up-regulation of the immune system, several immune-mediated adverse effects have been reported including colitis, dermatitis, hepatitis and rarely hypophysitis. The most frequent immune-mediated adverse effects described in literature include gastrointestinal toxicity such as diarrhea, colitis and case of colitis and ileitis. CASE PRESENTATION: In this paper we report an interesting case of immune-mediate ileitis without colitis in a 54 years old woman with metastatic melanoma treated with ipilimumab. We also discuss about case management and the possible pathological mechanisms considering also previous reports. CONCLUSIONS: The aim of this article is to support further investigations concerning epigenetic and genetic analysis in order to personalize biological therapy and to reduce immune related adverse events observed after ipilimumab administration.

Depiction of normal gastrointestinal anatomy with MDCT: comparison of low- and high-attenuation oral contrast media.

PURPOSE: To compare low- and high-attenuation oral contrast media for depiction of normal gastrointestinal anatomy with multidetector-row computed tomography (MDCT). MATERIALS AND METHODS: A prospective, randomized study of 90 consecutive patients without known or suspected gastrointestinal disease was conducted after the approval of our Institutional Review Board. All patients underwent IV contrast-enhanced abdominal and pelvic CT scans after oral administration of 900 ml of either low- or high-attenuation barium sulphate suspension. Using a five-point scale, two radiologists independently graded distention and wall visualization of stomach, duodenum, jejunum, and ileum. The degree of distention and wall visualization was compared using Mann-Whitney U-test. RESULTS: Duodenal, jejunal and ileal distention (p<0.05, <0.001, <0.001, respectively) and wall visualization (p<0.05, <0.01, <0.05, respectively) scores with low-attenuation contrast medium were significantly higher than those with high-attenuation barium sulphate preparation, for reader 1. Duodenal and jejunal wall visualization scores with low-attenuation contrast medium (p<0.05, <0.01, respectively) were significantly higher than those with high-attenuation contrast medium, for reader 2. Interobserver agreement was fair to good for both distention (kappa-range: 0.41-0.74) and wall visualization (kappa-range: 0.48-0.71). CONCLUSION: MDCT with low-attenuation contrast medium provides distention and wall visualization of the GI tract that is equal or better than high-attenuation contrast medium.

Behavior of hepatocellular adenoma on real-time low-mechanical index contrast-enhanced ultrasonography with a second-generation contrast agent.

OBJECTIVE: The purpose of this study was to describe the behavior of histologically proven hepatocellular adenoma (HCA) on low-mechanical index (MI) contrast-enhanced ultrasonography (CEUS). METHODS: A review of the databases from 4 academic hospitals revealed 18 patients (15 female and 3 male; mean age, 40 years; range, 25-71 years) with 25 histologically proven HCA lesions who were studied with CEUS at a low MI (0.04-0.1). RESULTS: Twenty-four of 25 lesions (96%; 95% confidence interval [CI], 80.5%-99.3%) showed high-intensity enhancement, scored as 3 on a scale of 0 to 3, whereas only 1 lesion (4%; 95% CI, 0.7%-19.5%) was scored as 2. The time of peak enhancement ranged between 10 and 19 seconds (average, 13 seconds). All but 1 of the 25 lesions (96%; 95% CI, 80.5%-99.3%) showed early homogeneous and centripetal enhancement during the hepatic arterial phase. No portal venous phase enhancement was observed in any lesion because all showed rapid wash-out (100%; 95% CI, 86.7%-100%). Twenty lesions (80%; 95% CI, 60.9%-91.1%) were found to be isoechoic to slightly hypoechoic during the portal phase, and 19 (76%; 95% CI, 56.6%-88.5%) were isoechoic to mildly hypoechoic, whereas 7 (24%; 95% CI, 11.5%-43.4%) were hypoechoic during the late phase. CONCLUSIONS: Contrast-enhanced ultrasonography is an effective technique for identifying the microvascular and macrovascular characteristics of HCA. Typically, HCA shows early (10-19 seconds) and centripetal enhancement during the arterial phase and isoechogenicity or mild hypoechogenicity during the portal phase, remaining slightly hypoechoic or isoechoic during the late phase in most cases.

Histologic assessment of biliary obstruction with different percutaneous endoluminal techniques.

BACKGROUND: Despite the sophisticated cross sectional image techniques currently available, a number of biliary stenosis or obstructions remain of an uncertain nature. In these pathological conditions, an "intrinsic" parietal alteration is the cause of biliary obstruction and it is very difficult to differentiate benign from malignant lesions using cross-sectional imaging procedures alone. We evaluated the efficacy of different endoluminal techniques to achieve a definitive pathological diagnosis in these situations. METHODS: Eighty patients underwent brushing, and or biopsy of the biliary tree through an existing transhepatic biliary drainage route. A subcoort of 12 patients needed balloon-dilatation of the bile duct and the material covering the balloon surface was also sent for pathological examination (balloon surface sampling). Pathological results were compared with surgical findings or with long-term clinical and instrumental follow-ups. Success rates, sensitivity, specificity, accuracy, confidential intervals, positive predictive value and negative predictive value of the three percutaneous techniques in differentiating benign from malignant disease were assessed.The agreement coefficient of biopsy and brushing with final diagnosis was calculated using the Cohen's "K" value. RESULTS: Fifty-six patients had malignant strictures confirmed by surgery, histology, and by clinical follow-ups. Success rates of brushing, balloon surface sampling, and biopsy were 90.7, 100, and 100%, respectively. The comparative efficacy of brushing, balloon-surface sampling, and biopsy resulted as follows: sensitivity of 47.8, 87.5, and 92.1%, respectively; specificity of 100% for all the techniques; accuracy of 69.2, 91.7 and 93.6%, Positive Predictive Value of 100% for all the procedures and Negative Predictive Value of 55, 80, and 75%, respectively. CONCLUSIONS: Percutaneous endoluminal biopsy is more accurate and sensitive than percutaneous bile duct brushing in the detection of malignant diseases (p < 0.01).

Contrast-enhanced sonography with SonoVue: enhancement patterns of benign focal liver lesions and correlation with dynamic gadobenate dimeglumine-enhanced MRI.

OBJECTIVE: Contrast-enhanced real-time low-mechanical-index sonography is a new diagnostic technique for the assessment of macro- and microcirculation. The purpose of our article is to describe contrast-enhancement patterns of different benign focal liver lesions using the second-generation contrast agent SonoVue and to compare these findings with those of gadobenate dimeglumine-enhanced MRI. CONCLUSION: SonoVue-enhanced real-time low-mechanical-index sonography provides specific contrast-enhancement patterns of different benign focal liver lesions, allowing accurate characterization. Findings on SonoVue-enhanced sonography correlate well with those obtained on gadobenate dimeglumine-enhanced MRI.

Contrast-enhanced US in the assessment of the ilio-caval axis in deep venous thrombosis.

PURPOSE: To assess the feasibility and the accuracy of a new technique in the evaluation of deep venous thrombosis (DVT) in the ilio-caval axis. MATERIALS AND METHODS: Thirty-eight patients with suspected DVT were prospectively examined with unenhanced and enhanced colour-Doppler ultrasonography, and ascending contrast venography. Thirty-five out of 38 patients underwent US phlebography, consisting in manual injection of Levovist (Schering Ag, Berlin, Germany) through a 21-G cannula in a suitable dorsal vein of the foot ipsilateral to the suspected DVT. Three patients in whom it was not possible to cannulate a dorsal vein of foot underwent contrast-enhanced US after injection of Levovist through an antecubital vein, but where excluded from the present study. A contrast venogram was nonetheless carried out in all out three patients for comparison with the US-phlebography findings. RESULTS: US-phlebography allowed better definition of the presence and extension of deep vein thrombosis in all patients, when compared to conventional color-Doppler US. In the evaluation of suspected acute thrombosis, the comparative efficacy of Doppler-US and US phlebography compared with ascending phlebography as the gold standard, was as follows: sensitivity of 85.7% and 90%, specificity of 71.4 and 100%, accuracy of 80.9 and 95.2%, PPV of 85.7, and 100%, and NPV of 71.4, and 75%, respectively. In the assessment of chronic thrombosis, US and US phlebography achieved a sensitivity of 90% and 100%, a specificity of 75% and 100%, an accuracy of 85.7% and 100%, a PPV of 100, 100%, a NPV of 87.5, 100%, respectively. No complications related to US phlebography were observed. CONCLUSIONS: US-phlebography is a promising tool in the assessment of deep vein thrombosis, being highly accurate and feasible. However, further studies based on larger series are mandatory to confirm our promising results and establish a standardised role for this new technique.