Differentiation between normal and metastatic lymph nodes in patients with skin melanoma: Preliminary findings using a DIXON-based whole-body MRI approach.

Purpose: Metastatic melanoma lymph nodes (MMLns) might be challenging to detect on MR-WBI, as both MMLns and normal lymph nodes (NLns) can show restricted water diffusion. Our purpose is to assess the potential contribution of the DIXON sequence in differentiating MMLns from NLns. Material and methods: We followed a cohort of 107 patients with stage IIIb/c and IV skin melanoma for 32 months using MR-WBI with DIXON, STIR, and DWI/ADC sequences. We compared signal intensity (SI) values of MMLns and NLns in the four series of the DIXON sequence (in/out-of-phase, fat_only, and water_only series). The fat fraction (SIfat_only/SIin) and the long:short axis ratio of MMLns were calculated. The fat fraction was also calculated in the fatty hila of NLns. Results: All MMLns (8 from 7 patients) showed SIout>SIin with a mean fat fraction of 10%. In 40 normal fatty hila (25 patients), the proportion of SIout>SIin was 100% and mean fat fraction was 89% (p<0.001 for fat fraction, Mann-Whitney U-test). In the cortex of NLns, a SIout>SIin pattern was identified in 41/113 cases from 19/40 patients. The median long:short axis ratio in MMLns was 1.13 (range 1.03-1.25). Conclusion: The combination of three features of MMLns (SIout>SIin, low-fat fraction and rounded shape) might hold promise in differentiating NLns from MMLns in patients with skin melanoma. Further research is warranted due to the small number of MMLns in our cohort.

Efficacy and safety of combination therapy with everolimus and sorafenib for recurrence of hepatocellular carcinoma after liver transplantation.

BACKGROUND: Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) is still associated with a dismal outcome. Combination therapy with everolimus (EVL) and vascular endothelial growth factor inhibitor sorafenib (SORA) is based on the role of both b-Raf and mammalian target of rapamycin/protein kinase B pathways in the pathogenesis of HCC and is being investigated in clinical practice. METHODS: This was a single-center retrospective analysis on LT recipients with unresectable HCC recurrence and undergoing combination therapy with EVL and SORA. Patients were included if they were switched to EVL+SORA at any time after surgery. Primary endpoint was overall survival (OS) after both LT and recurrence, and response to treatment based on the modified Response Evaluation Criteria in Solid Tumors (mRECIST) in the intention-to-treat (ITT) population. Secondary analysis was safety of combination therapy with EVL and SORA in the population of patients who received ≥1 dose of the study drug. RESULTS: Seven patients (100% male; median age 53 years [interquartile range (IQR) 9 years]) were considered for analysis. HCC recurrence was diagnosed at a median (IQR) interval since LT of 9 (126) months, and patients were administered EVL+SORA at a median interval since LT of 11 (126) months. Baseline immunosuppression was with tacrolimus (TAC) in 2 patients (28.6%), cyclosporine (CsA) in 2 (28.6%), and EVL monotherapy in 3 (42.8%). At a median (IQR) follow-up of 6.5 (14) months, 5 patients (71.4%) were alive, 4 of them (57.1%) with tumor progression according to the mRECIST criteria. Median (IQR) time to progression was 3.5 (12) months. Two patients died at a median (IQR) follow-up of 5 (1) months owing to tumor progression in 1 patient (14.3%) and sepsis in the other (14.3%). EVL monotherapy was achieved in 6 patients (85.7%), whereas 1patient (14.3%) could not withdraw from calcineurin inhibitor owing to acute rejection. Treatment complications were: hand-foot syndrome in 5 patients (71.4%), hypertension in 1 (14.3%), alopecia in 1 (14.3%), hypothyroidism in 1 (14.3%), diarrhea in 2 (28.6%), pruritus in 1 (14.3%), abdominal pain in 1 (14.3%), rash in 1 (14.3%), asthenia in 3 (42.8%), anorexia in 3 (42.8%), and hoarseness in 2 (28.6%). Adverse events led to temporary SORA discontinuation in 2 patients (28.6%) and to SORA dose reduction in 3 (42.8%). CONCLUSIONS: Treatment of HCC recurrence after LT with a combination regimen of EVL+ SORA is challenging because of SORA-related complications. Longer follow-up periods and larger series are needed to better capture the impact of such combination treatment on tumor progression and patient survival.

Radiofrequency thermal ablation of hepatocellular carcinoma: using contrast-enhanced harmonic power doppler sonography to assess treatment outcome.

OBJECTIVE: We evaluated the accuracy of contrast-enhanced harmonic power Doppler sonography in assessing the outcome of radiofrequency thermal ablation of hepatocellular carcinoma. SUBJECTS AND METHODS: Fifty patients with 65 hepatocellular carcinoma nodules (1-5 cm in diameter; mean diameter, 2.5 cm) were studied using unenhanced and contrast-enhanced harmonic power Doppler sonography before and after IV administration of a microbubble contrast agent. The examinations were repeated after treatment of the tumors with radiofrequency ablation. Findings of the Doppler studies were compared with those of dual-phase helical CT, which were used as points of reference for assessing treatment outcome. RESULTS: Before radiofrequency treatment, intratumoral blood flow was revealed by unenhanced power Doppler sonography in 48 (74%) of 65 hepatocellular carcinoma nodules. After injection of the contrast agent, intratumoral enhancement was observed in 61 (94%) of 65 hepatocellular carcinomas (p < 0.01). After radiofrequency treatment, all 51 (84%) of the 61 hepatocellular carcinomas found to be necrotic on helical CT scans failed to show enhancement on power Doppler sonograms. In nine of the 10 lesions that showed a residual viable tumor on helical CT scans, persistent intratumoral enhancement-matching the enhancing areas on helical CT images-was revealed by power Doppler sonography. These nine hepatocellular carcinomas were subjected to repeated radiofrequency thermal ablation with the guidance of contrast-enhanced power Doppler sonography. Complete necrosis was seen after the second treatment session in six of the nine lesions. CONCLUSION: Contrast-enhanced harmonic power Doppler sonography is an accurate technique for assessing the outcome of radiofrequency thermal ablation of hepatocellular carcinoma and may be useful in guiding additional treatment in patients with incomplete response to initial efforts.

Focal liver lesions: MR imaging-pathologic correlation.

Magnetic resonance signal intensity of focal liver lesions is affected by numerous pathologic factors. Lesion histologic features, such as cellularity, vascularity, stromal component, and intratumoral necrosis or hemorrhage, strongly affect T1 and T2 relaxation times. Additionally, intracellular content of certain substances, such as glycogen, fat, melanin, iron, and copper, may also have a substantial role in determining MR signal behavior. In this review we discuss the correlations between MR imaging features and pathologic findings in benign and malignant focal liver lesions. Knowledge of imaging-pathology correlations greatly assist in charac terizing focal lesions. Moreover, in certain tumor histotypes, such as hepatocellular carcinoma, careful analysis of lesion signal intensity may help predict the degree of tumor differentiation.

Percutaneous ablation of liver malignancies: imaging evaluation of treatment response.

Interventional procedures for percutaneous tumor ablation have gained an increasingly important role in the treatment of liver malignancies. After interventional therapies, diagnostic imaging has the key role to determine if the treated lesion is completely ablated or contains areas of residual viable neoplastic tissue. This is particularly important since in cases of incomplete necrosis of the lesions, treatment can be repeated, and tumor ablation can be further pursued. The evaluation of the therapeutic effect of the procedure arises different problems according to the histotype of the malignancy. In the case of hepatocellular carcinoma (HCC), detection of residual viable tumor is facilitated by the typical hypervascular pattern of this neoplasm. Contrast-enhanced US can be used to monitor tumor response, and, in cases of partial necrosis, to target the areas of residual viable tumor. With spiral CT or dynamic MR imaging, residual viable HCC is reliably depicted as it stands out in the arterial phase images against the unenhanced areas of coagulation necrosis. In the case of hypovascular metastases, a confident diagnosis of successfull ablation can be made when an area of thermal necrosis exceeding that of the original lesion is depicted. Peripheral inflammatory reaction following ablation procedures, that shows itself as an enhancing halo along the necrotic area boundary on spiral CT or dynamic MR images, should not be misinterpreted as tumor progression.

Assessment of therapeutic effect of liver tumor ablation procedures.

Interventional procedures for percutaneous tumor ablation have gained an increasingly important role in the treatment of liver malignancies. After interventional therapies, diagnostic imaging has the key role in determining if the treated lesion is completely ablated or contains areas of residual viable neoplastic tissue. This is particularly important since in case of incomplete necrosis of the lesion, treatment can be repeated, and tumor ablation can be further pursued. The evaluation of the therapeutic effect of the procedure leads to different problems according to the histotype of the malignancy. In the case of hepatocellular carcinoma, detection of residual viable tumor is facilitated by the typical hypervascular pattern of this neoplasm. Contrast-enhanced color Doppler ultrasonography can be used to monitor tumor response, and, in case of partial necrosis, to target the areas of residual viable tumor. With spiral computed tomography or dynamic magnetic resonance imaging, residual viable hepatocellular carcinoma tissue is reliably depicted as it stands out in the arterial phase images against the unenhanced areas of coagulation necrosis. In the case of hypovascular metastases, a confident diagnosis of successful ablation can be made when an area of thermal necrosis exceeding that of the original lesion is depicted. Peripheral inflammatory reaction following ablation procedures should not be misinterpreted as tumor progression.

Combination of interventional therapies in hepatocellular carcinoma.

Many interventional techniques aimed at achieving nonsurgical ablation of hepatocellular carcinoma have been developed and clinically tested over the last decade. Percutaneous image-guided therapies such as ethanol injection and radiofrequency thermal ablation provide an effective means for treating hepatocellular carcinoma lesions smaller than 3 cm, but do not ensure successful ablation of larger tumors. In view of the limitations of available interventional therapies, there is currently a focus on a multimodality strategy for the treatment of large hepatocellular carcinomas. Combination of transcatheter arterial chemoembolization and ethanol injection overcomes the weakness of each of the two procedures, enhancing local therapeutic effect and long-term survival. More recently, a new technique for single-session ablation of large hepatocellular carcinoma lesions has been devised by combining transcatheter hepatic arterial balloon occlusion/embolization and radiofrequency treatment. This combined approach substantially increases the thermal necrosis volume that can be created with respect to the conventional radiofrequency technique, as a result of the reduction of heat loss caused by convection. In a pilot multicentric clinical trial performed in 62 patients, successful ablation of hepatocellular carcinoma lesions ranging 3.5-8.5 cm in diameter was achieved in 82% of cases in the absence of major complications. This new technique seems to have the potential to replace other interventional methods for the treatment of large hepatocellular carcinoma.

MnDPDP-enhanced MRI vs dual-phase spiral CT in the detection of hepatocellular carcinoma in cirrhosis.

The objectives of this study were twofold: (a) to assess safety and tolerability of the hepatobiliary MR contrast agent MnDPDP; and (b) to investigate the sensitivity of MnDPDP-enhanced MRI, in comparison with dual-phase spiral CT, in the detection of hepatocellular carcinoma (HCC) in cirrhosis. Fifty patients with liver cirrhosis and histologically proven HCC were enrolled in a prospective phase-IIIB clinical trial. All patients underwent evaluation with dual-phase spiral CT and pre-contrast and post-contrast MRI at 1.5 T. The MR examination protocol included spin-echo (SE) and gradient-recalled-echo (GRE) T1-weighted images acquired before and 60-120 min after administration of 0.5 micromol/kg (0.5 ml/kg) MnDPDP (Teslascan, Nycomed Amersham, Oslo, Norway); and fast T2-weighted SE images obtained solely before contrast injection. Gold standard was provided by findings at Lipiodol CT in combination with follow-up spiral CT studies, which were repeated at 4-month intervals over a 10- to 27-month (mean +/- SD 20.1 +/- 5.1 months) follow-up period. No serious adverse event occurred. Eighty tumors ranging 0.8-9.1 cm in diameter (mean +/- SD 3.2 +/- 2.4 cm) were detected by Lipiodol CT or confirmed as cancerous foci by follow-up CT studies. Pre-contrast MRI detected 38 of 80 lesions (48%); MnDPDP-enhanced MRI, 65 of 80 lesions (81%); pre-contrast plus post-contrast MRI, 69 of 80 lesions (86%); and dual-phase spiral CT, 64 of 80 lesions (80%). The difference between unenhanced and MnDPDP-enhanced MRI was statistically significant (p < 0.001). The difference between MRI (pre-contrast plus post-contrast) and dual-phase spiral CT was not statistically significant (p = 0.33). The confidence in the final diagnosis, however, was significantly higher for MRI as compared with spiral CT (p<0.001). MnDPDP is a safe and well-tolerated hepatobiliary MR contrast agent. Magnetic resonance imaging with use of MnDPDP is significantly more sensitive than unenhanced MRI and as good as dual-phase spiral CT for detection of HCC in cirrhosis.

Laparoscopic radiofrequency thermal ablation of hepatocarcinoma: preliminary experience.

The objective was to evaluate the feasibility, safety, and effectiveness of radiofrequency thermal ablation (RFT), performed during laparoscopy with a cooled-tip electrode needle, in the treatment of neoplastic hepatic focal lesions. Seven patients with hepatocarcinoma (10 hepatic lesions) were treated during laparoscopy with RFT using a 100-watt RF generator and 17-gauge, dual-lumen, cooled-tip electrode needles with a 3-cm exposed tip. The mean exposure time was 12 minutes for each needle insertion. Spiral computed tomography scanning detected complete tumor necrosis in nine lesions; in one lesion, peripheral neoplastic tissue was detected, and percutaneous RFT was performed. Two patients during follow-up developed two new neoplastic lesions, treated with percutaneous ethanol injection. No recurrences of the treated lesions were seen after 6 months of follow up. Intraoperative RFT with a cooled-tip electrode needle is a safe and effective local treatment of hepatic focal lesions during laparoscopic surgery. Possible indications are large hepatocarcinoma (>5 cm), superficial lesions, multiple lesions, or tumor located near vascular or biliary structures.

Therapeutic effect of transcatheter arterial chemoembolization on hepatocellular carcinoma: evaluation with contrast-enhanced harmonic power Doppler ultrasound.

The aim of this study was to investigate the usefulness of contrast-enhanced harmonic power Doppler ultrasound (US) for the detection of residual viable hepatocellular carcinoma (HCC) after treatment with transcatheter arterial chemoembolization (TACE). Forty-seven patients with 68 HCC lesions 1.8-9.5 cm in diameter (mean +/- SD 4.3 +/- 1.7 cm) underwent contrast-enhanced power Doppler US, in the harmonic mode, before and after treatment with TACE. Unenhanced spiral CT and contrast-enhanced dynamic MR imaging were also performed to help establish the outcome of therapy. Before treatment, intratumoral blood flow signals were detected at contrast-enhanced harmonic power Doppler US in 65 (95%) of 68 lesions. After TACE, flow signals were no longer detectable in 22 of these 65 lesions, which showed complete response at spiral CT and dynamic MR imaging. In 38 (88%) of the 43 lesions with partial response, intratumoral flow signals were still identified at contrast-enhanced harmonic power Doppler US. Twenty-eight of these 38 lesions underwent additional treatment with percutaneous ethanol injection (PEI) using contrast-enhanced harmonic power Doppler US guidance. Complete response was seen after PEI in 23 of 28 lesions. Contrast-enhanced harmonic power Doppler US proved useful for assessing the therapeutic effect of TACE on HCC and for guiding additional treatment with PEI in cases of partial response.

Abdominal MR: liver and pancreas.

Following the introduction of rapid, high-quality scan techniques and the development of new, tissue-specific contrast agents, the applications of MRI for abdominal imaging are experiencing unprecedented growth. This article examines the current status of liver and pancreatic MRI, highlighting technical and methodological approach, use of contrast agents, and main clinical applications. The MRI technique appears to be the ideal diagnostic tool for detection and characterization of benign and malignant liver neoplasms, and for evaluating tumor response after nonsurgical treatments. Dynamic imaging after bolus injection of a gadolinium chelate is currently a fundamental component of an MRI examination of the liver in many instances. Optimal dynamic scanning depends on the use of a multisection spoiled gradient-echo technique that allows one to image the entire region of interest during a single suspended respiration. Images are obtained during four phases relative to the injection of the contrast agent: precontrast, arterial (pre-sinusoidal), portal (sinusoidal), and delayed (extracellular) phase. Liver-specific contrast agents, including hepatobiliary agents and reticuloendothelial system-targeted iron oxide particles, however, may offer advantages over gadolinium chelates in some clinical settings. Computed tomography is still preferred to MRI for imaging the pancreas. However, state-of-the-art MRI may currently be at least as accurate as spiral CT for depiction of inflammatory and neoplastic pancreatic diseases. Moreover, MRI has the advantage of allowing simultaneous investigation of the biliary tree, owing to cholangiopancreatography techniques. Hence, a comprehensive assessment of most pancreatic diseases can be achieved with a single examination.

Endorectal coil MR imaging findings in hemospermia.

The purpose of this study was to illustrate the spectrum of abnormalities found at endorectal coil magnetic resonance (MR) imaging in patients with hemospermia. Ninety patients aged between 23 and 71 years (mean age 41 years) presenting with hemospermia underwent evaluation with endorectal coil MR imaging at 1.5 T. Duration of hemospermia ranged between 5 days and 4 years (mean 15 months). MR examination protocol included T1-weighted spin-echo (SE) and T2-weighted fast SE MR images obtained in the sagittal, coronal, and axial planes. Abnormalities were observed on endorectal-coil MR images in 49 of 90 patients (54%). Blood within the seminal vesicle or the ejaculatory duct was recognized in 23 of 90 patients (25%). Dilatation of the seminal vesicles or the ejaculatory duct was observed in 31 of 90 patients (34%). Cystic lesions were identified in 14 cases, eight of which involved the utriculus and six the ejaculatory duct. Calculi within the seminal vesicles were depicted in seven patients. No malignant disease was demonstrated. In conclusion, despite the evidence that hemospermia is most often a benign and self-limiting condition, we found that endorectal coil MR imaging can detect abnormal findings in more than half of the patients, and may be helpful in assessing the level at which hemorrhage occurred and in defining the cause of the disease.

Radio-frequency thermal ablation of liver metastases with a cooled-tip electrode needle: results of a pilot clinical trial.

The aim of this study was to evaluate feasibility, safety, and effectiveness of radio-frequency (RF) thermal ablation, performed by using a cooled-tip electrode needle, in the treatment of liver metastases. Twenty-nine patients (20 males and 9 females; age range 43-77 years) with one to four hepatic metastases 1.1-4.8 cm in diameter (mean 2.9 +/- 0.8 cm) from previously resected intra-abdominal primary malignancies were treated. All patients were excluded from surgery and had partial or no response to chemotherapy. Radio-frequency ablation was performed by using a 100-W generator and 17-gauge, dual-lumen, cooled-tip electrode needles with a 2- to 3-cm exposed tip. Exposure time was 12 min for each needle insertion. Findings at spiral CT were used to assess the therapeutic response. A total of 127 insertions were performed (mean 2.4 +/- 1.7 insertions/lesion) during 84 treatment sessions (mean 1.6 +/- 0.7 sessions/lesion) in absence of major complications. Complete tumor response (i. e., unenhancing area of thermal necrosis larger than the treated tumor) was seen in 41 (77 %) of 53 lesions, including 33 (87 %) of 38 lesions 3 cm or less in diameter. After a mean follow-up period of 6.5 +/- 2.1 months (range 3-9 months), recurrence of the treated lesion was seen in 5 (12 %) of the 41 cases. New metastatic lesions appeared in 7 patients. Two patients died after 6 and 8 months, respectively. Of the 27 patients still in follow-up, 14 are currently free of disease. Radio-frequency thermal ablation with a cooled-tip electrode needle is a safe and effective local treatment for hepatic metastases 3 cm or less in greatest dimension.

Combined transcatheter arterial chemoembolization and percutaneous ethanol injection for the treatment of large hepatocellular carcinoma: local therapeutic effect and long-term survival rate.

The aim of our study was to investigate local therapeutic effects and long-term results of combined transcatheter arterial chemoembolization (TACE) and percutaneous ethanol injection (PEI) in the treatment of large hepatocellular carcinoma (HCC). Eight-six patients (67 males and 19 females, age range 48-75 years, mean age 65.1 years) with Child-Pugh class A (n = 48) or B (n = 38) liver cirrhosis and a large HCC (main tumor 3.1-8 cm in diameter with no more than two daughter nodules) were enrolled in a prospective study. All patients underwent a single TACE session followed by PEI. Follow-up ranged from 4 to 65 months (mean 27.8 months, median 26 months). No major complication occurred. The local therapeutic effect, as assessed on the basis of findings at CT and MR imaging, was complete response in 71 of 86 patients (82 %) and partial response in 15 of 86. Overall survival rates by the Kaplan-Meier method were 92 % at 1 year, 83 % at 2 years, 69 % at 3 years, 58 % at 4 years, and 47 % at 5 years. Survival of Child-Pugh A patients (75 % at 3 years and 59 % at 5 years) was significantly longer (p < 0.01) than that of Child-Pugh B patients (61 % at 3 years and 35 % at 5 years). Combined TACE and PEI is an effective treatment for large HCC.

Fatal thrombosis of the portal vein following single-session percutaneous ethanol injection therapy of hepatocellular carcinoma.

Two weeks after percutaneous ethanol injection therapy for hepatocellular carcinoma, performed by injecting 110 mL ethanol in a single session with general anesthesia, a 69-year-old woman with well-compensated liver cirrhosis developed an extensive thrombosis of the whole portal tree that caused severe uncorrectable ascites and progressive deterioration of her general condition, resulting in death 6 weeks after the procedure.

Detection of colorectal liver metastases: prospective comparison of unenhanced and ferumoxides-enhanced magnetic resonance imaging at 1.5 T, dual-phase spiral CT, and spiral CT during arterial portography.

The purpose of this study was to compare the efficacy of unenhanced and ferumoxides-enhanced magnetic resonance imaging with that of dual-phase spiral CT and spiral CT during arterial portography (CTAP) for the detection of colorectal liver metastases. Fourteen patients with liver metastases candidates for partial hepatectomy were examined with dual-phase spiral CT, unenhanced and ferumoxides-enhanced MR imaging at 1.5 T, and spiral CTAP. Imaging tests were read blinded, prospectively, quantitating number of lesions excepting CTAP which used US to exclude cysts. Subsequent intraoperative US and pathologic findings were correlated with preoperative imaging results. At surgery, 36 lesions 0.5-13 cm in diameter (mean+/-standard deviation, 2.9+/-2.1 cm) were identified. Dual-phase spiral CT depicted 21/36 (58%); precontrast MR imaging, 19/36 (53%); ferumoxides-enhanced MR imaging, 30/36 (83%); and spiral CTAP, 34/36 (94%) lesions. Ferumoxides-enhanced MR imaging was significantly more sensitive than spiral CT and unenhanced MR imaging (P < 0.01). The difference in sensitivity between ferumoxides-enhanced MR imaging and spiral CTAP was not statistically significant (P> 0.1). Spiral CTAP, however, depicted nine false-positive lesions (2 hemangiomas, 7 perfusion defects). The positive predictive value was 79% for spiral CTAP and 100% for combined pre- and postcontrast MR imaging. We conclude that ferumoxides-enhanced MR imaging is superior to unenhanced MR imaging and biphasic spiral CT for depiction of colorectal liver metastases. Further investigation is needed to clarify whether MR imaging with use of ferumoxides might replace spiral CTAP for preoperative evaluation of liver resection candidates.