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Purpose: To assess the feasibility of radiological stage-1 ALPPS, associating liver partition and portal vein ligation for staged hepatectomy, by combining portal vein embolization (PVE) with percutaneous intrahepatic split by ablation (PISA)., Materials and Methods: Three patients (mean age 65.0 ± 7.3 years) underwent PVE and PISA. PISA was performed 21 days after PVE by microwave ablation to create a continuous intrahepatic cutting plane. Abdominal CT examinations were performed before and after PVE and PISA. The future liver remnant (FLR) volume was calculated by semiautomatic segmentation, and increase was reported as a percentage of the pre-procedural volume. The FLR/body weight (FLR/BW) ratio was calculated; a ratio greater than 0.8% was considered sufficient for guaranteeing adequate liver function after surgery. The liver function before and after PISA was also evaluated by 99mTc-mebrofenin hepatobiliary scintigraphy. Patients' laboratory tests, performance status, ability to walk were assessed before and after PVE and PISA procedures., Results: No procedure-related complications were recorded. The FLR volume increase in each patient was 42.0, 33.1 and 30.4% within 21 days of PVE and 109.3, 68.1 and 71.7% within 10 days after PISA. The FLR/BW ratios were 0.76, 0.66, 0.63% and 1.13, 0.83, 0.83% after PVE and PISA procedures, respectively. Two patients underwent successful right hepatectomy; in one patient, despite 1.13% FLR/BW, surgery was not performed because of the absolute rejection of blood transfusion due to the patient's religious convictions., Conclusion: Radiological stage-1 ALPPS is a feasible, minimally invasive option to be further investigated to become an effective alternative to surgical stage-1 ALPPS.

Lymphoepithelioma-like hepatocellular carcinoma (LEL-HCC) is a rare form of undifferentiated carcinoma of the liver characterized by the presence of an abundant lymphoid infiltrate. Here, a case of LEL-HCC is described. An 81-year-old woman with a chronic hepatitis C infection was referred to the general surgery department of our hospital in August 2013 with a diagnosis of HCC. A past ultrasound examination had revealed a 60 mm-diameter nodular lesion in the third segment of the liver. After a needle biopsy, the lesion was diagnosed as HCC. The patient underwent surgery with a liver segmentectomy. Two additional nodes on the gastric wall were detected during the surgical operation. The histology of the removed specimen showed a poorly differentiated HCC with significant lymphoid stroma. Immunohistochemical studies revealed that the epithelial component was reactive for CK CAM5.2, CK8, CK18, CEA (polyclonal) and was focally positive for hepar-1 and that the lymphoid infiltrate was positive for CD3, CD4 and CD8. The tumor cells were negative for Epstein-Barr virus. The gastric nodes were ultimately determined to be two small gastrointestinal stromal tumors (GISTs). The synchronous occurrence of HCC and GIST is another very uncommon finding rarely described in the literature. Here, we report the clinicopathological features of our case, along with a review of the few cases present in the literature.

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., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose: To retrospectively evaluate agreement between modified RECIST (mRECIST) assessed at Computed Tomography (CT) and pathology in a large series of patients with hepatocellular carcinoma (HCC) who were transplanted after transarterial chemoembolization (TACE)., Materials and Methods: IRB approval was obtained. The study included 178 patients (M/F=155/23; mean age 55.8 ± 6.3 years) with HCC who were transplanted after TACE from January 1996 to December 2010 and with at least one CT examination before liver transplantation (LT). Two blinded independent readers retrospectively reviewed CT examinations, to assess tumor response to TACE according to mRECIST. Patients were classified in responders (complete and partial response) and non-responders (stable and progressive disease). On the explanted livers, percentage of tumor necrosis was classified as 100, >50 and <50%., Results: The mean interval between latest CT and LT was 57.4 ± 39.8 days. At latest CT examination, the objective response rate was 78.1% (139/178), with 86 cases (48.3%) of complete response (CR). A good intra- (k=0.75 and 0.86) and inter-observer (k=0.81) agreement was obtained. On a per-patient basis, agreement between mRECIST and pathology was obtained in 120 patients (67.4%), with 19 cases (10.7%) of underestimation and 39 cases (21.9%) of overestimation of tumor response at CT. CT sensitivity and specificity in differentiating between responders and non-responders were 93 and 82.9%, respectively. Out of 302 nodules, sensitivity and specificity of CT in detecting complete necrosis were 87.5 and 68.9%, respectively., Conclusions: CT can overestimate tumor response after TACE. Nonetheless, mRECIST assessed at CT after TACE are reproducible and reliable in differentiating responders and non-responders., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Purpose: To analyze Gd-EOB-DTPA-enhanced magnetic resonance (MR) findings of nodules (low-grade dysplastic nodules-LGDNs; high-grade dysplastic nodules-HGDN, and hepatocellular carcinoma-HCC), histologically identified on cirrhotic, explanted livers., Methods: IRB approval was obtained for this study. Thirty-four patients underwent Gd-EOB-DTPA-enhanced MR examinations (1.5T system), that included 20-min delayed hepatobiliary (HB) phase imaging, before undergoing orthotopic liver transplantation (OLT; mean time MR-OLT: 2.7 months). A total of 102 hepatic nodules were identified and analyzed at histopathological examination, and classified as LGDN, HGDN, and HCC. Two radiologists by consensus performed a quantitative (enhancement ratios, ERs) and a qualitative analyses of signal intensities of identified nodules on vascular dynamic phases (30-35 s after injection-arterial phase; 180-190 s after injection late phase) and on HB phases. Correlation between nodules MR patterns and histological classification was analyzed by means of dedicated statistical software., Results: No differences were appreciable among ERs of HGDN and HCCs on HB phase (P > 0.001). Lesions' enhancement on vascular dynamic and on HB phases significantly correlated to histological classification of nodules (P < 0.0001). Nodular hyperintensity on arterial phase and hypointensity on late phase were highly predictive for HCC (PPV 100%), with a moderate sensitivity (72.5%). Nodular hypointensity on HB phase was detected on 39/40 HCCs (sensitivity 97.5%) and in 21/30 HGDNs, whereas no LGDN showed it., Conclusions: Hyperenhancement on arterial phase and hypointensity on late phase are the most specific clues for the diagnosis of HCC. Hypointensity on HB phase shows a PPV of 100% in suggesting nodular premalignancy/malignancy, independently from nodular dynamic vascular enhancement.

Purpose: To retrospectively evaluate the clinical outcome of patients with hepatocellular carcinoma (HCC) who exceeded the Milan criteria, who underwent transarterial chemoembolization (TACE) before orthotopic liver transplantation (OLT), to determine the value of computed tomography (CT)-based tumor response to TACE as a preoperative selection criterion for OLT., Materials and Methods: The study included 33 patients with HCC who exceeded the Milan criteria and underwent OLT after TACE. Informed written consent was obtained before TACE and OLT. Institutional review board approval was not required. Tumor response to TACE was evaluated at 1 month with CT according to amended Response Evaluation Criteria in Solid Tumours (RECIST) guidelines. In the explanted liver, degree of tumor necrosis (> or = 90%, 50%-89%, or < 50%), residual tumor stage and grade, and presence of microvascular invasion were assessed. Follow-up after OLT ranged from 1 to 143 months., Results: After TACE, CT showed complete tumor response (CR) in 18 (55%) patients. On the explanted liver, tumor necrosis was rated 90% or greater in 20 (61%) patients, with a good correlation with CT. Microvascular invasion was observed in nine (27%) of 33 patients; none of them were reported to have a CR at CT. The 5-year cumulative survival rate after OLT was 72.5%; it was significantly (P = .003) higher in patients with a CR (94.4%) compared with patients with a partial response (PR) (45.4%) and stable disease (50%). The 5-year cumulative recurrence-free rate after OLT was 74.4%; it was not affected by the tumor nodule size and number, whereas it was significantly (P = .008) higher in patients with a CR (94.4%) compared with patients with a PR (46.7%) and stable disease (50%)., Conclusion: In patients with HCC who exceeded the Milan criteria, a CR after TACE, on the basis of amended RECIST guidelines, is associated with excellent posttransplantation outcomes. Therefore, 1-month response to TACE assessed at CT may represent a valid selection criterion for OLT., (RSNA, 2010)

Sinonasal undifferentiated carcinoma (SNUC) is a relatively newly described malignancy of the nasal cavity and paranasal sinuses with a reported 25% to 30% risk for distant metastases. We have reported herein the case of a patient who underwent orthotopic liver transplantation (OLT) for hepatic metastases of SNUC. At 13 months follow-up she is alive with no sign of local or distant-site recurrence. Despite the limited follow-up, the present case suggests that a long disease-free survival after primary surgery, absence of local-regional recurrence, and stability of disease after chemotherapy may represent selection criteria to refer patients for OLT. However, continued follow-up and larger series are necessary to test this hypothesis in the long-term and to assess the role of posttransplantation chemotherapy.

The development and progression of a hepatocellular carcinoma (HCC) in a chronically diseased liver, i.e., the carcinogenesis, comprise a multistep and long-term process. Morphologically, this process is associated with the presence of distinct nodular lesions in the liver that are called 'preneoplastic lesions.' These preneoplastic lesions are associated with and can precede the growth and progression of well-differentiated HCCs . The characterization of nodular lesions and demonstration of the multistep development of HCC in the cirrhotic liver by imaging modalities represent a challenging issue. The arterial hypervascular supply, depicted by different dynamic studies, represents a fundamental radiological criterion for the diagnosis of HCC in cirrhosis. Magnetic resonance (MR) imaging performed with tissue-specific contrast media can help to investigate the "grey area" of carcinogenesis, in which significant histological changes are already present without any imaging evidence of neoangiogenesis. The purpose of this review is to provide information on the properties of tissue-specific MR contrast agents and on their usefulness in the demonstration of the pathologic changes that take place at the level of the biliary and reticuloendothelial systems during the carcinogenetic process in liver cirrhosis.