High rate of cancer recurrence after DAA treatment in patients with prior hepatocellular carcinoma. Disruption of immune surveillance may facilitate the emergence of metastatic clones.

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Outcome predictors in patients with hepatocellular carcinoma (HCC) who are treated with percutaneous ablation are ill defined, and it is unknown if successful therapy is associated with improved survival. In our study, 282 cirrhotic patients with early nonsurgical HCC were treated with percutaneous ablation during a 15-year period. Single tumors were seen in 244 patients, and 2 to 3 nodules were seen in 38 patients. Initial complete response was achieved in 192 patients and was independently related to the size of the main tumor (P ‫؍‬ .015) and tumor stage (P ‫؍‬ .0001) (<2 cm, 96%; 2.1-3 cm, 78%; >3 cm, 56%; 2-3 nodules, 46%). At the end of follow-up, 80 patients presented sustained complete response. The 1-, 3-, and 5-year survival rates were 87%, 51%, and 27%, respectively. The independent predictors of survival were Child-Turcotte-Pugh class (P ‫؍‬ .0001) and initial complete response (P ‫؍‬ .006). Child-Turcotte-Pugh class A patients with initial complete response achieved 42% survival at 5 years; this figure increased to 63% in patients with tumors 2 cm or smaller. In conclusion, our results demonstrate that initial complete response to percutaneous ablation is associated with an improved survival in both Child-Turcotte-Pugh class A and B patients with nonsurgical HCC. Accordingly, initial complete tumor necrosis should be considered a relevant therapeutic target irrespective of tumor size and liver function. (HEPATOLOGY 2004;40:1352-1360

This randomized, controlled trial assessed the effect of transarterial embolization (TAE) (without associated chemotherapy) on the survival of patients with nonsurgical hepatocellular carcinoma (HCC). Eighty consecutive patients were randomized to treatment with embolization (Group A, n = 40), or to symptomatic treatment (Group B, n = 40), there being no differences between both groups regarding the degree of liver function impairment and tumor stage. Eighty-two percent of the patients presented a self-limited postembolization syndrome, without treatment-related mortality. Fifty-five percent of the treated cases exhibited a partial response, which resulted in a lower probability of tumor progression during follow-up (57% vs. 77% at 1 year; P < .005). However, after a median follow-up of 24 months (30 deaths in each group), there are no differences in survival (Group A: 49% and 13%; Group B: 50% and 27%, at 2 and 4 years, respectively; P = .72). The absence of differences was maintained even when dividing patients according to Child-Pugh's grade, Okuda stage, or performance status test (PST). Furthermore, there were no differences in the probability of complications or in the need of hospital admissions. In conclusion, TAE has a marked antitumoral effect associated to a slower growth of the tumor, but it does not improve the survival of patients with nonsurgical HCC.

From a theoretical point of view, orthotopic liver transplantation (OLT) should be considered the ideal therapeutic option for patients with hepatocellular carcinoma (HCC).This neoplasm usually appears in the setting of liver cirrhosis, 1,2 and thus, OLT would eliminate the tumor and the oncogenic underlying liver. However, the first series of OLT for HCC showed disappointing results. [3][4][5][6] The inclusion of patients with advanced HCC prompted a high recurrence rate (higher than 50% at 3 years) whereas the survival rate (20%-50% at 5 years) was clearly less than that of non-HCC patients. Subsequent reports showed that HCC stage is a key point in determining the success of OLT in these patients and suggested that patients with early HCC could benefit from OLT both in terms of recurrence and survival. 5,7-10 Thereby, the recurrence rate of patients with incidental tumors which were discovered at the time of the pathological examination of the explanted liver is negligible. 3,7 Finally, two recent studies have shown that if OLT is restricted only to patients with early HCC (some years ago these tumors would have been identified only in the explanted livers), the risk of recurrence is minimal and the survival is identical to that of patients without HCC. 11,12 These encouraging data would favor OLT as the first therapeutic option to be considered in patients with HCC 13 as surgical resection is hampered by a higher recurrence rate during follow up [14][15][16][17] ; however, OLT is a highly invasive procedure with potentially severe complications in the early, medium, and long-term follow up. In addition, it must be stressed that HCC in most of the patients arises on liver cirrhosis caused by infection with HBV or HCV, 2,18 which frequently infects the graft, 19,20 and that the progression of the liver disease may be faster than in immunologically competent individuals. 21 As previously reported, 22-25 the treatment schedule applied in our Liver Unit in patients with HCC considered OLT only for those patients with solitary tumors smaller than 5 cm in whom resection was contraindicated, whereas the stage according to the TNM staging system was not taken into account. The present study analyzes the outcome of the cohort of the first 58 HCC patients submitted to OLT following this pre-established treatment algorithm, describing the accuracy of the preoperative staging, the recurrence and survival data, and also the rate of viral infection of the new liver. PATIENTS AND METHODS PatientsBetween January 1989 and December 1995, 877 patients with HCC were diagnosed, staged, and treated in our Liver Unit according to a previously published schedule. [22][23][24][25] Patients with HCC were Abbreviations: HCC, hepatocellular carcinoma; OLT, orthotopic liver transplantation; TNM, tumor-node-metastasis classification system; pTNM, pathological tumor-nodemetastasis classification.From the

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This study assesses the magnetic resonance (MR) features of intrahepatic cholangiocarcinoma (ICC) in patients with cirrhosis with specific analysis of the contrast enhancement pattern. Cholangiocarcinoma may show increased contrast uptake in the arterial phase, and, if washout in the delayed venous phase were to be detected, the noninvasive diagnostic criteria proposed in the American Association for the Study of Liver Diseases guidelines would be refuted. We reviewed the MR findings of 25 patients with cirrhosis with 31 histologically confirmed ICC nodules. Signal intensity on basal T1-weighted and T2-weighted images and characteristics of enhancement after contrast administration on arterial, portal, and delayed phase were registered. Enhancement pattern was defined according to the behavior of the lesions in each phase, and dynamic pattern was described according to the progression of enhancement throughout the different phases. The most frequent pattern displayed by ICC was a progressive contrast uptake (80.6%). Stable contrast enhancement was registered in 19.4%. None of the ICCs showed a washout pattern, a profile that is specific for hepatocellular carcinoma (HCC). The ICC dynamic behavior differed significantly according to tumor size: progressive enhancement pattern was the most frequent (20 of 25 cases) in lesions larger than 20 mm, whereas the stable pattern was mainly identified in nodules smaller than 20 mm. The most characteristic MR contrast pattern in ICC in cirrhosis is a progressive contrast uptake throughout the different phases, whereas contrast washout at delayed phases is not observed. Because stable enhancement pattern without washout also can be registered in small HCC nodules, the evaluation of delayed phase is mandatory for a proper nodule characterization. If washout is not registered, a biopsy should be mandatory for diagnosis. (HEPATOLOGY 2009;50:791-798.)

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