Post liver transplant recurrence in patients with hepatocellular carcinoma: not necessarily the end of the road! (original) (raw)
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Transplantation Proceedings, 2007
Introduction. Liver transplantation (OLT) has been advocated as a good management option for patients with carcinoma hepatocellular (HCC). More recurrences are extrahepatic due to many pathological factors. Patients and Methods. From April 1986 to December 2003, we performed 95. OLTs for HCC including 73% men of mean age of 54.7 years and 25.3% not filling Mazzaferro's criteria. Results. The recurrence incidence was 15.8% (n ϭ 15), including only extrahepatic lesions in 11 (mainly lung recurrence, seven) and hepatic plus extrahepatic in four. Main late mortality was due to tumor recurrence (n ϭ 12, 33.3%). No differences were observed among sex, preoperative chemoembolization, age, Child, Okuda, etiology, or satellite nodules. A greater incidence of tumor recurrence was observed with a preoperative biopsy (45.5% vs 5.9%, P ϭ .0001); and alpha fetoprotein (AFP) Ͼ 200 ng/mL (37.5% vs 13.3%, P ϭ .08); known HCC (25.5% vs 3.1%, P ϭ .008); vascular invasion (42.1% vs 10.3%, P ϭ .001); Ͼ 5 cm single nodule (50% vs 13%, P ϭ .004); more than three nodules (50% vs 13.9%, P ϭ .01); moderately to poorly differentiated tumors (37.5% vs 12.7%, P ϭ .01); pTNM IV (50% vs 8.7%, P ϭ .0001); and not meeting Milan criteria (40.9% vs 9.2%, P ϭ .001). These are the same factors for extrahepatic recurrence. For hepatic recurrence the prognostic factors were: vascular invasion (15.8% vs 1.5%, P ϭ .008), more than three nodules (25% vs 2.5%, P ϭ .004), moderately to poorly differentiated tumors (18.8% vs 1.4%, P ϭ .003), pTNM IV (16.7% vs 1.4%, P ϭ .006), and not meeting Milan criteria (13.6% vs 1.5%, P ϭ .01). Conclusions. Recurrence incidence with Milan criteria was less than 10%, mainly extrahepatic (lung). Prognostic factors for tumor recurrence were pathological features, namely vascular invasion, more than three nodules, size larger than 5 cm, moderately to
– OBJECTIVE: Hepatocellular Car-cinoma (HCC) represents the fifth most common malignancy and the third cancer-related cause of death worldwide. Liver transplantation (LT) is an excellent treatment for patients with small HCC associated with cirrhosis. The purpose of this review is to investigate the possible strategies for the treatment of HCC recurrence after LT based on current clinical evidence. MATERIALS AND METHODS: A systematic literature search was performed independently by two of the authors using PubMed, EMBASE, Scopus and the Cochrane Library Central. The search was limited to studies in humans and to those reported in the English language. RESULTS: Thanks to the introduction of strict selection criteria, LT for HCC has achieved a survival rate of 85% at five years. However, the recurrence of HCC after transplantation remains a serious problem that affects about 20% of post-transplant cases. While most recurrences occur within the first 2 years, late recurrences have been described. The prognosis of recurrence is poor despite numerous proposals of the therapeutic option. Lower levels of immu-nosuppressive therapy and use of mammalian targets of rapamycin (mTORs) is a potential preventive strategy to reduce HCC recurrence post-Lt. Surgical resection and locoregional therapies (mainly TACE and RFA) play a very important role and are associated with improved survival. Conversely, multikinase inhibitors such as Sorafenib and their association with mTOR in-hibitors play a role in cases of advanced HCC recurrence not suitable for the surgical or abla-tive approach. CONCLUSIONS: Treating HCC recurrence is a multidisciplinary workup involving hepatolo-gists, surgeons, oncologists and radiologists in order to offer a patient-tailored therapy.
Journal of transplantation, 2010
Background. Factors affecting outcomes after orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC) have been extensively studied, but some of them have only recently been discovered or reassessed. Methods. We analyzed classical and more recently emerging variables with a hypothetical impact on recurrence-free survival (RFS) in a single-center series of 283 patients transplanted for HCC between 1997 and 2009. Results. Five-year patient survival and RFS were 75% and 86%, respectively. Thirty-four (12%) patients had HCC recurrence. Elevated preoperative alpha-fetoprotein (AFP) levels, preoperative treatments of HCC, unfulfilled Milan and up-to-seven criteria at final histology, poor tumor differentiation, and tumor microvascular invasion negatively affected RFS by univariate analysis. Milan and up-to-seven criteria applied preoperatively, and the use of m-TOR inhibitors did not reach statistical significance. Cox's proportional hazard model showed that only elevated AFP levels (Odds Ratio = 2.88; 95% C.I. = 1.43-5.80; P = .003), preoperative tumor treatments (Odds Ratio = 4.84; 95% C.I. = 1.42-16.42; P = .01), and microvascular invasion (Odds Ratio = 4.82; 95% C.I. = 1.87-12.41; P = .001) were predictors of lower RFS. Conclusions. Biological aggressiveness and preoperative tumor treatment, rather than traditional and expanded dimensional criteria, conditioned the outcomes in patients transplanted for HCC.
Journal of Gastrointestinal Surgery, 2008
Background Radiofrequency ablation (RFA) is an effective local ablation therapy for hepatocellular carcinoma (HCC) with favorable long-term outcome. There is no data on the analysis of recurrence pattern and its influence on long-term survival outcome after RFA in HCC patients. Aim of Study To evaluate the tumor recurrence pattern and its influence on long-term survival in patients with HCC treated with RFA. Patients and Methods From April 2001 to January 2005, 209 patients received RFA using internally cooled electrode as the sole treatment modality for HCC. Among them, 117 patients (56%) had unresectable HCC because of bilobar disease, poor liver function, and/or high medical risk for resection; whereas 92 patients (44%) underwent RFA as the primary treatment for small resectable HCC. The ablation procedure was performed through percutaneous (n=101), laparoscopic , or open approaches (n=91). The tumor recurrence pattern and long-term survival were analyzed. Multivariate analysis was carried out to identify independent prognostic factors affecting the overall survival of patients.
PLoS ONE, 2013
Background: In the treatment of hepatocellular carcinoma (HCC), hepatic resection has the advantage over radiofrequency ablation (RFA) in terms of systematic removal of a hepatic segment. Methods: We enrolled 303 consecutive patients of a single naïve HCC that had been treated by RFA at The University of Tokyo Hospital from 1999 to 2004. Recurrence was categorized as either intra-or extra-subsegmental as according to the Couinaud's segment of the original nodule. To assess the relationship between the subsegments of the original and recurrent nodules, we calculated the kappa coefficient. We assessed the risk factors for intra-and extra-subsegmental recurrence independently using univariate and multivariate Cox proportional hazard regression. We also assessed the impact of the mode of recurrence on the survival outcome. Results: During the follow-up period, 201 patients in our cohort showed tumor recurrence distributed in a total of 340 subsegments. Recurrence was categorized as exclusively intra-subsegmental, exclusively extra-subsegmental, and simultaneously intra-and extra-subsegmental in 40 (20%), 110 (55%), and 51 (25%) patients, respectively. The kappa coefficient was measured at 0.135 (95% CI, 0.079-0.190; P,0.001). Multivariate analysis revealed that of the tumor size, AFP value and platelet count were all risk factors for both intra-and extra-subsegmental recurrence. Of the patients in whom recurrent HCC was found to be exclusively intra-subsegmental, extra-subsegmental, and simultaneously intra-and extrasubsegmental, 37 (92.5%), 99 (90.8%) and 42 (82.3%), respectively, were treated using RFA. The survival outcomes after recurrence were similar between patients with an exclusively intra-or extra-subsegmental recurrence. Conclusions: The effectiveness of systematic subsegmentectomy may be limited in the patients with both HCC and chronic liver disease who frequently undergo multi-focal tumor recurrence.
Background: Despite the high complete necrosis rate of radiofrequency ablation (RFA), tumor recurrence, either local tumor recurrence or new tumor formation, remains a significant problem. Purpose of this study is to evaluate the pattern and risk factors for intrahepatic recurrence after percutaneous RFA for hepatocellular carcinoma (HCC). Methods: We studied 40 patients with 48 HCCs ( 3.5 cm) who were treated with percutaneous RFA. The mean follow-up period was 24.1 + 15.7 months. We evaluated the cumulative disease-free survival of overall intrahepatic recurrence, local tumor progression (LTP) and intrahepatic distant recurrence (IDR). Thirty host, tumoral and therapeutic risk factors were reviewed for significant tie-in correlation with recurrence: age; gender; whether RFA was the initial treatment for HCC or not; severity of liver disease; cause of liver cirrhosis; contact of tumor to major hepatic vessels and liver capsule; degree of approximation of tumor to the liver hilum; ablation time; degree of benign pre-ablational enhancement; sufficient safety margin; tumor multinodularity; tumor histological differentiation; tumor segmental location; maximum tumor diameter; degree of tumor pre-ablational enhancement at arterial phase CT, MRI or CT-angiography; and laboratory markers pre-and post-ablation (AFP, PIVKA II, TP, AST, ALT, ALP and TB). Results: The incidence of overall recurrence, LTP and IDR was 65, 23 and 52.5%, respectively. The cumulative disease-free survival rates were 54.6, 74.8 and 78.3% at 1 year, 27.3, 71.9 and 46.3% at 2 years and 20, 71.9 and 29.4 at 3 years, respectively. Univariate and multivariate analysis showed that the significant risk factors for LTP were: tumor size 2.3 cm, insufficient safety margin, multinodular tumor, tumors located at segments 8 and 5, and patient's age . 65 years (P , 0.05). No significant risk factor relationship for IDR could be detected. Conclusion: Our results would have clinical implications for advance warning and appropriate management of patients scheduled for RFA. Patients at risk of LTP should be closely monitored in the first year. Furthermore, regular long-term surveillance is essential for early detection and eradication of IDR.
World Journal of Surgical Oncology, 2015
Background: Despite progress in resection for colorectal liver metastases (CLM), the majority of patients experience recurrence. We aimed to evaluate factors influencing time to recurrence (TTR), treatment and post-recurrence survival (PRS) related to site of recurrence. Methods: This is a retrospective population-based cohort study (1998-2012) of consecutive patients without extrahepatic disease treated with resection for CLM in a referral centre. Results: A total of 311 patients underwent resection for CLM. After a median follow-up of 4.2 years (range 1.2-15.2), 209 (67.4 %) patients developed recurrence, hepatic 90, extrahepatic 59 and both 60. Median TTR was 14.0 months, and 5-year recurrence-free status was 25.7 %. Five-and 10-year overall survival (OS) was 38.8 and 22.0 %, respectively. Median OS was 45 months. A multivariate analysis displayed synchronous disease (hazard ratio (HR) 1.50), American Society of Anaesthesiologists (ASA) score (HR 1.40), increasing number (HR 1.24) and size of metastases (HR 1.08) to shorten TTR (all p < 0.05). Perioperative chemotherapy (n = 59) increased overall TTR (HR 0.63) and overall survival (OS; HR 0.55). Hepatic TTR was correlated to synchronous disease (HR 2.07), number of lesions (HR 1.20), R1 resection (HR 2.00) and ASA score (HR 1.69), whereas extrahepatic TTR was correlated to N stage of the primary (HR 1.79), number (HR 1.27) and size of metastases (HR 1.16). Single-site recurrence was most common (135 of 209, 64.5 %), while 58 patients had double-and 16 triple-site relapses. Median PRS was 24.3 months. There was a difference in median PRS (months) according to site of relapse: liver 30.5, lung 32.3, abdominal 22.0, liver and lung 14.3, others 14.8 (p = 0.002). Repeated liver resections were performed in n = 57 patients resulting in 40.6 months median OS and 36.8 % 5-year OS. Conclusions: An adverse overall TTR was correlated to number and size of metastases, ASA score and synchronous disease. Perioperative chemotherapy increased TTR and OS after surgery for CLM. Patients with solitary post-resection relapse in the liver or lungs had the potential for longevity due to multimodal treatment.