Article

Systematic Review of Efficacy and Outcomes of Salvage Liver Transplantation After Primary Hepatic Resection for Hepatocellular Carcinoma.

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Abstract

Upfront liver transplantation is the gold-standard in treatment of patients with hepatocellular carcinoma (HCC) and cirrhosis, but a shortage of donor organs negatively impacts on survival outcomes, with significant disease progression during long waiting lists. This systematic review evaluates the safety and efficacy of salvage liver transplantation as treatment for recurrent hepatocellular carcinoma after initial hepatic resection. Electronic searches of Pubmed, EMBASE and Medline databases identified 130 abstracts, from which 16 eligible studies comprising of 319 patients were selected for review. Studies adopting salvage liver transplantation (SLT) following primary hepatic resection for recurrent HCC, with more than five patients were included. Demographic details, morbidity and mortality indices and survival outcomes were collected from each study and tabulated. All patients included studies had liver cirrhosis, with the majority being Child-Pugh A (50%) and B (33%). The aetiology of liver disease was Hepatitis B in the majority of patients (84%). Disease recurrence occurred in 27-80% of patients at a median of 21.4 months (range 14.5-34) following initial resection. SLTs were performed on 41% of recurrences and were associated with biliary complications (8%), infection (11%), bleeding (8%) and vascular complications (7%). There were 18 peri-operative deaths (5.6%). The median 1, 3, and 5-year overall and disease-free survival was 89%, 80%, 62% and 86%, 68%, 67% respectively. Synthesis of available observational studies suggests that SLT following primary hepatic resection is a highly applicable strategy with long-term survival outcomes that are comparable to upfront liver transplantation.

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... Because the result of re-resection is excellent in cases with a long interval between initial surgery and tumor recurrence, reresection can be recommended particularly for patients with late intrahepatic recurrence 1-2 years after initial resection as long as vascular invasion of the tumor is not evident and liver function is tolerable to re-operation. In addition, salvage transplantation could result in an excellent diseasefree survival rate > 60% if the conditions of the patient and recurrent tumors are suitable for transplantation (153,154). Extrahepatic recurrence develops in 15-37% of cases after HCC resection, most frequently in the lungs followed by the abdominal cavity and bones (155). Metastatectomy can also be considered when the liver function can tolerate surgery and intrahepatic HCCs have been clearly treated or are controllable (156,157). ...
... Patients with HCCs beyond as well as within the Milan criteria should be initially treated with liver resection and can later be salvaged with LT if they develop recurrent HCC within the Milan criteria and is not too aggressive (153). The selection criteria for SLT are same as those for primary LT (153,154,232,(235)(236)(237)(238)(239). This is because the risk factors for HCC recurrence after SLT are similar to those of primary LT (236,240). ...
... Another concern is the potential for surgical difficulty following prior resection and postoperative complications, which may negate the benefit of an SLT. Meta-analyses and systemic reviews (154,234,241) show that the recipient outcomes of SLT are similar to those of primary LT with respect to overall and disease-free survival. ...
... In addition, salvage transplantation could result in an excellent disease-free survival rate >60% if the conditions of the patient and recurrent tumors are suitable for transplantation. 153,154 Extrahepatic recurrence develops in 15%-37% of cases after HCC resection, most frequently in the lungs followed by the abdominal cavity and bones. 155 Metastatectomy can also be considered when the liver function can tolerate surgery and intrahepatic HCCs have been clearly treated or are controllable. ...
... 153 The selection criteria for SLT are same as those for primary LT. 153,154,232,[235][236][237][238][239] This is because the risk factors for HCC recurrence after SLT are similar to those of primary LT. 236,240 Significant independent risk factors for HCC recurrence after SLT include microscopic vascular invasion, poor differentiation, satellite nodules, high AFP level, and tumor size and number. ...
... Another concern is the potential for surgical difficulty following prior resection and postoperative complications, which may negate the benefit of an SLT. Meta-analyses and systemic reviews 154,234,241 show that the recipient outcomes of SLT are similar to those of primary LT with respect to overall and disease-free survival. ...
... Comparison of primary LT and SLT for HCC within MC in recent studies revealed similar perioperative course, morbidity, overall survival, and disease-free survival [16,[23][24][25][26][27][28] , while a previous study showed the association of LT after resection and higher operative mortality, an increase of recurrence, and poorer outcomes [29] . In the systemic review by Chan et al [30] the median 5-year overall and disease-free survival rates in SLT are 62% and 67%, respectively. In the era of organ shortage, LR should be considered as the primary curative treatment for resectable tumors in compensated livers, and SLT is a safe and effective strategy for initial transplant-eligible patients when recurrent HCC or hepatic function deterioration occur [12] . ...
... Serological AFP > 400 ng/mL [49] > 1000 ng/mL [34,35] Tumor gross Tumor size > 3 cm [30] or > 5 cm [37,41,65] > 6 cm [35] Tumor number > 3 [65] ≥ 4 [35] Satellite nodules Yes [30,63,66] Yes [33] Tumor microscopic Tumor differentiation Intermediate, or poor differentiation, or undifferentiation [30,49,65] Poor differentiation, or undifferentiation [33] ...
... Serological AFP > 400 ng/mL [49] > 1000 ng/mL [34,35] Tumor gross Tumor size > 3 cm [30] or > 5 cm [37,41,65] > 6 cm [35] Tumor number > 3 [65] ≥ 4 [35] Satellite nodules Yes [30,63,66] Yes [33] Tumor microscopic Tumor differentiation Intermediate, or poor differentiation, or undifferentiation [30,49,65] Poor differentiation, or undifferentiation [33] ...
Article
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Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related death in the world. Radical treatment of HCC in early stages results in a long disease-free period and improved overall survival. The choice of optimal management strategy for HCC mainly depends on the severity of the underlying liver disease. For patients with decompensated liver cirrhosis and HCC within Milan criteria (MC), liver transplant (LT) is the choice of treatment. However, for patients with good residual liver reserve and HCC within MC, selection of other curative treatments such as liver resection (LR) or radiofrequency ablation may be a reasonable alternative. For patients without cirrhosis, LR can result in an overall survival similar to that provided by LT. Therefore, it is an accepted alternative to LT especially in areas with organ shortage. However, the cumulative 5-year recurrence rate of HCC post LR might be as high as 70%. For initial transplant-eligible (within MC) patients with recurrent HCC post LR, salvage liver transplant (SLT) was first proposed in 2000. However, most patients with recurrent HCC considered for SLT are untransplantable cases due to HCC recurrence beyond MC or comorbidity. Thus, the strategy of opting for SLT results in the loss of the opportunity of LT for these patients. Some authors proposed the concept of “de principe liver transplant” (i.e., prophylactic LT before HCC recurrence) to prevent losing the chance of LT for these potential candidates. Factors associated with the failure of SLT will be dissected and discussed in three parts: Patient, tumor, and underlying liver disease. Regarding patient-related factors, the rate of transplantability depends on patient compliance. Patients without regular follow-up tend to develop HCC recurrence beyond MC at the time of tumor detection. Advancing age is another factor related to severe comorbidities when LT is considered for HCC recurrence, and these elderly candidates become ineligible as time goes by. Regarding tumor-related factors, histopathological features of the resected specimen are used mostly for determining the prognosis of early HCC recurrences. Such prognostic factors include the presence of microvascular invasion, poor tumor differentiation, the presence of microsatellites, the presence of multiple tumors, and the presence of the gene-expressing signature associated with aggressive HCC. These prognostic factors might be used as a selection tool for SLT or prophylactic LT, while remaining mindful of the fact that most of them are also prognostic factors for post-transplant HCC recurrence. Regarding underlying liver disease-related factors, progression of chronic viral hepatitis and high viral load may contribute to the development of late (de novo) HCC recurrence as a consequence of sustained inflammatory reaction. However, correlation between the severity of liver fibrosis and tumor recurrence is still controversial. Some prognostic scoring systems that integrate these three factors have been proposed to predict recurrence patterns after LR for HCC. Theoretically, after excluding patients with high risk of post-transplant HCC recurrence, either by observation of a cancer-free period or by measurement of biological factors (such as alpha fetoprotein), prophylactic LT following curative resection of HCC could be considered for selected patients with high risk of recurrence to provide longer survival.
... The decision for conventional surgery is based on tumor size, on topographic location of the nodules, and, above all, on functional liver reserve and the expected waiting time [186,187]. Besides tumor control, better assessment of relevant histopathologic parameters of tumor biology is the rationale for complete tumor removal [183][184][185][186][187][188]. In the case of poor prognostic variables assessed at histopathologic analysis (such as MVI and poor tumor grading), early preemptive LT may be advised, before tumor recurrence will occur. ...
... In contrast, LT may be postponed, if these histopathologic variables are lacking. Such patients have to be embedded in a concise surveillance program and will be only candidates for LT when liver function is deteriorating or the tumor recurs (the so-called salvage LT) [48,49,[183][184][185][186][187][188]. ...
... Liver resection as primary treatment for HCC with salvage LT in mind for hepatic deterioration or tumor recurrence has been first described by Majno et al. [189] and proved to be the preferred approach. Several consecutive trials have demonstrated that salvage LT may be effectively performed for patients with HCC recurrence or liver function deterioration after LR [48,49,[183][184][185][186][187][188][189][190][191][192][193]. Only one initial large study performed by Adam et al. reported about higher operative mortality, an increased risk of posttransplant tumor recurrence, and poorer outcome after secondary versus primary LT [194]. ...
Article
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The implementation of the Milan criteria (MC) in 1996 has dramatically improved prognosis after liver transplantation (LT) in patients with hepatocellular carcinoma (HCC). Liver transplantation has, thereby, become the standard therapy for patients with “early-stage” HCC on liver cirrhosis. The MC were consequently adopted by United Network of Organ Sharing (UNOS) and Eurotransplant for prioritization of patients with HCC. Recent advancements in the knowledge about tumor biology, radiographic imaging techniques, locoregional interventional treatments, and immunosuppressive medications have raised a critical discussion, if the MC might be too restrictive and unjustified keeping away many patients from potentially curative LT. Numerous transplant groups have, therefore, increasingly focussed on a stepwise expansion of selection criteria, mainly based on tumor macromorphology, such as size and number of HCC nodules. Against the background of a dramatic shortage of donor organs, however, simple expansion of tumor macromorphology may not be appropriate to create a safe extended criteria system. In contrast, rather the implementation of reliable prognostic parameters of tumor biology into selection process prior to LT is mandatory. Furthermore, a multidisciplinary approach of pre-, peri-, and posttransplant modulating of the tumor and/or the patient has to be established for improving prognosis in this special subset of patients.
... At our center also, we favor a policy of resection-first in early HCC-cirr patients. In our own previous study of 17 SLT patients, we found a higher operative mortality, increased risk of recurrence, and worse long-term survival compared to PLT. 4 Subsequently, several single center studies, 5-9 reviews, and meta-analysis [10][11][12][13][14] showed conflicting results. These reviews and meta-analysis are heterogeneous in terms of patient selection (selection criteria for resection and LT), endpoints used to assess outcomes (OS, disease-free survival, or time to recurrence), timing for these endpoints (1, 3 years, infrequently 5 or 10 years), and above all definition of SLT itself (LT for HCC recurrence in some, and for progression of liver disease in others). ...
... If SLT is feasible after recurrence, the postoperative and longterm outcomes seem to be similar to PLT. [10][11][12][13][14] An additional advantage of the SLT strategy is that the good results with initial curative resection could help in avoiding immediate transplant and its attendant complications/immunosuppression, and could also extend the potential waiting time by theoretically solving the problem of tumor progression during the waiting period. 5,6,[24][25][26][27] A total of 4 meta-analysis and reviews 10,12-14 on the PLT versus SLT strategy have been published in the last 3 years. ...
... We found a better OS and DFS in groups LLT and PLT compared with group LR. The result of similar OS following PLT and SLT noted in various studies [10][11][12][13][14]34 also needs to be interpreted with a little caution. SLT group patients are ''a select group'' of recipients who have relatively preserved liver function, have a transplantable recurrence after resection (probably a favorable tumor biology), and are in a relatively better general condition. ...
Article
Background data: In compensated cirrhotics with early hepatocellular carcinoma (HCC-cirr), upfront liver resection (LR) and salvage liver transplantation (SLT) in case of recurrence may have outcomes comparable to primary LT (PLT). Objective: An intention-to-treat (ITT) analysis comparing PLT and SLT strategies. Methods: Of 130 HCC-cirr patients who underwent upfront LR (group LR), 90 (69%) recurred, 31 could undergo SLT (group SLT). During the same period, 366 patients were listed for LT (group LLT); 26 dropped-out (7.1%), 340 finally underwent PLT (group PLT). We compared survival between groups LR and LLT, LR and PLT, and PLT and SLT. Results: Feasibility of SLT strategy was 34% (31/90). In an ITT analysis, group LLT had better 5-yr/10-yr overall survival (OS) compared with group LR (68%/58% vs. 58%/35%; P = 0.008). Similarly, 5-yr/10-yr OS and disease-free survival (DFS) were better in group PLT versus group LR (OS 73%/63% vs. 58%/35%, P = 0.0007; DFS 69%/61% vs. 27%/21%, P < 0.0001). Upfront resection and microvascular tumor invasion were poor prognostic factors for both OS and DFS, presence of satellite tumor nodules additionally predicted worse DFS. Group SLT had similar postoperative and long-term outcomes compared with group PLT (starting from time of LT) (OS 54%/54% vs. 73%/63%, P = 0.35; DFS 48%/48% vs. 69%/61%, P = 0.18, respectively). Conclusions: In initially transplantable HCC-cirr patients, ITT survival was better in group PLT compared with group LR. SLT was feasible in only a third of patients who recurred after LR. Post SLT, short and long-term outcomes were comparable with PLT. Better patient selection for the "resection first" approach and early detection of recurrence may improve outcomes of the SLT strategy.
... At our center also, we favor a policy of resection-first in early HCC-cirr patients. In our own previous study of 17 SLT patients, we found a higher operative mortality, increased risk of recurrence, and worse long-term survival compared to PLT. 4 Subsequently, several single center studies, 5-9 reviews, and meta-analysis [10][11][12][13][14] showed conflicting results. These reviews and meta-analysis are heterogeneous in terms of patient selection (selection criteria for resection and LT), endpoints used to assess outcomes (OS, disease-free survival, or time to recurrence), timing for these endpoints (1, 3 years, infrequently 5 or 10 years), and above all definition of SLT itself (LT for HCC recurrence in some, and for progression of liver disease in others). ...
... If SLT is feasible after recurrence, the postoperative and longterm outcomes seem to be similar to PLT. [10][11][12][13][14] An additional advantage of the SLT strategy is that the good results with initial curative resection could help in avoiding immediate transplant and its attendant complications/immunosuppression, and could also extend the potential waiting time by theoretically solving the problem of tumor progression during the waiting period. 5,6,[24][25][26][27] A total of 4 meta-analysis and reviews 10,12-14 on the PLT versus SLT strategy have been published in the last 3 years. ...
... We found a better OS and DFS in groups LLT and PLT compared with group LR. The result of similar OS following PLT and SLT noted in various studies [10][11][12][13][14]34 also needs to be interpreted with a little caution. SLT group patients are ''a select group'' of recipients who have relatively preserved liver function, have a transplantable recurrence after resection (probably a favorable tumor biology), and are in a relatively better general condition. ...
... Because the result of re-resection is excellent in cases with a long interval between initial surgery and tumor recurrence, reresection can be recommended particularly for patients with late intrahepatic recurrence 1-2 years after initial resection as long as vascular invasion of the tumor is not evident and liver function is tolerable to re-operation. In addition, salvage transplantation could result in an excellent diseasefree survival rate > 60% if the conditions of the patient and recurrent tumors are suitable for transplantation (153,154). Extrahepatic recurrence develops in 15-37% of cases after HCC resection, most frequently in the lungs followed by the abdominal cavity and bones (155). Metastatectomy can also be considered when the liver function can tolerate surgery and intrahepatic HCCs have been clearly treated or are controllable (156,157). ...
... Patients with HCCs beyond as well as within the Milan criteria should be initially treated with liver resection and can later be salvaged with LT if they develop recurrent HCC within the Milan criteria and is not too aggressive (153). The selection criteria for SLT are same as those for primary LT (153,154,232,(235)(236)(237)(238)(239). This is because the risk factors for HCC recurrence after SLT are similar to those of primary LT (236,240). ...
... Another concern is the potential for surgical difficulty following prior resection and postoperative complications, which may negate the benefit of an SLT. Meta-analyses and systemic reviews (154,234,241) show that the recipient outcomes of SLT are similar to those of primary LT with respect to overall and disease-free survival. ...
Article
Full-text available
The guideline for the management of hepatocellular carcinoma (HCC) was first developed in 2003 and revised in 2009 by the Korean Liver Cancer Study Group and the National Cancer Center, Korea. Since then, many studies on HCC have been carried out in Korea and other countries. In particular, a substantial body of knowledge has been accumulated on diagnosis, staging, and treatment specific to Asian characteristics, especially Koreans, prompting the proposal of new strategies. Accordingly, the new guideline presented herein was developed on the basis of recent evidence and expert opinions. The primary targets of this guideline are patients with suspicious or newly diagnosed HCC. This guideline provides recommendations for the initial treatment of patients with newly diagnosed HCC.
... Because the result of re-resection is excellent in cases with a long interval between initial surgery and tumor recurrence, reresection can be recommended particularly for patients with late intrahepatic recurrence 1-2 years after initial resection as long as vascular invasion of the tumor is not evident and liver function is tolerable to re-operation. In addition, salvage transplantation could result in an excellent diseasefree survival rate > 60% if the conditions of the patient and recurrent tumors are suitable for transplantation (153,154). Extrahepatic recurrence develops in 15-37% of cases after HCC resection, most frequently in the lungs followed by the abdominal cavity and bones (155). Metastatectomy can also be considered when the liver function can tolerate surgery and intrahepatic HCCs have been clearly treated or are controllable (156,157). ...
... Patients with HCCs beyond as well as within the Milan criteria should be initially treated with liver resection and can later be salvaged with LT if they develop recurrent HCC within the Milan criteria and is not too aggressive (153). The selection criteria for SLT are same as those for primary LT (153,154,232,(235)(236)(237)(238)(239). This is because the risk factors for HCC recurrence after SLT are similar to those of primary LT (236,240). ...
... Another concern is the potential for surgical difficulty following prior resection and postoperative complications, which may negate the benefit of an SLT. Meta-analyses and systemic reviews (154,234,241) show that the recipient outcomes of SLT are similar to those of primary LT with respect to overall and disease-free survival. ...
Article
Full-text available
The guideline for the management of hepatocellular carcinoma (HCC) was first developed in 2003 and revised in 2009 by the Korean Liver Cancer Study Group and the National Cancer Center, Korea. Since then, many studies on HCC have been carried out in Korea and other countries. In particular, a substantial body of knowledge has been accumulated on diagnosis, staging, and treatment specific to Asian characteristics, especially Koreans, prompting the proposal of new strategies. Accordingly, the new guideline presented herein was developed on the basis of recent evidence and expert opinions. The primary targets of this guideline are patients with suspicious or newly diagnosed HCC. This guideline provides recommendations for the initial treatment of patients with newly diagnosed HCC.
... Salvage liver transplantation (SLT) has gained popularity in recent years for recurrent HCC because of its total removal of tumors and cure for underlying cirrhosis. In the literature, SLT offered a 5-year disease-free rate of 67%, 5-year overall survival rate of 62%, with morbidity rate of 34% and morality rate of 6.34%, which confirmed its safety, feasibility, and efficacy [31,32]. In addition, comparable survival outcomes were observed between SLT and repeat liver resection in a recent study [5]. ...
... The improvement in SLT therefore raise a question of whether repeat liver resection should be a preferred therapy for patients with preserved liver function and resectable recurrent HCC within Milan criteria. In our study, short-and long-term outcomes of both open and laparoscopic liver resection appear not to be inferior to that of SLT [31][32][33][34]. However, these results could not differentiate whether SLT or RR offers maximum benefits for patients with recurrent HCC. ...
Article
Full-text available
Background: Liver re-resection plays a paramount role in treatment of patients with posthepatectomy hepatocellular carcinoma (HCC) recurrence. Laparoscopic liver resection has been a feasible alternative to open surgery. However, whether laparoscopic liver re-resection for posthepatectomy HCC recurrence is better than open liver re-resection remains unknown. Method: From January 2008 to December 2015, 30 patients with recurrent HCC after prior liver resection underwent laparoscopic liver re-resection in our center. To minimize any confounding factors, a propensity score matching study using a patient ratio of 1:1 was conducted to compare the short- and long-term outcomes of patients who underwent laparoscopic or open liver re-resection. Result: With the open surgery group compared laparoscopic group, operative time was 207.50 versus 200.5 min (p = 0.903), blood loss was 400 versus 100 ml (p = 0.000196), blood transfusion rate was 43.3 versus 0.0% (p = 0.000046), complication rates were 30.0 versus 6.7% (p = 0.01), and hospital stay was 13.5 versus 9.5 days (p = 0.000008). The median follow-up was 35 months. The 1-year, 3-year, 5-year disease-free survival rates were 79.0, 51.0, and 31.9%, versus 78.3, 57.4, and 43.0%, respectively (p = 0.474). The 1-year, 3-year, and 5-year overall survival rates were 89.4, 75, and 67.5%, versus 96.7, 85.0, and 74.4%, respectively (p = 0.413). Conclusion: Laparoscopic liver re-resection for patients with posthepatectomy HCC recurrence provided comparable perioperative and oncological outcomes as open liver re-resection and can be a safe alternative to open procedure.
... In light of the current organ shortage, hepatic re section followed by salvage LT has also been suggested as a treatment strategy for HCC. A systematic review by Chan et al [53] demonstrated median overall survival at 1, 3 and 5years post LT was 89%, 80%, and 62% respectively. Additionally, tissue specimens obtained from a preLT resection can assist in selection of tumors with a favorable histopathological profile for LT [53] . ...
... A systematic review by Chan et al [53] demonstrated median overall survival at 1, 3 and 5years post LT was 89%, 80%, and 62% respectively. Additionally, tissue specimens obtained from a preLT resection can assist in selection of tumors with a favorable histopathological profile for LT [53] . Monitoring radiologic and laboratory (tumor markers) tumor response postLRT has been utilized to identify tumors with favorable biology; and in line with this current UNOS guidelines for organ allocation in the United States require listing HCC patients for 6 mo before qualification for HCC exception points [54] . ...
Article
Full-text available
Liver transplantation (LT) for hepatocellular carcinoma (HCC) has been established as a standard treatment in selected patients for the last two and a half decades. After initially dismal outcomes, the Milan criteria (MC) (single HCC ≤ 5 cm or up to 3 HCCs ≤ 3 cm) have been adopted worldwide to select HCC patients for LT, however cumulative experience has shown that MC can be too strict. This has led to the development of numerous expanded criteria worldwide. Morphometric expansions on MC as well as various criteria which incorporate biomarkers as surrogates of tumor biology have been described. HCC that presents beyond MC initially can be downstaged with locoregional therapy (LRT). Post-LRT monitoring aims to identify candidates with favorable tumor behavior. Similarly, tumor marker levels as response to LRT has been utilized as surrogate of tumor biology. Molecular signatures of HCC have also been correlated to outcomes; these have yet to be incorporated into HCC-LT selection criteria formally. The ongoing discrepancy between organ demand and supply makes patient selection the most challenging element of organ allocation. Further validation of extended HCC-LT criteria models and pre-LT treatment strategies are required.
... A combination including LR followed by LT used to treat deteriorating liver function and/or recurrent HCC, called salvage liver transplantation (sLT), was proposed by Majno [5]. Recently, numerous studies have considered sLT a promising strategy for HCC treatment because it has better short-and long-term outcomes than primary LT [5][6][7][8][9][10][11]. However, the selection criteria for sLT are still controversial, and additional studies are needed to provide a more convincing result to optimize therapeutic strategies for patients with recurrent HCC. ...
Article
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Objectives Salvage liver transplantation (sLT) is considered an effective method to treat hepatocellular carcinoma (HCC) recurrence. This multicenter research aimed to identify the prognostic factors associated with recurrence-free survival (RFS) and overall survival (OS) after sLT. Material and Methods A retrospective analysis of 114 patients who had undergone sLT for recurrent HCC between February 2012 and September 2020 was performed. The baseline and clinicopathological data of the patients were collected. Results The 1-, 3-, and 5-year RFS rates after sLT were 88.9%, 75.2%, and 69.2%, respectively, and the OS rates were 96.4%, 78.3%, and 70.8%. A time from liver resection (LR) to recurrence < 1 year, disease beyond the Milan criteria at sLT and macrotrabecular massive (MTM)-HCC were identified as risk factors for RFS and were further identified as independent risk factors. A time from LR to recurrence < 1 year, disease beyond the Milan criteria at sLT and MTM-HCC were also risk factors for OS and were further identified as independent risk factors. Conclusions Compared with primary liver transplantation (pLT), more prognostic factors are available from patients who had undergone LR. We suggest that in cases of HCC recurrence within 1 year after LR, disease beyond the Milan criteria at sLT and MTM-HCC patients, sLT should be used with caution.
... Salvage LT should be determined by carefully considering the shortage of liver grafts from deceased donors or the problems related to living donors. 359,375 However, the patients who undergo repeated resection are limited in clinical practice, since they have small residual liver parenchyma after resection and are at risk of additional recurrence. 376 For recurrent HCC which is not indicated for repeated hepatic resection, non-surgical local treatments, such as RFA and TACE, can be applied. ...
Article
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Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the fourth most common cancer among men in South Korea, where the prevalence of chronic hepatitis B infection is high in middle and old age. The current practice guidelines will provide useful and sensible advice for the clinical management of patients with HCC. A total of 49 experts in the fields of hepatology, oncology, surgery, radiology, and radiation oncology from the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2018 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions. These guidelines provide useful information and direction for all clinicians, trainees, and researchers in the diagnosis and treatment of HCC.
... This is being discussed due to donor shortage. According to recent studies, the long-term survival outcome of SLT was comparable to that of primary LT [51,52]. Therefore, PH can be considered as an alternative to primary LT as the primary treatment for patients with HCC accompanied by cirrhosis. ...
Article
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Backgrounds/aims: It is challenging to assess the efficacy of partial hepatectomy (PH) as a treatment option for patients with hepatocellular carcinoma (HCC) accompanied by cirrhosis. This study aimed to determine the cure fraction of PH for HCC accompanied by cirrhosis compared to that for HCC without cirrhosis. Methods: A systematic review was performed on outcomes of previous studies that compared recurrence-free survival (RFS) after PH in patients with HCC with or without cirrhosis. A meta-analysis was conducted to obtain the cumulative hazard ratio for two patient groups: cirrhosis and non-cirrhosis. Cure fractions after PH in both groups were determined using a cure model analysis. Results: A total of 18 studies were eligible for meta-analysis and 13 studies were selected for the cure model analysis. The cumulative hazard ratio for RFS of the cirrhosis group compared to that of the non-cirrhosis group was 1.66 (95% confidence interval [CI], 1.43-1.93). Survival data of 3,512 patients in both groups were reconstructed from survival curves of original articles for cure model analysis. The probability of being statistically cured after PH for HCC was 14.1% (95% CI, 10.6%-18.1%) in the cirrhosis group lower than that (32.5%) in the non-cirrhosis group (95% CI, 28.6%-36.4%). Conclusions: The prognosis after PH for HCC accompanied by cirrhosis is inferior to that for HCC without cirrhosis. However, a cure can be expected for one-seventh of patients with HCC accompanied by cirrhosis after PH.
... According to many retrospective studies, recurrent hepatectomy for intrahepatic recurrence has been recognized as an effective treatment with a 5-year OS rate of 52% (range, 22% to 83%) (152, 552,558). Salvage liver transplantation is one of the most effective treatments to increase disease-free survival and OS rates compared with repeated hepatectomy, but the occurrence of complications related to surgery (549) is significantly higher (559). However, the patients who undergo repeated resection are limited in clinical practice because they have a small residual liver parenchyma after resection and are at risk of recurrence (560). ...
Article
Full-text available
Hepatocellular carcinoma (HCC) is the fifth most common cancer globally and the fourth most common cancer in men in Korea, where the prevalence of chronic hepatitis B infection is high in middle-aged and elderly patients. These practice guidelines will provide useful and constructive advice for the clinical management of patients with HCC. A total of 44 experts in hepatology, oncology, surgery, radiology, and radiation oncology in the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2014 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions.
... Studies report that most of HCC result from the chronic infections of hepatitis B virus and/or hepatitis C virus, but the roles of other non-viral factors are relatively small [21][22][23]. ...
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Background Involvements of microRNA-22 (miR-22) in cancer have attracted much attention, but its role in diagnosis of hepatocellular carcinoma (HCC) is still largely unknown. Therefore, the aim of this study was to investigate the expression level and the prognostic value of miR-22 in HCC patients. Methods Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to evaluate serum level of miR-22 in 108 HCC patients and 67 healthy controls. The relationship between miR-22 expression level and clinicopathologic characteristics was analysed via chi-square test. Receiver operating characteristic (ROC) curve was built to estimate the diagnostic value of serum miR-22 in HCC. Results miR-22 expression was significantly down-regulated in HCC compared to that in healthy controls (p < .05). And the low miR-22 expression was significantly associated with vein invasion (p = .002), TNM stage (p = .013) and high serum levels of AFP (α-fetoprotein), ALT (alanine aminotransferase), AST (aspartate aminotransferase) and ALP (alkaline phosphatase. miR-22 had a high diagnostic value with area under the curve of 0.866 corresponding with a sensitivity of 89.3% and a specificity of 68.9%, respectively. Conclusion miR-22 expression was down-regulated in HCC patients. Serum miR-22 might be a novel diagnostic marker in HCC.
... Benefit from its total removal of tumors and cure for underlying cirrhosis, salvage liver transplantation has gained popularity in recent years for recurrent HCC [33]. Chan has reported salvage liver transplantation is a safe, feasible and effective therapy with a 5-year disease-free rate of 67%, 5-year overall survival rate of 62%, morbidity rate of 34% and morality rate of 6.34% for recurrent HCC [34]. However, Guerrini has reported short-and long-term outcomes of both laparoscopic and open liver resection appear not to be inferior to that of salvage liver transplantation [35], besides, few liver donors and high cost limit its application in clinical practice. ...
Article
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Background The purpose of this study is to compare the clinical outcomes of laparoscopic liver resection versus open liver resection for recurrent hepatocellular carcinoma (RHCC). Methods Published studies which investigated laparoscopic versus open liver resection for RHCC were identified, and meta-analysis was used for statistical analysis. Results Six studies were analyzed by meta-analysis method, and cumulative 335 cases were included in this study. Laparoscopic liver resection was performed in 145 cases, and open liver resection was performed in 190 cases. Meta-analysis showed that there was no difference in operative time and 90-day mortality between the laparoscopic group and the open group (p = 0.06 and p = 0.06 respectively); Nevertheless, compared with the open group, the laparoscopic group resulted in significantly lower rate of in-hospital complication (p < 0.0001), much less blood loss (p < 0.0001) and shorter postoperative hospital stay (p = 0.002). Conclusion Laparoscopic liver resection for RHCC offers a benefit of lower in-hospital complication rate, less blood loss, shorter postoperative hospital stay, while similar operative time and 90-day mortality as the open liver resection. Laparoscopic liver resection is feasible with satisfactory postoperative outcomes and can be a safe alternative treatment strategy to open procedure for RHCC.
... 152,552,558 Salvage liver transplantation is one of the most effective treatments to increase disease-free survival and OS rates compared with repeated hepatectomy, but the occurrence of complications related to surgery 549 is significantly higher. 559 However, the patients who undergo repeated resection are limited in clinical practice because they have a small residual liver parenchyma after resection and are at risk of recurrence. 560 Liver transplantation is more limited because of the shortage of donors. ...
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Hepatocellular carcinoma (HCC) is the fifth most common cancer globally and the fourth most common cancer in men in Korea, where the prevalence of chronic hepatitis B infection is high in middle-aged and elderly patients. These practice guidelines will provide useful and constructive advice for the clinical management of patients with HCC. A total of 44 experts in hepatology, oncology, surgery, radiology and radiation oncology in the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2014 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions.
... [2] Nonetheless, long term survival after hepatectomy remains unsatisfactory because of the high incidence of intrahepatic recurrence (up to 68%-98% of patients). [3] Thus, effective therapeutic strategies for intrahepatic recurrence are critical to prolonging survival after hepatectomy for HCC. For resectable recurrent HCC, repeat hepatectomy (RH) remains the preferred option. ...
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Aims: The aim of our systematic review was to compare the efficacy of salvage liver transplantation (SLT) versus curative locoregional therapy (CLRT) for patients with recurrent hepatocellular carcinoma (HCC). Methods: Studies comparing the SLT with CLRT for patients with recurrent HCC were selected from database of PubMed, EMBASE, and Cochrane library. The outcomes including overall survival, disease-free survival, and complications were abstracted. Individual and pooled odds ratio (OR) with 95% confidence interval of each outcome was analyzed. Results: Seven retrospective studies involving 840 patients were included. There is no difference between SLT and CLRT group regarding the1- and 3-year overall survival rates. However, the 5-year overall survival and 1-, 3-, 5-year disease-free survival were significantly higher after SLT than after CLRT (OR = 1.62, 95% CI 1.09-2.39, P = .02; OR = 4.08, 95% CI 1.95-8.54, P = .0002; OR = 3.63, 95% CI 2.21-5.95, P <.00001; OR = 5.71, 95% CI 2.63-12.42, P <.0001, respectively). But CLRT was associated with fewer complications and shorter hospital-stay compared with SLT. For SLT compared with repeat hepatectomy (RH), the subgroup analysis indicated that SLT group had a significantly higher 3- and 5-years disease-free survival than the RH group (OR = 3.23, 95% CI 1.45-7.20, P = .004; OR = 4.79, 95% CI 1.88-12.25, P = .001, respectively). Conclusion: The efficacy of SLT may be superior to that of CLRT in the treatment of recurrent HCC. However, considering the similar overall survival rate and current situation of donor shortage, RH is still an important option for recurrence HCC.
... The 5year recurrence-free survival result of 70% of SLT group is either comparable to or even better than the other reported series. 24,25,31,32 And this reported long-term diseasefree survival outcome is again better than the other treatment options for recurrent HCC (hepatic re-resection, RFA, TACE) in one previous series from the authors' center. 33 Such excellent result reflects the aggressiveness surgical approach with coherent patients' follow-up in the authors' center. ...
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Background: Whether primary liver transplantation (PLT) or upfront curative treatment with salvage liver transplantation (SLT) is a better treatment option for early hepatocellular carcinoma (HCC) is controversial. This study aims to compare the long-term survival starting from the time of primary treatment between the two approaches for early HCC using propensity score matching (PSM) analysis. Methods: From 1995 to 2014, 175 patients with early HCC undergoing either PLT (n = 149) or SLT (n = 26) were retrospectively reviewed in a prospectively collected database. Patients' demographic data, tumor characteristics, short-term and long-term outcome were compared between two groups after PSM. Results: After matching, the baseline characteristics were comparable between mPLT group (n = 45) and mSLT group (n = 25). The tumor recurrence rate after transplant was significantly higher in mSLT group than mPLT group (28% vs. 15.6%). Calculating from the time of primary treatment, the 1, 3, and 5-year overall survival rates were comparable between mPLT group (97.8%, 91.1% and 86.3%) and mSLT group (100%, 95% and 85%). However, the 1, 3, and 5-year recurrence-free survival rates were significantly better in mPLT group than mSLT group (95.6% vs. 90%, 86.6% vs. 80% and 84.3% vs. 70%). SLT approach and high pre-treatment serum alpha-fetoprotein level (>200 ηg/mL) were poor prognostic factors for recurrence-free survival after transplant. Conclusions: PLT may be a better treatment option for early HCC, whereas SLT approach for HCC should be cautiously considered under the circumstance of organ shortage.
... A synthesis of 16 studies comprising 319 patients suggests that SLT following primary hepatic resection is a highly applicable strategy with long-term survival outcomes that are comparable to upfront liver transplantation (17). A similar paper analyzed 111 patients who received SLT, including operative characteristics, survival rate, and prognostic factors, and put forward that primary liver resection can not only completely remove the tumor lesions, but also provide detailed information on the tumor before SLT, such as tumor size, tumor number, degree of differentiation, pathological type, with or without vascular invasion, and other important pathological data (18). ...
Article
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in China, primary liver transplantation (PLT) and hepatic resection are thought to be the prime and more reasonable treatment. But due to the situation of donor shortage and a higher risk of tumor recurrence, salvage liver transplantation (SLT) is gradually being applied to the patients with HCC, and is confirmed as an effective and feasible treatment for patients. However, the indications and transplantation criteria for SLT still remain controversial. This article reviews the benefits and controversies of SLT and provides an effective reference for the clinical practice. © Translational Gastroenterology and Hepatology. All rights reserved.
... Recent studies demonstrated that the surgical resection for PHC has a positive effect on a minority of patients; [43] however, the majority patients with untreated nonsurgical PHC die from tumor progression (63.2%) and liver failure (31.1%) in a brief period time relatively. Meanwhile, the survival rate, on average, was 3 months, as well as 7.8% for survival rates for 1-year. ...
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Background: Primary hepatic carcinoma (PHC) is the third commonest leading to cancer death around the world, and transarterial chemoembolization (TACE) has been proposed as the first-line therapeutic treatment for patients with unresectable PHC. This study aims to determine whether the combination of As2O3 and TACE is superior to alone TACE for achieving more clinical therapeutic efficacy, survival time, life quality and safety in patients with unresectable PHC. Methods: A comprehensive literature search was conducted on the clinical controlled trials comparing therapeutic effects of As2O3 & TACE versus alone TACE for unresectable PHC through English databases (including PubMed, Embase, and the Cochrane Library) and Chinese databases (including China Knowledge Resource Integrated Database, Wanfang Database, Weipu Database, and Chinese Biomedical Database). The last search was in 30 August 2017. A recursive search was performed with bibliographies of relevant studies. There were no language restrictions. Primary outcomes, defined a priori, were therapeutic responses (clinical effective rate and clinical benefit rate), survival time, life quality, and adverse events of As2O3 & TACE compared with alone TACE expressed as relative risk (RR) with 95% confidence intervals (CI). Results: 25 clinical controlled trials involving 1886 participants were included. We found that there were significant superiority associated with As2O3 & TACE compared with alone TACE in clinical benefit rate (RR: 1.24, 95% CI: 1.12-1.37), clinical effective rate (RR: 1.35, 95% CI: 1.17-1.55), 2-year survival rate (RR: 1.45, 95% CI: 1.20-1.75), and improving of KPS (RR: 1.31, 95% CI: 1.14-1.50). These associations were also observed in subgroups by intervened methods of As2O3 and pulmonary metastasis. Notably, the pooled relative risk of retention of sodium and water was obviously raised in patients with As2O3 & TACE therapy (RR: 16.616, 95% CI: 8.01 - 34.486). Conclusion: The superiority of adjuvant As2O3 therapy combined with TACE in PHC individuals will outweigh alone TACE therapy, especially in PHC populations with pulmonary metastasis.
... The current worldwide problem of organ shortage has led most transplant centers, especially in Asian countries, to pursue curative LR for early cases of HCC and perform LT on a rescue basis when the patient develops local recurrence. Though LR had been validated as an accepted alternative for early HCC cases in a context of organ shortage, it has been plagued by high incidence of recurrence reaching up to 80% in some series [15][16][17][18]. Moreover, the risk of non-transplantable tumor recurrences has been reported to be between 20% and 80%, putting those patients on the risk of potential loss of LT chance and hence dismal prognosis [10,19]. ...
Article
Background: Liver transplantation (LT) is the best radical treatment of hepatocellular carcinoma (HCC). Salvage liver transplantation (SalvLT) provides good outcomes for recurrent HCC cases after initial curative liver resection (LR). However, the salvage strategy is not feasible in all situations due to aggressive recurrences. Recently, sequential liver transplantation (SeqLT) was proposed for cases that show adverse pathological features after LR, thus LT is performed pre-emptively before recurrence. In this report, we compared the outcomes of SalvLT and SeqLT for surgical treatment of HCC. Material/Methods: One hundred and ten cases underwent LR for HCC, then were subjected to either SalvLT (n=91) or SeqLT (n=19), from January 2001 to December 2015. For cases that underwent several LR before LT, we collected the data of the last LR before transplantation. A comparison was made according to pre- and post-transplant clinical and pathological variables. Survival analysis and comparison between both pathways are provided. Results: The median interval (months) between LR and LT for the SeqLT group and the SalvLT group were 9.6 and 22.2, respectively. (p=0.01). The LR histopathological features were similar in both groups. In the SalvLT group, the histopathological comparison between the criteria of last LR and the criteria of liver explants revealed that 14 cases advanced from stage I to stage II, one cases from stage I to stage IIIa, one case from stage I to stage IIIb, one case from stage I to stage IIIc, three cases from stage II to stage IIIb and one case from stage II to stage IIIc. The overall rate of pathological upstaging in the SalvLT group was 27%. The incidence of post-transplant HCC recurrence was 5% (1/19) and 11% (10/91) for the SeqLT and SalvLT groups, respectively (p=0.4). The incidence of post-LT in-hospital mortality was 0% among the SeqLT group and 2% (2/91) among the SalvLT group. The estimated rates of five-year overall survival and cancer specific survival for the SeqLT group versus the SalvLT group were (92.3% versus 87.6%; p=0.4) and (92.3% versus 91.9%; p=0.7), respectively. Conclusions: The SeqLT approach might be associated with low incidence of cancer recurrence, better overall survival, and less operative mortality. Another possible benefit is the avoidance of aggressive non-transplantable HCC recurrences. More studies and/or randomization are required for highre evidence conclusions.
... The current worldwide problem of organ shortage has led most transplant centers, especially in Asian countries, to pursue curative LR for early cases of HCC and perform LT on a rescue basis when the patient develops local recurrence. Though LR had been validated as an accepted alternative for early HCC cases in a context of organ shortage, it has been plagued by high incidence of recurrence reaching up to 80% in some series [15][16][17][18]. Moreover, the risk of non-transplantable tumor recurrences has been reported to be between 20% and 80%, putting those patients on the risk of potential loss of LT chance and hence dismal prognosis [10,19]. ...
... PLT was proved to be significantly associated with better OS or RFS only in 4 researches 8, [16][17][18] . However, most studies showed a literally improved OS or RFS for PLT rather than SLT 6,7,9,[19][20][21][22][23] . Dispute might lie in the heterogeneous nature in SLT definition or process. ...
Article
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Hepatocellular carcinoma is the most common liver malignancy. Salvage liver transplantation (SLT) is viewed as a feasible cure for recurrence of HCC after resectomy, but the effect is under dispute. A retrospective study examined data at Renji Hospital for 239 transplants from January 2006 to December 2015, including 211 who received primary liver transplantation (PLT) and 28 who underwent SLT. A multivariable cox regression model was employed to pick out relative factors to overall survival (OS) and recurrence free survival (RFS). Propensity score matching (PSM) was used to balance the bias. Both OS and RFS were worse in SLT group than in PLT group, especially for those patients within Milan criteria. Our study demonstrates that SLT bears higher risk of recurrence and death than PLT, indicating that SLT should be given a more careful thought at performance.
... Pur ritenendo che il punto di partenza per il trattamento delle recidive di HCC debbano essere le indicazioni di trattamento per le prime diagnosi, alcune considerazioni specifiche per le recidive sono necessarie: 1) alcuni parametri aggiuntivi devono essere considerati: intervallo di tempo intercorso dal trattamento; sede della recidiva (locale vs. non locale); efficacia del trattamento precedente; tolleranza del paziente al trattamento precedente; dopo resezione epatica, dati anatomopatologici acquisiti; sacrificio di parenchima epatico al trattamento precedente (anatomico, funzionale e volumetrico) (146,307,308,(310)(311)(312)320), 2) una valutazione trapiantologia in caso di recidiva epatica dopo resezione o termoablazione in pazienti ancora potenziali candidabili a trapianto per età e comorbilità dovrebbe essere raccomandata in considerazione dell'elevato transplant benefit riportato dopo trapianto di salvataggio (153,321,322). ...
... Theoretically, LT is the most effective option for HCC because it not only radically removes the tumor but also cures the underlying hepatic disease (Befeler et al. 2005); however, the shortage of organs greatly limits the application of LT to all patients. SLT, raised by Majno et al. (2000), might relieve disease progression in patients waiting for LT and could reduce the number of transplantations required (Chan et al. 2014). ...
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PurposeThe prognosis for recipients with hepatocellular carcinoma (HCC) of salvage liver transplantation (SLT) versus those of primary liver transplantation (PLT) remains controversial. The objective of this study was to evaluate the clinical features and survival rate of SLT recipients. Methods Three hundred seventy-one patients with HCC transplanted at Shanghai General Hospital, China, between October 2001 and October 2011 were separated into PLT (n = 295) and SLT (n = 76) groups. Patient characteristics and survival curves were studied by univariate and multivariate analysis. A Milan criteria-stratified survival analysis was conducted. ResultsThe proportions of reoperation (11.8 vs. 5.4 %, P = 0.047) and early postoperative mortality (11.8 vs. 4.7 %, P = 0.032) were higher in the SLT group than in the PLT group. Recurrence free survival (RFS) rate and overall survival (OS) rate had no statistically significant differences after stratification using Milan criteria between the PLT group and SLT group. Alphafetoprotein >400 ng/mL (P = 0.011), microscopic vascular invasion (MVI) (P < 0.001), tumor node metastasis (TNM) staging (P = 0.006), and out of Milan criteria (P < 0.001) were independent risk factors for RFS, while MVI (P < 0.001), TNM staging (P = 0.009), and out of Milan criteria (P = 0.003) were factors for OS. In the multivariate logistic regression analysis, HCC recurrence was associated with MVI (OR = 4.196 [2.538–6.936], P < 0.001), and out of Milan criteria (OR = 2.704 [1.643–4.451], P < 0.001). Conclusions Our retrospective, single-center study demonstrated that SLT increases surgical difficulty; however, it has good post-transplantation OS and is a feasible alternative after HCC recurrence within Milan criteria.
... Hence, as long as a patient stays within the Milan criteria, salvage LT, that is, liver resection (or other locoregional therapies) for HCC as a first-line treatment in transplantable patients followed by transplantation, is an attractive option. [21] Resection has been reported to be more cost-effective than LT for early HCC within the Milan criteria, [22] and performing LT too soon after diagnosis was suggested as a factor that adversely affect patient outcomes. [23] Similar outcomes after LT have also been reported between primary versus salvage LDLT. ...
Article
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Patients with hepatocellular carcinoma (HCC) satisfying the Milan criteria are candidates for liver transplantation (LT), but locoregional therapies could be another options for them. A total of 1859 treatment-naïve HCC patients fulfilling the Milan criteria were analyzed. Survival tree analysis was performed to generate survival nodes with similar survival risks in 1729 non-LT group, and compared with the survival of 130 patients who received LT. Among patients who did not receive LT, survival tree analysis classified patients into 6 nodes according to Child-Pugh (CP) score, serum alphafetoprotein (AFP) levels, tumor size, and age, with different mortality risks (5-year survival rate of 87.3%, 77.5%, 65.8%, 64.7%, 44.0%, and 28.7% for nodes 1–6, respectively; P < 0.001). The overall survival of patients in nodes 1 (CP score 5 with AFP levels <5 ng/mL) and 2 (CP score 5 with maximal tumor size <2.5 cm) were comparable with that of patients who received LT (both P > 0.05), but the survival rates of patients in nodes 3 to 6 were worse than that of LT (P < 0.05 for all). In each survival node, survival differed slightly according to initial treatment modality for patients who did not receive LT. For patients who received LT, tumor stage at the time of LT was associated with long-term outcome. Certain groups of non-LT patients showed survival rates that were similar to the survival rates of LT patients. CP score, AFP levels, tumor size, and age were baseline factors that can help estimate the long-term outcomes of non-LT treatment. In addition, tumor stage at the time of LT and specific initial treatment modality in non-LT patients affected the long-term outcomes. These factors can help estimate the long-term outcomes of HCC patients diagnosed within the Milan criteria.
... Surgical resection followed by transplantation does not increase surgical risk nor impair survival [71] and a recent systematic review of 16 studies found that, of those 7 studies which reported salvage transplantation rates, the median rate of salvage transplantation was 41% after a median time to recurrence of 21 months. It concluded that salvage liver transplant following primary hepatic resection has 5year survival of 67%, which is comparable to upfront liver transplantation [72]. These results were also replicated by another meta-analysis which although did report increased operating time and blood loss in those patients undergoing salvage transplantation compared to primary transplantation, reported no difference in postoperative morbidity or perioperative mortality, length of hospital stay, or 5-year survival between the two approaches [73]. ...
Article
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Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide. The mainstay of treatment of HCC has been both resectional and transplantation surgery. It is well known that, in selected, optimized patients, hepatectomy for HCC may be an option, even in patients with underlying cirrhosis. Resectable patients with early HCC and underlying liver disease are however increasingly being considered for transplantation because of potential for better disease-free survival and resolution of underlying liver disease, although this approach is limited by the availability of donor livers, especially in resectable patients. Outcomes following liver transplantation improved dramatically for patients with HCC following the implementation of the Milan criteria in the late 1990s. Ever since, the rather restrictive nature of the Milan criteria has been challenged with good outcomes. There has also been an increase in the donor pool with marginal donors including organs retrieved following cardiac death being used. Even so, patients still continue to die while waiting for a liver transplant. In order to reduce this attrition, bridging techniques and methods for downstaging disease have evolved. Additionally new techniques for organ preservation have increased the prospect of this potentially curative procedure being available for a greater number of patients.
... Given the shortage of donor organs and the typical progression of HCC (which can cause patients to drop out of the transplant waiting list), LR followed by salvage LT has become widely accepted. Furthermore, salvage LT, defined as LR performed to bridge patients to transplantation and avoid dropout, has been shown to be highly effective, with short-and long-term postoperative survival outcomes comparable to upfront LT [9][10][11][12][13][14][15]. ...
Article
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Although salvage liver transplantation (LT) has been widely adopted as a treatment for recurrent hepatocellular carcinoma(HCC), candidate selection criteria have not been established. This single-center study aimed to identify risk factors associated with HCC recurrence and survival following salvage LT. The study included 74 patients treated with salvage LT between October 2001 and February 2013. The median follow-up was 37.2 months after LT. There were 29 cases of HCC recurrence and 31 deaths following LT. Microvascular invasion at the time of liver resection, a time interval to post-LR HCC recurrence of ≤ 12months, an alpha-fetoprotein level at LT greater than 200 ng/mL, and having undergone LT outside of the UCSF criteria were independent risk factors for HCC recurrence after salvage LT. Patients with no more than one risk factor had a 5-year recurrence-free survival rate of 71.2% compared to 15.9% in patients with two or more risk factors. These findings suggest that to avoid post-LT HCC recurrence and a dismal prognosis, patients with no more than one risk factor for recurrence should be given priority for salvage LT. These criteria may improve the outcomes of patients treated with salvage LT and facilitate the effective use of limited organ supplies.
Article
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Primary liver cancer is the sixth most commonly diagnosed cancer and was the third leading cause of cancer deaths worldwide in 2020. It includes hepatocellular carcinoma (HCC) (representing 75%-85% of cases), intrahepatic cholangiocarcinoma (representing 10%-15% of cases), and other rare types. The survival rate of patients with HCC has risen with improved surgical technology and perioperative management in recent years; however, high tumor recurrence rates continue to limit long-term survival, even after radical surgical resection (exceeding 50% recurrence). For resectable recurrent liver cancer, surgical removal [either salvage liver transplantation (SLT) or repeat hepatic resection] remains the most effective therapy that is potentially curative for recurrent HCC. Thus, here, we introduce surgical treatment for recurrent HCC. Areas Covered: A literature search was performed for recurrent HCC using Medline and PubMed up to August 2022. Expert commentary: In general, long-term survival after the re-resection of recurrent liver cancer is usually beneficial. SLT has equivalent outcomes to primary liver transplantation for unresectable recurrent illness in a selected group of patients; however, SLT is constrained by the supply of liver grafts. SLT seems to be inferior to repeat liver resection when considering operative and postoperative results but has the major advantage of disease-free survival. When considering the similar overall survival rate and the current situation of donor shortages, repeat liver resection remains an important option for recurrent HCC.
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Owing to its heterogeneous and highly aggressive nature, hepatocellular carcinoma (HCC) has a high recurrence rate, which is a non-negligible problem despite the increasing number of available treatment options. Recent clinical trials have attempted to reduce the recurrence and develop innovative treatment options for patients with recurrent HCC. In the event of liver remnant recurrence, the currently available treatment options include repeat hepatectomy, salvage liver transplantation, tumor ablation, transcatheter arterial chemoembolization, stereotactic body radiotherapy, systemic therapies, and combination therapy. In this review, we summarize the strategies to reduce the recurrence of high-risk tumors and aggressive therapies for recurrent HCC. Additionally, we discuss methods to prevent HCC recurrence and prognostic models constructed based on predictors of recurrence to develop an appropriate surveillance program.
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Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the fourth most common cancer among men in South Korea, where the prevalence of chronic hepatitis B infection is high in middle and old age. The current practice guidelines will provide useful and sensible advice for the clinical management of patients with HCC. A total of 49 experts in the fields of hepatology, oncology, surgery, radiology, and radiation oncology from the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2018 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions. These guidelines provide useful information and direction for all clinicians, trainees, and researchers in the diagnosis and treatment of HCC.
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BACKGROUND AND OBJECTIVES Noncommunicable diseases (NCDs) are chronic conditions requiring health care, education, social and community services, addressing prevention, treatment, and management. This review aimed to summarize and synthesize the available evidence on interventions from systematic reviews of high-burden NCDs and risk factors among school-aged children. METHODS The following databases were used for this research: Medline, Embase, The Cochrane Library, and the Campbell library. The search dates were from 2000 to 2021. We included systematic reviews that synthesized studies to evaluate intervention effectiveness in children aged 5 to 19 years globally. Two reviewers independently extracted data and assessed methodological quality of included reviews using the AMSTAR 2 tool. RESULTS Fifty studies were included. Asthma had the highest number of eligible reviews (n = 19). Of the reviews reporting the delivery platform, 27% (n = 16) reported outpatient settings, 13% (n = 8) home and community-based respectively, and 8% (n = 5) school-based platforms. Included reviews primarily (69%) reported high-income country data. This may limit the results’ generalizability for school-aged children and adolescents in low- and middle- income countries. CONCLUSIONS School-aged children and adolescents affected by NCDs require access to quality care, treatment, and support to effectively manage their diseases into adulthood. Strengthening research and the capacity of countries, especially low- and middle- income countries, for early screening, risk education and management of disease are crucial for NCD prevention and control.
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The results of treatment for early stage recurrent hepatocellular carcinoma (HCC) remain controversial. This study aimed to analyze the clinical outcomes of recurrent HCC within the Milan criteria following different treatment modalities except liver transplantation. From January 2006 to December 2016, 272 consecutive HCC patients who developed intrahepatic recurrence after hepatectomy that satisfied the Milan criteria and Child–Pugh class A or B liver function were retrospectively enrolled. The outcomes of repeat resection (RR), local ablative therapy (LAT), or transarterial chemoembolization (TACE) were reported, and the prognostic factors of survival were investigated. Among the 272 patients, 136 (50.0%), 71 (26.1%), and 65 (23.9%) received TACE, LAT, and RR treatments, respectively. Treatment-related complications were 9.5%, 11.3%, and 10.7%, respectively, in the three groups. No patient died of treatment-related complication. The 1-, 3-, and 5-year overall survival rates after recurrence were 95.0%, 54.2%, and 45.8%, respectively, in the RR group; 86.6%, 51.7%, and 42.4%, respectively, in the LAT group; and 77.2%, 46.5%, and 38.4%, respectively, in the TACE group. On multivariate analysis, three independent factors related to survival after recurrences were identified. A single tumor nodule and AFP < 200 ng/mL predicted better survival, while a disease-free interval ≤ 1 year was associated with poor outcomes. RR and LAT could achieve good survival outcomes in well-selected patients with recurrent HCC within the Milan criteria, while TACE was the main form of treatment when curative therapy was not considered feasible and the clinical outcomes were satisfactory.
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Following curative liver resection (LR), resectable tumor recurrence in patients with preserved liver function leads to deciding between a repeat LR and a salvage liver transplantation (LT), if a donor liver is available. This retrospective study compared survival outcomes and recurrence pattern following salvage living donor LT (LDLT) and repeat LR in patients with recurrent hepatocellular carcinoma (HCC). We reviewed the medical records of patients who underwent repeat LR (n = 163) or LDLT (n = 84) for recurrent HCC following curative resections, between January 2005 and December 2017 at a single institution. A 1:1 propensity score matching led to 42 patients per group. Disease‐specific and recurrence‐free survival were significantly better in the salvage LDLT group than in the repeat LR group (p = 0.042; HR = 2.40; 95% CI, 0.69–6.00 and p < 0.001; HR = 4.23; 95% CI, 2.05‐8.71, respectively). Despite significant differences in recurrence patterns between the two groups (p = 0.019), the patient death rates, after recurrence, were similar for both groups (p = 0.760). This study indicates that salvage LDLT is superior to repeat LR for treating patients with transplantable, intrahepatic HCC recurrence, even in patients with Child–Pugh class A liver cirrhosis.
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Background: Hepatocellular carcinoma (HCC) has a high rate of recurrence. This network meta-analysis aimed to compare the oncological prognosis of the conventional treatments for intrahepatic recurrent hepatocellular carcinoma (rHCC) and identify the optimal strategy. Methods: We conducted a literature search of online database, published between January 2009 and October 2019. Relevant studies analyzing the outcomes of the different interventions for rHCC were included. We synthesized the results using R software and the "gemtc" package. Results: A total of 21 studies involving 2818 patients were ultimately enrolled to be analyzed. We assessed five related therapeutic interventions and two oncological outcomes. The benefits orders of overall survival (OS) from largest to least were salvage liver transplantation (SLT), repeat hepatectomy (RH), radiofrequency ablation (RFA), stereotactic body radiation therapy (SBRT), and transarterial chemoembolization (TACE). For the benefits of recurrence-free survival (RFS), SLT and RH remained the top two treatments. Subgroup analysis of smaller (≤3cm) and larger (>3 cm) tumour reached similar results. Consistency and heterogeneity analysis did not show significant inconsistency and heterogeneity. Discussion: Our findings demonstrated that SLT and RH were the best two treatments for rHCC. Nevertheless, the selection of strategies should also depend on tumour characteristics and basic health situation.
Article
Background and aims: LR and LT are the standard curative options for early HCC. LT provides best long-term survival but is limited by organ shortage. LR, readily available, is hampered by high recurrence rates. Salvage liver transplantation is an efficient treatment of recurrences within criteria. The aim of the study was to identify preoperative predictors of non transplantable recurrence (NTR) to improve patient selection for upfront LR or LT at initial diagnosis. Study design: Consecutive LR for transplantable HCC between 2000 and 2015 were studied. A prediction model for NTR based on preoperative variables was developed using sub-distribution hazard ratio after multiple imputation and internal validation by bootstrapping. Model performance was evaluated by the concordance index after correction for optimism. Results: A total of 148 patients were included. Five-year overall survival and recurrence free survival were 73.6% and 29.3%, respectively (median follow-up 45.8 months). Recurrence rate was 54.8%. NTR rate was 38.2%. Preoperative model for NTR identified >1 nodule [sub-distribution hazard ratio 2.35 95% confidence interval (CI) 1.35-4.09], AFP >100 ng/mL (2.14 95% CI 1.17-3.93), and F4 fibrosis (1.93 95% CI 1.03-3.62). The apparent concordance index of the model was 0.664 after correction for optimism. In the presence of 0, 1, and ≥2 factors, NTR rates were 2.6%, 22.7%, and 40.9%, respectively. The number of prognostic factors was significantly associated with the pattern of recurrence (P = 0.001) and 5-year recurrence free survival (P < 0.001). Conclusions: Cirrhosis, >1 nodule, and AFP >100 ng/mL were identified as preoperative predictors of NTR. In the presence of 2 factors or more upfront transplantation should be probably preferred to resection in regard of organ availability. Other patients are good candidates for LR and salvage liver transplantation should be encouraged in eligible patients with recurrence.
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The goal of the Spanish Liver Transplantation Society (La Sociedad Española de Trasplante Hepático) is to promote and create consensus documents about current topics in liver transplantation with a multidisciplinary approach. To this end, on October 20, 2016, the 6th Consensus Document Meeting was held, with the participation of experts from the 24 authorized Spanish liver transplantation programs. This Edition discusses the following subjects, whose summary is offered below: (1) limits of simultaneous liver–kidney transplantation; (2) limits of elective liver re-transplantation; and (3) liver transplantation after resection and hepatocellular carcinoma with factors for a poor prognosis. The consensus conclusions for each of these topics are provided below.
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The goal of the Spanish Liver Transplantation Society (La Sociedad Española de Trasplante Hepático) is to promote and create consensus documents about current topics in liver transplantation with a multidisciplinary approach. To this end, on October 20, 2016, the 6 th Consensus Document Meeting was held, with the participation of experts from the 24 authorized Spanish liver transplantation programs. This Edition discusses the following subjects, whose summary is offered below: 1) limits of simultaneous liver-kidney transplantation; 2) limits of elective liver re-transplantation; and 3) liver transplantation after resection and hepatocellular carcinoma with factors for a poor prognosis. The consensus conclusions for each of these topics is provided below.
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The goal of the Spanish Liver Transplantation Society (La Sociedad Española de Trasplante Hepático) is to promote and create consensus documents about current topics in liver transplantation with a multidisciplinary approach. To this end, on October 20, 2016, the 6th Consensus Document Meeting was held, with the participation of experts from the 24 authorized Spanish liver transplantation programs. This Edition discusses the following subjects, whose summary is offered below: 1) limits of simultaneous liver-kidney transplantation; 2) limits of elective liver re-transplantation; and 3) liver transplantation after resection and hepatocellular carcinoma with factors for a poor prognosis. The consensus conclusions for each of these topics is provided below. Copyright © 2018. Publicado por Elsevier España, S.L.U.
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The goal of the Spanish Liver Transplantation Society (La Sociedad Española de Trasplante Hepático) is to promote and create consensus documents about current topics in liver transplantation with a multidisciplinary approach. To this end, on October 20, 2016, the 6th Consensus Document Meeting was held, with the participation of experts from the 24 authorized Spanish liver transplantation programs. This Edition discusses the following subjects, whose summary is offered below: 1) limits of simultaneous liver-kidney transplantation; 2) limits of elective liver re-transplantation; and 3) liver transplantation after resection and hepatocellular carcinoma with factors for a poor prognosis. The consensus conclusions for each of these topics is provided below. Copyright © 2018 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.
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Background: The positivity of positron emission tomography (PET) in hepatocellular carcinoma (HCC) correlates with aggressive tumor factors and poor survival. Adequate resection margin size is still a topic of debate. We analyzed the clinical implications of resection margin size in patients with HCC in terms of PET positivity. Methods: We retrospectively reviewed the medical records of 92 patients who underwent liver resection from March 2012 to October 2015. We investigated prognostic factors for recurrence and survival. We analyzed the correlation of resection margin size and PET positivity. Resection margins were classified as less than 1 cm and more than 1 cm. Results: Twenty six (31.3%) patients had PET-positive HCC. Multivariate analysis showed PET, satellite nodules, microvessel invasion, and multicentric occurrence were significant prognostic factors for HCC recurrence. Multivariate analysis also showed satellite nodules and microscopic portal vein invasion were significant prognostic factors for overall survival (OS). Resection margin size did not affect disease-free survival (DFS) (p = 0.681) or OS (p = 0.301) in patients with PET-negative HCC, but showed a difference in DFS [<1 cm at 11 months vs. ≥1 cm at 41 months (p = 0.188)] and OS [<1 cm at 28 months vs. ≥1 cm at 48 months (p < 0.001)] in patients with PET-positive HCC. Conclusions: PET has low sensitivity for HCC. However, it is useful to predict treatment outcomes after liver resection or liver transplantation for HCC. Although the extent of liver resection must be decided based on liver function, a resection margin size >1 cm may improve DFS and OS in patients with PET-positive HCC.
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Hepatocellular carcinoma (HCC) is a major cause of cancer-related death worldwide. In select patients, surgical treatment in the form of either resection or transplantation offers a curative option. The aims of this review are to (1) review the current American Association for the Study of Liver Diseases/European Association for the Study of the Liver guidelines on the surgical management of HCC and (2) review the proposed changes to these guidelines and analyze the strength of evidence underlying these proposals. Three authors identified the most relevant publications in the literature on liver resection and transplantation for HCC and analyzed the strength of evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) classification. In the United States, the liver allocation system provides priority for liver transplantation to patients with HCC within the Milan criteria. Current evidence suggests that liver transplantation may also be indicated in certain patient groups beyond Milan criteria, such as pediatric patients with large tumor burden or adult patients who are successfully downstaged. Patients with no underlying liver disease may also benefit from liver transplantation if the HCC is unresectable. In patients with no or minimal (compensated) liver disease and solitary HCC 2 cm, liver resection is warranted. If liver transplantation is not available or contraindicated, liver resection can be offered to patients with multinodular HCC, provided that the underlying liver disease is not decompensated. Many patients may benefit from surgical strategies adapted to local resources and policies hepatitis B prevalence, organ availability, etc). Although current low-quality evidence shows better overall survival with aggressive surgical strategies, this approach is limited to select patients. Larger and well-designed prospective studies are needed to better define the benefits and limits of such approach.
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Hepatocellular carcinoma (HCC) is the fifth most frequent cancer worldwide and in most cases it evolves on a cirrhotic liver, which requires a complex treatment strategy that includes different options. We present the case of a 62 years old patient, suffering from chronic HBV and HDV hepatitis, which was found, in 2011 with a 7 cm HCC located in the sixth segment of the liver and resected. Within less than a year, tumor relapse was detected (multiple nodules in the remaining sixth segment). Systemic chemotherapy (Sorafenib) started being administered and two TACE procedures were performed at one year and seven months difference. Despite that, the CT and MRI showed the evolution of the disease. The therapy was stopped and the patient was listed for liver transplantation and the procedure was performed. The thirteen months post transplantation assessment showed no sign of tumor relapse. Abbreviations: HCC-hepatocellular carcinoma, HBV-hepatitis B virus, HDV-hepatitis D virus, TACE-transcatheter arterial chemoembolisation, MRI-magnetic resonance imaging, LT-liver transplantation, PEI-percutaneous ethanol injections, UCSF-University of California, San Francisco, MELD-Model for End-Stage Liver Disease, BCLC-Barcelona Clinic Liver Cancer, HKLC-Hong Kong Liver Cancer, SLT-salvage liver transplantation
Article
Hepatocellular carcinoma (HCC) recurrence is one of the leading causes of death after orthotopic liver transplantation (OLT). The sixth complement component (C6) is a late-acting complement protein that participates in the assembly of the membrane attack complex, which has an indispensable role in innate and acquired immune responses, as well as cancer immune surveillance. However, studies assessing the association between C6 and HCC recurrence after OLT are scarce. This study aimed to evaluate the association of donor and recipient C6 single-nucleotide polymorphisms with the risk for HCC recurrence after OLT. A total of 71 adult patients who underwent primary LT for HCC were enrolled. HCC recurrence was observed in 26 (36.6%) patients. Ten single-nucleotide polymorphisms were genotyped and analyzed in both donor and recipient groups. Patients with the rs9200 heterozygous GA variant presented significantly higher HCC recurrence rates (54.17 vs 27.66%, P=0.028), and lower cumulative tumor-free survival and overall survival (P=0.006 and P=0.013, respectively) compared with those harboring the GG/AA genotype, in multivariate logistic regression and Cox regression analyses. The rs9200 heterozygous GA variant in C6 persisted as a statistically independent prognostic factor (P<0.05) for predicting HCC recurrence after OLT. In conclusion, recipient C6 rs9200 polymorphism is associated with HCC recurrence after OLT, and improves the predictive value of clinical models.Cancer Gene Therapy advance online publication, 13 May 2016; doi:10.1038/cgt.2016.7.
Article
Purpose of review: For patients with hepatic decompensation and hepatocellular carcinoma (HCC) within Milan criteria, liver transplantation provides the best long-term recurrence-free survival. However, there is controversy about the role of liver transplantation in other subgroups, including those with compensated cirrhosis, United Network for Organ Sharing (UNOS) T1 lesions, or HCC exceeding Milan criteria. Recent findings: For patients with compensated cirrhosis, surgical resection provides similar recurrence-free survival as liver transplantation and is the most cost-effective approach. Although a 'Wait and not Ablate' approach can facilitate priority listing in most patients with UNOS T1 lesions, nearly 10% will have rapid tumor growth beyond transplant criteria, thereby missing an opportunity for curative therapy. Patients exceeding Milan criteria have higher posttransplant recurrence rates and worse survival than those within Milan criteria, and any potential benefit of liver transplantation to these patients must be weighed against harms to others on the waiting list, particularly in areas with limited donor availability. Although downstaging may help select a subgroup of patients beyond Milan with good tumor biology and better prognosis, limitations of the current literature preclude rigorous evaluation. Summary: Until higher quality data become available that demonstrate transplant benefit in expanded criteria patients, liver transplantation should be reserved for patients within Milan criteria.
Article
Introduction: A decade ago we proposed to enlist for transplantation those patients with resected hepatocellular carcinoma (HCC) in whom pathology registered pejorative histological markers (microvascular invasion and/or satellites) (ab initio indication) and not wait for the appearance of recurrence. This study evaluates the outcome of this approach. Methods: From 1995 to 2012, 164 patients with HCC underwent resection. Eighty-five patients were potential candidates to liver transplantation (LT) and were considered for it upon detection of pejorative histological markers. Patients without these markers were followed and salvage LT was considered upon development of tumor recurrence/liver function impairment. Results: Thirty-seven patients were at high-risk and 48 at low-risk of recurrence at pathology. Twenty-three out of 37 high-risk patients recurred during follow-up, but in 9 of them the tumor burden extent contraindicated LT. Seventeen were finally transplanted: 10 of them presented recurrence at imaging/explant. After a median post-transplant follow-up of 50.9 months, HCC had recurred in 2 patients and 5 patients had died, the 5-year survival being 82.4%. Twenty-six of the 48 low-risk patients developed recurrence and 11 of them were transplanted. After a median post-transplant follow-up of 59 months, two patients developed recurrence and 5 died, their 5-year survival being 81.8%. Conclusions: Enlistment of patients at high-risk of recurrence after resection before recurrence development seems a valid strategy and is associated with excellent long-term outcome. Since early (<6 months) recurrence reflects an aggressive tumor behavior leading to tumor extent exceeding transplant criteria, we propose to wait at least 6 months before enlistment. However, once included in the waiting list, priority strategies should be implemented in order to reach effective transplantation prior to the appearance of recurrence. This article is protected by copyright. All rights reserved.
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Objectives Salvage liver transplantation (SLT) is a controversial technique that has been reported to be acceptable for the management of patients with recurrent hepatocellular carcinoma (HCC) after primary hepatic resection (HR). However, whether the number of times liver resection is performed has an impact on survival after SLT has not yet been reported. Design Retrospective study. Setting The level of care is primary and the study was carried out at only 1 centre. Participants The study included 59 patients who underwent SLT for HCC from September 2001 to December 2012. 51 patients underwent HR only once before SLT, while the remaining 8 patients underwent HR more than once before SLT (HR=2 [7], HR=3, [1]). Primary and secondary outcome measures In this study, the 1-year, 3-year and 5-year overall and tumour-free survival outcomes between the 2 groups were compared. Results There were no significant differences between patients who underwent HR once and those who underwent HR more than once with respect to overall or tumour-free survival after receiving SLT. The 1-year, 3-year and 5-year overall survival rates for patients who underwent HR once were 72.9%, 35.3% and 35.5% vs 50%, 50% and 50%, respectively (p=0.986), while the 1-year, 3-year and 5-year tumour-free survival rates for those who underwent HR more than once were 66.3%, 55.3% and 44.4% vs 40%, 40% and 40%, respectively (p=0.790). Conclusions There was no significant difference in the survival rate of patients who underwent HR once before SLT and those who underwent HR more than once. This suggests that SLT is a reasonable choice for patients who suffer from recurrent HCC after HR. Trial registration number This is a retrospective study and no registry or number is required.
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Background Salvage liver transplantation (SLT) is restricted to patients who develop hepatocellular carcinoma (HCC) recurrence within Milan criteria (MC). Little is known about outcomes for SLT in patients with recurrent HCC within University of California San Francisco (UCSF) criteria after liver resection (LR). Methods Between January 2001 and December 2011, 380 patients with HCC meeting UCSF criteria, 200 of which were resected (LR group) from a perspective of SLT in case of recurrence, and 180 directly underwent LT (PLT). We compared patient characteristics, perioperative and long-term outcomes between SLT and PLT groups. We also assessed the outcome of LR and PLT groups. Results Among the 200 patients in LR group, 86 (43%) developed HCC recurrence and 15/86 (17%) of these patients presented HCC recurrence outside UCSF criteria. Only 39 of the 86 patients underwent SLT, a transplantation rate of 45% of patients with HCC recurrence. Compared with PLT group, LR group showed lower overall survival rate (P = 0.005) and higher recurrence rate (P = 0.006). Although intraoperative blood loss and required blood transfusion were more frequent in SLT group, the perioperative mortality and posttransplant complications were similar in SLT and PLT groups. The overall survival and recurrence rates did not significantly differ between the two groups. When stratifying by graft type in the SLT group, overall survival and recurrence rates did not significantly differ between deceased donor LT (DDLT) and living donor LT (LDLT) groups. In the subgroup analysis by MC, similar results were observed between patients with recurrent HCC meeting MC and patients with recurrent HCC beyond MC but within UCSF criteria. Conclusion Our single institution experience demonstrated that prior hepatectomy and SLT for recurrent HCC within UCSF criteria was feasible and SLT could achieve the same outcome as PLT.
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To summarize the experience with salvage liver transplantation (SLT) for patients with recurrent hepatocellular carcinoma (HCC) after primary hepatic resection in a single center. A total of 376 adult patients with HCC underwent orthotopic liver transplantation (OLT) at Organ Transplantation Center, the First Affiliated Hospital of Sun Yat-sen University, between 2004 and 2008. Among these patients, 36 underwent SLT after primary liver curative resection due to intrahepatic recurrence. During the same period, one hundred and forty-seven patients with HCC within Milan criteria underwent primary OLT (PLTW group), the intra-operative and post-operative parameters were compared between these two groups. Furthermore, we compared tumor recurrence and patient survival of patients with SLT to 156 patients with HCC beyond Milan criteria (PLTB group). Cox Hazard regression was made to identify the risk factors for tumor recurrence. The median interval between initial liver resection and SLT was 35 months (1-63 months). The intraoperative blood loss (P<0.05) and transfusion volume (P<0.05) were larger in the SLT group than in the PLTW group. The operation time was longer in the SLT group (P<0.05). The post-operative complications incidence, tumor recurrence rate, patients' survival rate, and tumor-free survival rate were comparable between these two groups (all P>0.05). When compared to those patients with HCC beyond Milan criteria undergoing primary OLT, patients undergoing SLT achieved a better survival and a lower tumor recurrence. Cox Proportional Hazards model showed that vascular invasion, including macrovascular and microvascular invasion, as well as AFP level >400 IU/L were risk factors for tumor recurrence after LT. In comparison with primary OLT, although SLT is associated with increased operation difficulties, it provides a good option for patients with HCC recurrence after curative resection.
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Salvage liver transplantation (SLT) has been reported as being feasible for patients who develop recurrent hepatocellular carcinoma (HCC) after primary liver resection, but this finding remains controversial. We retrospectively studied the clinical characteristics of SLT recipients and conducted a comparison between SLT recipients and primary liver transplantation (PLT) recipients. A retrospective study examined data from the China Liver Transplant Registry (CLTR) for 6,975 transplants performed from January 1999 to December 2009. A total of 6,087 patients underwent PLT and 888 patients underwent SLT for recurrence. Living donor liver transplantation (LDLT) was performed in 389 patients, while 6,586 patients underwent deceased donor liver transplantation (DDLT). Kaplan-Meier curves were used to compare survival rates. The 1-year, 3-year, and 5-year overall survival of SLT recipients was similar to that of PLT recipients: 73.00%, 51.77%, and 45.84% vs. 74.49%, 55.10%, and 48.81%, respectively (P = 0.260). The 1-year, 3-year and 5-year disease-free survival of SLT recipients was inferior to that of PLT recipients: 64.79%, 45.57%, and 37.78% vs. 66.39%, 50.39%, and 43.50%, respectively (P = 0.048). Similar survival results were observed for SLT and PLT within both the LDLT and DDLT recipients. Within the SLT group, the 1-year, 3-year, and 5-year overall survival for LDLT and DDLT recipients was similar: 93.33%, 74.67%, and 74.67% vs. 80.13%, 62.10%, and 54.18% (P = 0.281), as was the disease-free survival: 84.85%, 62.85%, and 62.85% vs. 70.54%, 53.94%, and 43.57% (P = 0.462). Our study demonstrates that for selected patients, SLT has similar survival to that of PLT, indicating that SLT is acceptable for patients with recurrent HCC after liver resection. Given the limited organ donor pool, salvage LDLT might be considered as a possible treatment.
Article
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Hepatocellular carcinoma (HCC) is a major cause of morbidity and mortality worldwide. Liver transplantation offers a potential cure for this otherwise devastating disease. The selection of the most appropriate candidates is paramount in an era of graft shortage. To review systematically the role of liver transplantation in the management of HCC in current clinical practice. An electronic literature search using PUBMED (1980-2010) was performed. Search terms included HCC, hepatoma, liver cancer, and liver transplantation. Liver transplantation is a highly successful treatment for HCC, in patients within Milan criteria (MC), defined as a solitary tumour ≤50 mm in diameter or ≤3 tumours ≤30 mm in diameter in the absence of extra-hepatic or vascular spread. Other eligibility criteria for liver transplantation are also used in clinical practice, such as the University of California, San Francisco criteria, with outcomes comparable to MC. Loco-regional therapies have a role in the bridging treatment of HCC by minimising wait-list drop-out secondary to tumour progression. Beyond MC, encouraging results have been demonstrated for patients with down-staged tumours. Post-liver transplantation, there is no evidence to support a specific immunosuppressive regimen. In the context of an insufficient cadaveric donor pool to meet demand, the role of adult living donation may be increasingly important. Liver transplantation offers a curative therapy for selected patients with HCC. The optimisation of eligibility criteria is paramount to ensure that maximum benefit is accrued. Although wait-list therapies have been incorporated into clinical practice, additional high quality data are required to support this strategy.
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Recurrent hepatocellular carcinoma (HCC) after curative resection usually originates from intrahepatic metastasis (IM) or multicentric occurrence (MO). The long-term outcomes of repeat hepatic resection in patients with different types of recurrence have not been evaluated in a large number of patients. The surgical indications for recurrent HCC remain controversial. The purpose of this study was to investigate long-term outcomes of repeat hepatic resection and clinicopathologic factors associated with different types of recurrent HCC, and to single out principle differentiating factors between IM and MO. 82 patients who underwent repeat hepatic resection for recurrent HCC were retrospectively studied. The recurrent type was evaluated by histopathologic analysis of primary and recurrent HCC. The recurrence and survival rates as well as clinicopathologic factors associated with different types of recurrence were analyzed. 45 patients (54.9%) had confirmed with IM, and 37 patients (45.1%) had with MO. The recurrence rates in the MO patients after initial or repeat resection were significantly lower than those in the IM patients (p < 0.001). The overall survival rates in the MO patients after initial or repeat resection were significantly higher than those in the IM patients (p < 0.001). Recurrence-free time was identified as the most significant differentiating factor between IM and MO. A recurrence-free time of 18 months after initial resection was a significant cutoff time point for differentiating between IM and MO. A recurrence-free time of less than or equal to 18 months and microvascular invasion at repeat resection were independent adverse prognostic factors for overall survival after repeat hepatic resection. Repeat hepatic resection resulted in much higher survival rates in the MO patients than in the IM patients. Repeat hepatic resection could be recommended for those patients in whom the recurrent HCC occurs more than 18 months after initial resection.
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We compared the long-term outcomes of resection and transplantation for hepatocellular carcinoma (HCC) while satisfying the University of California at San Francisco criteria. HCC patients who underwent liver resection (n = 746) and transplantation (n = 54) between 2001 and 2007 were reviewed. Overall and disease-free survival rates were evaluated using the Kaplan-Meier estimator, and independent prognostic factors were determined using the Cox proportional regression model. The presence of cirrhosis was used to divide the patients into groups. The patients who received primary transplantation were further analyzed. Nine years after surgery, the patients' overall survival was similar in the resection and transplantation groups (75.9 and 77.2%, respectively). Furthermore, the recurrence rate in the resection group was higher than that in the transplantation group (65 vs. 34.4%; adjusted hazard ratio, 3.27; range, 1.76-6.08), especially for cirrhosis patients (adjusted hazard ratio, 4.28; range, 2.14-8.56). The results suggested that noncirrhotic patients who underwent resection had a better survival advantage than primary liver transplant recipients did (adjusted hazard ratio, 0.46; range, 0.18-1.21). However, noncirrhotic patients had higher recurrence rates (59.2 vs. 15.8%; adjusted hazard ratio, 3.98; range, 1.26-12.58). Similar trends were noted in patients with hepatitis B virus infection and/or a single tumor. Long-term survival rates after liver transplantation and resection were similar, but the latter was associated with a higher recurrence rate.
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To compare post-orthotopic liver transplantation (OLT) survival between patients with recurrent hepatocellular carcinoma (HCC) after partial hepatectomy and those who received de novo OLT for HCC and to assess the risk factors associated with post-OLT mortality. From July 2003 to August 2005, 77 consecutive HCC patients underwent OLT, including 15 patients with recurrent HCC after partial hepatectomy for tumor resection (the rescue OLT group) and 62 patients with de novo OLT for HCC (the de novo OLT group). Thirty-three demographic, clinical, histological, laboratory, intra-operative and post-operative variables were analyzed. Survival was calculated by the Kaplan-Meier method. Univariable and multivariable analyses were also performed. The median age of the patients was 49.0 years. The median follow-up was 20 mo. Three patients (20.0%) in the rescue OLT group and 15 patients (24.2%) in the de novo OLT group died during the follow-up period (P = 0.73). The 30-day mortality of OLT was 6.7% for the rescue OLT group vs 1.6% for the de novo OLT group (P = 0.27). Cox proportional hazards model showed that pre-OLT hyperbilirubinemia, the requirement of post-OLT transfusion, the size of the tumor, and family history of HCC were significantly associated with a higher hazard for mortality. There are no significant differences in survival/mortality rates between OLT as de novo therapy and OLT as a rescue therapy for patients with hcc. Pre-OLT hyperbilirubinemia, post-OLT requirement of transfusion, large tumor size and family history of HCC are associated with a poor survival outcome.
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Surgical resection and liver transplantation offer a 5-year survival greater than 70% in patients with hepatocellular carcinoma, but the high recurrence rate impairs long-term outcome after resection. Pathological data such as vascular invasion and detection of additional nodules predict recurrence and divide patients into high and low risk profile. Based on this, we proposed salvage liver transplant to resected patients in whom pathology evidenced high recurrence risk even in the absence of proven residual disease. From January 1995 to August 2003 we have evaluated 1,638 patients. Resection was indicated in 77 patients, but only 17 (22%) (all cirrhotics, 14 hepatitis C virus+) were optimal candidates for both resection and transplantation. Of them, 8 exhibited a high risk profile at pathology and were offered transplantation. Among the 8 high risk patients, 7 presented recurrence, compared with only 2 of the 9 at low risk (P = .012). Two of the high risk patients refused transplant and developed multifocal disease during follow-up. The other 6 were enlisted and all but 1 had tumor foci in the explant. Only 1 presented extrahepatic dissemination early after transplant and died 4 months later. The others are free of disease after a median follow-up of 45 months. Two recurrences were detected in low risk patients, 1 of them being transplanted 18 months after surgery. These data in a small series of patients confirm that pathological parameters identify patients at higher risk of recurrence, which allow them to be listed for liver transplantation without proven malignant disease. In conclusion, this policy is clinically effective and could further improve the outcome of resected patients.
Article
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Liver resection (LR) for patients with small hepatocellular carcinoma (HCC) with preserved liver function, employing liver transplantation (LT) as a salvage procedure (SLT) in the event of HCC recurrence, is a debated strategy. From 1996 to 2005, we treated 227 cirrhotic patients with HCC transplantable: 80 LRs and 147 LTs of 293 listed for transplantation. Among 80 patients eligible for transplantation who underwent LR, 39 (49%) developed HCC recurrence and 12/39 (31%) of these patients presented HCC recurrence outside Milan criteria. Only 10 of the 39 patients underwent LT, a transplantation rate of 26% of patients with HCC recurrence. According to intention-to-treat analysis of transplantable HCC patients who underwent LR (n = 80), compared to all those listed for transplantation (n = 293), 5-year overall survival was 66% in the LR group versus 58% in patients listed for LT, respectively (p = NS); 5-year disease-free survival was 41% in the LR group versus 54% in patients listed for LT (p = NS). Comparable 5-year overall (62% vs. 73%, p = NS) and disease-free (48% vs. 71%, p = NS) survival rates were obtained for SLT and primary LT for HCC, respectively. LR is a valid treatment for small HCC and in the event of recurrence, SLT is a safe and effective procedure.
Article
Each year, hepatocellular carcinoma is diagnosed in more than half a million people worldwide, including approximately 20,000 new cases in the United States.(1,2) Liver cancer is the fifth most common cancer in men and the seventh in women. Most of the burden of disease (85%) is borne in developing countries, with the highest incidence rates reported in regions where infection with hepatitis B virus (HBV) is endemic: Southeast Asia and sub-Saharan Africa (Fig. 1).(3) Hepatocellular carcinoma rarely occurs before the age of 40 years and reaches a peak at approximately 70 years of age. Rates of liver cancer among men are two to four times as high as the rates among women. Hepatocellular carcinoma related to infection with hepatitis C virus (HCV) has become the fastest-rising cause of cancer-related death in the United States, and during the past two decades, the incidence of hepatocellular carcinoma in the United States has tripled while the 5-year survival rate has remained below 12%(2) (Fig. 2). The greatest proportional increase in cases of hepatocellular carcinoma has been seen among Hispanics and whites between 45 and 60 years of age.(4)
Article
Objective: To evaluate the efficacy of salvage liver transplantation (SLT), repeated hepatic resection (RR) and repeated radiofrequency ablation (rRFA) for patients with postoperative tumor recurrence. Summary Background data: The optimal treatment strategy for patients with recurrent hepatocellular carcinoma (rHCC) remains unclear. Methods: From January 1993 and September 2009, 532 patients received either hepatic resections or RFA for HCC within Milan criteria. In all, 220 patients developed intrahepatic recurrences and 87 of them were selected for SLT (n=19), RR (n=24) or rRFA (n=44). Their clinicopathological data were reviewed and survival outcomes were assessed by Kaplan Meier methods. Results: 74 out of 220 patients (33.6%) developed rHCC within Milan criteria. The median MELD scores for SLT, RR and rRFA were 10.7, 7.2 and 8.3 (P<0.001). The 1-, 3- and 5-year tumor-free survivals for SLT were 68.4%, 57.9% and 57.9%; for RHR were 69.7%, 49.3% and 49.3%; and for rRFA were 40.0%, 19.8% and 10.6% respectively (p=0.001). For rHCC within Milan criteria, the 1-, 3- and 5-year tumor-free survival rates for SLT were all 60%; for RR were 70.2%, 48.0% and 48.0%; and for RFA were 41.0%, 20.3% and 10.9% respectively (p=0.004). After adjustments of MELD score, the 5-year survivals for SLT, RR and rRFA were 50.0%, 48.0% and 21.4% (P=0.004). Subgroup analysis showed that SLT and RR attained comparable survival outcomes, but both treatments attained significantly better survival outcomes than rRFA (P<0.001). Conclusions: SLT is an efficacious treatment for patients with rHCC and should be considered when RR is not feasible. © 2013 American Association for the Study of Liver Diseases.
Article
Introduction: Liver transplantation (LT) after liver resection (LR) for hepatocellular carcinoma (HCC) recurrence may be associated with poor patient long-term results and higher perioperative patient morbidity and mortality. This study focused on short-term and long-term outcomes of LT recipients due to HCC recurrence after LR in a single-institution cohort, and in highly comparable case-matched subgroups. Methods: Between 2000 and 2009, 570 consecutive patients with documented HCC underwent LR (n=355, 62.2%) or LT (n=215, 37.8%) at our Institute. The case-matched analysis was between 2 groups: group A1, LT recipients who had already undergone LR (n=26); group B1, LT recipients who had not already undergone LR (n=26). Results: Patient morbidity was higher in the A1 group in terms of packed red blood cell units transfused, fresh frozen plasma units transfused, median operative time, postoperative bleeding, and postoperative reoperations. No differences were detected in terms of patient mortality, patient survival, and patient recurrence-free survival at the univariate and multivariate analysis. Conclusions: Although LT among patients who have already undergone LR is associated with higher risk of patient morbidity, patient long-term survival and recurrence-free survival is not impaired. Therefore, there do not seem to be any valid reasons to deny the chance of LT to patients who have already undergone LR.
Article
Long-term outcomes of patients who experience recurrence after liver resection (LR) of hepatocellular carcinoma (HCC) are uncertain. The characteristics of 58 patients were obtained from a retrospective database at two time points: primary resection and recurrence. Patterns of recurrence, treatment strategies, and long-term survival rates were analyzed. The recurrence was inside the Milan criteria (Milan+) in 19 patients (32.7 %), 11 of whom were already eligible for a liver transplant (LT) at the time of primary liver resection (LR). Treatment of the recurrence included the following procedures: salvage LT (n = 6; 10.3 %), repeat LR (n = 7; 12.1 %), percutaneous radiofrequency ablation (RFA) and/or transarterial chemoembolization (TACE) (n = 24; 41.3 %), systemic chemotherapy (n = 15; 25.8 %), and best supportive care (n = 12; 20.7 %). With a mean follow-up of 26.9 ± 27.9 months, the overall 1-, 3-, and 5-year survival rates of the 58 patients with HCC recurrence after primary LR were 57.3, 42.5, and 35.3 %, respectively. In the multivariate analysis the presence of esophageal varices (p = 0.001), an AFP level >200 μg/L (p = 0.03) and a Milan- recurrence pattern (p = 0.05) were independent predictors of decreased survival. The overall 5-year survival of patients who experienced Milan+ recurrence was comparable to that of Milan+ patients who underwent primary LR (62.5 % vs. 66.3 %, p = 0.48). Aggressive management of recurrent HCC after upfront LR improves patient survival. The pattern of recurrence is an independent predictor of survival which can be used as a selection criterion for salvage LT.
Article
Hepatocellular carcinoma is the sixth most prevalent cancer and the third most frequent cause of cancer-related death. Patients with cirrhosis are at highest risk of developing this malignant disease, and ultrasonography every 6 months is recommended. Surveillance with ultrasonography allows diagnosis at early stages when the tumour might be curable by resection, liver transplantation, or ablation, and 5-year survival higher than 50% can be achieved. Patients with small solitary tumours and very well preserved liver function are the best candidates for surgical resection. Liver transplantation is most beneficial for individuals who are not good candidates for resection, especially those within Milano criteria (solitary tumour ≤5 cm and up to three nodules ≤3 cm). Donor shortage greatly limits its applicability. Percutaneous ablation is the most frequently used treatment but its effectiveness is limited by tumour size and localisation. In asymptomatic patients with multifocal disease without vascular invasion or extrahepatic spread not amenable to curative treatments, chemoembolisation can provide survival benefit. Findings of randomised trials of sorafenib have shown survival benefits for individuals with advanced hepatocellular carcinoma, suggesting that molecular-targeted therapies could be effective in this chemoresistant cancer. Research is active in the area of pathogenesis and treatment of hepatocellular carcinoma.
Article
Salvage liver transplantation (LT) has been proposed for patients with a small hepatocellular carcinoma (HCC) and preserved liver function. Few reports have been issued on salvage LT in a living-donor (LD) LT setting. Therefore, we performed this study to evaluate differences in tumor invasiveness and other risk factors on survival after salvage versus primary LDLT. Between September 1996 and December 2008, 324 patients with HCC underwent LT. We excluded 138 patient from the analysis, leaving 186 HCC patients for analysis, including 17 (9.1%) who had undergone earlier resection, the salvage LDLT cohort. The other 169 patients underwent primary LDLT. Intrahepatic metastasis, Edmonson-Steiner histologic grade, microscopic vascular invasion, and preoperative serum alpha-fetoprotein levels significantly influenced tumor recurrence. Microscopic vascular invasion, intrahepatic metastasis, Edmonson-Steiner histologic grade, and treatment by salvage LDLT were significantly associated with poor patient survival univariate analysis. However, only microscopic vascular invasion was significant on multivariate analysis. The treatment modality (primary or salvage LDLT) was not observed to affect overall or disease-free survival significantly on multivariate analysis. Disease-free survival was significantly better in the primary than in the salvage LDLT group. Furthermore, patients in the primary LDLT group tended to show better survival. However, when stratified by the presence or absence of microscopic vascular invasion, no significant group difference was found for overall or disease-free survival among those without versus with microscopic vascular invasion. Five-year overall survival after primary versus salvage LDLT were similar when differences in tumor pathologic features, such as microscopic vascular invasion, were taken into account. Multivariate analysis showed that the treatment itself was not a significant prognostic factor for survival.
Article
Hepatocellular carcinoma (HCC) is the leading malignant tumor in Taiwan. The majority of HCC patients are diagnosed in late stages and therefore in eligible for potentially curative treatments. Locoregional therapy has been advocated as an effective treatment for patients with advanced HCCs. The aim of this study was to evaluate the outcomes of HCC downstaged patients after locoregional therapy to allow eligibility for liver transplantation. From January 2004 to June 2010, 161 patients with HCCs underwent liver transplantation including 51 (31.6%) who exceeded the University of California-San Francisco (UCSF) who had undergone successful locoregional therapy to be downstaged within these criteria. Among the downstaged patients, 48 (94.1%) underwent transarterial embolization; 7 (13.8%), percutaneous ethanol injection; 24 (47.1%), radiofrequency ablation; 15 (29.4%), surgical resection, and 34 (66.7%), combined treatment. The overall 1- and 5-year survival rates of all HCC patients (n=161) were 93.2% and 80.5%. The overall 1- and 5-year survival rates of downstaged (n=51) versus non-downstaged (n=110) subjects were 94.1% versus 83.7% and 92.7% versus 78.9%, respectively (P=.727). There are 15 (9.2%) HCC recurrences. The overall 1- and 5-year tumor-free rates of all HCC patients were 94.8% and 87.2%. The overall 1- and 5-year tumor-free rates between downstaged versus non-downstaged patients were 93.9% and 90.1% versus 95.2% and 86.0%, respectively (P=.812). Patients with advanced HCC exceeding the UCSF/Milan criteria can be downstaged to fit the criteria using locoregional therapy. Importantly, successfully downstaged patients who are transplanted show excellent tumor-free and overall survival rates, similar to fit-criteria group.
Article
Many patients are diagnosed with hepatocellular carcinoma (HCC) within the Milan criteria. In Korea, these patients are preferentially treated with locoregional therapy (LRT) instead of living donor liver transplantation. We investigated the effectiveness of LRT in liver transplant recipients who met the Milan criteria at the time of HCC diagnosis and investigated risk factors for HCC recurrence. We retrospectively reviewed the medical records of patients diagnosed with HCC who met the Milan criteria between 2002 and 2008. We performed 101 liver transplants for HCC during the study period. Seventy-one patients (70%) underwent pretransplant LRT. The disease-free survival rates at 1, 3, and 5 years in patients who received LRT were 96.6%, 93.1%, and 93.1%, and in those who did not receive LRT, 94.2%, 83.4%, and 83.4%, respectively. There were no differences between the 2 groups. Multivariate analysis showed that a low Model for End-Stage Liver Disease (MELD) score and microvascular invasion were independent predictors of HCC recurrence after transplantation. The MELD scores and rate of microvascular invasion were not statistically different in patients with or without previous LRT. Pretransplant LRT for patients with HCC who met the Milan criteria at the time of diagnosis did not provide a clear benefit with respect to HCC recurrence after transplantation. If patients have suitable living donors, those who meet the Milan criteria should undergo a liver transplantation as soon as possible.
Article
Liver resection (LR) for patients with small hepatocellular carcinoma (HCC) with preserved liver function, employing liver transplantation (LT) as a salvage procedure (SLT) in the event of HCC recurrence, is a debated strategy. From 1996 to 2005, we treated 227 cirrhotic patients with HCC transplantable: 80 LRs and 147 LTs of 293 listed for transplantation. Among 80 patients eligible for transplantation who underwent LR, 39 (49%) developed HCC recurrence and 12/39 (31%) of these patients presented HCC recurrence outside Milan criteria. Only 10 of the 39 patients underwent LT, a transplantation rate of 26% of patients with HCC recurrence. According to intention-to-treat analysis of transplantable HCC patients who underwent LR (n = 80), compared to all those listed for transplantation (n = 293), 5-year overall survival was 66% in the LR group versus 58% in patients listed for LT, respectively (p = NS); 5-year disease-free survival was 41% in the LR group versus 54% in patients listed for LT (p = NS). Com
Article
Primary transplantation offers longer life-expectancy in comparison to hepatic resection (HR) for hepatocellular carcinoma (HCC) followed by salvage transplantation; however, livers not used for primary transplantation can be reallocated to the remaining waiting-list patients, thus, the harm caused to resected patients could be balanced, or outweighed, by the benefit obtained from reallocation of livers originating from HCC patients first being resected. A Markov model was developed to investigate this issue based on literature data or estimated from the United Network for Organ Sharing database. Markov model shows that primary transplantation offers longer life-expectancy in comparison to HR and salvage transplantation if 5-year posttransplant survival remains higher than 60%. The balance between the harm for resected patients and the benefit for the remaining waiting list depends on (a) the proportion of HCC candidates, (b) the percentage shifted to HR and (c) the median expected time-to-transplant.
Article
Little is known about outcomes and indications for living donor liver transplantation in patients with recurrent hepatocellular carcinoma after liver resection. We analyzed retrospectively 176 patients with hepatocellular carcinoma who underwent living donor liver transplantation at our institute between February 1999 and December 2009. Among 128 of 176 patients with a history of pretreatment for hepatocellular carcinoma, 19 patients underwent radical liver resection. We compared patient characteristics, intraoperative blood loss, operative duration, and long-term outcomes including overall survival and recurrence rates between patients who had received hepatectomy, other pretreatments, and no pretreatments. The surgical duration was significantly longer in patients with pretransplant hepatectomy than in those who had undergone other types of pretreatment (n = 109) or none (n = 48), whereas intraoperative blood loss did not differ among the 3 groups. Overall survival and recurrence rates did not significantly differ among the 3 groups. In patients with pretransplant hepatectomy, survival rates were significantly higher among patients who met the Kyoto criteria (≤10 tumors, all ≤5 cm in diameter and serum des-gamma-carboxy prothrombin levels ≤400 mAU/mL; n = 15) than those with values that exceeded the Kyoto criteria (n = 4) (5-year survival rates, 93% vs 25%, P = .005). Similarly, recurrence rates were significantly lower among patients meeting than exceeding the Kyoto criteria (5-year recurrence rates, 10% vs 67%, P = .011). Patients with hepatocellular carcinoma recurrence after liver resection can safely undergo living donor liver transplantation. Long-term outcomes can be particularly favorable in patients who meet the Kyoto criteria.
Article
Unlabelled: Liver resection (LR) for hepatocellular carcinoma (HCC) as the first-line treatment in transplantable patients followed by "salvage transplantation" (ST) in case of recurrence is an attractive concept. The aim was to identify patients who gain benefit from this approach in an intention-to-treat study. From 1998 to 2008, among 329 potential candidates for liver transplantation (LT) with HCC within the Milan criteria (MC), 138 with good liver function were resected (LR group) from a perspective of ST in case of recurrence, and 191 were listed for LT first (LT group). The two groups were compared on an intention-to-treat basis with special reference to management of recurrences and transplantability after LR. Univariate and multivariate analyses were performed to identify resected patients who developed recurrence beyond MC. Five-year overall and disease-free survival was similar in both groups: LT versus LR group, 60% versus 77% and 56% versus 40%, respectively. Among the 138 patients in the LR group, 20 underwent LT before recurrence, 39 (28%) had ST, and 51 (37%) with recurrence were not transplanted including 21 within MC who were excluded for advanced age, acquired comorbidities, or refusal and 30 (22%) with recurrence beyond MC. Predictive factors for nontransplantability due to recurrence beyond MC included microscopic vascular invasion (hazard ratio [HR] 2.38 [range, 1.10-7.29]), satellite nodules (HR 2.46 [range, 1.01-6.68]), tumor size > 3 cm (HR 1.34 [range, 1.03-3.12]), poorly differentiated tumor (HR 3.18 [range, 1.31-7.70]), and liver cirrhosis (HR 1.90 [range, 1.04-3.12]). Conclusion: The high risk of failure of ST after initial LR for HCC within MC suggests the use of tissue analysis as a selection criterion. The salvage LT strategy should be restricted to patients with favorable oncological factors.
Article
To investigate the trend of the posthepatectomy survival outcomes of hepatocellular carcinoma (HCC) patients by analysis of a prospective cohort of 1198 patients over a 20-year period. The hospital mortality rate of hepatectomy for HCC has improved but the long-term survival rate remains unsatisfactory. We reported an improvement of survival results 10 years ago. It was not known whether there has been further improvement of results in recent years. The patients were categorized into two 10-year periods: period 1, before 1999 (group 1, n = 390) and period 2, after 1999 (group 2, n = 808). Patients in group 2 were managed according to a modified protocol and technique established in previous years. The patients in group 2 were older and had a higher incidence of comorbid illness and cirrhosis. They had a lower hospital mortality rate (3.1% vs 6.2%, P = 0.012) and longer 5-year overall survival (54.8% vs 42.1%, P < 0.001) and disease-free survival rates (34.8% vs 24%, P = 0.0024). An improvement in the overall survival rate was observed in patients with cirrhosis, those undergoing major hepatectomy, and those with tumors of tumor-node-metastasis stages II, IIIA, and IVA. A significant increase in the survival rates was also seen in patients whose tumors were considered transplantable by the Milan criteria (72.5% vs 62.7%, P = 0.0237). Multivariate analysis showed a significantly more favorable patient survival for hepatectomy in period 2. A continuous improvement of survival outcomes after hepatectomy for HCC was achieved in the past 20 years even in patients with advanced diseases. Hepatectomy remains the treatment of choice for resectable HCC in a predominantly hepatitis B virus-based Asian population.
Article
The global burden of cancer continues to increase largely because of the aging and growth of the world population alongside an increasing adoption of cancer-causing behaviors, particularly smoking, in economically developing countries. Based on the GLOBOCAN 2008 estimates, about 12.7 million cancer cases and 7.6 million cancer deaths are estimated to have occurred in 2008; of these, 56% of the cases and 64% of the deaths occurred in the economically developing world. Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death among females, accounting for 23% of the total cancer cases and 14% of the cancer deaths. Lung cancer is the leading cancer site in males, comprising 17% of the total new cancer cases and 23% of the total cancer deaths. Breast cancer is now also the leading cause of cancer death among females in economically developing countries, a shift from the previous decade during which the most common cause of cancer death was cervical cancer. Further, the mortality burden for lung cancer among females in developing countries is as high as the burden for cervical cancer, with each accounting for 11% of the total female cancer deaths. Although overall cancer incidence rates in the developing world are half those seen in the developed world in both sexes, the overall cancer mortality rates are generally similar. Cancer survival tends to be poorer in developing countries, most likely because of a combination of a late stage at diagnosis and limited access to timely and standard treatment. A substantial proportion of the worldwide burden of cancer could be prevented through the application of existing cancer control knowledge and by implementing programs for tobacco control, vaccination (for liver and cervical cancers), and early detection and treatment, as well as public health campaigns promoting physical activity and a healthier dietary intake. Clinicians, public health professionals, and policy makers can play an active role in accelerating the application of such interventions globally.
Article
The present study was designed to explore the safety and feasibility of laparoscopic re-resection of recurrent liver tumors. Among 120 hepatocellular carcinoma patients who received laparoscopic hepatectomy, six were carefully selected to receive laparoscopic re-resection. Surgical indications were evaluated by specific selection criteria for tumor location, size, metastases, vessel invasion, and liver function. Four patients received laparoscopic partial hepatectomy, and two received laparoscopic anatomical left lateral lobe resection. Results were analyzed retrospectively. The six surgeries (four laparoscopic partial hepatectomies, two laparoscopic anatomical left lateral lobe resections) were successfully performed with no intraoperative complications. Mean operative time was 140.83 ± 35.69 min, mean blood loss was 283.33 ± 256.25 ml, and mean hospital stay was 5.67 ± 1.63 days. Our experience with carefully selected cases meeting specific criteria suggests that laparoscopic hepatic re-resection is a safe, feasible procedure that may offer multiple benefits for treating recurrent hepatocellular carcinoma.
Article
The aim of this study was to ascertain the outcome of liver transplantation (LT) due to hepatocellular carcinoma (HCC) in patients who had undergone previous liver resection (LR) for HCC. A case-control study (1:2) was designed to compare patients who underwent LT due to HCC recurrence with a previous LR for HCC (study group) with those who underwent LT for primary HCC but without previous LR (control group). From January 1990 to December 2007, a total of 303 cirrhotic patients with primary HCC were evaluated for surgery. Primary LT was performed in 191 and LR in 100. When HCC recurrence was diagnosed after LR (69/100), 17 of the 69 (25%) patients underwent LT (study group). The median follow-up was 70 months (12.7-203.0 months). Disease-free survivals at 1, 3, and 5 years in the study group versus the control group were 86%, 68%, 58% vs. 97%, 93%, 89%, respectively (p < 0.04). The 1-, 3-, and 5-year actuarial patient survivals in the study group versus the control group were 59%, 52%, 52% vs. 85%, 76%, 65%, respectively (p = NS). Patients of the study group were divided into two groups according to the time to recurrence after LR: group 1 was <1 year, and group 2 was >1 year. Recurrence after LT was 75% in group 1 vs. 15.4% in group 2 (p < 0.03). The 1-, 3-, and 5-year actuarial patient survivals were 25%, 0%, 0% in group 1 and 69%, 69%, 69% in group 2, p < 0.02). Liver transplantation can be safely performed after a previous LR for HCC. Patients with recurrence during the first year after hepatectomy have a poor prognosis after LT.
Article
Transplantation is the treatment of choice for hepatocellular carcinoma (HCC) meeting the Milan criteria. HCC and chronic liver diseases have distinct natural histories for which an equitable transplant policy must account. We enrolled and prospectively followed at a single center 206 consecutive HCC patients that presented within the Milan criteria. Patients were treated per the Barcelona Clinic Liver Cancer (BCLC) algorithm; 95% received resection, ablation, or transarterial chemoembolization. The median follow-up was 16 months. Progression occurred in 84 patients, and 8 patients died. Risk factors for the time to disease progression (death or progression beyond T2) were analyzed in 170 patients with a complete data set. Risk factors with the strongest relationship to progression included tumor diameter and tumor persistence/recurrence after local therapy (hazard ratios of 1.51 and 2.75, respectively, when transplanted patients were censored at the time of transplantation and hazard ratios of 1.53 and 3.66, respectively, when transplantation was counted as an event; P < or = 0.0001). To evaluate the current Model for End-Stage Liver Disease (MELD) exception, we compared the expected progression rate (PR) with our observed PR in 133 stage T2 patients. The current policy resulted in a large overestimation of the PR for T2 HCC and an unsatisfactory performance [Harrell's concordance index (C index) = 0.60, transplant censored; C index = 0.55, transplant as progression]. Risk factors for progression that were identified by univariate analysis were considered for multivariate analysis. With these risk factors and the patients' natural MELD scores, an adjusted model applicable to organ allocation was generated, and this decreased the discrepancy between the expected and observed PRs (C index = 0.66, transplant censored; C index = 0.69, transplant as progression). In conclusion, the current MELD exception largely overestimates progression in T2 patients treated according to the BCLC guidelines. The tumor response to resective or ablative treatment can predict tumor progression beyond the Milan criteria, and it should be taken into account in models designed to prioritize organ allocation.
Article
Primary transplantation offers longer life-expectancy in comparison to hepatic resection (HR) for hepatocellular carcinoma (HCC) followed by salvage transplantation; however, livers not used for primary transplantation can be reallocated to the remaining waiting-list patients, thus, the harm caused to resected patients could be balanced, or outweighed, by the benefit obtained from reallocation of livers originating from HCC patients first being resected. A Markov model was developed to investigate this issue based on literature data or estimated from the United Network for Organ Sharing database. Markov model shows that primary transplantation offers longer life-expectancy in comparison to HR and salvage transplantation if 5-year posttransplant survival remains higher than 60%. The balance between the harm for resected patients and the ben