Management of hepatocellular carcinoma. Clin Liver Dis. Global estimates of cancer prevalence for 27 sites in the adult population in Int J Cancer.
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AIM: To detect whether the up-to-seven should be used as inclusion criteria for liver transplantation for hepatocellular carcinoma.
These patients were divided into three groups according to the characteristics of their tumors tumor diameter, tumor number : the Milan criteria group Group 1 , the in up-to-seven group Group 2 and the out up-to-seven group Group 3. Then, we compared long-term survival and tumor recurrence of these three groups. RESULTS: The baseline characteristics of transplant recipients were comparable among these three groups, except for the type of liver graft deceased donor liver transplant or live donor liver transplantation.
The 1-, 3-, and 5-year overall survival and tumor-free survival rate for the Milan criteria group were Core tip: The up-to-seven criteria were introduced several years ago, but there is still no consensus about their effectiveness. Two hundred and twenty patients were divided into three groups according to the characteristics of their tumors: the 1-, 3-, and 5-year overall survival and tumor-free survival rate for the Milan criteria group were higher than that in the up-to-seven criteria group.
So considering that patients in the up-to-seven criteria group exhibited a considerable but lower survival rate compared with the Milan criteria group, the up-to-seven criteria should be used carefully and selectively. Hepatocellular carcinoma HCC is a major health problem worldwide and is the sixth most common cancer and the third most common cause of cancer death[ 1 ].
This disease is especially problematic for Asian countries, which have a high prevalence of hepatitis B virus HBV and hepatitis C virus infection[ 2 ]. Effective management of early HCC includes resection, radiofrequency ablation and liver transplantation LT. Liver transplantation remains the best treatment for small HCC resulting from chronic liver disease, as it both removes the neoplastic lesion and eliminates the underlying disease in a single procedure. Stringent inclusion criteria have been adopted to ensure tumor free survival after LT.
Due to the favorable results that have been achieved, i. Several years later, based on greater experience, some groups argued that the Milan criteria should be expanded, as a substantial number of patients with HCC exceeding these criteria could also greatly benefit from transplantation[ 6 - 10 ].
Several groups argued the Milan criteria were too strict and excluded some HCC patients from LT, despite the possibility of benefit, and that the criteria should be expanded.
Therefore, the Milan group Mazzaferro et al[ 11 ] attempted to expand the Milan criteria and create a new set called the up-to-seven criteria new Milan criteria : hepatocellular carcinomas with seven as the sum of the size of the largest tumor in cm and the number of tumors.
Following this study, several other studies demonstrated that the up-to-seven criteria could be useful as a model for evaluating potential candidates for liver transplantation to treat HCC[ 12 - 15 ]. Although the up-to-seven criteria have been analyzed all over the world, they have not been as widely accepted as the Milan criteria, even 4 years after their conception. Therefore, in our study, we compared the outcomes of Milan criteria patients with those of up-to-seven criteria patients, and then we evaluated the effectiveness of the up-to-seven criteria as inclusion criteria for HCC LT.
All of these patients were diagnosed with HCC based on pre-operative imaging studies, and the diagnoses were confirmed by pathology. Patients with cholangio-hepatocellular cancer or other liver diseases were excluded from this study. All of the tumor characteristics were evaluated by histological examination. Of these cases, 58 patients met the Milan criteria Group 1 , 90 patients met the up-to-seven criteria Group 2 and patients did not meet either the Milan criteria or up-to-seven criteria Group 3.
We retrospectively collected the data of these three groups and then compared their baseline characteristics, intraoperative data, post-operative recovery and long-term survival, including the overall survival, tumor-free survival and recurrence rate. In our study, the grafts for liver transplantation were from living right lobe donors and deceased donors.
No prisoners were included as donors, and all of the whole liver grafts were donations after cardiac death. All of these donations were volunteered by the donor or the family. For grafts that came from living donors, the donor was required to be within three degrees of consanguinity with the recipient, as verified by a DNA test, and all of the living donor liver transplantations were performed after obtaining approval from the Ethics Committee of the West China Hospital and local authorities.
All of the donations were voluntary and altruistic. We informed the donors and their families of the possible risks of donor hepatectomy. Written consent was provided by the donors for the storage of their information in the hospital database and its use for research.
The surgical procedures performed on the donor and the recipients are described in our previous reports[ 17 - 19 ]. Routine post-LT triple-immunosuppressive treatment in our center includes tacrolimus or cyclosporin, mycophenolate mofetil, and steroids.
The doses of tacrolimus and cyclosporine were adjusted based on the measured serum level. All of the data were managed and analyzed using SPSS The overall survival and tumor-free survival rates were calculated and compared using Kaplan-Meier analysis. Only tumor-related deaths were included in the recurrence-free survival analysis. The log-rank test was performed to compare survival curves. Over six years, HCC patients underwent LT at our transplantation center, and all of them were followed up for at least 5 years.
There were no significant differences among three groups with respect to recipient gender, age, or body mass index BMI. The most common etiology of cirrhosis was hepatitis B infection.
There were only 2 cases of hepatitis C infection. However, fewer patients underwent LDLT in the out up-to-seven group: The pre-LT liver function, determined by the Meld score and Child score, were also not different among the three groups. There were also no differences among the three groups with respect to donor characteristics, including donor age, BMI and donor risk index.
Baseline, tumor characteristics, and overall and tumor-free survival rates of the liver transplantation recipients. The out up-to-seven criteria group had the highest tumor number, followed by the up-to-seven criteria group. There were no diffused targets in either the Milan group or the up-to-seven criteria group. However, there were 34 cases with diffused targets in the out up-to-seven criteria group. Seventy-on cases were diagnosed with macrovascular invasion by pre-LT imaging scans, and the diagnoses were confirmed by histological examination.
One new target was found in the explanted liver of a patient in the Milan group, and 3 new targets were found in the up-to-seven group. The diameters of these new targets ranged from 0. The length of follow-up for all the patients in our study was at least 5 years, and no significant differences were observed among the groups. The 1-, 3-, and 5-year overall and tumor-free survival rates of Milan criteria group were superior to those of the up-to-seven patients [ The most common reason for mortality within 1 year was complications, and not tumor recurrence, for the Milan criteria group and up-to-seven criteria group none of the patients in the Milan criteria group and 2 patients However, most of the 26 However, 1 year after LT, the most common cause of mortality for all three groups was tumor recurrence.
The most common site of recurrence was the liver graft for all three groups, and lung metastasis was the second common site of recurrence. Although more patients were diagnosed with recurrence or metastasis in the out up-to-seven group than in the other groups, the site of recurrence or metastasis was not significantly different among the three groups. In the 71 cases who were diagnosed with macrovascular invasion, 54 Survival and tumor recurrence.
Other: Lung and brain 1 case , lung and spine liver, lung and bone. All of the baseline characteristics were comparable among the three groups, except for the source of the liver graft, as there were many fewer living donor liver transplantations in the up-to-seven group compared with the Milan criteria group. The main reason for this selective bias was the absence of a national organ allocation system such as the United Network for Organ Sharing in China; the lack of such a system means that the criteria for HCC living donor liver transplantation are much stricter than deceased donor liver transplantation because living donor liver graft harvest involves potential risks to donors, including death[ 18 , 21 ].
However, this bias was assumed to have no impact on our analyses, as the results of another of our studies indicated that there were no significant differences in postoperative complications, tumor recurrence rate, survival rate, and HBV recurrence between deceased donor liver transplant DDLT and live donor liver transplantation LDLT patients[ 22 ].
Some published papers[ 25 ] have even indicated that early graft regeneration and features specific to living-donor liver transplantation LDLT may adversely influence the recurrence of HCC. Our data indicated that LDLT was performed more frequently in the Milan criteria group, so this selective bias did not affect the long-term survival rate. Since the Milan criteria for HCC LT were proposed in , dozens of models from all over the world have been developed to expand the indications for LT for patients with HCC without compromising overall or tumor-free survival compared with patients who underwent LT based on the Milan criteria.
The main aim of expanding the Milan criteria was to include more HCC patients but maintain comparable outcomes. Although few reports have suggested that tumor involvement in the portal branches is a contraindication for LT[ 26 , 27 ], there is general agreement among various researchers that patients presenting macrovascular invasion or extrahepatic spread should be excluded from LT given the unacceptable rate of recurrence[ 10 ]; this presumption was confirmed by our analysis, which showed a very high recurrence rate However, the proposed expanded criteria appear to be vague: the upper diameter of a single tumor ranges from 5 to 9 cm[ 6 , 28 - 30 ], and the highest number of tumors ranges from 3 to unlimited[ 6 , 28 , 29 , 31 ].
Some published studies did not even impose upper limits on the tumor number or diameter[ 32 , 33 ]. Thirteen years after the Milan criteria were developed, the Mazzaferro group proposed an expanded set of criteria called the up-to-seven criteria new Milan criteria. In their study, the 5-year overall survival rate for Milan group patients was However, for the up-to-seven criteria patients, the overall survival rate in our study was Several studies have evaluated the effectiveness of using the up-to-seven criteria as inclusion criteria for HCC LT[ 14 , 15 ].
Their results showed that the post liver transplantation survival rates were However, there is still some disagreement regarding the up-to-seven criteria. In a letter to Mazzaferro and his colleagues, Sotiropoulos et al[ 13 ] stated that although the up-to-seven criteria are based on objective tumor characteristics such as tumor size, tumor number, and microvascular invasion, these characteristics represent pathology findings and not preoperative objective tumor characteristics, and therefore, the up-to-seven criteria are illusive and not applicable in clinical practice.
In the present study, 71 patients Our data on the tumor characteristics for this analysis all come from pre-operative imaging data and were confirmed by the histological examination.
Only a few targets 4 cases were found in the explanted liver. We did not evaluate the new targets in the out up-to-seven group because there were some cases with diffused tumors, so finding and calculating new tumor targets would have been very difficult in these patients. Our Milan criteria patients exhibited a Although the up-to-seven criteria group included 90 patients, which was much higher than the number of patients in the Milan criteria group 53 cases , the main aim of expanding the Milan criteria was to include more HCC patients without compromising outcomes; this, in our study, long-term 5-year survival was much lower in the up-to-seven group.
The further the criteria are expanded, the higher the risk in terms of survival[ 4 ]. However, although the survival rate in the up-to-seven criteria group was lower than that in the Milan criteria group, the 5-year overall survival rate was still considerable at Meanwhile, the overall survival rate of patients who met the up-to-seven criteria was much higher than those who did not meet up-to-seven criteria 5-year survival rate: These comparisons suggest that the up-to-seven criteria may be accepted.
The limitations of this study include the fact that these data were retrospectively collected and analyzed. A future randomized study would be the best way to evaluate the effectiveness of the up-to-seven criteria as inclusion criteria for HCC LT. However, this ideal design would be very difficult to implement due to logistical challenges.
In addition, a large multicenter study comparing a larger number of patients with HCC LT would be ideal for future analyses. In conclusion, considering the differences in long-term outcome, care should be taken when using the up-to-seven criteria rather than the Milan criteria to include HCC patients in LT.
Liver transplantation remains the best treatment for small hepatocellular carcinoma HCC resulting from chronic liver disease.
Several years later, based on greater experience, some groups argued that the Milan criteria should be expanded. Therefore, the Milan group attempted to expand the Milan criteria and create a new set called the up-to-seven criteria new Milan criteria : HCCs with seven as the sum of the size of the largest tumor and the number of tumors.
The up-to-seven criteria were introduced several years ago, but there is still no consensus about their effectiveness.
2014, Número 3
In transplantation medicine , the Milan criteria are set of criteria applied in consideration of patients with cirrhosis and hepatocellular carcinoma HCC for liver transplantation with intent to cure their disease. Their significance derives from a landmark study in 48 patients by Mazzaferro et al which showed that selecting cases for transplantation according to specific strict criteria led to improved overall and disease-free survival at a 4-year time point. Given the limitations of the original Mazzaferro study, including the small number of patients and limited inclusion criteria, there is ongoing discussion and controversy regarding the appropriate criteria for transplant. Some have advocated for the use of expanded guidelines for liver transplantation in the setting of HCC. In , Yao et al. From Wikipedia, the free encyclopedia. Controversy and Research [ edit ] Given the limitations of the original Mazzaferro study, including the small number of patients and limited inclusion criteria, there is ongoing discussion and controversy regarding the appropriate criteria for transplant.
Up-to-seven criteria for hepatocellular carcinoma liver transplantation: A single center analysis
AIM: To detect whether the up-to-seven should be used as inclusion criteria for liver transplantation for hepatocellular carcinoma. These patients were divided into three groups according to the characteristics of their tumors tumor diameter, tumor number : the Milan criteria group Group 1 , the in up-to-seven group Group 2 and the out up-to-seven group Group 3. Then, we compared long-term survival and tumor recurrence of these three groups. RESULTS: The baseline characteristics of transplant recipients were comparable among these three groups, except for the type of liver graft deceased donor liver transplant or live donor liver transplantation. The 1-, 3-, and 5-year overall survival and tumor-free survival rate for the Milan criteria group were Core tip: The up-to-seven criteria were introduced several years ago, but there is still no consensus about their effectiveness.
The Milan criteria are a generally accepted set of criteria used to assess suitability in patients for liver transplantation with cirrhosis and hepatocellular carcinoma. Please Note: You can also scroll through stacks with your mouse wheel or the keyboard arrow keys. Updating… Please wait. Unable to process the form. Check for errors and try again.
2019, Número 3
Liver transplantation for hepatic tumors: a systematic review. World J Gastroenterol. A novel prognostic nomogram accurately predicts hepatocellular carcinoma recurrence after liver transplantation: analysis of consecutive liver transplant recipients. J Am Coll Surg.