Transcatheter arterial chemoembolisation (TACE) is the treatment of choice for intermediate stage hepatocellular carcinoma (HCC). Doxorubicin-loaded drug-eluting beads (DEB)-TACE is expected to ...improve the performance of conventional TACE (cTACE). The aim of this study was to compare DEB-TACE with cTACE in terms of time-to-tumour progression (TTP), adverse events (AEs), and 2-year survival.
Patients were randomised one-to-one to undergo cTACE or DEB-TACE and followed-up for at least 2 years or until death. Transcatheter arterial chemoembolisation was repeated 'on-demand'.
We enrolled 177 patients: 89 underwent DEB-TACE and 88 cTACE. The median number of procedures was 2 in each arm, and the in-hospital stay was 3 and 4 days, respectively (P=0.323). No differences were found in local and overall tumour response. The median TTP was 9 months in both arms. The AE incidence and severity did not differ between the arms, except for post-procedural pain, more frequent and severe after cTACE (P<0.001). The 1- and 2-year survival rates were 86.2% and 56.8% after DEB-TACE and 83.5% and 55.4% after cTACE (P=0.949). Eastern Cooperative Oncology Group (ECOG), serum albumin, and tumour number independently predicted survival (P<0.05).
The DEB-TACE and the cTACE are equally effective and safe, with the only advantage of DEB-TACE being less post-procedural abdominal pain.
Background
The benefit of surgical intervention for cancer should be estimated in relation to the life expectancy of the general population. The aim of this study was to provide a measure of relative ...survival after hepatectomy for hepatocellular carcinoma (HCC).
Methods
Consecutive patients with liver cirrhosis and HCC who underwent hepatectomy were divided into age quartiles for analysis. Short‐ and mid‐term survival rates were used to estimate survival until death for all patients, in relation to age and other co‐variables. Years of life lost (YLL) were estimated using a reference cohort, derived from the general population matched for sex, age and year of diagnosis.
Results
Some 919 patients were included in the study. The following age quartiles were identified: less than 60 years (229 patients), 60–66 years (230), 67–70 years (231) and over 70 years (229). Postoperative mortality rates were similar between age quartiles, as were survival rates up to 3 years (P = 0·404). A statistically significant reduction in 5–10‐year survival rates was observed with ageing (P = 0·001). Relative survival calculation showed that the youngest age quartile (less than 60 years) experienced the longest entire postoperative lifespan (15·6 years) but also the greatest number of YLL (11·0 years). Patients aged over 70 years had the shortest entire postoperative lifespan (6·4 years) but also the smallest number of YLL (3·7 years).
Conclusion
Although survival after liver resection for HCC is shortest in elderly patients, relative survival estimates suggest that hepatectomy can be of benefit in these patients, with a small loss of the entire individual lifespan.
Hepatectomy for HCC of benefit in elderly
The presence of an intrahepatic cholangiocarcinoma (iCCA) in a cirrhotic liver is a contraindication for liver transplantation in most centers worldwide. Recent investigations have shown that “very ...early” iCCA (single tumors ≤2 cm) may have acceptable results after liver transplantation. This study further evaluates this finding in a larger international multicenter cohort. The study group was composed of those patients who were transplanted for hepatocellular carcinoma or decompensated cirrhosis and found to have an iCCA at explant pathology. Patients were divided into those with “very early” iCCA and those with “advanced” disease (single tumor >2 cm or multifocal disease). Between January 2000 and December 2013, 81 patients were found to have an iCCA at explant; 33 had separate nodules of iCCA and hepatocellular carcinoma, and 48 had only iCCA (study group). Within the study group, 15/48 (31%) constituted the “very early” iCCA group and 33/48 (69%) the “advanced” group. There were no significant differences between groups in preoperative characteristics. At explant, the median size of the largest tumor was larger in the “advanced” group (3.1 2.5‐4.4 versus 1.6 1.5‐1.8). After a median follow‐up of 35 (13.5‐76.4) months, the 1‐year, 3‐year, and 5‐year cumulative risks of recurrence were, respectively, 7%, 18%, and 18% in the very early iCCA group versus 30%, 47%, and 61% in the advanced iCCA group, P = 0.01. The 1‐year, 3‐year, and 5‐year actuarial survival rates were, respectively, 93%, 84%, and 65% in the very early iCCA group versus 79%, 50%, and 45% in the advanced iCCA group, P = 0.02. Conclusion: Patients with cirrhosis and very early iCCA may become candidates for liver transplantation; a prospective multicenter clinical trial is needed to further confirm these results. (Hepatology 2016;64:1178‐1188)
Background
When comparing the efficacy of surgical and non‐surgical therapies for hepatocellular carcinoma (HCC), a major limitation is the causal inference problem. This concerns the impossibility ...of seeing both outcomes of two different treatments for the same individual at the same time because one is inevitably missing. This aspect can be addressed methodologically by estimating the so‐called average treatment effect (ATE).
Methods
To estimate the ATE of hepatic resection over locoregional therapies for HCC, data from patients treated in two tertiary care settings between August 2000 and December 2014 were used to obtain counterfactual outcomes using an inverse probability weight survival adjustment.
Results
A total of 1585 patients were enrolled: 815 underwent hepatic resection, 337 radiofrequency ablation (RFA) and 433 transarterial chemoembolization (TACE). The option of operating on all patients who had tumour ablation returned an ATE of +9·8 months for resection (effect size 0·111; adjusted P = 0·064). The option of operating on all patients who had TACE returned an ATE of +27·9 months (effect size 0·383; adjusted P < 0·001). The ATE of surgery was negligible in patients undergoing ablation for very early HCCs (effect size 0·027; adjusted P = 0·627), independently of albumin–bilirubin (ALBI) grade; or in patients with ALBI liver function grade 2 (effect size 0·083; adjusted P = 0·213), independently of tumour stage. In all other instances, the ATE of surgery was notably greater. Operating on patients who had TACE with multinodular HCC beyond the Milan criteria resulted in a mild ATE (effect size 0·140; adjusted P = 0·037).
Conclusion
ATE estimation suggests that hepatic resection is a better treatment option than ablation and TACE in patients with HCC.
Resection is better
Background & Aims Number-needed-to-treat is used in assessing the effectiveness of a health-care intervention, and reports the number of patients who need to be treated to prevent one additional bad ...outcome. Although largely used in medical literature, there are no studies measuring the benefit of liver transplantation (LT) over hepatic resection (HR) for hepatocellular carcinoma (HCC) in terms of “Number of patients needed to transplant (NTT).” Methods Exclusion criteria: Child-Turcotte-Pugh (CTP) Classes B–C, very large (>10 cm) and multi-nodular (>2 nodules) tumours, macroscopic vascular invasion and extra-hepatic metastases. Study population: 1028 HCC cirrhotic patients from one Eastern (n = 441) and two Western (n = 587) surgical units. Patient survival observed after HR by proportional hazard regression model was compared to that predicted after LT by the Metroticket calculator. The benefit obtainable from LT compared to resection was analysed in relationship with number of nodules (modelled as ordinal variable: single vs. oligonodular), size of largest nodule (modelled as a continuous variable), presence of microscopic vascular invasion (MVI), and time horizon from surgery (5-year vs. 10-year). Results 330 patients were beyond the Milan criteria (32%) and 597 (58%) had MVI. The prevalence of MVI was 52% in patients within Milan criteria and 71% in those beyond ( p <0.0001). In the 5-year transplant benefit analysis, nodule size and HCC number were positive predictors of transplant benefit, while MVI had a strong negative impact on NTT. Transplantation performed as an effective therapy (NTT <5) only in oligonodular HCC with largest diameter >3 cm (beyond conventional LT criteria) when MVI was absent. The 10-year scenario increased drastically the transplant benefit in all subgroups of resectable patients, and LT became an effective therapy (NTT <5) for all patients without MVI whenever tumor extension and for oligonodular HCC with MVI within conventional LT criteria. Conclusions Based on NTT analysis, the adopted time horizon (5-year vs. 10-year scenario) is the main factor influencing the benefit of LT in patients with resectable HCC and Child A cirrhosis.
Surveillance for hepatocellular carcinoma (HCC) is recommended in patients with cirrhosis. As α-fetoprotein (AFP) is considered a poor surveillance test, we tested the performance of its changes over ...time.
Eighty patients were diagnosed with HCC (cases) during semiannual surveillance with ultrasonography and AFP measurement were recruited and matched for age, gender, etiology and Child-Pugh class with 160 contemporary cancer-free controls undergoing the same surveillance training group (TG). As a validation group (VG) we considered 36 subsequent patients diagnosed with HCC, matched 1 : 3 with contemporary cancer-free controls. α-Fetoprotein values at the time of HCC diagnosis (T0) and its changes over the 12 (Δ12) and 6 months (Δ6) before cancer detection were considered.
In both TG and VG, >80% of HCCs were found at an early stage. In TG, AFP significantly increased over time only in cases. T0 AFP and a positive Δ6 were independently associated with HCC diagnosis (odds ratio: 1.031 and 2.402, respectively). The area under the curve of T0 AFP was 0.76 and its best cutoff (BC) was 10 ng ml(-1) (sensitivity 66.3%, specificity 80.6%). The combination of AFP >10 ng ml(-1) or a positive Δ6 composite α-fetoprotein index (CAI) increased the sensitivity to 80% with a negative predictive value (NPV) of 86.2%. Negative predictive value rose to 99%, considering a cancer prevalence of 3%. In the VG, the AFP-BC was again 10 ng ml(-1) (sensitivity 66.7%, specificity 88.9%), and CAI sensitivity was 80.6% with a NPV value of 90.5%.
CAI achieves adequate sensitivity and NPV as a surveillance test for the early detection of HCC in cirrhosis.
The therapeutic value of repeat hepatic resection (rHR) or radiofrequency ablation (RFA) for recurrent hepatocellular carcinoma (HCC) is unknown. This study aimed to investigate the safety and ...efficacy of rHR or RFA.
This was a retrospective multicentre study of patients with recurrent HCC within the Milan criteria who underwent rHR or RFA at nine university hospitals in China and Italy between January 2003 and January 2018. Survival after rHR or RFA was examined in unadjusted analyses and after propensity score matching (1 : 1).
Of 847 patients included, 307 and 540 underwent rHR and RFA respectively. Median overall survival was 73.5 and 67.0 months after rHR and RFA respectively (hazard ratio 1.01 (95 per cent c.i. 0.81 to 1.26)). Median recurrence-free survival was longer after rHR versus RFA (23.6 versus 15.2 months; hazard ratio 0.76 (95 per cent c.i. 0.65 to 0.89)). These results were confirmed after propensity score matching. RFA was associated with lower morbidity of grade 3 and above (0.6 versus 6.2 per cent; P < 0.001) and shorter hospital stay (8.0 versus 3.0 days, P < 0.001) than rHR.
rHR was associated with longer recurrence-free survival but not overall survival compared with RFA.
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.
By intention to treat analysis of survival of transplantable HCC patients who underwent liver resection (LR) compared to those listed for transplantation, this study shows that LR for patients with small HCC with preserved liver function, employing LT as a salvage procedure (SLT) in the event of HCC recurrence, is a safe and effective strategy. See also editorial by Botha in this issue on page 1085.
Background
Bacterial infection in patients with liver failure can lead to a dramatic clinical deterioration. The indications for liver transplantation and outcome in these patients is still ...controversial.
Methods
All adult patients who underwent liver transplantation between 1 January 2010 and 31 December 2015 were selected from an institutional database. Characteristics of the donors and recipients, and clinical, biochemical and surgical parameters were retrieved from the database. Post‐transplant survival rates and complications, including grade III–IV complications according to the Dindo–Clavien classification, were compared between patients with an infection 1 month before transplantation and patients without an infection.
Results
Eighty‐four patients with an infection had statistically significant higher Model for End‐stage Liver Disease (MELD), D‐MELD and Balance of Risk (BAR) scores and a higher rate of acute‐on‐chronic liver failure compared with findings in 343 patients with no infection. The rate of infection after liver transplantation was higher in patients who had an infection before the operation: 48 per cent versus 30·6 per cent in those with no infection before transplantation (P = 0·003). The percentage of patients with a postoperative complication (42 versus 40·5 per cent respectively; P = 0·849) and the 90‐day mortality rate (8 versus 6·4 per cent; P = 0·531) was no different between the groups. Multivariable analysis showed that a BAR score greater than 18 and acute‐on‐chronic liver failure were independent predictors of 90‐day mortality.
Conclusion
Bacterial infection 1 month before liver transplantation is related to a higher rate of infection after transplantation, but does not lead to a worse outcome.
No adverse outcomes
VirtualTouch is a new technique recently proposed to evaluate liver stiffness during B-mode ultrasonography. The goal of the present study was to analyze the diagnostic accuracy of VirtualTouch in ...the diagnosis of cirrhosis and its correlation with transient elastography (Fibroscan).
A total of 133 patients with chronic liver disease were enrolled. 90 of 133 underwent VirtualTouch and transient elastography and 70 patients assessed with VirtualTouch were submitted to liver biopsy. Stiffness was assessed by both techniques in the right liver lobe. The diagnostic accuracy for cirrhosis was first assessed in the 90 patients submitted to transient elastography with > 13 kPa (47 % of patients) as diagnostic for cirrhosis values. The best cut-off for cirrhosis with VirtualTouch was then tested in the 70 patients with biopsy (cirrhosis in 38 % of patients). 41 patients were assessed by VirtualTouch by two different operators.
The VirtualTouch values in controls, chronic hepatitis and cirrhosis were respectively 113, 147 and 255 cm/sec. The AUROC of liver VirtualTouch for the diagnosis of cirrhosis (reference Fibroscan) was 0.941 with 175 cm/sec as the best cut-off (sensitivity 93.0 %; specificity 85.1 %). VirtualTouch confirmed good performance also in patients with bioptic diagnosis of cirrhosis (AUROC 0.908, sensitivity 81.5 %, specificity 88.4 %,). The correlation of VirtualTouch with transient elastography was strict (r = 0.891) and the correlation in VirtualTouch measurements between two operators was also good (r = 0.874).
VirtualTouch is able to identify the presence of cirrhosis with good accuracy, shows good interobserver reproducibility and the correlation of its values with those obtained by transient elastography with Fibroscan is good.
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