Renal failure in patients with hepatocellular carcinoma and ascites undergoing transarterial chemoembolization

Background: Ascites is often present in patients with hepatocellular carcinoma (HCC) with cirrhosis. Advanced cirrhosis may predispose to renal dysfunction. Acute renal failure (ARF) may occur after transarterial chemoembolization (TACE) for HCC because of radiocontrast agents. This study aimed to investigate the incidence and risk factors of ARF and prognostic predictors in HCC patients with ascites undergoing TACE. Methods: A total of 591 HCC patients receiving TACE were enrolled. Results: In a mean follow‐up duration of 19±17 months, 239 (40.4%) patients undergoing TACE died. Ascites, which was present in 91 (15.4%) patients at entry, independently predicted a poor prognosis in the Cox proportional hazard model [risk ratio (RR): 1.71, P=0.002]. Of these, 11 (12.6%) of 87 patients with complete follow‐up developed ARF after TACE. Serum albumin level <3.3 g/dl (odds ratio: 7.3, P=0.009) was the only independent risk factor associated with ARF in the logistic regression analysis. ARF (RR: 2.17, P=0.036), α‐fetoprotein >400 ng/ml (RR: 1.84, P=0.04), multiple tumours (RR: 2.11, P=0.013), tumour size ≥5 cm (RR: 2.32, P=0.006) and serum sodium level <139 mmol/L (RR: 2.4, P=0.005) were independent poor prognostic predictors for HCC patients with ascites receiving TACE. Conclusions: Pre‐existing ascites is associated with increased mortality in HCC patients receiving TACE. In HCC patients with ascites, hypoalbuminaemia is associated with the occurrence of post‐TACE ARF. Post‐TACE ARF is a poor prognostic predictor in this subset of HCC patients.     

Selecting a prognostic renal surrogate for patients with hepatocellular carcinoma undergoing transarterial chemoembolization

Background and Aim: Renal insufficiency (RI) often coexists with hepatocellular carcinoma (HCC) and predicts a poor outcome in patients receiving transarterial chemoembolization (TACE). The modification of diet in renal disease (MDRD) and chronic kidney disease epidemiology collaboration (CKD‐EPI) equations are used to provide estimated glomerular filtration rate (eGFR). This study aimed to determine a prognsotic renal surrogate for outcome prediction in HCC patients receiving TACE. Methods: A total of 684 patients with HCC undergoing TACE were retrospectively analyzed. The prognostic ability between the MDRD and CKD‐EPI equation was compared by the Akaike information criterion (AIC). Results: Patients were categorized by eGFR into > 60, 30–60 and < 30 mL/min per 1.73 m² (equivalent to CKD stages 1–2, 3, and 4–5, respectively) groups. The eGFR generated by the MDRD equation had a better predictive accuracy by having a lower AIC score (3234.5) compared to the CKD‐EPI equation (3236.7). The adjusted risk ratio for patients with eGFR 30–60 mL/min per 1.73 m² by the MDRD was 1.313 (P = 0.041) compared with patients with eGFR > 60 mL/min per 1.73 m² in the multivariate Cox model. The eGFR defined by the MDRD equation consistently had better prognostic ability when patients were stratified by the Child‐Turcotte‐Pugh score of 5 and > 5 and Cancer of the Liver Italian Program score 0 to 1 and > 1. Conclusions: The eGFR according the MDRD equation may provide better prognostic accuracy than the CKD‐EPI equation independent of liver functional reserve and tumor staging, and is a more feasible renal surrogate for outcome prediction in CKD stage 1–3 HCC patients receiving TACE.     

Sorafenib in a hepatocellular carcinoma patient with end‐stage renal failure: A pharmacokinetic study

The efficacy of sorafenib against hepatocellular carcinoma (HCC) has been extensively reported. However, there is little information available about the use of sorafenib for HCC patients with end‐stage renal failure. We herein report the safe introduction of sorafenib therapy for a HCC patient on hemodialysis. A 63‐year‐old man had received multidisciplinary treatments, including transarterial chemoembolization (TACE) and radiofrequency ablation, for HCC since 1996, and had been undergoing hemodialysis since 2005. He also underwent TACE for multiple liver recurrence of HCC in 2011. Sorafenib therapy (200 mg/day) started 8 days after the TACE. The pharmacokinetic parameters of sorafenib and its active metabolite, M‐2, were within the reference levels observed in patients with normal renal function 8 and 9 days after the initiation of sorafenib. The dose of sorafenib was reduced to 200 mg every other day on day 154 due to hypertension and general fatigue. Because of the progression of disease after 5 months, sorafenib was withdrawn on day 180. He was admitted to the emergency department because of a high fever during hemodialysis on day 201, and died of septic shock induced by Staphylococcus lugdunensis on day 203. Sorafenib was well tolerated at an initial dose of 200 mg/day for a HCC patient undergoing hemodialysis, thus indicating that renal failure is not necessarily a contraindication for sorafenib therapy.     

Differential prognostic impact of renal insufficiency on patients with hepatocellular carcinoma: a propensity score analysis and staging strategy

Background and Aim: Renal insufficiency (RI) can coexist in patients with hepatocellular carcinoma (HCC). This study analyzed the prognostic impact of RI on patients with HCC and determined the optimal staging strategy for these patients. Methods: RI was defined as an estimated glomerular filtration rate <60 mL/min/1.73 m². A total of 502 and 1701 HCC patients with and without RI, respectively, were enrolled. One‐to‐one matched patient cohorts according to treatments were built by using the propensity model. The prognostic ability of the Cancer of the Liver Italian Program, Barcelona Clinic Liver Cancer, Japan Integrated Scoring, and Taipei Integrated Scoring (TIS) systems in HCC patients with RI was compared by using the Akaike information criterion (AIC). Results: For patients undergoing percutaneous ablation and transarterial chemoembolization (TACE), RI was significantly associated with decreased long‐term survival (P = 0.001 and 0.004, respectively). In patients receiving resection and other treatments, there were no significant survival differences between patients with and without RI. With similar demographics generated in the propensity model, significantly decreased survival was found in patients with RI in the TACE group (P = 0.018), but not in the resection, percutaneous ablation, and other treatment groups. Among HCC patients with RI, the TIS system had the lowest AIC value. Conclusions: RI is often present in patients with HCC and predicts a poor outcome in patients undergoing TACE. The survival of HCC patients receiving resection, percutaneous ablation, and other treatments is not affected by RI. The TIS staging system is a more feasible prognostic model for HCC patients with RI.     

Systematic review of neoadjuvant transarterial chemoembolization for resectable hepatocellular carcinoma

Resection of hepatocellular carcinoma (HCC) offers the only hope for cure. However, in patients undergoing resection, recurrences, in particular, intrahepatic recurrence are common. The effectiveness of transarterial chemoembolization (TACE) as a neoadjuvant therapy for unresectable HCC was exploited by numerous liver units and employed preoperatively in the setting of resectable HCC with an aim to prevent recurrence and prolong survival. A systematic literature search of databases (Medline and PubMed) to identify published studies of TACE administered preoperatively as a neoadjuvant treatment for resectable HCC was undertaken. A systematic review by tabulation of the results was performed with disease‐free survival (DFS) as the primary endpoint. Overall survival (OS), rate of pathological response, impact on surgical morbidity and mortality and pattern of recurrences were secondary endpoints of this review. Eighteen studies; three randomized trials and 15 observational studies were evaluated. This comprised of 3927 patients, of which, 1293 underwent neoadjuvant TACE. The median DFS in the TACE and non‐TACE group ranged from 10 to 46 and 8 to 52 months, respectively, with 67% of studies reporting similar DFS between groups despite higher extent of tumour necrosis from the resected specimens indicating a higher rate of pathological response (partial TACE 27–72% vs. non‐TACE 23–52%; complete TACE 0–28% vs. non‐TACE zero), with no difference in surgical morbidity and mortality outcome. No conclusion could be drawn with respect to OS. Both randomized and non‐randomized trials suggest the use of TACE preoperatively as a neoadjuvant treatment in resectable HCC is a safe and efficacious procedure with high rates of pathological responses. However, it does not appear to improve DFS.     

Analysis of aggressiveness factors in hepatocellular carcinoma patients undergoing transarterial chemoembolization

AIM To investigate novel predictors of survival in hepatocellular carcinoma(HCC) patients following transarterial chemoembolization(TACE).METHODS One hundred sixty seven patients with un-resectable HCC were retrospectively analyzed to identify factors that might contribute to their HCC biology and aggressiveness. We correlated routine laboratory results(total bilirubin, AST, ALKP, GGTP, albumin etc.) to maximum tumor diameter, number of tumor nodules, portal vein thrombosis and blood alpha-fetoprotein levels. These 4 parameters were previously combined to form an aggressiveness index(AgI). We used The Wilcoxon ranksum(Mann-Whitney), to test the correlation between the AgI categories and liver function parameters. The Cox proportional hazards model was applied to evaluate the categories of AgI associated with overall survival. RESULTS The AgI was strongly correlated with survival in this novel patient population. Three year survival probability for AgI or 4 was 42.4% vs 61.8%; P 0.0863 respectively. Several factors independently correlated with AgI using univariate multiple logistic regression of AgI with 8 laboratory parameters. Lower albumin levels had an OR of 2.56(95%CI: 1.120-5.863 P 0.026), elevated Alkaline phosphatase and gamma glutamyl transpeptidase(GGTP) had ORs of 1.01(95%CI: 1.003-1.026, P 0.017) and 0.99(95%CI: 0.99-1.00, P 0.053) respectively. In a Cox proportional hazard model combining mortality for AgI score and liver function parameters, only GGTP levels and the AgI were independently associated with survival. An AgI 4 had HR for mortality of 2.18(95%CI: 1.108-4.310, P 0.024). GGTP's single unit change had a HR for mortality of 1.003(95%CI: 1.001-1.006, P 0.016). These were considered in the final multivariate model with the total cohort. An AgI 4 had a HR for mortality of 2.26(95%CI: 1.184-4.327, P 0.016). GGTP had a HR of 1.003(95%CI: 1.001-1.004, P 0.001).CONCLUSION Our study validates the AgI in a new population with un-resectable HCC patients undergoing TACE. The analysis establishes a correlation between GGTP and the AgI.     

Determination of risk factors for fever after transarterial chemoembolization with drug-eluting beads for hepatocellular carcinoma

This study was to identify risk factors affecting postembolization fever (PEF) of CalliSpheres drug-eluting bead transarterial chemoembolization (DEB-TACE) in the treatment of primary hepatocellular carcinoma (HCC).One hundred eighty-eight consecutive patients with HCC who underwent DEB-TACE with fever between June 2017 and May 2019 were included in this retrospective study. The patients were divided into 4 groups based on the severity of posttransarterial chemoembolization (TACE) fever according to the degrees of body temperature. Univariate analysis and multivariate logistics regression were performed to identify potential risk factors for post-TACE fever.In the stepwise multiple regression analysis, pre-TACE blood urea, small particle size and Cental liqefction (P < .05) were independent risk factors of severe post-TACE fever (P < .05, respectively). Portal vein thrombosis (P < .01), Child-Pugh stage (P < .01), and cycles of DEB-TACE (P < .05) were independent risk factors for clinical death, PEF was not associated with clinical death (P = .754) and 6-month survival (P = .524) in the univariate analysis. Moreover, multivariate Cox regression was performed, and Child-Pugh stage (B vs A) (P = .040) and portal vein thrombosis (yes vs no) (P = .033) were independent factors predicting unfavorable overall survival in HCC patients.Pre-TACE blood urea, small particle size, and Cental liqefction were significantly correlated with the occurrence fever after DEB-TACE. Therefore, these factors should be taken into full consideration for the relief of fever. However, PEF after D-TACE was not associated with clinical death and 6-month survival rate.     

Prognostic factors for survival in patients with unresectable hepatocellular carcinoma undergoing chemoembolization with doxorubicin drug-eluting beads: a preliminary study

Background:

Transarterial chemoembolization (TACE) with drug-eluting beads (DEB) is a new treatment modality. Little is known about prognostic factors affecting survival after DEB TACE for patients with hepatocellular carcinoma (HCC).

Methods:

Patients who underwent TACE with doxorubicin DEB for unresectable HCC during 2006–2008 were studied. Survival was calculated from the day of first transcatheter therapy. Survival analysis was performed using Kaplan–Meier estimations. Survival curves were compared using the log-rank test.

Results:

Fifty patients underwent chemoembolization with doxorubicin DEB. They included 39 women and 11 men, with a median age of 57.5 years (range 28–91 years). Eighteen patients died during the study period and 32 remained alive. Overall survival rates at 6 months, 1 year and 2 years from the first administration of doxorubicin DEB TACE were 71%, 65% and 51%, respectively. Prognostic factors found to be significant on univariate analysis were Child–Pugh class, Okuda staging, bilirubin > 2 mg/dl, albumin < 3.0 g/dl, Model for End-stage Liver Disease (MELD) score, serum alphafetoprotein (AFP), Cancer of the Liver Italian Programme (CLIP) score, tumour satisfying Milan criteria, Eastern Cooperative Oncology Group (ECOG) performance status (PS) and Barcelona Clinic Liver Cancer (BCLC) staging.

Conclusions:

Child–Pugh class, Okuda staging, bilirubin > 2 mg/dl, albumin < 3 g/dl, MELD score, serum AFP, CLIP score, Milan criteria, ECOG PS and BCLC staging were found to be prognostic markers of survival after treatment with doxorubicin DEB TACE in patients with unresectable HCC.     

Prospective cohort study of transarterial chemoembolization for unresectable hepatocellular carcinoma in 8510 patients

BACKGROUND & AIMS: To elucidate the survival of the patients with unresectable hepatocellular carcinoma (HCC) who underwent transcatheter arterial lipiodol chemoembolization (TACE) and to analyze the factors affecting the survivals. METHODS: During the last 8 years, a nationwide prospective cohort study was performed in 8510 patients with unresectable HCC who underwent TACE using emulsion of lipiodol and anticancer agents followed by gelatin sponge particles as an initial treatment. Exclusion criteria were extrahepatic metastases and/or any previous treatment prior to the present TACE. The primary end point was survival. The survival rates were calculated by the Kaplan-Meier method. The multivariate analyses for the factors affecting survival were evaluated by the Cox proportional hazard model. The mean follow-up period was 1.77 years. RESULTS: For overall survival rates by TACE, median and 1-, 3-, 5-, and 7-year survivals were 34 months, 82%, 47%, 26%, and 16%, respectively. Both the degree of liver damage and the tumor-node-metastasis (TNM) system proposed by the Liver Cancer Study Group of Japan demonstrated good stratification of survivals (P = .0001). The multivariate analyses showed significant difference in degree of liver damage (P = .0001), alpha-fetoprotein value (P = .0001), maximum tumor size (P = .0001), number of lesions (P = .0001), and portal vein invasion (P = .0001). The last 3 factors could be replaced by TNM stage. The TACE-related mortality rate after the initial therapy was .5%. CONCLUSIONS: TACE showed safe therapeutic modality with a 5-year survival of 26% for unresectable HCC patients. The degrees of liver damage, TNM stage, and alpha-fetoprotein values were independent risk factors for patient survival.     

Outcome of hepatectomy for hepatocellular carcinoma in patients with renal dysfunction

Objectives

There are few reports on the efficacy of hepatectomy for hepatocellular carcinoma (HCC) in patients with renal dysfunction (RD). This study aimed to clarify the validity of hepatectomy for treating HCC in RD patients, and to compare postoperative courses in RD and non-RD patients.

Methods

The clinical features of 722 HCC patients who underwent curative hepatectomy between 1986 and 2009 were retrospectively reviewed. Seventeen patients (2.4%) with preoperative serum creatinine levels of >2.0 mg/dl were defined as the RD group, and, of these, seven who did not receive preoperative haemodialysis were defined as borderline patients. Clinicopathological characteristics and postoperative outcomes were compared between the RD group (n = 17) and the non-RD group (n = 705). The postoperative courses of borderline patients were reviewed in detail.

Results

Overall survival (P = 0.177) and disease-free survival (P = 0.942) after hepatectomy did not differ significantly between the groups. Incidences of massive ascites (35.3% vs. 14.3%; P = 0.034) and pleural effusion (52.9% vs. 17.6%; P = 0.001), defined as massive effusion (ME), were significantly higher in the RD group than in the non-RD group. Hypoalbuminaemia (≤2.8 g/dl; P = 0.031), heavy blood loss (≥1000 ml; P = 0.012) and intraoperative blood transfusion (P = 0.007) were risk factors for ME. Among the borderline patients, serum creatinine values were not increased immediately after surgery and four patients underwent haemodialysis.

Conclusions

Preoperative hypoalbuminaemia, heavy blood loss and blood transfusion are independent risk factors for ME in RD patients. Preoperative improvement of anaemia and reduction of blood loss by meticulous surgical techniques may prevent ME in RD patients who require hepatectomy for HCC.     

Combined hepatocellular carcinoma and neuroendocrine carcinoma with sarcomatous change of the liver after transarterial chemoembolization

Primary hepatic neuroendocrine carcinoma is rare and its origin is not clearly understood. An admixture of hepatocellular carcinoma (HCC) and neuroendocrine carcinoma is particularly rare. Here, we report a patient with an extremely rare combination of HCC and neuroendocrine carcinoma of the liver. To our knowledge, this is the first reported case in which the carcinoma showed sarcomatous change. The patient was a 76‐year‐old man who had received outpatient treatment for chronic hepatitis C. On abdominal computed tomography (CT), the hepatic tumor was enhanced in the arterial phase but its density was lower than that of normal liver in the portal phases. His serum α‐fetoprotein (AFP) level was very high. Therefore, transarterial chemoembolization (TACE) was performed based on the diagnosis of HCC. Ten months after TACE, his serum AFP level had increased to the level measured before TACE. Partial hepatectomy was performed because CT revealed poor enhancement of the recurrent tumor. Histopathologically, the tumor consisted of two distinct components: moderately differentiated HCC was intermingled with a neuroendocrine carcinoma, which was accompanied by sarcomatous changes. Immunohistochemically, the neuroendocrine carcinoma cells were positive for CD56, chromogranin A and neuron‐specific enolase, and negative for AFP. The sarcomatous area was positive for AE1/3 and CD56, consistent with sarcomatous change of neuroendocrine carcinoma. The neuroendocrine carcinoma and/or sarcomatous change may have been due to phenotypic changes and/or dedifferentiation of HCC induced by TACE. Six months after surgery, the patient was diagnosed with metastasis of the neuroendocrine carcinoma to sacral bone. He died 7 months after surgery.     

Alpha-fetoprotein in patients with hepatocellular carcinoma after transcatheter arterial embolization

To assess the usefulness of alpha-fetoprotein (AFP) in monitoring treatment effects of transcatheter arterial embolization (TAE) in hepatocellular carcinoma (HCC) patients, a total of 31 sets of AFP levels after TAE in 21 HCC patients were analysed by linear regression between logarithmic AFP levels and days. Eleven sets of AFP data with poor linear declination were accompanied with poor TAE results except in one patient who had chronic hepatitis with acute exacerbations. Twenty sets of data with good linear declination in the first month after TAE indicated good TAE results. Seven of them showed no evidence of tumour recurrence nor elevated AFP levels within a follow-up of 6 months. The mean, standard deviation and range of half-lives of AFP in the non-recurrent group were 5.0, 1.6 and 2.9-7.2 days, respectively. The others experienced late tumour recurrence that was detected by rebound of AFP levels except one who had another non-AFP-secreting HCC. Thus, the results might be used as a reference in monitoring the treatment effects of TAE and the timing selection of repeated TAE.     

Massive bleeding from a gastric erosion after transcatheter arterial chemoembolization for hepatocellular carcinoma in a patient with mild haemophilia A.

We observed massive bleeding from a gastric erosion following transcatheter arterial chemoembolization (TAE) in a patient with mild haemophilia A. A 78-year-old haemophiliac (factor VIII level over 60%) received TAE with farmorubicin and spongel. Haematemesis and melena with loss of consciousness occurred 3 days [corrected] after TAE, and endoscopy revealed superficial erosions with oozing. Toxic effects of the anticancer drug in conjunction with the bleeding disorder may have caused the massive bleeding. We should always consider the possibility of unexpected complications in patients with bleeding disorders; gastrointestinal bleeding can develop during treatment for liver tumours.     

Analysis of survival predictors in a prospective cohort of patients undergoing transarterial chemoembolization for hepatocellular carcinoma in a single Canadian centre

Background

Despite advances in the treatment of hepatocellular carcinoma (HCC), a great proportion of patients are eligible only for palliative therapy for reasons of advanced-stage disease or poor hepatic reserve. The use of transarterial chemoembolization (TACE) in the palliation of non-resectable HCC has shown a survival benefit in European and Asian populations. The aim of this study was to assess the efficacy of TACE by analysing overall 5-year survival, interval changes of tumour size and serum alpha-fetoprotein (AFP) levels in a prospective North American cohort.

Methods

From September 2005 to December 2010, 46 candidates for TACE were enrolled in the study. Collectively, they underwent 102 TACE treatments. Data on tumour response, serum AFP and survival were prospectively collected.

Results

In compensated cirrhotic patients, serial treatment with TACE had a stabilizing effect on tumour size and reduced serum AFP levels during the first 12 months. Overall survival rates at 1, 2 and 3 years were 69%, 58% and 20%, respectively. Younger individuals and patients with a lower body mass index, affected by early-stage HCC with involvement of a single lobe, had better survival in univariate analysis. After adjustment for risk factors, early tumour stage (T1 and T2 vs. T3 and T4) at diagnosis was the only statistically significant predictor for survival.

Conclusions

In compensated cirrhotic patients, TACE is an effective palliative intervention and HCC stage at diagnosis seems to be the most important predictor of longterm outcomes.