Xu Zhu

Impact of Serum Vascular Endothelial Growth Factor on Prognosis in Patients with Unresectable Hepatocellular Carcinoma after Transarterial Chemoembolization

ObjectiveTo investigate the expression level of serum vascular endothelial growth factor (VEGF) in patients with unresectable hepatocellular carcinoma (HCC) and its relationship with the clinicopathological characteristics, and to assess the impact of serum VEGF as a predictive factor for HCC prognosis during transarterial chemoembolization (TACE) treatments.MethodsSerum VEGF levels were measured using enzyme-linked immunosorbent assay (ELISA) in 60 random patients who underwent TACE or transarterial infusion (TAI) for unresectable HCC between May and September 2008 and 12 healthy volunteers were also involved in this study to serve as control. All patients’ clinicopathological features were retrospectively analyzed. Serum VEGF levels were correlated with clinicopathological features of the HCC patients. The patients’ survival rates were analyzed with Kaplan-Meier survival curves and compared by the log-rank test. The prognostic significance of serum VEGF levels and factors related to survival rate were evaluated by univariate and multivariate analysis.ResultsThe median serum VEGF level in the HCC patients was 285 pg/ml (range 14–1,207 pg/ml), significantly higher than that of healthy controls (P=0.021). The serum VEGF levels were significantly correlated with platelet counts (r=0.396, P=0.002) but not other clinicopathological features. Patients with serum VEGF level >285 pg/ml had worse overall survival compared with those with serum VEGF level <285 pg/ml (P=0.002). By multivariate analysis, the serum VEGF level was a significant prognostic factor.ConclusionHigh serum VEGF levels may predict poor prognosis of HCC after TACE. This study highlights the importance of tumor biomarker as a prognostic predictor in TACE therapy for HCC, which has an intrinsic problem of unavailability of histopathological prognostic features.

Management of Delayed Post-Pancreaticoduodenectomy Arterial Bleeding: Interventional Radiological Treatment First

Objective: To investigate the diagnosis and treatment of delayed post-pancreaticoduodenectomy arterial bleeding (DPPAB). Methods: Records of 336 patients who underwent pancreaticoduodenectomy (PD) between January 2000 and December 2010 were retrospectively analyzed. Detailed data of patients with DPPAB were assessed by a thorough review of medical records. Results: 14 patients developed DPPAB. The mean time interval between the initial surgery and DPPAB was 33 days (range 7–72). Three patients experienced sentinel bleeding 5–8 days before DPPAB. All DPPAB patients had intra-abdominal septic complications before bleeding. The overall prevalence of success of angiography and transcatheter arterial embolization (TAE) was 85.7% (12/14), including 3 patients who achieved complete hemostasis by TAE after unsuccessful re-laparotomy. The prevalence of mortality of DPPAB was 28.6% (4/14). After hemostasis was achieved, intra-abdominal septic complications were controlled by percutaneous catheter drainage or re-laparotomy with drain replacement. Conclusion: Angiography and TAE are recommended as the first-line diagnostic and treatment choice for DPPAB, respectively. Surgical intervention should be preserved to eliminate the cause of bleeding.

Transcatheter arterial chemoembolization for gastrointestinal stromal tumors with liver metastases

AIM To evaluate the efficacy and safety of transcatheter arterial chemoembolization (TACE) for gastrointestinal stromal tumor (GIST) with liver metastases after the failure of tyrosine kinase inhibitors (TKIs). METHODS Patients with histologically confirmed CD117-positive GIST with liver metastases who were resistant and/or intolerant to prior imatinib and/or sunitinib and who received TACE for at least one treatment cycle or only best supportive care and TKI reintroduction were eligible for the study. The patients were divided into two groups: those in TACE group received TACE treatment containing 5-20 mL iodized oil and 40-80 mg doxorubicin hydrochloride and TKI reintroduction or best supportive care, those in control group only received TKI reintroduction or best supportive care. The primary end-point was overall survival and the secondary end-points were, progression-free survival (PFS), response rates, and safety. RESULTS Sixty patients admitted between June 2008 and October 2011 were eligible for this study, including 22 in TACE group and 38 in control group. In the TACE group, 12 (54.5%) achieved liver partial response, 5 (22.7%) had stable disease, and 5 (22.7%) had liver progressive disease. Disease control rate of liver metastases was 77.3% in the TACE group and 39.5% in the control group. The median liver PFS in TACE group was 47.1 wk (95% CI: 23.9-70.3). The median PFS in TACE group was longer than in control group (30.0 wk, 95% CI: 20.1-39.9 vs 12.9 wk, 95% CI: 11.9-13.9) (P = 0.0001). The median overall survival in TACE group was also longer than in control group (68.5 wk, 95% CI: 57.4-79.6 vs 25.7 wk, 95% CI: 23.2-28.2) (P = 0.0001). TACE treatment significantly reduced the risk of death (hazard ratio: 0.109). Patients without extrahepatic metastases treated with TACE had significantly better prognosis. Most of the adverse events were of grade 1 or 2 and tolerable. CONCLUSION TACE is effective and well tolerated in GIST patients with liver metastases after TKI failure, and it may be an optional treatment for this disease.

A comparative study between Embosphere® and conventional transcatheter arterial chemoembolization for treatment of unresectable liver metastasis from GIST

OBJECTIVE Transcatheter arterial chemoembolization (TACE) is a standard treatment for hepatocellular carcinoma (HCC) and/or some unresectable liver metastasis tumors. Hypervascular liver metastatic lesions such as metastasis from gastrointestinal stromal tumor (GIST) are an indication for transcatheter arterial embolization (TAE). The purpose of this study was to evaluate the efficacy and safety of Embosphere(®)-TAE (Embo-TAE) in comparison with conventional TACE (cTACE) for the treatment of liver metastasis from GIST. METHODS A total of 45 patients who underwent TACE between Aug 2008 and Feb 2013 were enrolled. Patients with GIST who underwent TAE with Embosphere(®) (n=19) were compared with controls who received cTACE (n=26). The primary end points were treatment response and treatment-related adverse events. The secondary end points were progression-free survival (PFS) and overall survival (OS). RESULTS The treatment response of Embo-TAE group was significantly higher than that of the cTACE group (P<0.001). The PFS was significantly better in the Embosphere(®)-group than in the cTACE group (56.6 and 42.1 weeks, respectively; P=0.003). However, there was no statistically significant difference in liver toxicity between the two groups (P>0.05). The median OS in the Embo-TAE group was longer than that in the cTACE group (74.0 weeks, 95% CI: 68.2-79.8 vs. 61.7 weeks, 95% CI: 56.2-67.2 weeks) (unadjusted P=0.045). The use of Embo-TAE significantly reduced the risk of death in patients with GIST with liver metastases according to the Cox proportional hazards regression model [hazard ratio (HR): 0.149; 95% CI: 0.064-0.475]. CONCLUSIONS TAE with Embosphere(®) showed better treatment response and delayed tumor progression compared with cTACE. There was no significant difference in treatment-related hepatic toxicities. Embo-TAE thus appears to be a feasible and promising approach in the treatment of liver metastasis from GIST.

Phase II Study of Hepatic Arterial Infusion Chemotherapy with Oxaliplatin and 5-Fluorouracil for Advanced Perihilar Cholangiocarcinoma

Purpose To evaluate the efficacy and safety of hepatic arterial infusion (HAI) of oxaliplatin and 5-fluorouracil for advanced perihilar cholangiocarcinoma (PCC) in this prospective phase II study. Materials and Methods The protocol was approved by the local ethics committee, and all patients gave informed consent. Patients with nonresectable PCC were included in a prospective, open phase II study investigating HAI through interventionally implanted port catheters. HAI consisted of infusions of oxaliplatin 40 mg/m2 for 2 hours, followed by 5-fluorouracil 800 mg/m2 for 22 hours on days 1-3 every 3-4 weeks. A maximum of six cycles of HAI were applied for tumor control patients followed by maintenance with oral capecitabine until tumor progression. The primary end points were tumor response and progression-free survival (PFS). The secondary end points were local PFS, overall survival, and adverse events. Kaplan-Meier methodology and Cox regression analysis were used to evaluate the risk factors for survival. Results Between 2012 and 2015, 37 patients were enrolled. The overall response rate was 67.6% (25 of 37), and the disease control rate was 89.2% (33 of 37). Median PFS, local PFS, and overall survival were 12.2, 25.0, and 20.5 months, respectively. All three survival lengths in patients with periductal infiltrating pattern were found to be significantly longer than those in patients with mass-forming pattern (P < .001, hazard ratio < 0.2). Macroscopic growth patterns (P = .018) and number of HAI cycles (P < .001) were independent risk factors of survival. The most frequent adverse events were grades 1 and 2 gastrointestinal side effects and sensory neuropathy in 31 (83.8%) and 28 (75.7%) patients, respectively. Conclusion HAI with oxaliplatin and 5-fluorouracil may be an encouraging treatment choice for advanced PCC due to its high tumor control, survival benefit, and low toxicity, especially in patients with periductal infiltrating pattern.

Hepatic artery infusion with raltitrexed or 5-fluorouracil for colorectal cancer liver metastasis

AIM To evaluate the efficiency and safety of hepatic artery infusion chemotherapy (HAIC) using raltitrexed or 5-fluorouracil for colorectal cancer (CRC) liver metastasis (CRCLM). METHODS A retrospective analysis of patients with unresectable CRCLM who failed systemic chemotherapy and were subsequently treated with HAIC at our institute from May 2013 to April 2015 was performed. A total of 24 patients were treated with 5-fluorouracil, and 18 patients were treated with raltitrexed. RESULTS The median survival time (MST) from diagnosis of CRC was 40.8 mo in the oxaliplatin plus raltitrexed (TOMOX) arm and 33.5 mo in the oxaliplatin plus 5-fluorouracil (FOLFOX) arm (P = 0.802). MST from first HAIC was 20.6 mo in the TOMOX arm and 15.4 mo in the FOLFOX arm (P = 0.734). Median progression-free survival (PFS) from first HAIC was 4.9 mo and 6.6 mo, respectively, in the TOMOX arm and FOLFOX arm (P = 0.215). Leukopenia (P = 0.026) was more common in the FOLFOX arm, and hepatic disorder (P = 0.039) was more common in the TOMOX arm. There were no treatment-related deaths in the TOMOX arm and one treatment-related death in the FOLFOX arm. Analysis of prognostic factors indicated that response to HAIC was a significant factor related to survival. CONCLUSION No significant difference in survival was observed between the TOMOX and FOLFOX arms. HAIC treatment with either TOMOX or FOLFOX was demonstrated as an efficient and safe alternative choice.

Low-dose, short-interval target vessel regional chemotherapy through the hepatic artery combined with transarterial embolization in gastric cancer patients with liver metastases after failure of first-line or second-line chemotherapy: a preliminary analysis.

The objective of this study is to evaluate the efficacy and safety of combining low-dose, short-interval target vessel regional chemotherapy delivered through the hepatic artery (TVRCLDSI) with transarterial embolization (TAE) in advanced gastric cancer (AGC) patients with liver metastases after failure of first-line or second-line chemotherapy. All AGC patients with hepatic metastases had an indwelling arterial catheter placed in the hepatic artery and hepatic metastases were embolized with ultrafluid lipiodol, followed by two to three TVRCLDSI treatments in one cycle. After 3 weeks, the efficacy of TVRCLDSI treatment was evaluated using computed tomography (CT) or MRI scans before starting the next cycle. Follow-up assessments were performed every 2 months. The patients received a median of 7 (2–33) TVRCLDSI treatments together with TAE. All 22 AGC patients received a total of 191 TVRCLDSI treatments, which included 80.1% FOLFOX, 11.0% FOLFIRI, and 8.9% DC treatments. The median time-to-progression was 5.97 months; the median survival time was 11.6 months; and the 1-year and 2-year survival rates were 45.5 and 9.1%, respectively. The median overall survival from the diagnosis of liver metastasis (mOSLM) was 19.3 months. The most common side effects were grade I–II of abdominal pain, nausea, and vomiting. Combining TAE and TVRCLDSI administration through the hepatic artery for AGC patients with liver metastases resulted in decreased overall dose of chemotherapy, alleviation of side effects, and increased QOL of patient. This approach can be used as salvage therapy for AGC patients with predominant liver metastases after failure of intravenous chemotherapy.

Target hepatic artery regional chemotherapy and bevacizumab perfusion in liver metastatic colorectal cancer after failure of first-line or second-line systemic chemotherapy.

Colorectal cancer liver metastasis (CRLM) is a refractory disease after failure of first-line or second-line chemotherapy. Bevacizumab is recommended as first-line therapy for advanced colorectal cancer, but is unproven in CRLM through the hepatic artery. We report favorable outcomes with targeted vessel regional chemotherapy (TVRC) for liver metastatic gastric cancer. TVRC with FOLFOX and bevacizumab perfusion through the hepatic artery was attempted for CRLM for efficacy and safety evaluation. In a single-institution retrospective observational study, 246 patients with CRLM after at least first-line or second-line failure of systemic chemotherapy received TVRC with FOLFOX (i.e. oxaliplatin, leucovorin, and 5-fluorouracil). Of 246 patients, 63 were enrolled into two groups: group 1 (n=30) received bevacizumab and TVRC following tumor progression during previous TVRC treatments; group 2 (n=33) received TVRC plus bevacizumab for CRLM on initiating TVRC. There were no significant differences in the median survival time (14.7 vs. 13.2 months, P=0.367), although the median time to progression was significant (3.3 vs. 5.5 months, P=0.026) between groups. No severe adverse events related to TVRC plus bevacizumab perfusion occurred. Target vessel regional chemotherapy with FOLFOX plus bevacizumab perfusion through the hepatic artery was effective and safe in CRLM. The optimal combination of TVRC and bevacizumab needs further confirmation in future phase II–III clinical trials.

Chemoembolization alone vs combined chemoembolization and hepatic arterial infusion chemotherapy in inoperable hepatocellular carcinoma patients.

AIM To compare the efficacy and safety of chemoembolization alone or chemoembolization combined with hepatic arterial infusion chemotherapy (HAIC), including oxaliplatin (OXA), 5-fluorouracil (5-FU) and folinic acid (CF), in inoperable hepatocellular carcinoma (HCC) without distant metastasis. METHODS Eighty-four inoperable HCC patients were enrolled. Thirty-nine patients underwent chemoembolization alone, and the other 45 patients underwent chemoembolization + HAIC (OXA/5-FU/CF) treatment non-randomly. The progression free survival (PFS), objective response rate (ORR), disease control rate (DCR) and adverse reactions were compared between the two groups. RESULTS A significant difference in the ORR was observed between the chemoembolization alone and chemoembolization + HAIC groups. There was no statistically significant difference in DCR between the two groups. The median PFS (mPFS) showed a significant difference between the two groups. For patients with BCLC stage A/B disease, with or without vessel invasion, the chemoembolization + HAIC group showed better mPFS when compared to chemoembolization alone, but no significant difference was found in patients with BCLC stage C disease. The parameter of pain (grade III-IV) in the chemoembolization + HAIC group was increased statistically. CONCLUSION Chemoembolization combined with HAIC with OXA/5-FU/CF may be safe and more effective than chemoembolization alone for inoperable HCC patients without distant metastasis.

Prognostic factors for transarterial chemoembolization combined with sustained oxaliplatin-based hepatic arterial infusion chemotherapy of colorectal cancer liver metastasis

Objective To investigate the prognostic factors in chemorefractory colorectal cancer liver metastasis (CRCLM) patients treated by transarterial chemoembolization (TACE) and sustained hepatic arterial infusion chemotherapy (HAIC). Methods Between 2006 and 2015, 162 patients who underwent 763 TACE and HAIC in total were enrolled in this retrospective study, including 110 males and 52 females, with a median age of 60 (range, 26–83) years. Prognostic factors were assessed with Log-rank test, Cox univariate and multivariate analyses. Results The median survival time (MST) and median progression-free survival (PFS) of the 162 patients from first TACE/HAIC were 15.6 months and 5.5 months respectively. Normal serum carbohydrate antigen 19-9 (CA19-9, <37 U/mL) (P<0.001) and carbohydrate antigen 72-4 (CA72-4, <6.7 U/mL) (P=0.026), combination with other local treatment (liver radiotherapy or liver radiofrequency ablation) (P=0.034) and response to TACE/HAIC (P<0.001) were significant factors related to survival after TACE/HAIC in univariate analysis. A multivariate analysis revealed that normal serum CA19-9 (P<0.001), response to TACE/HAIC (P<0.001) and combination with other local treatment (P=0.001) were independent factors among them. Conclusions Our findings indicate that serum CA19-9 <37 U/mL and response to TACE/HAIC are significant prognostic indicators for this combined treatment, and treated with other local treatment could reach a considerable survival benefit for CRCLM. This could be useful for making decisions regarding the treatment of CRCLM.