Efficacy and predictive factors of transarterial chemoembolization combined with lenvatinib plus programmed cell death protein-1 inhibition for unresectable hepatocellular carcinoma

BACKGROUND The efficacy and safety of transarterial chemoembolization(TACE)combined with lenvatinib plus programmed cell death protein-1(PD-1)for unresectable hepato-cellular carcinoma(HCC)have rarely been evaluated and it is unknown which factors are related to efficacy.AIM To evaluate the efficacy and independent predictive factors of TACE combined with lenvatinib plus PD-1 inhibitors for unresectable HCC.METHODS This study retrospectively enrolled patients with unresectable HCC who received TACE/lenvatinib/PD-1 treatment between March 2019 and April 2022.Overall survival(OS)and progression-free survival(PFS)were determined.The objective response rate(ORR)and disease control rate(DCR)were evaluated in accordance with the modified Response Evaluation Criteria in Solid Tumors.Additionally,the prognostic factors affecting the clinical outcome were assessed.RESULTS One hundred and two patients were enrolled with a median follow-up duration of 12.63 months.The median OS was 26.43 months(95%CI:17.00-35.87),and the median PFS was 10.07 months(95%CI:8.50-11.65).The ORR and DCR were 61.76%and 81.37%,respectively.The patients with Barcelona Clinic Liver Cancer Classification(BCLC)B stage,early neutrophil-to-lymphocyte ratio(NLR)response(decrease),or early alpha-fetoprotein(AFP)response(decrease>20%)had superior OS and PFS than their counterparts.CONCLUSION This study showed that TACE/lenvatinib/PD-1 treatment was well tolerated with encouraging efficacy in patients with unresectable HCC.The patients with BCLC B-stage disease with early NLR response(decrease)and early AFP response(decrease>20%)may achieve better clinical outcomes with this triple therapy.

Transcatheter arterial chemoembolization followed by immediate radiofrequency ablation for large solitary hepatocellular carcinomas

AIM: To assess the technical safety and efficacy of transcatheter arterial chemoembolization (TACE) combined with immediate radiofrequency ablation (RFA) for large hepatocellular carcinomas (HCC) (maximum diameter ≥ 5 cm). METHODS: Individual lesions in 18 patients with HCCs (mean maximum diameter: 7.5 cm; range: 5.1-15.5 cm) were treated by TACE combined with percutaneous RFA between January 2010 and June 2012. All of the patients had previously undergone one to four cycles of TACE treatment. Regular imaging and laboratory tests were performed to evaluate the rate of technical success, technique-related complications, local-regional tumor responses, recurrence-free survival time and survival rate after treatment.RESULTS: Technical success was achieved for all 18 visible HCCs. Complete response (CR) was observed in 17 cases, and partial response was observed in 1 case 1 mo after intervention. The CR rate was 94.4%. Local tumors were mainly characterized by coagulative necrosis. During follow-up (2-29 mo), the mean recurrencefree survival time was 16.8 ± 4.0 mo in 17 cases of CR. The estimated overall survival rate at 6, 12, and 18 mo was 100%. No major complications were observed. Levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the blood of 17 patients transiently increased on the third day after treatment (ALT 200.4 ± 63.4 U/L vs 24.7 ± 9.3 U/L, P < 0.05; AST 228.1 ± 25.4 U/L vs 32.7 ± 6.8 U/L, P < 0.05). Severe pain occurred in three patients, which was controlled with morphine and fentanyl. CONCLUSION: TACE combined with immediate RFA is a safe and effective treatment for large solitary HCCs. Severe pain is a major side effect, but can be controlled by morphine.

Management of surgical splenorenal shunt-related hepatic myelopathy with endovascular interventional techniques

We present a case with hepatic myelopathy(HM) due to a surgical splenorenal shunt that was successfully treated by endovascular interventional techniques.A 39-year-old man presented with progressive spastic paraparesis of his lower limbs 14 mo after a splenorenal shunt.A portal venogram identified a widened patent splenorenal shunt.We used an occlusion balloon catheter initially to occlude the shunt.Further monitoring of the patient revealed a decrease in his serum ammonia level and an improvement in leg strength.We then used an Amplatzer vascular plug(AVP) to enable closure of the shunt.During the follow up period of 7 mo,the patient experienced significant clinical improvement and normalization of blood ammonia,without any complications.Occlusion of a surgically created splenorenal shunt with AVP represents an alternative therapy to surgery or coil embolization that can help to relieve shunt-induced HM symptoms.

Stent-grafts placement for treatment of massive hemorrhage from ruptured hepatic artery after pancreaticoduodenectomy

AIM:To present a series of cases with life-threatening hemorrhage from ruptured hepatic artery pseudoaneurysm after pancreaticoduodenectomy(PD) treated with placement of stent-grafts.METHODS:Massive hemorrhage from ruptured hepatic artery pseudoaneurysm after PD in 9 patients(6 men,3 women) at the age of 23-75 years(mean 48 years),were treated with placement of percutaneous endovascular balloon-expandable coronary stent-grafts.All patients were not suitable for embolization because of a non-patent portal vein.One or more stent-grafts,ranging 3-6 mm in diameter and 16-55 mm in length,were placed to exclude ruptured pseudoaneurysm.Followup data,including clinical condition,liver function tests,and Doppler ultrasound examination,were recorded at the outpatient clinic.RESULTS:Immediate technical success was achieved in all the 9 patients.All stent-grafts were deployed in the intended position for immediate cessation of bleeding and preservation of satisfactory hepatic arterial blood flow.No significant procedure-related complications occurred.Recurrent bleeding occurred in 2 patients at 16 and 24 h,respectively,after placement of stent-grafts and treated with surgical revision.One patient died of sepsis 12 d after the interventional procedure.The remaining 6 patients were survived when they were discharged.The mean follow-up time was 10.5 mo(range 4-16 mo).No patient had recurrent bleeding after discharge.Doppler ultrasound examination verified the patency of hepatic artery and stent-grafts during the follow-up.CONCLUSION:Placement of stent-grafts is an effective and safe procedure for acute life-threatening hemorrhage from ruptured hepatic artery pseudoaneurysm.

Simultaneous transarterial chemoembolization and radiofrequency ablation for large hepatocellular carcinoma

BACKGROUND Hepatocellular carcinoma(HCC)is a common cancer and a leading cause of tumor-related death.Patients with large HCC(≥8 cm)are at an advanced stage and have poor prognosis,and hepatic resection may not be suitable,and the incidence of postoperative recurrence is high.AIM To evaluate recurrence and mid-term survival of patients with large HCC treated by transcatheter arterial chemoembolization(TACE)and radiofrequency ablation(RFA).METHODS This was a retrospective study.From 2010 to 2013,46 consecutive patients with large HCC were treated with simultaneous TACE and RFA.Thirty-five of 46 patients had a single tumor.Progression-free survival(PFS)and overall survival(OS)were analyzed at 2 years and 3 years,respectively.RESULTS Forty-six patients treated by simultaneous TACE and RFA had no significant complications and treatment was successful.After 3 years,median PFS and OS were 10.21±1.58 mo and 26.44±2.26 mo,retrospectively.The survival rate was 67.5%after 2 years and 55.67%after 3 years.CONCLUSION These preliminary data show that simultaneous TACE and RFA are safe and effective for large HCC.

Transcatheter Arterial Chemoembolization Combined with Simultaneous Computed Tomography-guided Radiofrequency Ablation for Large Hepatocellular Carcinomas

Background： Currently, the treatment of large hepatocellular carcinoma （HCC） is still a challenging problem. Transcatheter arterial chemoembolization （TACE） is the main treatment for intermediate end-stage HCC, while it is only a palliative and not a curative treatment due to the existence of residual tumors, and radiofrequency ablation （RFA） has limitations in complete ablation of large HCC. We hypothesized that TACE combined with simultaneous RFA （herein referred to as TACE ＋ RFA） could improve the efficacy and survival of large HCC. This study aimed to investigate the feasibility, efficacy, and safety ofTACE ＋ RFA on single large HCC. Methods： A total of 66 patients with single large HCC （≥5 cm in diameter） were recruited between February 2010 and June 2016. TACE was first performed and computed tomography was performed immediately after TACE, and the lesions with poor lipiodol deposition were subjected to simultaneous RFA. The success rate, technique-related complications, liver and kidney functions, serum alpha-fetoprotein （AFP） levels, progression-tree survival （PFS）, median survival time （MST）, focal control rate, and long-term survival rate were evaluated. Results： TACE ＋ RFA were performed smoothly in all the patients with the success rate of 100%. Intra- and post-operative severe complications were not observed. There were no marked differences in mean alanine transaminase or aspartate transaminase before TACE ＋ RFA compared with 7 days alter TACE ＋ RFA （all P 〉 0.05）. In 57 AFP-positive patients, the levels of serum AFP were reduced by 100.0%, 100.0%, and 94.7% at 1,3, and 6 months after TACE ＋ RFA, respectively; the tumor control rates （complete remission ＋ partial remission） were 100.0% （66/66）, 92.4% （61/66）, 87.9% （58/66）, and 70.1% （39/55） at 1,3, 6, and 12 months after TACE ＋ RFA, respectively. Patients were followed up for 7 82 months after TACE ＋ RFA. The MST was 18.3 months, PFS was 14.2 ± 6.2 months, and the 1-, 3-, and 5-year survival rates were 93.2% （55/59）, 42.5% （17/40）, and 27.2% （9/33）, respectively. Conclusion： TACE ＋ RFA is safe, feasible, and effective in enhancing the focal control rate and survival rate of patients with large HCC.

Prostatic Arterial Embolization with Small Sized Particles for the Treatment of Lower Urinary Tract Symptoms Due to Large Benign Prostatic Hyperplasia： Preliminary Results

Background：The clinical failure after prostatic artery embolization （PAE） with conventional particles was relatively high,in treatment for lower urinary tract symptoms （LUTS） due to benign prostatic hyperplasia （BPH）.We reported the results of PAE with combined polyvinyl alcohol particles 50 μm and 100 μm in size as a primary treatment in 24 patients with severe LUTS secondary to large BPH.Methods：From July 2012 to June 2014,we performed PAE in 24 patients （65-85 years,mean 74.5 years） with severe LUTS due to large BPH （≥80 cm^3） and refractory to medical therapy.Embolization was performed using combination of 50 μm and 100 μm in particles size.Clinical follow-up was performed using the International Prostate Symptom Score （IPSS）,quality of life （QoL）,peak urinary floW （Qmax）,postvoid residual （PVR） volume,the International Index of Erectile Function （IIEF）,prostatic specific antigen （PSA）,and prostatic volume measured by magnetic resonance imaging at 1,3,6,and every 6-month thereafter.Technical success was defined when PAE was completed in at least one pelvic side.Clinical success was defined as the improvement of both symptoms and QoL.A Student＇s t-test for paired samples was used.Results：PAE was technically successful in 22 patients （92%）.Bilateral PAE was performed in 19 （86%） patients and unilateral in 3 （14%） patients.Follow-up data were available for 22 patients observed for mean of 14 months.The clinical improvement at 1,3,6,and 12-month was 91%,91%,88%,and 83%,respectively.At 6-month follow-up,the mean IPSS,QoL,PVR,and Qmax were from 27 to 8 （P =0.001）,from 4.5 to 2.0 （P =0.002）,from 140.0 ml to 55.0 ml （P =0.002）,and from 6.0 ml/s to 13.0 ml/s （P =0.001）,respectively.The mean prostate volume decreased from 110 cm3 to 67.0 cm3 （mean reduction of 39.1%;P =0.00 1）.The PSA and IIEF improvements after PAE did not differ from pre-PAE significantly.No major adverse events were noted.Conclusions：The combination of 50μm and 100 μm particles for PAE is a safe and effective treatment method for patients with severe LUTS due to large BPH,which further improves the clinical results of PAE.

Angio-Computed Tomograph-Guided Immediate Lipiodol Computed Tomograph for Diagnosis of Small Hepatocellular Carcinoma Lesions during Transarterial Chemoembolization

Background： The diagnosis and treatment of small hepatocellular carcinoma （HCC） play a vital role in the prognosis of patients with HCC. The purpose of our study was to evaluate anglo-computed tomography （angio-CT）-guided immediate lipiodol CT （a CT scan performed immediately after transarterial chemoembolization [TACE]） in the diagnosis of potential HCCs ≤1 cm in diameter. Methods： This study retrospectively analyzed 31 patients diagnosed with HCCs after routine imaging （contrast-enhanced CT or magnetic resonance imaging） or pathologic examinations with undefined or undetermined tumor lesions （diameter 〈1 cm） from February 2016 to September 2016. After TACE guided by digital subtraction angiography of the angio-CT system, potential HCC lesions with a diameter ≤1 cm were diagnosed by immediate lipiodol CT. The number of well-demarcated lesions was recorded to calculate the true positive rate. The correlation between the number of small HCCs detected by immediate lipiodol CT and the size of HCC lesions （diameter 〉1 cm） diagnosed preoperatively was analyzed 1 month after TACE. A paired t-test was used to analyze differences in liver function. Pearson analysis was used to analyze correlation. Chi-square test was used to compare the rates. Results： Fifty-eight lesions were detected on preoperative routine imaging examinations in 31 patients including 15 lesions with a diameter ≤ 1 cm. Ninety-one lesions were detected on immediate lipiodol CT, of which 48 had a diameter ≤ 1 cm. After 1 month, CT showed that 45 lesions had lipiodol deposition and three lesions had lipiodol clearance. Correlation analysis showed that the number of small HCCs detected by lipiodol CT was positively correlated with the size of HCC lesions diagnosed by conventional imaging examination （R^2 - 0.54, P 〈 0.05）. Conclusion： Immediate lipiodol CT may be a useful tool in the diagnosis of potential HCC lesions with a diameter of ≤1 cm.

Transarterial Embolization for Treatment of Symptomatic Polycystic Liver Disease： More than 2-year Follow-up

Background： Currently, treatment of symptomatic polycystic liver disease （PLD） is still a challenging problem, especially for these patients who are not feasible for surgery. Minimally invasive options such as laparoscopic fenestration and percutaneous cyst aspiration with sclerotherapy demonstrated disappointing results due to multiple lesions. Because the cysts in PLD are mostly supplied from hepatic arteries but not from portal veins, transcatheter arterial embolization （TAE） of the hepatic artery branches that supply the major hepatic cysts can lead to shrinkage of the cyst and liver size, relieve symptoms, and improve nutritional status. This study aimed to evaluate the effectiveness of TAE with a mixture of N-butyl-2-cyanoacrylate （NBCA） and iodized oil for patients with severe symptomatic PLD during a more than 2-year follow-up, Methods： Institutional review board had approved this study. Written informed consent was obtained from all patients. From February 2007 to December 2014, twenty-three patients （20 women and 3 men; mean age, 49.0 ± 14.5 years） infeasible for surgical treatments underwent TAE. Changes in the abdominal circumferences, volumes of intrahepatic cysts, hepatic parenchyma volume, and whole liver, clinical symptoms, laboratory data, and complications were evaluated after TAE. Results： Technical success was achieved in all cases. No procedure-related major complications occurred. The median follow-up period after TAE was 48.5 months （interquartile range, 30.0-72.0 months）. PLD-related severe symptoms were improved remarkably in 86% of the treated patients; TAE failed to benefit in four patients （four patients did not benefit from TAE）. The mean maximum abdominal circumference decreased significantly from 1 06.0± 8.0 cm to 87.0 ± 15.0 cm （P = 0.021）. The mean intrahepatic cystic volume reduction rates compared with pre-TAE were 36% at 12 months, 37% at 24 months, and 38% at 36 months after TAE （P 〈 0.05）. The mean liver volume reduction rates were 32% at 12 months, 31% at 24 months, and 33% at 36 months （P 〈 0.05）. Conclusions： TAE with the mixture of NBCA and iodized oil appears to be a safe and effective treatment method for patients with symptomatic PLD, especially for those who are not good candidates for surgical treatments, to improve both hepatic volume and hepatic cysts volume.

A report of a new late toxic effect of lenvatinib

To the Editor:Hepatocellular carcinoma(HCC)is the third most lethal malignancy globally.[1]Besides sorafenib,lenvatinib is currently the second approved targeted agent for the first-line treatment of HCC in 2018.Lenvatinib is an oral multikinase inhibitor that targets vascular endothelial growth factor(VEGF)receptors 1 to 3,fibroblast growth factor receptors 1 to 4,platelet-derived growth factor receptor a,RET,and KIT.[2]Patients who received lenvatinib experienced diarrhoea,and alope and more instances of hypertension,proteinuria,and hypothyroidism.Here,we report two patients that developed irreversible pancreatic atrophy as a novel adverse event of lenvatinib.