Hepatic Artery Infusion Chemotherapy for Primary and Secondary Malignancies of the Liver: State of the Art and Current High-Level Evidence.

BACKGROUND: Hepatic artery infusion chemotherapy (HAI) has been proposed as a valuable adjunct for multimodal therapy of primary and secondary liver malignancies. This review provides an overview of the currently available evidence of HAI, taking into account tumor response and long-term oncologic outcome. SUMMARY: In colorectal liver metastases (CRLM), HAI in combination with systemic therapy leads to high response rates (85-90%) and conversion to resectablity in primary unresectable disease in up to 50%. HAI in combination with systemic therapy in CRLM in the adjuvant setting shows promising long-term outcomes with up to 50% 10-year survival in a large, non-randomized single-center cohort. For hepatocellular carcinoma patients, response rates as high as 20-40% have been reported for HAI and long-term outcomes compare well to other therapies. Similarly, survival for patients with unresectable intrahepatic cholangiocarcinoma 3 years after treatment with HAI is reported as high as 34%, which compares well to trials of systemic therapy where 3-year survival is usually below 5%. However, evidence is mainly limited by highly selected, heterogenous patient groups, and outdated chemotherapy regimens. The largest body of evidence stems from small, often non-randomized cohorts, predominantly from highly specialized single centers. KEY MESSAGE: In well-selected patients with primary and secondary liver malignancies, HAI might improve response rates and, possibly, long-term survival. Results of ongoing randomized trials will show whether a wider adoption of HAI is justified, particularly to increase rates of resectability in advanced malignant diseases confined to the liver.

Efficacy of various adjuvant chemotherapy methods in preventing liver metastasis from potentially curative colorectal cancer: A systematic review network meta-analysis of randomized clinical trials.

PURPOSE: Various chemotherapy administration methods have been used to prevent liver metastasis (LM) in patients with colorectal cancer (CRC). This network meta-analysis evaluated the efficacy of these different methods in preventing LM in CRC patients who underwent curative surgery. METHOD: A systematic search of randomized controlled trials reporting the efficacy of various adjuvant chemotherapy methods in patients with colorectal cancer who underwent curative surgery was conducted. The primary outcome was the LM rate. RESULTS: This network meta-analysis included 19 studies reporting on 12,588 participants, comparing portal vein infusion chemotherapy (PVIC) versus hepatic arterial infusion chemotherapy (HAIC) versus systematic chemotherapy (SC) versus surgery alone. The HAIC group had the lowest LM rate when compared to the other three groups (odds ratio [OR] of PVIC vs. HAIC: 1.86; OR of SC vs. HAIC: 1.98; and HAIC vs. surgery alone: 0.43). The LM rate did not differ significantly between PVIC, SC, and surgery alone. The recurrence rates were lower for PVIC and HAIC than for surgery alone (the ORs for PVIC and HAIC were 0.73 [95% CI: 0.58-0.92] and 0.45 [95% CI: 0.26-0.77]). The mortality rates of patients undergoing PVIC and HAIC were lower than that of patients undergoing surgery alone (the ORs for PVIC and HAIC were 0.77 [95% CI: 0.64-0.93] and 0.49 [95% CI: 0.24-0.98]). Anastomotic leakage, cardiopulmonary leakage, diarrhea, nausea and vomiting, oral ulceration, wound infection, or ileus did not differ significantly between the four groups. PVIC showed the highest hepatic toxicity rate compared to those for SC, HAIC, and surgery alone. CONCLUSION: HAIC might be a satisfactory method for preventing LM in patients with CRC undergoing curative surgery.

Renal and hepatic artery embolization with Pickering gel emulsion of lipiodol in rabbit.

OBJECTIVE: This research aimed to evaluate the feasibility of a novel liquid embolic agent Pickering gel emulsion of lipiodol (PGEL) for renal and hepatic artery embolization in the rabbit experimental model. METHODS: Embolization was performed in the right renal artery of 24 adult New Zealand White rabbits and 24 VX2 tumors in the left liver lobe. The rabbits were randomly allocated to four treatment groups (n = 6 per group): (A) normal saline (NS), (B) lipiodol, (C) 180-300 µm polyvinyl alcohol (PVA), and (D) PGEL. RESULTS: Renal artery embolization in normal rabbits and transarterial embolization (TAE) in VX2 tumor-bearing rabbits indicated that PGEL achieved a better embolization effect for a longer time than lipiodol and PVA. The tumor growth ratio of the PGEL group was significantly lower than that of the NS, lipiodol, and PVA groups at 3 (P < 0.001) and 7 (P < 0.001) days after embolization. In addition, hematoxylin and eosin and immunohistochemical staining revealed that the tumor necrosis ratio was higher in the PGEL group than in the NS, lipiodol, and PVA groups (P < 0.01), and the expression levels of HIF-1α, VEGF, and CD31 decreased after PGEL embolization compared with the lipiodol and PVA treatments. CONCLUSION: PGEL is an effective embolic material that provides immediate and total occlusion of the renal artery and may be a potential therapeutic embolic agent for TAE of HCC.

Usefulness of ethiodized oil and gelatin sponge particles for delaying the washout of indocyanine green from the liver in swine.

PURPOSE: To assess the effect of ethiodized oil (EO) and gelatin sponge particles (GS) on delaying the washout of indocyanine green (ICG) from the liver in swine. METHODS: Fifteen swine were divided into 3 groups: injection of a mixture of ICG and water-soluble contrast medium (CM) followed by embolization with GS (group A), injection of a mixture of ICG and EO (group B) and injection of a mixture of ICG and EO followed by embolization with GS (group C). The liver surface was observed using an infrared camera system during and at 1, 2, 3, and 6 h after the procedure to measure ICG contrast. Livers were removed at 6 h for histopathological examination. RESULTS: The contrast ratio between injected and non-injected regions at 6 h was 1.45 ± 0.44 in group A, 1.89 ± 0.37 in group B, and 3.62 ± 0.76 in group C. The contrast ratio in group C was significantly greater than that in groups A and B (P = 0.032 and 0.033, respectively). CONCLUSIONS: EO and GS delayed the washout of ICG from the liver in swine and may extend intraoperative navigation in clinical use. Indocyanine green (ICG) mixed with ethiodized oil (EO) was injected into the left hepatic artery in swine, and the artery was embolized with gelatin sponge particles (GS). We confirmed that ICG remained in the liver parenchyma up to 6 h after the procedure. EO and GS delayed the washout of ICG from the liver in swine.

Efficacy of Lipid Nanoparticle-Loaded Sorafenib Combined with Hepatic Artery Chemoembolization in the Treatment of Primary Hepatocellular Carcinoma Complicated with Microvascular Invasion.

This work was to evaluate the therapeutic effect of lipid nanoparticle-loaded sorafenib combined with transcatheter artery chemoembolization (TACE) in patients with primary hepatocellular carcinoma (HC) complicated with microvascular invasion (MVI). In this work, 102 patients with primary HC combined with MVI after radical resection were divided into 4 groups according to different treatment methods. Experimental group 1 was treated with lipid nanoparticle-loaded sorafenib combined with TACE treatment group; experimental group 2 was treated with lipid nanoparticle-loaded sorafenib treatment group; experimental group 3 was TACE treatment group; control group was postoperative routine nursing group. Sorafenib lipid nanoparticles were prepared. The basic information, operation, MVI degree, tumor recurrence, and survival time of patients in each group were recorded and compared to evaluate the therapeutic effect of combined way. No great difference was found in MVI grade, average age, sex ratio, preoperative tumor markers, tumor size, number of patients with liver cirrhosis, operation time, and intraoperative bleeding among the four groups (P > 0.05). In addition, the tumor free survival time (TFST), overall survival time (OST), and postoperative 1-year and 2-year survival rates of patients in test group 1 were greatly higher than those in single mode treatment group and control group (P < 0.05). In summary, sorafenib nanoparticles combined with TACE can improve the survival status of patients after resection and delay the time of postoperative tumor recurrence.

Hepatic arterial infusion pump chemotherapy combined with systemic therapy for patients with advanced colorectal liver metastases: Outcomes in a newly established program.

BACKGROUND AND OBJECTIVES: Colorectal liver metastasis (CRLM) is a leading cause of morbidity and mortality in patients with colorectal cancer. Hepatic arterial infusion (HAI) chemotherapy has been demonstrated to improve survival in patients with resected CRLM and to facilitate conversion of technically unresectable disease. METHODS: Between 2016 and 2018, n = 22 HAI pumps were placed for CRLM. All patients received systemic chemotherapy concurrently with HAI floxuridine/dexamethasone. Overall survival (OS) and progression-free survival (PFS) were assessed using the Kaplan-Meier method. RESULTS: HAI pumps were placed in seven patients with completely resected CRLM and 15 patients with unresectable disease. Twenty-one patients received HAI floxuridine with a median of 5 total HAI cycles (interquartile range: 4-7). Biliary sclerosis was the most common HAI-related complication (n = 5, 24%). Of the 13 patients treated to convert unresectable CRLM, 3 (23%) underwent hepatic resection with curative intent after a median of 7 HAI cycles (range: 4-10). For all HAI patients, the mean OS was 26.7 months from CRLM diagnosis, while the median PFS and hepatic PFS from pump placement were 9 and 13 months, respectively. CONCLUSION: Concomitant HAI and systemic therapy can be utilized at multidisciplinary programs for patients with advanced CRLM, both in the adjuvant setting and to facilitate conversion of unresectable disease.

[Prehepatectomy Chemotherapy Using Circadian Chrono-HAI for Liver Metastases from Colorectal Cancer].

We investigated the safety and efficacy of circadian chronotherapy via the hepatic artery(chrono-HAI)as a prehepatectomy chemotherapy for initially unresectable colorectal liver metastases. Five-day course of chrono-HAI using 5-FU, l-LV, and L-OHP plus systemic panitumumab with 9-day interval were administered to 24 patients with failure for previous chemotherapy. Response rate and Grade 3 adverse effect(AE) were 63% and 54%, respectively. Among 22 patients( excluding 2 CR patients), conversion surgery could be performed in 10(45%). Two-year overall survival of patients with surgery (58%)was longer in those without(20%, p=0.057). Although incidence of AE was a bit high, chrono-HAI plus systemic panitumumab is an effective prehepatectomy chemotherapy for patients with aggressive colorectal liver metastases.

Clinical efficacy of targeted therapy, immunotherapy combined with hepatic artery infusion chemotherapy (FOLFOX), and lipiodol embolization in the treatment of unresectable hepatocarcinoma.

To evaluate the clinical efficacy of targeted therapy and immunotherapy combined with hepatic arterial infusion chemotherapy (HAIC) of FOLFOX and lipiodol embolization in the treatment of unresectable hepatocellular carcinoma. Patients included in the study were those who received targeted therapy and immunotherapy combined with HAIC of FOLFOX and lipiodol embolization in Zhongshan People's Hospital from December 2020 to June 2021 for unresectable hepatocellular carcinoma. Evaluation indicators included objective response rate (ORR), median progression-free survival (mPFS), median duration of response (mDOR), 1-year overall survival rate (OS), surgical conversion rate, and adverse events. Treatment response was assessed using Response Evaluation Criteria in Solid Tumors (mRECIST and RECIST v1.1). A total of 35 patients were included in this study, 30 of whom completed treatment evaluation. According to mRECIST evaluation criteria, the objective response rate (ORR) was 83.3% (25/30); the complete response (CR) was 60% (18/30); the partial response (PR) was 23.3% (7/30), and stable disease (SD) was 16.7% (5/30). The mDOR was 10.3 months (95% Cl: 8.27-NE), and the mPFS was 13.2 months (95% CI: 10.3-NE); the surgical conversion rate was 30.0% (9/30). The 1-year OS was 96.7%. There were no serious surgical complications and grade 4 or 5 adverse events of targeted therapy, immunotherapy and HAIC. Some patients had grade 3 adverse reactions in gastrointestinal toxicity or hepatotoxicity, and the adverse reactions were improved after corresponding symptomatic treatment. We concluded that HAIC of FOLFOX and lipiodol embolization combined with targeted therapy and immunotherapy had a significant curative effect in the treatment of unresectable hepatocellular carcinoma, with no serious adverse reactions and a high rate of surgical conversion rate.

Hepatic Artery Injection of 131I-Metuximab Combined with Transcatheter Arterial Chemoembolization for Unresectable Hepatocellular Carcinoma: A Prospective Nonrandomized, Multicenter Clinical Trial.

This prospective nonrandomized, multicenter clinical trial was performed to investigate the efficacy and safety of 131I-labeled metuximab in adjuvant treatment of unresectable hepatocellular carcinoma. Methods: Patients were assigned to treatment with transcatheter arterial chemoembolization (TACE) combined with 131I-metuximab or TACE alone. The primary outcome was overall tumor recurrence. The secondary outcomes were safety and overall survival. Results: The median time to tumor recurrence was 6 mo in the TACE + 131I-metuximab group (n = 160) and 3 mo in the TACE group (n = 160) (hazard ratio, 0.55; 95% CI, 0.43-0.70; P < 0.001). The median overall survival was 28 mo in the TACE + 131I-metuximab group and 19 mo in the TACE group (hazard ratio, 0.62; 95% CI, 0.47-0.82; P = 0.001). Conclusion: TACE + 131I-metuximab showed a greater antirecurrence benefit, significantly improved the 5-y survival of patients with advanced hepatocellular carcinoma, and was well tolerated by patients.

Transcatheter arterial embolization for massive hemobilia with N-butyl cyanoacrylate (NBCA) Glubran 2.

BACKGROUND: Massive hemobilia is a life-threatening condition and therapeutic challenge. Few studies have demonstrated the use of N-butyl cyanoacrylate (NBCA) for massive hemobilia. PURPOSE: To investigate the efficacy and safety of transcatheter arterial embolization (TAE) using NBCA Glubran 2 for massive hemobilia. MATERIAL AND METHODS: Between January 2012 and December 2019, the data of 26 patients (mean age 63.4 ± 12.6 years) with massive hemobilia were retrospectively evaluated for TAE using NBCA. The patients' baseline characteristics, severities of hemobilia, and imaging findings were collected. Emergent TAE was performed using 1:2-1:4 mixtures of NBCA and ethiodized oil. Technical success, clinical success, procedure-related complications, and follow-up outcomes were assessed. RESULTS: Pre-procedure arteriography demonstrated injuries to the right hepatic artery (n = 24) and cystic artery (n = 2). Initial coil embolization distal to the lesions was required in 5 (19.2%) patients to control high blood flow and prevent end-organ damage. After a mean treatment time of 11.2 ± 5.3 min, technical success was achieved in 100% of the patients without non-target embolization and catheter adhesion. Clinical success was achieved in 25 (96.2%) patients. Major complications were noted in 1 (3.8%) patient with gallbladder necrosis. During a median follow-up time of 16.5 months (range 3-24 months), two patients died due to carcinomas, whereas none of the patients experienced recurrent hemobilia, embolic material migration, or post-embolization complications. CONCLUSION: NBCA embolization for massive hemobilia is associated with rapid and effective hemostasis, as well as few major complications. This treatment modality may be a promising alternative to coil embolization.

Adjuvant intra-arterial chemotherapy for patients with resected colorectal liver metastases: a systematic review and meta-analysis.

BACKGROUND: The practice of adjuvant hepatic arterial infusion chemotherapy (HAIC) for colorectal liver metastasis (CRLM) varies widely. This meta-analysis investigates the effectiveness of adjuvant HAIC and the influence of variations in HAIC treatment in patients with resected CRLM. METHODS: PRISMA guidelines were followed for this study. The search was limited to comparative studies (HAIC vs non-HAIC) for overall survival. Subgroup meta-analyses using random-effects were performed for type of intra-arterial drug, method of catheter insertion, use of concomitant adjuvant systemic chemotherapy, and study design. RESULTS: Eighteen eligible studies were identified. After excluding overlapping cohorts, fifteen studies were included in the quantitative analysis, corresponding to 3584 patients. HAIC was associated with an improved overall survival (pooled hazard ratio (HR) 0.77; 95%CI 0.64-0.93). Survival benefit of HAIC was most pronounced in studies using floxuridine (HR 0.76; 95%CI: 0.62-0.94), surgical catheter insertion with subcutaneous pump (HR 0.71; 95%CI: 0.61-0.84), and concomitant adjuvant systemic chemotherapy (HR 0.75; 95%CI: 0.59-0.96). The pooled HR of RCTs was 0.91 (95%CI 0.72-1.14), of which only 3 used floxuridine. CONCLUSION: Adjuvant HAIC is a promising treatment for patients with resectable CRLM, in particular HAIC with floxuridine using a surgically placed catheter and a subcutaneous pump, and concomitant systemic chemotherapy.

Intraarterial contrast-enhanced ultrasound to predict the short-term tumour response of hepatocellular carcinoma to Transarterial chemoembolization with Lipiodol.

BACKGROUND: Transarterial chemoembolization (TACE) is an effective locoregional therapy in hepatocellular carcinoma (HCC). However, it is difficult to predict the tumour response (TR) of TACE intraprocedurally. The aim of this study was to predict the TR after TACE (1-3 months) in HCC patients using intraprocedural intraarterial contrast enhanced ultrasound (IA-CEUS). METHODS: In this case-control study, consecutive patients who received TACE in our hospital from September 2018 to May 2019 were enrolled. IA-CEUS was performed before and after TACE. Postoperative contrast-enhanced liver MRI was performed 1-3 months after TACE as the gold standard. According to the modified Response Evaluation Criteria in Solid Tumours (mRECIST), ultrasonic manifestations were compared between the complete remission (CR) group and non-CR group by univariate and multivariate analyses. A logistic predictive model was established and validated, and its diagnostic efficiency was evaluated. RESULTS: Forty-four patients with sixty-one lesions were enrolled in the study. Multivariate analysis identified, the risk factors as a large lesion diameter (OR: 1.84; 95% confidence interval [CI]: 1.009, 3.080; P = 0.020), a larger dimension of non-enhancing area in superior mesenteric artery (SMA)-CEUS than the size in B-mode ultrasound preoperatively (OR: 3.379; 95% CI: 1.346,8.484; P = 0.010), presence of corona enhancement in hepatic artery (HA)-CEUS postoperatively (OR: 6.642; 95% CI: 1.214, 36.331; P = 0.029), and decreased corona enhancement thickness (per centimetre) postoperatively (OR: 0.025; 95% CI: 0.006,0.718; P = 0.025). The area under the receiver operating characteristic curve (AUROC) of the predictive model was 0.904 (95% CI: 0.804, 0.966; P < 0.001). The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 81.08, 91.67, 85.25, 93.75, and 75.86%, respectively. Leave-one-out cross-validation (LOOCV) showed that the accuracy was 77.05%. CONCLUSIONS: Intraprocedural IA-CEUS can be used to predict the TR in HCC patients after TACE.

Efficacy and safety of sorafenib combined with TACE in the treatment of advanced hepatocellular carcinoma: A meta-analysis.

PURPOSE: Sorafenib combined with transcatheter arterial chemoembolization (TACE) is one of the common methods in the clinical treatment of advanced hepatocellular carcinoma (HCC), but its efficacy and safety are still controversial. Therefore, we used meta-analysis to evaluate the efficacy and safety of sorafenib combined with TACE in the treatment of advanced HCC. METHODS: Up to March 14, 2021, the databases of PubMed, EMBASE, Cochrane Library, CNKI and Wanfang were searched, and the randomized controlled clinical trials (RCTs) of sorafenib combined with TACE in the treatment of primary HCC were included. Two researchers independently screened the literature, extracted data and evaluated the quality according to the inclusion and exclusion criteria. Revman5.4 software was used for meta-analysis. RESULTS: A total of 3076 patients were included in 23 studies, including sorafenib combined with TACE group (n=1542) and TACE group (n=1534). The results of meta-analysis showed that sorafenib combined with TACE could increase the objective response rate (ORR) (RR=1.35, 95%CI: 1.24-1.48, p<0.00001), disease control rate (DCR) (RR=1.19, 95%CI: 1.11-1.28, p<0.00001), prolong the time of disease progression (TTP) (HR=0.80, 95%CI: 0.70-0.92, p=0.001), reduce the expression level of alpha-fetoprotein (AFP) (SMD=2.01, 95%CI: 1.27-2.75, p<0.00001) and vascular endothelial growth factor (VEGF) (SMD=2.62, 95% CI: 1.35-3.90, p<0.0001) in serum. However, the overall survival (OS) was not prolonged (HR=0.86, 95%CI: 0.73-1.02, p=0.09). The incidences of fatigue, diarrhea, elevated bilirubin, skin reaction of hands and feet, rash, hypertension and oral mucosal inflammation in sorafenib combined with TACE group were higher than those in TACE group (p<0.05). CONCLUSION: Sorafenib combined with TACE has some clinical benefits compared with TACE alone, but it does not seem to prolong the OS of patients with HCC, and the incidence of adverse reactions is higher, so more high-quality RCTs are needed to further study the efficacy of the combination regimen.

Efficacy of sorafenib combined with transcatheter hepatic arterial chemoembolization in treating intermediate-advanced hepatocellular carcinoma.

PURPOSE: To explore the efficacy and safety of sorafenib combined with transcatheter hepatic arterial chemoembolization (TACE) in the treatment of intermediate-advanced hepatocellular carcinoma (HCC). METHODS: A total of 132 intermediate-advanced HCC patients were divided into two groups, namely, control group (n=66, TACE) and Sorafenib group (n=66, TACE combined with sorafenib). Then, the clinical efficacy and incidence rate of adverse reactions were compared s. Besides, the levels of tumor markers and liver function indicators were detected before and after treatment. Additionally, the survival of patients was followed up and recorded. RESULTS: The overall response rate (ORR) and clinical benefit rate (CBR) were significantly higher in Sorafenib group than those in control group. Both Sorafenib group and control group exhibited significantly lowered levels of serum AFP, CEA, CA125 and CA19-9 after treatment compared with those before treatment. In addition, such levels were prominently lower in Sorafenib group than those in control group after treatment. Compared with those before treatment, the levels of total bilirubin (TBil) and alanine aminotransferase (ALT), liver function indexes, significantly rose, while the albumin (Alb) level had no obvious changes in the two groups after treatment. Besides, the liver function indexes displayed no statistically significant differences between the two groups after treatment. Based on the results of follow-up, the median overall survival (OS) and 3-year OS were 16.83 months and 25.8% in Sorafenib group and 12.48 months and 15.2% in control group, respectively. CONCLUSION: Sorafenib combined with TACE achieves better clinical efficacy in the treatment of intermediate-advanced HCC in contrast with TACE alone, which is able to significantly reduce the levels of serum tumor markers and prolong the survival of patients, and results in tolerable adverse reactions.

Induction of Contralateral Hepatic Hypertrophy by Unilobar Yttrium-90 Transarterial Radioembolization versus Portal Vein Embolization: An Animal Study.

PURPOSE: To compare hepatic hypertrophy in the contralateral lobe achieved by unilobar transarterial radioembolization (TARE) versus portal vein embolization (PVE) in a swine model. METHODS: After an escalation study to determine the optimum dose to achieve hypertrophy after unilobar TARE in 4 animals, 16 pigs were treated by TARE (yttrium-90 resin microspheres) or PVE (lipiodol/n-butyl cyanoacrylate). Liver volume was calculated based on CT before treatment and during 6 months of follow-up. Independent t-test (P < .05) was used to compare hypertrophy. The relationship between hypertrophy after TARE and absorbed dose was calculated using the Pearson correlation. RESULTS: At 2 and 4 weeks after treatment, a significantly higher degree of future liver remnant hypertrophy was observed in the PVE group versus the TARE group, with a median volume gain of 31% (interquartile range [IQR]: 16%-66%) for PVE versus 23% (IQR: 6%-36%) for TARE after 2 weeks and 51% (IQR: 47%-69%) for PVE versus 29% (IQR: 20%-50%) for TARE after 4 weeks. After 3 and 6 months, hypertrophy converged without a statistically significant difference, with a volume gain of 103% (IQR: 86%-119%) for PVE versus 82% (IQR: 70%-96%) for TARE after 3 months and 115% (IQR: 70%-46%) for PVE versus 86% (IQR: 58%-111%) for TARE after 6 months. A strong correlation was observed between radiation dose (median 162 Gy, IQR: 139-175) and hypertrophy. CONCLUSIONS: PVE resulted in rapid hypertrophy within 1 month of the procedure, followed by a plateau, whereas TARE resulted in comparable hypertrophy by 3-6 months. TARE-induced hypertrophy correlated with radiation absorbed dose.

[A Case in Which Multiple Post-Operatively Recurring Hepatocellular Carcinomas Showed a Positive Response to Sorafenib-Hepatic Arterial Infusion Chemotherapy (HAIC)Sequential Therapy].

A male patient in his 70s underwent a right lobectomy because of a hepatocellular carcinoma(HCC)located in the right lobe(S6)of his liver. Eleven months after surgery, contrast-enhanced CT showed multiple masses in the residual liver, which were diagnosed as HCC recurrence. He was then treated with hepatic arterial infusion chemotherapy(HAIC). Ten months after the recurrence, the liver tumors progressed. Therefore, treatment was switched to sorafenib(400 mg/day orally)and HAIC(low-dose FP: 5-FU 250 mg plus CDDP 5 mg 5 days/week 4 weeks)sequential therapy. The patient received 2 cycles of sorafenib-HAIC sequential therapy for 11 months, and his liver tumors shrunk considerably. Unfortunately, 24 months after the recurrence of HCC, he died of respiratory failure. The cause of his death was officially determined to be primary lung cancer. An autopsy revealed that most tissues were necrotic, and only a small number of viable tumor cells were present in the liver tumors. This suggests that sorafenib-HAIC sequential therapy was significantly effective in targeting the multiple HCCs in this case.

A novel irinotecan-lipiodol nanoemulsion for intravascular administration: pharmacokinetics and biodistribution in the normal and tumor bearing rat liver.

Colorectal cancer is one of the most common cancers in the United States and treatment options are limited for patients who develop liver metastases. Several chemotherapeutic regimens have been used for transvascular liver-directed therapy in the treatment of colorectal liver metastases without clear evidence of superiority of one therapy over another. We describe the development of a novel nanoemulsion through combining irinotecan (IRI), a first line systemic agent used for the treatment of colon cancer, with lipiodol, an oily contrast medium derived from poppy seed oil, and evaluated its pharmacokinetic and biodistribution profile as a function of portal venous chemoembolization (PVCE) versus transarterial chemoembolization (TACE) delivery. The Tessari technique was used to create a stable emulsion (20 mg IRI mixed with 2 mL lipiodol) with resultant particle size ranging from 28.9 nm to 56.4 nm. Pharmacokinetic profile established through venous sampling in Buffalo rats demonstrate that the area under the curve (AUC0-∞) of IRI was significantly less after PVCE with IRI-lipiodol as compared to IRI alone (131 vs. 316 µg*min/mL, p-value = .023), suggesting significantly higher amounts of IRI retention in the liver with the IRI-lipiodol nanoemulsion via first-pass extraction. Subseqent biodistribution studies in tumor-bearing WAG/Rjj rats revealed more IRI present in the tumor following TACE versus PVCE (29.19 ± 12.33 µg/g versus 3.42 ± 1.62; p-value = .0033) or IV (29.19 ± 12.33 µg/g versus 1.05 ± 0.47; p-value = .0035). The IRI-lipiodol nanoemulsion demonstrated an acceptable hepatotoxicity profile in all routes of administration. In conclusion, the IRI-lipiodol nanoemulsion via TACE showed promise and warrants further investigation as an option for the treatment of metastatic colorectal cancer.