Pharmacokinetics and Early Tumor Response to Conventional Transarterial Chemoembolization with Sorafenib and Doxorubicin in a VX2 Rabbit Tumor Model

PurposeTo investigate the pharmacokinetics (PK) and early effects of conventional transarterial chemoembolization (TACE) using sorafenib and doxorubicin on tumor necrosis, hypoxia markers, and angiogenesis in a rabbit VX2 liver tumor model.Materials and MethodsVX2 tumor-laden New Zealand White rabbits (N = 16) were divided into 2 groups: 1 group was treated with hepatic arterial administration of ethiodized oil and doxorubicin emulsion (DOX-TACE), and the other group was treated with ethiodized oil, sorafenib, and doxorubicin emulsion (SORA-DOX-TACE). Animals were killed within 3 days of the procedure. Levels of sorafenib and doxorubicin were measured in blood, tumor, and adjacent liver using mass spectrometry. Tumor necrosis was determined by histopathological examination. Intratumoral hypoxia-inducible factor (HIF) 1α, vascular endothelial growth factor (VEGF), and microvessel density (MVD) were determined by immunohistochemistry.ResultsThe median intratumoral concentration of sorafenib in the SORA-DOX-TACE group was 17.7 μg/mL (interquartile range [IQR], 7.42–33.5 μg/mL), and its maximal plasma concentration (C_max) was 0.164 μg/mL (IQR, 0.0798–0.528 μg/mL). The intratumoral concentration and C_max of doxorubicin were similar between the groups: 4.08 μg/mL (IQR, 3.18–4.79 μg/mL) and 0.677 μg/mL (IQR, 0.315–1.23 μg/mL), respectively, in the DOX-TACE group and 1.68 μg/mL (IQR, 0.795–4.08 μg/mL) and 0.298 μg/mL (IQR, 0.241–0.64 μg/mL), respectively, in the SORA-DOX-TACE group. HIF-1α expression was increased in the SORA-DOX-TACE group than in the DOX-TACE group. Tumor volume, tumor necrosis, VEGF expression, and MVD were similar between the 2 groups.ConclusionsThe addition of sorafenib to DOX-TACE delivered to VX2 liver tumors resulted in high intratumoral and low systemic concentrations of sorafenib without altering the PK of doxorubicin.     

The effect of trans arterial chemoembolization in the management of intrahepatic cholangiocarcinoma. A systematic review and meta-analysis

BackgroundA comprehensive re-evaluation on the role of trans-arterial chemoembolization (TACE) in patients with intrahepatic cholangiocarcinoma.MethodsA thorough database searching was performed in PubMed, EMBASE, and the Cochrane Library. Eligible studies were restricted to comparative studies between TACE and non-TACE cohorts. RevMan5.3 software and Stata 13.0 software were used for statistical analyses. The primary endpoint of our study was long-term survival.ResultsA total of 11 studies with 2036 patients were finally identified. Pooled results revealed that patients receiving TACE had a significantly better overall survival (OS) versus those without TACE (P < 0.05). Subgroup analyses were performed according to different types of TACE. Prophylactic post-surgical TACE (PPTACE) was associated with a significantly better OS versus those without PPTACE (P < 0.05). Palliative TACE (PTACE) also achieved a significantly better OS compared with those with supportive treatment (ST) only (P < 0.00001). However, TACE had no impact on disease-free survival (P = 0.87) and was less effective than surgical resection (P = 0.003).ConclusionPPTACE has a remarkable impact on OS versus those with surgical resections only and should be regularly performed. Regarding patients with unresectable disease, apart from conventional ST, adjuvant PTACE is also recommended. Upcoming prospective randomized controlled trials are warranted for further validation.     

Microwave Ablation as Bridging to Liver Transplant for Patients with Hepatocellular Carcinoma: A Single-Center Retrospective Analysis

PurposeTo evaluate the efficacy and safety of microwave (MW) ablation as first-line locoregional therapy (LRT) for bridging patients with hepatocellular carcinoma (HCC) to liver transplant.Materials and MethodsThis retrospective study evaluated 88 patients who received percutaneous MW ablation for 141 tumors as first-line LRT for HCC and who were listed for liver transplantation at a single medical center between 2011 and 2019. The overall survival (OS) rate statuses after liver transplant, waitlist retention, and disease progression were evaluated using the Kaplan-Meier techniques.ResultsAmong the 88 patients (72 men and 16 women; mean age, 60 years; Model for End-Stage Liver Disease score, 11.2) who were listed for transplant, the median waitlist time was 9.4 months (interquartile range, 5.5–18.9). Seventy-one (80.7%) patients received transplant after a median waitlist time of 8.5 months. Seventeen (19.3%) patients were removed from the waitlist; of these, 4 (4.5%) were removed because of tumors outside of the Milan criteria (HCC-specific dropout). No difference in tumor size or alpha-fetoprotein was observed in the transplanted versus nontransplanted patients at the time of ablation (2.1 vs 2.1 cm and 34.4 vs 34.7 ng/mL for transplanted vs nontransplanted, respectively; P > .05). Five (5.1%) of the 88 patients experienced adverse events after ablation; however, they all recovered. There were no cases of tract seeding. The local tumor progression (LTP) rate was 7.2%. The OS status after liver transplant at 5 years was 76.7%, and the disease-specific survival after LTP was 89.6%, with a median follow-up of 61 months for all patients.ConclusionsMW ablation appears to be safe and effective for bridging patients with HCC to liver transplant without waitlist removal from seeding, adverse events, or LTP.     

Drug-Eluting Embolics Chemoembolization for the Management of Recurrent or Advanced Head and Neck Cancer

PurposeTo characterize the safety, tolerability, and efficacy of chemoembolization using drug-eluting embolic (DEE) microspheres in patients with recurrent and advanced head and neck cancer.Materials and MethodsIn this retrospective study, 32 patients (mean age, 57.2 years ± 2.8; 17 women) with recurrent (n = 16) and advanced (n = 16) head and neck cancer were treated with chemoembolization using DEE microspheres loaded with doxorubicin. Treatment response, overall survival, local progression-free survival, and adverse events were evaluated.ResultsAt 6 months after the procedure, the objective response and disease control rates were 25% and 69%, respectively. The median overall survival and local progression-free survival were 14.5 and 13.6 months, respectively. Seven (22%) patients experienced adverse events after the chemoembolization procedure. All the adverse events were related to postembolization syndrome, including vomiting and nausea (n = 1), pyrexia (n = 2), and localized pain (n = 7). No severe adverse events or procedure-related deaths were observed.ConclusionsChemoembolization using DEE microspheres was safe and tolerable in patients with recurrent and advanced head and neck cancer.     

肝细胞癌TACE术后病灶存活或复发18F-FDGPET/CT和增强CT诊断价值Meta分析

目的采用Meta分析方法评价¹⁸F-脱氧葡萄糖正电子发射计算机体层摄影(¹⁸F-FDG PET/CT)和增强CT(CECT)诊断经导管肝动脉化疗栓塞术(TACE)术后存活或复发病灶的临床价值。方法根据PRISMA报告规范开展Meta分析。检索PubMed、Embase、Cochrane Library、Web of Science、中国知网、万方和维普数据库中¹⁸F-FDG PET/CT和CECT诊断TACE术后存活或复发病灶的临床研究,时间至2019-04。由2位研究人员独立筛选文献、提取资料,根据诊断准确性研究质量评价工具-2(QUADAS-2)评价纳入研究的偏倚风险后,采用Stata 12.0软件进行Meta分析,计算其汇总敏感度(Sen)和特异度(Spe),绘制受试者工作特征曲线(SROC)并计算曲线下面积(AUC)。结果共纳入10篇¹⁸F-FDG PET/CT及13篇CECT诊断TACE术后存活或复发病灶的原始研究,分别包括322例患者的467个病灶和748例患者的943个病灶。Meta分析显示,¹⁸F-FDG PET/CT诊断TACE术后存活或复发病灶的Sen=0.92(95%CI为0.87~0.94)、Spe=0.95(95%CI为0.82~0.99)、AUC=0.97(95%CI为0.93~0.99);CECT诊断TACE术后存活或复发病灶的Sen=0.72(95%CI为0.66~0.78)、Spe=0.99(95%CI为0.93~1.00)、AUC=0.87(95%CI为0.83~0.89)。此外,CECT诊断TACE术后存活或复发Sen(Z=2.34,P=0.02)和AUC(Z=2.21,P=0.03)值低于¹⁸F-FDG PET/CT,差异有统计学意义。结论相比于CECT,¹⁸F-FDG PET/CT对TACE术后存活或复发病灶具有较高诊断效能,可视为TACE术后存活或复发病灶有效的影像学诊断方法。     

Reduced nontarget embolization and increased targeted delivery with a reflux-control microcatheter in a swine model

PurposeTo evaluate the potential differences in non-target embolization and vessel microsphere filling of a reflux-control microcatheter (RCM) compared to a standard end-hole microcatheter (SEHM) in a swine model.Materials and methodsRadiopaque microspheres were injected with both RCM and SEHM (2.4-Fr and 2.7-Fr) in the kidneys of a preclinical swine model. Transarterial renal embolization procedures with RCM or SEHM were performed in both kidneys of 14 pigs. Renal arteries were selectively embolized with an automated injection protocol of radio-opaque microspheres. Ex-vivo X-ray microtomography images of the kidneys were utilized to evaluate the embolization by quantification of the deposition of injected microspheres in the target vs. the non-target area of injection. X-ray microtomography images were blindly analyzed by five interventional radiologists. The degree of vessel filling and the non-target embolization were quantified using a scale from 1 to 5 for each parameter. An analysis of variance was used to compare the paired scores.ResultsTotal volumes of radio-opaque microspheres injected were similar for RCM (11.5 ± 3.6 [SD] mL; range: 6–17 mL) and SEHM (10.6 ± 5.2 [SD] mL; range: 4–19 mL) (P = 0.38). The voxels enhanced ratio in the target (T) vs. non-target (NT) areas was greater with RCM (T = 98.3% vs. NT = 1.7%) than with SEHM (T = 89% vs. NT = 11%) but the difference was not significant (P = 0.30). The total score blindly given by the five interventional radiologists was significantly different between RCM (12.3 ± 2.1 [SD]; range: 6–15) and the standard catheter (11.3 ± 2.5 [SD]; range: 4–15) (P = 0.0073), with a significant decrease of non-target embolization for RCM (3.8 ± 1.3 [SD]; range: 3.5–4.2) compared to SEHM (3.2 ± 1.5 [SD]; range: 2.9–3.5) (P = 0.014).ConclusionIn an animal model, RCM microcatheters reduce the risk of non-target embolization from 11% to 1.7%, increasing the delivery of microspheres of 98% to the target vessels, compared to SEHM microcatheters.     

Transarterial chemoembolization <i>vs.</i> liver resection as initial treatment for hepatocellular carcinoma occurring exclusively in caudate lobe: A retrospective propensity matching analysis

Treatment of hepatocellular carcinoma (HCC) in the caudate lobe is technically challenging. This retrospective study was designed to evaluate the clinical outcome of both superselective transcatheter arterial chemoembolization (TACE) and liver resection (LR) for HCC occurring exclusively in the caudate lobe. From January 2008 to September 2021, a total of 129 patients were diagnosed with HCC of the caudate lobe. The Cox proportional hazard model was used to analyze the potential clinical factors and established prognostic nomograms with interval validation. Of the total number of patients, 78 received TACE and 51 received LR. The overall survival (OS) rates (TACE vs. LR) at 1, 2, 3, 4, and 5 years were 83.9% vs. 71.0%; 74.2% vs. 61.3%; 58.1% vs. 48.4%; 45.2% vs. 45.2%; and 32.3% vs. 25.0%, respectively. However, subgroup analysis revealed that TACE was superior to LR for treating patients with stage IIb Chinese liver cancer (CNLC-IIb) in the entire cohort (p = 0.002). Interestingly, no difference was found between TACE and LR in the treatment outcomes of CNLC-IIa HCC (p = 0.6). Based on Child-Pugh A and B calculations, TACE tended to lead to a better OS than LR (p = 0.081 and 0.16, respectively). Multivariate analysis showed that Child-Pugh score, CNLC stage, ascites, alpha fetoprotein (AFP), tumor size, and anti-HCV are related to OS. Predictive nomograms for 1, 2, and 3 years were performed. Based on this study, TACE may provide a longer OS than liver resection for patients with CNLC-IIb HCC of the caudate lobe. Because this suggestion is limited by the study design and relatively small sample size, additional randomized controlled trials are needed.     

Spontaneous rupture of hepatocellular carcinoma: Optimal timing of partial hepatectomy

BackgroundPartial hepatectomy has been used to treat patients with resectable hepatocellular carcinoma (HCC) which spontaneously ruptured. It is still controversial as to whether emergency partial hepatectomy (EmPH) should be carried out at the time of rupture, or the patients should initially be managed by operative or non-operative treatment to stop the bleeding, followed by staged early or delayed partial hepatectomy when the patient's condition becomes stable.MethodsConsecutive 10-year patients with ruptured HCC managed at our center were included in this study. Patients who underwent partial hepatectomy were further subdivided into the EmPH group, the staged early partial hepatectomy (SEPH) group, and the staged delayed partial hepatectomy (SDPH) group. Univariate and multivariate analyses of factors affecting overall survival(OS) were conducted before and after propensity score matching analyses amongst the included patients. OS, postoperative mortality, recurrence free survival (RFS), and peritoneal metastatic rates were compared. The risk factors of peritoneal metastases were determined using the COX regression analysis.ResultsThe 130 patients who underwent partial hepatectomy were subdivided into the EmPH group (surgery at the time of rupture, n = 30), the SEPH group (surgery ≤ 8 days of rupture, n = 67), and the SDPH group (surgery > 8 days of rupture, n = 33). The remaining 86 patients underwent non-surgical treatment. Partial hepatectomy was an independent predictor of better OS (HR 2.792, P < 0.001). For resectable HCC, the 30-day mortality, OS, and RFS were similar between the EmPH group, and the staged partial hepatectomy (SPH) group which included the patients who underwent SEPH and SDPH. The SEPH group had significantly better OS and RFS. Multivariate COX regression analysis demonstrated that SDPH was strongly associated with postoperative peritoneal dissemination (OR 28.775, P = 0.003).ConclusionPartial hepatectomy provided significantly better survival than non-surgical treatment for patients who presented with ruptured HCC. Early partial hepatectomy within 8 days of rupture which included EmPH (carefully selected) and SEPH, resulted in significantly less patients with peritoneal dissemination and better long-term survival outcomes (especially RFS) than SDPH.