Recommended 10-Year Follow-Up Strategy for Small Hepatocellular Carcinoma After Radiofrequency Ablation: A Cost-Effectiveness Evaluation.

INTRODUCTION: An optimal follow-up schedule for small (≤3-cm) hepatocellular carcinoma (HCC) after radiofrequency ablation (RFA) remains unclear in clinical guidelines. We aimed to assess the cost-effectiveness of follow-up strategies in patients with small HCC after RFA. METHODS: In total, 11,243 patients were collected from global institutions to calculate recurrence rates. Subsequently, a Markov model covering a 10-year period was developed to compare 25 surveillance strategies involving different surveillance techniques (computed tomography [CT], magnetic resonance imaging or ultrasonography [US], and α-fetoprotein [AFP]) and intervals (3 or 6 months). The study endpoint was incremental cost-effectiveness ratio (ICER), which represented additional cost per incremental quality-adjusted life year. Sensitivity analysis was conducted by varying the values of input parameters to observe the ICER. RESULTS: In a base case analysis, the dominant strategy was CT every 3 months during an initial 2 years, followed by semiannual CT, and then switch to biannual the combination of US screening and AFP testing after 5 years (m3_CT-m6_CT-m6_USAFP), with an ICER of $68,570.92 compared with the "not followed" strategy. One-way sensitivity analysis showed the ICER consistently remained below the willingness-to-pay threshold of $100,000.00. In a probabilistic sensitivity analysis, m3_CT-m6_CT-m6_USAFP was the most cost-effective approach in 95.6% of simulated scenarios at a willingness-to-pay threshold. DISCUSSION: For small HCC after RFA, the recommended follow-up strategy is CT, with scans scheduled every 3 months for the first 2 years, every 6 months thereafter, and transition to biannual the combination of US screening and AFP testing after 5 years.

Hepatic arterial infusion therapy for advanced hepatocellular carcinoma after systemic treatment failure: Multicenter, real-world study.

AIM: The study was conducted to evaluate the feasibility and safety profile of hepatic arterial infusion chemotherapy with oxaliplatin, 5-fluorouracil, and leucovorin (HAIC-FOLFOX) as an alternative therapeutic choice for patients with advanced hepatocellular carcinoma (HCC) that is refractory to systemic treatment including immune checkpoint blockades or molecular targeting agents. METHODS: Two hundred and forty five consecutive patients with advanced HCC who received HAIC-FOLFOX treatment after systemic treatment failure were retrospectively reviewed in six institutions and their survival, tumor response, and tolerance were assessed. RESULTS: The median overall survival (OS) and progression-free survival of the 209 included participants were 10.5 months (95% confidence interval [CI], 8.1-12.9) and 6.0 months (95% CI, 5.1-6.9), respectively. According to Response Evaluation Criteria in Solid Tumors 1.1 criteria, the objective response rate was 21.1%, and the disease control rate was 64.6%. Multivariate analysis of risk factors of OS were albumin-bilirubin grade (2 and 3 vs. 1, hazard ratio [HR] 1.57; 95% CI, 1.05-2.34; p = 0.028), tumor number (>3 vs. 1-3, HR 2.18; 95% CI, 1.10-4.34; p = 0.026), extrahepatic spread (present vs. absent, HR 1.61, 95% CI, 1.06-2.45; p = 0.027), synchronous systemic treatment (present vs. absent, HR 0.55, 95% CI, 0.37-0.83; p = 0.004) and treatment response (responder vs. nonresponder, HR 0.30, 95% CI, 0.17-0.53; p < 0.001). Grade 3-4 adverse events (AEs) occurred in 59 (28.2%) HCC patients. All AEs were manageable, and deaths related to hepatic artery infusion chemotherapy treatment were not observed. CONCLUSIONS: Our findings support the effectiveness and safety of HAIC-FOLFOX treatment for patients with advanced HCC who have failed systemic treatment.

Hypoxic Hepatocellular Carcinoma Cells Acquire Arsenic Trioxide Resistance by Upregulating HIF-1α Expression.

BACKGROUND: Although arsenic trioxide (ATO) is used in the treatment of advanced hepatocellular carcinoma (HCC) in clinical trials, it is not satisfactory in terms of improving HCC patients' overall survival. Intratumoral hypoxia and overexpression of hypoxia-inducible factor-1α (HIF-1α) may result in ATO resistance and tumor progression. AIMS: We investigated the mechanisms involving HIF-1α expression and acquired ATO chemoresistance in HCC cells and mice. METHODS: The therapeutic effects of ATO in normoxic and hypoxic HCC cells were assessed using cell viability and apoptosis assays in vitro and a xenograft model in vivo. mRNA and protein expression of HIF-1α, P-glycoprotein, and VEGF were measured by qRT-PCR and western blotting. HIF-1α inhibition was performed to investigate the mechanism of ATO resistance. VEGF secretion was tested using ELISA and tube formation assays. RESULTS: Compared to normoxic cells, hypoxic HCC cells were more resistant to ATO, with higher IC50 values and less apoptosis, and upregulated HIF-1α protein expression, accompanied with the enhancement of P-glycoprotein and VEGF synthesis after ATO treatment. VEGF secretion was elevated in the supernatant of ATO-treated HCC cells, and this change can potentiate angiogenesis in vitro. HIF-1α inhibition attenuated ATO resistance and angiogenesis and promoted the anticancer effects of ATO both in vitro and in vivo by downregulating therapy-induced P-glycoprotein and VEGF overexpression. CONCLUSIONS: Hypoxic HCC cells acquire ATO resistance by upregulating HIF-1α levels; thus, combining ATO with a HIF-1α-targeting agent may lead to enhanced antitumor effects in HCC.

A nomogram to predict survival of patients with intermediate-stage hepatocellular carcinoma after transarterial chemoembolization combined with microwave ablation.

OBJECTIVES: To develop a prognostic nomogram based on the albumin-bilirubin (ALBI) grade for prediction of the long-term survival of patients with intermediate-stage hepatocellular carcinoma (HCC) after transarterial chemoembolization combined with microwave ablation (TACE-MWA). METHODS: We retrospectively studied 546 consecutive patients with intermediate-stage HCC according to the Barcelona Clinic Liver Cancer guidelines who underwent TACE-MWA between January 2000 and December 2016. Overall survival (OS) and progression-free survival (PFS) were analyzed. The predictive value of the ALBI grade was investigated. The prognostic nomogram was constructed using the independent predictors assessed by the multivariate Cox proportional hazards model. RESULTS: After a median follow-up of 35.0 months (range, 4.0-221.0 months), 380 patients had died. The median OS was 35.0 months (95% confidence interval (CI), 30.84-39.16 months), and the median PFS was 6.5 months (95% CI, 6.13-6.87 months). The ALBI grade was validated as an independent predictor of OS (p < 0.001). Multivariate analyses showed that Eastern Cooperative Oncology Group performance status score more than 0, presence of liver cirrhosis, a-fetoprotein level above 400 ng/mL, tumor size greater than 5 cm, tumor number more than 3, advanced ALBI grade, and treatment sessions of TACE or MWA fewer than 3 were independently associated with overall mortality. The prognostic nomogram incorporating these eight predictors achieved good calibration and discriminatory abilities with a concordance index of 0.770 (95% CI, 0.746-0.795). CONCLUSIONS: The prognostic nomogram based on the ALBI grade resulted in reliable efficacy for prediction of individualized OS in patients with intermediate-stage HCC after TACE-MWA. KEY POINTS: • TACE-MWA was associated with a median overall survival of 35.0 months for patients with intermediate-stage HCC. • A prognostic nomogram was built to predict individualized survival of patients with intermediate-stage HCC after TACE-MWA. • The prognostic nomogram incorporating eight predictors achieved good calibration and discriminatory abilities with a concordance index of 0.770.

Comparison of hydrochloric acid infusion radiofrequency ablation with microwave ablation in an ex vivo liver model.

Objectives: To compare sizes and shapes of ablation zones resulting from hydrochloric acid infusion radiofrequency ablation (HRFA) and microwave ablation (MWA), using normal saline infusion radiofrequency ablation (NSRFA) as a control, at a variety of matched power settings and ablation durations, in an ex vivo bovine liver model.Methods: A total of 90 ablation procedures were performed, using each of three modalities: NSRFA, HRFA, and MWA. For each modality, five ablation procedures were performed for each combination of power (80 W, 100 W, or 120 W) and duration (5, 10, 20, 30, 45, or 60 min). The size of ablation zones were compared using ANOVA, the Kruskal-Wallis test, or generalized linear regression.Results: For ablation durations up to 30 min, mean transverse diameter (TD) after HRFA and MWA did not differ significantly (ß = 0.13, p = .20). For ablation durations greater than 30 min, mean TD was significantly larger after HRFA than after MWA (ß = 1.657, p < .001). The largest TD (9.46 cm) resulted from HRFA performed with 100 W power for 60 min.Conclusions: Compared to MWA, monopolar HRFA with power settings of 80 W-120 W and durations of less than 30 min showed no significant difference. When duration of more than 30 min, HRFA created larger ablation zones than MWA.

CT-Guided Percutaneous Gastrostomy without Preliminary Placement of a Nasogastric Tube.

Percutaneous radiologic gastrostomy (PRG) requires preliminary gastric inflation through a nasogastric tube (NGT) to safely perform gastric puncture. However, in case of pharyngeal or esophageal obstruction, NGT placement may be impossible even with a hydrophilic angiography catheter and wire. This brief report describes percutaneous computed tomography (CT)-guided gastrostomy with a 2-stick approach without nasogastric insufflation in 13 patients. Technical success rate was 100% with a mean of 1.8 punctures ± 1.0 to access the gastric lumen. Traversal of the colon and liver with a 22-gauge needle was necessary in 4 and 1 patients, respectively. There were no major complications. Minor complications occurred in 6 patients (46%). CT-guided percutaneous gastrostomy is technically feasible with minimal morbidity.

Predictive value of the albumin-bilirubin grade on long-term outcomes of CT-guided percutaneous microwave ablation in intrahepatic cholangiocarcinoma.

PURPOSE: To assess the efficacy of the albumin-bilirubin (ALBI) grade on assessing long-term outcomes of computed tomography (CT)-guided percutaneous microwave ablation (CT-PMWA) in the treatment of patients with intrahepatic cholangiocarcinoma (ICC). METHODS: Between April 2011 and March 2018, 78 patients who underwent CT-PMWA were enrolled in this study. Overall survival (OS) and recurrence-free survival (RFS) were compared in the groups stratified by the ALBI grade and Child-Pugh score. Cox proportional hazard regression analyses were performed to determine independent predictors of OS and RFS. RESULTS: After a median follow-up of 22.7 months (range 1-86.7 months), 67 patients had died. The cumulative 1-, 3-, and 5-year OS rates were 89.5%, 52.2%, and 35.0%, respectively. Stratified by the ALBI grade, the cumulative 1-, 3-, and 5-year OS rates were 100%, 69.2%, and 25.6% for patients with the grade 1, respectively. For patients with the ALBI grade 2, the cumulative 1-, 3-, and 5-year OS rates were 41.0%, 10.3%, and 10.3%, respectively. Patients with a hepatic function of the ALBI grade 1 had significantly higher OS rates than patients with the ALBI grade 2 (p < .001). The multivariate analysis showed tumor size (Hazard Ratio[HR] 95% Confidence Interval[CI]:9.03[1.01-80.52], p = .049) and the ALBI grade (HR[95%CI]:9.56[1.58-58.00], p = .014) were associated with OS, and tumor size (HR: 2.03[0.69-8.04], p = .049) was associated with RFS. CONCLUSIONS: The preliminary data of this study showed the ALBI grade was effective to predict long-term outcomes of CT-PMWA in ICCs. Further study is necessary to validate our results by a large, multi-center patient cohort.

Comparison of albumin-bilirubin grade, platelet-albumin-bilirubin grade and Child-Turcotte-Pugh class for prediction of survival in patients with large hepatocellular carcinoma after transarterial chemoembolization combined with microwave ablation.

Purpose: To compare the predictive value of albumin-bilirubin (ALBI) grade, platelet-ALBI (PALBI) grade and Child-Turcotte-Pugh (CTP) class in patients with large hepatocellular carcinoma (HCC) after transarterial chemoembolization (TACE) combined with microwave ablation (TACE-MWA). Methods: A total of 349 consecutive HCC patients (89.1% male; mean [± SD] age 53.4 ± 12.27 years) from three medical centers, who underwent TACE-MWA for up to 3 HCCs with maximum diameters of 5.1-8.0 cm between January 2000 and June 2018, were investigated. Overall survival (OS) and progression-free survival (PFS) were analyzed. The prognostic performances of ALBI grade, PALBI grade and CTP class were compared. Results: TACE procedures were performed using lobaplatin (20-50 mg), epirubicin (30-60 mg), lipiodol (5-25 mL) and gelatin sponge particles (350-560 µm). The end point of the TACE procedure was stasis of blood flow in the feeder artery. The median follow-up duration was 28.0 months, the median OS was 28.0 months (95% confidence interval [CI] 23.55-32.45 months), and the median PFS was 4.8 months (95% CI 4.26-5.34 months). Patients with a ablation margin size of 11-15 mm experienced better PFS than those with a margin size of 6-10 or 0-5 mm (median, 6.5 versus [vs] 4.0 vs 2.3 months; p < .001). PALBI grade demonstrated significantly greater area under the curve values than ALBI grade or CTP class in predicting 1-, 3- and 5-year OS. Conclusions: PALBI grade provided better predictive value than ALBI grade or CTP class in patients with large HCCs after TACE-MWA.

Safety and effect on ablation size of hydrochloric acid-perfused radiofrequency ablation in animal livers.

PURPOSE: Our objective was to determine the safety and ablation size of hydrochloric acid-perfused radiofrequency ablation (HCl-RFA) in liver tissues, prospectively using in vivo rabbit and ex vivo porcine liver models. MATERIALS AND METHODS: The livers in 30 rabbits were treated in vivo with perfusions of normal saline (controls) and HCl concentrations of 5%, 10%, 15%, and 20%, during RFA at 103 °C and 30 W for 3 min. For each experimental setting, six ablations were created. Safety was assessed by comparing baseline weight and selected laboratory values with those at 2, 7, and 14 days' post-ablation, and by histopathological analysis. The livers in 25 pigs were treated ex vivo with the same five perfusions during RFA at 103 °C, at both 30 W and 60 W, for 30 min. Ablation diameters and volumes were measured by two examiners. RESULTS: Rabbit weights and selected laboratory values did not differ significantly from baseline to 7 and 14 days' post-ablation, liver tissues outside the ablation zones were normal histologically, and adjacent organs showed no macroscopic damage. The mean ablation volumes in the porcine livers treated with HCl-RFA were all larger than those treated with normal saline perfusion during RFA (NS-RFA), at both 30 W and 60 W (p < 0.001). The largest ablation volume and transverse diameter were observed in the porcine livers during 10% HCl-RFA at 60 W, measuring 179.22 (SD = 24.79) cm3 and 6.84 (SD = 0.36) cm, respectively. CONCLUSIONS: Based on our experiments, HCl-RFA in the liver appears to be as safe as NS-RFA while also resulting in larger ablation zones.

Increasing radiofrequency ablation volumes with the use of internally cooled electrodes and injected hydrochloric acid in ex vivo bovine livers.

PURPOSE: We used an impedance-controlled generator with an internally cooled electrode to perform radiofrequency ablation (RFA) in ex vivo bovine livers, with a single injection of either 38.5% sodium chloride (NaCl) or 10% hydrochloric acid (HCl), to determine the relative effects of these two solutions on tissue impedance, temperature and ablation volume. MATERIALS AND METHODS: We performed 10 ablations each with injections of NaCl (NaCl-RFA), HCl (HCl-RFA) or nothing (RFA-alone), with a power setting of 200 W for 15 minutes. We recorded tissue impedance before and after injection. We logged temperatures obtained from thermocouple probes positioned 5, 10, 15 and 20 mm from the internally cooled RF electrode. After ablation, we measured ablation zone longitudinal and transverse diameters, and we calculated a spherical ratio (SR) for each ablation. RESULTS: Mean post-injection impedance of 30.3 (standard deviation [SD] 2.5) ohms for HCl was significantly lower than that of 55.4 (SD 3.5) ohms for NaCl (p < .001). Mean maximum temperatures recorded at each respective distance from the RFA electrode were all highest for HCl-RFA and lowest for RFA-alone (p < .001). Mean longitudinal and transverse diameters after HCl-RFA (5.50 [SD 0.25] cm and 5.28 [SD 0.22] cm, respectively) were significantly larger than those after NaCl-RFA (4.24 [SD 0.35] cm and 3.55 [SD 0.43] cm, respectively) and after RFA-alone (3.60 [SD 0.10] cm and 2.70 [SD 0.13] cm, respectively) (p < .001). Mean SR after HCl-RFA (0.93, SD 0.02) was significantly higher than mean SR after NaCl-RFA (0.76, SD 0.06) and RFA-alone (0.72, SD 0.04) (p < .001). CONCLUSION: Monopolar, impedance-controlled RFA, with an internally cooled electrode and a single 10% HCl injection may allow larger tumors to be treated, potentially resulting in improved patient outcomes.

Regional thermochemotherapy versus hepatic arterial infusion chemotherapy for palliative treatment of advanced hilar cholangiocarcinoma: a retrospective controlled study.

OBJECTIVES: To retrospectively assess the efficacy of regional thermochemotherapy (TCT) compared with hepatic arterial infusion chemotherapy (HAIC)-alone for palliative treatment of advanced hilar cholangiocarcinoma (HC) and to determine the prognostic factors associated with survival. METHODS: Forty-three consecutive patients with advanced HC underwent regional TCT (TCT group) and HAIC (HAIC group). We analyzed baseline characteristics, overall survival (OS), progression-free survival (PFS), stent patency time (SPT), adverse events (AEs), and prognostic factors for OS between the two groups. RESULTS: OS of patients treated with regional TCT was significantly longer compared to that of patients treated with HAIC (median OS: 20.3 vs. 13.2 months, P = 0.004), and SPT and PFS were significantly increased in the TCT group compared with the HAIC group (median SPT: 26.5 vs. 10.5 months, P < 0.001; median PFS: 16.5 vs. 10.2 months, P = 0.001). TCT and metal stent insertion were two independent prognostic factors associated with survival. The treatment-related AEs were tolerable and similar in the two groups, except for hilar pain (34.6 %) and skin rashes (24.6 %) in the TCT group. CONCLUSIONS: Our results show that regional TCT is safe and more effective than HAIC-alone and may be a promising option for palliative treatment of advanced HC. Metal stenting before TCT appears to improve patients' OS. KEY POINTS: • Regional TCT is a novel combination for palliative treatment of advanced HC • Our data showed significantly promising outcomes in the TCT group • HC patients with metal stenting appeared to derive greater benefit from TCT.

[Effect analysis of multi-electrode synchronous radiofrequency ablation and conventional single electrode overlapping ablation].

OBJECTIVE: To explore the different effects in ex vivo bovine liver between multiple cool-tip internally cooled electrodes synchronous radiofrequency ablation via switching controller and conventional single electrode overlapping radiofrequency ablation. METHOD: The above two methods were used to ablate in ex vivo bovine liver respectively. Electrode exposed end was 3 cm or 4 cm in length. The morphological characteristics of lesions created by two methods were observed, the sizes of the ablated lesions were measured and compared. RESULT: The formation of lesions ablated by both two methods was ellipsoidal. The longitudinal diameter, transverse diameter, front-end diameter and volume of the lesions ablated 16 mins by multi-electrode synchronous radiofrequency ablation via switching controller were (7.12 ± 0.52) cm, (5.71 ± 0.47) cm, (1.77 ± 0.29) cm, (102 ± 20) cm³, respectively. All of them are larger than the lesions ablated 36 mins by conventional single electrode overlapping radiofrequency ablation (P<0.01). At the same 16 mins, multi-electrode synchronous radiofrequency ablation via switching controller created longer longitudinal diameter and large volume (P<0.01) with longer exposed end electrodes (4 cm vs 3 cm). But the transverse diameter, the front-end diameter had no statistical difference (P>0.05). CONCLUSION: Compared with the conventional single electrode overlapping radiofrequency ablation, multi-electrode synchronous radiofrequency ablation via switching controller create larger lesion in the shorter time. It may provide a new attempt for the clinical treatment of large hepatocellular carcinoma.

[Analyze the factors influencing multi-electrode synchronous radiofrequency ablation via switching controller in ex vivo bovine liver].

OBJECTIVE: To investigate the effects of different electrode exposed end and different ablated time on lesion size of Cool-tip multi-electrode synchronous radiofrequency ablation via switching controller in ex vivo bovine liver. METHOD: Twelve combinations of different electrode exposed end (2 cm, 3 cm and 4 cm) were used, and different ablated time (12, 16, 20 and 24 mins) was as experimental parameter. Ablated lesions in longitudinal diameter, transverse diameter and volume were measured. Analyze the factors influencing the lesion size with ANOVA or t test. RESULTS: The ablated lesions with 3 cm exposed end electrodes were more stable and the spheroidal rate is more close to 1. When ablated 24 mins with 4 cm exposed end electrodes, the longitudinal diameter, transverse diameter and volume were (7.66±0.21), (6.50±0.34) cm and (172±12) cm3, respectively. When the ablated time was constant, the lesions increased with the exposed end length of the electrodes increased. All the data among groups was statistically significant (P<0.01) unless the transverse diameters between 3 and 4 cm exposed end electrode. When the exposed end length of electrodes was constant, the lesions increased with the ablated time increased as a whole. But there was no significant difference in most of the adjacent groups. Only the longitudinal diameters and volumes of 4 cm exposed end electrodes between 20 and 24 min were statistically significant (P<0.05). CONCLUSION: Within the experimental range, the lesion size ablated by Cool-tip multi-electrode synchronous radiofrequency ablation via switching controller increased with the electrode exposed end and ablated time increased. The spheroidal rate of the ablated lesions with 3 cm exposed end is more close to 1.

Efficacy and safety of HAIC combined with tyrosine kinase inhibitors versus HAIC monotherapy for advanced hepatocellular carcinoma: a multicenter propensity score matching analysis.

Purpose: This study aimed to assess the clinical efficacy and safety of the combined approach involving hepatic arterial infusion chemotherapy (HAIC) and tyrosine kinase inhibitors (TKIs) for the treatment of advanced hepatocellular carcinoma (HCC). Patients and methods: In this multicenter retrospective study conducted from January 2020 to December 2023, we reviewed advanced HCC patients who were treated either with HAIC alone or with a combination of HAIC and TKIs. To address initial disparities between the two groups, we employed propensity score matching (PSM). Tumor response evaluation was performed following RECIST 1.1 criteria. We compared survival outcomes, including overall survival (OS), progression-free survival (PFS), and objective response rate (ORR), between the two treatment groups. Safety assessments were conducted for all patients. Results: Following the eligibility review, 138 patients underwent combined treatment with HAIC and TKIs (HT group), while 198 patients received HAIC monotherapy (HA group) and met the inclusion criteria for enrollment in this study. After PSM, 107 patients were assigned to each group. The HT group exhibited a longer median OS (18.0 versus 8.8 months; hazard ratio [HR], 0.52, p < 0.001) compared to the HA group. Median PFS was also longer in the HT group, although without statistical significance (6.0 versus 4.7 months; HR, 0.85, p = 0.265). The HT group demonstrated a higher ORR (41.1% versus 25.2%; p = 0.020). No significant differences were observed between the two groups in the incidence of all adverse events (AEs) or grade 3/4 AEs (any grade: 81.2% for HT versus 78.8% for HA, p = 0.68; grade 3/4: 18.1% for HT versus 13.6% for HA, p = 0.29). Importantly, all AEs were manageable and acceptable. Notably, no grade 5 AEs occurred in either group. Conclusion: Combination therapy involving HAIC and TKIs effectively prolonged survival in advanced HCC patients. It represented a preferable alternative to HAIC monotherapy, with manageable safety.

Additional Hepatic Arterial Infusion Chemotherapy to Sorafenib Was Cost-Effective for Hepatocellular Carcinoma with Major Portal Vein Tumor Thrombosis.

Purpose: The combination of sorafenib and hepatic arterial infusion chemotherapy (SoHAIC) has shown to enhance overall survival rates in patients with advanced hepatocellular carcinoma and major portal vein tumor thrombosis (HCC-Vp3-4) compared to sorafenib alone. Our objective was to evaluate the cost-effectiveness of SoHAIC versus sorafenib for the treatment of HCC-Vp3-4, taking into account the viewpoint of Chinese healthcare payers. Methods: This pharmacoeconomic study employed a Markov model to assess the cost-effectiveness of treating HCC-Vp3-4 with SoHAIC in comparison to sorafenib. The patient characteristics were drawn from individuals from the trial conducted between June 2017 and November 2019, with cost and health value data sourced from published literature. The primary outcome measure in this research was the incremental cost-effectiveness ratio (ICER), which indicates the additional cost per quality-adjusted life year (QALY). The willingness-to-pay (WTP) threshold per QALY was set at $30,492.00. Furthermore, 1-way sensitivity and probabilistic sensitivity analyses were carried out to validate the consistency of the results. Results: In the baseline scenario, sorafenib resulted in 0.42 QALY at a cost of $10,507.89, while SoHAIC generated 1.66 QALY at a cost of $32,971.56. When comparing SoHAIC to sorafenib, the ICER was $18,237.20 per QALY, which was below the WTP threshold per QALY. Furthermore, the 1-way sensitivity analysis demonstrated that the ICER remained within the WTP threshold despite fluctuations in variables. In the probabilistic sensitivity analysis, SoHAIC had a 98.8% probability of being cost-effective at the WTP threshold, considering a wide range of parameters. Conclusion: In this cost-effectiveness evaluation, SoHAIC demonstrated cost-effectiveness over sorafenib for HCC with major portal vein tumor thrombosis, as observed from the perspective of a Chinese payer.

Serum amyloid A promotes glycolysis of neutrophils during PD-1 blockade resistance in hepatocellular carcinoma.

The response to programmed death-1 (PD-1) blockade varies in hepatocellular carcinoma (HCC). We utilize a panel of 16 serum factors to show that a circulating level of serum amyloid A (SAA) > 20.0 mg/L has the highest accuracy in predicting anti-PD-1 resistance in HCC. Further experiments show a correlation between peritumoral SAA expression and circulating SAA levels in patients with progressive disease after PD-1 inhibition. In vitro experiments demonstrate that SAA induces neutrophils to express PD-L1 through glycolytic activation via an LDHA/STAT3 pathway and to release oncostatin M, thereby attenuating cytotoxic T cell function. In vivo, genetic or pharmacological inhibition of STAT3 or SAA eliminates neutrophil-mediated immunosuppression and enhances antitumor efficacy of anti-PD-1 treatment. This study indicates that SAA may be a critical inflammatory cytokine implicated in anti-PD-1 resistance in HCC. Targeting SAA-induced PD-L1+ neutrophils through STAT3 or SAA inhibition may present a potential approach for overcoming anti-PD1 resistance.

[Effects of intra-arterial infusion of 3-bromopyruvate on metastases and survival benefit of hepatic VX2 tumor in rabbits].

OBJECTIVE: To evaluate the metastasis and survival of an intra-arterial infusion of 3-bromopyruvate (3-BrPA) on hepatic VX2 tumor in rabbits. METHODS: VX2 tumor was implanted in left lateral lobe of liver of 18 white New Zealand rabbits. The animals were randomized into 3 groups (n = 6 each) and underwent an intra-arterial infusion of phosphate-buffered saline or 3-BrPA via hepatic artery at 14 days post-implantation. At 28 days post-implantation, 3 rabbits in each group were sacrificed. The abdomen of these rabbits was opened and inspected for metastases. Then the survival of the remaining rabbits was observed. RESULTS: At 28 days post-implantation, in PBS group, there were intrahepatic metastasis and abdominal cavity dissemination (n = 3), renal metastases (n = 2) and lung metastases (n = 2); in early 3-BrPA infusion group, intrahepatic metastasis (n = 2), abdominal cavity dissemination (n = 1) and lung metastases (n = 1); in late 3-BrPA infusion group, intrahepatic metastasis (n = 1) and lung metastases (n = 1). The survival of the remaining animals was observed. Rabbits in early 3-BrPA infusion group survived significantly longer than those in PBS group [(27 ± 5) vs (17 ± 3) days, P = 0.041]; rabbits in late 3-BrPA infusion group [(42 ± 6) days] survived significantly longer than those in early 3-BrPA infusion group (P = 0.007). CONCLUSION: An intra-arterial infusion of 3-BrPA could reduce metastasis and prolong survival in rabbits with hepatic VX2 tumor. The earlier the infusion, the better the outcome.

The combined orthodontic and restorative treatment for patients with malocclusion and dentition defects: A randomized controlled trial.

BACKGROUND: To explore the effects of a combined orthodontic and restorative approach on chewing, swallowing, and language function in patients with malocclusion and dental defects. METHODS: A total of 112 patients with malocclusion and dentition defects admitted to the Lianyungang Hospital of Traditional Chinese Medicine from June 2019 to June 2022 were prospectively selected. The patients were divided into study and control groups using a simple random number table method, with 56 patients in each group. The control group received routine restoration, whereas the study group received a combination of orthodontic and restorative treatments. The chewing function, swallowing and language function, and gingival periodontal condition before and after treatment in both groups were compared using t-test or Wilcoxon test, while treatment satisfaction were compared using chi-square test or Fisher exact test. RESULTS: After treatment, maximum area frame bite force/max movie force in both groups increased compared to before treatment, while occlusion time, bite force distrbution balance, and standard deviation hue decreased compared to before treatment. Moreover, maximum area frame bite force/max movie force in the study group was higher than that in the control group, whereas occlusion time, bite force distrbution balance, and standard deviation hue were lower than those in the control group (P < .05). The swallowing and language function scores of the study group were higher than those of the control group (P < .05). After treatment, the bleeding index, plaque index, and probing depth of both groups decreased compared to before treatment, and the study group was lower than the control group (P < .05). The treatment satisfaction of the study group (94.64%) was higher than that of the control group (82.14%) (P < .05). CONCLUSION: Adopting a combined orthodontic and restorative approach to intervene in patients with malocclusion and dentition defects is beneficial for improving their periodontal condition, effectively restoring chewing, swallowing, and language functions, and achieving high patient satisfaction.

Cost-effectiveness and prognostic model of hepatic arterial infusion chemotherapy for hepatocellular carcinoma with high tumor burden and/or Vp4 tumor thrombus compared with sorafenib: a post-hoc analysis of the FOHAIC-1 trial.

OBJECTIVES: The phase III FOHAIC-1 trial revealed that hepatic arterial infusion of chemotherapy (HAIC) improved overall survival compared to sorafenib in the high-risk hepatocellular carcinoma (HCC). This study therefore set out to evaluate the cost-effectiveness and establish a prognostic clinico-radiological score of HAIC. MATERIALS AND METHODS: A total of 409 patients with high-risk HCC who received HAIC between 2014 and 2020 were included. A Markov model was applied in the cost-effectiveness analysis using data from the FOHAIC-1 trial. In prognosis analysis, a clinico-radiological score was developed using a Cox-regression model and subsequently confirmed in the internal validation and test cohorts. The area under the curve from receiver operator characteristic analysis was used to assess the performance of the clinico-radiological score. RESULTS: HAIC resulted in an incremental cost-effectiveness ratio of $10190.41/quality-adjusted life years compared to sorafenib, which was lower than the willingness-to-pay threshold. Probabilistic sensitivity analysis predicted a ≥99.9% probability that the incremental cost-effectiveness ratio was below the willingness-to-pay. The Cox analysis identified five factors, namely extrahepatic metastasis (m), arterial enhancing type (a), tumor number (nu), albumin-bilirubin index (a), and involved lobe (l), which together comprise the clinico-radiological score (HAIC-manual). Patients were classified into three groups based on the number of factors present, with cutoffs at 2 and 4 factors. The stratified median overall survival for these groups were 21.6, 10.0, and 5.9 months, respectively ( P <0.001). These findings were verified through internal validation and test cohorts with a significance level of P ≤0.01. The time-dependent area under the curve from receiver operator characteristic for the ability of the HAIC-manual to predict survival in 1, 2, and 3 years were 0.71, 0.76, and 0.78, which significantly outperformed existing staging systems. CONCLUSION: HAIC is a promising and cost-effective strategy for patients with high-risk HCC. The clinico-radiological score may be a simple prognostic tool for predicting HAIC treatment.

[Interstitial implantation of ¹²5I seed therapy for recurrent ovarian cancer].

OBJECTIVE: To explore the feasibility, short-term efficacies and complications of computed tomography (CT)-guided ¹²5I interstitial implant therapy for recurrent ovarian cancer. METHODS: From October 2009 to November 2010, a total of 25 lesions for 12 patients were diagnosed as recurrent ovarian cancer by positron emission tomography/computed tomography (PET/CT). Among 25 lesions, 21 underwent ¹²5I seed implantation. And 4 lesions of liver and spleen in one patient were treated with microwave ablation. Nine patients underwent 2 - 6 cycles of chemotherapy after seeding. There were 11 lesions with diameter > 2 cm and 10 ≤ 2 cm. According to the area of physiologic 18FDG uptake in lesions, the treatment plans were formulated by computerized treatment planning system (TPS) and Memorial Sloan-Ketterin nomograph. The matched peripheral dose (MPD) was 145 Gy in target mass. A median of 20.5 seeds per patient (range: 9 - 45) were implanted. The efficacies were evaluated by CT and 18F-FDG PET/CT findings. RESULTS: One patient died of renal failure while the other patients survived during a median follow-up of 15 mouths (range: 9 - 19). Ten lesions showed complete remission, 6 partial remission and 5 progressive disease. The effective rate was 76.2% (16/21). Compared with those > 2 cm, the lesions ≤ 2 cm in diameter had a better local control rate by Fisher's exact test (P = 0.035). The hepatic and renal lesions treated by microwave ablation showed inactivation on PET/CT. Only one patient suffered from sciatic nerve injury caused by punctuation and numbness and pain of right lower extremity were persistent. There was no onset of the complications of radiation injury, such as intestinal fistula and proctitis. CONCLUSION: The CT-guided ¹²5I interstitial implant therapy for recurrent ovarian cancer yields excellent short-term efficacies with fewer complications. The combined modality of ¹²5I interstitial implant and chemotherapy may further improve the patient outcomes.