Extrahepatic Progression Research Articles

Specific metabolic impairments indicate loss of sustained liver improvements in metabolic dysfunction-associated steatotic liver disease treatment.

High liver fat content (LFC) induces increased risks of both hepatic and extrahepatic progression in metabolic dysfunction-associated steatotic liver disease (MASLD), while maintaining a significant decline in magnetic resonance imaging-based proton density fat fraction (MRI-PDFF) (≥30% decline relative to baseline) without worsening fibrosis results in improved histological severity and prognosis. However, the factors associated with the loss of sustained responses to treatment remain unclear, and we aim to identify them. Consecutive treatment-naïve MASLD patients between January 2015 and February 2022, with follow-up until April 2023, were included in this prospective cohort study. LFC quantified by MRI-PDFF and liver stiffness measurements (LSM) determined by two-dimensional shear wave elastography (2D-SWE) were evaluated at weeks 0, 24 and 48. MRI-PDFF response was defined as a ≥30% relative decline in PDFF values, and LSM response was defined as a ≥1 stage decline from baseline. A total of 602 MASLD patients were enrolled. Of the 303 patients with a 24-week MRI-PDFF response and complete follow-up of 48 weeks, the rate of loss of MRI-PDFF response was 29.4%, and multivariable logistic regression analyses showed that 24-week insulin resistance (IR), still regular exercise and caloric restriction after 24 weeks, and the relative decline in LFC were risk factors for loss of MRI-PDFF response. Loss of LSM response at 48 weeks occurred in 15.9% of patients, and multivariable analysis confirmed 24-week serum total bile acid (TBA) levels and the relative decline in TBA from baseline as independent predictors. No significant association was found at 48 weeks between loss of MRI-PDFF response and loss of LSM response. MASLD patients with IR and high TBA levels are at higher risks of subsequent diminished sustained improvements of steatosis and fibrosis, respectively.

PD-1 inhibitor combined with ablation in liver metastasis: A retrospective, multicenter study.

e14644 Background: This study aimed to retrospectively evaluate the efficacy of ablation combined with programmed cell death protein 1 (PD-1) inhibitor versus PD-1 inhibitor monotherapy in patients with liver metastasis. Methods: We retrospectively enrolled patients with liver metastasis who received PD-1 inhibitor therapy with or without ablation at three medical institutions between January 2017 and September 2022. Progression-free survival (PFS) and 1-year survival rates were compared after propensity score matching. Additionally, intrahepatic and extrahepatic lesion progression and treatment-related adverse events were recorded during follow-up. Finally, prognostic factors for the combined therapy group were analyzed. Results: We included 172 patients and classified them into the combined therapy and PD-1 inhibitor monotherapy (n = 86 each) groups. Patients in the combined therapy group had better median PFS and 1-year survival rates than those in the PD-1 inhibitor monotherapy group. Combined therapy was an independent prognostic factor for PFS in the univariate and multivariate analyses. New lesions constituted the main pattern of progression, with combined therapy showing significantly lower intrahepatic progression, but similar extrahepatic progression rates. Adverse events associated with PD-1 inhibitors were comparable between the two groups. Additionally, 8 (9.3%) patients experienced ablation-related complications. However, neither univariate, nor multivariate analyses revealed the predictive factors for PFS in the combined therapy group. Conclusions: Ablation combined with a PD-1 inhibitor was superior to PD-1 inhibitor monotherapy in improving the survival of patients with liver metastasis.

Tumor burden affects the progression pattern on the prognosis in patients treated with sorafenib.

The study aims to analyze the impact of different progression patterns and tumor burden size on survival of HCC patients, as well as their interactions, through a retrospective cohort study. The study involved 538 patients who had undergone treatment with sorafenib and had shown radiographic progression. The progression pattern was analyzed using Cox regression by including an interaction term between progression pattern and tumor burden, which was then visualized through a graphical analysis. Tumor burden was categorized into low, medium, and high subgroups based on the six-and-twelve criteria, allowing for an exploration of the effect of progression pattern on survival in different tumor burden situations. Compared to patients with only intrahepatic progression (NIH/IHG) with an overall survival (OS) of 14.1/19.9 months and post-progression survival (PPS) of 8.1/13.1 months respectively, patients with extrahepatic lesions (NEH/EHG) had worse overall and postprogressive survival (OS: 9.3/9.2 months, PPS: 4.9/5.1 months). The hazard ratio for extrahepatic progression (NEH/EHG) compared to intrahepatic progression (NIH/IHG) at low, medium, and high tumor burden were [HR 2.729, 95%CI 1.189-6.263], [HR 1.755, 95%CI 1.269-2.427], and [HR 1.117, 95%CI 0.832-1.499], respectively. The study concluded that the interaction between the tumor progression patterns and tumor burden significantly affects the prognosis of HCC patients. As the tumor burden increases, the sensitivity of the patient's risk of death to the progression pattern decreases. These findings are valuable in personalized treatment and trial design.

Transarterial chemoembolization combined with radiofrequency ablation for medium and large hepatocellular carcinoma: insufficient ablation is associated with intrahepatic distant metastasis and extrahepatic metastasis.

To compare the prognosis of complete and insufficient ablation of transarterial chemoembolization (TACE) combined with radiofrequency ablation (RFA) in treating medium and large hepatocellular carcinoma (HCC) and to explore the differences in recurrence patterns between the two groups. Patients´ medical records and imaging data of patients with confirmed HCC from January 2014 to January 2022 were collected. These patients were divided into 2 groups: complete ablation (n=172) and insufficient ablation (n=171). Overall survival (OS) and progression-free survival (PFS) were estimated by the Kaplan-Meier curve and the log-rank test was used to compared. Fisher's exact test was used to compare recurrence patterns between the two groups. The median OS time was 72.8 months (95%CI:69.5-76.1) and 62.0 months (95%CI: 55.3-68.7) in the complete and insufficient ablation groups, respectively. The median PFS time in the complete ablation group was 67.8 months (95% CI: 65.2-70.4) and 38.6 months (95%CI: 29.8-47.4) in the insufficient ablation group. The OS and PFS rates of the complete ablation group were significantly better than those of the insufficient ablation group (P<0.001). In the complete ablation group, 25(41%) patients experienced local tumor progression(LTP), 36(59%) experienced intrahepatic distant progression(IDP), and 0(0%) experienced extrahepatic progression (EP). In the insufficient ablation group, 51 (32.1%) patients experienced LTP, 96 (60.4%) experienced IDP, and 12 (7.5%) experienced EP. The progression patterns of the two groups were statistically significant (P=0.039). Insufficient ablation indicates a poor survival outcome of TACE combined with RFA for medium and large HCC and can promote intrahepatic distant and extrahepatic metastasis.

Image-guided percutaneous ablation of hepatic epithelioid hemangioendothelioma.

Disease control and survival following percutaneous ablation of hepatic epithelioid hemangioendothelioma (EHE) was studied retrospectively. Six patients underwent 16 image-guided ablation procedures to treat 35 liver tumors from 2015 to 2022 (17 microwave ablation, 9 irreversible electroporation, 8 cryoablation, and 1 radiofrequency ablation). Technical success, local progression, intrahepatic progression, distant progression, overall survival, and adverse events were assessed. Four of six (67%) patients were treatment naïve prior to ablation. The mean length of imaging follow-up from first ablation procedure was 43.0 ± 31.2months. Thirty-three of 35 (94.3%) ablated tumors did not progress locally. Three of 6 patients (50%) had new intrahepatic progression and underwent repeat ablation or systemic treatment. No extrahepatic progression was observed. One patient died from EHE 2.7years after initial diagnosis. No severe adverse events occurred. Percutaneous ablation is feasible, often in a staged fashion, and may provide favorable intermediate to long-term disease control for patients with hepatic EHE.

Progression patterns in patients with advanced hepatocellular carcinoma treated with local therapy, targeted drugs, and PD-1/PD-L1 inhibitors.

To explore the progression patterns of advanced hepatocellular carcinoma (HCC) in patients treated with a combination of local therapies, targeted drugs, and PD-1/PD-L1 inhibitors. A retrospective study involving 86 patients with Barcelona Clinic Liver Cancer stage C HCC was conducted between August 2018 and April 2022. All patients received local therapy, targeted drugs, and PD-1/PD-L1 inhibitors. Disease progression was evaluated using computed tomography or magnetic resonance imaging after combination therapy. Peripheral blood immune cells were analyzed using flow cytometry. For intrahepatic progression, the median time to first progression was 5.3 months in 60 patients (95% confidence interval (CI): 2.3-7.1 months), and the median time to second progression was 9.3 months in 40 patients (95% CI: 4.8-11.8 months, p < 0.0001). For extrahepatic progression, the median time to first progression was 5.8 months in 61 patients (95% CI: 1.6-8.4 months), and the median time to second progression was 8.7 months in 39 patients (95% CI: 4.5-10.9 months, p < 0.0001). The common sites of extrahepatic progression are the lymph nodes and lungs. The percentages of PD-1+ cells gradually decreased after combination treatment but then gradually increased at follow-up in extrahepatic progression. The percentages of CD3+ T cells, CD3+CD4+ T cells, CD3+CD8+ T cells and CD16+CD56+ cells exhibited different trends in intrahepatic and extrahepatic progression. After combination treatment, patients with advanced HCC exhibit different characteristics of disease progression and composition of peripheral blood immune cells. Lymph nodes and lungs were the most susceptible sites for disease progression.

Efficacy of additional locoregional therapy based on systemic therapy after intrahepatic progression for BCLC stage B/C hepatocellular carcinoma: A real-world study

BackgroundThe leading course of death in patients with advanced hepatocellular carcinoma (HCC) is intrahepatic progression and associated hepatic failure. The study aimed to evaluate the efficacy of locoregional therapy targeting intrahepatic lesions after intrahepatic progression for advanced HCC. MethodsConsecutive 263 HCC patients who received lenvatinib combined with immunotherapy were reviewed. Until to last follow-up, 178 patients had disease progression:107 patients had intrahepatic progression (IP group) with or without extrahepatic progression, and 71 patients only had extrahepatic progression (EP group). After intrahepatic progression, 47 patients received systemic therapy (Systemic group), 23 patients received locoregional-systemic therapy (Loco-systemic group), and 37 patients received best supportive therapy (Supportive group). ResultsThe EP group showed significantly longer OS (overall survival) than the IP group (not reached vs 16.2 months, P = 0.009). Median OS was significantly longer in the Loco-systemic group (20.3 v 8.8 months; P = 0.03) than in the Systemic group. The median PFS (progression-free survival) was 11.7 months in the Loco-systemic group and 5.3 months in the Systemic group (P = 0.046). In patients who progressed fast in first-line treatment, there was no significant difference in OS and PFS between the two groups. ConclusionIntrahepatic progression was associated with a poorer survival outcome compared with extrahepatic progression in advanced HCC. After intrahepatic progression, additional locoregional therapy based on systemic therapy may offer clinical benefits on OS and PFS in second-line treatment, the benefits were limited to patients who had once achieved tumor control during their first-line treatments.

Predictors of extrahepatic progression in patients with hepatocellular carcinoma receiving transarterial chemoembolization

Predictors of extrahepatic progression in patients with hepatocellular carcinoma receiving transarterial chemoembolization

External validation of subclassification system and progression pattern analysis in hepatocelluar carcinoma with macroscopic vascular invasion

Background and purposeThe present study aimed to validate the performance of a previously proposed subclassification model to predict prognosis after combined transarterial chemoembolization (TACE) and external beam radiotherapy (RT) for hepatocellular carcinoma (HCC) with macrovascular invasion (MVI) in an independent cohort that received the same first-line treatment for the patients with the similar disease extent characteristics, and analyzed the progression patterns as well as progression-free survival (PFS). Materials and methodsThis study was conducted using prospectively collected data from the XXXXX HCC registry for newly diagnosed, previously untreated HCC between 2005 and 2018. Finally, 417 patients who satisfied the eligibility criteria were included and analyzed. ResultsThe median PFS and overall survival (OS) were 5.2 and 13.9 months, respectively. Similar to a previous study, subclassification of patients into very low-, low-, intermediate-, and high-risk groups showed a median OS of 98.4, 18.3, 9.7, and 5.8 months, respectively (P < 0.001). Additionally, subclassification of patients into the very low-, low-, intermediate-, and high-risk groups showed median PFS of 18.7, 6.7, 3.3, and 2.3 months, respectively (p < 0.001). Overall, intrahepatic progression was the most common pattern of progression; however, extrahepatic progression was more common in the intermediate- and high-risk groups. ConclusionThe previously proposed subclassification model was successfully validated in an independent cohort. Treatment modification should be considered in the intermediate- and high-risk patient groups because of their frequent extrahepatic as well as intrahepatic progressions after combined TACE and RT.

Clinical Efficacy of Hypofractionated Proton Beam Therapy for Intrahepatic Cholangiocarcinoma.

Forty-seven patients with intrahepatic cholangiocarcinoma (IHCC) who received proton beam therapy (PBT) were analyzed to evaluate the clinical efficacy and safety of hypofractionated PBT in patients with inoperable or recurrent IHCC. The median prescribed dose of PBT was 63.3 GyE (range: 45-80 GyE) in 10 fractions, and the median duration of follow-up in all the patients was 18.3 months (range: 2.4-89.9 months). Disease progression occurred in 35 of the 47 (74.5%) patients; local, intrahepatic, and extrahepatic progression occurred in 5 (10.6%), 20 (42.6%), and 29 (61.7%) patients, respectively. The 2-year freedom from local progression (FFLP), progression-free survival (PFS), overall survival (OS) rates, and median time of OS were 86.9% (95% confidence interval [CI], 74.4-99.4%), 16.8% (95% CI, 4.3-29.3%), 42.7% (95% CI, 28.0-57.4%), and 21.9 months (95% CI, 16.2-28.3 months), respectively; grade ≥ 3 adverse events were observed in four (8.5%) patients. In selected patients with localized disease (no viable tumors outside of the PBT sites), the median time of OS was 33.8 months (95% CI, 5.4-62.3). These findings suggest that hypofractionated PBT is safe and could offer a high rate of FFLP and promising OS in patients with inoperable or recurrent IHCC.

Proton Beam Therapy for Treatment-Naïve Hepatocellular Carcinoma and Prognostic Significance of Albumin-Bilirubin (ALBI) Grade.

Simple SummaryProton beam therapy (PBT) has not been generally recommended as an initial treatment for hepatocellular carcinoma (HCC) due to the insufficiency of data on PBT for treatment-naïve HCC until now, and albumin-bilirubin (ALBI) grade has been shown to be an effective assessment of liver dysfunction and more discriminatory for survival than the Child–Pugh classification. This study evaluated the efficacy of PBT as first-line treatment in treatment-naïve HCC and assessed the prognostic significance of ALBI grade in these patients. Our findings showed that PBT could result in comparable local tumor control and survival outcomes in treatment-naïve HCC patients to those of other recommended first-line treatments, with a safe toxicity profile compared to our institutional cohort data and previous other studies, and ALBI grade and tumor stage were independent predicting factors for overall survival.To evaluate the efficacy of proton beam therapy (PBT) as an initial treatment in treatment-naïve hepatocellular carcinoma (HCC) patients and to assess the prognostic significance of albumin-bilirubin (ALBI) grade, 46 treatment-naïve HCC patients treated with PBT were analyzed. The ALBI grade distribution was grade 1 in 11 (23.9%) patients, grade 2 in 34 (73.9%) patients, and grade 3 in 1 (2.2%) patient. The median duration of follow-up was 56.5 months (95% confidence interval [CI], 48.2–64.7). Among the 46 patients, disease progression was observed in 23 (50%) patients: local progression in 3 (6.5%) patients; intrahepatic progression in 22 (47.8%); and extrahepatic progression in 5 (10.9%). The 5-year freedom from local progression (FFLP), progression-free survival (PFS), and overall survival (OS) rates were 92.7% (95% CI, 84.7–100.7), 43.3% (95% CI, 28.2–58.4), and 69.2% (95% CI, 54.9–83.5), respectively. In multivariate analysis, there were no independent factors for FFLP (p > 0.05 each), but tumor stage and ALBI grade were independent factors for PFS and OS (p < 0.05 each). PBT could result in comparable OS in treatment-naïve HCC patients to other recommended first-line treatments, and ALBI grade, in addition to tumor stage, could be useful for predicting OS.

Artisan trial protocol: A single center, open-label, phase II trial of the safety and efficacy of TheraSphere selective internal radiation therapy (SIRT) in the treatment of inoperable metastatic (liver) neuroendocrine neoplasia (NENs).

e16208 Background: Patients(pts) with NENs present with advanced, unresectable disease, with liver metastases. Liver metastases dictates prognosis. SIRT allows targeted high dose radiation directly to tumours, with relative sparing of the surrounding liver tissue. ArTisaN is a phase II study assessing efficacy and tolerability of SIRT using TheraSpheres for management of liver metastases secondary to NENs. Methods: Pts with liver dominant NENs will receive up to 2 TheraSphere treatments. Pts will be followed until disease progression for up to 2-years. Primary endpoints: objective response rate (ORR) within the treated liver volume, incidence of adverse events. Secondary endpoints: progression-free survival (PFS), overall (OS) and quality of life (EORTC QLQ-C30 and QLQ-GI.NET21). Assuming ORR 40%, sample size 24 patients-95% confidence interval will extend 20% in either direction. Results: 13 pts completed therapy: 69% female, primary site: 23% pancreatic, 31% small bowel. Grade: 54%-1, 46% - 2. 69% had previously received more than one line of systemic therapy including 7 who had previously received peptide receptor radiotherapy. 92% received bilobar treatment-average dose 2.49GBq administered. Hepatic ORR-69%. Grade 3 treatment related events occurred in 2 patients–1 ischaemic limb and 1 radiation induced hepatitis. Quality of life-maintained across all parameters. At the time of analysis, 5 pts had progressed, 3 had extrahepatic progression. Median PFS was 15.4 months (95%CI 11.5-19.4) and median OS was 18.5months (95%CI 7.4-29.6). Conclusions: Theraspheres is a safe and effective therapy for the management of patients with liver dominant disease from NENs. Clinical trial information: NCT04362436.

Percutaneous Thermal Segmentectomy: Proof of Concept.

To report the multicenter retrospective experience on combination of balloon-occluded MWA(b-MWA) followed by balloon-occluded TACE(b-TACE) in patients with liver malignancies > 3cm, focusing on appearance and volume of necrotic area, safety profile and oncological results. Twenty-three patients with liver primary malignancies (hepatocellular carcinoma,HCC = 18; intrahepatic cholangiocarcinoma,iCC = 2) and metastasis (colorectal cancer metastasis = 1;sarcoma metastasis = 1;breast metastasis = 1) were treated. Maximum mean diameter of lesions was 4.4cm (± 1cm). Treatments were performed using a single-step approach:b-MWA was performed after balloon-microcatheter inflation, followed by b-TACE (with epirubicin or irinotecan). Necrotic area shape and discrepancy with the expected volume of necrosis suggested by vendor's ablation chart were assessed at post-procedural CT. Complications were categorized according to CIRSE classification. Oncological results at 1 and 3-6months were evaluated using m-RECIST(HCC) and RECISTv1.1(metastasis/iCC). Mean volume of necrotic area was 75cm3 (± 36). Discrepancy with vendor chart consisted in a medium percentage of volumetric incrementation of necrotic area of 103.2% (± 99.8). Non-spherical shape was observed in 22/23 patients (95.7%). No complications occurred; Post-embolization syndrome occurred in 12/23patients. Complete response and partial response were, respectively, 91, 3% (21/23) and 8.7% (2/23) at 1month, 85.7% (18/21) and 9.5% (2/21) at 3-6months. Progression of disease was 4.7% (1/21) at 3-6months for extra-hepatic progression. Among partial responders, average percentage of tumor volume debulking was 78.8% (± 9.8%). b-MWA followed by b-TACE in a single-step procedure led to larger necrotic areas than the proposed by vendors ablation chart, non-spherical in shape and corresponded to the vascular segment occluded during ablation. This permitted to safely achieve promising oncological results in patients with > 3cm tumors.

Successful Combined S Systemic-Regional Chemotherapy for Advanced Intrahepatic Cholangiocarcinoma: Report of Two Cases

We present two patients with advanced unresectable intrahepatic cholangiocarcinoma successfully treated with combined systemic-regional chemotherapy. Intra-arterial treatment included oily chemoembolization and chemoinfusion (GEMOX) with additional systemic chemotherapy (GEMCIS). Chemotherapy did not stop after extrahepatic progression: metastases to the lungs and bones. Continuous symptomatic nutritional support allowed to minimize chemotherapeutic toxicity and to maintain good quality of life. One patient is still alive for more than 4 years, the other died of tumor progression in three years ten months. The importance of factors contributing to the long-term survival of patients with advanced intrahepatic cholangiocarcinoma is considered.

Disease control and failure patterns of unresectable hepatocellular carcinoma following transarterial radioembolization with yttrium-90 microspheres and with/without sorafenib.

BACKGROUNDImpressive survival outcome of our previous study in unresectable hepatocellular carcinoma (HCC) patients undergoing yttrium-90 glass microspheres transarterial radioembolization (TARE) with/without sorafenib according to individuals’ disease burden, i.e., intrahepatic tumor load (IHT) and adverse disease features (ADFs) might partly be confounded by other treatments and underlying hepatic function. Therefore, a dedicated study focusing on treatment response and assessment of failure patterns might be a way to improve treatment outcome in addition to patient selection based on the disease burden.AIMTo assess the tumor response, disease control and patterns of disease progression following TARE with/without sorafenib in unresectable HCC patients.METHODSThis retrospective study was conducted in successful TARE procedures with available pre- and post-treatment imaging studies (n = 169). Three treatment subgroups were (1) TARE only (TARE_alone) for IHT ≤ 50% without ADFs, i.e., macrovascular invasion, extrahepatic disease (EHD) and infiltrative/ill-defined HCC (n = 63); (2) TARE with sorafenib (TARE_sorafenib) for IHT > 50% and/or presence of ADFs (n = 81); and (3) TARE only for patients who could not receive sorafenib due to contraindication or intolerance (TARE_no_sorafenib) (n = 25). Objective response rate (ORR; consisted of complete response (CR) and partial response (PR)), disease control rate (DCR; consisted of CR, PR and stable disease) and failure patterns of treated, intrahepatic and extrahepatic sites were assessed using the modified response evaluation criteria in solid tumors. Time to progression (TTP) was calculated from TARE to the first radiologic progression at any site using Kaplan-Meier method. Identification of prognostic factors for TTP using the univariate Kaplan-Meier method and multivariate Cox proportional hazard model were performed in major population subgroups, TARE_alone and TARE_sorafenib.RESULTSThe median radiologic follow-up time was 4.4 mo (range 0.5-48.8). In treated area, ORR was highest in TARE_sorafenib (53.1%), followed by TARE_alone (41.3%) and TARE_no_sorafenib (16%). In intrahepatic area, DCR remained highest in TARE_sorafenib (84%), followed by TARE_alone (79.4%) and TARE_no_sorafenib (44%). The overall DCR was highest in TARE_alone (79.4%), followed by TARE_sorafenib (71.6%) and TARE_no_sorafenib (40%). Dominant failure patterns were intrahepatic for both TARE_alone (44.5%) and TARE_sorafenib (38.4%). Extrahepatic progression was more common in TARE_sorafenib (32%) and TARE_no_sorafenib (40%) than in TARE_alone (12.7%). TTP was longest in TARE_alone (8.6 mo; 95%CI: 3.4-13.8), followed by TARE_sorafenib (5.1 mo; 95%CI: 4.0-6.2) and TARE_no_sorafenib (2.7 mo; 95%CI: 2.2-3.1). Pre-existing EHD (HR: 0.37, 95%CI: 0.24-0.56, P < 0.001) was a sole prognostic factor for TTP in TARE_sorafenib with no prognostic factor for TTP in TARE_alone.CONCLUSIONTARE with/without sorafenib according to individuals’ disease burden provided DCR approximately 70% with intrahepatic progression as dominant failure pattern. Extrahepatic progression was more common in procedures with initially high disease burden.

Effect of partial splenic embolization on transarterial chemoembolization for hepatocellular carcinoma with hypersplenism

This study retrospectively studied transarterial chemoembolization (TACE) combined with partial splenic embolization (PSE) in the treatment of hepatocellular carcinoma (HCC) with severe hypersplenism.Seventy patients with HCC in Barcelona Clinic Liver Cancer (BCLC) stage B or C with hypersplenism were divided into non-partial splenic embolization group (N-PSE, n = 51) and partial splenic embolization group (PSE, n = 19). The N-PSE group was further divided into N-PSE with mild to moderate hypersplenism (N-PSE-M, 47 cases) and N-PSE with severe hypersplenism (N-PSE-S, 4 cases).In the PSE group, leukocytes, neutrophils, lymphocytes, and platelets were significantly increased (P < .05) and were significantly different from that in the N-PSE group (P < .05). In the N-PSE group, except for a slight increase in neutrophils, other blood cells were decreased, including lymphocytes that were significantly decreased (P < .05). There was no significant difference in the changes of liver function between the 2 groups before and after surgery (P > .05). The analysis showed a significant increase in ascites after 6 months of TACE in the N-PSE group (P < .05). According to the follow-up results, the median overall survival (OS) in the PSE group was 24.47 ± 3.68 (months) and progression-free survival (PFS) was 12.63 ± 4.98 (months). Regardless of OS or PFS, the PSE group was superior to the N-PSE group and its subgroups, with a statistically significant difference in PFS between the N-PSE group and PSE group (P < .05). Moreover, the time of extrahepatic progression was significantly earlier in the N-PSE group than in the PSE group (P < .05). N-PSE-S group had the worst prognosis, and PFS and OS were worse than the other 2 groups, suggesting that PSE in severe hypersplenism may improve PFS and OS.In patients with HCC and severe hypersplenism, TACE should be actively combined with PSE treatment.

Does significantly elevated lung shunt fraction (LSF >20%) promote extrahepatic progression in patients with hepatocellular carcinoma treated with radioembolization?

Radioembolization with yttrium-90 (Y-90) is an effective locoregional therapy for primary and metastatic liver tumors, but its use is restricted or contraindicated for patients with elevated lung shunt fraction (LSF) because of an increased risk of developing pulmonary adverse events, including but not limited to radiation pneumonitis. Elevated LSF is also thought to be correlated with liver tumor progression and metastases. In this retrospective cohort study, we examine rates of metastasis development, rates of adverse events and overall survival (OS) in 23 patients with hepatocellular carcinoma (HCC) and elevated LSF >20% on Tc-99 m macroaggregated albumin scan treated with Y-90 radioembolization at our institution from 2005 to 2016. To minimize confounding variables, patients with baseline extrahepatic metastases or portal vein tumor thrombosis were excluded. Kaplan-Meier estimates were performed for OS and time to development of metastases. No patient developed clinical and imaging signs of radiation pneumonitis. Median intention to treat OS from day of radioembolization was 21.3 months; median censored OS was 14.7 months. Five out of 23 patients (22%) developed at least one metastasis during follow-up, for an incidence of 20 per 1000 patient-years (compared to the historical rate of 6 per 1000 patient-years for HCC patients in general). HCC patients with LSF >20% treated with Y-90 radioembolization have acceptable toxicities and appear to have a rate of extrahepatic tumor development (22%) higher than expected for patients with HCC.

Type of Necrosis Influences Prognosis in Hepatocellular Carcinoma After the First Transarterial Chemoembolization.

BackgroundHepatocellular carcinoma (HCC) is one of the most common tumors. Transarterial chemoembolization (TACE) is the first choice of treatment for intermediate HCC and an important treatment option for advanced HCC. This retrospective study compared the prognosis between patients showing coagulative necrosis and patients showing liquefactive necrosis after the first TACE procedure.Material/MethodsWe divided 171 patients with Barcelona Clinic Liver Cancer (BCLC) Stage B or C HCC into 2 groups; a coagulative necrosis group (79 patients) and a liquefactive necrosis group (92 patients). The coagulative and liquefactive necroses were identified by computed tomography after the first TACE procedure. Kaplan-Meier analysis was used to identify the differences in the overall survival (OS) and progression-free survival (PFS) between the 2 groups, and the associated risk factors and safety of TACE were analyzed.ResultsThe median OS durations were 23.27±1.40 months and 8.83±2.15 months (P=0.004) and the median PFS durations were 9.33±0.96 months and 3.70±0.44 months (P=0.002) in the coagulative necrosis and liquefactive necrosis groups, respectively. Intrahepatic in situ progression, new intrahepatic metastasis, and extrahepatic progression occurred significantly earlier in the liquefactive necrosis group (P<0.05). Univariate analysis and multivariate analyses showed liquefactive necrosis was the main risk factor for OS. There was no significant difference in the hepatic function impairment or post-embolism syndrome after TACE.ConclusionsAfter the first TACE procedure, the patients with liquefactive necrosis experienced recurrence and metastasis earlier and had a worse prognosis. Therefore, these patients should be considered for earlier administration of targeted therapies or immunotherapies after TACE.

Liver Transplantation for Glycogen Storage Disease Type IV.

Glycogen storage disease type IV (GSD IV) is a rare autosomal recessive disorder caused by glycogen–branching enzyme (GBE) deficiency, leading to accumulation of amylopectin–like glycogen that may damage affected tissues. The clinical manifestations of GSD IV are heterogeneous; one of which is the classic manifestation of progressive hepatic fibrosis. There is no specific treatment available for GSD IV. Currently, liver transplantation is an option. It is crucial to evaluate long–term outcomes of liver transplantation. We reviewed the published literature for GSD IV patients undergoing liver transplantation. To date, some successful liver transplantations have increased the quantity and quality of life in patients. Although the extrahepatic manifestations of GSD IV may still progress after transplantation, especially cardiomyopathy. Patients with cardiac involvement are candidates for cardiac transplantation. Liver transplantation remains the only effective therapeutic option for treatment of GSD IV. However, liver transplantation may not alter the extrahepatic progression of GSD IV. Patients should be carefully assessed before liver transplantation.

Mode of progression after radioembolization in patients with colorectal cancer liver metastases

BackgroundRadioembolization is an established treatment modality in colorectal cancer patients with liver-dominant disease in a salvage setting. Selection of patients who will benefit most is of vital importance. The aim of this study was to assess response (and mode of progression) at 3 months after radioembolization and the impact of baseline characteristics.MethodsThree months after radioembolization with either yttrium-90 resin/glass or holmium-166, anatomic response, according to RECIST 1.1, was evaluated in 90 patients. Correlations between baseline characteristics and efficacy were evaluated. For more detailed analysis of progressive disease as a dismal clinical entity, distinction was made between intra- and extrahepatic progression, and between progression of existing metastases and new metastases.ResultsForty-two patients (47%) had extrahepatic disease (up to five ≥ 1 cm lung nodules, and ≤ 2 cm lymph nodes) at baseline. No patients showed complete response, 5 (5.5%) patients had partial response, 16 (17.8%) had stable disease, and 69 (76.7%) had progressive disease. Most progressive patients (67/69; 97%) had new metastases (intra-hepatic N = 11, extrahepatic N = 32; or both N = 24). Significantly fewer patients had progressive disease in the group of patients presenting without extrahepatic metastases at baseline (63% versus 93%; p = 0.0016). Median overall survival in patients with extrahepatic disease was 6.5 months, versus 10 months in patients without extrahepatic disease at baseline (hazard ratio 1.79, 95%CI 1.24–2.57).ConclusionsResponse at 3-month follow-up and survival were heavily influenced by new metastases. Patients with extrahepatic disease at baseline had a worse outcome compared to patients without.