Hepatic "pregnancy": hepatocellular carcinoma with extensive extrahepatic growth.
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ABSTRACT:
SUBMITTER: Ferreira AR
PROVIDER: S-EPMC10432283 | biostudies-literature | 2023 Aug
REPOSITORIES: biostudies-literature
Publications
Hepatic "pregnancy": hepatocellular carcinoma with extensive extrahepatic growth.
Ferreira Ana Rita AR Castro Bárbara B Martins José Daniel JD Varanda João J Costa Alexandre A Pereira Bela B Oliveira Manuel M
Hepatobiliary surgery and nutrition 20230709 4
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Project description:Extrahepatic metastasis (EHM) of hepatocellular carcinoma (HCC) has increasingly been seen due to improved survival with effective management of intrahepatic lesions. The presence of EHM indicates an advanced stage of HCC, for which systemic therapy serves as the standard treatment modality. Since the approval of Sorafenib as the first systemic agent in 2007, it took almost a decade to show its efficacy in both first and further lines of setting until the landscape of systemic drugs was finally expanded. Moreover, with inspiring results from immunotherapy trials in HCC, it appears that the introduction of immunotherapy may lead to an evolution in the portfolio of HCC treatment. Although the locoregional approach in the management of EHM is not recommended for advanced-stage HCC, efforts have been made to demonstrate its efficacy in symptom relief and potential benefit for overall survival. This review provides a summary of recent updates of the systemic agents in the treatment of advanced HCC, with an emphasis on aggressive locoregional management of EHM by various treatment modalities.
| S-EPMC8316954 | biostudies-literature
Project description:Most patients with advanced hepatocellular carcinoma (HCC) ultimately experience tumor progression after first-line systemic therapies. Systemic therapy is generally recommended as second-line treatment for advanced HCC in the major guidelines. Combining apatinib with hepatic arterial infusion chemotherapy (HAIC) likely drives synergistic activity on advanced HCC with extrahepatic metastasis. This phase II trial (ChiCTR2000029082) aimed to assess efficacy and safety of this combination in patients with HCC with extrahepatic metastasis who have progressed after first-line systemic therapies. The primary end point was the objective response rate (ORR). The secondary endpoints were progress-free survival (PFS), disease control rate (DCR), 6- and 12-month survival rates, overall survival (OS), and adverse events (AEs). Thirty-nine patients received oral treatment with apatinib, and hepatic artery infusion oxaliplatinplus raltitrexed. Per RECIST v1.1, the ORR and DCR was 53.8% and 89.7% in the patients population, respectively. The median PFS and OS was 6.2 months and 11.3 months, respectively. The 6- and 12-month survival rates were 81.7% and 44.1%, respectively. All AEs were manageable by medication or dose modifications. Apatinib plus HAIC for second-line therapy in advanced HCC with extrahepatic metastasis shows promising efficacy and manageable toxicities.
| S-EPMC11473759 | biostudies-literature
Project description:BackgroundLenvatinib plus Programmed Death-1 (PD-1) inhibitors (LEN-P) have been recommended in China for patients with advanced hepatocellular carcinoma (HCC). However, they provide limited survival benefits to patients with extrahepatic metastases. We aimed to investigate whether combining hepatic arterial infusion chemotherapy (HAIC) with LEN-P could improve its efficacy.Materials and methodsThis multi-center cohort study included patients with HCC extrahepatic metastases who received HAIC combined with LEN-P (HAIC-LEN-P group, n=127) or LEN-P alone (n=103) as the primary systemic treatment between January 2019 and December 2022. Baseline data were balanced using a one-to-one propensity score matching (PSM) and inverse probability of treatment weighting (IPTW).ResultsAfter PSM, the HAIC-LEN-P group significantly extended the median overall survival (mOS) and median progression-free survival (mPFS), compared with the LEN-P group (mOS: 27.0 months vs. 9.0 months, P<0.001; mPFS: 8.0 months vs. 3.0 months, P=0.001). After IPTW, the mOS (hazard ratio (HR)=0.384, P<0.001) and mPFS (HR=0.507, P<0.001) were significantly higher in the HAIC-LEN-P group than in the LEN-P group. The HAIC-LEN-P group's objective response rate was twice as high as that of the LEN-P group (PSM cohort: 67.3% vs. 29.1%, P<0.001; IPTW cohort: 66.1% vs. 27.8%, P<0.001). Moreover, the HAIC-LEN-P group exhibited no noticeable increase in the percentages of grade 3 and 4 adverse events compared with the LEN-P group (P>0.05).ConclusionHAIC can improve the efficacy of LEN-P in patients with HCC extrahepatic metastases and may be an alternative treatment for advanced HCC management.
| S-EPMC11254277 | biostudies-literature
Project description:Extrahepatic recurrence (EHR) after curative hepatectomy for hepatocellular carcinoma (HCC) is associated with a poor prognosis. We investigated the features of EHR and identified its predictive factors. This retrospective study included 398 treatment-naive patients who underwent curative hepatectomy for HCC at two tertiary hospitals. Multivariate Cox-regression analysis was performed to identify the variables associated with EHR. EHR was diagnosed in 94 patients (23.6%) over a median follow-up period of 5.92 years, most commonly in the lungs (42.6%). The 5-/10-year cumulative rates of HCC recurrence and EHR were 63.0%/75.6% and 18.1%/35.0%, respectively. The median time to EHR was 2.06 years. Intrahepatic HCC recurrence was not observed in 38.3% of patients on EHR diagnosis. On multivariate analysis, pathologic modified Union for International Cancer Control stage (III, IVa), surgical margin involvement, tumor necrosis, sum of tumor size > 7 cm, and macrovascular invasion were predictive factors of EHR. Four risk levels and their respective EHR rates were defined as follows: very low risk, 1-/5-year, 3.1%/11.6%; low risk, 1-/5-year, 12.0%/27.7%; intermediate risk, 1-/5-year, 36.3%/60.9%; and high risk, 1-year, 100.0%. Our predictive model clarifies the clinical course of EHR and could improve the follow-up strategy to improve outcomes.
| S-EPMC8217564 | biostudies-literature
Project description:Fibrolamellar hepatocellular carcinoma (FL-HCC) is a rare primary liver tumor that typically presents at an advanced stage in early adolescents and adults with no underlying liver disease. Surgical resection is the first-line treatment, and patients who are not surgical candidates face limited treatment options with poor long-term outcomes. Herein we report the first documented, technically successful treatment of FL-HCC with extrahepatic spread using transarterial radioembolization (TARE) in a 16-year-old male patient with surgically unresectable disease. Subsequent imaging revealed tumor necrosis and a 20% reduction in size, and the patient survived 20 months post-treatment, a marked improvement relative to historical data in the literature. Further research should examine the potential role of yttrium-90 TARE in the treatment of FL-HCC patients with metastatic disease.
| S-EPMC7566208 | biostudies-literature
Project description:BackgroundSorafenib is the recommended treatment for advanced hepatocellular carcinoma (HCC), but transarterial chemoembolization (TACE) is performed in individual cases with limited extrahepatic spread. The aim of this study was to compare the outcome of patients with HCC and extrahepatic disease (EHD) treated with sorafenib and TACE.MethodsA total of 172 patients with HCC and EHD treated with sorafenib (n = 98) or TACE (n = 74) at three German referral centers (Hannover, Mainz and Hamburg) were included in this study. In order to reduce selection bias, patients were matched for significant demographic differences using a propensity score analysis.ResultsPatients with liver cirrhosis, higher extrahepatic tumor burden and/or infiltration of adjacent organs/structures were significantly more often treated with sorafenib. Median overall survival (OS) was similar for sorafenib- and TACE-treated patients (7 versus 8 months, p = 0.312). In a propensity score analysis matched for demographic differences, median OS remained similar with 4 versus 8 months for sorafenib versus TACE (p = 0.613).ConclusionTreatment with TACE is not inferior to treatment with sorafenib in patients with limited EHD of HCC. TACE represents an effective therapeutic option in selected patients with EHD.
| S-EPMC5833223 | biostudies-literature
Project description:Identification of extrahepatic metastases (EHM) of hepatocellular carcinoma (HCC) has been paradoxically increasing due to an increase in the survival of HCC patients. However, metastasis of HCC to the skeletal muscle tissue is extremely rare. We describe a unique case of HCC metastasizing to the paravertebral muscle. A 55-year-old man with a history of hepatitis B cirrhosis underwent partial liver resection with complete removal of HCC. Three months later, a computed tomography (CT) scan showed intrahepatic recurrence. The tumors were treated with yttrium-90 microspheres, trans-catheter arterial chemoembolization, and sorafenib. Six months later, a CT scan showed an enhancing lesion of the left paravertebral muscle that on biopsy were consistent with metastatic HCC. The tumor was treated with stereotactic hypo-fractionated image-guided radiation therapy (SHFRT). A follow-up scan 3 mo post-radiotherapy revealed a stable appearance of the paravertebral muscle metastasis. Because of the progression in the intrahepatic tumors, the patient was treated with capecitabine, which was changed to dasatinib 6 mo later. The patient passed away three years after the primary surgical resection. Management of EHM poses an extreme challenge. This is the first case of HCC with EHM to the paravertebral muscle in which stability of disease was achieved using SHFRT. This case highlights the importance of early detection of hepatitis B viral infection and initiation of anti-viral therapy to decrease recurrence of HCC and prevent EHM.
| S-EPMC5550763 | biostudies-other
Project description:Background and aimExtrahepatic metastasis (EHM) of hepatocellular carcinoma (HCC) leads to a worse prognosis. We aimed to develop a nomogram based on noninvasive pretreatment clinical data to predict EHM of HCC sooner.MethodsThree cohorts containing 1820, 479, and 988 HCC patients were enrolled from three hospitals in different regions in Taiwan and served as the training and validation cohorts. Pretreatment clinical data were analyzed by Cox regression modeling for independent risk factors of EHM.ResultsPlatelet count ≥ 200 × 103/μL, serum alfa-fetoprotein ≥ 100 ng/dL, tumor size ≥ 3 cm, tumor number > 1, and macrovascular invasion were independent risk factors for EHM and were used to develop a nomogram. This nomogram had concordance indices of 0.733 (95% confidence interval [CI]: 0.688-0.778) and 0.739 (95% CI: 0.692-0.787) for the prediction of EHM during a 5-year follow-up duration in the training and validation cohorts, respectively. A nomogram score > 61 implied a high risk of EHM (hazard ratio [HR] = 3.83; 95% CI: 2.77-5.31, P < 0.001).ConclusionWe have developed a nomogram that could accurately predict EHM of HCC and be readily available for formulating individualized treatment for all individual HCC patients to improve therapeutic efficacy.
| S-EPMC6386739 | biostudies-literature
Project description:BackgroundThe long-term prognosis after surgery of patients with hepatocellular carcinoma (HCC) and extrahepatic bile duct tumor thrombus (Ex-BDTT) remains unknown. We aimed to identify the surgical outcomes of patients with HCC and Ex-BDTT.MethodsA total of 138 patients with Ex-BDTT who underwent hepatectomy with preservation of the extrahepatic bile duct from five large hospitals in China between January 2009 and December 2017 were included. The Cox proportional hazards model was used to analyze overall survival (OS) and recurrence-free survival (RFS).ResultsWith a median follow-up of 60 months (range, 1-127.8 months), the median OS and RFS of the patients were 28.6 and 8.9 months, respectively. The 1-, 3-, and 5-year OS rates of HCC patients with Ex-BDTT were 71.7%, 41.2%, and 33.5%, respectively, and the corresponding RFS rates were 43.5%, 21.7%, and 20.0%, respectively. Multivariate analysis identified that major hepatectomy, R0 resection, and major vascular invasion were independent prognostic factors for OS and RFS. In addition, preoperative serum total bilirubin ≥ 4.2 mg/dL was an independent prognostic factor for RFS.ConclusionMajor hepatectomy with preservation of the extrahepatic bile duct can provide favorable long-term survival for HCC patients with Ex-BDTT.
| S-EPMC10726108 | biostudies-literature
Project description:BackgroundA combination of tyrosine kinase inhibitors (TKIs) and anti-PD-1 antibodies with local regional therapy has elicited yield substantial clinical benefits in patients who have hepatocellular carcinoma (HCC) with extrahepatic metastases. Using this treatment strategy to convert HCC patients with extrahepatic metastases from unresectable to resectable has not yet been reported.MethodsConsecutive hepatocellular carcinoma patients with extrahepatic metastases who received first-line therapy with a combination of TKIs and anti-PD-1 antibodies and at least one local regional therapy were analysed.ResultsNine patients with localized disease who received first-line systemic therapy were enrolled. At baseline, all of them had oligometastatic disease, namely, Barcelona Clinic Liver Cancer stage C (or Chinese Liver Cancer stage IIIB). The most common treatment administered was lenvatinib plus anti-PD-1 antibody and transarterial chemoembolization, and the median time span from systemic therapy to surgery was 3.2 (IQR, 2.8-6.2) months. Three patients achieved a pathological complete response. Six patients underwent laparoscopic surgery, and the other 3 patients underwent open surgery. After a median follow-up of 10.2 (IQR, 8.6-20.0) months, 7 patients survived without disease recurrence, and 2 experienced tumour recurrence. All patients had any-grade AEs, and 55.6% of the patients experienced grade 3 AEs. Fatigue was the most common AE, followed by elevated aminotransferase levels and hypertension.ConclusionsStereotactic therapy is a feasible conversion therapy for HCC patients with extrahepatic metastases to become resectable. This is the first study to analyse therapeutic outcomes of patients receiving these therapies for HCC with extrahepatic metastases.
| S-EPMC8350994 | biostudies-literature