• Humans
• Liver Neoplasms/therapy
• Liver Neoplasms/mortality
• Liver Neoplasms/secondary
• Liver Neoplasms/surgery
• Carcinoma, Hepatocellular/therapy
• Carcinoma, Hepatocellular/mortality
• Carcinoma, Hepatocellular/secondary
• Carcinoma, Hepatocellular/surgery
• Carcinoma, Hepatocellular/pathology
• Lung Neoplasms/therapy
• Lung Neoplasms/mortality
• Lung Neoplasms/pathology
• Prevalence
• Treatment Outcome
• Risk Factors
• Male
• Female

• hepatocellular carcinoma
• metastasectomy
• prognosis
• pulmonary metastasis
• survival

• NRF-2022R1F1A1071409 National Research Foundation of Korea

• lung cancer
• lung metastases
• metastasectomy
• pulmonary metastasectomy

• Humans
• Carcinoma, Hepatocellular/pathology
• Liver Neoplasms/pathology
• Lung Neoplasms/secondary
• Lung/pathology

• conversion therapy
• hepatocellular carcinoma
• review
• surgery

• Adult
• Aged
• Aged, 80 and over
• Cohort Studies
• Female
• Gastrointestinal Neoplasms/mortality
• Gastrointestinal Neoplasms/pathology
• Humans
• Kaplan-Meier Estimate
• Lung Neoplasms/mortality
• Lung Neoplasms/pathology
• Lung Neoplasms/secondary
• Lung Neoplasms/therapy
• Male
• Middle Aged
• Retrospective Studies

• Extrahepatic metastasis
• Hepatocellular carcinoma
• Immunotherapy
• Locoregional therapy
• Systemic therapy
• Targeted therapy

• Pulmonary metastases; hepatocellular carcinoma; solid tumor; ablation; survival analysis

Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) results in poor survival outcome. This study assessed the clinical outcomes of pulmonary metastasectomy in LT recipients with pulmonary metastasis of HCC in a high-volume transplant center and analyzed factors prognostic of survival following metastasectomy.

This study analyzed outcomes in 52 patients who underwent pulmonary resection due to pulmonary metastasis as the first recurrence of HCC after LT from January 2004 to December 2017 in a single center.

The 52 enrolled patients included 46 men and 6 women, aged 56.0±6.6 years. Their 1-, 3-, and 5-year survival rates after pulmonary resection were 75.0%, 43.5%, and 33.9%, respectively. The 1-, 3-, and 5-year survival rates were 85.3%, 47.1%, and 34.2%, respectively, in patients with further metastases and 55.6%, 38.1%, and 38.1%, respectively, in patients without further metastases (P=0.45). The size and number of pulmonary metastatic nodules were unrelated to survival rates (all P>0.10). A shorter recurrence-free period after LT (hazard ratio [HR]=0.553, P=0.006), elevated alpha-fetoprotein concentration at metastasectomy (HR=2.142, P=0.03), and adjuvant chemotherapy after metastasectomy (HR=3.79, P=0.003) were independent risk factors for survival after metastasectomy.

Pulmonary metastasectomy for HCC recurrence in LT recipients showed favorable survival outcomes. Independent risk factors for survival after metastasectomy included recurrence-free survival after LT, alpha-fetoprotein level at metastasectomy, and adjuvant chemotherapy after metastasectomy.

To investigate the prognostic factors and survival analysis of patients with hepatocellular carcinoma with distant metastasis.

The clinical data of 3,126 patients with distant metastasis of hepatocellular carcinoma from 2010 to 2015 were extracted from SEER database, and the correlation between the location of distant metastasis of hepatocellular carcinoma and prognosis was retrospectively analyzed. Patients were grouped according to different metastatic sites. The clinical characteristics of each group were compared by chi-square test, the survival curve was drawn by Kaplan-Meier method, Log-rank test was used for univariate analysis, and Cox regression for multivariate analysis. And use propensity score matching (PSM) to reduce differences in baseline characteristics.

Before PSM, the prognosis of patients with hepatocellular carcinoma with lung metastasis is worse than that of patients without lung metastasis. And there was no statistically significant difference with or without bone metastases.Patients with one type of organ metastasis had better prognosis than those with multiple organ metastasis. Among patients with organ metastasis, bone metastasis has a better prognosis than patients with lung metastasis. After PSM, patients with HCC with bone metastases had a worse prognosis than those without bone metastases (P<0.05). Univariate analysis showed that the degree of tumor differentiation, T stage, N stage, primary tumor and metastatic surgery, radiotherapy and chemotherapy, tumor size, single organ metastasis, the number of metastatic organs, and the combination of metastatic organs were related to the prognosis of patients with distant metastasis of hepatocellular carcinoma (P < 0.05). Multiariate analysis showed that age ≥52 years old, male, low degree of tumor differentiation, N1 stage, no primary surgery, no chemoradiotherapy, tumor size > 6cm, and multi-organ metastasis were independent influencing factors for poor prognosis in patients with metastatic hepatocellular carcinoma.

The lung is the most common site of distant metastasis of hepatocellular carcinoma. Single organ metastasis has better prognosis than multiple organ metastasis. Age ≥52 years old, male, low degree of tumor differentiation, N1 stage, no primary surgery, no chemoradiotherapy, tumor size > 6cm, and multi-organ metastasis were independent influencing factors for poor overall survival and cancer-specific survival prognosis in patients with metastatic hepatocellular carcinoma.

• SEER database
• distant metastasis
• hepatocellular carcinoma
• prognosis
• survival analysis

• Cancer
• Lung metastases
• Metastasectomy
• Pulmonary metastasectomy
• Survival

Repeat surgical resection (redo) for pulmonary metastases is a questionable, albeit intriguing topic. We performed an extensive review of the literature, to specifically analyze results of redo pulmonary metastasectomies. We reviewed a total of 3,523 papers. Among these, 2,019 were excluded for redundancy and 1,105 because they were not completely retrievable. Out of 399 eligible papers, 183 had missing information or missing abstract, while 96 lacked data on survival. A total of 120 papers dated from 1991 onwards were finally included. Data regarding mortality, major morbidity, prognostic factors and long-term survivals of the first redo pulmonary metastasectomies were retrieved and analyzed. Homogeneity of data was affected by the lack of guidelines for redo pulmonary metastasectomy and the risks of bias when comparing different studies has to be considered. According to the histology sub-types, redo metastasectomies papers were grouped as: colorectal (n=42), sarcomas (n=36), others (n=20) and all histologies (n=22); the total number of patients was 3,015. Data about chemotherapy were reported in half of the papers, whereas targeted or immunotherapy in 9. None of these associated therapies, except chemotherapy in two records, did significantly modify outcomes. Disease-free interval before the redo procedure was the prevailing prognostic factor and nearly all papers showed a significant correlation between patients’ comorbidities and prognosis. No perioperative mortality was reported, while perioperative major morbidity was overall quite low. Where available, overall survival after the first redo metastasectomy ranged from 10 to 72 months, with a 5-years survival of approximately 50%. The site of first recurrence after the redo procedure was mainly lung. Despite the data retrievable from literature are heterogeneous and confounding, we can state that redo lung metastasectomy is worthwhile when the lesions are resectable and the perioperative risk is low. At present, there are no “non-surgical” therapeutic options to replace redo pulmonary metastasectomies.

• Pulmonary metastasectomy
• immune therapy
• redo metastasectomy
• target therapy

Extrahepatic metastasis (EHM) of hepatocellular carcinoma (HCC) is associated with poor outcomes. However, the clinical features and risk factors of EHM of HCC after radiofrequency ablation (RFA) remain unclear.

To elucidate the characteristics and risk factors of EHM after RFA for HCC.

From January 2008 to December 2017, we retrospectively enrolled 661 patients who underwent RFA as first-line treatment for HCC at 2 tertiary hospitals. The inclusion criteria were age ≥ 18 years, a diagnosis of HCC, and treatment-naivety. Abdominal computed tomography (CT) or magnetic resonance imaging (MRI) and alpha-fetoprotein measurements were routinely performed at 1 mo after RFA and followed-up at intervals of 3-6 mo. Univariate analyses were performed using the chi-squared test or Student’s t-test, and univariate and multivariate analyses were performed via logistic regression, as appropriate.

EHM was diagnosed in 44 patients (6.7%) during a median follow-up period of 1204 days. The 10-year cumulative rate of HCC recurrence and EHM was 92.7% and 33.7%, respectively. Initial recurrence was most often intrahepatic, and the rate of extrahepatic recurrence at initial recurrence was only 1.2%. The median time to the diagnosis of EHM was 2.68 years, and 68.2% of patients developed EHM within 2 years of the first recurrence, regardless of recurrence-free survival and 75.0% of patients developed EHM within 5 years after first recurrence. EHM was mostly diagnosed via abdominal CT/MRI in 33 (75.0%) and 38 of 44 patients (86.4%) with EHM had either positive abdominal CT scan results or serum AFP level elevation. In multivariate analysis, recurrence-free survival < 2 years, ablation zone/tumor size < 2, and alpha-fetoprotein level > 400 IU/mL were associated with a high EHM risk.

EHM occurs following multiple intrahepatic recurrences after RFA and combined contrast-enhanced abdominal CT and serum AFP were useful for surveillance. Patients especially with high-risk factors require close follow-up for EHM.

• Hepatocellular carcinoma
• Metastasis
• Radiofrequency ablation
• Surveillance
• Risk factor

• Adolescent
• Carcinoma, Hepatocellular/diagnostic imaging
• Carcinoma, Hepatocellular/surgery
• Catheter Ablation/adverse effects
• Humans
• Liver Neoplasms/diagnostic imaging
• Liver Neoplasms/surgery
• Neoplasm Recurrence, Local/epidemiology
• Radiofrequency Ablation/adverse effects
• Retrospective Studies
• Treatment Outcome

• Bone and bones
• Brain
• Hepatocellular carcinoma
• Lung
• Neoplasm metastasis

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols/therapeutic use
• Carcinoma, Hepatocellular/pathology
• Carcinoma, Hepatocellular/secondary
• Carcinoma, Hepatocellular/therapy
• Chemoembolization, Therapeutic/methods
• Cisplatin/administration & dosage
• Feasibility Studies
• Female
• Fluorouracil/administration & dosage
• Humans
• Liver Neoplasms/pathology
• Lung Neoplasms/secondary
• Lung Neoplasms/therapy
• Male
• Mediastinal Neoplasms/secondary
• Mediastinal Neoplasms/therapy
• Middle Aged
• Mitomycin/administration & dosage
• Retreatment
• Tumor Burden
• Young Adult

• Hepatopancreatobiliary carcinomas
• Pulmonary metastasis
• Surgery

• Extrahepatic metastasis
• Hepatocellular carcinoma
• Outcome
• Prognosis prediction
• Surgery

Hepatocellular cancer (HCC) is increasing dramatically in incidence in Europe and the United States due mainly to the hepatitis C epidemic and, to a lesser extent, increased body mass index of the population. In the fairly recent past, HCC was largely considered as untreatable due to detection mainly at late stages and lack of effective drugs for treatment. Several advances have led to changes in the prognosis of HCC. Screening of high-risk populations has allowed for earlier detection in some studies. If found at an early stage, liver transplantation not only cures the usual underlying cirrhosis but has cure rates for HCC in the range of 60% in recent series. Larger lesions can sometimes be cured by partial hepatic resection assuming the remaining liver is not too damaged to sustain liver functions after surgery. Vaccination for hepatitis B has led to reduction in the incidence of HCC. Significant improvements in antiviral treatments for both hepatitis B and hepatitis C may be having an impact on the incidence of HCC as well. It is still generally held that a finding of metastases precludes cure of HCC. We here report the case of a patient who presented with a large HCC in the context of occult hepatitis C infection. The primary tumor was resected. Over a year later, he developed a lung metastasis that was resected as well. He has not shown recurrence for 6 years since the metastasectomy. We review the recent literature on resection of lung metastases from HCC.

• Hepatitis C
• Hepatocellular cancer
• Lung metastases
• Metastasectomy