Extrahepatic Metastasis Of Hepatocellular Carcinoma Research Articles

Exploring extrahepatic metastasis of hepatocellular carcinoma based on methylation driver genes and establishing a prognostic model for hepatocellular carcinoma

BackgroundHepatocellular carcinoma (HCC), theseventh most common cancer worldwide, is characterized by a high mortality rate, advanced diagnosis, and susceptibility to extrahepatic metastasis. Numerous studies have shown that DNA methylation is a crucial factor in epigenetic modifications and regulation of carcinogenesis. MethodsHCC patient data were sourced from the TCGA dataset as a training set, while GSE116174 was used as an external validation set for verification. Differential methylation and expression analyses were performed on HCC samples with and without extrahepatic metastasis. In the intersecting genes, the relationship between methylation and expression levels of the intersecting genes was analyzed. Genes with a correlation coefficient≥|0.30| and P<0.05 were identified as methylation driver genes. Cox regression analysis was conducted to identify genes associated with HCC prognosis and establish a risk score. Subsequently, a prognostic model was established and validated using Cox regression analysis incorporating the risk score and other clinical factors. Using immunohistochemistry to evaluate the expression of DHX58 and EIF5A2 in HCC tissues with and without extrahepatic metastasis. Immunoinfiltration analysis was performed on the HCC samples using CIBERSORT. ResultsOur research identified eight methylation driver genes for HCC extrahepatic metastasis, of which two genes (DHX58 and EIF5A2) were associated with HCC patient prognosis. And the study further constructed and validated the risk score and prognostic model. Immunoinfiltration analysis showed that M0 macrophage abundance was correlated with the prognosis of HCC patients. Immunohistochemistry revealed differences in DHX58 and EIF5A2 expression between HCC tissues with and without extrahepatic metastasis, consistent with our bioinformatics findings.

Incidentally found parotid gland lesion in 18F-FDG PET/CT for staging evaluation of patients with hepatocellular carcinoma: remote possibility of metastatic tumor or second primary salivary gland malignancy

ObjectivesWe primarily aimed to evaluate whether parotid incidental lesion (PIL) in 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) for staging evaluation of patients with hepatocellular carcinoma (HCC) would represent a possibility of extrahepatic metastasis or second primary malignancy (SPM). Additionally, we explored the incidence of PIL in HCC patients and examined any associated risk factors.MethodsWe retrospectively analyzed patients with HCC who underwent 18F-FDG PET/CT at our institution from 2010 to 2022. The pathological findings of PILs in HCC patients were investigated for confirmatory identification of the risk of HCC metastasis or SPM in parotid gland. Healthy controls received 18F-FDG PET/CT for health screening were also enrolled to compare the incidence of PILs with HCC patients. Various parameters associated with patient demographics and characteristics of HCC were analyzed to find the related factors of PILs.ResultsA total of 17,674 patients with HCC and 2,090 healthy individuals who had undergone 18F-FDG PET/CT scans were enrolled in the analyses. Among the 54 HCC patients who underwent pathological confirmation for PILs, benign primary parotid tumor was most commonly observed (n = 43 [79.6%]); however, no malignant lesions were detected, including HCC metastasis. The incidence of PILs was higher in patients diagnosed with HCC compared with the control group (485 [2.7%] vs. 23 [1.1%], p = 0.002). Analysis for the risk factors for PILs revealed that patient age, sex, and positive viral markers were significantly associated with the incidence of PILs in patients with HCC (all p < 0.001).ConclusionsOur study demonstrates that PILs are more frequently identified in patients with HCC on 18F-FDG PET/CT. However, no malignant PIL, including extrahepatic metastasis of HCC, was identified. Therefore, the presence of PIL should not impede or delay the treatment process for patients with HCC. Additionally, we suggested that for future swift and straightforward differential diagnoses of PIL, the development of additional protocols within the PET/CT imaging could be beneficial.

Treatment strategy for lymph node metastasis of hepatocellular carcinoma using an ICG navigation system: a case report

BackgroundSince indocyanine green (ICG) accumulates selectively in hepatocellular carcinoma (HCC) cells, it can be used to detect metastatic lesions. Lymph node metastasis of HCC is rarely observed, both simultaneously and metachronously. Therefore, it is sometimes difficult to identify metachronous lymph nodes during salvage surgery because of prior surgery. Herein, we report a case in which lymph node metastasis of HCC was successfully resected using an ICG navigation system.Case presentationThe patient was a 62-year-old man who had undergone radical liver resection for HCC 8 years ago. During surveillance, contrast-enhanced computed tomography (CT) revealed a mass in the hepatic hilum. Various diagnostic modalities suggested that the patient had a solitary metastatic lymph node of HCC, and extirpation of the tumor was planned. Intraoperative ICG fluorescence imaging allowed surgeons to clearly identify the target lesion. Histopathologically, the tumor was confirmed to be a lymph node metastasis of HCC. The patient’s postoperative course was uneventful, and he remains alive without recurrence 2 years after the second surgery.ConclusionIntraoperative navigation surgery by ICG fluorescence imaging was useful for the safe resection of extrahepatic metastasis of HCC in a complicated situation.

Primary Tumor Radiomic Model for Identifying Extrahepatic Metastasis of Hepatocellular Carcinoma Based on Contrast Enhanced Computed Tomography.

This study aimed to identify radiomic features of primary tumor and develop a model for indicating extrahepatic metastasis of hepatocellular carcinoma (HCC). Contrast-enhanced computed tomographic (CT) images of 177 HCC cases, including 26 metastatic (MET) and 151 non-metastatic (non-MET), were retrospectively collected and analyzed. For each case, 851 radiomic features, which quantify shape, intensity, texture, and heterogeneity within the segmented volume of the largest HCC tumor in arterial phase, were extracted using Pyradiomics. The dataset was randomly split into training and test sets. Synthetic Minority Oversampling Technique (SMOTE) was performed to augment the training set to 145 MET and 145 non-MET cases. The test set consists of six MET and six non-MET cases. The external validation set is comprised of 20 MET and 25 non-MET cases collected from an independent clinical unit. Logistic regression and support vector machine (SVM) models were identified based on the features selected using the stepwise forward method while the deep convolution neural network, visual geometry group 16 (VGG16), was trained using CT images directly. Grey-level size zone matrix (GLSZM) features constitute four of eight selected predictors of metastasis due to their perceptiveness to the tumor heterogeneity. The radiomic logistic regression model yielded an area under receiver operating characteristic curve (AUROC) of 0.944 on the test set and an AUROC of 0.744 on the external validation set. Logistic regression revealed no significant difference with SVM in the performance and outperformed VGG16 significantly. As extrahepatic metastasis workups, such as chest CT and bone scintigraphy, are standard but exhaustive, radiomic model facilitates a cost-effective method for stratifying HCC patients into eligibility groups of these workups.

Extrahepatic metastasis of hepatocellular carcinoma: A Malaysian case series

Introduction: Hepatocellular carcinoma (HCC) is a primary malignancy which arises from hepatocytes. It is the sixth most commonly diagnosed cancer and the third leading cause of cancer death worldwide in 2020. It predominantly metastasizes via the hematogenous route. However, there are possibility of distant metastasis via the lymphatic and bone dissemination in a few of HCC cases. Case Series: We report two atypical cases of HCC with distant metastasis to cervical lymph node and bone in Malaysia. The first case reported is a HCC case of extrahepatic metastasis to cervical lymph node and the second case is a HCC case of extrahepatic metastasis to right femur. Conclusion: The patients with atypical site of distant metastasis from HCC have poor prognosis. Overall physical examination should be done to prevent overlook for all the patients with HCC.

Soleus Muscle Single Metastasis from Hepatocellular Carcinoma.

Extrahepatic metastases of hepatocellular carcinoma (HCC) are associated with poor prognosis, while such lesions in skeletal muscles are extremely rare. A unique case of skeletal metastasis in the soleus muscle in a 76-year-old male patient with HCC is reported. The patient presented with a painful palpable mass in his left calf. Magnetic resonance imaging (MRI) revealed a contrast-enhancing lesion in the soleus muscle, while core needle biopsy showed metastatic lesion from the HCC. Due to the poor overall condition of the patient, no further treatment was performed, while he passed away three months later. Hepatocellular carcinoma represents an aggressive tumor, with poor prognosis, especially in cases of extra-hepatic metastases. Such lesions have a reported incidence of about 15%. Extra-hepatic metastasis to the skeletal muscles is extremely rare, with only 21 more such cases reported in the literature so far. No clear therapeutic strategies exist for such cases. Thus, it is of utmost importance to detect similar cases in early stages for a possible better prognosis and clearer understanding of the therapeutic options, including surgical and loco-regional treatments.

Rare case of hepatocellular carcinoma metastasis to urinary bladder: A case report

BACKGROUNDHepatocellular carcinoma (HCC) is a primary liver cancer with high prevalence and mortality. There are many cases of advanced HCC at the time of diagnosis. Treatment methods and prognosis are different depends on whether metastasis is present. Thus, it is necessary to make an accurate evaluation at the time of diagnosis. Extrahepatic metastases of HCC usually occur through hematogenous spread or through adjacent organs such as the peritoneum. Metastasis to the urinary bladder alone is rare. Here, we report a rare case of biopsy-proven solitary metastasis of HCC to the bladder in a 60-year-old woman. CASE SUMMARYA 60-year-old female patient was found to be positive for hepatitis B surface antigen by chance after abdominal ultrasonography showed abnormal findings. Thus, liver dynamic computed tomography (CT) was performed. The patient visited the hospital for further examination. Ultrasound and CT showed 3.6 cm sized arterial enhancing mass in segment 5 and an infiltrative mass in segment 8. The patient was diagnosed with HCC through liver dynamic magnetic resonance imaging and liver biopsy. Afterwards, she underwent two transcatheter arterial chemoembolizations within five months for HCC. During follow-up, a newly appeared bladder tumor was found on liver dynamic CT. She underwent transurethral resection of the bladder tumor for diagnosis and treatment. The tissue was confirmed as metastatic HCC. CONCLUSIONAlthough rare, metastasis to urinary bladder from HCC can occur without evidence of other distant metastases. Thus, regular follow-up imaging examination and clinical attention are required.

Metastatic hepatocellular carcinoma to the bone diagnosed by fine needle aspiration in a veteran population.

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and it may present initially with extrahepatic spread in 5%-15% cases. It most commonly metastasizes to lungs, lymph nodes and adrenal glands. Skeletal metastases from HCC are uncommon and carry a very poor prognosis. We retrospectively reviewed all fine needle aspiration (FNA) specimens of metastatic HCC at our institution from January 1994 to March 2021 using the SNOMED search computer option. Relevant clinical information was obtained from the review of patient's electronic medical records. There were 36 FNAs of metastatic HCC over a period of 27 years. Six patients (16.7%) were found to have skeletal metastases. All six patients were males with a median age of 59 years (54-71 years) and their lesions were osteolytic. The most common site of metastases was vertebra (3/50%). Most patients (67%) had bone metastases as an initial presentation, without prior history of HCC. The mean survival after the diagnosis of skeletal metastases was only 8 months. Detection of extrahepatic HCC to bone is important to avoid any unwanted surgical intervention. In our patient population, the most common site of skeletal metastases from HCC was vertebra, therefore in FNAs of vertebral lytic masses, metastatic HCC should be considered. On FNA, extrahepatic metastases of HCC can mimic other poorly differentiated tumors. They behave in an aggressive fashion, resulting in a grim prognosis. Cytological substrates can be used for future molecular testing, if needed.

Intraoperative indocyanine green fluorescence navigation facilitated complete removal of lymph node metastases from hepatocellular carcinoma

Indocyanine green (ICG) is a fluorescent dye that selectively accumulates in primary hepatocellular carcinoma (HCC) as well as in extrahepatic metastases of HCC. Reported here is a case of metachronous lymph node (LN) metastases from HCC that were resected using ICG fluorescence navigation. A man in his 70s was referred to this department for suspected LN metastasis from HCC. Computed tomography revealed an enlarged suprapancreatic LN. After a laparotomy, an ICG fluorescence imaging system intraoperatively revealed strong fluorescence of this LN, which was then easily resected. An examination after the removal of the LN revealed fluorescence from the adjacent lymphatic tissue as well, so an additional resection was performed. Pathologically, both LNs were confirmed to be metastases from HCC. In this case, some lymphatic tissue metastases from HCC could not be identified prior to surgery, but intraoperative use of ICG fluorescence navigation facilitated their complete removal.

Colonic metastasis of hepatocellular carcinoma with repeated retroperitoneal bleeding: a case report

BackgroundColonic metastasis is uncommon in patients with hepatocellular carcinoma (HCC). In the past, extrahepatic metastasis of HCC was not treated aggressively because of its poor prognosis. Herein, we describe the case of a patient with HCC who survived for 30 months following resection of a metastatic tumor in the ascending colon.Case presentationAn 80-year-old man presented at our hospital with symptoms of abdominal pain on the right side and fever. He had undergone transcatheter arterial chemoembolization and posterior segment resection of the liver because of HCC, followed by radiofrequency ablation for a recurrent intrahepatic lesion 5 and 3 years, respectively, prior to the visit. He was diagnosed with retroperitoneal hematoma, which was thought to be associated with diverticulitis and an extramural tumor in the ascending colon. A definitive diagnosis could not be reached; however, a right hemicolectomy of the colon was performed because of progression to anemia. A pathological examination revealed a metastatic tumor in the ascending colon extending from the subserosal layer to the muscularis propria layer. The patient was treated with lenvatinib after surgery, but presented with intrahepatic recurrence, lymph node metastasis, and peritoneal dissemination metastasis 15 months later. The progression of the disease could not be controlled and his postoperative survival time was 30 months.ConclusionResection of metastasis of HCC might contribute to prolonged survival in cases, where radical resection is possible.

A case of simultaneous abdominal wall metastasis of hepatocellular carcinoma with long-term relapse-free survival after laparoscopic resection

We report our experience of an extremely rare case of a simultaneous extrahepatic metastasis of hepatocellular carcinoma (HCC) with long-term relapse-free survival, treated by laparoscopic resection of an abdominal wall tumor and subsequent radiofrequency ablation (RFA) of an intrahepatic lesion. A 76-year-old man visited a local clinic for right lower abdominal pain. He was treated with antibiotics and the symptom resolved. However, a mass was detected in the same region and he was referred to our hospital for further evaluation. Computed tomography (CT) of the abdomen showed a mass 5 cm in diameter, raising suspicions of an intra-abdominal tumor. Laparoscopic surgery was performed, and the tumor was found in the abdominal wall and completely resected. Histopathological examination yielded a diagnosis of extrahepatic HCC. Post-operative positron emission tomography (PET)-CT showed increased uptake of fluorodeoxyglucose in segment 3 (S3) of the liver. On performing a liver biopsy, HCC was diagnosed. Subsequently, the S3 lesion was treated with radiofrequency ablation. The patient has remained relapse-free for 6 years without further treatments.

Prognostic Significance of Platelet-to-Lymphocyte Ratio (PLR) in Extrahepatic Metastasis of Hepatocellular Carcinoma After Curative Resection.

BackgroundThe prognosis for patients diagnosed of hepatocellular carcinoma (HCC) who have extrahepatic metastasis after liver resection is unsatisfactory. This study aimed to find out the relationship between the inflammation-related indexes and metastasis.MethodsOne thousand three hundred and sixty-six patients diagnosed of HCC who underwent curative resection were included in this study and divided into metastasis group (n=180) and non-metastasis group (n=1186). A receiver operating characteristic (ROC) curve was constructed to estimate the optimal cut-off value for inflammation-related indexes. Independent risk factors were identified by Cox regression analysis. The metastasis rate was analyzed by the Kaplan-Meier method, then the subgroup analyses were taken.ResultsThe cut-off values of NLR, PLR, LMR, NγLR, PNLR, and PNI were 2.65, 107.67, 5.47, 134.52, 335.03, and 51.23, respectively. Multivariate Cox analysis revealed that elevated serum AFP level (P=0.004), tumor size more than 5cm (P<0.001), multiple tumors (P=0.040), and higher PLR (P=0.042) were independent risk factors associated with extrahepatic metastasis. The Kaplan-Meier method showed that the high PLR group has a higher extrahepatic metastasis rate than the low PLR group. Meanwhile, the results of subgroup analyses were consistent with the conclusion.ConclusionThe PLR is an independent risk factor of extrahepatic metastasis after radical hepatectomy for HCC patients. The high PLR indicates a higher rate of extrahepatic metastasis.

Safety and Local Efficacy of Laser Ablation for the Extrahepatic Metastasis of Hepatocellular Carcinoma: An Available Treatment Strategy

Thermal ablation plays an important role in the treatment of extrahepatic metastasis of hepatocellular carcinoma (HCC). Yet laser ablation (LA), as a safe thermal ablative modality, is less investigated in this field. In this study, the safety and local effectiveness of LA in the treatment for the extrahepatic metastasis of HCC were evaluated. From May 2012 to May 2019, 17 patients (13 males and 4 females; mean age, 54.1 ± 14.6 years; age range, 34–80 years), who underwent LA for treatment of extrahepatic metastasis of HCC at the First Affiliated Hospital of Sun Yat-sen University, were retrospectively enrolled in this study. Local effectiveness, complications, local tumor progression (LTP), and overall survival (OS) were evaluated. Finally, a total of 28 LA treated extrahepatic metastatic lesions of HCC were reviewed. Neither LA-related mortality nor major complication occurred. Complete ablation (CA) was achieved in 20 out of 28 lesions (71.4%). During the follow-up (mean, 19.5 ± 12.8 months; range, 5–42.7 months), LTP developed in 4 out of 20 lesions with CA (20%). Four patients died of tumor progression or multiple organ dysfunction syndrome. The accumulative one- and three-year OS rates were 79.0% and 65.8%, respectively. In conclusion, LA is a safe and effective therapeutic option in the treatment of extrahepatic metastasis of HCC. Further studies are necessary to evaluate the benefit of LA.

Preoperative PET-CT is useful for predicting recurrent extrahepatic metastasis of hepatocellular carcinoma after resection

PurposeIn recent years, it has been reported that use of 18F-FDG PET-CT can reveal the degree of hepatocellular carcinoma malignancy. We evaluate the ability of a preoperative 18F-FDG PET-CT to predict the recurrence of extrahepatic metastasis of HCC after surgery. MethodsWe retrospectively examined 67 patients who received 18F-FDG PET-CT prior to curative hepatic resection for HCC between April 2010 and March 2016. Multivariate Cox regression analysis was performed to identify the factors associated with recurrence of extrahepatic metastasis of HCC after surgery. We also evaluated the sensitivity, specifity, positive predictive value, negative predictive value and accuracy of diagnosis of 18F-FDG PET-CT for recurrent extrahepatic metastasis of HCC after surgery. ResultsThe multivariate analysis identified a tumor-to-normal liver standardized uptake value ratio (TNR) ≥ 1.53 (hazard ratio [HR], 0.037; P = 0.003), multiple tumor nodules (HR, 0.121; P = 0.007), and presence of microvascular invasion (HR, 0.094; P = 0.003) as independent predictors of distant metastasis recurrence. A TNR ≥ 1.53 showed a sensitivity of 91.7 %, specificity of 76.4 %, positive predictive value of 45.8 %, negative predictive value of 97.7 %, and accuracy of 79.1 % for diagnosing distant metastasis recurrence of HCC. In a binomial logistic regression analysis of tumor factors associated with a TNR ≥ 1.53, poor tumor differentiation and large tumor size were significant factors. Conclusion18F-FDG PET-CT and microvascular invasion may be useful for predicting the recurrence of extrahepatic metastasis of HCC after surgery.

Role of multidetector computed tomography in detection of extrahepatic metastases of hepatocellular carcinoma

Role of multidetector computed tomography in detection of extrahepatic metastases of hepatocellular carcinoma

2323 Bone Metastasis as Index Presentation of Hepatocellular Carcinoma

INTRODUCTION: Hepatocellular carcinoma (HCC) is the most common primary tumor of the liver, and the fifth most common cancer worldwide Extrahepatic mestastasis rarely occurs in patients with early course HCC. Bone metastasis as the initial presentation of HCC is even more rare. Here we present an unusual case of Bone metastasis to the ninth rib as the index presentation of HCC. CASE DESCRIPTION/METHODS: The patient is a 60 year old male with a medical history of hypertension, hepatitis C virus, hyperlipidemia, rheumatoid arthritis and chronic obstructive pulmonary disease who presented to the emergency department complaining of right upper quadrant pain for one week. Physical exam was notable for tenderness over the patients right ninth rib. The rest of the physical exam was unremarkable. Notable laboratory workup included a complete blood count and comprehensive metabolic panel within normal limits. Notable imaging included a computed tomography of the abdomen showing a mass over the ninth rib with multiple foci in liver. The next day an alpha fetoprotein (AFP) level was ordered and returned elevated at 1139.0 ng/ml. Other tumor markers including carcinoembryonic antigen (CEA), carbohydrate antigen 19 9 (CA 19 9) and prostate specific antigen (PSA) were within normal limits. Interventional radiology was then consulted and performed a biopsy of the ninth rib mass which showed metastatic carcinoma with a primary of hepatocellular malignancy. This diagnosis was supported by positive staining with Hep-Par 1. Following this diagnosis the oncology service was consulted and recommended palliative radiotherapy to the ninth rib and starting treatment with Sorafenib. The patient was then discharged with pain medications and follow up appointments. DISCUSSION: Common risk factors for the development of HCC include Hepatitis B, Hepatitis C, Aflatoxin exposure, and cirrhosis of any cause (including alcohol). The most common sites of extra-hepatic metastasis of HCC are lung, lymph node, musculoskeletal, and adrenal gland. Isolated bone metastasis of HCC is rare occurring in only 9.5% of patients. Symptoms associated with HCC include right upper quadrant pain, jaundice and ascites in more advanced cases. Treatment of metastatic HCC to bone includes chemotherapy and targeted radiotherapy. More recently Bisphosphonates have also been shown to have success.

Clinical Factors Predictive of a Better Prognosis of Pulmonary Metastasectomy for Hepatocellular Carcinoma

The lung is the most common site of extrahepatic metastasis of hepatocellular carcinoma (HCC). The aim of this study was to identify prognostic factors for pulmonary metastasectomy of HCC. One hundred three patients who underwent pulmonary metastasectomy for HCC between January 2005 and December 2016 were retrospectively evaluated. Patient demographic data and characteristics of the primary tumors and pulmonary metastasis were investigated to identify factors significantly correlated with prognosis. Of 103 patients, 75 (72.8%) had 1 site pulmonary metastasis, 22 (21.4%) had 2, and 6 (5.8%) had 3 or more. Liver recurrence at the time of pulmonary metastasectomy was noted in 34 patients. The estimated 5-year overall survival rate was 38.5% after pulmonary metastasectomy. Univariate prognostic analysis showed that liver recurrence at the time of pulmonary metastasectomy, extent of resection, laterality of pulmonary metastasis, tumor location, number of metastatic sites, and metastatic tumor size were significantly associated with favorable overall survival after pulmonary metastasectomy. Multivariate analysis revealed that liver recurrence at the time of pulmonary metastasectomy and the number of metastatic sites wereindependent prognostic factors. Subgroup analysis with a combination of these 2 independent prognostic factors revealed 5-year overall survival rates for patients with 0, 1, and 2 risk factors of 58.5%, 23.8%, and 0.0%, respectively. Pulmonary metastasectomy is a safe and effective treatment for well-selected patients with pulmonary metastasis of HCC. Liver recurrence at the time of pulmonary metastasectomy and the number of metastatic sites were identified as independent prognostic factors. The number of risk factors significantly influenced patient survival.

Clinicopathological features and differential diagnosis of hepatocellular carcinoma in extrahepatic metastases.

Extrahepatic metastasis of hepatocellular carcinoma (HCC) may cause a diagnostic problem. All 195 cases of histologic and immunostained sections were reviewed retrospectively in one center. The expression of arginase-1 (Arg-1), hepatocyte paraffin-1 (HepPar-1), glypican-3 (GPC-3), and α-Fetoprotein (AFP) was evaluated. Eighty cases of metastatic tumors of the liver were also collected to verify their effectiveness. Totally 151 cases had previous history of HCC, in whom 49 had history of liver transplantation. Forty-four cases were diagnosed as metastatic HCC at initial presentation. The most common extrahepatic metastatic sites were bone (57%), followed by lung, lymph node, etc. Around 19 cases were positive for 1 marker, 22 were positive for 2 markers, 95 were positive for 3 markers, and 59 were positive for 4 markers. With the number of antibody increased in the panel, the negative cases decreased. The sensitivity of ARG, GPC-3, HepPar-1, and AFP was 82.6%, 89.2%, 83.6% and 53.8%, and the specificity was 98.3%, 94.8%, 96.2% and 100%, respectively. These data suggest that the panel of ARG-1, GPC-3, HepPar-1 and AFP has a high sensitivity and specificity to differentiate HCC from non-HCC. This study indicated that HCC should be considered when diagnosing metastasis of unclear origin. It is recommended to use the panel of ARG-1, GPC-3, HepPar-1 and AFP to differentiate HCC from non-HCC in extrahepatic metastasis, because of their sensitivity and specificity, especially in poorly differentiated lesions.

Nomogram predicting extrahepatic metastasis of hepatocellular carcinoma based on commonly available clinical data.

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.

Long-Term Outcomes of Ante-Situm Resection and Auto-Transplantation in Conventionally Unresectable Hepatocellular Carcinoma: A Single-Center Experience.

BackgroundAnte-situm resection and auto-transplantation (ante-situm for short) provides a more aggressive approach to conventionally unresectable hepatocellular carcinoma (HCC). We described the long-term outcomes of patients with HCCs who underwent this technique.Material/MethodsBetween October 2005 and December 2016, we performed 23 ante-situm liver resections. We evaluated postoperative complications, 90-day mortality, recurrence, and long-term survival rates, and reviewed the literature on this topic.ResultsFive types of complications associated with six patients were observed.: 1) primary nonfunctioning liver, thus receiving a liver transplantation; 2) initial poor liver function with recovery two weeks after treatment; 3) diagnoses of portal vein tumor thrombosis, biliary fistula, and small-for-size syndrome, respectively. The median follow-up was 3.6 years; 12 out of 23 patients were alive at the end of the study. One patient who had hepatic recurrence was lost to follow-up after three months. One patient died of multiple organ dysfunction syndrome after the operation, nine patients died due to hepatic recurrence and/or extrahepatic metastasis of HCC. The one-year, three-year, five-year, and 10-year survival rates were 65.2%, 56.5%, 50.9%, and 20.3%, respectively. The one-year, three-year, five-year, and 10-year recurrence rates were 60.9%, 50.7%, 50.7%, and 50.7%, respectively. The chi-square test revealed the patients with recurrence after ante-situm technique were more likely to have poor prognosis (mortality of patients with recurrence versus no-recurrence: 88.9% versus 14.3%, p<0.05) and a strong association was evidenced by Cramer’s V statistic (Cramer’s V=0.734).ConclusionsAnte-situm procedure showed benefits in select patients with HCCs who had contraindications for conventional resection operations. In our case series, the ante-situm technique resulted in lower mortality compared to other ex-vivo hepatic resection techniques reported in the literature and similar long-term efficacy compared to cases of HCCs suitable for conventional resections. HCCs recurrence was a major risk factor associated with the survival rate of ante-situm technique.