Extrahepatic Hepatocellular Carcinoma Research Articles

Enhanced staging of extrahepatic hepatocellular carcinoma metastasis through dual-tracer PET/computed tomography: a systematic review and meta-analysis.

The aim of this study was to quantify the diagnostic value of dual-tracer PET/computed tomography (CT) with 11C-acetate and fluorodeoxyglucose (FDG) in per-lesion and per-patient and its effect on clinical decision-making for choosing the most appropriate management. The study protocol is registered a priori at https://osf.io/rvm75/. PubMed, Web of Science, Embase, and Cochrane Library were searched for relevant studies until 1 June 2023. Studies regarding the review question were included. The Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) was used to assess bias risk. Per-lesion and per-patient diagnostic performance were calculated for: (1) 11C-acetate alone; (2) FDG alone; and (3) dual tracer of 11C-acetate and FDG. A direct comparison of these three combinations was made. The possible sources of statistical heterogeneity were also examined. We also calculated the percentage change in clinical decision-making when dual-tracer PET/CT was added to conventional imaging routinely used for metastatic evaluation (CT/MRI). Grading of Recommendations, Assessment, Development, and Evaluations tool was used to evaluate the certainty of evidence. Eight studies including 521 patients and 672 metastatic lesions were included. Dual-tracer PET/CT had a per-lesion sensitivity of 96.3% [95% confidence interval (CI), 91.8-98.4%] and per-patient sensitivity of 95.5% (95% CI, 89.1-98.2%) which were highly superior to either of tracers alone. Per-patient specificity was 98.5% (84.1-99.9%) which was similar to either of tracers alone. Overall, 9.3% (95% CI, 4.7-13.9%) of the patients had their management beneficially altered by adding dual-tracer PET/CT to their conventional CT/MRI results. Dual-tracer PET/CT substantially outperforms single-tracer methods in detecting extrahepatic hepatocellular carcinoma metastases, evidencing its reliability and significant role in refining clinical management strategies based on robust diagnostic performance.

Expanding the therapeutic armamentarium for advanced hepatocellular carcinoma: successful transarterial chemoembolization of peritoneal extrahepatic metastasis.

Hepatocellular carcinoma (HCC) is predominantly known for its intrahepatic manifestations, yet extrahepatic dissemination, particularly intraperitoneal, remains rare. Herein, we present the very first case of successful transarterial chemoembolization (TACE) for an extrahepatic peritoneal HCC nodule. This intervention underscores the potential efficacy of TACE as a viable alternative to surgery in cases where arterial vessels supplying the lesion do not nourish vital parenchymal organs.

Liver-directed moderately hypo-fractionated radiotherapy combined with pembrolizumab and bevacizumab for advanced hepatocellular carcinoma: a retrospective observational study of 23 cases.

Programmed cell death protein 1 (PD-1) or its ligand (PD-L1) monoclonal antibody combined with bevacizumab (a monoclonal antibody targeting vascular endothelial growth factor) has been established as first-line systemic treatment for advanced hepatocellular carcinoma (HCC). Radiotherapy is a crucial local treatment for HCC. Mutual efficacy enhancement has been reported between radiotherapy, anti-angiogenesis therapy and immunotherapy in preclinical researches, but not been validated in clinical practice. Whether radiotherapy can enhance efficacy of anti-PD-1 immunotherapy plus bevacizumab for HCC remains unclear. This retrospective observational study aimed to appraise efficacy and safety of the combination of radiotherapy with pembrolizumab (a PD-1 monoclonal antibody) and bevacizumab for advanced HCC for the first time. Patients with advanced HCC treated by intrahepatic tumor-directed moderately hypo-fractionated radiotherapy combined with pembrolizumab and bevacizumab were consecutively included. Clinicopathological characteristics, therapeutic outcomes and treatment-related adverse events (TRAEs) were recorded and evaluated. A total of 23 patients were eventually enrolled. Median cycles of pembrolizumab and bevacizumab were 4 (median, 1-8) and 4 (median, 1-9) cycles. The objective response rates and disease control rates of irradiated intrahepatic HCC and non-irradiated extrahepatic HCC were 34.8% [95% confidence interval (CI), 16.4-57.3%] vs. 10.0% (95% CI, 1.2-31.7%), and 91.3% (95% CI, 72.0-98.9%) vs. 70.0% (95% CI, 45.7-88.1%), respectively. The median progression-free survival (PFS) and overall survival (OS) were 6.6 (95% CI, 4.7-8.5) and 18.3 (95% CI, 8.2-33.6) months, and 12-month PFS and OS rates were 17.5% (95% CI, 7.0-28.0%) and 60.9% (95% CI, 50.7-71.1%). Two patients (8.7%) with locally advanced, unresectable HCC eventually underwent curative resection of tumors after this trimodal treatment. Eighteen patients (78.3%) had ≥ grade 3 TRAEs, with myelosuppression and transaminase increase as the most common. This study firstly reported that combining radiotherapy with pembrolizumab and bevacizumab was preliminarily a feasible and effective therapeutic choice for advanced HCC in despite of more TRAEs. This tri-modal regimen may be a potential conversion therapy for unresectable, locally advanced HCC. The limitations of this study are its retrospective nature and small sample size; therefore, big-sample prospective studies are warranted to further investigate this tri-modal regimen.

The impact of extrahepatic hepatocellular carcinoma metastases on survival in a Sub-Saharan African patient cohort

The impact of extrahepatic hepatocellular carcinoma metastases on survival in a Sub-Saharan African patient cohort

Salvage Ablative Radiation Therapy for Isolated Intraabdominal Recurrences of Hepatocellular Carcinoma

<h3>Purpose/Objective(s)</h3> The standard of care for extrahepatic hepatocellular carcinoma (HCC) is a systemic therapy. However, some patients present with limited intra-abdominal disease that might benefit from local ablative radiation therapy (RT) with, or instead of, systemic therapy. This study explores outcomes of ablative RT for isolated intra-abdominal recurrences from HCC. <h3>Materials/Methods</h3> A single-institution retrospective chart review was conducted from 2013 to 2021. Inclusion criteria were any patient with HCC that had limited disease in an abdominal lymph node (LN) or adrenal gland (AG) treated with salvage ablative RT. The primary outcome was local control (LC) in the target lesion. Secondary outcomes were progression-free survival (PFS) and overall survival (OS) from the time of recurrence after completing RT. <h3>Results</h3> 31 patients met inclusion criteria, of which 21 (67.7%) had a recurrence in a LN while 10 (32.2%) had recurrences in an AG. 19 (90%) of LN recurrences were in the portal region. The median time from initial HCC diagnosis to extrahepatic recurrence was 18 months (range 0 to 152 months). Among all patients, 21 patients received immunotherapy (prior, concurrent, or after) in addition to salvage RT. 27 (87.1%) patients received salvage SBRT, and 4 (12.9%) patients received fractionated RT. The median dose was 4500 in 5 fractions. LC, as defined as no progression in target lesion, was 100%. The median PFS, defined by recurrence or death, was 18 months. The median OS was 29 months. There was a statistical difference in OS in patients that received IO and RT vs. RT alone (p=0.038) in favor of RT alone. There was no significant difference in OS for a LN recurrence versus salvage RT for an AG recurrence (p=0.389). <h3>Conclusion</h3> Salvage ablative RT, with or without immunotherapy, can produce meaningful PFS and OS in well-selected patients with limited intra-abdominal extrahepatic recurrence of HCC. This benefit appears the same for LN recurrences and AG metastases and might be independent of immunotherapy. Prospective data are needed to verify these results.

N-acetyl-galactosamine modified metal-organic frameworks to inhibit the growth and pulmonary metastasis of liver cancer stem cells through targeted chemotherapy and starvation therapy

Hepatocellular carcinoma (HCC) is a common high-mortality malignancy which still needs efficient treatments. HCC patients undergoing extrahepatic metastases are mostly with unsatisfactory prognosis. Therefore, specific attention has been paid to extrahepatic HCC metastasis. We integrated Sorafenib (Sor) and glucose oxidase (GOx) into a N-acetyl-galactosamine (GalNAc) modified zeolitic imidazolate framework (ZIF-8), designated as SG@GR-ZIF-8, for targeted bimodal therapies of chemotherapy and starvation therapy against HCC. The hepatic delivery of SG@GR-ZIF was mediated by the specific recognition of GalNAc residues with asialoglycoprotein (ASGPR) on the liver cell surface. Sor is a clinically approved anti-proliferation and anti-angiogenesis drug for advanced HCC treatment. GOx can efficiently induce cell death and disturb malignant progression by suppressing glucose supply of cancer cells, which is highly associated with metabolic rewiring in metastasis. The nano-formulation exhibit significant anti-metastatic HCC activity against C5WN1 cells, a liver cancer stem cell-like cell line with tumorigenicity and pulmonary metastasis activity. In a subcutaneous C5WN1-tumor carrying mouse model, SG@GR-ZIF exhibits potent synergistic anti-tumor activity with a tumor inhibition rate of 89% and a prolonged survival status. The growth and pulmonary metastasis of HCC in an orthotopic mouse model of HCC was remarkably suppressed in SG@GR-ZIF treated group. The therapeutic strategy targeting energy supply combined with first-line treatment holds great promise for the future treatment of metastatic HCC. Statement of significanceSG@GR-ZIF, a N-acetyl-galactosamine modified metal-organic framework carrying Sorafenib and glucose oxidase, was fabricated for treating metastatic hepatocellular carcinoma (HCC). Sorafenib is an anti-proliferation and anti-angiogenesis drug for advanced HCC treatment. Glucose oxidase blocks energy demand in HCC metastasis by depleting glucose. C5WN1 was used for therapeutic evaluations as a liver cancer stem cell-like cell line with tumorigenicity and pulmonary metastasis activity. In subcutaneous C5WN1-tumor bearing mice, SG@GR-ZIF exhibited a tumor inhibition rate of 89% and prolonged survival period. In orthotopic C5WN1-tumor carrying mice, the growth and pulmonary metastasis of hepatocarcinoma was remarkably suppressed by SG@GR-ZIF. Together, this study suggests the great potential of synergistic chemo/starvation therapy mediated by SG@GR-ZIF for treating metastatic HCC.

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.

Lung and lymph node metastases from hepatocellular carcinoma: Comparison of pathological aspects.

Extrahepatic metastasis from hepatocellular carcinoma (HCC) is a catastrophic event, yet organ-specific pathological characteristics of metastatic HCC remain unclear. We aimed to characterize the pathological aspects of HCC metastases to various organs. We collected intrahepatic HCC (cohort 1, n=322) and extrahepatic metastatic HCC (cohort 2, n=130) samples. Clinicopathological evaluation and immunostaining for K19, CD34, αSMA, fibroblast-associated protein (FAP), CAIX, VEGF, PD-L1, CD3, CD8, Foxp3, CD163 and epithelial-mesenchymal transition (EMT)-related markers were performed. Independent factors for extrahepatic metastasis included BCLC stage B-C, microvascular invasion (MVI), vessels encapsulating tumour clusters (VETC)-HCC, K19 and FAP expression, and CD163+ macrophage infiltration (cohort 1, P<.05 for all). Lung metastases (n=63) had the highest proportion of VETC-HCC and macrotrabecular-massive (MTM)-HCC. Lymph node metastases (n=19) showed significantly high rates of EMT-high features, K19 expression, fibrous tumour stroma with αSMA and FAP expression, high immune cell infiltration, PD-L1 expression (combined positive score), CD3+, CD8+, Foxp3+ T cell and CD163+ macrophage infiltration (adjusted P<.05 for all). In both cohorts, EMT-high HCCs showed higher rates of K19 expression, fibrous tumour stroma, high immune cell infiltration, PD-L1 expression and CD3+ T cell infiltration, whereas EMT-low HCCs were more frequent among VETC-HCCs (P<.05 for all). Overall phenotypic features were not significantly different between paired primary-metastatic HCCs (n=32). Metastatic HCCs to various organs showed different pathological features. VETC and MTM subtypes were related to lung metastasis, whereas K19 expression, EMT-high features with fibrous tumour stroma and high immune cell infiltration were related to lymph node metastasis.

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.

Hepatocellular carcinoma with tumor thrombus in bile duct: A proposal of new classification according to resectability of primary lesion.

BACKGROUNDHepatocellular carcinoma (HCC) with tumor thrombus in the bile duct (BDTT) is easily misdiagnosed or mistreated due to the clinicopathological diversity of the thrombus and its relationship with primary lesions.AIMTo propose a new classification for HCC with BDTT in order to guide its diagnosis and treatment.METHODSA retrospective review of the diagnosis and treatment experience regarding seven typical HCC patients with BDTT between January 2010 and December 2019 was conducted.RESULTSBDTT was preoperatively confirmed by computed tomography/magnetic resonance imaging in only four patients. Three patients with recurrent HCC and one patient with first-occurring HCC had no visible intrahepatic tumors; of these, misdiagnosis occurred in two patients, and three patients died. One patient was mistreated as having common bile duct stones, and another patient with a history of multiple recurrent HCC was misdiagnosed until obvious biliary dilation could be detected. Only one patient who received hepatectomy accompanied by BDTT extraction exhibited disease-free survival during the follow-up period. A new classification was proposed for HCC with BDTT as follows: HCC with microscopic BDTT (Type I); resectable primary or recurrent HCC mass in the liver with BDTT (Type II); BDTT without an obvious HCC mass in the liver (Type III) and BDTT accompanied with unresectable intra- or extrahepatic HCC lesions (Type IV).CONCLUSIONWe herein propose a new classification system for HCC with BDTT to reflect its pathological characteristics and emphasize the significance of primary tumor resectability in its treatment.

Favorable outcomes of surgical resection for extrahepatic recurrent hepatocellular carcinoma

Repeat resection for intrahepatic recurrent hepatocellular carcinoma (HCC) is effective for the long-term survival of patients; however, little is known about the surgical outcomes of extrahepatic nodules. The aim of this study is to investigate whether resection can contribute to the survival of patients with extrahepatic recurrent HCC. Under the conditions that intrahepatic recurrent HCC was absent or controlled by locoregional therapies, patients who had resectable extrahepatic recurrent HCC in the lymph nodes, adrenal gland, peritoneum, lung, or brain were included in this study. The survival of patients who did (Surgical group) and did not (Non-surgical group, underwent other therapies) undergo resection for extrahepatic recurrent HCC was compared. Thirty-eight and 26 patients were included in the Surgical and Non-surgical groups, respectively. No patient had severe postoperative complications. After a median follow-up of 1.2 (range, 0.2-8.8) years, the median cumulative incidence of extrahepatic recurrent HCC was 1.2years (95% confidence interval [CI], 0.4-3.5) in the Surgical group. The median overall survival was 5.3 (95% CI, 2.5-8.8) and 1.1 (0.8-2.3) years in the Surgical and Non-surgical groups, respectively (P< 0.001). The 5-year rates of survival were 60.5% and 9.1% in the Surgical and Non-surgical groups, respectively. Surgical resection, α-fetoprotein, disease-free interval, and metastasis at the adrenal gland were the independent factors for overall survival. Due to the favorable surgical outcomes, resection should be considered as one of the therapeutic choices for patients with extrahepatic recurrent HCC if intrahepatic recurrent HCC can be controlled by locoregional therapies.

18 F]-Fluoro-2-deoxy-D-galactose positron emission tomography/computed tomography as complementary imaging tool in patients with hepatocellular carcinoma.

Positron emission tomography (PET) with the liver-specific tracer [18 F]-fluoro-2-deoxy-D-galactose (18 F-FDGal) can be used for imaging of hepatocellular carcinoma (HCC). Curative intended and locoregional treatments of HCC require absence of extrahepatic disease. The aim of this prospective study was to determine whether adding 18 F-FDGal PET/CT to standard work-up changes the planned treatment in patients with HCC deemed suitable for curative or locoregional treatment. Fifty patients with HCC were included at our tertiary liver centre. The primary study outcome was a change in treatment strategy. A subgroup of 29 patients was also examined with [18 F]-fluoro-2-deoxy-D-glucose (18 F-FDG) PET/CT for comparison. 18 F-FDGal PET/CT detected eight extrahepatic HCC metastases in six patients (12%), which were primarily not detected by ceCT or MRI. These findings led to a change in treatment in five patients (10%). One of the eight extrahepatic HCC foci was also detected by 18 F-FDG PET/CT. A total of 85 malignant intrahepatic foci were examined, 12 of these were new findings by 18 F-FDGal PET/CT which had a sensitivity of 71%, highest for large foci. None of the additional intrahepatic foci found by 18 F-FDGal PET changed the planned treatment. For the detection of extrahepatic HCC metastases, 18 F-FDGal PET/CT was superior both to standard clinical work-up with contrast-enhanced CT, and/or MRI, and to 18 F-FDG PET/CT in patients deemed suitable for locoregional treatment. 18 F-FDGal PET/CT led to a change in the planned treatment in 10% of the patients whereas 18 F-FDG PET/CT did not change the planned treatment in any patient.

Association Between PNPLA3 rs738409 C>G Variant and Liver-Related Outcomes in Patients With Nonalcoholic Fatty Liver Disease

Patients with nonalcoholic fatty liver disease (NAFLD) have an increased risk for liver-related complications, such as decompensation, hepatocellular carcinoma (HCC), and death; the severity of liver fibrosis and metabolic comorbidities are the main risk factors. A single nucleotide polymorphism in patatin-like phospholipase domain-containing-3 (PNPLA3) gene is associated with higher prevalence of liver damage and HCC, but there are no data from prospective studies of outcomes of patients with this polymorphism. We investigated whether the common rs738409 variant in PNPLA3 gene associates with the occurrence of liver-related events and death in a large cohort of patients with NAFLD. We followed 471 consecutive individuals at a hospital in Italy with a diagnosis of NAFLD based on histologic factors or a diagnosis of compensated NAFLD-related cirrhosis based on clinical factors for at least 6 months, from March 2004 through December 2018. We collected data on the occurrence of hepatic and extrahepatic outcomes, including decompensation and HCC, cardiovascular events and extrahepatic cancers, and overall and liver-related death. We detected the rs738409 G>C polymorphism in DNA from patient blood samples using the TaqMan assay. During a median follow-up time of 64.6 months (range 6.1-175 months) 26 cases of decompensation, 13 HCCs, and 16 deaths (12 liver-related) were recorded. All liver-related events, including liver-related death, occurred in patients with F3 fibrosis or cirrhosis. The prevalence of PNPLA3 rs738409 GG, GT, and TT genotypes was 31.8%, 45.6%, and 22.6%, respectively. After adjusting for clinical, metabolic, and histologic risk factors, PNPLA3 C>G variant was associated with a higher risk of decompensation (hazard ratio [HR], 2.10; 95% CI, 1.03-4.29; P = .04), HCC (HR, 2.68; 95% CI, 1.01-7.26; P = .04), and liver-related death (HR, 3.64; 95% CI, 1.18-11.2; P=.02) by multivariate Cox regression analysis. In the subgroup of 162 patients with F3 fibrosis or cirrhosis, we confirmed the independent association between the PNPLA3 variant and decompensation (HR, 2.00; 95% CI, 1.01-3.97; P = .04), HCC (HR, 2.66; 95% CI, 1.02-7.13; P=.04), and liver-related death (HR, 3.64, 95% CI, 1.18-11.2; P = .02). We found no association between PNPLA3 genotype and cardiovascular events, extrahepatic cancers, or overall mortality. Patients with NAFLD carrying PNPLA3 rs738409 G>C variant are at higher risk of liver-related events and death.

Radiotherapy for HCC: Ready for prime time?

SummaryStereotactic body radiation therapy (SBRT) has an evolving role in the management of hepatocellular carcinoma (HCC), largely due to recent advances in imaging technology. Often utilized in situations where other locoregional therapies are not feasible, SBRT has been demonstrated to be an effective treatment that confers high rates of durable local control. However, there is limited evidence to firmly establish its place in the treatment paradigm for HCC. In this article, we review the current evidence and highlight specific considerations in the multiple settings where SBRT may be used, including for primary HCC treatment and bridging/downstaging, as well as exploring the potential for SBRT in the treatment of extrahepatic oligo-metastatic HCC.

Metastatic Hepatocellular Carcinoma Presenting as Extensive Bone Metastasis

Hepatocellular carcinoma(HCC) is a primary malignancy of the liver and occurs mainly in patients with underlying chronic liver disease or cirrhosis. It is considered the third leading cause of cancer death worldwide. Here, we present a rare case of HCC with diffuse bone metastasis. 57 y.o. male with past history of Chronic Hepatits B & C presented with diffuse body aches associated with jaundice. Exam did not show any ascites or stigmata of cirrhosis. Relevant labs included: AST 62 ALT 53 Alk Phos 231 T Bili 1.6 INR 1.0 Alb 3.5 CEA 1.46 AFP 5.1. Multiple hepatic lesions seen on imaging were initially concerning for metastatic disease. Bone imaging revealed diffuse lytic lesions, with the largest in the right sacrum. No clear primary malignancy was identified, so patient underwent EGD and colonoscopy, which were negative. A sacral bone biopsy was performed, revealing atypical cells with abundant cytoplasm and abnormal nuclei (Image 1); further reticulin (Image 2), arginase, and heppar (Image 3) staining confirmed malignant hepatic cells. Patient was diagnosed with primary HCC with bone metastasis, Child Pugh score A. Due to the advanced nature of presentation, patient opted for Hospice care. HCC is often seen with early metastasis to lungs, abdominal lymph nodes, central nervous system, and bones—further decreasing median survival. Current treatment options for extra-hepatic HCC generalized to all metastatic types recommends palliative chemotherapy if Child Pugh A/B, and advises only symptomatic treatment if Child Pugh C. HCC with bony metastasis is rare, and is associated with even higher mortality rates and median survival of 3 months without treatment. Chemotherapy with Sorafenib can prolong median survival by on average 2 months, but with significant effect on standard of life due to side effects. Radiation therapy has shown improvement in pain without improved mortality. Other symptomatic treatment includes palliative stents, vitamin D, calcium, and pain control. In deciding care for HCC with bony metastasis, the net clinical benefit of each treatment must be considered by weighing the improvement in survival time versus quality of life. Interventions should focus on maximizing the individual's self-established quality-adjusted life years. Therefore, careful discussion is needed in each case to determine the best option for each patient.2311_A Figure 1. Bone biopsy showing atypical cells with abundant cytoplasm and enlarged round to ovoid nuclei. Together with staining patterns is consistent with HCC.2311_B Figure 2. Reticulin immunohistochemical stain suggestive of hepatic origin.2311_C Figure 3. Heppar immunohistochemical stain positive consistent with cells of hepatic origin.

Clinical investigation on transarterial chemoembolization with indigenous drug-eluting beads in treatment of unresectable hepatocellular carcinoma

Objective: To evaluate the efficacy and safety of drug-eluding beads transarterial chemoembolization (DEB-TACE) in treatment of unrecectable hepatocellular carcinoma (HCC). Methods: The clinical data of 42 consecutive HCC patients undergoing TACE were retrospectively analyzed, including 20 cases received conventional TACE (cTACE group) and 22 cases received TACE with epirubicine-loaded microspheres (CalliSpheres ®) (DEB-TACE group). MRI scans were performed 1 week before and 1, 3 and 6 months after initial therapy. The response to treatment, disease recurrence, complications and adverse effects were documented and compared between two groups. Results: There were no significant differences in 1-month, 3-month and 6-month objective response rate (CR+PR) and disease control rate (CR+PR+SD), disease recurrence, complications and adverse effects of interventional therapy between cTACE group and DEB-TACE group. Additionally, there were no significant differences about locoregional biliary injuries, intrahepatic biloma, and newly detected intra- or extrahepatic HCC on MRI between cTACE group and DEB-TACE group. Conclusion: There were no statistically significant differences between cTACE group and DEB-TACE group with regard to the short-term response, disease recurrence, complications and side effects. Hepatic-locoregional complications may be more frequent in DEB-TACE group than those in cTACE group.

Surgical resection of recurrent extrahepatic hepatocellular carcinoma with tumor thrombus extending into the right atrium under cardiopulmonary bypass: a case report and review of the literature.

BackgroundRecurrent hepatocellular carcinoma accompanied by a right atrial tumor thrombus is rare. No standard treatment modality has been established. Surgical treatment may be the only curative treatment; however, surgery has been considered high risk. We herein describe a patient who underwent resection of a recurrent right atrial tumor thrombus under normothermic cardiopulmonary bypass on a beating heart.Case presentationA 60-year-old man underwent a right hepatectomy for hepatocellular carcinoma with diaphragm invasion. During the preoperative cardiac screening, he was diagnosed with an old myocardial infarction with triple-vessel coronary disease. Percutaneous coronary intervention was performed for the left anterior descending artery and left circumflex coronary artery. High-grade stenosis remained in his right coronary artery. Nine months later, computed tomography showed recurrent hepatocellular carcinoma in the diaphragm and a tumor thrombus extending from the suprahepatic inferior vena cava into the right atrium. Surgical resection of the recurrent tumor was performed through a right subcostal incision with xiphoid extension and median sternotomy. The recurrent tumor was incised with the diaphragm and pericardium. Intraoperative ultrasonography revealed that the tumor thrombus was free from right atrium wall invasion and that the right atrium could be clamped just proximal to the tumor thrombus. The right atrium, infrahepatic vena cava, left and middle hepatic veins, and hepatoduodenal ligament were encircled. Cardiopulmonary bypass was performed to prevent ischemic heart disease caused by intraoperative hypotension. Total hepatic vascular exclusion was then performed under normothermic cardiopulmonary bypass on heart beating. The inferior vena cava wall was incised. The tumor thrombus with the diaphragmatic recurrent tumor was resected en bloc. The patient had a favorable clinical course without any complications.ConclusionThe recurrent hepatocellular carcinoma in the diaphragm and the right atrial tumor thrombus were safely resected using normothermic cardiopulmonary bypass on heart beating.

Hepatitis and Solitary Left Renal Mass: Renal Hepatocellular Carcinoma

Solitary renal tumours are often primary clear cell carcinoma. A 48-year-old man with chronic hepatitis, hepatocellular carcinoma (HCC), and orthotropic liver transplant 6years ago presented with a solitary left renal mass. Histology revealed metastatic HCC of the left kidney with extensive reactive changes in lymph nodes. Interestingly, biopsy of the transplanted liver showed no evidence of HCC recurrence. Metastatic disease to the kidney often disseminate locally through transcelomic spread, or hematogenous affecting both kidneys. It is important to recognize extrahepatic HCC metastases to the contralateral kidney, especially in patients with active hepatitis, and radical lymph node clearance is needed.

Body mass index above 24 is beneficial for the 6-month survival rate in hepatocellular carcinoma patients with extrahepatic metastases.

To investigate the effect of overweight status on the 6-month survival rate in patients with extrahepatic hepatocellular carcinoma (HCC). We retrospectively analyzed the records of 51 patients with hepatocellular carcinoma and extrahepatic metastases between 2007 and 2010 before treatment. The associations among overweight status (body mass index [BMI] >24 kg/m2), demographic variables, and survival outcome were analyzed by univariate and multivariate analysis. BMI>24 kg/m2 was significantly associated with the 6-month survival rate (p=0.042). Gender (p=0.149), Child Pugh classification (p=0.149), Okuda staging (p=0.093), and albumin concentration >3.5 mg/dL (p=0.082) showed marginal survival benefits in univariate analysis. Multivariate analysis confirmed that BMI >24 kg/m2 was an independent prognostic factor for the 6-month survival rate (p=0.03). BMI >24 kg/m2 was associated with an improved 6-month survival rate in patients with extrahepatic metastatic hepatocellular carcinoma.

Sorafenib and a novel immune therapy in lung metastasis from hepatocellular carcinoma following hepatectomy: A case report.

Sorafenib is the standard therapeutic strategy for recurrent hepatocellular carcinoma (HCC) following hepatectomy. However, only few patients truly benefit from this therapy. Thus, new strategies combined with sorafenib are urgently required. We herein present the case of a patient with hepatic and extrahepatic HCC recurrence following hepatectomy, who was treated by combined sorafenib, focused ultrasound knife and DRibbles-pulsed dendritic cell (DC) vaccine. Enzyme-Linked ImmunoSpot assay (ELISPOT) and intracellular staining (ICS) analysis were used to detect the secretion of interferon (IFN)-γ by T cells at different timepoints of the vaccine in order to evaluate the patient's specific T-cell response to SMMC-7721-derived DRibbles vaccine. The α-fetoprotein level decreased from 103,295 to 5 ng/ml and the patient displayed improved liver function, an Eastern Cooperative Oncology Group performance status score of 0, remission of liver metastases and disappearance of the lung metastases 8 months post-combination therapy. The computed tomography scan revealed the disappearance of liver metastases 2 years post-combination therapy. The ELISPOT data revealed a low antigen-specific T-cell response 4 weeks after the first vaccine cycle and the response decreased to nearly zero prior to the second cycle. However, high antigen-specific T-cell response was observed 2 weeks after the second vaccine cycle and did not decrease, even after 10 months, which was consistent with the result of the ICS analysis, which demonstrated that most of the secreted IFN-γ was produced by CD4+ T cells, whereas a low CD8+ T-cell response was observed (0.429 vs. 0.0665%, respectively). Our results demonstrated that antigen-specific T-cell response aimed to treat recurrent HCC may be induced through stimulation by the DC-DRibbles vaccine. The success of the treatment supports the combination of sorafenib, focused ultrasound knife and DC-DRibbles vaccine as a therapeutic strategy for patients with HCC recurrence following hepatectomy.