Portal Invasion Research Articles

Outcome of liver resection for intrahepatic cholangiocarcinoma with macroscopic vascular invasion. Analysis of a multi-institutional database

Background: Surgery is the standard treatment of intrahepatic cholangiocarcinoma (ICC). In presence of macroscopic vascular invasion (Macrovasc), the outcome of resection is still to elucidate. Methods: A multi-institutional series of ICC patients was analysed. The 247 patients undergoing resection without operative mortality were included. Preoperative imaging and pathology data were reviewed to identify Macrovasc. Results: Of the analyzed patients, 82 (33%) had Macrovasc: 39 of a portal branch, 21 of a hepatic vein, and 22 of both. Patients with Macrovasc had larger tumors (>50 mm 65 vs. 44%, p=0.002) and more N+ (44 vs. 30%, p=0.068). Patients with Macrovasc had lower survival (3-year OS 47 vs. 61%, p=0.025). Lower OS was observed for both hepatic vein Macrovasc (3-year OS 40.1%, p=0.032) and portal Macrovasc (44.7%, p=0.010). The level of portal invasion (1st- vs. 2nd-order branches) did not modify prognosis (p=0.813). If both a hepatic vein and a portal branch had Macrovasc the prognosis further decreased (3-year OS 29.1%), but was still higher than unresected patients (0% at 24 months, p<0.001). At the multivariable analysis, hepatic vein invasion was a negative prognostic factor of OS (p=0.041, OR=1.709). Additional prognostic factors were N+ (p< 0.001), R1 resection (p=0.040), ICC size >50 mm (p=0.040) and number>1 (p<0.001). Conclusion: One-third of patients with ICC have Macrovasc. It is a negative prognostic factor, but not a contraindication to surgery because complete resection may confer a survival benefit.

Outcome of liver resection for intrahepatic cholangiocarcinoma with macroscopic vascular invasion. Analysis of a multi-institutional database

Background: Surgery is the standard treatment of intrahepatic cholangiocarcinoma (ICC). In presence of macroscopic vascular invasion (Macrovasc), the outcome of resection is still to elucidate. Methods: A multi-institutional series of ICC patients was analysed. The 247 patients undergoing resection without operative mortality were included. Preoperative imaging and pathology data were reviewed to identify Macrovasc. Results: Of the analyzed patients, 82 (33%) had Macrovasc: 39 of a portal branch, 21 of a hepatic vein, and 22 of both. Patients with Macrovasc had larger tumors (>50 mm 65 vs. 44%, p=0.002) and more N+ (44 vs. 30%, p=0.068). Patients with Macrovasc had lower survival (3-year OS 47 vs. 61%, p=0.025). Lower OS was observed for both hepatic vein Macrovasc (3-year OS 40.1%, p=0.032) and portal Macrovasc (44.7%, p=0.010). The level of portal invasion (1st- vs. 2nd-order branches) did not modify prognosis (p=0.813). If both a hepatic vein and a portal branch had Macrovasc the prognosis further decreased (3-year OS 29.1%), but was still higher than unresected patients (0% at 24 months, p<0.001). At the multivariable analysis, hepatic vein invasion was a negative prognostic factor of OS (p=0.041, OR=1.709). Additional prognostic factors were N+ (p< 0.001), R1 resection (p=0.040), ICC size >50 mm (p=0.040) and number>1 (p<0.001). Conclusion: One-third of patients with ICC have Macrovasc. It is a negative prognostic factor, but not a contraindication to surgery because complete resection may confer a survival benefit.

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Prognostic Impact of Portal System Invasion in Pancreatic Cancer Based on Image Classification.

This study aimed to clarify the correlation between image classification and the pathological degree of portal system invasion (PSI) and to evaluate the prognostic impact of PSI in pancreatic cancer (PC). Pancreatic cancer patients with surgical resections (head, n = 244; body and tail, n = 80) were enrolled in this study. Based on imaging findings, portal vein (PV) invasion was classified as type A (absent), B (unilateral narrowing), C (bilateral narrowing), or D (stenosis or obstruction with collaterals). Splenic vein (SPV) invasion was classified as type α (absent), β (stenosis), or γ (obstruction). The pathological grade of venous invasion was classified as grade 0 (no invasion), 1 (tunica adventitia), 2 (tunica media), or 3 (tunica intima). In PV and SPV invasions, image classification and pathological grade showed significant correlation (PV: ρ = 0.696; SPV: ρ = 0.681). Patients with PV invasion deeper than type B exhibited significantly poorer survival than type A (P < 0.0001). In contrast, there was no difference in survival among types α, β, and γ. Image classification was correlated with the pathological grade of PSI in PC. Although not applicable for SPV invasion, image classification of PV invasion is a robust indicator for PC prognosis.

Prognostic impact of portal system invasion based on tumor location in pancreatic cancer

Objective: The aim of this study was to clarify the correlation between image classification and degree of pathological invasion of portal system, and evaluate the prognostic impact in pancreatic cancer. Methods: Between January 2003 and June 2017, a total of 324 resected pancreatic cancer patients (head; 244, body and tail; 80) were enrolled. As image findings, portal vein (PV) invasion was classified into type A (absent), B (unilateral narrowing), C (bilateral narrowing), and D (stenosis or obstruction with collaterals), whereas, splenic vein (SPV) invasion was classified as type α (absent), β (stenosis), and γ (obstruction). Pathological grade of portal system invasion was classified into: grade 0 (no invasion), 1 (tunica adventitia), 2 (tunica media), and 3 (tunica intima). Results: Both in PV and SPV invasions, there was a significant correlation between image classification and pathological grade (PV; P < 0.0001, SPV; P < 0.0001, respectively). In head cancer, type A had a significant better survival than type ≥ B (P < 0.0001). Whereas in body and tail cancer, there was no difference among type α, β and γ. In multivariate analysis, type B (P = 0.0003), C (P = 0.007) in head cancer and lymph node metastases (P = 0.0003) in body and tail cancer were the independent prognostic factors. Conclusion: Image classification was correlated with pathological grade in portal system invasion in pancreatic cancer. Image classification in PV invasion can be used for prognostic prediction, but not in SPV.

Hepatocellular Carcinoma with Portal Vein Tumor Involvement: Best Management Strategies.

Portal vein tumor thrombosis (PVTT) commonly occurs in patients with hepatocellular carcinoma (HCC). Patients with PVTT usually have an aggressive disease course, decreased liver function reserve, limited treatment options, higher recurrence rates after treatment, and, therefore, worse overall survival. Among untreated HCC patients with PVTT, the median overall survival has been reported as low as 2 to 4 months. Historically, many aspects of PVTT have impacted the theoretical and practical safety and efficacy of treatment, for example, disordered blood flow and associated impairment of liver function, heat-sink effects of blood flow in the area of the PVTT, and risk of recurrence due to tumor location in the blood vessel. The current Barcelona Clinic Liver Cancer staging system categorizes HCC patients with PVTT as advanced stage, for which the standard of care is targeted therapy with sorafenib. However, sorafenib is associated with only marginal benefits among patients with PVTT. First-line lenvatinib, which was shown to be noninferior to sorafenib, excluded patients with main portal trunk invasion. Regorafenib and nivolumab, an immune-based therapy, were recently approved in the United States for second-line therapy after sorafenib. Preliminary results for cabozantinib suggest a benefit in the second-/third-line after sorafenib failure. In addition, rapid advances in many fields (surgery, interventional radiology, nuclear medicine, and immunotherapy) have increased the potential treatment options for the management of this complex disease entity. A large portion of the emerging evidence focuses on the broader category of advanced HCC of which PVTT is a subgroup. While many of these studies show promising results, the efficacy among PVTT patients requires validation in prospective studies. Real-world data may help fill the evidence gap for patients not eligible for clinical trials due to common hepatic function requirements. The variety of new treatment advances for the heterogeneous and complex disease entity of HCC with PVTT means that personalized, multidisciplinary management may be necessary to achieve optimal outcomes. In this narrative review, we summarize the evolving management strategies for patients with HCC and PVTT.

Portal and superior mesenteric vein resection in radical pancreatectomy for pancreatic cancer

Radical resection remains essential for prolonging survival and increasing the possibility of cure in pancreatic cancer. However, few patients are resectable at the time of diagnosis, with a portion of patients presenting with portal and superior mesenteric vein invasion and regarded as resectable or locally advanced disease. Venous resection in pancreatectomy enables achievement of tumor-free margins in patients with venous invasion. This review provides an overview of preoperative evaluation, resection and reconstruction types, vascular grafts selection, morbidity, mortality and survival in radical pancreatectomy with portal and superior mesenteric vein resection. Key words: Pancreatic neoplasms; Vascular resection; Portal vein; Superior mesenteric vein

Multibipolar Radiofrequency Ablation for the Treatment of Mass-Forming and Infiltrative Hepatocellular Carcinomas > 5 cm: Long-Term Results

Aims and Background: Only few patients with cirrhosis and hepatocellular carcinoma (HCC) larger than 5 cm are amenable to resection or straight liver transplantation, and in such circumstances, multibipolar radiofrequency ablation (mbp-RFA) could be a reliable alternative. This study was aimed to assess the long-term outcome in patients treated with mbp-RFA for unresectable HCC > 5 cm. Methods: Eighty-three consecutive patients with cirrhosis (median age 70 years [37–93 years], 67 males, BCLC A/B/C: 54/21/8, 74 naive) with up to three HCCs, the largest > 5 cm in diameter (median: 6.2 cm, 5.1–9 cm, 22 infiltrative forms, 12 with segmental portal invasion of which 10 were infiltrative forms) were treated with mbp-RFA. Overall (OS) and recurrence-free (RFS) survival and their associated predictive factors were assessed. Results: Complete ablation was observed in 78/83 (94%) patients. Thirty-one side effects occurred, including 6 (7%) severe complications. After a median follow-up of 26.1 months (1–112 months), in naive patients the 3- and 5-year OS was 51% (38–62) and 24% (13–36), 63 and 30% for mass-forming and 25 and 6% for infiltrative form, respectively. Infiltrative form (HR: 2.5 [1.33–4.69], p = 0.004) was the only independent OS predictor. In naive patients with mass-forming and infiltrative form, the 3- and 5-year RFS were 47 and 17 and 18 and 18%, respectively. Alpha-fetoprotein (HR: 2.86 [1.32–6.21], p = 0.008), multinodular form (HR: 2.74 [1.4–5.38], p = 0.003) and infiltrative form (HR: 3.43 [1.67–7.01], p = 0.0007) were independent RFS predictors. Conclusions: mbp-RFA offers good OS in inoperable patients with cirrhosis and large HCC, with acceptable safety profile. For infiltrative forms, although mbp-RFA leads to complete responses in more than 80% cases, few only remain tumor progression-free in long-term.

Clinical Implication of the Relationship Between High Mobility Group Box-1 and Tumor Differentiation in Hepatocellular Carcinoma.

High mobility group box-1 (HMGB1) induces the release of proinflammatory cytokines and chemokines as a late-acting mediator of inflammation. Hepatocellular carcinoma (HCC) is a typical inflammation-related cancer. However, little is known about the relationship between HCC and HMGB1 and its receptor RAGE (receptor for advanced glycation end products). This study analyzes the clinicopathological relevance of HMGB1 expression level and the effect of HMGB1 expression on the characteristics of HCC. Samples from 75 HCC patients including 13 with positive hepatitis B surface antigen and 36 with hepatitis C antibody were studied. The expression of HMGB1 in paired cancer and non-cancerous tissues from patients with HCC was assessed using reverse-transcription polymerase chain reaction (RT-PCR) and western blotting. Quantitative RT-PCR data were analyzed in association with the clinicopathological factors of patients with HCC. The expression of HMGB1 mRNA in HCC was high in well-differentiated tumors, but declined as tumors dedifferentiated to moderately and poorly differentiated HCC. The levels of HMGB1 mRNA showed a negative correlation with the presence of portal invasion (p=0.005) and the rise of serum PIVKA-II (p=0.034). There was no clear correlation between HMGB1 expression and proliferation activity of HCC using Ki-67 staining. In HCC, HMGB1 expression level correlated inversely with tumor differentiation. The RAGE-HMGB1 interaction may play a greater role in the early stages of HCC tumorigenesis than during cancer development.

The down-regulation of the CYP2C19 gene is associated with aggressive tumor potential and the poorer recurrence-free survival of hepatocellular carcinoma

Project HOPE (High-tech Omics-based Patient Evaluation) began in 2014 using integrated gene expression profiling (GEP) of cancer tissues as well as diathesis of each patient who underwent an operation at our institution. The aim of this study was to clarify the association between the expression of cytochrome P450s (CYP) genes and recurrence of hepatocellular carcinoma (HCC). The present study included 92 patients. Genes with aberrant expression were selected based on a ≥10-fold difference in the expression between tumor and non-tumor tissues. The GEP analysis showed that the down-regulated genes in tumor tissue were CYP3A4 in 56 patients (61%), CYP2C8 in 44 patients (48%), CYP2C19 in 30 patients (33%), CYP2D6 in 11 patients (12%), CYP3A5 in 7 patients (8%) and CYP1B1 in 2 patients (2%). There was no patients with down-regulation of the CYP17A1 gene. A multivariate analysis revealed that the presence of microscopic portal invasion (hazard ratio [HR] 2.57, 95% confidence interval [CI] 1.30–5.05 P = 0.006), the presence of intrahepatic-metastasis (HR 3.09 95% CI 1.52–6.29 P = 0.002) and down-regulation of the CYP2C19 gene (HR 3.69 95% CI 1.83–7.46 P < 0.001) were independent predictors for the recurrence-free survival (RFS). The down-regulation of the CYP2C19 gene were correlated with the RFS in HCC.

A case of the cirrhotic patient performed living donor liver transplantation after carbon-ion radiotherapy for hepatocellular carcinoma

The patient was a 50-year-old female with an initial diagnosis of a single hepatocellular carcinoma in liver cirrhosis. The tumor was located in the posterior liver segment (S7) and measured 5cm with a rapid growth rate and portal invasion. The pre-treatment Child-Pugh (C-P) was grade A (six points). The total prescribed dose of carbon-ion radiotherapy (C-ion RT) was 60Gy (relative biological effectiveness) given in 4 fractions. Thereafter, tumor shrinkage and rapid decrease of the serum alpha-fetoprotein level were observed. At 1-year follow-up a new lesion was diagnosed in the left lobe and the underlying liver failure had worsened to C-P grade B (eight points). Thus, she was recommended to undergo living-donor liver transplantation (LDLT). The postoperative course was uneventful. At pathological examination, no viable tumor cells in the region treated with C-ion RT were detected. At the time of the last follow-up, the patient was in overall good general condition with no signs of tumor recurrence.

Expression of microRNA 638 and sex-determining region Y-box 2 in hepatocellular carcinoma: Association between clinicopathological features and prognosis.

The aim of the present study was to determine the expression profile of microRNA 638 (miR-638) and sex-determining region Y-box 2 (SOX2) in hepatocellular carcinoma (HCC), and to investigate their association with clinicopathological features and survival. Reverse transcription-quantitative polymerase chain reaction analysis was used to investigate miR-638 and SOX2 expression in 78 patients with HCC. Western blot and immunohistochemical analyses were performed in order to determine SOX2 protein expression in HCC samples. Combined with the clinical postoperative follow-up data, the expression of miR-638 and SOX2 and the association between this and the prognostic values of patients with HCC were statistically analyzed. The results of the present study confirmed that miR-638 expression in tumor tissues was significantly downregulated (P<0.001), while SOX2 expression was significantly increased, compared with healthy control tissues (P<0.05). In addition, a significant inverse correlation between miR-638 and SOX2 expression was also observed in the HCC tissues (r=-0.675; P<0.05). Clinicopathological correlation analysis demonstrated that reduced miR-638 and elevated SOX2 expression was significantly associated with the Tumor-Node-Metastasis stage and portal vascular invasion (P<0.05). However, no significant differences were observed in other clinicopathological features, including age, sex, tumor size, tumor differentiation and hepatitis status (P>0.05). Notably, follow-up analysis revealed that patients with HCC with low miR-638 expression and high SOX2 expression tended to have a significantly shorter postoperative survival time (P<0.001). It was concluded that miR-638 may serve a vital role in the occurrence and progression of HCC by regulating SOX2 expression and thus, that miR-638 and SOX2 may be critical as novel diagnostic and prognostic biomarkers for HCC.

Prognostic significance of poorly differentiated clusters and tumor budding in colorectal liver metastases.

Histomorphological features have been described as prognostic factors after resection of colorectal liver metastases (CLM). The objectives of this study were to assess the prognostic significance of tumor budding (TB) and poorly differentiated clusters (PDC) among CLM, and their association with other prognostic factors. We evaluated 229 patients who underwent a first resection of CLM. Slides stained by HE were assessed for TB, PDC, tumor border pattern, peritumoral pseudocapsule, peritumoral, and intratumoral inflammatory infiltrate. Lymphatic and portal invasion were evaluated through D2-40 and CD34 antibody. Factors independently associated with poor overall survival were nodules>4 (P = 0.002), presence of PDC G3 (P = 0.007), portal invasion (P = 0.005), and absence of tumor pseudocapsule (P = 0.006). Factors independently associated with disease-free survival included number of nodules>4 (P < 0.001), presence of PDC G3 (P = 0.005), infiltrative border (P = 0.031), portal invasion (P = 0.006), and absent/mild peritumoral inflammatory infiltrate (P = 0.002). PDC and TB were also associated with histological factors, as portal invasion (TB), peritumoral inflammatory infiltration (PDC), infiltrative border, and absence of tumor pseudocapsule (TB and PDC). This is the first study demonstrating PDC as a prognostic factor in CLM. TB was also a prognostic factor, but it was not an independent predictor of survival.

BCLC subclassification and tumour characteristics to provide prognostication of outcomes in an Asian population of locally advanced hepatocellular carcinoma treated using selective internal radiation therapy with Yttrium-90.

443 Background: Selective internal radiation therapy (SIRT) with Yttrium-90 (Y90) is preferentially used in locally advanced hepatocellular carcinoma (HCC) patients in the Barcelona clinic liver cancer (BCLC) B or C cohort. However, the BCLC B cohort has a wide heterogeneity. To address this, Bolondi et al. proposed a BCLC B subclassification system. Additionally, the BCLC C cohort is also diverse in their Child-Pugh (CP) stage and extent of portal vein thrombosis (PVT). The effect of these subclassifications on survival outcomes has not been studied in HCC patients treated using SIRT. Methods: 392 HCC patients treated using SIRT from 1st January 2008 to 17th March 2017 were analyzed. These patients were classified according to the proposed subclassification system for the BCLC B cohort, and CP stage for the BCLC C cohort, and their survival outcomes reviewed. Results: 293 patients met the study’s inclusion criteria. For B1/B2/B3/B4/ C CP-A and C CP-B, the median OS was 48.3/28.7/14.4/13.7/12.8 and 6.6 months respectively. Overall comparison between the subgroups for median OS reached statistical significance (p &lt; 0.001). The Cox proportional-hazards regression analysis found that tumour location defined as unilobar or bilobar disease significantly influenced median OS. In the BCLC C cohort, the extent of portal vein invasion significantly influenced median OS (p &lt; 0.001). For the BCLC C CP-A group, median OS for segmental/sectoral branch invasion, right and/or left portal vein invasion and main portal vein trunk invasion was 24.1, 12.8 and 6.5 months respectively. Conclusions: Bolondi et al.’s subclassification system optimizes prognostic prediction by reducing the clinical heterogeneity in BCLC B HCC patients treated using SIRT. However tumour location, unaccounted for in the proposed subclassification, is also an important prognosticator. For the BCLC C cohort CP stage, extent of PVT, and tumour location were important predictors of treatment outcomes.

Initial and maintenance dose of sorafenib in female patients with advanced hepatocellular carcinoma should be modified to maximize therapeutic effect.

497 Background: Sorafenib is the only approved first-line agent in patients with advanced HCC and patients who showed progressive disease after sorafenib therapy have an opportunity to receive regorafeib as 2nd-line agent. Therefore, it is very important to maintain sorafenib therapy until sorafenib resistance occurs. We retrospectively analyzed initial and maintenance dose especially in female patients. Methods: A total of 232 patients with advanced HCC who received sorafenib in our institution from July, 2009 until May, 2017 were enrolled. Overall survival (OS), radiological response evaluated by modified RECIST criteria and dose of sorafenib were analyzed. Results: The 232 patients included 179 males and 53 females, with a mean age of 71 ± 9 years. The majority of patients (N = 131, 56.4%) were HCV Ab positive and HBs Ag was positive in 29 patients. Eighty-six patients had extrahepatic metastasis and 50 patients showed major portal invasion defined as VP3 or VP4 by Liver Cancer Study Group of Japan. The overall survival rates of the 232 patients at 6, 12 and 18 were 72.4%, 53.6% and 41.9%, and MST was 14 months. In all patients no existence of major portal invasion, serum Albumin level ≧3.5g/dl before administration of sorafenib, and post-sorafenib anticancer therapy were independently associated with OS. The mean age of female patients was 75 years and mean body weight was 49kg. In female patients only 5 patients (9.4%) showed over 60kg. The dose reduction of sorafenib was necessary in all female patients and 26 female patients could receive post-sorafenib anticancer therapy including regorafenib. The muscle mass calculated by direct segmental multifrequency bioelectrical impedance analysis method was associated with duration of sorafenib therapy, dose reduction of sorafenib and possibility of post-sorafenib anticancer therapy. Conclusions: The modification of sorafenib dose according to sex and muscle mass is clinically important to improve overall survival in patients with advanced HCC treated with sorafenib. It is associated with duration of sorafenib therapy and the possibility for induction of other therapies after sorafenib failure.

Effectiveness of Particle Radiotherapy in Various Stages of Hepatocellular Carcinoma: A Pilot Study

Aim: We analyzed the effectiveness of external particle radiotherapy (PRT) as an alternative therapy for various stages of hepatocellular carcinoma (HCC). Methods: Eighty-three patients with HCC underwent PRT in our hospital from 2007 to 2015 (proton beam radiation in 58 patients and carbon ion radiation in 25 patients), including patients with early-stage HCC (single HCC measuring ≤3 cm, Barcelona Clinic Liver Cancer [BCLC] stage 0 or A) (group A, n = 30), those with intermediate-stage HCC (HCCs measuring ≥3 cm but inoperable or multinodular and transcatheter arterial embolization [TACE]-refractory, BCLC stage B) (group B, n = 31), and those with advanced-stage HCC (HCC with portal invasion or extrahepatic metastasis) (group C, n = 22). The median radiation dose was 72.6 GyE (range 50–74) for proton beam radiation and 45.0 GyE (range 45–52.8) for carbon beam radiation. Local control ability was defined as continuous shrinkage of the tumor size without development of new lesions for ≥6 months after PRT. Results: The rates of local control of the target tumor at 6 months, 1 year, and 2 years were 91.9, 86.3, and 84.8%, respectively. The overall survival rates at 1, 2, and 3 years were 83.0, 65.6, and 55.1%, respectively. Patients in group A showed the best survival rates (100.0% at 1 year and 85.9% at 2 years). The 1-year survival rate was poor in group C (63.6%) despite a good local tumor control rate of 74.7%. The overall survival rates were significantly better in groups A and B than in group C. Conclusions: The local control rates after PRT were sufficiently high compared to TACE or sorafenib. Thus, PRT should be adopted for patients with difficult-to-treat HCC in the early and intermediate stages.

Combined transcatheter arterial chemoembolization and radiofrequency ablation in single-session for solitary hepatocellular carcinoma larger than 7cm.

To evaluate technical feasibility and treatment results of combined transcatheter arterial chemoembolization (TACE) and radiofrequency ablation (RFA) in single-session for solitary hepatocellular carcinoma (HCC) larger than 7cm in diameter. Institutional review board approved this retrospective study. Written informed consent was obtained from all patients. Between June 2007 and July 2013, 87 patients (75 men, 12 women; mean age, 55.5 years±15.0) with solitary HCC with a mean maximum diameter of 9.5cm±2.4 (range, 7.1-13.5cm) not feasible for surgical resection underwent combined TACE and RFA in a single-session. Immediately following TACE, RFA was performed under fluoroscopy and CB-CT guidance. The primary endpoint was overall survival (OS). The secondary endpoints were technical safety and local tumor progression (LTP) rates. OS and time to progression (TTP) were analyzed with the Kaplan-Meier method. Univariate and multivariate analyses were performed to identify prognostic factors affecting OS and TTP. Technical success of combined TACE and RFA in a single-session was achieved in all patients (100%). On 1-month follow-up MRI, complete response (CR) was observed in 76 of 87 patients (87.4 %), partial response (PR) in 8 and stable disease (SD) in 3 patients. The median follow-up period was 49.5 months (interquartile range, 30.0-70.0 months). The median OS was 39 months (range, 15-86 months). The cumulative OS rates at 1, 3 and 5 years were 100%, 65.5% and 47.5%, respectively. The estimated 1, 3 and 5 year LTP rates were 0 %, 29.9% and 55.2 %, respectively. Univariate and multivariate analyses showed a tumor larger than 10.0cm (P<0.05) and presence of portal vein branch invasion (P<0.05) led to the worst prognosis. No major complications were noted. Combined use of TACE and RFA in single-session is a safe and effective option in the treatment of patients with solitary large HCC (>7cm) not amenable to surgery.

Evaluation of hepatocellular carcinoma spread via the portal system by 3-dimensional mapping

Background/PurposeThe pattern of tumor cell spread via the portal system has not been fully clarified in patients with hepatocellular carcinoma (HCC). This study aimed to evaluate the intrahepatic distribution of cancer cells derived from the main tumor by assessing histological portal invasion and/or intrahepatic metastasis (vp/im). MethodsIn 14 patients who underwent anatomical resection of primary solitary HCC ≤ 50 mm in diameter, vp/im were examined pathologically, and the sites of the lesions were reproduced on preoperative 3D-CT images. The number of vp/im and the distance of each lesion from the tumor margin were also determined. ResultsThe tumor diameter was <30 mm in seven patients (smaller HCCs) and 30–50 mm in seven patients (larger HCCs). 3D mapping revealed that almost all vp/im were localized to the peritumoral area within one cm of the tumor margin in smaller HCCs, whereas vp/im seemed to spread extensively to the feeding 3rd level portal branches in larger HCCs. The number of vp/im was greater in patients with larger HCCs than in those with smaller HCCs. Conclusions3D mapping suggested tumor cells of HCC spread via the portal vein extensively in several cases.

Down-regulation of metabolic proteins in hepatocellular carcinoma with portal vein thrombosis

BackgroundHepatocellular carcinoma is an aggressive malignancy with poor prognosis and easy to recur even the tumor is totally removed by surgery. Portal vascular invasion is one of the major factors contributing to tumor recurrence and poor prognosis. However, why hepatocellular carcinoma is easy to grow into vessels is unclear.MethodsSurgical specimens from seven hepatocellular carcinoma patients with portal vein thrombosis and seven patients without vascular invasion were utilized to analyze protein expression by proteomic technique. The proteins in the tumors were separated by 2-dimensional electrophoresis. Protein patterns in the gels were recorded as digitalized images. The differences of expression in hepatocellular carcinoma with or without portal vein thrombosis were identified by mass spectrometry.ResultsClinically, the tumors with portal vein thrombosis were larger than those without portal vein thrombosis. The median survival time for the patients with portal vein thrombosis was much shorter [4 (ranged 2.5–47) vs. 53 (ranged 33–85) months, p = 0.002]. By analyzing the protein expression in cancer tissues with or without portal vein thrombosis, the differences of protein expression were mainly metabolic enzymes. Carbonic anhydrase I, betaine–homocysteine S-methyltransferase 1, fumarate hydratase, isovaleryl-CoA dehydrogenase, short-chain specific acyl-CoA dehydrogenase and arginase-1 were all down-regulated in the tumors with portal vein thrombosis.ConclusionMetabolic enzymes and cytosol carbonic anhydrases were downregulated in hepatocellular carcinoma with portal vein thrombus. The deficiency of metabolic enzymes and cytosol carbonic anhydrases may alter cellular metabolisms and acid–base balance in hepatocellular carcinoma, which may facilitate to invade portal vein.

Routine Staging Using Chest Computed Tomography in Workup of Treatment-Naïve Hepatocellular Carcinoma Prior to Locoregional Therapy: Is There a Need?

The lung is the most common site of distal metastasis in patients with hepatocellular carcinoma (HCC), as seen in more than half of patients with extrahepatic disease. The incidence of pulmonary metastasis in all patients with HCC, however, remains low (between 4.5% to 20%). Their presence, nevertheless, contraindicates curative locoregional therapies. The role of staging chest computed tomography (CT) before locoregional treatment is not well defined. This study aimed to assess the utility of pre-treatment chest CT prior to locoregional therapy. Retrospective review of continuous cases of treatment-naïve HCC referred for locoregional therapy from 2004 to 2013 was performed. Patients with pre-treatment chest CT were evaluated for the presence of pulmonary metastases. HCC features (size, numbers, vascular invasion, nodal status and bone metastases) were recorded. Univariate analysis and multivariate logistic regression were performed for significant association. A total of 780 patients were reviewed, of which 135 received staging chest CT. Pulmonary metastases (n = 17, 12.6%), benign lesions (n = 41, 30.4%) and indeterminate lesions (n = 11, 8.1%) were detected. Among the indeterminate lesions, there were losses to follow-up (n = 2) and deaths within the study period (n = 3). All patients with pulmonary metastases were declined locoregional therapy. Univariate analysis showed statistical significant association between pulmonary metastases with the number of intrahepatic lesions (P <0.01), primary tumour size (P = 0.018) and presence of vascular invasion (P <0.01). On multivariate analysis, the number of intrahepatic lesions (OR: 9.7; 95% CI, 1.6 to 57.2; P = 0.012) and presence of both hepatic and portal venous invasions (OR: 11.8; 95% CI, 1.1 to 128.8; P = 0.043) were the 2 independent positive predictors of pulmonary metastases. The prevalence of pulmonary metastasis is low in HCC and our study does not support the routine use of staging chest CT in all treatment-naïve patients. It can, however, be considered in cases with multiple lesions or vascular invasion.