Absence Of Portal Vein Thrombosis Research Articles

Examining disparities in the receipt of curative treatment for hepatocellular cancer (HCC): A multicenter retrospective study from 2016-2023.

1582 Background: Prior studies suggested disparities in hepatocellular cancer (HCC) treatment and outcomes based on region, race, and socioeconomic status. After the implementation of the Affordable Care Act, including Michigan’s Medicaid Expansion in 2014, there’s increased interest in how these changes affect HCC care. The study examines factors influencing curative treatment receipt and existing disparities, as a step toward intervention strategies. Methods: This is a retrospective study of HCC patients at 6 community-based (4 university-affiliated) hospitals, in Michigan from Jan 2016-Sep 2023. Patients without imaging or histologic confirmation were excluded. Factors associated with receiving curative treatment were determined using both univariate and multivariable logistic regressions. Analysis was done using SPSS 28, with a p-value<0.05 indicating statistical significance. Results: Of 680 HCC patients screened, 347 were analyzed. The mean age was 70 years, and 71% were male. 78.3% were White and 16.9% Black. 53.9% had private insurance and 35% had government insurance. Primary HCC etiologies were alcohol and hepatitis C virus (HCV) infection; 74.4% had cirrhosis. Barcelona Clinic Liver Cancer (BCLC) stages varied: A (10.6%), B (28.2%), C (36.4%), and D (24.8%). 59.4% underwent curative treatment (4.6% resection, 30.3% liver-directed, 13.3% systemic, 10.1% combination), while 38.3% had best supportive care. Univariate analysis identified many factors associated with receipt of curative treatment, including race (White>Black), insurance (private>government), earlier BCLC stages, ECOG 0/1/2, Child-Pugh A, lower MELD-Na score (mean=12), <400 alpha-fetoprotein levels, and better liver function (Bilirubin, INR, albumin). Tumor characteristics, such as smaller size, absence of metastasis, and absence of portal vein thrombosis, were also associated with receipt of curative treatment. Overall, the one-year survival rate was 64% for those who had curative treatment and 35% for best supportive care. All with p-value<0.05. Multivariable analysis showed Black patients (OR: 0.21, CI: 0.051-0.881) with larger tumors (OR:0.89, CI: 0.783-1.00) and lower albumin levels (OR:3.81, CI: 1.649-8.805) at presentation were less likely to receive curative treatment than White. Black patients were also diagnosed at a younger age (66.7 vs. 71.0 years, p=0.01), more advanced BCLC stages C/D (74% vs. 57%, p=0.04) on presentation, and HCV coinfection (58% vs. 32%, p<0.001) than White. Median survival for Black and White were 757 days and 823 days, respectively (p=0.89). Conclusions: Black patients with larger tumors and low albumin are less likely to receive curative treatment than White. HCV coinfection in the Black population suggests a focus area for early intervention. Further investigation of HCC disparities across various settings is warranted.

The association between portal vein thrombosis and rebleeding after non-urgent endoscopic treatment of esophagogastric varices

Objective: To investigate the association between portal vein thrombosis and rebleeding after non-urgent endoscopic treatment of esophagogastric varices. Methods: The cirrhotic patients with esophagogastric varices diagnosed in the People's Hospital of Zhengzhou University from January 2017 to March 2023 were retrospectively collected. The patients were divided into thrombotic group and non-thrombotic group according to the presence or absence of portal vein thrombosis. The failure rate of endoscopic treatment and rebleeding rate in different periods were compared between the two groups. Receiver operating characteristic (ROC) curve was used to select the best cutoff value of gastric varicose diameter that affected total rebleeding during follow-up in both groups. The influencing factors of rebleeding within 12 and 36 months in both groups were analyzed, and the influencing factors of rebleeding within 36 months in thrombus group were further analyzed. Results: A total of 106 patients were enrolled, including 53 patients in the thrombotic group [male 37, female 16, aged 18-78 (54±13) years] and 53 patients in the non-thrombotic group [male 37, female 16, aged 27-83 (55±12) years]. The follow-up time of the two groups were (20±15) and (25±15) months, respectively. The total rebleeding rate in the thrombotic group was higher than that in the non-thrombotic group [30.2% (16/53) vs 13.2% (7/53), P˂0.05]. The rebleeding rates within 6, 12, 24 and 36 months in the thrombotic group were higher than those in the non-thrombotic group [18.9% (10/53) vs 5.7% (3/53), 18.9% (10/53) vs 5.7% (3/53), 28.3% (15/53) vs 9.4% (5/53), 30.2% (16/53) vs 11.3% (6/53), all P˂0.05]. The best cut-off value of the diameter of gastric varices that affects the total rebleeding in the two groups was 10.4 mm (10 mm was selected as the best cut-off value for the convenience of practical clinical application). Hemoglobin ˂ 85 g/L (HR=0.202, 95%CI: 0.043-0.953, P=0.043), 10 mm ˂ the diameter of GV ≤ 15 mm (HR=5.321, 95%CI: 1.161-24.390, P=0.031) and endoscopic variceal ligation combined with endoscopic tissue adhesive injection (EVL+ETAI) (HR=7.172, 95%CI: 1.910-26.930, P=0.004) were the risk factors for the first gastroesophageal variceal rebleeding within 12 months after non-urgent endoscopic treatment. EVL+ETAI (HR=3.811, 95%CI: 1.441-10.084, P=0.007) and portal vein thrombosis (HR=4.026, 95%CI: 1.483-10.932, P=0.006) were the risk factors for the first gastroesophageal variceal rebleeding within 36 months after non-urgent endoscopic treatment. The study found that, 10 mm ˂ the diameter of GV ≤ 15 mm (HR=7.503, 95%CI: 1.568-35.890, P=0.012) was the risk factor for rebleeding within 36 months in the thrombotic group. Conclusion: Portal vein thrombosis is a risk factor for rebleeding after non-urgent endoscopic treatment of esophagogastric varices.

S3154 A Case of Portal Hypertension in a Patient With JAK2 Mutation in Absence of Portal Vein Thrombosis

S3154 A Case of Portal Hypertension in a Patient With JAK2 Mutation in Absence of Portal Vein Thrombosis

Portal Vein Thrombosis in Patients with Liver Cirrhosis: What Went Wrong?

This study aimed to explore inflammatory biomarkers, stool's functional bacterial groups and their possible link to portal vein thrombosis (PVT) in patients with liver cirrhosis (LC). An observational study of 300 participants: 200 inhospital cirrhotic patients, who met inclusion criteria, equally assigned into two groups, based on the presence or absence of PVT and 100 healthy controls was carried out. The PVT group displayed significant differences related to older age, cigarettes smoking history, emergency admission, higher Child-Pugh score, metabolic related disorders and nonalcoholic fatty liver disease, as well as non-obstructive aspects, with chronic thrombi. The PVT group exhibited significant differences related to biomarkers such as tumor necrosis factor (TNF)-alpha, C-reactive protein (CRP), D-dimers (D-D), as well as gut overall dysbiosis (DB) and alteration of different functional bacterial groups of the gut microbiota. Strong positive correlations were observed between PVT severity, and TNF-alpha, CRP, D-D as well as lipopolysaccharide (LPS) positive bacteria. Esophageal varices, age and abdominal pain were independent predictors for PVT severity as well as CRP, TNF-alpha and D-D. Patients with LC and PVT displayed elevation of TNF-alpha, CRP, D-D alterations of the functional gut microbiota, as well as several morphological and clinical particularities. Although the LPS positive gut microbiota was linked to inflammatory biomarkers and PVT severity, it was not proven to be an independent predictor of the PVT severity like CRP, TNF-alpha and D-D.

Discordance among aggressiveness characteristics of hepatocellular carcinoma: Portal vein thrombosis and multifocality, related to tumor size, but not to serum alpha-fetoprotein level

Background and aimsHepatocellular carcinoma (HCC) is characterized by several clinically important prognostic parameters, including portal vein thrombosis (PVT), tumor multifocality, and serum alpha-fetoprotein (AFP) levels, in addition to maximum tumor diameter (MTD). However, associations among these parameters have not been thoroughly examined. Thus, the study aimed to investigate the correlations among these HCC characteristics in a prospectively collected database. MethodsAn 8080 HCC patient database derived from our weekly HCC council meeting was examined with respect to the correlations at baseline patient presentation between increases in MTD and changes in the percentage of patients with PVT, multifocality, or AFP levels. ResultsThe percentage of patients with PVT and with multifocality (tumor nodule numbers ≥3) significantly increased with enlarging MTD, regardless of the serum AFP level, showing the independence of PVT and multifocality on AFP. The percentage of patients with multifocality increased with enlarging MTD, in the presence or absence of PVT, showing the independence of multifocality from PVT. Therefore, discordance was found between different tumor parameters. ConclusionsA statistically significant association was found between PVT and MTD and between multifocality and MTD, all three of which are independent of AFP. PVT and multifocality appeared to be independent of each other. Although PVT and multifocality were independent of AFP, they were also augmented with high serum AFP levels. The results suggest the possibility of multiple pathways of tumor progression in the later stages of HCC development.

Novel Benchmark Values for Redo Liver Transplantation: Does the Outcome Justify the Effort?

To define benchmark cutoffs for redo liver transplantation (redo-LT). In the era of organ shortage, redo-LT is frequently discussed in terms of expected poor outcome and wasteful resources. However, there is a lack of benchmark data to reliably evaluate outcomes after redo-LT. We collected data on redo-LT between January 2010 and December 2018 from 22 high-volume transplant centers. Benchmark cases were defined as recipients with model of end stage liver disease (MELD) score ≤25, absence of portal vein thrombosis, no mechanical ventilation at the time of surgery, receiving a graft from a donor after brain death. Also, high-urgent priority and early redo-LT including those for primary nonfunction (PNF) or hepatic artery thrombosis were excluded. Benchmark cutoffs were derived from the 75th percentile of the medians of all benchmark centers. Of 1110 redo-LT, 373 (34%) cases qualified as benchmark cases. Among these cases, the rate of postoperative complications until discharge was 76%, and increased up to 87% at 1-year, respectively. One-year overall survival rate was excellent with 90%. Benchmark cutoffs included Comprehensive Complication Index CCI ® at 1-year of ≤72, and in-hospital and 1-year mortality rates of ≤13% and ≤15%, respectively. In contrast, patients who received a redo-LT for PNF showed worse outcomes with some values dramatically outside the redo-LT benchmarks. This study shows that redo-LT achieves good outcome when looking at benchmark scenarios. However, this figure changes in high-risk redo-LT, as for example in PNF. This analysis objectifies for the first-time results and efforts for redo-LT and can serve as a basis for discussion about the use of scarce resources.

Novel benchmark values for redo liver transplantation – does the outcome justify the effort?

Abstract Objective In the era of organ shortage, redo liver transplantation (reLT) is frequently discussed in terms of expected poor outcome, high cost and therefore wasteful resources. However, there is a lack of benchmark data to reliably assess outcomes after reLT. The aim of this study was to define the ideal reLT case, and to establish clinically relevant benchmark values for best achievable outcome in reLT. Methods We collected data on reLT between January 2010 and December 2018 from 22 high volume transplant centers on three continents. Benchmark cases were defined as recipients with model of end-stage liver disease score <=25, absence of portal vein thrombosis, no mechanical ventilation before surgery, receiving a graft from a donor after brain death. In addition, early reLT including those for primary non-function (PNF) were excluded. Clinically relevant endpoints covering intra- and postoperative course were selected and complications were graded by severity using the Clavien-Dindo classification and the comprehensive complication index (CCI). The benchmark cutoff for each outcome was derived from the 75th percentile of the median values of all benchmark centers, indicating the “best achievable” result. To assess the utility of the newly established benchmark values, we analyzed patients who received reLT for PNF (non-benchmark patients). Results Out of 1110 reLT 413 (37.2%) qualified as benchmark cases. Benchmark values included: Length of intensive care unit and hospital stay: <=6 and <=24 days, respectively; Clavien-Dindo grade >=3a complications and the CCI at 1 year: <=76% and <=72.2, respectively; in-hospital and 1-year mortality rates: <=14.0% and <=14.3%, respectively. The cutoffs for transplant-specific complications such as biliary complications at 1 year, outflow problems at 1 year and hepatic artery thrombosis at discharge were <=27.3%, <=2.5% and <=4.8%, respectively. Patients receiving a reLT for PNF showed mean outcome values all outside the reLT benchmark values. In-hospital mortality rate was 34.4% and the mean CCI at discharge 68.8. Conclusion ReLT remains associated with high morbidity and mortality. The availability of benchmark values for outcome parameters of reLT may serve for comparison in any future analyses of individuals, patient groups, or centers, but also in the evaluation of new therapeutic strategies and principles.

Application of Color Doppler Ultrasound in the Treatment of Vascular Diseases Around the Cardia

Objective: This paper uses color Doppler ultrasound technology to study the hemodynamic characteristics of portal hypertension and splenectomy plus pericardial vascular disruption, to understand the pathogenesis of portal hypertension, and to understand the spleen. The effects of resection and pericardial vascular dissection on portal vein and hepatic artery hemodynamics were analyzed. Methods: Nine male in our hospital’s hepatobiliary surgery from January 2017 to December 2018 were selected. The preoperative upper gastrointestinal barium meal or gastroscopy confirmed that all patients had moderate to severe esophageal and gastric fundus. The surgical method was splenectomy and pericardial vascular disconnection. Color Doppler ultrasound was performed on portal vein and hepatic arterial hemodynamics to observe the presence or absence of portal vein thrombosis. Result: Preoperative hemodynamic status of the case group: the diameter of the hepatic artery was (0.34±0.01) cm, the value is 0.34 cm; the maximum flow velocity of the hepatic artery was (64.6±5.0) cm/s, the value of 64.7 cm/s; The postoperative hemodynamic status of the case group: the diameter of the hepatic artery was (0.41±0.02) cm, the value of 0.41 cm; the maximum flow velocity of the hepatic artery was (88.5±6.1) cm/s, the value of 89.6 cm/s. Conclusion: Color Doppler ultrasound has obvious application value in the treatment of pericardial vascular diseases. 1 splenectomy and pericardial vascular disconnection can increase the flow of hepatic artery, and reduce the total blood flow into the liver after surgery. The proportion of hepatic arterial blood flow increased, and the oxygen supply to increase.

Efficacy and Safety of the Combination of Pravastatin and Sorafenib for the Treatment of Advanced Hepatocellular Carcinoma (ESTAHEP Clinical Trial).

Pravastatin has demonstrated anti-tumor activity in preclinical and clinical studies. This multicentric randomized double-blind placebo-controlled phase II study (NCT01418729) investigated the efficacy and safety of sorafenib + pravastatin combination on the overall survival (OS) and time to progression (TTP) of patients with advanced hepatocellular carcinoma (aHCC). A total of 31 patients were randomized. Median OS did not differ between both groups (12.4 months for the sorafenib + pravastatin group vs. 11.6 months for the control group). Of note, however, the radiological TTP was higher in patients treated with sorafenib + pravastatin than in the control group (9.9 months vs. 3.2 months; p = 0.008). Considering all the study population, the presence of portal vein thrombosis (PVT) was associated with worse OS, being lower in patients with PVT compared to patients without PVT (6.3 months vs. 14.8 months; p = 0.026). Data also showed a decrease in OS in patients with vascular invasion (VI) compared to patients who did not present it (6.3 months vs. 14.8 months; p = 0.041). The group of patients without dermatological events (DE) showed lower OS (6.9 months vs. 14.5 months; p = 0.049). In conclusion, combination of sorafenib + pravastatin was safe and well-tolerated, prolonging the TTP of patients with aHCC but not improving the OS compared to sorafenib + placebo. The absence of PVT and VI and the development of DE are positive prognostic factors of sorafenib response.

Can pretransplant TIPS be harmful in liver transplantation? A propensity score matching analysis

BackgroundTransjugular intrahepatic portosystemic shunt has been established as an effective treatment for complicated portal hypertension. This retrospective study investigated the effect of pretransplant transjugular intrahepatic portosystemic shunt placement on intraoperative graft hemodynamics and surgical outcomes after liver transplantation. MethodsOf 1,081 patients who underwent liver transplantation between January 2007 and June 2017 at Cleveland Clinic (OH, USA), 130 patients had transjugular intrahepatic portosystemic shunt placement before liver transplant. We performed a 1:2 propensity score matching to compare intraoperative graft hemodynamics and surgical outcomes between the transjugular intrahepatic portosystemic shunt group (n = 130) and the no-transjugular intrahepatic portosystemic shunt group (n = 260). ResultsThe transjugular intrahepatic portosystemic shunt did not increase operative time, the volume of blood transfusion, duration of hospital stay, or complication rates. Graft and patient survivals were similar between the groups. Mean intraoperative cardiac output and graft portal flow in the transjugular intrahepatic portosystemic shunt group were greater than in the no-transjugular intrahepatic portosystemic shunt group (P = .03 and P = .003, respectively). In multivariate analysis, male sex, younger age, low platelet count, absence of portal vein thrombosis, and pretransplant transjugular intrahepatic portosystemic shunt placement were independently associated with increased portal flow volume (P < or = 0.03 each). Transjugular intrahepatic portosystemic shunt malposition was observed in 17 patients (13.1%). The 1-year patient survival was 70.6% with transjugular intrahepatic portosystemic shunt malposition and 92.0% without transjugular intrahepatic portosystemic shunt malposition (P = .01). ConclusionOur findings suggest that pretransplant transjugular intrahepatic portosystemic shunt placement increases graft portal flow but does not compromise surgical outcomes after liver transplantation. Transjugular intrahepatic portosystemic shunt malposition, however, is not uncommon and may increase the complexity of transplantation.

Risk factors for portal vein thrombosis in cirrhotic patients and the influences of anticoagulation on esophagogastric variceal bleeding

Objective To investigate the associated factors and the independent risk factors for portal vein thrombosis (PVT) in cirrhotic patients and assess the influences of anticoagulation on esophagogastric variceal bleeding (EGVB) in these patients. Methods From January 2012 to December 2012, 239 cirrhotic patients were diagnosed in our hospital. According to the presence or absence of portal vein thrombosis (PVT), they were divided into thrombus group (33 cases) and control group (206 cases). According to the presence or absence of EGVB in thrombus group, they were divided into bleeding group (10 cases) and non bleeding group (23 cases). According to whether anticoagulant therapy was used in thrombus group, they were divided into anticoagulant group (10 cases) and non anticoagulant group (23 cases). The risk factors of each group and its control group were observed and compared. Results The thrombus group had a lower level of the albumin (ALB) , higher level of count of platelet (PLT), diameter of main portal vein (MPV), propotion of diabetes prevalence and history of splenectomy compared with the control group (P 0.05]. Conclusions ⑴ PLT, ALB, MPV, and a history of diabetes or splenectomy are risk factors for cirrhosis combined with PVT, and PLT and MPV are independent risk factors. ⑵ The incidence of EGVB increased with the increasing severity of esophagogastric varicose vein. The endoscopic variceal sequential treatment can contribute a significant reduction of EGVB in cirrhosis complicated by PVT. ⑶ Anticoagulant therapy may not raise the incidence of EGVB in cirrhotic patients with PVT. Key words: Liver cirrhosis; Venous thrombosis; Portal vein; Anticoagulants; Gastrointestinal hemorrhage

The prognostic factors between different viral etiologies among advanced hepatocellular carcinoma patients receiving sorafenib treatment.

Sorafenib is currently the first-line therapy for advanced hepatocellular carcinoma (aHCC) patients. However, the outcomes and prognostic factors of sorafenib therapy have not been well investigated. We aimed to investigate the pretreatment factors and outcomes among Taiwanese aHCC patients receiving sorafenib treatment. A total of 347 patients with aHCC and well-compensated liver cirrhosis (Child-Pugh A) status receiving sorafenib were consecutively enrolled from March 2013 through December 2016. Pre-treatment clinical data and viral hepatitis markers were collected and analyzed with their outcomes. The primary endpoint of the study was overall survival. The factors associated with overall survival were also investigated. The median overall survival of all the patients was 238 days (range, 9-1504 days) with a 1-year overall survival of 43.2%. Positive hepatitis B surface antigen and absence of portal vein thrombosis (PVT) were independent factors associated with better overall survival. The median duration of sorafenib therapy was 93.0 days (range, 4-1504 days). After stopping sorafenib, the median survival was 93.0 days (range, 1-1254 days). The 1-year survival after stopping sorafenib was 21.2%. In chronic hepatitis B patients, total bilirubin level was the only factor associated with overall survival. Hepatitis C antibody RNA negativity, tumor size, PVT, and white blood cell count were the independent factors associated with survival among those chronic hepatitis C patients. There were different prognostic factors stratified by viral etiologies in aHCC patients receiving sorafenib. Viral eradication increased survival in chronic hepatitis C patients.

Tu1581 – Outcomes of Trans-Jugular Intrahepatic Portosystemic Stent Shunting in the Presence Or Absence of Portal Vein Thrombosis

Tu1581 – Outcomes of Trans-Jugular Intrahepatic Portosystemic Stent Shunting in the Presence Or Absence of Portal Vein Thrombosis

Porto-sinusoidal vascular disease: proposal and description of a novel entity

Portal hypertension in the absence of portal vein thrombosis and without cirrhosis, but with mild or moderate alterations of liver histology (eg, obliterative venopathy, nodular regenerative hyperplasia, or incomplete septal cirrhosis) is being increasingly recognised. Owing to the heterogeneity of causes and histological findings, a substantial number of terms have been used to describe such idiopathic non-cirrhotic portal hypertension. Patients with the same clinical and histological features exist, but without portal hypertension at the time of diagnosis. Therefore, improved criteria are needed to define this form of liver disease. Here, we propose the term porto-sinusoidal vascular disease, since all lesions found involve the portal venules or sinusoids. The definition of this entity is based on the characteristic absence of cirrhosis with or without signs of portal hypertension or histological lesions. The presence of known causes of liver disease does not rule out porto-sinusoidal vascular disease, but specific causes of vascular liver disease are excluded from its definition. The diagnosis of porto-sinusoidal vascular disease is based on liver biopsy and might include signs specific for portal hypertension with normal or mildly elevated liver stiffness values and no complete portal vein thrombosis. We provide simple diagnostic criteria, because agreement on a uniform nomenclature is an essential requirement for future collaborative studies.

Portal vein thrombosis in patients with liver cirrhosis and its impact on early and long-term outcomes after liver transplantation.

Portal vein thrombosis (PVT) is a common complication amongst patients with liver cirrhosis. The PVT risk factors and its impact on post liver transplant outcome has not been well defined, yet. This study aimed to investigate PVT prevalence, its risk factors and influence on early and long-term outcomes after liver transplantation. Adult (>18years) patients with liver cirrhosis undergoing liver transplantation between March 2013 to March 2015 were included. Presence or absence of PVT was recorded at transplant. PVT risk factors in patients with liver cirrhosis and its impact on early and long-term outcomes were analysed. Portal vein thrombosis was diagnosed in 174 patients (17.3%). Large oesophageal varices (grade II and III vs grade I) (OR: 2.5; 95% CI: 1.46-4.26; P=0.001), diabetes mellitus before transplantation (OR: 2.03; 95% CI: 1.13-3.64; P=0.017) and cryptogenic-NASH (OR: 1.36; 95% CI: 1.08-1.72; P=0.008) as a cause of underlying liver disease were the independent risk factors for PVT. PVT (OR: 2.05; 95% CI: 1.10-3.81; P=0.023) was an independent predictor of early (within 90days) posttransplant mortality, but did not influence long-term survival. Portal vein thrombosis prevalence is high in pretransplant period. NASH related cirrhosis and diabetes mellitus might be risk factors for PVT. More intense screening of these patients for PVT is warranted.

Single administration of Selective Internal Radiation Therapy versus continuous treatment with sorafeNIB in locally advanced hepatocellular carcinoma (SIRveNIB): study protocol for a phase iii randomized controlled trial

BackgroundApproximately 20 % of hepatocellular carcinoma (HCC) patients diagnosed in the early stages may benefit from potentially curative ablative therapies such as surgical resection, transplantation or radiofrequency ablation. For patients not eligible for such options, prognosis is poor. Sorafenib and Selective Internal Radiation Therapy (SIRT) are clinically proven treatment options in patients with unresectable HCC, and this study aims to assess overall survival following either SIRT or Sorafenib therapy for locally advanced HCC patients.MethodsThis investigator-initiated, multi-centre, open-label, randomized, controlled trial will enrol 360 patients with locally advanced HCC, as defined by Barcelona Clinic Liver Cancer stage B or stage C, without distant metastases, and which is not amenable to immediate curative treatment. Exclusion criteria include previous systemic therapy, metastatic disease, complete occlusion of the main portal vein, or a Child-Pugh score of >7. Eligible patients will be randomised 1:1 and stratified by centre and presence or absence of portal vein thrombosis to receive either a single administration of SIRT using yttrium-90 resin microspheres (SIR-Spheres®, Sirtex Medical Limited, Sydney, Australia) targeted at HCC in the liver by the trans-arterial route or continuous oral Sorafenib (Nexavar®, Bayer Pharma AG, Berlin, Germany) at a dose of 400 mg twice daily until disease progression, no further response, complete regression or unacceptable toxicity. Patients for both the Sorafenib and SIRT arms will be followed-up every 4 weeks for the first 3 months and 12 weekly thereafter. Overall survival is the primary endpoint, assessed for the intention-to-treat population. Secondary endpoints are tumour response rate, time-to-tumour progression, progression free survival, quality of life and down-staging to receive potentially curative therapy.DiscussionDefinitive data comparing these two therapies will help to determine clinical practice in the large group of patients with locally advanced HCC and improve outcomes for such patients.Trial registrationClinicalTrials.gov identifier, NCT01135056, first received 24, May 2010.

Clinical parameters predictive of outcomes in sorafenib‐treated patients with advanced hepatocellular carcinoma

Sorafenib is an orally active multikinase inhibitor approved for the treatment of advanced hepatocellular carcinoma (HCC). However, clinical parameters that may predict the treatment outcomes in sorafenib-treated advanced HCC patients remains unknown. A total of 99 advanced (BCLC C) HCC patients treated with sorafenib as an initial treatment modality from January 2007 to December 2011 were retrospectively reviewed. Overall survival was the primary endpoint for the analysis. Various clinical parameters including tumour stage and adverse effects to sorafenib were analysed. Univariate and multivariate analysis were carried out to identify clinical parameters predictive of the effect of sorafenib. There were 86 males and 13 females included in this study, with a median age of 53 years. The median overall survival was 91 days. Sixty-nine patients had Child-Pugh class A cirrhosis and 30 patients had Child-Pugh class B cirrhosis. Hepatitis B virus was the predominant cause of HCC (75.8%). Noted adverse effects were hand-foot syndrome, diarrhoea, fatigue, abdominal pain, nausea and stomatitis. The presence of hand-foot syndrome and diarrhoea and the absence of portal vein thrombosis and lymph node metastasis predicted a better overall survival in the multivariate analysis. Excluding the absence of lymph node metastasis, the same parameters were associated with a longer radiological time to progression. Advanced HCC patients treated with sorafenib who experienced hand-foot syndrome and diarrhoea showed better overall survival than patients without these side effects. These side effects may be used as clinical parameters predictive of sorafenib response in patients with HCC.

Factors Affecting Survival following Chemoembolization with Doxorubicin-eluting Microspheres for Inoperable Hepatocellular Carcinoma

PurposeTo assess factors associated with better overall survival (OS) and progression-free survival (PFS) following chemoembolization with doxorubicin-eluting microspheres for inoperable hepatocellular carcinoma (HCC) Materials and MethodsData of 130 patients (104 men; median age, 62 y) with inoperable HCC who underwent successful DEB chemoembolization with 100–300 -μm LC Bead particles loaded with 50 mg doxorubicin per vial were reviewed following human research committee approval. Effects of various clinical, imaging, and response factors on OS and PFS were assessed by univariate Kaplan–Meier survival analysis. Multiple Cox regression with backward elimination was performed for terms found significant (P≤.05) on univariate analysis. ResultsThe number of DEB chemoembolization procedures per patient ranged from one to four (mean, 2±1). The median PFS and OS were 5.7 months (95% confidence interval, 4.6–7.6 mo) and 14.7 months (95% confidence interval, 12.3–19.7 mo), respectively. On multivariate Cox regression, Cancer of the Liver Italian Program (CLIP) score of 1 or lower, necrosis of more than 50%, and response or stable disease per Response Evaluation Criteria In Solid Tumors after DEB chemoembolization were associated with better PFS. CLIP score of 1 or lower, Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 1 or lower, absence of portal vein (PV) thrombosis, and necrosis greater than 50% following DEB chemoembolization were associated with better OS. ConclusionsCLIP score of 1 or lower and necrosis of more than 50% are independent variables affecting PFS and OS after DEB chemoembolization, whereas absence of PV thrombosis and ECOG PS of 1 or lower affected OS but not PFS.

A randomized study on lipiodal ethanol mixture (LEM) versus transarterial chemoembolization (TACE) for treatment of hepatocellular carcinoma (HCC): Report of a preplanned interim analysis.

e14528 Background: Transarterial injection of LEM produces long-lasting embolization of both arteriolar feeders and peribiliary plexus of HCC leading to infarction of tumor. Our group previously reported the efficacy and safety of LEM for HCC in a phase II clinical trial (Yu et al. J Vasc Interv Radiol. 2008). We initiated a randomized study to compare LEM vs. TACE in HCC. (NCT00467974). Methods: Major eligibility criteria: histologically confirmed HCC; unresectable disease without distant metastases; size ≤15cm; absence of portal vein thrombosis. Consented patients (Pts) were randomized into LEM vs. TACE stratified by tumor size and number. Pts were prospectively followed up and assessed with computed tomography (CT) every 8 weeks. The primary endpoint is overall survival (OS) and secondary endpoints include progression free survival (PFS), RECIST response rate (RR) and toxicity. An interim analysis is planned after recruitment of 70 pts. Results: From 07 to 10, total 70 pts were enrolled. 2 pts withdrew consent and were excluded from the analysis. There were no differences in baseline characteristics between LEM and TACE. Male:Female=53:15; Mean Age=64; Tumor size≤7: &gt;7cm=45:23; Child A:B=55:13. The median follow-up was 2.3 years. The OS of LEM was 25.32 months(m) vs. TACE 22.56m (p=0.38). PFS of LEM was 9.00m vs. TACE 7.8m (p=0.50). Partial response of LEM vs. TACE was 30% vs. 18% (p=0.52); disease control rate of LEM vs. TACE was 80% vs. 70% (p=0.39). Commonest G3 or above toxicities include ALT elevation (LEM 22.2% vs. TACE 9.4%); hyperbilirubinemia (LEM 19.4% vs. 9.4%); pain (LEM 0% vs. TACE 4%). Except pain, there were no differences of toxicities between LEM and TACE after procedure (p=0.04). Conclusions: At interim analysis, LEM showed comparable efficacy and toxicity profile to TACE. A trend of better OS, PFS and RR was observed in LEM arm but statistically insignificant. Further accrual and follow-up is ongoing.

Portal vein thrombosis and arterioportal shunts: effects on tumor response after chemoembolization of hepatocellular carcinoma.

To evaluate the effect of portal vein thrombosis and arterioportal shunts on local tumor response in advanced cases of unresectable hepatocellular carcinoma treated by transarterial chemoembolization. A retrospective study included 39 patients (mean age: 66.4 years, range: 45-79 years, SD: 7) with unresectable hepatocellular carcinoma (HCC) who were treated with repetitive transarterial chemoembolization (TACE) in the period between March 2006 and October 2009. The effect of portal vein thrombosis (PVT) (in 19 out of 39 patients), the presence of arterioportal shunt (APS) (in 7 out of 39), the underlying liver pathology, Child-Pugh score, initial tumor volume, number of tumors and tumor margin definition on imaging were correlated with the local tumor response after TACE. The initial and end therapy local tumor responses were evaluated according to the response evaluation criteria in solid tumors (RECIST) and magnetic resonance imaging volumetric measurements. The treatment protocols were well tolerated by all patients with no major complications. Local tumor response for all patients according to RECIST criteria were partial response in one patient (2.6%), stable disease in 34 patients (87.1%), and progressive disease in 4 patients (10.2%). The MR volumetric measurements showed that the PVT, APS, underlying liver pathology and tumor margin definition were statistically significant prognostic factors for the local tumor response (P = 0.018, P = 0.008, P = 0.034 and P = 0.001, respectively). The overall 6-, 12- and 18-mo survival rates from the initial TACE were 79.5%, 37.5% and 21%, respectively. TACE may be exploited safely for palliative tumor control in patients with advanced unresectable HCC; however, tumor response is significantly affected by the presence or absence of PVT and APS.