Brachytherapy with Iodine-125 seeds for treatment of portal vein-branch tumor thrombus in patients with hepatocellular carcinoma

Background There is currently no widely-accepted consensus for the management of hepatocellular carcinoma with portal vein tumor thrombus. We evaluate the safety and efficacy of ultrasound-guided percutaneous brachytherapy with iodine-125 seeds for the treatment of hepatocellular carcinoma with portal vein-branch tumor thrombus (PVBTT). Methods Sixty-nine hepatocellular carcinoma patients with PVBTT were enrolled; 34 received transarterial chemoembolization (TACE) combined with iodine-125 seeds implanted in the PVBTT; 35 were treated with TACE alone. Adverse events, objective response rate, disease control rate, progression-free survival, and overall survival were compared between the two groups. Tumor responses of PVBTT and intrahepatic tumor were correlated. Multivariate and subgroup analyses were conducted for overall survival. Results No grade 3 or 4 adverse events were recorded, and there was no difference in grade 1 or 2 adverse events between the two groups. Objective response rate and disease control rate for PVBTT were 58.9 and 91.2%, respectively, in the combined treatment group, which were significantly greater than the 5.7 and 54.3% rates, respectively, in the TACE-alone group (both p’s ≤ 0.001). Intrahepatic tumor response was positively correlated with the PVBTT response (γ = 0.782, p < 0.01). Survival outcomes were better in the combined treatment group than in the TACE-alone group: the median progression-free survival for PVBTT was 9 months versus 3 months (HR = 0.187 [95% CI: 0.101, 0.345], p < 0.001), and the median overall survival was 11 months versus 7 months (HR = 0.448 [95% CI: 0.265, 0.758], p = 0.003). Multivariate analysis revealed that application of brachytherapy and lower grade PVBTT (Vp1 + Vp2 vs. Vp3) were protective predictors of overall survival. In stratified analysis, the benefit of overall survival was more significant in the subgroup of PVBTT Vp1 + Vp2 rather than in Vp3. Conclusions The combination of iodine-125 seed brachytherapy guided by ultrasound and TACE is a convenient, safe, and effective treatment for patients with HCC and PVBTT, conferring a better survival benefit than TACE alone.

Rescue radiofrequency ablation or percutaneous ethanol injection: a strategy for failed RALPPS stage-1 in patients with cirrhosis-related hepatocellular carcinoma

Background The future liver remnant (FLR) faces a risk of poor growth in patients with cirrhosis-related hepatocellular carcinoma (HCC) after stage-1 radiofrequency-assisted ALPPS (RALPPS). The present study presents a strategy to trigger further FLR growth using supplementary radiofrequency ablation (RFA) and percutaneous ethanol injection (PEI). Methods At RALPPS stage-1 the portal vein branch was ligated, followed by intraoperative RFA creating a coagulated avascular area between the FLR and the deportalized lobes. During the interstage period, patients not achieving sufficient liver size (≥ 40%) within 2–3 weeks underwent additional percutaneous RFA/PEI of the deportalized lobes (rescue RFA/PEI) in an attempt to further stimulate FLR growth. Results Seven patients underwent rescue RFA/PEI after RALPPS stage-1. In total five RFAs and eight PEIs were applied in these patients. The kinetic growth rate (KGR) was highest the first week after RALPPS stage-1 (10%, range − 1% to 15%), and then dropped to 1.5% (0–9%) in the second week (p < 0.05). With rescue RFA/PEI applied, KGR increased significantly to 4% (2–5%) compared with that before the rescue procedures (p < 0.05). Five patients proceeded to RALPPS stage-2. Two patients failed: In one patient the FLR remained at a constant level even after four rescue PEIs. The other patient developed metastasis. Except one patient died after RALPPS stage-2, no severe complications (Clavien-Dindo ≥ IIIb) occurred among remaining six patients. Conclusions Rescue RFA/PEI may provide an alternative to trigger further growth of the FLR in patients with cirrhosis-related HCC showing insufficient FLR after RALPPS stage-1. Trial registration Retrospectively registered.

Morphometric Characteristics of the Portal Vein According to Multispiral Computed Tomography

The article discusses the variability of the linear dimensions of the portal vein depending on gender and age. In modern foreign and Russian literature, there is no uniform information about the variant portal vein anatomy. Data on the extreme forms and on the range of anatomical differences in the portal vein vary considerably. All this requires the need for a more detailed study of the morphometric characteristics of the portal vein branch. Computed tomography, in contrast to dissection on a corpse, allows an in vivo study of various morphometric characteristics of the portal vein.The aim of the study is to identify patterns of variability in the linear dimensions of the portal vein in persons of different sex and age.Material and methods. The study material consisted of multispiral computed tomography images of the abdominal cavity with contrast enhancement taken in 100 patients. The study included results of 56 men and 44 women, divided into 4 age groups: 1) first mature age, 2) second mature age, 3) the elderly, 4) the senile. The length of the portal vein was measured between the angle formed at the junction of the superior mesenteric and splenic veins and the angle formed by the branches of the portal vein at the hepatic hilum. The diameter of the vessel was measured at the midpoint of the distance between the proximal and distal points.Results. The length of the portal vein in the general sample was 66.45±8.49 mm, and its diameter was 11.84±1.93 mm. In women, the length of the portal vein was 64.37±6.6 mm, and its diameter was 11.33±1.83 mm, respectively. In men, both the length and diameter of the black vein were significantly greater than in women and constituted 68.09±9.4 mm and 12.24±1.91 mm, respectively. No statistically significant correlation of the studied parameters with age was detected.

Protective effects of pumpkin (Cucurbita pepo L.) seed oil on rat liver damage induced by chronic alcohol consumption

Pumpkin seed oil (PSO) possesses a protective potential against liver injury due to the presence of biologically active ingredients. Adult male albino rats were administrated PSO (per os, 2 mL/kg b.w./day) and a 12% ethanol solution in water, ad libitum, with an average intake of 8.14 g of ethanol/kg bw/day for 6 weeks. Congestion, hepatic central vein dilation, portal vein branch dilation, Kupffer cell hyperplasia, fatty liver changes, hepatocyte focal necrosis were observed after daily alcohol intake. All observed changes were reduced when PSO was ingested with ethanol. PSO intake itself induced discrete cellular edema, congestion and slight dilatation of the central and portal vain branches. Chronic ethanol intake elevated catalase (CAT) activity and glutathione reductase (GR) protein expression; concomitant PSO intake had no effect on CAT activity or GR protein expression. PSO intake decreased the activities of GR, glutathione-S-transferase (GST) and xanthine oxidase (XOD) in the liver, probably due to the ingestion of antioxidants. Intake of PSO and ethanol significantly decreased cytosolic superoxide dismutase (SOD1) and increased NF-?B protein expression compared to ethanol intake, suggesting that the protective effects of PSO were mediated by the NF-?B signaling pathway. Our results reveal a therapeutic potential of PSO in alcoholic liver disease.

Portal vein thrombosis in Fontan-associated liver disease

A 25-year-old patient with signs of cirrhosis on ultrasound and CT presented with portal vein thrombosis on routine follow-up examinations; retrograde hepatic wedge angiography demonstrated only the right-sided portal vein branch. Development of a portosystemic collateral vessel to the left-sided renal vein prevented signs of hypersplenism. This unique complication of portal vein thrombosis should be considered during long-term surveillance.

Hepatocellular carcinoma with tumor thrombus in portal vein branch: Transarterial chemoembolization combined with Iodine125 brachytherapy versus transarterial chemoembolization combined with sorafenib.

e15646 Background: Patients with hepatocellular carcinoma (HCC) accompanied with portal vein tumor thrombus (PVTT) have a poor prognosis. Although transarterial chemoembolization (TACE) plus sorafenib (TACE-S) could lead to an improved survival than TACE alone in HCC patients with first- or second-branch PVTT (branch PVTT), the survival was very limited. We compared the safety and efficacy of TACE plus Iodine125 brachytherapy (TACE-I) with TACE-S in patients with unresectable HCC and branch PVTT. Methods: The medical records of consecutive patients with HCC and branch PVTT who underwent TACE-I (TACE-I group) or TACE-S (TACE-S group) from January 2015 to December 2017 were retrospectively evaluated. Iodine125 seeds were implanted into the PVTT under CT guidance 3-5 days after the initial TACE. The matched peripheral dose of Iodine125 brachytherapy was set to be 120-140 Gy. Sorafenib was administered 400 mg twice daily. Outcomes of patients who underwent TACE-I, including adverse events, treatment responses, time to progression (TTP), and overall survival (OS), were compared with those of patients who underwent TACE-S. Results: One hundred and twenty patients were included in the analysis; 62 patients underwent TACE-I and 58 underwent TACE-S. The overall incidence of adverse events was significantly lower in TACE-I group than in TACE-S group (58.1% vs. 93.1%, P < .001), and incidence of grade 3 or higher adverse events also was significantly lower in TACE-I group than in TACE-S group (3.2% vs. 27.6%, P < .001). PVTT OR rates at 12 weeks (58.1% vs. 13.8%, P < .001) and at 24 weeks after the treatment (68.9 % vs. 10.9%, P < .001) in TACE-I group were higher than those in TACE-S group. TACE-I led to significantly longer TTP (median, 11.2 months vs. 6.2 months, P < .001) and OS (median, 20.9 months vs. 14.0 months, P < .001) than TACE-S. In uni- and multivariable analyses, TACE-I treatment, PVTT extent, tumor size ≥10 cm, PVTT OR at 12 weeks, and intrahepatic tumor OR at 12 weeks were independent prognostic factors for OS. Conclusions: TACE-I had less side effects and may improve OS than TACE-S for HCC patients with branch PVTT.

Protective effects of whey on rat liver damage induced by chronic alcohol intake

In 2012, alcohol liver disease resulted in 3.3 million—5.9% of global deaths. This study introduced whey protection capacity against chronic alcohol-induced liver injury. Rats were orally administered to 12% ethanol solution in water (ad libitum, average 8.14 g of ethanol/kg body weight (b.w.)/day) alone or combined with whey ( per os, 2 g/kg b.w./day). After 6-week treatment, chronic ethanol consumption induced significant histopathological liver changes: congestion, central vein dilation, hepatic portal vein branch dilation, Kupffer cells hyperplasia, fatty liver changes, and hepatocytes focal necrosis. Ethanol significantly increased liver catalase activity and glutathione reductase protein expression without significant effects on antioxidative enzymes: glutathione peroxidase (GPx), copper–zinc-containing superoxide dismutase (CuZnSOD) and manganese-containing superoxide dismutase (MnSOD). Co-treatment with whey significantly attenuated pathohistological changes induced by ethanol ingestion and increased GSH-Px and nuclear factor kappa B (NF-κB) protein expression. Our results showed positive effects of whey on liver chronically exposed to ethanol, which seem to be associated with NF-κB-GPx signaling.

Stereotactic body radiation therapy for hepatocellular carcinoma with macrovascular invasion.

428 Background: In patients with hepatocellular carcinoma (HCC), macrovascular invasion (MVI) is associated with a poor prognosis. This study describes long-term outcomes of patients with HCC and MVI treated with stereotactic body radiation therapy (SBRT). Methods: Patients with HCC and MVI who were treated with SBRT from January 2003 to December 2016 were eligible for analysis. Patients who had extrahepatic disease or who had prior liver transplant were excluded. Demographical, clinical, and treatment variables were collected, under IRB approval. The degree of vascular invasion was quantified into two categories: main portal vein branch/IVC and distal portal/hepatic vein. Results: 128 eligible pts with HCC and MVI were treated with SBRT ( > 4.5 Gy/fraction). The median age was 61 yrs (range: 39 to 90 yrs). Underlying liver disease was hepatitis B in 23%, hepatitis C in 45%, other in 20%; no known liver disease in 12%. Baseline Child-Pugh (CP) score was A5 in 67%, A6 in 20%, B7 or higher in 13%. 35% received previous liver-directed therapies. Median HCC volume was 153.7 mL (range: 3.9 to 1,813.5 mL). Median AFP was 205 ug/L (range: 1 to 171,154 ug/L). Median SBRT dose was 33.3 Gy (range: 27 to 54 Gy) in 6 fractions. Local control at 1 year was 87.4% (95% CI 78.6 to 96.1%). SBRT dose or HCC volume were not significant on univariate analysis. Median overall survival was 18.3 months (95% CI 11.2 to 21.4 months). ECOG PS > 1 (HR:1.73, p = 0.03), CP score (HR: 1.67, p = 0.04), and treatment between 2004 and 2010 (HR: 2.28, p = 0.0009) were significant on multivariable analysis, while SBRT dose, HCC volume, and degree of vascular invasion were not. In 35 patients who received sorafenib following SBRT, median survival was 38.5 months (95% CI 17.23 to 43.16 months). 4/128 pts. developed GI bleeding and 35/112 patients with liver function evaluable at baseline and 3 months had a deterioration in CP class. Conclusions: SBRT was associated with excellent outcomes for patients with HCC and MVI. Randomized phase III trials of SBRT are warranted and ongoing.

Portal Vein Tract Embolization After Percutaneous Transhepatic Biliary Interventions

Bleeding complications during percutaneous biliary intervention result from injury to the hepatic artery, hepatic vein, or portal vein. If bleeding originating from a hepatic artery branch is suspected, hepatic arteriography should be performed with and without the drainage catheter in place over a wire, and subselective embolization can be performed if a suitable target is identified. If a bleeding hepatic artery branch is not identified, bleeding from a portal vein branch is suspected. Treatment of portal vein injuries is challenging in this situation because obtaining direct percutaneous portal vein access is ill-advised. Although injuries to the hepatic artery or vein can often be treated by tract tamponade or arterial embolization, iatrogenic communication between the portal vein and biliary system can be difficult to treat effectively. This chapter presents a method to identify portal vein-to-biliary tract communications via cholangiography, with subsequent embolization via the transhepatic tract.