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Objective Mapping the long-term prognosis of Budd-Chiari syndrome (BCS) is difficult, as the prognosis is associated with changes in the liver function. The present study evaluated the time course changes in the liver function in a treatment group with percutaneous old balloon angioplasty (POBA) and a non-treatment group using the albumin-bilirubin score (ALBI) and Child-Pugh score during long-term follow-up. Methods In this retrospective study, 13 consecutive patients diagnosed with BCS at our hospital between 2007 and 2020 were categorized into a treatment group (n=8), which received POBA, and a non-treatment group (n=5). Differences in the liver function in the ALBI and Child-Pugh scores between the initial visit and one- and three-year follow-up were calculated and statistically evaluated. We investigated the changes in the liver function during the long-term follow-up, including events such as re-stenosis and re-treatment. Results While the Child-Pugh scores in the treatment group did not differ significantly between the initial visit and 1- or 3-year follow-up, the ALBI scores in this group improved significantly between the initial visit and the 1- or 3-year follow-up visit (p=0.0078 and 0.0156, respectively). The liver function according to the ALBI score in the treatment group showed gradual improvement from the initial value but gradual worsening in the non-treatment group. The ALBI scores also revealed that the liver function varies according to re-stenosis and re-POBA in BCS patients. Conclusion Unlike the Child-Pugh score, the ALBI score was able to capture changes in the liver function of BCS patients during the long-term course of BCS.

Hepatocellular carcinoma (HCC) with bile duct invasion is considered rare. A case in which a fragment of intraductal tumor dropped into the common bile duct after transarterial chemoembolization (TACE) and caused abdominal pain, and obstructive jaundice secondary to biliary obstruction is presented. This case was successfully managed by emergent endoscopic sphincterotomy. Physicians should recognize one of the complications due to TACE for HCC with intraductal tumor invasion.

Stomal varices are rare and ectopic varices defined as dilated portosystemic collateral veins located in sites other than the gastro-esophageal region. These sometimes cause recurrent bleedings and can be life-threatening. Optimal treatments have yet to be established. We report 3 cases of repetitive bleeding stomal varices in which resolution of bleeding was obtained over the medium term with minimally invasive approaches including balloon-occluded retrograde transvenous obliteration and variceal embolization by ultrasound-guided direct puncture. Rebleeding did not occur in any patients within 2-15 months of follow-up. Serious complications over Clavien-Dindo grade I were not found.

Introduction: Lenvatinib has been approved as a systemic therapy for patients with unresectable hepatocellular carcinoma (HCC). We recently experienced lenvatinib-induced tumor-related hemorrhage in patients with HCC. The full details of tumor-related hemorrhage as a lenvatinib-related adverse event have not been elucidated. Methods: This was a retrospective single-center study that enrolled consecutive patients treated with lenvatinib for unresectable HCC from April 2018 to February 2020. Results: Sixty-eight consecutive patients were enrolled in this study. Among them, 5 cases developed intraperitoneal or intratumoral hemorrhages. The patients with hemorrhage had larger tumors (maximum tumor size, 97.5 ± 46.4 and 38.2 ± 28.8 mm, respectively; p = 0.009) than the patients without hemorrhage. The dosing period of lenvatinib (median, 3 and 93 days, respectively; p < 0.001) and the survival time from initial administration of lenvatinib (median, 77 and 495 days, respectively; p < 0.001) of the patients with hemorrhage were shorter than those of the patients without hemorrhage. Especially, in 4 cases with large HCCs (maximum tumor diameter was >90 mm), tumor hemorrhage with vascular lake-like phenomenon was evident, although most tumor blood flow was suppressed. Discussion/Conclusion: It becomes clear that lenvatinib treatment brings about tumor-related hemorrhages despite rapid suppression of tumor blood flow. We speculate that lenvatinib quickly blocks the feeding circulation, resulting in tumor hemorrhage by necrosis. Clinicians should pay careful attention to the development of life-threatening hemorrhages when treating large HCCs with lenvatinib.

An 87-year-old man with hepatocellular carcinoma (HCC) presented with right-sided chest pain. Computed tomography revealed right bloody pleural effusion and an extravasation from an arterially enhanced mass in the right seventh posterior intercostal space. These findings indicated hemothorax from a rupture of HCC metastasis to the chest wall. Angiography of the intercostal arteries confirmed a hypervascular tumor, and transcatheter arterial embolization resulted in hemostasis. He was discharged with palliative care and remains alive after 9 months. Although hemothorax represents an unusual, life-threatening complication of HCC, our case suggests that transcatheter treatment can achieve hemostasis and a favorable survival even in elderly patients.

Purpose Portal venous system thrombosis is a complication of partial splenic artery embolization, and pre-treatment risk assessment is thus important. The purpose of this study was to identify the risk factors for portal venous system thrombosis after partial splenic artery embolization. Materials and methods We retrospectively analyzed 67 consecutive patients who underwent contrast-enhanced computed tomography before and after first partial splenic artery embolization between July 2007 and October 2018. As risk factors, we investigated age, sex, hematological data, liver function, steroid use, heparin use, and findings from pre- and post-treatment computed tomography. Uni- and multivariate analyses were performed to evaluate the relationship between thrombus appearance or growth and these factors. Values of p Results Partial splenic artery embolization was technically successful in all 67 patients. Nine patients showed appearance or growth of thrombus. Univariate analysis showed maximum diameter of the splenic vein before treatment (p = 0.0076), percentage of infarcted spleen (p = 0.017), and volume of infarcted spleen (p = 0.022) as significant risk factors. Multivariate analysis showed significant differences in maximum diameter of the splenic vein before treatment (p = 0.041) and percentage of infarcted spleen (p = 0.023). According to receiver operating characteristic analysis, cutoffs for maximum diameter of the splenic vein and percentage of infarcted spleen for distinguishing the appearance or growth of thrombus were 17 mm and 58.2%. Conclusion Large maximum diameter of the splenic vein before partial splenic artery embolization and high percentage of infarcted spleen after partial splenic artery embolization were identified as risk factors for portal venous system thrombosis. Level of Evidence Level 4, Case Series

Background/aim There is rapid progression and widespread use of patient-derived tumor xenografts (PDX) in translational pancreatic cancer research. This study aimed to establish a liver transplant PDX model using cryopreserved primary pancreatic ductal adenocarcinoma (PDAC). Patients and methods Primary PDAC from 10 patients were cryopreserved and transplanted into immunodeficient mice using the liver pocket method. H&E staining and immunohistochemical staining, such as Ki-67, p53, Smad4, and MUC1 were used to evaluate engraftment and histological similarities. Results Patient-derived xenograft placement was successful in six cases (60%), and 10 mice (33.3%). The Ki-67 index of primary PDAC and the cryopreservation duration were significantly related to successful engraftment (p=0.003 and p=0.007, respectively). Conclusion In this study, we succeeded in establishing a liver transplant PDX mouse model as a preclinical platform. The successful engraftment was affected by the cryopreservation duration and could be detected by the Ki-67 index.

Uterine artery embolization (UAE) is a type of noninvasive treatment for symptomatic uterine fibroids. One of the complications of UAE is fibroid expulsion. Here, we report a case of a 45-year-old woman who underwent UAE for an intramural fibroid, which resulted in fibroid expulsion. To the best of our knowledge, there are only few reports of expulsion of intramural fibroids. The process of fibroid protrusion from the myometrium into the uterine cavity was depicted on magnetic resonance imaging (MRI) in this case. We discuss the risk factors and mechanisms of fibroid expulsion after UAE.

Objective Balloon-occluded retrograde transvenous obliteration (B-RTO) for gastric varices (GV) is associated with drawbacks including a postoperative increase in portal pressure and the risk of subsequent worsening of esophageal varices (EV). Selective B-RTO that embolizes only the varices may have the potential to minimize such risks. The aim of this study is to retrospectively compare the postoperative course of patients after selective B-RTO (Group S) and conventional B-RTO (Group B). Methods One hundred four patients treated from January 2007 to April 2012 were classified into Groups S (n=5) and B (n=99). In the univariate analysis, the volume of 5% ethanolamine oleate iopamiodol (EOI) administered at baseline and the GV blood flow on endoscopic ultrasound after B-RTO were considered as covariates. The rates of GV recurrence and EV aggravation was also compared between Groups B and S. Results In Group S, the volume of 5% EOI was significantly lower (Group S vs. Group B: 14.6±5.5 vs. 28.5±16.4 mL; p=0.0012) and the rate of EV aggravation was lower in comparison to Group B (p=0.045). However, in Group S, the rate of complete eradication of GV blood flow was significantly lower (Group S vs. Group B: 0% vs. 89.9%; p

Objective Therapeutic predictors derived from the venous pressure before therapy have not been identified for Budd-Chiari syndrome (BCS). The aim of this study was to determine whether or not measuring the distal pressure or pressure gradient was useful for predicting treatment efficacy in BCS. Methods We retrospectively analyzed seven consecutive patients diagnosed with symptomatic BCS at our hospital between 2008 and 2017. Distal and proximal venous pressures at occlusion sites of BCS were measured before treatment in all cases. The pressure gradient was defined as the difference between distal and proximal venous pressures. A receiver operating characteristics (ROC) analysis was performed for venous pressures. Results Percutaneous old balloon angioplasty (POBA) was performed in seven cases, with technical success achieved in all cases (100%). No complications were encountered. The median primary patency was 574 (interquartile range, 439.5-1,056.5) days. The 1-year primary patency rate was 71.73%. Six cases (85.7%) showed resolution of symptoms, representing clinical success. The ROC analysis revealed a high distal pressure (area under the ROC curve = 0.83, cut-off=12 mmHg) as a predictor of treatment efficacy of POBA for symptomatic BCS. In addition, the pressure gradient was considered significant from a clinical perspective, because the 6 successful cases with resolution of symptoms showed a large pressure gradient (range, 8-21 mmHg) before treatment, whereas the failed case showed a relatively small pressure gradient (7 mmHg). Conclusion High distal pressure and a large pressure gradient might predict the treatment efficacy of balloon angioplasty for symptomatic BCS.

A 66-year-old man presented with liver cirrhosis due to non-alcoholic steatohepatitis and hyperammonemia. Contrast-enhanced CT showed a dilated and tortuous splenorenal shunt and a large venous aneurysm in the shunt. The venous aneurysm showed gradual enlargement over 10 years and worsening hyperammonemia, so balloon-occluded retrograde transvenous obliteration was performed. Under balloon occlusion, 5% ethanolamine oleate was injected from a microcatheter into the venous aneurysm, which was subsequently embolized with microcoils. Contrast-enhanced CT after the procedure showed complete thrombosis of the venous aneurysm. 10 months later, the venous aneurysm reduced in size, and hyperammonemia had improved.

The propensity of uveal melanoma to metastasize to the liver hinders the accrual of micro-metastatic and end-stage disease tissue samples and restricts the investigation of metastatic uveal melanoma (MUM). Pre-clinical experimental animal models of MUM can help elucidate the pathophysiology of metastatic lesions and provide a tool for designing new therapeutic approaches for MUM. Here, we present an advanced model of hepatic metastases that enables quantitatively visualizing the development of individual hepatic tumor clones and estimating their growth kinetics and colonization efficiency. Similar to clinically observed liver metastases, these models enable the assessment of growth kinetics of the liver micro-metastases and the testing of therapeutic approaches for the treatment of MUM. © 2021 Wiley Periodicals LLC. Basic Protocol 1: Experimental patient-derived xenograft mouse model of metastatic uveal melanoma Basic Protocol 2: Experimental liver micro-metastatic mouse model using splenic injection of metastatic uveal melanoma cells.

Uveal melanoma (UM) is the most common cancer of the eye in adults. Up to 50% of UM patients subsequently develop metastases, especially in the liver. It has been reported that the retinoblastoma (RB) pathway is deregulated in more than 90% of UM despite the rarity of mutations in the RB1 gene itself. CDK4/6 inhibition (CDK4/6i) is a rational strategy for treatment of UM. In this report, we investigated the antiproliferative activity of a selective CDK4/6 inhibitor on metastatic UM. A CDK4/6 inhibitor suppressed UM cell lines growth in in vitro and in vivo experiments. Hepatocyte growth factor (HGF) decreased the effect of CDK4/6 inhibitor on metastatic UM cell lines. When CDK4/6i was combined with cMET inhibitor, enhanced growth suppression was observed in metastatic UM tumors grown in human-HGF knock-in xenograft mouse models. HGF is enriched in the liver and the majority of liver metastases from UM express activated forms of cMET, therefore, signaling through cMET could contribute to the resistance mechanisms against CDK4/6i, especially in UM patients with hepatic metastasis. Together, these results provide a rationale for the use of cMET inhibitor in combination with a CDK4/6 inhibitor for the treatment of metastatic UM.

Background Colonic varices are rare among ectopic varices. A previous report demonstrated that once bleeding from colonic varices occurs, it can be fatal. Several treatments for colonic varices exist, including surgical, endoscopic, and endovascular treatments; however, management of colonic varices has not been standardized. For colonic varices, minimally invasive therapies would be desirable. Balloon-occluded retrograde transvenous obliteration (B-RTO) is one of the treatment options for colonic varices to prevent their rupture. Two cases of successful conventional B-RTO for these varices have already been reported. However, B-RTO using coil-assisted retrograde transvenous obliteration II (CARTO-II) procedure for these varices has not been reported. Case presentation A 71-year-old male patient had liver cirrhosis caused by hepatitis C virus infection. A varix was located at the ascending colon, which was coincidentally found on colonic endoscopy. Contrast-enhanced computed tomography (CT) showed that the feeder vein was the ileocolic vein and that the main draining vein was the right renal vein. Physicians concluded that treatment was required to avoid the risk of death from massive bleeding due to varix rupture. However, endoscopic and surgical treatments were difficult due to the anatomical location of the varix and the high risk of operative compilations, respectively. This ascending colonic varix was treated by balloon-occluded retrograde transvenous obliteration (B-RTO) using coil-assisted retrograde transvenous obliteration II (CARTO-II) procedure via the right renal vein. There were no complications during the procedure and no recurrences for 36 months during long-term follow-up. Conclusions CARTO-II can be one of the effective treatment techniques for ascending colonic varices.

Multidetector row computed tomography (CT) scanners perform dynamic scanning and have a wide scan range. Time-resolved three-dimensional CT (i.e., 4D CT) has recently enabled visualization of flow in neurovascular vessels. We hypothesized that 4D CT technology would be a useful and non-invasive method for visualizing the flow dynamics of the portal circulation. The aim of this study was to evaluate the technical feasibility of 4D CT for visualizing flow dynamics in the portal circulation using 320-detector-row CT. 4D CT images of 18 consecutive patients with portal circulation including gastrorenal shunt were retrospectively evaluated for their ability to generate flow dynamics of the portal circulation. Flow dynamics could be visualized by 4D CT in 68 of the 72 vessels in the portal vein, splenic vein, superior mesenteric vein, and gastrorenal shunt. Flow direction could not be identified in four vessels, all of them being superior mesenteric veins. Flow direction was recognized on 4D CT in the 68 vessels of the portal circulation. A preliminary validation study revealed that flow direction of all 19 vessels in the portal circulation had concordance between 4D CT and color Doppler ultrasound. 4D CT could visualize flow dynamics of the portal circulation. Supplementary Information The online version contains supplementary material available at 10.1186/s41747-020-00197-8.

Treatment options for metastatic osteosarcoma are limited. The present study aimed to evaluate whether radiofrequency ablation (RFA) combined with intratumoural OK-432 injection induces systemic anti-tumour immunity in rat osteosarcoma model. Eighty of 145 rats were assigned to four groups to evaluate overall survival and tumour size: control (no treatment), RFA-only, OK-432, and RFA-OK-432. The remaining 65 were assigned for histological examination. Maximum diameters of tibial and lung tumours were determined. Tumour samples were histologically examined using haematoxylin-eosin and immunohistochemical staining. Overall survival was significantly prolonged in the RFA-OK-432 group compared to the RFA-only and OK-432 groups. Only rats in the RFA-OK-432 group exhibited significant decreases in maximum tumour diameter after treatment. Ki-67-positive tumour cells in the RFA-OK-432 group were significantly stained negative on immunohistochemical analysis as opposed to those in the RFA-only and OK-432 groups. The number of CD11c+, OX-62+, CD4+, and CD8 + cells significantly increased in the RFA-OK-432 group compared to the RFA-only group. RFA with intratumoural OK-432 injection resulted in distant tumour suppression, prolonged survival, and increased dendritic cells, cytotoxic T cells, IFN-γ, and TNF-α, whereas RFA or OK-432 alone did not produce this effect. This combination may induce an abscopal effect in human osteosarcoma.

Objective Radiofrequency ablation (RFA) is less effective for large tumors > 3 cm in diameter. Various studies of combination therapy using RFA and other treatments have been conducted to improve the results of RFA treatment of lung tumors, survival was extended in a tumor model when RFA was followed by concomitant use of systemic chemotherapy. Bevacizumab (BCM) is a one of molecular target drugs. Numerous clinical trials and reports have shown BCM’s effect when used in combination with cisplatin (CDDP) in lung tumor. Our objective is to evaluate the survival of concurrent, combined use of radiofrequency ablation and BCM, and platinum-doublet chemotherapy [CDDP/paclitaxel (PTX)] in a rabbit VX2 lung tumor. Results Survival times of the RFA alone, CDDP/PTX, CDDP/PTX/BCM, RFA/CDDP/PTX, and RFA/CDDP/PTX/BCM groups were significantly prolonged compared to that of the control group (P = 0.0055, P = 0.0055, P = 0.0004, P = 0.0002, P = 0.0019, respectively). Survival of the RFA/CDDP/PTX/BCM group was not significantly prolonged compared to the RFA alone (P = 0.53) and CDDP/PTX/BCM group (P = 0.68), while showing a significantly shorter survival time than that of the RFA/CDDP/PTX group (P = 0.017). The addition to BCM with combination RFA and systemic therapy with CDDP/PTX did not have a positive effect on survival.

Background Metastatic uveal melanoma is a highly fatal disease; most patients die from their hepatic metastasis within 1 year. A major drawback in the development of new treatments for metastatic uveal melanoma is the difficulty in obtaining appropriate cell lines and the lack of appropriate animal models. Patient-derived xenograft (PDX) tumor models, bearing ectopically implanted tumors at a subcutaneous site, have been developed. However, these ectopically implanted PDX models have obstacles to translational research, including a low engraftment rate, slow tumor growth, and biological changes after multiple passages due to the different microenvironment. To overcome these limitations, we developed a new method to directly transplant biopsy specimens to the liver of immunocompromised mice. Results By using two metastatic uveal melanoma cell lines, we demonstrated that the liver provides a more suitable microenvironment for tumor growth compared to subcutaneous sites and that surgical orthotopic implantation (SOI) of tumor pieces allows the creation of a liver tumor in immunocompromised mice. Subsequently, 10 of 12 hepatic metastasis specimens from patients were successfully xenografted into the immunocompromised mice (83.3% success rate) using SOI, including 8 of 10 needle biopsy specimens (80%). Additionally, four cryopreserved PDX tumors were re-implanted to new mice and re-establishment of PDX tumors was confirmed in all four mice. The serially passaged xenograft tumors as well as the re-implanted tumors after cryopreservation were similar to the original patient tumors in histologic, genomic, and proteomic expression profiles. CT imaging was effective for detecting and monitoring PDX tumors in the liver of living mice. The expression of Ki67 in original patient tumors was a predictive factor for implanted tumor growth and the success of serial passages in PDX mice. Conclusions Surgical orthotopic implantation of hepatic metastasis from uveal melanoma is highly successful in the establishment of orthotopic PDX models, enhancing their practical utility for research applications. By using CT scan, tumor growth can be monitored, which is beneficial to evaluate treatment effects in interventional studies. Electronic supplementary material The online version of this article (doi:10.1186/s12967-017-1247-z) contains supplementary material, which is available to authorized users.

Patients with metastatic uveal melanoma usually die within 1 year of diagnosis, emphasizing an urgent need to develop new treatment strategies. The liver is the most common site of metastasis. Mitogen-activated protein kinase kinase (MEK) inhibitors improve survival in V600 BRAF–mutated cutaneous melanoma patients but have limited efficacy in patients with uveal melanoma. Our previous work showed that hepatocyte growth factor (HGF) signaling elicits resistance to MEK inhibitors in metastatic uveal melanoma. In this study, we demonstrate that expression of two BH3-only family proteins, Bim-EL and Bmf, contributes to HGF-mediated resistance to MEK inhibitors. Targeting HGF/cMET signaling with LY2875358, a neutralizing and internalizing anti-cMET bivalent antibody, and LY2801653, a dual cMET/RON inhibitor, overcomes resistance to trametinib provided by exogenous HGF and by conditioned medium from primary hepatic stellate cells. We further determined that activation of PI3Kα/γ/δ isoforms mediates the resistance to MEK inhibitors by HGF. Combination of LY2801653 with trametinib decreases AKT phosphorylation and promotes proapoptotic PARP cleavage in metastatic uveal melanoma explants. Together, our data support the notion that selectively blocking cMET signaling or PI3K isoforms in metastatic uveal melanoma may break the intrinsic resistance to MEK inhibitors provided by factors from stromal cells in the liver. Mol Cancer Ther; 16(3); 516–28. ©2017 AACR.

In recent decades, subcutaneously implanted patient-derived xenograft tumors or cultured human cell lines have been increasingly recognized as more representative models to study human cancers in immunodeficient mice than traditional established human cell lines in vitro. Recently, orthotopically implanted patient-derived tumor xenograft (PDX) models in mice have been developed to better replicate features of patient tumors. A liver orthotopic xenograft mouse model is expected to be a useful cancer research platform, providing insights into tumor biology and drug therapy. However, liver orthotopic tumor implantation is generally complicated. Here we describe our protocols for the orthotopic implantation of patient-derived liver-metastatic uveal melanoma tumors. We cultured human liver metastatic uveal melanoma cell lines into immunodeficient mice. The protocols can result in consistently high technical success rates using either a surgical orthotopic implantation technique with chunks of patient-derived uveal melanoma tumor or a needle injection technique with cultured human cell line. We also describe protocols for CT scanning to detect interior liver tumors and for re-implantation techniques using cryopreserved tumors to achieve re-engraftment. Together, these protocols provide a better platform for liver orthotopic tumor mouse models of liver metastatic uveal melanoma in translational research.

Purpose To investigate the technical feasibility, safety and clinical outcomes of coil-assisted retrograde transvenous obliteration II (CARTO-II) for gastric varices (GV). Materials and Methods Thirty-six consecutive patients who had undergone CARTO-II between June 2016 and April 2018 were included in the study. In the CARTO procedure, coil embolization of the drainage vein is performed “before” injection of the sclerosant to replace the use of balloon catheter. In the CARTO-II procedure, coil embolization of the drainage vein was performed “after” injection of the sclerosant to prevent migration of the sclerosant. CARTO-II was performed with ethanolamine oleate iopamidol, and the balloon catheter was immediately removed after coil placement. Technical and clinical success rates, number of coils used, presence or absence of severe complications, timing of the procedure, and rate of GV recurrence after the procedure were analyzed retrospectively. Results In all patients, GV sclerosis, coil placement and removal of the balloon catheter were successfully completed. The technical success rate was 100%. No patients experienced severe complications such as coil migration or pulmonary embolization. The mean number of metallic coils used per procedure was 3.36. Mean length of the procedure was 132.8 min. Contrast-enhanced computed tomography after CARTO-II confirmed complete variceal thrombosis in all cases. The recurrence rate of GV during follow-up was 2.8% (mean follow-up, 207 days). Conclusion CARTO-II was feasible and safe and could be performed relatively quickly. The number of coils used and the rate of GV recurrence were both low. CARTO-II may have an important role to play in the management of GV.

To investigate predictive factors and cutoff value of transient elastography (TE) measurements for assessing improvement in liver function after balloon-occluded retrograde transvenous obliteration (BRTO) for gastric varices (GV).Retrospective analysis was performed of 50 consecutive patients followed for3 months after BRTO, who had undergone TE before BRTO between January 2011 and February 2015. The correlation between change in liver function (total bilirubin, albumin, and prothrombin time) and baseline liver function values and liver stiffness measurement (LSM) by TE was evaluated by Pearson correlation test. Receiver operating characteristic curves were used to determine cutoff values for discriminating between patients who had improved liver function and patients who did not. The time interval from BRTO to aggravation of esophageal varices (EV) (worsening morphology, development of new varices, or variceal rupture) grouped by cutoff values was also analyzed.Serum albumin was significantly improved at 3 months after BRTO (3.57 g/dL vs 3.74 g/dL, P.001). There was a significant negative correlation between change in albumin and baseline LSM (r = -0.50, P.001). The best cutoff point for LSM was ≤ 22.9 kPa, with sensitivity and specificity of 78.4% and 69.2%, respectively, for predicting which patients would have improved albumin after BRTO. Among 33 patients, 29 (88%) patients had improved albumin. The 1-year progression rate of EV after BRTO was 13.6% in patients with LSM ≤ 22.9 kPa.The predictive factor for improvement in albumin after BRTO was lower LSM (≤ 22.9 kPa) using TE.

Objective: To determine the utility of low-dose gelatin sponge particles and 5% ethanolamine oleate iopamidol (EOI) mixture in retrograde transvenous obliteration (GERTO) for gastric varices (GV). Methods: 57 consecutive patients who underwent balloon-occluded retrograde transvenous obliteration (B-RTO) for GV were divided into three groups with Hirota’s grade by balloon-occluded retrograde transvenous venography. Hirota’s Grade 1 patients were assigned to G1 group and underwent treatment with 5% EOI. Grade ≥ 2 patients prior to August 2015 were G ≥ 2 group treated with 5% EOI, and those treated thereafter were GERTO group. The amount of EOI used per unit GV volume (EOI/GV ratio), the times to embolization and recurrence rate of GV were evaluated. Results: The EOI/GV ratio was 0.66 ± 0.19 in G1, 1.5 ± 0.8 in G ≥ 2, and 0.58 ± 0.23 in GERTO (G ≥ 2 vs GERTO, p < 0.0001). The times to embolization were 26.5 ± 10.5 min for G1, 39.2 ± 26.8 for G ≥ 2, and 21.4 ± 9.4 for GERTO (G ≥ 2 vs GERTO, p = 0.005). The recurrence rate was not significantly different in any of the groups. Conclusion: GERTO was performed in lower amount of sclerosants and in less time compared to conventional B-RTO in Hirota’s grade ≥2. Advances in knowledge: Feasibility of low-dose gelatin sponge particles and 5% EOI mixture as sclerosants for GV.

To identify the risk factors for local recurrence in hepatocellular carcinoma (HCC) patients treated with transcatheter arterial chemoembolization (TACE) with drug-eluting beads (DEB-TACE). In this retrospective study, 35 patients (27 males, 8 females; median age 73 years) with 116 tumors (median size 14 mm) treated with DEB-TACE from May 2014 to September 2018 were evaluated. Age, sex, etiology, Child–Pugh class, alpha-fetoprotein, des-gamma-carboxyprothrombin, previous conventional TACE, tumor location, tumor size, tumor number, contact with the liver surface, level of embolization, corona enhancement on CT during hepatic arteriography, vascular lakes, additional embolization with gelatin sponge particles, and supplying vessels on digital subtraction angiography (DSA) after embolization were analyzed. Univariate analysis showed that advanced age, female, large tumor, contact with the liver surface, and residual supplying vessels were significant risk factors for local recurrence (p = 0.012, 0.0013, 0.0023, 0.025, and

Uveal melanoma (UM) is a rare type of melanoma, although it is the most common primary ocular malignant tumor in adults. Nearly one-half the patients with primary UM subsequently develop systemic metastasis, preferentially to the liver. Currently, no treatment is effective for UM hepatic metastasis, and the prognosis is universally poor. The main challenge in designing a treatment strategy for UM hepatic metastasis is the lack of suitable animal models. We developed two orthotopic mouse models for human UM hepatic metastases: direct hepatic implantation model (intrahepatic dissemination model) and splenic-implantation model (hematogenous dissemination model) and investigated the tumorgenesis in the liver. A human UM cell line, established from a hepatic metastasis and nonobese diabetic severe combined immunodeficient γ mice, were used for development of in vivo tumor models. In the direct hepatic implantation model, a localized tumor developed in the liver in all cases and intrahepatic dissemination was subsequently seen in about one-half of cases. However, in the splenic implantation model, multiple hepatic metastases were observed after splenic implantation. Hepatic tumors subsequently seeded intra-abdominal metastasis; however, lung metastases were not seen. These findings are consistent with those observed in human UM hepatic metastases. These orthotopic mouse models offer useful tools to investigate the biological behavior of human UM cells in the liver.

Balloon-occluded retrograde transvenous obliteration (B-RTO) has shown great potential in controlling acute gastric variceal hemorrhage, although rebleeding related to the procedure may occur in a small percentage of patients. The purpose of this study was to identify risk factors of perioperative rebleeding and prognostic factors of postoperative survival in B-RTO performed for acute episodes of gastric variceal hemorrhage. We retrospectively analyzed 39 consecutive patients who underwent B-RTO for gastric variceal rupture at our hospital between June 2003 and May 2011. Uni- and multi-variate analyses were performed to assess risk factors for perioperative rebleeding and prognostic factors for postoperative survival. Surgical success and complete eradication of varices were achieved in 36 cases (92.3 %) and 35 cases (89.7 %), respectively. Six patients experienced rebleeding either intraoperatively (n = 3) or within 1 h after B-RTO (n = 3). Child-Pugh class C was identified as a risk factor for rebleeding on univariate (P = 0.018) and multivariate analyses (odds ratio, 6.003; P = 0.014). With a median follow-up of 23 months (range 0–106.6 months), overall survival rates at 1, 3, and 5 years were 91.7, 74.7, and 67.2 %, respectively. Multivariate analyses revealed Child-Pugh class C as a prognostic factor for survival (relative risk, 4.014; P = 0.023). Although B-RTO is generally effective in the treatment of acute gastric variceal rupture, patients classified as Child-Pugh class C have a higher risk of perioperative rebleeding and shorter survival.

To evaluate survival and distant tumor growth after radiofrequency ablation (RFA) and local OK-432 injection at a single tumor site in a rabbit model with intra- and extrahepatic VX2 tumors and to examine the effect of this combination therapy, which we termed immuno-radiofrequency ablation (immunoRFA), on systemic antitumor immunity in a rechallenge test. Our institutional animal care committee approved all experiments. VX2 tumors were implanted to three sites: two in the liver and one in the left ear. Rabbits were randomized into four groups of seven to receive control, RFA alone, OK-432 alone, and immunoRFA treatments at a single liver tumor at 1 week after implantation. Untreated liver and ear tumor volumes were measured after the treatment. As the rechallenge test, tumors were reimplanted into the right ear of rabbits, which survived the 35 weeks and were followed up without additional treatment. Statistical significance was examined by log-rank test for survival and Student’s t test for tumor volume. Survival was significantly prolonged in the immunoRFA group compared to the other three groups (P

Uveal melanoma (UM) is the most common cancer of the eye in adults. Up to 50% of UM patients subsequently develop metastases, especially in the liver, for which no effective treatment has been identified. It has been reported that the retinoblastoma (RB) pathway is deregulated in more than 90% of UM despite the rarity of mutations in the RB1 gene itself. Cyclin D1 over-expression and inactivation of p16INK4a in UM are frequently present and make the RB protein constitutively hyperphosphorylated and functionally inactivated; therefore, CDK4/6 inhibition (CDK4/6i) is a rational strategy for treatment of UM. In this report, we investigated the antiproliferative activity of a selective CDK4/6 inhibitor on metastatic UM. A CDK4/6 inhibitor induced G0-G1 arrest in all three metastatic UM cell lines and suppressed their growth in in vitro and in vivo experiments. Interestingly, hepatocyte growth factor (HGF) decreased the effect of CDK4/6 inhibitor on metastatic UM cell lines and protected the metastatic UM cells from CDK4/6 inhibitor-induced cellular senescence. When CDK4/6i was combined with MET inhibitor, enhanced growth suppression was observed in metastatic UM tumors grown in human-HGF knock-in xenograft mouse models. HGF is enriched in the liver and the majority of liver metastases from UM express activated forms of MET; therefore, signaling through MET could contribute to the resistance mechanisms against CDK4/6i, especially in UM patients with hepatic metastasis. Together, these results provide a rationale for the use of MET inhibitor in combination with a CDK4/6 inhibitor for the treatment of metastatic UM. Citation Format: Masahiro Ohara, Kengo Saito, Ken Kageyama, Mizue Terai, Hanyin Cheng, Andrew E. Aplin, Takami Sato. Dual targeting of CDK4/6 and MET in metastatic uveal melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2301.

The clinical success of cell-based therapeutic angiogenesis has been limited in diabetic patients with critical limb ischemia. We previously reported that an injectable cell scaffold (ICS), which is a nano-scaled hydroxyapatite (HAp)-coated polymer microsphere, enhances therapeutic angiogenesis. Subsequently, we developed a modified ICS for clinical use, measuring 50 μm in diameter using poly(l-lactide-co-e-caprolactone) as a biodegradable polymer, which achieved appropriately accelerated absorption in vivo. The aim of the present study was to evaluate the effectiveness of this practical ICS in diabetic hindlimb ischemia. Bone-marrow mononuclear cells (BMNCs) were intramuscularly injected, without or with a practical ICS, into the ischemic hindlimbs of mice (BMNCs or ICS+BMNCs group, respectively). Kaplan-Meier analysis demonstrated that the beneficial effects of BMNC transplantation for limb salvage after ischemic surgery were almost entirely abrogated in streptozotocin-induced diabetic mice. In contrast, injection of ICS+BMNCs revealed significant limb salvage in diabetic mice to a similar extent as in non-diabetic mice. The number of apoptotic transplanted BMNCs was 1.8-fold higher in diabetic mice 10 days after transplantation compared to non-diabetic mice, while that in the ICS+BMNCs group was markedly lower (8.3% of that in the BMNCs group) even in diabetic mice. The proangiogenic factors VEGF and FGF2, also known as antiapoptotic factors, mostly co-localized with transplanted GFP-positive BMNCs that were closely aggregated around the ICS in ischemic tissue. In conclusion, the practical ICS significantly augmented cell-based therapeutic angiogenesis even in diabetic animals, through local accumulation of proangiogenic factors and antiapoptotic effects in transplanted cells.

Purpose To evaluate whether the combination of radiofrequency (RF) ablation and local injection of the immunostimulant Mycobacterium bovis bacillus Calmette–Guerin (BCG) induces systemic antitumor immunity. Materials and Methods Japanese White rabbits with lung and auricle VX2 tumors were randomized into three groups: control (n = 8; no treatment), RF ablation only (n = 8; RF ablation to the lung tumor), and RF ablation with local BCG injection into the lung tumor (n = 8). Treatments were performed 1 week after tumor implantation. Survival was evaluated with Kaplan–Meier method and log-rank test. Weekly mean volume and specific growth rate (SGR) of auricle tumors were calculated, and comparisons were made by Mann–Whitney test. Results Median survival of control, RF-only, and RF/BCG groups were 23, 41.5, and 103.5 days, respectively. Survival was significantly prolonged in the RF-only and RF/BCG groups compared with the control group ( P = .034 and P =.003, respectively), but no significant difference was found between the RF-only and RF/BCG groups ( P = .279). Only in the RF/BCG group was mean auricle tumor volume decreased 5 weeks after implantation. No significant difference in SGR was found between the control and RF-only groups ( P = .959), but SGR in the RF/BCG group was significantly lower than in the control group ( P = .005). Conclusions The combination of RF ablation and local injection of BCG resulted in distant tumor suppression compared with the control group, whereas RF ablation alone did not produce this effect. Therefore, the combination of RF ablation and local injection of BCG may induce systemic antitumor immunity.

To examine differences in neointimal hyperplasia (NIH) after placing a self-expanding (SE) stent across size-discrepant vessels.The subjects were 6 beagles, and the target vessels were the abdominal aorta and the external iliac artery (EIA). A nitinol SE stent was placed which was normal-sized in the aorta and oversized in the EIA. Angiography and intravascular ultrasound (IVUS) were performed immediately and after 1 and 3 months; histopathologic examinations were then performed. Furthermore, the chronic outward force (COF) on the same type of stent was investigated in vitro.On IVUS, thickened intima was seen on the EIA at 1 month (5.1 ± 4.2 mm(2)) and at 3 months (7.8 ± 2.5 mm(2)). For the aorta, thickening of the intima was negligible at any time. Histopathologically, the percentage of the vessel obliterated by NIH was significantly greater on the iliac side than on the aortic side (33.2 ± 10.4 vs. 13.4 ± 4.4 %). The COF exerted when stent diameter reached that of the EIA and the aorta was 0.73 and 0.17 N/mm(2), respectively.When a non-tapered stent is placed in vessels with a large discrepancy in diameter, attention must be paid to increased NIH in the oversized side.

To evaluate whether antitumor immunity is enhanced systemically by combining radiofrequency ablation (RFA) and local injection of an immunostimulant, OK-432.Experiments were approved by the institutional animal care committee. Experimental Japanese rabbits inoculated with VX2 tumors in the lung and the auricle were randomized into four groups of eight: control (supportive care), RFA (RFA of lung tumor), OK-432 (direct injection of OK-432 into lung tumor), and combination therapy (lung RFA and direct OK-432 injection into lung tumor). All procedures were performed 1 week after implantation of VX2 tumors (week 1). In addition, a VX2 tumor rechallenge test was performed in the RFA and combination therapy groups. Survival time was evaluated by means of the Kaplan-Meier method and by using the log-rank test for intergroup comparison. Mean auricle tumor volumes were calculated every week. Specific growth rates (SGRs) were calculated and compared by using the Mann-Whitney test.The median survival times of the control, RFA, OK-432, and combination therapy groups were 23, 36.5, 46.5, and 105 days, respectively. Survival was significantly prolonged in the combination therapy group when compared with the other three groups (P.05). The mean auricle tumor volume decreased only in the combination therapy group. The mean auricle tumor volumes of the combination therapy group from week 1 to week 7 were 205, 339, 264, 227, 143, 127, and 115 mm(3). SGR in the combination therapy group became significantly smaller than those in the other three groups (P.05). In the rechallenge test, the volume of all reimplanted tumors decreased.Combining RFA with local injection of immunostimulant OK-432 may lead to indirectly activation of systemic antitumor immunity.

Metastatic uveal melanoma (UM) patients usually die within one year, emphasizing an urgent need to develop new treatment strategies. Mitogen-activated protein kinase kinase (MEK) inhibitors improve survival in cutaneous melanoma patients but have limited efficacy in UM patients. Our previous work show that HGF-cMET signaling provides resistance to MEK inhibitors in metastatic UM cells. In this study, we further investigated the mechanisms of HGF-driven resistance to MEK inhibitors in metastatic UM cells. Cellular signaling pathway analysis was carried out to determine the role of downstream Bcl2 family members in overcoming trametinib-mediated apoptosis by HGF in metastatic UM cells. A new class of clinical grade cMET antibody and inhibitor were tested for their capacity to revert the resistance to trametinib mediated by HGF and tumor microenvironment. Selective inhibitors were utilized to determine the PI3K isoform dependency of metastatic UM cells in HGF-mediated protection against trametinib in metastatic UM cells. We demonstrate that the expression of two BH3-only family proteins, Bim-EL and Bmf, is upregulated in trametinib treated cells, but returns to basal levels upon HGF treatment in these cells. Targeting HGF-cMET signaling with LY2875358, a neutralizing and internalizing anti-cMET bivalent antibody, and LY2801653, a dual cMET/RON inhibitor overcomes resistance to trametinib provided by exogenous HGF and by conditioned medium from primary hepatic stellate cells. PI3Kβ-sparing inhibitor GDC0032 effectively blocks HGF-induced AKT phosphorylation and HGF-mediated resistance in trametinib treated cells in growth assays. In conclusion, our data suggest that HGF promotes resistance to MEK inhibitors through modulating Bim-EL and Bmf expression in UM cells. Our data also support the notion that selectively blocking PI3K isoform activities or cMET signaling may delay the onset of resistance to MEK inhibitors provided by tumor microenvironment in metastatic uveal melanoma. Citation Format: Hanyin Cheng, Ken Kageyama, Timothy Purwin, Connie Liao, Mizue Terai, Takami Sato, Andrew Aplin. Co-targeting HGF-cMET signaling with MEK inhibitors in metastatic uveal melanoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4664.

The prognosis of metastatic uveal melanoma (UM) is extremely poor. Approximately 90% of patients with metastatic UM die from hepatic metastasis. Controlling hepatic metastases has been a rational approach to extend survival. This raises an urgent need to develop a novel mouse model for further investigation. Patient-derived tumor xenograft (PDX) mouse model provides potential benefit through a personalized medicine approach. This model may be useful for predictions of clinical outcomes, drug efficacy and biomarker identification. Most PDX models, including UM PDX models, are made by ectopic subcutaneous implantation. Subcutaneous PDX models have some obstacles in translational research due to differences in anatomic microenvironment from tumor origin, low engraftment rate, and slow tumor growth. Our goal was to develop an orthotopic PDX model of liver metastatic UM which would overcome these difficulties. In developing our model, we first compared the differences in growth in a liver with a subcutaneous site using two UM cell lines (UM001 and UM004) in NSG mice, to ascertain which site is a more suitable tumor microenvironment. Second, we investigated the feasibility of surgical orthotopic implantation (SOI) of tumor masses to develop a practical liver tumor xenograft mouse model with UM cell lines in 20 mice. Finally, we tried to establish an orthotopic PDX mouse model of liver metastatic UM in 5 mice. We also evaluated concordance for tumor characteristics between pre-implant and post-implant tumors. Our results showed that the liver was a more suitable microenvironment to grow the two UM cell lines compared to the subcutaneous site. UM001 engrafted in the liver, whereas it did not engraft in the subcutaneous site. UM004 displayed more rapid growth in the liver compared to the subcutaneous site. A new SOI of tumor chunk was created to develop a practical liver tumor xenograft model. Donor tumors, which were generated in the liver after injecting UM cell lines, were surgically transplanted into the liver of recipient mice. The new SOI was successfully performed in all 20 mice without adverse events. Recipient mice formed tumors in the liver after SOI. For comparison, the tumor chunks of UM cell lines were also implanted subcutaneously, in which we were able to show that the growth was more rapid in the liver. Both donor and recipient tumors had matching tumor characteristics in histological and proteomic analysis. We established an orthotopic PDX mouse model of liver metastatic UM with a new SOI method. The success rate of engraftment was 80% (4/5) within 6 months. Tumor characteristics of both patient's original tumors and xenograft mouse tumors matched in histological, genomic and proteomic analysis. This new SOI method can establish a patient-derived liver metastatic uveal melanoma xenograft model in NSG mouse at a highly successful rate. Citation Format: Ken Kageyama, Masahiro Ohara, Kengo Saito, Shinji Ozaki, Mizue Terai, Andrew E. Aplin, Michael J. Mastrangelo, Takami Sato. Feasibility of surgical orthotopic implantation for establishment of patient-derived liver metastatic uveal melanoma xenograft model in NSG mouse. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 623.

Two cases of gastric varices were treated by balloon-occluded retrograde transvenous obliteration via the pericardiophrenic vein at our hospital, and both were successful. One case developed left hydrothorax. Gastric varices did not bled and esophageal varices were not aggravated in both cases for 24-30 months thereafter. These outcomes indicate the feasibility of balloon-occluded retrograde transvenous obliteration via the pericardiophrenic vein.

The purpose of this study was to characterize the imaging spectrum of benign notochordal cell tumors (BNCTs) and chondromas and to determine if this helped in differentiating BNCTs from chordomas.Thirty-eight patients pathologically diagnosed with chordomas were reviewed and ultimately diagnosed to have five BNCTs and 33 chordomas. The following radiologic findings were reevaluated by two radiologists by consensus: extraosseous extension, osseous change on CT or conventional tomography, T2-weighted MR signal intensity, T2-weighted signal homogeneity, and contrast-enhanced T1-weighted MR signal intensity. Fisher's exact test was performed to determine statistical significance.Our study yielded five results. First, four of five BNCTs (80%) were intraosseous, whereas 31 of 33 chordomas (94%) were both intra- and extraosseous (p0.0001). Second, all BNCTs showed mild osteosclerosis without bone destruction; all chordomas showed variable osteolysis (p = 0.0092). Third, all BNCTs and 28 of 33 chordomas (85%) showed hyperintensity on T2-weighted images (p0.05). Fourth, four of five BNCTs (80%) and 27 of 33 chordomas (82%) were heterogeneous on T2-weighted images (p0.05). Fifth, no BNCTs enhanced, whereas all chordomas variably enhanced (p0.0001).Radiologic studies may allow distinction of BNCTs from chordomas.

The aim of this study was to examine the actual temperature during lung radiofrequency ablation (RFA) and pathological changes due to thermal damage in the pleural tissue of the chest wall in a rabbit model.The study was conducted on 14 Japanese white rabbits with normal lungs. Under computed tomography guidance, the electrode with a 2-cm expandable tip was inserted into the lower lung lobe and positioned so the tip of the needle touched the thoracic wall upon expansion. A thermometer was inserted 5 mm lateral to the point of electrode insertion. RFA was applied at 30 W (n = 7) or 15 W (n = 7) until maximum impedance (i.e., roll-off) or for 4 min at the longest. Local tissue temperature was recorded. The chest wall was dissected out immediately after RFA for histological examination.The mean (+/- SD) maximum tissue temperature at 30 W (86.7 degrees +/- 10.0 degrees C) was not significantly different from that at 15 W (82.1 degrees +/- 6.2 degrees C). The mean ablation time to increase tissue temperature to 50 degrees , 60 degrees , and 70 degrees C was faster at 30 W (13, 27, and 49 s, respectively) than at 15 W (13, 56, and 115 s, respectively) (P0.05). Histological examination showed pleural sloughing at the point of needle insertion and ring-shaped thermal injury in the chest wall.With rabbit lung RFA near the chest wall, ablation immediately below the pleura resulted in a rise of local tissue temperature to80 degrees C and thermal injury.

Background: Circulating tumor cells (CTCs) represent a surrogate biomarker for hematogenous metastases. The detection of CTCs has gained increasing interest for prediction of clinical outcome. However, it remains to be determined whether uveal melanoma cells circulating in a peripheral vein predict systemic recurrence and poorer overall prognosis. Uveal melanoma, the most common primary cancer of the eye in adults, is unique in that the uveal tract is devoid of lymphatics. Since systemic recurrence develops exclusively via hematogenous spread, patients with uveal melanomas present a special opportunity to explore the prognostic potential of CTCs. Although the lung is the first organ through which venous drainage from the affected eye passes and indeed the only organ through which all venous blood must pass, 80-95% of systemic metastases are found first in the liver without development of lung metastases. To address these issues, we investigated the numbers of CTCs in paired arterial (femoral) and venous (antecubital) blood specimens obtained from uveal melanoma patients with hepatic metastases. Methods: CTCs in blood specimens were measured in 17 uveal melanoma patients with multiple hepatic metastases, including 10 patients with liver-only metastases and 7 patients with hepatic and extra-hepatic metastases. Peripheral arterial and venous blood specimens were collected at the same time prior to liver directed treatment. CTCs were analyzed using CellTracks Circulating melanoma Cell Kit by CellSearch System. The clinical information and sources of blood specimens were blinded when CTCs were analyzed. Result: CTCs were detectable from all 17 arterial blood specimens (100%) (median 5, range 1 to 168). In contrast, much smaller numbers of CTCs were detectable in 52.9% (9/17) of venous blood specimens (median 1, range 0 to 8) from the same patients. In terms of degree of tumor burden, patients who have hepatic as well as extra-hepatic metastasis showed higher numbers of arterial CTCs (median 12, range 5 to 168), compared to patients who have liver-only metastasis (median 4, range 1 to 11). More importantly, there is no significant correlation between numbers of arterial CTCs and the degree of tumor volume in the liver in patients who have liver-only metastases. Conclusions: Using this technology, the detection of uveal melanoma cells in peripheral blood is feasible. Peripheral capillary beds effectively filter CTCs from venous blood; thus venous blood might not be the best source for measurement of CTCs in patients with metastatic uveal melanoma. The paucity of clinically evident non-hepatic metastases despite the effective filtration by peripheral capillary beds remains unexplained and may be a demonstration of the “seed and soil” hypothesis. CTCs are a non-invasive source of uveal melanoma cells for evaluating tumor biology. Further investigation is warranted. Citation Format: Mizue Terai, Zhaomei Mu, David Eschelman, Carin Gonsalves, Ken Kageyama, Michael J. Mastrangelo, Marlana Orloff, Ryan Weight, Massimo Cristofanilli, Takami Sato. Detection of circulating melanoma cells in paired arterial and venous specimens from uveal melanoma patients with hepatic metastatic. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 384. doi:10.1158/1538-7445.AM2015-384

Background CTCs provide prognostic information and their application is under investigation in multiple tumor types. Of the multiple variables inherent in any such process, none is more important to outcome than the appropriateness of the sample source. To address this question, we investigated CTCs in paired peripheral venous and arterial blood specimens obtained from stage IV uveal melanoma patients. Methods Blood specimens were obtained from both common femoral arteries and antecubital veins in 17 uveal melanoma patients with multiple hepatic metastases for CTC measurements. Finding CTCs were detectable with greater frequency (100%) and in larger numbers (median 5, range 1 to 168) in all arterial blood specimens than in venous samples (52.9%; median 1, range 0 to 8). Patients with hepatic as well as extra-hepatic metastasis showed higher number of arterial CTCs, compared to patients with liver-only metastasis (p=0.003). There was no significant association between the number of arterial CTCs and the tumor burden within the liver in patients who had liver-only metastases. Interpretation Our data indicate that arterial blood specimens might be a better source of circulating uveal melanoma cells. Although less conveniently processed, perhaps arterial blood should be evaluated as sample source for measurement of CTCs.