Anti-PD-1 antibody monotherapy versus anti-PD-1 plus anti-CTLA-4 combination therapy as first-line immunotherapy in unresectable or metastatic mucosal melanoma: a retrospective, multicenter study of 329 Japanese cases (JMAC study).

BACKGROUND: Anti-programmed cell death protein 1 (PD-1) antibody monotherapy (PD1) has led to favorable responses in advanced non-acral cutaneous melanoma among Caucasian populations; however, recent studies suggest that this therapy has limited efficacy in mucosal melanoma (MCM). Thus, advanced MCM patients are candidates for PD1 plus anti-cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) combination therapy (PD1 + CTLA4). Data on the efficacy of immunotherapy in MCM, however, are limited. We aimed to compare the efficacies of PD1 and PD1 + CTLA4 in Japanese advanced MCM patients. PATIENTS AND METHODS: We retrospectively assessed advanced MCM patients treated with PD1 or PD1 + CTLA4 at 24 Japanese institutions. Patient baseline characteristics, clinical responses (RECIST), progression-free survival (PFS), and overall survival (OS) were estimated using Kaplan-Meier analysis, and toxicity was assessed to estimate the efficacy and safety of PD1 and PD1 + CTLA4. RESULTS: Altogether, 329 patients with advanced MCM were included in this study. PD1 and PD1 + CTLA4 were used in 263 and 66 patients, respectively. Baseline characteristics were similar between both treatment groups, except for age (median age 71 versus 65 years; P < 0.001). No significant differences were observed between the PD1 and PD1 + CTLA4 groups with respect to objective response rate (26% versus 29%; P = 0.26) or PFS and OS (median PFS 5.9 months versus 6.8 months; P = 0.55, median OS 20.4 months versus 20.1 months; P = 0.55). Cox multivariate survival analysis revealed that PD1 + CTLA4 did not prolong PFS and OS (PFS: hazard ratio 0.83, 95% confidence interval 0.58-1.19, P = 0.30; OS: HR 0.89, 95% confidence interval 0.57-1.38, P = 0.59). The rate of ≥grade 3 immune-related adverse events was higher in the PD1 + CTLA4 group than in the PD1 group (53% versus 17%; P < 0.001). CONCLUSIONS: First-line PD1 + CTLA4 demonstrated comparable clinical efficacy to PD1 in Japanese MCM patients, but with a higher rate of immune-related adverse events.

Development of a dose distribution shifter to fit inside the collimator of a Boron Neutron Capture Therapy irradiation system to treat superficial tumours.

The Kansai BNCT Medical Center has a cyclotron based epithermal neutron source for clinical Boron Neutron Capture Therapy. The system accelerates a proton to an energy of 30 MeV which strikes a beryllium target producing fast neutrons which are moderated down to epithermal neutrons for BNCT use. While clinical studies in the past have shown BNCT to be highly effective for malignant melanoma of the skin, to apply BNCT for superficial lesions using this system it is necessary to shift the thermal neutron distribution so that the maximum dose occurs near the surface. A dose distribution shifter was designed to fit inside the collimator to further moderate the neutrons to increase the surface dose and reduce the dose to the underlying normal tissue. Pure polyethylene was selected, and a Monte Carlo simulation was performed to determine the optimum thickness of the polyethylene slab. Compared with the original neutron beam, the shifter increased the thermal neutron flux at the skin by approximately 4 times. The measured and simulated central axis depth distribution and off axis distribution of the thermal neutron flux were found to be in good agreement. Compared with a 2 cm thick water equivalent bolus, a 26% increase in the thermal neutron flux at the surface was obtained, which would reduce the treatment time by approximately 29%. The DDS is a safe, simple and an effective tool for the treatment of superficial tumours for BNCT if an initially fast neutron beam requires moderation to maximise the thermal neutron flux at the tissue surface.

Emotion regulation processes and middle-aged Japanese women's health.

OBJECTIVES: Emotion regulation processes, such as mindfulness, self-compassion, and acceptance, have been discussed as modifiable psychological factors related to middle-aged women's psychological distress and adjustment. Although these emotion regulation factors have been discussed separately, the question remains of which factors reflect the most variance in middle-aged women's health. Therefore, this study aimed to reveal the most relevant explanatory variable for middle-aged women's health: mindfulness, self-compassion, or acceptance. METHOD: A total of 200 middle-aged women completed self-reported measures of depressive symptoms, menopausal symptoms, physical quality of life, mental quality of life, and well-being. RESULTS: Correlation analysis showed that mindfulness, self-compassion, and acceptance were significantly associated with all variables of psychological distress and adjustment. Hierarchical multiple regression analysis revealed that acceptance significantly explained the most variance of depressive symptoms, menopausal symptoms, and mental quality of life. On the other hand, self-compassion significantly explained the greatest variance in well-being. CONCLUSIONS: These findings suggest that, for middle-aged women, 'acceptance' is an important explanatory variable of psychological distress and 'self-compassion' is an important variable of psychological adjustment.

Anti-PD1 checkpoint inhibitor therapy in acral melanoma: a multicenter study of 193 Japanese patients.

BACKGROUND: Acral melanoma (AM) is an epidemiologically and molecularly distinct entity that is underrepresented in clinical trials on immunotherapy in melanoma. We aimed to analyze the efficacy of anti-programmed cell death 1 (anti-PD-1) antibodies in advanced AM. PATIENTS AND METHODS: We retrospectively evaluated unresectable stage III or stage IV AM patients treated with an anti-PD-1 antibody in any line at 21 Japanese institutions between 2014 and 2018. The clinicobiologic characteristics, objective response rate (ORR, RECIST), survival estimated using Kaplan-Meier analysis, and toxicity (Common Terminology Criteria for Adverse Events 4.0.) were analyzed to estimate the efficacy of the anti-PD-1 antibodies. RESULTS: In total, 193 patients (nail apparatus, 70; palm and sole, 123) were included in the study. Anti-PD-1 antibody was used as first-line therapy in 143 patients (74.1%). Baseline lactate dehydrogenase (LDH) was within the normal concentration in 102 patients (52.8%). The ORR of all patients was 16.6% (complete response, 3.1%; partial response, 13.5%), and the median overall survival (OS) was 18.1 months. Normal LDH concentrations showed a significantly stronger association with better OS than abnormal concentrations (median OS 24.9 versus 10.7 months; P < 0.001). Although baseline characteristics were similar between the nail apparatus and the palm and sole groups, ORR was significantly lower in the nail apparatus group [6/70 patients (8.6%) versus 26/123 patients (21.1%); P = 0.026]. Moreover, the median OS in this group was significantly poorer (12.8 versus 22.3 months; P = 0.03). CONCLUSIONS: Anti-PD-1 antibodies have limited efficacy in AM patients. Notably, patients with nail apparatus melanoma had poorer response and survival, making nail apparatus melanoma a strong candidate for further research on the efficacy of novel combination therapies with immune checkpoint inhibitors.

A GABAergic Maf-expressing interneuron subset regulates the speed of locomotion in Drosophila.

Interneurons (INs) coordinate motoneuron activity to generate appropriate patterns of muscle contractions, providing animals with the ability to adjust their body posture and to move over a range of speeds. In Drosophila larvae several IN subtypes have been morphologically described and their function well documented. However, the general lack of molecular characterization of those INs prevents the identification of evolutionary counterparts in other animals, limiting our understanding of the principles underlying neuronal circuit organization and function. Here we characterize a restricted subset of neurons in the nerve cord expressing the Maf transcription factor Traffic Jam (TJ). We found that TJ+ neurons are highly diverse and selective activation of these different subtypes disrupts larval body posture and induces specific locomotor behaviors. Finally, we show that a small subset of TJ+ GABAergic INs, singled out by the expression of a unique transcription factors code, controls larval crawling speed.

Phase II study of ipilimumab monotherapy in Japanese patients with advanced melanoma.

PURPOSE: Ipilimumab is designed to block cytotoxic T-lymphocyte antigen-4 to augment antitumor T cell responses. In studies of predominantly Caucasian patients with advanced melanoma, ipilimumab was associated with durable response, long-term survival benefit, and a manageable safety profile. This phase II study assessed the safety of ipilimumab in Japanese patients with unresectable stage III or IV melanoma. METHODS: Patients received ipilimumab 3 mg/kg every 3 weeks for four doses. The database lock for the original analysis was in August 2014. Overall survival, progression-free survival, and data on deaths were based on an updated, follow-up analysis (database lock April 2015). RESULTS: Data are reported from 20 patients. Fifteen patients (75 %) received all four doses of ipilimumab during induction. Twelve patients (60 %) had at least one drug-related adverse event (AE), and no patients discontinued due to a drug-related AE. There were no deaths related to study drug. The most common drug-related AEs were rash (n = 7), pyrexia (n = 3), increased aspartate aminotransferase (AST; n = 3), and increased alanine aminotransferase (ALT; n = 3). Twelve patients (60 %) reported immune-related AEs (irAEs); most frequent were skin (n = 9) and liver (n = 3) disorders. Grade 3 irAEs were ALT and AST elevation (n = 2) and diabetes mellitus (n = 1). Two patients had a partial response and two had stable disease, yielding a 20 % disease control rate. Median overall survival and progression-free survival were 8.71 and 2.74 months, respectively. CONCLUSION: Ipilimumab 3 mg/kg had a manageable AE profile in this Japanese patient population with clinical outcomes similar to that in Caucasian patients. CLINICALTRIALS. GOV IDENTIFIER: NCT01990859.

Pelvic organ cross-sensitization to enhance bladder and urethral pain behaviors in rats with experimental colitis.

Neural cross-sensitization has been postulated as a mechanism underlying overlaps of chronic pelvic pain disorders such as bladder pain syndrome/interstitial cystitis (BPS/IC) and irritable bowel syndrome (IBS). Animals with experimental colitis have been used to study the underlying mechanisms for overlapped pelvic pain symptoms, and shown to exhibit bladder overactivity evidenced by frequent voiding; however, it has not directly been evaluated whether pain sensation derived from the lower urinary tract is enhanced in colitis models. Also, the cross-sensitization between the colon and urethra has not been studied previously. In the present study, we therefore investigated pain behaviors induced by nociceptive stimuli in the lower urinary tract and the involvement of C-fiber afferent pathways using rats with colitis induced by intracolonic application of 2,4,6-trinitrobenzenesulfonic acid (TNBS). In TNBS-induced colitis rats at 10 days, intravesical application of resiniferatoxin (RTx) induced a significantly greater number of episodes of both licking and freezing behaviors, which were reduced by capsaicin-sensitive C-fiber afferent desensitization. Histochemical studies using fluorescent dye tracers injected into the colon, bladder or urethra showed that dichotomized afferent neurons comprised 6.9-14.5% of L1, L6 and S1 dorsal root ganglion (DRG) neurons innervating the colon or the lower urinary tract. Transient receptor potential vanilloid 1 (TRPV1) mRNA expression was significantly increased in, the bladder, urethra and S1 DRG in colitis rats. An increase in myeloperoxidase (MPO) activity was found in the colon, but not in the bladder or urethra after intracolonic TNBS treatment. These results indicate that TNBS-induced colitis increased pain sensitivity in the bladder and urethra via activation of C-fiber afferent pathways due to colon-to-bladder and colon-to-urethral cross-sensitization, suggesting the contribution of pelvic organ cross-sensitization mechanisms to overlapped pain symptoms in BPS/IC and IBS.

Mechanisms inducing autonomic dysreflexia during urinary bladder distention in rats with spinal cord injury.

OBJECTIVES: This study investigated the mechanisms inducing autonomic dysreflexia due to enhanced bladder-to-vascular reflexes in rats with spinal cord injury (SCI). METHODS: SCI was produced by the transection of the Th4-5 spinal cord in female Sprague-Dawley rats. At 4 weeks after SCI, changes in blood pressure during graded increases in intravesical pressure (20-60 cm H2O) were measured in spinal-intact (SI) and SCI rats under urethane anesthesia. In five animals, effects of C-fiber desensitization induced by intravesical application of resiniferatoxin (RTX), a TRPV1 agonist, on the bladder-to-vascular reflex were also examined. Nerve growth factor (NGF) levels of mucosa and detrusor muscle layers of the bladder were measured by enzyme-linked immunosorbent assay. The expression levels of TRPV1 and TRPA1 channels were also examined in laser captured bladder afferent neurons obtained from L6 DRG, which were labeled by DiI injected into the bladder wall. RESULTS: In SI and SCI rats, systemic arterial blood pressure was increased in a pressure-dependent manner during increases in the intravesical pressure, with significantly higher blood pressure elevation at the intravesical pressure of 20 cm H2O in SCI rats vs SI rats. The arterial blood pressure responses to bladder distention were significantly reduced by RTX-induced desensitization of C-fiber bladder afferent pathways. SCI rats had higher NGF protein levels in the bladder and higher TRPV1 and TRPA1 mRNA levels in bladder afferent neurons compared with SI rats. CONCLUSIONS: The bladder-to-vascular reflex induced by TRPV1-expressing C-fiber afferents during bladder distention is enhanced after SCI in association with increased expression of NGF in the bladder and TRP channels in bladder afferent neurons.

Evaluation of genetic introgression from domesticated pigs into the Ryukyu wild boar population on Iriomote Island in Japan.

We evaluated genetic introgression from domesticated pigs into the Ryukyu wild boar (RWB) population on Iriomote Island based on their genetic structure and diversity. We used a combination of mitochondrial DNA D-loop region (596 bp) polymorphisms and 23 microsatellite markers. RWBs (n = 130) were collected from 18 locations on Iriomote Island and compared with 66 reference samples of European and Asian domestic pigs. We identified six distinct haplotypes, involving 22 single nucleotide polymorphisms (including one insertion) in the RWB population. The phylogenetic tree had two branches: the RWB group and domestic lineage. Fourteen of 130 RWBs (10.8%) belonged to the European domestic lineage, including 11 RWBs from the Panari Islands, northwest of Iriomote Main Island (IMI). The heterozygosity values, total number of alleles, number of effective alleles and polymorphism information content of the RWB groups were lower than those of the European domestic groups. The RWB population on IMI had a lower heterozygous deficiency index (FIS = 0.059) than did the other populations, which indicates that this population was more inbred. There was a large genetic distance (FST = 0.560) between RWBs on IMI and the Meishan populations. Structure analysis using the 23 microsatellite markers revealed that 16 RWBs had an admixture pattern between RWB and domesticated pig breeds. These results suggest that gene flow may have occurred from domestic pigs to RWBs and demonstrate that there was low genetic variation in the IMI population.

Structural basis for the altered drug sensitivities of non-small cell lung cancer-associated mutants of human epidermal growth factor receptor.

The epidermal growth factor receptor (EGFR) has an essential role in multiple signaling pathways, including cell proliferation and migration, through extracellular ligand binding and subsequent activation of its intracellular tyrosine kinase (TK) domain. The non-small cell lung cancer (NSCLC)-associated EGFR mutants, L858R and G719S, are constitutively active and oncogenic. They display sensitivity to TK inhibitors, including gefitinib and erlotinib. In contrast, the secondary mutation of the gatekeeper residue, T790M, reportedly confers inhibitor resistance on the oncogenic EGFR mutants. In this study, our biochemical analyses revealed that the introduction of the T790M mutation confers gefitinib resistance on the G719S mutant. The G719S/T790M double mutant has enhanced activity and retains high gefitinib-binding affinity. The T790M mutation increases the ATP affinity of the G719S mutant, explaining the acquired drug resistance of the double mutant. Structural analyses of the G719S/T790M double mutant, as well as the wild type and the G719S and L858R mutants, revealed that the T790M mutation stabilizes the hydrophobic spine of the active EGFR-TK conformation. The Met790 side chain of the G719S/T790M double mutant, in the apo form and gefitinib- and AMPPNP-bound forms, adopts different conformations that explain the accommodation of these ligands. In the L858R mutant structure, the active-site cleft is expanded by the repositioning of Phe723 within the P-loop. Notably, the introduction of the F723A mutation greatly enhanced the gefitinib sensitivity of the wild-type EGFR in vivo, supporting our hypothesis that the expansion of the active-site cleft results in enhanced gefitinib sensitivity. Taken together, our results provide a structural basis for the altered drug sensitivities caused by distinct NSCLC-associated EGFR mutations.

Selective blockade of apoptosis by in vivo electroporation-mediated gene transfer combined with portal infusion of plasmid DNA attenuates liver cirrhosis.

AIM: The purpose of the present study was to determine whether in vivo electroporation could achieve selective blockade of apoptosis in a rat liver cirrhosis model. METHODS: A dimethylnitrosamine (DMN)-induced rat liver cirrhosis model was used. In vivo electroporation was performed after portal vein infusion of plasmid DNA. pFas-Fc plasmid DNA was used to block the apoptotic pathway. pUC/HGF and pCAGGS/EGFP were used as positive and negative controls, respectively. Liver collagen content was evaluated by hydroxyproline assay two weeks after gene transfer. Terminal deoxynucleotidyltransferase dUTP nick end-labeling was simultaneously performed in the liver to evaluate suppression of apoptosis. Survival analysis was performed using 10 rats that received the sFas gene, 10 that received the HGF gene, and 13 that received the GFP gene. RESULTS: The apoptotic cell index in the DMN-injected liver was significantly lower in rats that received the sFas gene compared with the negative control. The collagen content of the DMN-injected liver was also lower in rats that received the sFas gene compared with the negative control. There was no significant difference in the apoptotic cell index and collagen content of rats that received the sFas and HGF genes. Ten weeks after the initiation of DMN treatment, the survival rates with the sFas, HGF, and GFP genes were 56%, 100%, and 0, respectively. CONCLUSION: Selective blockade of apoptosis by in vivo electroporation-mediated gene transfer improved the apoptotic cell index, hydroxyproline content, and survival rate. Soluble Fas gene therapy using in vivo electroporation can be a safe and efficient therapy for liver cirrhosis in rats.

The effect of adaptive iterative dose reduction on image quality in 320-detector row CT coronary angiography.

OBJECTIVE: To evaluate the effect of adaptive iterative dose reduction (AIDR) on image noise and image quality as compared with standard filtered back projection (FBP) in 320-detector row CT coronary angiography (CTCA). METHODS: 50 patients (14 females, mean age 68 ± 9 years) who underwent CTCA (100 kV or 120 kV, 400-580 mA) within a single heartbeat were enrolled. Studies were reconstructed with FBP and subsequently AIDR. Image noise, vessel contrast and contrast-to-noise ratio (CNR) in the coronary arteries were evaluated. Overall image quality for coronary arteries was assessed using a five-point scale (1, non-diagnostic; 5, excellent). RESULTS: All the examinations were performed in a single heartbeat. Image noise in the aorta was significantly lower in data sets reconstructed with AIDR than in those reconstructed with FBP (21.4 ± 3.1 HU vs 36.9 ± 4.5 HU; p<0.001). No significant differences were observed between FBP and AIDR for the mean vessel contrast (HU) in the proximal coronary arteries. Consequently, CNRs in the proximal coronary arteries were higher in the AIDR group than in the FBP group (p<0.001). The mean image quality score was improved by AIDR (3.75 ± 0.38 vs 4.24 ± 0.38; p<0.001). CONCLUSION: The use of AIDR reduces image noise and improves image quality in 320-detector row CTCA.

Reduction of the total injection volume of contrast material with a short injection duration in 64-detector row CT coronary angiography.

The ability of short injection duration of contrast material to reduce the total injection volume in 64-detector row CT coronary angiography was investigated. 45 patients were divided into three groups: (i) those receiving 0.8 ml kg(-1) of contrast material (350 mgI ml(-1)) injected with a fixed duration of 14 s (Group A; n = 16); (ii) those receiving 0.8 ml kg(-1) of contrast material injected with a fixed duration of 10 s (Group B; n = 15); and (iii) those receiving 0.7 ml kg(-1) of contrast material injected with a fixed duration of 10 s (Group C; n = 14). All patients then received 20 ml of saline. Contrast densities of the ascending aorta and proximal and distal coronary arteries were assessed where vessel diameters were >2.0 mm. The mean enhancement value in the ascending aorta for Group B was significantly higher than that for Groups A and C (p<0.05), whereas there was no significant difference between Groups A and C. All enhancement values in the coronary arteries were higher than 250 Hounsfield units. The mean enhancement value for each coronary artery in Group B was significantly higher than that for Group A (p<0.05), whereas there was no significant difference between Groups A and C. In conclusion, a short injection duration allows a reduction in the total volume of contrast material from 0.8 ml kg(-1) to 0.7 ml kg(-1) while a steady contrast enhancement is maintained in the ascending aorta and coronary arteries.

Depositional records of plutonium and (137)Cs released from Nagasaki atomic bomb in sediment of Nishiyama reservoir at Nagasaki.

In a sediment core of Nishiyama reservoir at Nagasaki city, depth profiles of (240)Pu/(239)Pu isotopic ratio, (239+240)Pu and (137)Cs activities were determined. Sediments containing plutonium and (137)Cs, which were deposited immediately after a detonation of Nagasaki atomic bomb, were identified in the core. Observed below the sediments were macroscopic charcoals, providing evidence for initial deposit of the fallout of the Nagasaki atomic bomb. This is the first entire depositional records of plutonium and (137)Cs released from the Nagasaki atomic bomb together with those from atmospheric nuclear tests.

Bronchoscopy-guided radiofrequency ablation as a potential novel therapeutic tool.

The aim of the current study was to assess the safety of bronchoscopy-guided radiofrequency ablation (RFA) and compare the effectiveness between new internal cooled-RFA and standard noncooled-RFA. Normal lungs from sheep were used (n=6). Internal cooled-RFA and standard noncooled-RFA were set to assess the most suitable RFA conditions, such as power output, flow rate and ablation time. Internal cooled-RFA was then applied under the most optimal conditions of power output and flow rate for 15, 30, 60 and 120 s, and two water temperatures either room temperature (RT) water or cold water. Criteria for the most appropriate conditions were set over 15 s of ablation time and 50 degrees C of the tip's temperature. Internal cooled-RFA had no complications. Standard noncooled-RFA was complicated with bronchial bleeding after RFA. On the basis of the histological findings, average temperature and average output, the most appropriate conditions of the cooled-RFA were a power output of 30 W and flow rate of 30 or 40 mL.min(-1). The cooled-RFA using cold water caused a smaller, more discrete, lesion compared with that using RT water. Bronchoscopy-guided internal cooled-radiofrequency ablation was an effective, safe and feasible procedure that could become a potential therapeutic tool in managing lung pathology.

Usefulness of saline pushing in reduction of contrast material dose in abdominal CT: evaluation of time-density curve for the aorta, portal vein and liver.

The effects of saline pushing after contrast material injection were investigated as well as the possibility for this technique to reduce contrast material doses in liver CT examinations. 52 patients were divided randomly into three groups: 100 ml of contrast material (300 mg I ml(-1)) only (A; n = 19), 100 ml of contrast material pushed with 50 ml of saline solution (B; n = 17), and 85 ml of contrast material pushed with 50 ml of saline solution (C; n = 16). Single-level images were obtained at the level of the main portal vein after the initiation of contrast material injection. There were no significant differences in the mean peak enhancement values (PE) and the mean time to peak enhancement values (TPE) of the aorta between the three groups. The mean PE of the portal vein in group B increased 21 HU over that in group A (p<0.05), and there was no significant difference between groups A and C. The mean PE of the liver in group B increased 7 HU over that in group A (p<0.05), and there was no significant difference between groups A and C. The mean TPE of the portal vein was shorter by 4 s (p<0.05), and that of the liver was shorter by 5 s (p<0.05) in group C compared with those in group A. In conclusion, saline pushing increases the enhancement values of the portal vein and liver, and allows a contrast material dose reduction of 15 ml without decreasing hepatic and vascular enhancement at adequate scan timing.

Plutonium isotopes derived from Nagasaki atomic bomb in the sediment of Nishiyama reservoir at Nagasaki, Japan.

The source of plutonium in sediments deposited at Nishiyama reservoir at Nagasaki was characterized by their (240)Pu/(239)Pu atom ratio. The average ratio was approximately 0.03, except in two layers. The main source of the plutonium was the Nagasaki atomic bomb. The plutonium continues to flow into the reservoir even now. The (240)Pu/(239)Pu atom ratios in two layers were higher than the average, which showed that plutonium in these layers were made of those of nuclear tests added to those of the atomic bomb.

Effect of saline pushing after contrast material injection in abdominal multidetector computed tomography with the use of different iodine concentrations.

PURPOSE: To investigate whether saline pushing after contrast material improves hepatic vascular and parenchymal enhancement, and to determine whether this technique permits decreased contrast material concentration. MATERIAL AND METHODS: 120 patients who underwent hepatic multidetector computed tomography were divided randomly into four groups (Groups A-D): receiving 100 ml of contrast material (300 mgI/ml) only (A) or with 50 ml of saline solution (B); or 100 ml of contrast material (350 mgI/ml) only (C) or with 50 ml of saline solution (D). Computed tomography (CT) values of the aorta in the arterial phase, the portal vein in the portal venous inflow phase, and the liver in the hepatic phase were measured. Visualization of the hepatic artery and the portal vein by 3D CT angiography was evaluated as well. RESULTS: Although the enhancement values of the aorta were not improved significantly with saline pushing, they continued at a high level to the latter slices with saline pushing. The enhancement value of the portal vein increased significantly and CT portography was improved with saline pushing. The enhancement value of the liver was not improved significantly using saline pushing. In a comparison between groups B and C, the enhancement values of the aorta and portal vein and the visualization of CT arteriography and portography were not statistically different. CONCLUSION: The saline pushing technique can contribute to a decrease in contrast material concentration for 3D CT arteriography and portography.