Efficacy and safety of sorafenib plus vitamin K treatment for hepatocellular carcinoma: A phase II, randomized study.

The previous retrospective study suggested that dosing vitamin K may enhance the anticancer action of sorafenib against hepatocellular carcinoma. To confirm it, we performed a phase II, randomized, open-label study. Patients with hepatocellular carcinoma were randomly assigned to receive sorafenib + vitamin K2 (menatetrenone, 45 mg daily, orally) or sorafenib only. Between 1 May 2012 and 1 May 2016, 68 patients were screened. Forty-four eligible patients were assigned at a 1:1 ratio to each cohort. The objective response rate in the vitamin K-dosed group was significantly higher than that in the sorafenib only group (27.3% vs 4.5%, respectively; p = 0.039). The median time of progression-free survival was significantly extended in the vitamin K-dosed group compared with the sorafenib only group (4.9 months vs 2.7 months, respectively; hazard ratio (HR), 0.44; 95% confidence interval (CI): 0.21-0.89; p = 0.018). Although there was no significant difference between the two groups in the median time of overall survival, patients in the vitamin K-dosed group with a complete response or partial response achieved a significantly extended median time of overall survival compared with the other patients in the vitamin K-dosed group or the patients in the sorafenib only group (26.1 months vs 9.0 months; HR, 0.34; 95% CI: 0.11-0.95; p = 0.046 or 11.5 months; HR, 0.16; 95% CI: 0.034-0.70; p = 0.006, respectively). Dosing vitamin K could augment the anticancer action of sorafenib against HCC.

Clinical Impact of Vitamin K Dosing on Sorafenib Treatment for Hepatocellular Carcinoma.

Background: Some researchers have suggested that vitamin K enhances the antitumor effect of sorafenib for hepatocellular carcinoma (HCC) in vitro and in vivo. In this study, we examined the clinical impact of vitamin K dosing for sorafenib treatment. Methods: Twenty-nine out of 65 patients treated with sorafenib for HCC were simultaneously dosed with vitamin K. We retrospectively investigated progression-free survival (PFS) and overall survival (OS) in the vitamin K-dosed group and sorafenib alone group. We also examined the changes in serum des-γ-carboxy prothrombin (DCP) levels, which vitamin K is involved with. Results: The median PFS was prolonged in the sorafenib + vitamin K group compared with the sorafenib alone group (6.0 months and 2.0 months, respectively; P<0.001, hazard ratio〔HR〕: 0.25). The median OS was also significantly extended (12.5 months vs. 10.0 months; P=0.009, HR: 0.47). Despite suppressed tumor growth, serum DCP levels had increased in cases of disease-controlled patients in the sorafenib alone group 8 weeks after the beginning of treatment, (2.28±0.91 to 2.64±1.03, P= 0.048). In contrast, the serum DCP levels of the sorafenib + vitamin K group had declined both in patients with controlled disease and in patients with progressive disease (1.97±0.57 to 1.29±0.28, P=0.002 and 2.90±1.32 to 1.78±0.53, P=0.034, respectively). Conclusions: To the best of our knowledge, this is the first clinical report showing enhanced antitumor action of sorafenib by vitamin K. Our clinical findings suggest that vitamin K may have the synergistic effect by suppressing production of DCP, a tumor growth and angiogenesis factor.

Therapeutic sclerosis of a small liver cyst that caused obstructive jaundice.

The authors describe the case of a small liver cyst (2 cm in diameter) causing obstructive jaundice that was treated with aspiration and therapeutic sclerosis. The procedure was performed with use of a microcatheter and wire system to access the cyst, which was injected with minocycline hydrochloride. At present, 9 months after treatment, the levels of hepatobiliary enzymes are within normal ranges, and no sign of cyst regrowth has been detected on imaging.

[Case of giant renal arteriovenous fistula in a long-term hemodialysis patient].

We report a case of giant left renal arteriovenous fistula (AVF). A 36-year-old man was diagnosed with chronic glomerulonephritis (CGN) by biopsy on the left kidney 11 years ago. He had been receiving hemodialysis for end-stage kidney disease from CGN since 10 years ago. A left renal cystic lesion was found and he was referred to our department for examination and treatment. He was diagnosed as having left AVF using imaging techniques (computed tomography, magnetic resonance imaging and Color Doppler ultra sonography). He underwent embolization of left renal artery using microcoils. After the surgery, there were no major complications, and there were no signs reccurence. AVF in a long-term dialysis patient is rare. We report this case and summarize the cases reported in Japan.

Application of pixel truncation to reduce intensity artifacts in myocardial SPECT imaging with Tc-99m tetrofosmin.

BACKGROUND: Technetium 99m-labeled radiopharmaceuticals accumulate in the liver and gallbladder, where they generate intensity artifacts that can result in misdiagnosis of myocardial single photon emission computed tomography (SPECT) images. This study identifies and eliminates factors affecting the magnitude and appearance of intensity artifacts in a gallbladder-heart phantom. METHODS AND RESULTS: The myocardium and background compartments of a phantom were filled with Tc-99m at concentrations of 320 and 26.1 kBq/mL, respectively. A disposable plastic syringe containing 5 mL of Tc-99m as a model of the gallbladder was fixed in a position lateral to the heart phantom. Artifact intensity was determined on SPECT images over a specific activity range in the syringe (28.6, 6.6, and 0.2 MBq/mL). Among 72 projection images, those with maximal heart counts in the region of interest were selected. Counts above and below 110% of the maximal heart count in all projection images were excluded and reconstructed, respectively. At 28.6 and 6.6 MBq/mL, excessive artifacts generated cold pixels immediately around the source, whereas lower activity (0.2 MBq/mL) caused the artifacts to disappear. Truncating the counts in the gallbladder caused the intensity artifacts at specific activities of 28.6 and 6.6 MBq/mL to disappear. CONCLUSIONS: The magnitude and appearance of intensity artifacts depend on contrast between extracardiac activities in the same slices of the heart in myocardial SPECT images with Tc-99m tetrofosmin, and pixel truncation can eliminate them.