Twenty‐four patients with various solid tumors including metastatic liver cancer and cancer of the lung, gallbladder, and pancreas were treated with a lipophilic macromolecular drug, copoly(styrene‐maleic acid) conjugated neocarzinostatin (SMANCS). The drug was dissolved in a lipid contrast medium Lipiodol and administered by catheterizing the respective feeding arteries under x‐ray monitoring. The advantages of this therapy include: (1) selective deposition of Lipiodol with the anti‐cancer drug in the target tumor, (2) a pronounced and long‐lasting anti‐cancer effect, (3) enhanced visulization of the tumor on x‐ray examinations for a prolonged period which also facilitated the long‐term follow‐up, (4) semiquantitative evaluation of the dosage regimen by x‐ray examination before further administration, (5) general applicability due to procedural simplicity, and (6) little side effect. Since the amount of Lipiodol and SMANCS used per administration for a patient (1.0–5.0 ml; 1.0–5.0 mg) was far less that the anticipated toxicity (LD50 of Lipiodol = 95 ml/60 kg, dog, intravenously; and that of SMANCS = 3.4 mg/kg, mouse, IV), no deleterious effects to such critical organs as the brain, heart, lung, liver, or kidneys were observed upon radiologic and general clinical examination.

In six adult patients with nonresectable liver cancer, as well as in mature New Zealand white rabbits with implanted VX2 carcinoma in the liver, the artery feeding the hepatic lobe with the malignant lesion was ligated, and an oily contrast medium (Lipiodol Ultra‐Fluid) was injected into the hepatoproximal lumen of the ligated artery of the liver with carcinoma. The oily contrast medium was detected in all the branches of the artery injected, and thereafter was found only in tumor tissue for 7 days experimentally and for 16 months clinically. Taking advantage of this phenomenon, the therapeutic effect of the injection of an oily anticancer drug (bleomycin oil suspension) into the hepatoproximal lumen of the ligated hepatic artery was investigated in rabbits with VX2 carcinoma of the liver. The mean concentration level of bleomycin in the tumor tissue was 2.4 ± 0.4 μg/g 1 week after the injection of bleomycin oil suspension (1.5 mg potency/kg) in three rabbits. However, its concentration level in nontumorous tissue of the liver was undetectably low in two rabbits, but 0.6 μg/g in the third rabbit. The group of rabbits receiving an injection of bleomycin oil suspension into the ligated artery had a significantly longer mean survival time than those of the experimental group receiving an injection of saline solution of bleomycin into the ligated artery as well as the three other groups treated (P < 0.02, N = 5 for each group). It may be concluded that an oily anticancer drug injected into the hepatoproximal lumen of the ligated hepatic artery can intensify the anticancer effects of a ligation of the hepatic artery for liver cancer. Cancer 52:2193‐2200, 1983.

Seven patients with a giant-cell tumor involving the distal end of the radius were treated with en bloc resection and reconstruction with a free vascularized fibular graft. Two patients with stage 2 disease of Enneking's surgical staging and grade 2 of Campanacci's radiographic grading system were reconstructed with an articular fibular head graft. Five patients with stage 3 and grade 3 disease underwent wrist arthrodesis using fibular shaft transfer. There was radiographic evidence of bone union at the host-graft junctions in all cases. No local recurrence was seen in any of the patients at the most recent follow-up examinations. There were six good and one excellent functional results. Wrist arthroplasty using a vascularized fibula head graft is the best procedure for a stage 2 or grade 2 giant-cell tumor of the distal end of the radius. In cases of stage 3 or grade 3 disease, wrist arthrodesis using a vascularized fibular shaft graft is indicated.

No abstract

Prostate cancer is one of the most prevalent malignancies and is the second leading cause of cancer-related deaths in men. Fruit and vegetable consumption is a novel, non-toxic therapeutic approach that can be used to prevent and treat prostate cancer. Citrus peels and their extracts have been reported to have potent pharmacological activities and health benefits due to the abundance of flavonoids in citrus fruits, particularly in the peels. Our previous studies demonstrated that oral administration of Gold Lotion (GL), an extract of multiple varieties of citrus peels containing abundant flavonoids, including a large percentage of polymethoxyflavones (PMFs), effectively suppressed azoxymethane (AOM)-induced colonic tumorigenesis. However, the efficacy of GL against prostate cancer has not yet been investigated. Here, we explored the anti-tumor effects of GL using a human prostate tumor xenograft mouse model. Our data demonstrated that treatment with GL by both intraperitoneal (i.p.) injection and oral administration dramatically reduced both the weights (57%-100% inhibition) and volumes (78%-94% inhibition) of the tumors without any observed toxicity. These inhibitory effects were accompanied by mechanistic down-regulation of the protein levels of inflammatory enzymes (inducible nitric oxide synthase, iNOS and cyclooxygenase-2, COX-2), metastasis (matrix metallopeptidase-2, MMP-2 and MMP-9), angiogenesis (vascular endothelial growth factor, VEGF), and proliferative molecules, as well as by the induction of apoptosis in prostate tumors. Our findings suggest that GL is an effective anti-cancer agent that may potentially serve as a novel therapeutic option for prostate cancer treatment.

Background Protection from lethal ventricular arrhythmias leading to sudden cardiac death (SCD) is a crucial challenge after acute myocardial infarction (AMI). Cardiac sympathetic and parasympathetic activity can be noninvasively assessed using heart rate variability (HRV) and heart rate turbulence (HRT). The EMBODY trial was designed to determine whether the Sodium–glucose cotransporter 2 (SGLT2) inhibitor improves cardiac nerve activity. Methods This prospective, multicenter, randomized, double-blind, placebo-controlled trial included patients with AMI and type 2 diabetes mellitus (T2DM) in Japan; 105 patients were randomized (1:1) to receive once-daily 10-mg empagliflozin or placebo. The primary endpoints were changes in HRV, e.g., the standard deviation of all 5-min mean normal RR intervals (SDANN) and the low-frequency–to–high-frequency (LF/HF) ratio from baseline to 24 weeks. Secondary endpoints were changes in other sudden cardiac death (SCD) surrogate markers such as HRT. Results Overall, 96 patients were included (46, empagliflozin group; 50, placebo group). The changes in SDANN were + 11.6 and + 9.1 ms in the empagliflozin (P = 0.02) and placebo groups (P = 0.06), respectively. Change in LF/HF ratio was – 0.57 and – 0.17 in the empagliflozin (P = 0.01) and placebo groups (P = 0.43), respectively. Significant improvement was noted in HRT only in the empagliflozin group (P = 0.01). Whereas intergroup comparison on HRV and HRT showed no significant difference between the empagliflozin and placebo groups. Compared with the placebo group, the empagliflozin group showed significant decreases in body weight, systolic blood pressure, and uric acid. In the empagliflozin group, no adverse events were observed. Conclusions This is the first randomized clinical data to evaluate the effect of empagliflozin on cardiac sympathetic and parasympathetic activity in patients with T2DM and AMI. Early SGLT2 inhibitor administration in AMI patients with T2DM might be effective in improving cardiac nerve activity without any adverse events. Trial Registration: The EMBODY trial was registered by the UMIN in November 2017 (ID: 000030158). UMIN000030158; https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000034442.

Citrus peel or its extract has been reported to exhibit a broad spectrum of biological activity. Herein, we report the first investigation of inhibitory effects of a formulated product from citrus peel extract, gold lotion (GL), on azoxymethane-induced colonic tumorigenesis. We have demonstrated that oral feeding of GL decreased the number of aberrant crypt foci (ACF), particularly large size of ACF in colonic tissues of mice. Both gene and protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were suppressed by GL treatment. The in vivo data have revealed for the first time that the citrus peel extract-GL-is an effective antitumor agent mechanistically downregulating the protein levels of iNOS, COX-2, ornithine decarboxylase, vascular endothelial growth factor, and matrix metallopeptidase 9 in colonic tissues of mice, suggesting that GL is a novel functional natural product capable of preventing inflammation-associated colon tumorigenesis.

Summary In the early period following radical hepatectomy for hepatoma, recurrences in the remaining liver are frequently found. In regenerating liver, implantation and growth of tumour cells released into the portal system during surgical treatment might be promoted. We examined the relationship between liver regeneration and the formation of metastases following hepatic resection. Intraportal injections of rat ascites containing hepatoma AH130 cells at a concentration of 1 x IO' cells 0.2 ml-l were made at various periods following two thirds liver resection in rats. Tumour cell injections immediately at 24 h after surgery resulted in an increased number of hepatic metastases compared with control animals. Tumour cell injections 2 weeks after hepatectomy, however, had no significant difference in effect compared with control rats. In contrast, tumour cells injected immediately after removal of half of the caudate lobe resulted in the same number of metastases as control animals. These results demonstrate that the number of artificially induced hepatic metastases was increased during an initial period of active liver regeneration and was proportional to the volume of hepatectomy.The effect of 5-fluorouracil (5FU) or mitomycin C (MMC) as inhibitors of hepatic regeneration on liver metastasis after hepatectomy was studied. The administration of 5FU (20mg kg-') or MMC (0.2 mg kg-') immediately, 24 and 48 h after hepatectomy resulted in a marked reduction in metastatic lesions. The administration of 5FU caused delays in weight gain and decreases in the wet weight of remaining liver, while MMC had no effect on either. Accordingly, results of 5FU administration may be due to inhibitory effects on liver regeneration whilst that of MMC administration may be due to cytocidal antitumour effect. The effect of OK-432 as an immunoactivator on the implantation and growth of tumour cells in regenerating liver was also studied. Pretreatment with OK-432, 0.5 mg intraperitoneally on 7 consecutive days, had no effect on hepatic metastases.The pathophysiology of liver regeneration may enhance hematogenous hepatic metastasis and release of tumour cells during surgical manipulation may represent an important cause of recurrence following hepatic resection.Recent advances in preoperative diagnostic techniques and intraoperative ultrasonography have provided a greater ability to determine the number, location, and extent of liver lesions (Kanematsu et al., 1985; Makuuchi et al., 1987). Despite their application to the surgical resection of liver malignancies, however, recurrences are frequently found in the early postoperative period. It as yet remains unclear whether such lesions are due to pre-existing microscopic disease, result from surgical manipulation, or both.According to Okuda et al. (1977), intrahepatic arterioportal anastomosis is demonstrated in 63.2% of patients with hepatocellular carcinoma, and retrograde flow of the portal vein trunk is seen in 25.4% as revealed by angiography. Therefore, tumour cell release into the p...