Previous animal studies have established that the intra-articular injection of holmium-166-chitosan complex (DW-166HC) causes effective necrosis of the inflamed synovium with litle leakage of radioactivity from the injected joint. Based on these findings, we conducted a phase I/IIa study to examine the biodistribution of DW-166HC and to assess the safety of DW-166HC for the treatment of knee synovitis in patients with rheumatoid arthritis (RA). A total of 16 patients [1 man, 15 women; median age 49 (range 36-65) years] who had RA knee synovitis refractory to disease-modifying anti-rheumatic drug treatments of > 3 months' duration were randomly assigned to three treatment groups with different radiation doses of DW-166HC: 370 MBq (n = 6), 555 MBq (n = 5) and 740 MBq (n = 5). In each treatment group, blood and urine radioactivity were analysed by beta counter and biodistribution of the injected DW-166HC was evaluated using a gamma scan camera. Clinical assessment was done according to three variables (evaluation method): knee joint pain (visual analogue scale), range of motion (goniometry) and joint swelling (circumference of knee joint). The duration of follow-up observation was 3 months. Following the intra-articular injection of DW-166HC, the blood radioactivity was little changed from the baseline measurement and the accumulated radioactivity excreted in urine was minimal. Gamma scan study indicated that most of the injected radiochemical was localized within the injected joint cavity, and the extra-articular leakage was negligible at 24 h after the injection: brain, 0.3%; lung, 0.6%; abdomen, 0.7%; and pelvis, 0.8%. Major adverse events were transient post-injection knee joint pain and swelling. These results suggest that DW-166HC might be a safe agent for radiation synovectomy, particularly for the treatment of knee synovitis of RA, and further trials in a larger patient population are warranted to evaluate the therapeutic efficacy of DW-166HC.
Although several studies demonstrated the poor prognosis of young patients with gastric cancer, there were few reports about the survival of young patients who underwent radical surgery. We retrospectively reviewed the hospital records of 697 patients with curatively resected locally advanced gastric cancer to compare the pathologic findings and prognosis of young patients (aged < 40 years; 91 patients) with those of older (aged > or = 40 years; 606 patients) patients. There were no significant differences in location of tumors, Borrmann types, tumor invasion, and pathologic stage between both age groups. Despite the male predominance in older patients, the male-to-female ratio was nearly equal in young patients (p = 0.022). A significantly higher percentage of young patients showed poorly differentiated histology including signet ring cell and undifferentiated carcinoma than older patients (p < 0.0001). Adjuvant chemotherapy was more frequently performed in the young patients with a variety of different regimens (85.7 vs. 72.3%; p = 0.009). The 5-year overall survival rate revealed no statistically significant differences between the young and older patients (53.1 vs. 56.6%; p = 0.820). In conclusion, the young patients with curatively resected locally advanced gastric cancer showed similar survival compared to that of older patients.
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