[The incidence of gastrointestinal bleeding, thromboembolic events, and gastrointestinal perforation in metastatic or unresectable gastric cancer during chemotherapy].

UNLABELLED: The incidence of gastrointestinal bleeding, thromboembolic events and gastrointestinal perforation during chemotherapy with metastatic or unresectable gastric cancer has been unknown. To clarify the incidence of these events, we reviewed the clinical records of our hospital. PATIENTS AND METHODS: We investigated metastatic or unresectable gastric cancer patients who received chemotherapy during January 2002 to December 2006. Grade≥3 (CTCAE v3.0) adverse events from the first day of chemotherapy to 1 month after the last day of chemotherapy were investigated. RESULTS: A total of 292 patients received chemotherapy. Patient characteristics were as follows: median age 63.5 years (range, 28 to 87); performance status 0/1/2/3: 129/129/31/3; male: female, 206:86, histopathological type intestinal/diffuse/unclassified-adenocarcinoma/others: 91/139/58/4. We found the incidence of Grade≥3 gastrointestinal bleeding in 7 patients (2.4%), thromboembolic events in 5 patients (1.7%) and gastrointestinal perforation in 3 patients (1.0%). Thromboembolic events in patients under 55 years of age were associated with a higher incidence (p=0. 0046). CONCLUSION: The incidence was not so high as expected. We should be aware of the frequency of these toxicities in the treatment of gastric cancer.

Formation of proteoglycan and collagen-rich scaffold-free stiff cartilaginous tissue using two-step culture methods with combinations of growth factors.

Tissue-engineered cartilage may be expected to serve as an alternative to autologous chondrocyte transplantation treatment. Several methods for producing cartilaginous tissue have been reported. In this study, we describe the production of scaffold-free stiff cartilaginous tissue of pig and human, using allogeneic serum and growth factors. The tissue was formed in a mold using chondrocytes recovered from alginate bead culture and maintained in a medium with transforming growth factor-beta and several other additives. In the case of porcine tissue, the tear strength of the tissue and the contents of proteoglycan (PG) and collagen per unit of DNA increased dose-dependently with transforming growth factor-beta. The length of culture was significantly and positively correlated with thickness, tear strength, and PG and collagen contents. Tear strength showed positive high correlations with both PG and collagen contents. A positive correlation was also seen between PG content and collagen content. Similar results were obtained with human cartilaginous tissue formed from chondrocytes expanded in monolayer culture. Further, an in vivo pilot study using pig articular cartilage defect model demonstrated that the cartilaginous tissue was well integrated with surrounding tissue at 13 weeks after the implantation. In conclusion, we successfully produced implantable scaffold-free stiff cartilaginous tissue, which characterized high PG and collagen contents.

Oversulfated chondroitin sulfate-E binds to BMP-4 and enhances osteoblast differentiation.

Small leucine-rich proteoglycans, such as biglycan, and their side chain sulfated glycosaminoglycans (GAGs), have been suggested to be involved in bone formation and mineralization processes. The present study was designed to investigate whether chondroitin sulfate (CS), one of the GAG, and its oversulfated structures coupled with bone morphogenetic protein-4 (BMP-4) alter the differentiation and subsequent mineralization of MC3T3-E1 osteoblastic cells. CS-E, one of the oversulfated CS structure, enhanced cell growth, alkaline phosphatase (ALP) activity, collagen deposition, and mineralization whereas heparin enhanced only ALP activity and mineralization. As well as CS-E, CS-H, and CPS also enhanced the mineralization of the cells. CS-E enhanced the mineralization of the cells by interacting with protein in the conditioned medium. CS-E induced mineralization was significantly inhibited by an antibody against BMP-4. The addition of exogenous BMP-4 further increased the capacity of CS-E to enhance mineralization. Fluorescence correlation spectroscopy method using fluoresceinamine-labeled GAG revealed that the oversulfated GAGs have a high affinity for BMP-4. The disaccharide analysis of the cells indicated that MC3T3-E1 cells are capable of producing oversulfated structures of CS by themselves. The lack of CS from the cells after chondroitinase treatment resulted in the inhibition of mineralization. These results in the present study indicate that oversulfated CS, which possesses 4,6-disulfates in N-acetyl-galactosamine, binds to BMP-4 and promotes osteoblast differentiation and subsequent mineralization.

[Safety and efficacy analysis of FOLFOX4 regimen in elderly compared to younger colorectal cancer patients].

The number of elderly patients with colorectal cancer is increasing in Japan. They have the opportunity to receive chemotherapy similar to non-elderly patients because of the development of new drug agents and improvement of supportive therapy. We analyzed retrospectively 184 patients (32 aged >or= 70, 75 or= 3 adverse events. The FOLFOX4 regimen maintains its efficacy/safety ratio in elderly patients with good performance status with colorectal cancer in Japan.

[Drug information brochure for patients undergoing FOLFOX 4 chemotherapy based on survey of adverse reactions].

We have been collecting data on the adverse reaction of FOLFOX 4 chemotherapy in our hospital from April 2005 to October retrospectively, by electronic clinical records. A retrospective study of 123 patients receiving FOLFOX 4 for advanced colorectal cancer was conducted. Survey results showed high incidences of hemotoxicity (52.8%), chronic sensory neuropathy (16.2%) and allergic reactions (15.4%). In the initial FOLFOX 4 therapy, appetite loss (60.1%), vomiting (19.5%) and acute sensory neuropathy (33.3%) were observed. We prepared a brochure in order to minimize inter-individual differences in pharmaceutical care and drug consultation by clinical pharmacists and to ensure the accurate understanding of patients. We feel sure that this kind of activity will help us to provide better pharmaceutical care for patients.

The effects of intraarticularly injected sodium hyaluronate on levels of intact aggrecan and nitric oxide in the joint fluid of patients with knee osteoarthritis.

OBJECTIVE: Intraarticular injections of sodium hyaluronate (Na-HA) appear effective in reducing subjective symptoms of osteoarthritis (OA) and may also have protective effects on the cartilage matrix. The present study analyzed the suppressive effects of Na-HA on the release and degradation of aggrecan and on levels of nitric oxide (NO) in the joint fluid of patients with knee OA. DESIGN: Sixteen OA patients with knee joint effusion were treated by 5 weekly intraarticular injections of Na-HA. Prior to each Na-HA injection, joint fluid was collected to determine the levels of chondroitin 4-sulfate (C4S) and chondroitin 6-sulfate (C6S), intact aggrecan and NO. RESULTS: One week after the final injection, the joint fluid levels of C4S, C6S, and NO were significantly decreased. In contrast, the joint fluid level of intact aggrecan was stable during the series of Na-HA injections. A trend was seen for a positive correlation (P < 0.1) between the clinical score and C4S or C6S joint fluid levels, and for a negative correlation between the joint fluid levels of intact aggrecan and C4S or C6S. No significant correlations were observed between joint fluid levels of NO, the clinical score, and levels of C4S, C6S, and intact aggrecan. CONCLUSION: The results of this study suggest that intraarticularly injected Na-HA is able to improve the clinical symptoms of OA partially based on its ability to reduce the release and degradation of aggrecan and/or to enhance the synthesis of aggrecan in the joint tissues of the patients with knee OA. While Na-HA also reduces the NO level in the joint fluid of patients with knee OA, this effect may be independent from the other effects of Na-HA.

A randomized clinical trial comparing transjugular intrahepatic portosystemic shunt with endoscopic sclerotherapy in the long-term management of patients with cirrhosis after recent variceal hemorrhage.

The aim of this study was to compare the efficacy of transjugular intrahepatic portosystemic shunt (TIPS) with that of endoscopic sclerotherapy (ES) in the long-term management of patients with cirrhosis after variceal bleeding. Seventy-eight consecutive cirrhotic patients with recent variceal bleeding were randomly allocated to either TIPS (n=38) or ES (n=40). All patients were in good condition at randomization. The mean follow-up was 1116+/-92 days in the TIPS group and 1047+/-102 days in the ES group. Differences in rebleeding from any source (18.4% vs. 32.5%) and esophageal variceal rebleeding (15.7% vs. 27.5%) were not significantly different between the two groups (P>0.05). The mortality rates were similar in both treatment groups. Shunt dysfunction was noted in 27 patients (71%) in the TIPS group. There were more numbers of rehospitalization during follow-up in the TIPS group than in the ES group (2.6+/-0.4 vs. 1.1+/-0.2) (P<0.01). TIPS and ES are equally effective in the prevention of variceal rebleeding. However, TIPS is associated with high incidence of shunt dysfunction, which lead to more rehospitalization. Therefore, TIPS may not be a first-line treatment for the prevention of variceal rebleeding in cirrhotic patients who are in stable condition.