[Risk Factors for Oxaliplatin-Induced Phlebitis and Venous Pain, and Evaluation of the Preventive Effect of Preheating with a Hot Compress for Administration of Oxaliplatin].

Venous pain induced by oxaliplatin(L-OHP)is a clinical issue related to adherence to the Cape OX regimen. To prevent LOHP- induced venous pain, we provided nursing care to outpatients who were administered a preheated L -OHP diluted solution using a hot compress. We retrospectively evaluated the risk factors for colorectal cancer patients who had L -OHP induced phlebitis and venous pain. Furthermore, the preventive effect of nursing care was compared between inpatients and outpatients from January 2010 to March 2012. At the L-OHP administration site, any symptoms were defined as phlebitis, whereas pain was defined as venous pain. A total of 132 treatment courses among 31 patients were evaluated. Multivariate logistic regression analysis revealed that both phlebitis and venous pain were significantly more common in female patients (adjusted odds ratio, 2.357; 95%CI: 1.053-5.418; and adjusted odds ratio, 5.754; 95%CI: 2.119-18.567, respectively). The prevalence of phlebitis and venous pain did not differ between inpatients and outpatients (phlebitis, 61.3% vs 67.7%; venous pain, 29.0%vs 19.4%). These results suggest that administration of L-OHP via a central venous route should be considered in female patients.

Risk factors for discontinuation of s-1 adjuvant chemotherapy for gastric cancer.

PURPOSE: The aim of this study was to clarify the risk factors for discontinuing tegafur/gimeracil/oteracil potassium (S-1) adjuvant chemotherapy following gastrectomy in patients with gastric cancer. METHODS: We retrospectively investigated patients with curatively-resected gastric cancer who received S-1 adjuvant chemotherapy. S-1 was administered orally at 80-120 mg/day, depending on body surface area, on days 1-28 every 6 weeks for 1 year. The dose and treatment schedule were modified at the clinicians' discretion, according to toxicity. RESULTS: Seventy-one patients were included in the study, 26 of whom discontinued S-1 therapy. The relapse-free survival rates in the S-1-completed and S-1-discontinuation groups at 5 years post-surgery were 88.1% and 55.8%, respectively. The overall survival rates in the S-1-completed and S-1-discontinuation groups at 5 years post-surgery were 89.4% and 59.8%, respectively. The hazard ratios for relapse and death were significantly lower in the S-1-completed group compared with those in the S-1-discontinuation group (0.18; p<0.001 and 0.19; p=0.002, respectively). Multivariate logistic regression analysis revealed that S-1 discontinuation was significantly associated with an initial overdose of S-1, having stage I cancer, creatinine clearance <66 mL/min, and a side effect of nausea. CONCLUSIONS: These results suggest that assessing renal function to avoid initial overdose of S-1, together with the early management of side effects, may support the continuation of S-1 adjuvant chemotherapy in patients with gastric cancer.

[Preventive trial of preheating administration of oxaliplatin-diluted solution in combination with a hot compress for oxaliplatin-induced venous pain].

Venous pain induced by oxaliplatin (L-OHP) is a clinical problem in relation to adherence in the CapeOX regimen. We investigated the preventive effect of nursing care preheating administration of L-OHP a hot compress for colorectal cancer patients who received L-OHP via the peripheral venous route between January 2010 and January 2011. L-OHP was diluted in 500 mL of 5% glucose and administered by 2 hours. We evaluated a total of 64 courses among fifteen patients. The presence of any symptoms, any pain with or without touch, and some symptoms of numbness at the L-OHP-administered arm were defined as phlebitis, venous pain, and acute peripheral neuropathy, respectively. The prevalence of phlebitis, venous pain, and acute peripheral neuropathy in the nursing care group was 56.5%, 32.6%, and 25.8%, respectively, which was not significantly less in comparison with the control group (72.2%, 38.9%, and 54.5%, respectively). These results suggest that both types of nursing care, preheating administration and a hot compress, may be effective for the relief of acute peripheral neuropathy induced by L-OHP.

Protective effect of adeno-mediated human Bcl-xL gene transfer to the mouse liver in a partial ischemia/reperfusion model.

BACKGROUND: The protective effect of heat preconditioning has been ascribed to the induction of heat shock proteins (HSP) in the liver. We detected an increase in Bcl-xL expression prior to HSP 70 expression in the rat liver after heat preconditioning. The net effect of overexpression of human Bcl-xL with a recombinant adenovector was estimated in a partial ischemia/reperfusion model of the mouse liver. MATERIALS AND METHODS: The time courses of the expression of HSP, Bcl-xL, Bcl-2, Bax, and Bag-1 in the SD rat liver after heat preconditioning were studied by Western blotting. The localizations of Bcl-xL, Bcl-2, and Bax at 6 h after preconditioning were examined by immunostaining. The expression of Bcl-xL in the C57/BL mouse liver after intravenous injection of the recombinant adenovector was assessed by Western blotting and immunostaining. The protective effect of overexpression of Bcl-xL was estimated in a 60-min partial ischemia/reperfusion model of the mouse liver. RESULTS: The expression of Bcl-xL peaked 12 h after heat preconditioning. The overexpression of Bcl-xL decreased enzyme release, histological cell injury, and the number of TUNEL-positive cells. CONCLUSION: Transfer of the human Bcl-xL gene to the liver had a protective effect against ischemia/reperfusion injury in a mouse model.

Oncolytic gene therapy combined with double suicide genes for human bile duct cancer in nude mouse models.

BACKGROUND: The prognosis of bile duct cancer is quite poor because of the low resection rate and the tolerance of the cancer to chemotherapy and radiotherapy. We investigated the feasibility of an oncolytic adenovector with two suicide genes for the treatment of bile duct cancer. MATERIALS AND METHODS: We developed a new conditionally replicating adenovirus (AxE1CAUT) with the uracil phosphoribosyltransferase (UPRT) gene and the herpes simplex virus thymidine kinase (HSV-tk) gene, and compared its antitumor effects with a replication defective adenovector (AxCAUT) that has both the UPRT and HSV-tk genes. We evaluated the effects of these adenoviruses with 5-fluorouracil (5-FU) and/or ganciclovir (GCV) on human cholangiocarcinoma cells (HuCCT1, with mutant p53) in vitro and in vivo. RESULTS: The drug sensitivity of HuCCT1 cells to 5-FU and/or GCV was increased with an increase in the multiplicity of infection (MOI). The antitumor effect increased when 5-FU and GCV were given at the same time. Subcutaneous tumors of nude mice directly injected with AxCAUT showed a higher response to 5-FU/GCV than 5-FU or GCV alone, but there was no difference between AxCAUT and AxE1CAUT. However, AxE1CAUT with 5-FU/GCV produced a decrease in tumor weight and better survival than AxCAUT in a peritoneal dissemination model infected by intraperitoneal administration of the adenovectors. CONCLUSION: Oncolytic double suicide gene therapy is effective against human cholangiocarcinoma cells in nude mouse models.

[Two cases of advanced pancreas cancer treated with GTX: combined use of gemcitabine, docetaxel and capecitabine].

Two cases of advanced pancreas cancer were treated with GTX. One cycle was 3 weeks, capecitabine (1,000 mg/m(2)/day) was administered from day 1 to 14, and GEM 750 mg/m(2) and DOC 30 mg/m(2) were drip-infused on day 4 and 11. A 62-year-old man with pancreas head cancer and 2 liver metastases was treated with GEM 1,000 mg/m(2)/week at weeks 1, 2, and 3, and drug-free week 4 for 3 cycles, but was PD. After 3 cycles of GTX, the liver metastases decreased in size, and thereafter tumor markers became lowest after 7 cycles. The patient was shifted to another regimen after 14 cycles for 9 months of GTX. A 75-year-old man with pancreas head cancer and vascular invasion has been treated with GTX. As leukopenia was seen after the first cycle, the administration doses were reduced and GTX has been continued for a total 13 cycles. The tumor reduced in size and tumor markers decreased. GTX is suitable for outpatient chemotherapy with mild adverse effects.

Adenovirus-mediated p53 gene transfer to the bile duct by direct administration into the bile in a rat cholangitis model.

BACKGROUND: Hepatolithiasis is a common disease in East Asia and its aggravating factor is bile duct stenosis because of refractory cholangitis. This study investigated the feasibility of gene therapy for bile duct stenosis by administration of p53 adenoviral vectors into the bile. MATERIALS AND METHODS: Adenoviral vectors (AxCALacZ or AxCAhp53) were injected transpapillarily into the bile in the bile duct in a rat model of cholangitis. The extent and duration of the gene expression was evaluated with X-gal staining and p53 immunostaining. The bile duct tissue was examined to evaluate the inhibitory effect on the proliferative changes at 3 and 7 days after administration, and Ki-67 labeling index was determined. RESULTS: beta-galactosidase was expressed in the bile duct epithelia, the bile duct wall and the surrounding connective tissue. The expression of beta-galactosidase was detected at 4 weeks after the administration. Mean thickness of the bile duct wall at 7 days was 343.2 +/- 14.0 microm for the AxCAhp53 group, 446.5 +/- 25.3 microm for the AxCALacZ group and 447.1 +/- 53.4 microm for the control group. The proliferation of the bile duct wall was significantly suppressed in the AxCAhp53 group (P < 0.05). Maximum thickness was 408.0 +/- 23.9 microm for the AxCAhp53 group (P < 0.05), 650.0 +/- 49.3 microm for the AxCALacZ group, and 590.0 +/- 64.3 microm for the control group. Mean Ki-67 labeling index for the three groups was 20.7% (P < 0.05), 34.4% and 37.4%, respectively. CONCLUSIONS: P53 gene transfer by administration of the adenoviral vector into the bile suppressed the proliferative changes in the bile duct in a rat cholangitis model.