ACTN4 copy number increase as a predictive biomarker for chemoradiotherapy of locally advanced pancreatic cancer.

BACKGROUND: Several clinical trials have compared chemotherapy alone and chemoradiotherapy (CRT) for locally advanced pancreatic cancer (LAPC) treatment. However, predictive biomarkers for optimal therapy of LAPC remain to be identified.We retrospectively estimated amplification of the ACTN4 gene to determine its usefulness as a predictive biomarker for LAPC. METHODS: The copy number of ACTN4 in 91 biopsy specimens of LAPC before treatment was evaluated using fluorescence in situ hybridisation (FISH). RESULTS: There were no statistically significant differences in overall survival (OS) or progression-free survival (PFS) of LAPC between patients treated with chemotherapy alone or with CRT. In a subgroup analysis of patients treated with CRT, patients with a copy number increase (CNI) of ACTN4 had a worse prognosis of OS than those with a normal copy number (NCN) of ACTN4 (P=0.0005, log-rank test). However, OS in the subgroup treated with chemotherapy alone was not significantly different between patients with a CNI and a NCN of ACTN4. In the patients with a NCN of ACTN4, the median survival time of PFS in CRT-treated patients was longer than that of patients treated with chemotherapy alone (P=0.049). CONCLUSIONS: The copy number of ACTN4 is a predictive biomarker for CRT of LAPC.

Strategies for management of bile duct injury during laparoscopic cholecystectomy.

We encountered 10 patients with bile duct injuries during laparoscopic cholecystectomy. Their causes were electrocautery in 2 patients, misjudgment in 2, mechanical injury in 3, aberrant bile duct in 2, and weakness of the bile duct wall in one. The sites of injury were cystic duct in 4 patients, common bile duct in 2, aberrant bile duct in 2, common hepatic duct in one, and common bile duct plus right hepatic duct in one. Treatments for the injuries discovered intraoperatively consisted of T-tube drainage above in 2 patients, re-ligation of the cystic duct in one, ligation of an aberrant bile duct in one, simple suture and T-tube in one, and choledochojejunostomy in one. In the remaining 4 patients discovered postoperatively, 2 were conservatively treated by endoscopic retrograde biliary drainage. The duration of hospitalization was 9-12 days in the 4 patients with simple suture or ligation, 10-21 days in 2 cases of bile drainage, and 34-43 days in 3 with T-tube drainage. The patient with choledochojejunostomy suffered repeated cholangitis, resulting in hepatic abscess with hospitalization for 6 months. Since laparoscopic surgery should be minimally invasive, meticulous attention is necessary before and during surgery to avoid bile duct injury.

[Efficacy of combination chemotherapy with mitoxantrone, vincristine, doxifluridine and prednisolone for recurrence of breast cancer].

We treated fifteen patients with recurrent breast cancer by a combination of mitoxantrone (8 mg/m i.v., day 1), vincristine (1.2 mg/m i.v., day 1), doxifluridine (800 mg/body po, everyday) and prednisolone (30 mg/body po, day 1-7). Cycles were repeated every 3 weeks and all patients received more than 2 cycles. A response to treatment was observed in 9 of 15 evaluable patients (60.0%) with 4 complete remissions and 5 partial remissions. Eight patients were previously exposed to anthracyclines. In 5 of 7 cases with no previous chemotherapy, treatment was effective, and in 4 of 8 cases previous chemotherapy was effective. The toxicity was primarily leucopenia (86.7%), and 9 patients received G-CSF therapy. Other toxicities (alopecia, neurologic and general fatigue) were mild. Two patients with heart failure were recognized and treated with other therapy. This chemotherapy is effective for the treatment of recurrent breast cancer.

[Two patients with far advanced gastric cancer responding to combination chemotherapy with 5-FU and CDDP].

Combination chemotherapy with 5-FU and CDDP was given to two patients with far advanced gastric cancer. One patient was associated with metastases of lung, liver, pancreas and Virchow and periaortic lymph nodes, and the other was associated with metastases of periaortic lymph nodes and malignant ascitis. The regimen consisted of 5-FU 1,000 mg/m2 (day 1-5, continuous infusion) and CDDP 100 mg/m2 (day 3, 1 hr drip infusion). The interval was from the 6th to the 21st day. The response to chemotherapy showed shrinking of primary gastric lesions and metastases of liver, pancreas and periaortic lymph nodes, and disappearance of Virchow lymph nodes and malignant ascitis. Adverse reactions were thrombocytopenia (Grade 4), leukocytopenia (Grade 3), stomatitis (Grade 1, 3), vomiting (Grade 1, 2) and peripheral neuropathy (Grade 3). This therapy is thought to be effective against far advanced gastric cancer.

The anti-platelet effect of niceritrol in patients with arteriosclerosis and the relationship of the lipid-lowering effect to the anti-platelet effect.

A hypolipidemic agent, pentaerythritol tetranicotinate (niceritrol) yields nicotinic acid upon hydrolysis in vivo, but niceritrol is hardly soluble in distilled water, so that the effects of nicotinic acid on platelet aggregation in vitro were studied. Nicotinic acid inhibited in vitro platelet aggregation induced by ADP, collagen and adrenaline. Twenty patients (61.4 +/- 2.4 years (mean +/- S.E.)) with ischemic heart disease, cerebral infarction, transient cerebral ischemic attack and hypercholesterolemia were given niceritrol orally at 750 mg per day for 8 weeks. Significant decreases in ADP-, collagen- and adrenaline-induced platelet aggregation were observed at 4 and 8 weeks after niceritrol treatment. There was a significant correlation between the rates of changes in platelet aggregation and those in plasma total cholesterol or plasma LDL-cholesterol before treatment and 8 weeks following treatment. The results indicate that niceritrol has inhibitory effects on platelet aggregation not only caused by its direct action on platelet but mediated by its secondary action due to decrease in blood lipids.