Long-term effects of mass screening for neuroblastoma in infancy

Eighty-four neuroblastoma patients were treated at the Department of Pediatrics, Kyoto Prefectural University of Medicine, during the 27 years from 1962 to 1988. They were divided into three groups: 35 cases in phase 1, the 12 years before mass screening from 1962 to 1974; 22 in phase 2, the 8 years after the onset of mass screening by a qualitative vanillylmandelic acid (VMA) test from 1974 to 1982; and 27 in phase 3, the recent 6 years from 1983 to 1988, after the introduction of mass screening by quantitative assay for VMA and homovanillic acid using high performance liquid chromatography. The clinical findings of these patients were compared for each phase. In Kyoto, the number of annual neuroblastoma cases diagnosed under 1 year of age increased from 0.58 in phase 1 to 1.50 in phase 2 and 3.17 in phase 3. The number of cases over 2 years of age decreased from 2.00 in phase 1 to 0.88 in phase 2 and 1.00 in phase 3. Survival rates increased from 17.1% (six of 35) in phase 1 to 54.5% (12 of 22) in phase 2 and 85.2% (23 of 27) in phase 3. The annual number of neuroblastoma deaths decreased from 2.42 in phase 1 to 1.25 in phase 2 and 0.67 in phase 3. Mass screening for neuroblastoma in infancy has increased the long-term survival rates of neuroblastoma cases treated at this hospital.     

Hepatocyte growth factor levels in bone marrow plasma of patients with leukaemia and its gene expression in leukaemic blast cells.

Hepatocyte growth factor (HGF) has been known as a multiple function factor, which also stimulates early haematopoiesis. In this study, we found that HGF was expressed at both the RNA and protein levels in acute myeloid leukaemia (AML) and chronic myeloid leukaemia (CML). In patients with AML (n = 20) and CML (n = 5), bone marrow plasma HGF concentrations were 20.44 +/- 6.26 (mean +/- s.e.) ng ml-1 and 7.17 +/- 0.53 ng ml-1 respectively. These were significantly higher (P < 0.01) than the value for normal subjects (n = 26): mean 0.92 +/- 0.09 ng ml-1. Constitutive HGF production was observed in freshly prepared leukaemic blast cells from three patients with high HGF levels of bone marrow plasma. Expression of HGF mRNA was correlated with bone marrow plasma HGF levels. After complete remission was obtained in six patients, bone marrow plasma HGF levels were significantly decreased. In contrast, the HGF mRNA was less abundantly expressed in acute lymphoid leukaemia (ALL). In patients with ALL (n = 5), bone marrow plasma HGF concentration (0.69 +/- 0.14 ng ml-1) remained low within the value for normal subjects. These results suggest that some populations of myeloid lineage cells have the ability to produce HGF.     

Reconstruction of right ventricular outflow tract with stentless xenografts in Ross procedure

To investigate whether the use of a stentless porcine aortic xenograft can be an alternative for right ventricular outflow tract (RVOT) reconstruction during the Ross procedure, 9 patients underwent the Ross procedure and RVOT reconstruction with a stentless xenograft since January 2000. After the aortic valve was replaced with a pulmonary autograft, a stentless xenograft with a xeno- pericardial roll was implanted in the RVOT. One patient required subsequent aortic valve replacement because of severe regurgitation of the pulmonary autograft. All patients recovered well from the operation. The right ventricle-pulmonary arterial pressure gradient was 18 +/- 7 mm Hg at discharge and was not significantly increased during the 2-year follow-up period. Although 1 patient died of ventricular arrhythmia 5 months after, his cardiac function was normal, and transpulmonary valve pressure was 19 mm Hg in the follow-up. The other 7 patients are currently in New York Heart Association functional Class I. Although long-term follow-up is required to explain the durability, the stentless xenograft with a pericardial roll is considered to be an alternative for reconstruction of the RVOT within 2 years after the Ross procedure.     

Dysfunction of the p53 tumor suppressor pathway in head and neck cancer

It is important to examine the abnormality of the entire p53 tumor suppressor pathway in head and neck cancer. We examined the mRNA expressions of p53 regulatory factors, p33ING1 and p14ARF, and a p53-target gene, p21WAF1 in head and neck cancer. Nine of 14 benign pleomorphic adenomas (PAs) and 7 of 8 malignant salivary gland tumors (MSGTs) expressed p33ING1 mRNA. Thirteen of 14 PAs expressed p14ARF mRNA, however, only 1 of 8 MSGTs expressed p14ARF mRNA. Eight of 14 PAs and 7 of 8 MSGTs expressed p21WAF1 mRNA. In salivary gland tumors, there was clear correlation between the expression of p33ING1 and p21WAF1 (p<0.0001, r2=0.53). However, there was no correlation between the expression of p14ARF and p21WAF1 (p=0.6543, r2=0.009). Twenty-six of 28 oral squamous cell carcinomas (SCCs) expressed p33ING1 mRNA. Nineteen of 28 oral SCCs expressed p14ARF mRNA. All of the oral SCCs expressed p21WAF1 mRNA. In oral SCCs, the expressions of both p33ING1 (p=0.009, r2=0.181) and p14ARF (p=0.0009, r2=0.271) correlated with the expression of p21WAF1. Interestingly, 24 of 26 oral SCCs (92%) showed either abnormality of p53 itself or loss of expression of p53 regulatory factors, p33ING or p14ARF. These results suggest that head and neck cancer often involve the dysfunction of p53 tumor suppressor pathway.     

Gemcitabine in elderly patients with unresectable pancreas cancer

The efficacy and safety of gemcitabine at a starting dose of 1,000 mg/m2 administrated once a week for 3 weeks with 1 week's rest was investigated in elderly 11 patients with unresectable pancreatic cancer. Objective response was not documented. However, pain intensity, analgesic consumption and Karnofsky Performance Status (KPS) were frequently improved. In total, a clinical benefit was observed in 8 out of 11 (73%) patients. Toxicity was mild and well tolerated. These results suggest that gemcitabine had a superior clinical benefit and a mild toxicity profile. Gemcitabine should be the standard treatment in elderly patients with unresectable pancreatic cancer.     

Randomized trial evaluating a new 0.5% fluorouracil formulation demonstrates efficacy after 1-, 2-, or 4-week treatment in patients with actinic keratosis

The efficacy and safety of a new 0.5% fluorouracil topical cream were compared with vehicle control for the treatment of actinic keratosis (AK). Active treatment applied once daily for 1, 2, or 4 weeks was more effective than vehicle control in achieving reduction from baseline in lesion counts and lesion clearance. Active treatment also resulted in significantly better global assessments of overall improvement. Treatment was effective regardless of the number of baseline lesions. Although longer treatment duration correlated with greater efficacy, treatment for 1, 2, or 4 weeks was effective. This new microsphere-based fluorouracil formulation was generally well tolerated; adverse events were primarily limited to facial irritation that resolved quickly after treatment. This new treatment provides a safe alternative to the topical fluorouracil formulations currently available for the 1-, 2-, or 4-week treatment of AK.