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Hepatitis in children with haemophilia was historically most often associated with transfusion-transmitted infections. However, with the use of recombinant clotting factor concentrates, acquisition of such infections has now become rare. We studied the profile of hepatitis in North-American children with haemophilia in the modern era of safe blood products and excess childhood obesity. A total of 173 boys (<18 years) registered in the Pediatric Comprehensive Care Haemophilia Program were included in this retrospective study. Hospital records were reviewed for baseline data, serial height and weight measurements and serial alanine aminotransferase (ALT) levels. A body mass index (BMI) ranking was available for 170 boys, of whom 25 (14.7%, 95% CI 9.7-20.9%) were obese. The rate of obesity was higher in severe haemophilic boys. Compared with the general childhood population, the rate of obesity trended towards being higher in young haemophilic boys (2-5 years), but was similar in other age groups. A persistently high ALT (≥80 U L(-1) ) was documented in 5 boys and was associated with obesity. Three boys had clinical and imaging studies compatible with non-alcoholic fatty liver disease (NAFLD). Overweight and obesity are common among haemophilic boys, especially those who are younger and with severe disease. In this large group of haemophilic boys, chronic viral hepatitis was rare and NAFLD was a more common cause of liver disease. Overweight and obese haemophilic boys should be evaluated for NAFLD and interventional programmes should be designed to reduce the potential complications associated with obesity.

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Although there have been many therapeutic trials of chemotherapy for primary hepatoma, few have been controlled and the results of treatment have been disappointing. The present report is concerned with a controlled trial of chemotherapy alone versus radiotherapy followed by chemotherapy in 18 patients with primary hepatoma. Ten patients received quadruple chemotherapy (5-flurouracil, cyclophosphamide, methotrerate, and vincristine). These patients survived considerably longer (21 weeks) than eight patients who received radiotherapy followed by the same chemotherapy regime (12 weeks). Further analysis of these results suggested that length of survival in both treatment groups was related to age, length of history, levels of serum bilirubin and aspartate transaminase, and to the presence of cirrhosis or ascites. According to these criteria, patients were subdivided into two grades of disease. For patients with less severe disease (grade A), median survival after chemotherapy alone (54 weeks) was longer than after radiotherapy followed by chemotherapy (24 weeks). Survival of patients with severe disease (grade B) was equally poor in both treatment groups (5 weeks, chemotherapy; 7 5 weeks radiotherapy followed by chemotherapy). In conclusion, these results show that quadruple chemotherapy alone is a valuable form of therapy for grade A patients. Neither form of therapy, however, was of any benefit for grade B patients. is unfortunately applicable to only a minority of patients, as both lobes of the liver are so frequently involved. This is also not possible in the presence of cirrhosis, which is found in

Summary In a prospective controlled clinical trial, 108 patients with pancreatic adenocarcinoma were randomly allocated to receive tamoxifen 20 mg b.d., cyproterone acetate 100 mg t.d.s. or no active treatment. The median survival of those receiving tamoxifen was longer than either of the other two groups (5.25 compared to 4.25 and 3 months, respectively) but this difference did not achieve statistical significance. Cox regression analysis of 12 clinical and biochemical features showed that, for the entire group of patients, survival was significantly longer in younger patients, those undergoing surgical bypass and those with better initial performance status. However, even when adjustment was made to allow for the distribution of these prognostic variables within the three groups, the difference in survival still did not achieve statistical significance. No side-effects attributable to treatment was observed.Carcinoma of the pancreas accounts for approximately 6,500 deaths per year in the United Kingdom, a figure exceeded only by cancers of the lung, colon, breast and stomach (HMSO 1986(HMSO , 1988 Levin, 1981) and the overall 5-year survival rate is currently less than 1 % (Aoki & Ogawa, 1978;Bender et al., 1982). Cytotoxic chemotherapy has proved disappointing and while in the only controlled trial previously carried out survival was significantly prolonged, side-effects were severe and no patient survived longer than 2 years (Mallinson et al., 1980). Following the detection of sex-hormone receptors in pancreatic carcinoma tissue (Greenway et al., 1981;Satake et al., 1982;Sica et al., 1984), and evidence that manipulation of the hormonal environment could influence the growth rate of these tumours in experimental animal models (Greenway et al., 1982) there have been a number of reports suggesting that treatment with tamoxifen, an anti-oestrogen, may prolong survival (Theve et al., 1983;Tonnesen & Kemp-Jensen, 1986;Wong et al., 1987). However, the number of patients reported has been small and in no series was there a contemporary untreated control group. We now report a prospective randomised trial comparing the efficacy of tamoxifen, cyproterone acetate (an anti-androgen), and no specific treatment in 108 patients with unresectable pancreatic adenocarcinoma. Patients and trial designOn the basis of our previous experience the median survival of patients with pancreatic carcinoma, from the time of diagnosis, is in the order of 3 months. To detect a treatment which leads to a doubling of median survival, with 95% power, it was calculated that a minimum of 35 patients would be required in each group. Between 1984 and 1987, 108 patients were recruited from the eight participating centres (Table I). All patients gave informed consent, and the protocol was approved by the local ethical committees of the participating institutions.For recruitment into the study patients were required to have histological or cytological confirmation of pancreatic adenocarcinoma, or what were, in the opinion of the referr- ing physic...

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Hepatitis A and B vaccines are highly effective tools that can greatly reduce infection risk in the bleeding disorder population. Although hepatitis A and B immunization for individuals with bleeding disorders is universally recommended, various advisory bodies often differ with respect to many practical aspects of vaccination. To review the published literature and guidelines and form a practical, comprehensive and consistent approach to hepatitis A and B immunization for individuals with bleeding disorders. We reviewed published immunization guidelines from North American immunization advisory bodies and published statements from North American and international haemophilia advisory bodies. A search of the MEDLINE database was performed to find original published literature pertaining to hepatitis A or B immunization of patients with haemophilia or bleeding disorder patients that provided supporting or refuting evidence for advisory body guidelines. Various advisory bodies' immunization guidelines regarding individuals with bleeding disorders have contradictory statements and often did not clarify issues (e.g. post vaccination surveillance). Published literature addressing immunization in bleeding disorder patients is sparse and mostly examines route of vaccine administration, complications and corresponding antibody response. Although the risk of hepatitis A and B infection is low, the use of simple measures such as vaccination is reasonable and advocated by haemophilia advisory bodies. Following our review of the available literature and North American guidelines, we have developed comprehensive and practical recommendations addressing hepatitis A and B immunization for the bleeding disorder population that may be applicable in Bleeding Disorder clinics.

Background Children ≤36 months with Diffuse Intrinsic Pontine Glioma (DIPG) have increased long-term survival (LTS, overall survival (OS) ≥24 months). Understanding distinguishing characteristics in this population is critical to improving outcomes. Methods Patients ≤36 months at diagnosis enrolled on the International DIPG Registry (IDIPGR) with central imaging confirmation were included. Presentation, clinical course, imaging, pathology and molecular findings were analyzed. Results Among 1183 patients in IDIPGR, 40 were eligible (median age: 29 months). Median OS was 15 months. Twelve patients (30%) were LTS, 3 (7.5%) very long-term survivors ≥ 5 years. Among 8 untreated patients, median OS was 2 months. Patients enrolled in the registry but excluded from our study by central radiology review or tissue diagnosis had median OS of 7 months. All but 1 LTS received radiation. Among 32 treated patients, 1-, 2-, 3-, and 5-year OS rates were 68.8%, 31.2%, 15.6% and 12.5%, respectively. LTS had longer duration of presenting symptoms (p=0.018). No imaging features were predictive of outcome. Tissue and genomic data were available in 18 (45%) and 10 patients, respectively. Among 9 with known H3K27M status, 6 had a mutation. Conclusions Children ≤36 months demonstrated significantly more LTS, with an improved median OS of 15 months; 92% of LTS received radiation. Median OS in untreated children was 2 months, compared to 17 months for treated children. LTS had longer duration of symptoms. Excluded patients demonstrated a lower OS, contradicting the hypothesis that children ≤36 months with DIPG show improved outcomes due to misdiagnosis.