Orlistat treatment of unconjugated hyperbilirubinemia in Crigler-Najjar disease: A randomized controlled trial

Unconjugated hyperbilirubinemia in Crigler-Najjar (CN) disease is conventionally treated with phototherapy and phenobarbital. Orlistat treatment increases fecal fat excretion and decreases plasma unconjugated bifirubin (UCB) concentrations in Gunn rats, the animal model for CN disease. We determined in CN patients the effects of orlistat treatment on plasma UCB concentrations, and on fecal excretion of fat and UCB. A randomized, placebo-controlled, double-blind, cross-over trial was conducted in 16 patients, simultaneous with their regular treatment (phototherapy, n = 11, and/or phenobarbital, n = 6). Patients received orlistat or place bo, each for 4-6 wk. Compared with placebo, orlistat increased fecal fat excretion (+333%) and fecal UCB excretion (+43%). Orlistat treatment significantly decreased plasma UCB concentration (-9%). In 7 of 16 patients, the decrease in plasma UCB levels was clinically relevant (>10%, mean 21%). In patients with a clinically relevant response, plasma UCB concentrations during orlistat were strongly, negatively correlated with fecal fat excretion (r = -0.93). Clinically relevant response to orlistat treatment was not correlated with age, sex, CN type, BMI, or co-treatment with phototherapy or phenobarbital, but appeared correlated with a relatively lower dietary fat intake. In conclusion, orlistat treatment decreases plasma UCB concentrations, particularly in a subgroup of CN patients. Dietary fat intake may determine the responsiveness to orlistat treatment

Serum Immunoreactive Cationic Trypsinogen - a Useful Indicator of Severe Exocrine Dysfunction in the Pediatric-Patient Without Cystic-Fibrosis

We evaluated serum cationic trypsinogen as a marker of exocrine pancreatic function in children without cystic fibrosis. The ability of this test to determine steatorrhoea of pancreatic origin, and its relationship to a wide range of exocrine pancreatic function were assessed. Serum trypsinogen was measured in 32 children with steatorrhoea, 10 with pancreatic and 22 with non-pancreatic causes. In patients with pancreatic steatorrhoea, serum cationic trypsinogen was 4·9±4·9 μg/l (mean ±SD), significantly below values in patients with non-pancreatic steatorrhoea (47·0±22·1 μg/l, p<0·001) and 50 control subjects (31·4±7·4 μg/l, p<0·001). Serum cationic trypsinogen values in patients with pancreatic steatorrhoea all fell below the lower limit of our control range and below all values for patients with non-pancreatic steatorrhoea. Serum cationic trypsinogen was also evaluated against pancreatic trypsin output in 47 patients (range 0·2-17·0 yr) who underwent a hormonal pancreatic stimulation test. In 17 patients, serum cationic trypsinogen was low (<-2SD or 16·6 μg/l), and associated with greatly impaired pancreatic trypsin output, ranging from 0-8% of mean normal trypsin output. Five of these 17 patients did not have steatorrhoea. In 30 patients with normal or raised serum cationic trypsinogen (≥16·6 μg/l), pancreatic trypsin output ranged from 15-183% of mean normal values. In conclusion, low serum cationic trypsinogen suggests severely impaired exocrine pancreatic function, with sensitivity extending above the steatorrhoeic threshold. In the presence of steatorrhoea, low serum cationic trypsinogen indicates a pancreatic aetiology. Normal serum cationic trypsinogen, however, does not exclude impaired pancreatic function, above the steatorrhoeic threshold

Simulation techniques in hyperthermia treatment planning

Clinical trials have shown that hyperthermia (HT), i.e. an increase of tissue temperature to 39-44°C, significantly enhance radiotherapy and chemotherapy effectiveness (1). Driven by the developments in computational techniques and computing power, personalized hyperthermia treatment planning (HTP) has matured and has become a powerful tool for optimizing treatment quality. Electromagnetic, ultrasound, and thermal simulations using realistic clinical setups are now being performed to achieve patient-specific treatment optimization. In addition, extensive studies aimed to properly implement novel HT tools and techniques, and to assess the quality of HT, are becoming more common. In this paper, we review the simulation tools and techniques developed for clinical hyperthermia, and evaluate their current status on the path from “model” to “clinic”. In addition, we illustrate the major techniques employed for validation and optimization. HTP has become an essential tool for improvement, control, and assessment of HT treatment quality. As such, it plays a pivotal role in the quest to establish HT as an efficacious addition to multi-modality treatment of cancer