Natural History of Perinatal and Infantile Hypophosphatasia: A Retrospective Study.

OBJECTIVE: To report clinical characteristics and medical history data obtained retrospectively for a large cohort of pediatric patients with perinatal and infantile hypophosphatasia. STUDY DESIGN: Medical records from academic medical centers known to diagnose and/or treat hypophosphatasia were reviewed. Patients born between 1970 and 2011 with hypophosphatasia and any of the following signs/symptoms at age <6 months were eligible: vitamin B6-dependent seizures, respiratory compromise, or rachitic chest deformity (NCT01419028). Patient demographics and characteristics, respiratory support requirements, invasive ventilator-free survival, and further complications of hypophosphatasia were followed for up to the first 5 years of life. RESULTS: Forty-eight patients represented 12 study sites in 7 countries; 13 patients were alive, and 35 were dead (including 1 stillborn). Chest deformity, respiratory distress, respiratory failure (as conditioned by the eligibility criteria), failure to thrive, and elevated calcium levels were present in >70% of patients between birth and age 5 years. Vitamin B6-dependent seizures and respiratory distress and failure were associated significantly (P < .05) with the risk of early death. Serum alkaline phosphatase activity in all 41 patients tested (mean [SD]: 18.1 [15.4] U/L) was below the mean lower limit of normal of the reference ranges of the various laboratories (88.2 U/L). Among the 45 patients with relevant data, 29 had received respiratory support, of whom 26 had died at the time of data collection. The likelihood of invasive ventilator-free survival for this cohort decreased to 63% at 3 months, 54% at 6 months, 31% at 12 months, and 25% at 5 years. CONCLUSIONS: Patients with perinatal or infantile hypophosphatasia and vitamin B6-dependent seizures, with or without significant respiratory distress or chest deformities, have high morbidity and mortality in the first 5 years of life. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01419028.

Pancreas exocrine replacement therapy is associated with increased survival following pancreatoduodenectomy for periampullary malignancy.

BACKGROUND: Although many patients undergoing pancreatoduodenectomy (PD) for cancer have pancreatic exocrine insufficiency, pancreatic enzyme replacement therapy (PERT) is not routinely used, and effects upon post-operative survival are unclear. METHODS: This review of patients undergoing PD for periampullary malignancy sought to test for an association between PERT and overall survival, with post-hoc subgroup analysis performed after stratifying patients by the year of surgery, pancreatic duct width and tumour type. RESULTS: Some 202/469 (43.1%) patients received PERT. After accounting for pathological variables and chemotherapy, PERT use was found to be independently associated with improved survival on multivariable analysis [HR 0.72 (95% CI: 0.52-0.99), p = 0.044] and on propensity matched analysis (p = 0.009). The effect of PERT upon improved survival was predominantly observed amongst patients with a dilated pancreatic duct (≥3 mm). DISCUSSION: PERT use was independently associated with improved survival following PD for cancer. The validity of this observation is supported by an effect largely confined to those patients with a dilated pancreatic duct. The nutritional status of patients undergoing PD for cancer needs further investigation and the effects of PERT require verification in further clinical studies.