Cementless total hip arthroplasty in Paget’s disease of bone: a retrospective review

Paget’s disease of bone (PDB) is a localised chronic osteopathy leading to bone deformities, bone hypervascularity, structural weakness and altered joint biomechanics. The pelvis and upper femur are frequently involved, resulting in disabling hip disease, and total hip arthroplasty (THA) may be required. We performed a retrospective study on the management and the outcome of 39 uncemented hydroxyapatite fully-coated THA in patients with PDB of the hip. The follow-up averaged 79.4 months (range 24–194). Functional scores improved significantly and, using the Harris hip score, 84% of patients had an excellent clinical outcome at the latest follow-up. Despite one case of an uncemented acetabular component with probable loosening, no implant revision had been required at our latest follow-up. Signs of implant loosening were found to be significantly more frequent in patients with active disease. For this reason, we advocate the use of pre-operative medication with bisphosphonates to reduce disease activity. Another benefit of this treatment is the significant decrease of intra-operative blood loss. Provided the control of disease activity in the pre-operative period with bisphosphonates is achieved, good outcome of cementless THAs can be expected. Bisphosphonates reduced the risk of implant loosening and excessive intra-operative blood loss

A Phase I Dose-Escalation Study of Lenalidomide in Combination with Gemcitabine in Patients with Advanced Pancreatic Cancer

Purpose Lenalidomide have both immunomodulatory and anti-angiogenic properties which could confer anti-cancer effects. The aim of this study was to assess the feasibility of combining lenalidomide with the standard treatment gemcitabine in pancreatic cancer patients with advanced disease. Patients and Methods Eligible patients had locally advanced or metastatic adenocarcinoma of the pancreas. Patients received lenalidomide days 1-21 orally and gemcitabine 1000 mg/m(2) intravenously (days 1, 8 and 15), each 28 day cycle. Three cohorts of lenalidomide were examined (Cohort I = 15 mg, Cohort II = 20 mg and Cohort III = 25 mg daily). The maximum tolerated dose (MTD) of lenalidomide given in combination with gemcitabine was defined as the highest dose level at which no more than one out of four (25%) subjects experiences a dose-limiting toxicity (DLT). Patients should also be able to receive daily low molecular weight heparin (LMWH) (e.g. dalteparin 5000 IU s.c. daily) as a prophylactic anticoagulant for venous thromboembolic events (VTEs). Twelve patients (n = 4, n = 3 and n = 5 in cohort I, II and III, respectively) were enrolled in this study. Results Median duration of treatment was 11 weeks (range 1-66), and median number of treatment cycles were three (range 1-14). The only DLT was a cardiac failure grade 3 in cohort III. Frequent treatment-related adverse events (AEs) (all grades) included neutropenia, leucopenia and fatigue (83% each, but there was no febrile neutropenia); thrombocytopenia (75%); dermatological toxicity (75%); diarrhea and nausea (42% each); and neuropathy (42%). Discussion This phase I study demonstrates the feasibility of the combination of lenalidomide and gemcitabine as first-line treatment in patients with advanced pancreatic cancer. The tolerability profile demonstrated in the dose escalation schedule of lenalidomide suggests the dosing of lenalidomide to be 25 mg daily on days 1-21 with standard dosing of gemcitabine and merits further evaluation in a phase II trial