Spontaneous Bilateral Femoral Fractures After High-Dose Zoledronic Acid.

The authors report a case of spontaneous bilateral diaphyseal femoral fractures believed to be caused by oversuppression of bone remodeling as a result of long-term, high-dose treatment with bisphosphonate. The patient reported pain in both thighs before the fractures. Typical pathologic changes appeared on both femoral radiograph and bone scan before the fractures. Several hours after admission to the emergency department of the authors' institution, the patient underwent closed reduction and internal fixation with intramedullary nails for the bilateral femoral diaphyseal fractures. Treatment with zoledronic acid was immediately discontinued. In recent years, low-energy femoral diaphyseal fractures in patients undergoing long-term bisphosphonate treatment have been reported. It is believed that the prolonged treatment causes long-term suppression of bone remodeling and accumulation of microdamage. It is important to observe patients who are undergoing bisphosphonate treatment carefully. In this case study, the authors report the patient's unique medical history.

Liver retransplantation: a model for determining long-term survival.

BACKGROUND: Because of the worse results from retransplantation in relation to the initial liver transplantation, there is a need to refine the indication for retransplantation, such that fair distribution of this benefit is obtained. METHODS: This was a study of 139 patients who underwent liver retransplantation. Thirty variables were studied: 18 relating to the recipient and 12 to the donor. All the independent variables were initially compared with the length of survival using univariate analyses. Variables presenting significance were compared with the dependent variable of length of survival, to determine which factors were related to longer survival among patients, when evaluated together. RESULTS: A multivariate model for determining long-term survival among patients with retransplants was built up using the following variables: recipient's age, creatinine, urgency of retransplantation and early failure of the first graft. Through this multivariate model it was possible to determine a score that was categorized according to tertile distributions (below the 33rd percentile, score <24; 33rd to 66th percentile, 24 < or = score < or = 32; above the 66th percentile, score > 32). One-year, 3-year, and 5-year patient survival rates following retransplantation were respectively 85%, 82%, and 77% for scores <24; 69%, 66%, and 61% for scores between 24 and 32; and 21%, 19%, and 16% for scores >32 (P < 0.0001). CONCLUSION: The variables of recipient's age, creatinine, urgency of retransplantation, and early failure of the initial transplantation were factors that were independently related to the long-term survival of patients with liver retransplants.

Oxaliplatin plus irinotecan and FU-FOL combination and pharmacokinetic analysis in advanced colorectal cancer patients.

This phase I-II trial was designed to assess the effect of irinotecan on oxaliplatin pharmacokinetics and to determine the MDT of both drugs when administered in combination. Treatment was repeated every 2 weeks. Pharmacokinetic studies were performed on cycle 1 and 2 to assess the best sequence and detect any interaction between the two drugs. Thirty-four patients with advanced colorectal cancer were enrolled; 28 of them (82%) had liver involvement. The main toxicities were neutropenia and delayed diarrhea; 5 patients (14%) experienced febrile neutropenia. Dose-limiting toxicity was experienced at levels 1/2/3/4/5 by 4/10, 1/6, 3/6, 3/8, and 3/4 patients, respectively. Fifteen patients responded (2 CR; 13 PR) for an ORR of 44%. No pharmacokinetic interactions between irinotecan and oxaliplatin were detected. The recommended dose for future phase II trials is oxaliplatin 85 mg/m and irinotecan 180 mg/m2 on day 1 combined with 5FU/leucovorin according to the de Gramont regimen at days 2 and 3. Twenty-nine percent of patients underwent secondary hepatectomy with curative intent, and two of them are long-term disease-free survivors. It would appear that the dose and schedule defined by this trial could be proposed as front-line therapy for advanced colorectal carcinoma to establish rapid disease control and to permit patients to proceed to surgery.