Time to onset of bisphosphonate-related osteonecrosis of the jaws: a multicentre retrospective cohort study.

OBJECTIVES: Osteonecrosis of the jaw (ONJ) is a potentially severe adverse effect of bisphosphonates (BP). Although the risk of ONJ increases with increasing duration of BP treatment, there are currently no reliable estimates of the ONJ time to onset (TTO). The objective of this study was to estimate the TTO and associated risk factors in BP-treated patients. SUBJECTS AND METHODS: Retrospective analysis of data from 22 secondary care centres in seven countries relevant to 349 patients who developed BP-related ONJ between 2004 and 2012. RESULTS: The median (95%CI) TTO was 6.0 years in patients treated with alendronate (n = 88) and 2.2 years in those treated with zoledronate (n = 218). Multivariable Cox regression showed that dentoalveolar surgery was inversely associated, and the use of antiangiogenics directly associated, with the TTO in patients with cancer treated with zoledronate. CONCLUSIONS: The incidence of ONJ increases with the duration of BP therapy, with notable differences observed with respect to BP type and potency, route of administration and underlying disease. When data are stratified by BP type, a time of 6.0 and 2.2 years of oral alendronate and intravenous zoledronate therapy, respectively, is required for 50% of patients to develop ONJ. After stratification by disease, a time of 5.3 and 2.2 years of BP therapy is required for 50% of patients with osteoporosis and cancer, respectively, to develop ONJ. These findings have significant implications for the design of future clinical studies and the development of risk-reduction strategies aimed at either assessing or modulating the risk of ONJ associated with BP.

Bone metastases from breast cancer treated with calcitonin. Case report.

A case of bone metastases from breast cancer is reported. After 6 months of therapy with calcitonin, the skeletal radiological examination showed an evident change in the roentgenographic pattern of a large metastasis of the left femur. A possible relationship between the calcitonin treatment and the radiological change is discussed.

[The use of urokinase and ammonium chloride in unblocking a central venous catheter in a child with acute lymphoblastic leukemia]. / Uso dell'urokinasi e del cloruro d'ammonio nella disostruzione di un catetere venoso centrale in un bambino con leucemia linfoblastica acuta.

Central venous catheter (C.V.C.) mechanical obstruction in immunocompromised patients can yield several complications sometime life-threatening and can be promptly solved by thrombolytic treatment. The authors describe a case of a child affected by acute lymphoblastic leukemia and experiencing an obstruction of his C.V.C. very difficult to treat with conventional urokinase treatment. Thinking the lack of success to be attributed to a calcium thrombus, the Authors before pulling out the C.V.C., made use of ammonium chloride solution in order to obtain the disappearance of the little bag covering the tip of C.V.C. The treatment was successful as confirmed by the contrast medium examination and the use of C.V.C. lasted for several months without other mechanical obstruction. In our best knowledge this is one of the first attempts with such ammonium chloride solution which have been used successful and rather safely. The only drug induced symptoms were constituted by mild and transient vomiting. Owing to this positive experience the authors believe useful to confirm this treatment in other cases. In this contest an experienced hematoncology team must take care of C.V.C. related complications.

Nitroderm TTS in exercise-induced angina pectoris--a randomized double-blind study.

Nitroderm TTS is a new transdermal delivery system for nitroglycerin, consisting of a self adhesive disc from which the drug diffuses into the skin at a predetermined rate through a microporous membrane. In an acute, randomized, double-blind, within-patient study, a TTS formulation releasing 10 mg of nitroglycerin over 24 hours (TTS 10) was compared with placebo and isosorbide dinitrate (ISDN) 20 mg slow-release. TTS 10, ISDN and placebo were given on 3 successive days, according to a 3 X 3 latin square design 3 times replicated, to 9 in-patients with coronary heart disease and stable exercise-induced angina pectoris. At rest, both TTS 10 and ISDN significantly lowered lying (p less than 0.05) and standing (p less than 0.01) systolic blood pressure as compared to placebo, but there was no difference between the 2 active treatments. On the symptoms-limited cycloergometric exercise test, carried out 4 hours post-dosing, both TTS 10 and ISDN significantly (p less than 0.05) improved exercise tolerance in respect to placebo. Treatments were well tolerated. In conclusion, both TTS 10 and ISDN, 4 hours post-dosing, are superior to placebo in improving exercise tolerance in patients with coronary heart disease and exercise-induced angina pectoris. The transdermal therapeutic system, allowing constant plasma nitroglycerin levels over 24 hours, has the advantage of once daily administration.

Randomised study of radical surgery versus radiotherapy for stage Ib-IIa cervical cancer.

BACKGROUND: Stage Ib and IIa cervical carcinoma can be cured by radical surgery or radiotherapy. These two procedures are equally effective, but differ in associated morbidity and type of complications. In this prospective randomised trial of radiotherapy versus surgery, our aim was to assess the 5-year survival and the rate and pattern of complications and recurrences associated with each treatment. METHODS: Between September, 1986, and December, 1991, 469 women with newly diagnosed stage Ib and IIa cervical carcinoma were referred to our institute. 343 eligible patients were randomised: 172 to surgery and 171 to radical radiotherapy. Adjuvant radiotherapy was delivered after surgery for women with surgical stage pT2b or greater, less than 3 mm of safe cervical stroma, cut-through, or positive nodes. The primary outcome measures were 5-year survival and the rate of complications. The analysis of survival and recurrence was by intention to treat and analysis of complications was by treatment delivered. FINDINGS: 170 patients in the surgery group and 167 in the radiotherapy group were included in the intention-to-treat analysis; scheduled treatment was delivered to 169 and 158 women, respectively, 62 of 114 women with cervical diameters of 4 cm or smaller and 46 of 55 with diameters larger than 4 cm received adjuvant therapy. After a median follow-up of 87 (range 57-120) months, 5-year overall and disease-free survival were identical in the surgery and radiotherapy groups (83% and 74%, respectively, for both groups), 86 women developed recurrent disease: 42 (25%) in the surgery group and 44 (26%) in the radiotherapy group. Significant factors for survival in univariate and multivariate analyses were: cervical diameter, positive lymphangiography, and adeno-carcinomatous histotype. 48 (28%) surgery-group patients had severe morbidity compared with 19 (12%) radiotherapy-group patients (p = 0.0004). INTERPRETATION: There is no treatment of choice for early-stage cervical carcinoma in terms of overall or disease-free survival. The combination of surgery and radiotherapy has the worst morbidity, especially urological complications. The optimum therapy for each patient should take account of clinical factors such as menopausal status, age, medical illness, histological type, and cervical diameter to yield the best cure with minimum complications.

Percutaneous treatment of iliac aneurysms and pseudoaneurysms with Cragg Endopro System 1 stent-grafts.

PURPOSE: To evaluate the feasibility and short-term follow-up results of treating iliac aneurysms by the Cragg Endopro System 1 stent-graft. METHODS: Nine lesions (two pseudoaneurysms and seven atherosclerotic aneurysms) were treated in eight patients by percutaneous implantation of a total of 10 stent-grafts. The procedure was followed by anticoagulation with heparin for 6 days, then antiplatelet therapy. Follow-up was by color Doppler ultrasound scan at 2 days and 3 months after the procedure for all patients, and by venous digital subtraction angiography and/or angio-CT up to 12 months later for four patients. RESULTS: Initial clinical success rate was 100% and there were two minor complications. In one case the delivery system was faulty resulting in failure to deploy the stent-graft. An additional device had to be used. At 3-12 months all prostheses were patent but one patient (12.5%) had a minimal pergraft leak. CONCLUSION: Percutaneous stent-grafting with this device is a safe and efficacious treatment of iliac artery aneurysms.

[Digital radiography in urography]. / La radiografia digitale in urografia.

The clinical utility was evaluated of a computed radiographic system in urography. The system (FCR 101, Philips Medical Systems, Inc., Shelton, CT) is based on a photo-stimulatable phosphor screen (imaging plate) for X-ray image detection and storage. The X-ray information recorded on the imaging plate is converted into digital from and processed by means of a computer. After processing is completed, the digitized image is reversed back to analogic signals, which modulate the intensity of a laser beam scanning the image on a single-emulsion film (Fuji CR 633). Two hundred IVP's were obtained in four groups, of 50 patients each, with normal azotemic values by rapid infusion of a low osmolality contrast medium (iopamidol 150 mgI/ml). While conventional radiographs were performed on the first group of patients with the injection of 0.6 gI/kg body weight of contrast medium, digital examinations were carried out, in the remaining three groups, with the injection of 0.6, 0.3 and 0.12 gI/kg, respectively. The digital images were processed with the "Abdomen-routine" program. A specific algorithm was implemented in order to reduce the excessive contrast resolution of the bladder, which is due to the characteristics of the nonionic contrast medium and enhanced by the reading program. The image details were evaluated by two observers and then statistically analyzed with nonparametric tests. Statistical analysis did not show any difference in the quality of digital and screen-film images. Image processing improved some inadequate images, by reducing the contrast resolution of the bladder, and allowed a better detection of some details. Low doses (0.3 gI/kg) of a low osmolality (150 mgI/kg) contrast medium were enough to obtain good images. Another biological advantage was obtained by a consistent radiation dose reduction (about 40%).