Osteoid osteoma and osteoid osteoma-mimicking lesions: biopsy findings, distinctive MDCT features and treatment by radiofrequency ablation.

OBJECTIVE: To report the biopsy findings of osteoid osteoma (OO) and OO-mimicking lesions, assess their distinctive multidetector computed tomography (MDCT) features and evaluate treatment by radiofrequency ablation (RFA). METHODS: In this multicentric retrospective study, 80 patients (54 male, 26 female, mean age 24.1 years, range 5-48) with presumed (clinical and MDCT features) OO were treated by percutaneous RFA between May 2002 and June 2009. Per-procedural biopsies were always performed. The following MDCT features were assessed: skeletal distribution and location within the bone, size, central calcification, surrounding osteosclerosis and periosteal reaction. Clinical success of RFA was evaluated. RESULTS: Histopathological diagnoses were: 54 inconclusive biopsies, 16 OO, 10 OO-mimicking lesions (5 chronic osteomyelitis, 3 chondroblastoma, 1 eosinophilic granuloma, 1 fibrous dysplasia). OO-mimicking lesions were significantly greater in size (p = 0.001) and presented non-significant trends towards medullary location (p = 0.246), moderate surrounding osteosclerosis (p = 0.189) and less periosteal reaction (p = 0.197), compared with OO. Primary success for ablation of OO-mimicking lesions was 100% at 1 month, 85.7% at 6 and 12 months, and 66.7% at 24 months. Secondary success was 100%. CONCLUSION: Larger size, medullary location, less surrounding osteosclerosis and periosteal reaction on MDCT may help differentiate OO-mimicking lesions from OO. OO-mimicking lesions are safely and successfully treated by RFA.

Hypertension artérielle réfractaire au traitement due au syndrome d'apnées du sommeil et à la prise de médicaments [Obstructive sleep apnea and drugs as causes of treatment-resistant hypertension].

Treatment-resistant hypertension is still common despite the availability of several types of antihypertensive agents acting by different mechanisms. The existence of refractory hypertension should lead to rule out "white-coat hypertension", poor adherence to prescribed drugs as well as classical causes of secondary hypertension such as renal artery stenosis, primary aldosteronism, pheochromocytoma and renal disease. It is also important to consider the possible existence of obstructive sleep apnea or the regular intake of vasopressive drugs or substances.

Traitement non chirurgical des rectites postactiniques ou radiques chroniques [Non-surgical treatment of acute and late radiation proctitis]

Pelvic external radiotherapy with or without brachytherapy plays an important role in the management of pelvic cancers. Despite recent technical innovations including conformal three-dimensional (3D) external beam radiotherapy and more recently intensity modulated radiotherapy (IMRT), local side effects can occur secondary to normal tissue damage caused by ionising radiation. Morbidity depends on the anatomic position of the rectum within the pelvis and the fast turnover rate of the mucosa, as well as the characteristics of the radiation treatment and patient co-morbidities. Medical management is sometimes complex and merits herein a short review.

Evaluation of organ-specific peripheral doses after 2-dimensional, 3-dimensional and hybrid intensity modulated radiation therapy for breast cancer based on Monte Carlo and convolution/superposition algorithms: implications for secondary cancer risk assessment.

To make a comprehensive evaluation of organ-specific out-of-field doses using Monte Carlo (MC) simulations for different breast cancer irradiation techniques and to compare results with a commercial treatment planning system (TPS). Three breast radiotherapy techniques using 6MV tangential photon beams were compared: (a) 2DRT (open rectangular fields), (b) 3DCRT (conformal wedged fields), and (c) hybrid IMRT (open conformal+modulated fields). Over 35 organs were contoured in a whole-body CT scan and organ-specific dose distributions were determined with MC and the TPS. Large differences in out-of-field doses were observed between MC and TPS calculations, even for organs close to the target volume such as the heart, the lungs and the contralateral breast (up to 70% difference). MC simulations showed that a large fraction of the out-of-field dose comes from the out-of-field head scatter fluence (>40%) which is not adequately modeled by the TPS. Based on MC simulations, the 3DCRT technique using external wedges yielded significantly higher doses (up to a factor 4-5 in the pelvis) than the 2DRT and the hybrid IMRT techniques which yielded similar out-of-field doses. In sharp contrast to popular belief, the IMRT technique investigated here does not increase the out-of-field dose compared to conventional techniques and may offer the most optimal plan. The 3DCRT technique with external wedges yields the largest out-of-field doses. For accurate out-of-field dose assessment, a commercial TPS should not be used, even for organs near the target volume (contralateral breast, lungs, heart).

Efficacy of Brief Behavioral Treatment for Chronic Insomnia in Older Adults

��Report: Background�� Chronic insomnia is a common health problemwith substantial consequences in older adults. Cognitive behavioraltreatments are efficacious but not widely available. The aimof this study was to test the efficacy of brief behavioral treatmentfor insomnia (BBTI) vs an information control (IC) condition.��Methods�� A total of 79 older adults (mean age, 71.7 years;54 women [70%]) with chronic insomnia and common comorbiditieswere recruited from the community and 1 primary care clinic.Participants were randomly assigned to either BBTI, consistingof individualized behavioral instructions delivered in 2 interventionsessions and 2 telephone calls, or IC, consisting of printededucational material. Both interventions were delivered by anurse clinician. The primary outcome was categorically definedtreatment response at 4 weeks, based on sleep questionnairesand diaries. Secondary outcomes included self-report symptomand health measures, sleep diaries, actigraphy, and polysomnography.��Conclusion�� We found that BBTI is a simple, efficacious,and durable intervention for chronic insomnia in older adultsthat has potential for dissemination across medical settings.����������

An international, randomized, double-blind, placebo-controlled, phase III trial of pregabalin monotherapy in treatment of patients with fibromyalgia.

OBJECTIVE: To evaluate the efficacy and safety of pregabalin monotherapy versus placebo for symptomatic pain relief and improvement of patient global assessment in patients with fibromyalgia (FM) enrolled from countries outside the United States. METHODS: This international, multicenter, double-blind, placebo-controlled trial randomly assigned 747 patients with FM to placebo or 300, 450, or 600 mg/day pregabalin twice daily for 14 weeks. Primary efficacy measures were endpoint mean pain scores and Patient Global Impression of Change (PGIC). Secondary outcomes included assessments of sleep and function. RESULTS: Patients in the 450 mg/day pregabalin group showed significant improvements versus placebo in endpoint mean pain score (-0.56; p = 0.0132), PGIC (73% improved vs 56% placebo; p = 0.0017), and function [Fibromyalgia Impact Questionnaire (FIQ) total score -5.85; p = 0.0012]. PGIC was also significant for 600 mg/day pregabalin (69% improved; p = 0.0227). Results for these endpoints were nonsignificant for pregabalin at 300 mg/day and for pain and FIQ score at 600 mg/day. Early onset of pain relief was seen, with separation from placebo detected by Week 1 in all pregabalin groups. All pregabalin doses demonstrated superiority to placebo on the Medical Outcomes Study-Sleep Scale Sleep Disturbance subscale and the Sleep Quality diary. Dizziness and somnolence were the most frequently reported adverse events. CONCLUSION: Pregabalin demonstrated modest efficacy in pain, global assessment, and function in FM at 450 mg/day, and improved sleep across all dose levels, but it did not provide consistent evidence of benefit at 300 and 600 mg/day in this study. Pregabalin was generally well tolerated for the treatment of FM. (Clinical trial registry NCT00333866).

Efficacy And Safety Of Baerveldt Aqueous Shunts In Glaucoma Secondary To Anterior Segment Irradiation, For Uveal Melanoma

Purpose: Elevated IOP is commonly associated with iris and ciliary body melanoma. Traditional management requires the majority of eyes to undergo enucleation. The authors describe the first series of Baerveldt aqueous shunts in eyes with uveal melanoma, treated by total anterior segment irradiation.Methods: 25 consecutive patients with unilateral iris melanoma were prospectively recruited after obtaining informed consent. All patients underwent anterior segment proton beam irradiation, corneal limbal autografts and Baerveldt tube implantation at Jules Gonin Eye Hospital, Lausanne. Postoperative examinations were performed on day 1, weeks 1,3,6,9 and months 3,6,12 and annually thereafter. Success was defined as: IOP </=18mmHg (definition A); IOP </= 21mmHg and 20% reduction in IOP (definition B). All complications were recorded.Results: Mean age was 53; mean follow up, 10.3 months; mean interval to treatment following irradiation, 2.4 years; mean pre-op IOP was 29.9 mmHg; mean post-op IOP 14.1 mmHg; mean pre-op medications 3.0; post-op medications 1.3. Success rates were, definition A: 95%; definition B: 90%. Only11% had minor complications and there were no sight-threatening complications. Aggressive ocular hypertension was observed in the several eyes prior to shunt implantation. Two eyes were enucleated for non-glaucoma related sequelae.Conclusions: Baerveldt aqueous shunts are safe and efficacious following total anterior segment irradiation for uveal melanoma. The novel interdisciplinary approach improved ocular retention rates, offering a promising alternative to current management algorithms.

Access to diagnosis and treatment of Chagas disease/infection in endemic and non-endemic countries in the XXI century

In this article, Médicos Sin Fronteras (MSF) Spain faces the challenge of selecting, piecing together, and conveying in the clearest possible way, the main lessons learnt over the course of the last seven years in the world of medical care for Chagas disease. More than two thousand children under the age of 14 have been treated; the majority of whom come from rural Latin American areas with difficult access. It is based on these lessons learnt, through mistakes and successes, that MSF advocates that medical care for patients with Chagas disease be a reality, in a manner which is inclusive (not exclusive), integrated (with medical, psychological, social, and educational components), and in which the patient is actively followed. This must be a multi-disease approach with permanent quality controls in place based on primary health care (PHC). Rapid diagnostic tests and new medications should be available, as well as therapeutic plans and patient management (including side effects) with standardised flows for medical care for patients within PHC in relation to secondary and tertiary level, inclusive of epidemiological surveillance systems.

Insuffisance rénale severe sur maladie des emboles de cholestérol: controverses thérapeutiques revisitées [Severe renal insufficiency secondary to renal cholesterol emboli: therapeutical options revisited]

Disseminated cholesterol crystal embolism is observed in elderly men with severe atherosclerosis. This syndrome may be triggered by arterial catheterizations, major vascular surgery, thrombolytic and/or anticoagulation treatment. Cutaneous signs, subacute renal insufficiency, a marked inflammatory syndrome and eosinophilia are common. Immunologic testing is normal except for hypocomplementaemia. The diagnosis may be confirmed by biopsy (skin, gastrointestinal or renal), and/or by a fundoscopic examination. The treatment consists in withdrawing all form of anticoagulation, proscribing vascular surgery and arterial catheterization, prescribing aspirin and statins, and controlling arterial blood pressure. Corticosteroids may be given in refractory cases. The prognosis of cholesterol crystal embolism is poor but may be improved by statins.

Hypertension artérielle réfractaire au traitement due au syndrome d'apnées du sommeil et à la prise de médicaments [Obstructive sleep apnea and drugs as causes of treatment-resistant hypertension].

Treatment-resistant hypertension is still common despite the availability of several types of antihypertensive agents acting by different mechanisms. The existence of refractory hypertension should lead to rule out "white-coat hypertension", poor adherence to prescribed drugs as well as classical causes of secondary hypertension such as renal artery stenosis, primary aldosteronism, pheochromocytoma and renal disease. It is also important to consider the possible existence of obstructive sleep apnea or the regular intake of vasopressive drugs or substances.

Treatment rationale and study design for a phase III, double-blind, placebo-controlled study of maintenance pemetrexed plus best supportive care versus best supportive care immediately following induction treatment with pemetrexed plus cisplatin for advanced nonsquamous non-small cell lung cancer.

BACKGROUND: To improve the efficacy of first-line therapy for advanced non-small cell lung cancer (NSCLC), additional maintenance chemotherapy may be given after initial induction chemotherapy in patients who did not progress during the initial treatment, rather than waiting for disease progression to administer second-line treatment. Maintenance therapy may consist of an agent that either was or was not present in the induction regimen. The antifolate pemetrexed is efficacious in combination with cisplatin for first-line treatment of advanced NSCLC and has shown efficacy as a maintenance agent in studies in which it was not included in the induction regimen. We designed a phase III study to determine if pemetrexed maintenance therapy improves progression-free survival (PFS) and overall survival (OS) after cisplatin/pemetrexed induction therapy in patients with advanced nonsquamous NSCLC. Furthermore, since evidence suggests expression levels of thymidylate synthase, the primary target of pemetrexed, may be associated with responsiveness to pemetrexed, translational research will address whether thymidylate synthase expression correlates with efficacy outcomes of pemetrexed. METHODS/DESIGN: Approximately 900 patients will receive four cycles of induction chemotherapy consisting of pemetrexed (500 mg/m2) and cisplatin (75 mg/m2) on day 1 of a 21-day cycle. Patients with an Eastern Cooperative Oncology Group performance status of 0 or 1 who have not progressed during induction therapy will randomly receive (in a 2:1 ratio) one of two double-blind maintenance regimens: pemetrexed (500 mg/m2 on day 1 of a 21-day cycle) plus best supportive care (BSC) or placebo plus BSC. The primary objective is to compare PFS between treatment arms. Secondary objectives include a fully powered analysis of OS, objective tumor response rate, patient-reported outcomes, resource utilization, and toxicity. Tumor specimens for translational research will be obtained from consenting patients before induction treatment, with a second biopsy performed in eligible patients following the induction phase. DISCUSSION: Although using a drug as maintenance therapy that was not used in the induction regimen exposes patients to an agent with a different mechanism of action, evidence suggests that continued use of an agent present in the induction regimen as maintenance therapy enables the identification of patients most likely to benefit from maintenance treatment.

Late pulmonary metastases of renal cell carcinoma immediatelyafter post-transplantation immunosuppressive treatment: a case report

INTRODUCTION We report a case of pulmonary metastatic recurrence of renal adenocarcinoma soon after radical nephrectomy that was followed by renal transplant and immunosuppressive medication. Increased risk of metastatic recurrence of renal cell carcinoma should be considered in the immediate post-transplant period when immunosuppressive medication is administered, even if nephrectomy had been performed many years earlier. CASE PRESENTATION In 1986 the patient demonstrated renal insufficiency secondary to mesangial glomerulonephritis. In 1992 he underwent left side radical nephrectomy with histopathological diagnosis of clear cell adenocarcinoma. Mesangial glomerulonephritis in the remaining right kidney progressed to end-stage renal failure. In October 2000 he received a kidney transplant from a cadaver and commenced immunosuppressive medication. Two months later, several nodules were found in his lungs, which were identified as metastases from the primary renal tumor that had been removed with the diseased kidney 8 years earlier. CONCLUSION Recurrence of renal cell carcinoma metastases points to tumor dormancy and reflects a misbalance between effective tumor immune surveillance and immune escape. This case demonstrates that a state of tumor dormancy can be interrupted soon after administration of immunosuppressant medication.

Improvement in secondary hyperparathyroidism due to drug adherence monitoring in dialysis patients.

BACKGROUND: Poor medication adherence is a frequent cause of treatment failure but is difficult to diagnose. In this study we have evaluated the impact of measuring adherence to cinacalcet-HCl and phosphate binders in dialysis patients with uncontrolled secondary hyperparathyroidism. METHODS: 7 chronic dialysis patients with iPTH-levels >= 300 pg/ml despite treatment with >= 60 mg cinacalcet-HCl were included. Medication adherence was measured using the "Medication Events Monitoring System" during 3 months, followed by another 3-month period without monitoring. The adherence results were monthly discussed with the patients, as well as strategies to improve them. RESULTS: During monitoring, the percentage of prescribed doses taken was higher for cinacalcet-HCl (87.4%) and sevelamer (86.3%) than for calcium acetate (76.1%), as was the taking adherence (81.9% vs. 57.3% vs. 49.1%) but not the percentage of drug holidays (12.3% vs. 4.5% vs. 3.6%). Mean PO4 levels (from 2.24 +/- 0.6 mmol/l to 1.73 +/- 0.41 mmol/l; p = 0.14) and Ca++ x PO4 product (4.73 +/- 1.43 to 3.41 +/- 1.04 mmol2/l2; p = 0.12) improved and iPTH-level improved significantly from 916 +/- 618 pg/ml to 442 +/- 326 pg/ml (p = 0.04), without any change in medication. However, as drug monitoring was interrupted, all laboratory parameters worsened again. CONCLUSIONS: Assessment of drug adherence helped to document episodes of non-compliance and helped to avoid seemingly necessary dose increases.

Zebrafish Based Small Molecule Screening For Retinoblastoma Treatment.

2320 composés chimiques ont été screenés à l'aide d'une lignée transgénique de zébrafish. Cette lignée comportait un gène humain fortement exprimé très tôt dans le développement et la croissance de différentes tumeurs, dont celle du rétinoblastome. L'activation de ce gène induisait la mort des embryons de lâ lignée transgénique. Nous avons donc pu identifier des composés agissant sur l'effet létal de ce gène. Cette étude a permis d'isoler plusieurs composés dont 1 très intéressant, l'Amitriptyline. Ce composé induit une inhibition de la prolifération et une induction d'apoptose dans les cellules humaines de rétinoblastome mais également dans d'autres cellules cancéreuses dont les ostéosarcomes connus. L'ostéosarçome est connu pour faire partie des cancers secondaires dû au rétinoblastome dans la forme héréditaire notamment. Ce composé induit la survie des embryons et réduit également le niveau d'expression de la protéine humaine intégrée dans la lignée de poisson zèbre transgénique de 50%. Le niveau d'expression de ce gène est également réduit de 50 à 60% dans des cultures cellulaire de rétinoblastome humain. L'inhibition de la prolifération a été démontrée par la réduction d'ATP dans plusieurs lignées cellulaires lorsque celles-ci sont traitées avec ce composé. L'induction d'apoptose a été démontrée par induction 10 fois plus élevée des éléments pro-apoptotiques caspase-3 et caspase-7 ainsi que par l'augmentation 10 fois plus élevée d'un élément anti-apoptotique bcl-2. Ces résultats permettent de croire que ce composé pourrait être utilisé pour traiter le rétinoblastome humain. -- Background: Retinoblastoma is a rare malignant tumor. This disease is the most prevalent intraocular cancer in childhood with an incidence of 1 in 15,000 live births. Many therapies are available to treat retinoblastoma, but best treatments are individually selected according to cases. Cryotherapy, thermotherapy, laser therapy including brachytherapy, radiation therapy and chemotherapy are some examples. New drug and new treatments discovery is essential for cancer therapy including retinoblastoma. Purpose: A vertebrate model as zebrafish for retinoblastoma would provide many advantages especially to perform drug screening. The high number of fertilized eggs per mating, the rapidity of extra¬utero development, the available genetic manipulation, the easy manipulations under a microscope, the ability to dispense embryos in 96-well plates and the direct incubation of chemical compounds in fish water are some examples of the advantages. Therefore, we design a transgenic zebrafish carrying a human gene implicated in retinoblastoma development and maintenance. Results: With the small compounds screening, several compounds were isolated. One of these compounds, Amitriptyline demonstrated proliferation inhibition and apoptosis in human retinoblastoma cells, U20S osteosarcoma cells and MBA-231 breast cancer cells. Osteosarcoma is known as secondary cancer due to retinoblastoma. Amitriptyline induced survival in our zebrafish transgenic line and 50% reduction of the integrated gene expression. In retinoblastoma cultured cells, the expression of this gene was also reduced in a range of 50-60 %. Proliferation inhibition was demonstrated by ATP luminescence assay. Apoptosis was demonstrated by a 10-fold induction of caspase-3 and caspase-7, two pro-apoptotic elements and by a 10-fold reduction of bcl-2 anti-apoptotic element. Conclusion: The results suggest that Amitriptyline could be used to treat human retinoblastoma in the near future.

Sevelamer hydrochloride: A novel treatment of hyperphosphatemia associated with tumor lysis syndrome in children

Background. Sevelamer is a phosphate-binder used effectively for the treatment of hyperphosphatemia in patients treated with dialysis. Objectives. To describe the safety of sevelamer in children with hyperphosphatemia secondary to tumor lysis syndrome and the serum phosphate concentrations observed following its administration. Procedure. A retrospective chart review of all children with leukemia/lymphoma diagnosed between November 2002 and April 2004 who received sevelamer during their initial admission was conducted. We monitored the effects of sevelamer on serum phosphate concentration, calcium/phosphate product and renal function at hours 24, 48, and 72 from sevelamer initiation. Results. Thirteen patients received sevelamer during the Study period. Their median age was 13 years (range 2.7-17.9) and eight were boys. Nine children had acute lymphoblastic leukemia, one had acute myeloid leukemia and 3 had non-Hodgkin's lymphoma. The most frequently used dose of sevelamer was 400 mg orally twice daily. The median duration of sevelamer therapy was 2 days (range 1 -7). Two children were excluded from the efficacy analysis due to concurrent use of dialysis. Mean serum phosphate levels decreased after sevelamer administration, in eleven patients, from a baseline 2.2 mmol/L +/- 0.4 (95% Cl, 1.7-3.1) to 1.1 mmol/L +/- 0.2 at hour 72 (95%Cl, 0.6-1.5). The only toxicity attributed to sevelamer was mild vomiting in three patients. Conclusions. Sevelamer appears to be effective and tolerable for the treatment of hyperphosphatemia associated with tumor lysis syndrome.