Helical tomotherapy (HT) for the treatment of anal canal cancer: preliminary clinical results, and dosimetric comparison between HT and intensity-modulated or 3D conformal radiotherapy

Background: To report a single-center experience in 19 patients (pts) with anal canal cancer treated with helical tomotherapy (HT) and concurrent chemotherapy, and compare the dosimetric results with fixed-field intensitymodulated radiotherapy (IMRT) and 3D conformal radiotherapy (3D RT). Materials and Methods: Between 2007 and 2008, 19 consecutive pts were treated with HT and concurrent CT for anal canal cancer. Median age was 59 years (range, 38−83), and female/male ratio was 14/5. The majority of the pts had T2 or T3 tumours (68.4%), and 52.6% had positive lymph nodes. In all 19 pts, pelvic and inguinal nodes, and tumour irradiation was given using HT upto a median dose of 36 Gy (1.8 Gy/fr) followed by a 1-week gap. A boost dose of 23.4 Gy (1.8 Gy/fr) was delivered to the tumour and involved nodes using 3DRT (n = 12), HT (n = 6), or IMRT (n = 1). Simultaneous integrated boost was used in none of the pts. All but one patient with a T1N0 tumour received concomitant mitomycin/5- fluorouracil (n = 12) or mitomycin/capecitabin (n = 7) CT. Toxicity was scored according to the Common Terminology Criteria for Adverse Events (NCICTCAE v3.0). HT plans and treatments were generated using Tomotherapy, Inc., software and hardware; and 3D or IMRT boost plans with the CMS treatment planning system (TPS), using 6−18 MV photons from a Siemens Primus accelerator. For dosimetric comparison, computed tomography data sets of 10 pts were imported into the TPS, and 3D and 5-field step-andshoot IMRT plans were generated for each case. Plans were optimized with the aim of assessing organs at risk (OAR) and healthy-tissue sparing while enforcing highly conformal target coverage, and evaluated by dose-volume histograms (DVH) of planning target volumes (PTV) and OAR. Results: With a median follow-up of 13 months (range, 3−18), all pts are alive and well; except one patient developing local recurrence at 12 months. No patient developed grade 3 or more acute toxicity. No unplanned treatment interruption was necessary because of toxicity. With 360-degree-of-freedom beam projection, HT showed an advantage over 3D or IMRT plans in terms of dose conformity around the PTV, and dose gradients were steeper outside the PTV, resulting in reduced doses to OARs. Using HT, acute toxicity was acceptable, and seemed to be better than historical standards. Conclusion: We conclude that HT combined with concurrent chemotherapy for anal canal cancer is effective and tolerable. Compared to 3DRT or 5-field IMRT, there is better conformity around the PTV, and OAR sparing.

Traitement des fibroses pulmonaires idiopathiques [Treatment of idiopathic pulmonary fibrosis]

Idiopathic pulmonary fibrosis still has to be diagnosed by elimination. Neoplasm, toxic treatments, collagen vascular disease, professional exposure or diagnosis such as sarcoidosis have to be ruled out. The repercussions on gas exchange are the most reliable indications of the severity of the disease, the pulmonary function test or chest x-rays alone being often misleading. Transbronchic biopsies, thoracotomy or thoracoscopies provide a precise diagnosis. In many cases only broncho-alveolar lavage and a high resolution CT-scan are performed to rule out infection or tumor and to assess the inflammatory state of the disease. Due to the often poor prognosis of this disease and its often poor response to steroids, the role of cytostatic drugs, cyclosporine and colchicine, and of pulmonary graft is discussed.

Comparative randomised trial of high and conventional doses of praziquantel in the treatment of schistosomiasis mansoni

The efficacy of oral praziquantel in the treatment of schistosomiasis has been considered low by most public health institutions. In this paper, we compared the efficacy of two dosages of praziquantel (80 mg/kg vs. 50 mg/kg) in patients with chronic schistosomiasis mansoni. Two hundred eighty-eight patients with schistosomiasis from a community in Brazil were randomly divided into two groups: 145 patients (Group 1) received 80 mg/kg body weight of oral praziquantel divided in two equal doses with 1 h interval and 143 patients (Group 2) received 50 mg/kg body weight of oral praziquantel. To keep the study masked, patients in Group 2 received placebo 1 h after the first dose. All patients were subjected to clinical and ultrasonographic examination. Cure assessment was performed by repeating two stool examinations, by a quantitative method, at 30, 90 and 180 days after treatment. The morbidity of schistosomiasis was low, with a few cases of light periportal thickening and 16 cases of mild splenomegaly. The cure rates were 89.7% for Group 1 and 83.9% for Group 2. There was no difference in the efficacy of both therapeutic dosages of praziquantel assayed. The adverse reactions were more frequent with higher dosage.

The benefits of using selenium in the treatment of Chagas disease: prevention of right ventricle chamber dilatation and reversion of Trypanosoma cruzi-induced acute and chronic cardiomyopathy in mice

Cardiac damage is a frequent manifestation of Chagas disease, which is caused by the parasite Trypanosoma cruzi. Selenium (Se) is an essential micronutrient, the deficiency of which has been implicated in the development of cardiomyopathy. Our group has previously demonstrated that Se supplementation prevents myocardial damage during acute T. cruzi infection in mice. In this study, we analyzed the effect of Se treatment in cases of T. cruzi infection using prevention and reversion schemes. In the Se prevention scheme, mice were given Se supplements (2 ppm) starting two weeks prior to inoculation with T. cruzi(Brazil strain) and continuing until 120 days post-infection (dpi). In the Se reversion scheme, mice were treated with Se (4 ppm) for 100 days, starting at 160 dpi. Dilatation of the right ventricle was observed in the infected control group at both phases of T. cruzi infection, but it was not observed in the infected group that received Se treatment. Surviving infected mice that were submitted to the Se reversion scheme presented normal P wave values and reduced inflammation of the pericardium. These data indicate that Se treatment prevents right ventricular chamber increase and thus can be proposed as an adjuvant therapy for cardiac alterations already established by T. cruziinfection.

Eligibility for and outcome of treatment of latent tuberculosis infection in a cohort of HIV-infected people in Spain

BACKGROUND Previous studies have demonstrated the efficacy of treatment for latent tuberculosis infection (TLTBI) in persons infected with the human immunodeficiency virus, but few studies have investigated the operational aspects of implementing TLTBI in the co-infected population.The study objectives were to describe eligibility for TLTBI as well as treatment prescription, initiation and completion in an HIV-infected Spanish cohort and to investigate factors associated with treatment completion. METHODS Subjects were prospectively identified between 2000 and 2003 at ten HIV hospital-based clinics in Spain. Data were obtained from clinical records. Associations were measured using the odds ratio (OR) and its 95% confidence interval (95% CI). RESULTS A total of 1242 subjects were recruited and 846 (68.1%) were evaluated for TLTBI. Of these, 181 (21.4%) were eligible for TLTBI either because they were tuberculin skin test (TST) positive (121) or because their TST was negative/unknown but they were known contacts of a TB case or had impaired immunity (60). Of the patients eligible for TLTBI, 122 (67.4%) initiated TLTBI: 99 (81.1%) were treated with isoniazid for 6, 9 or 12 months; and 23 (18.9%) with short-course regimens including rifampin plus isoniazid and/or pyrazinamide. In total, 70 patients (57.4%) completed treatment, 39 (32.0%) defaulted, 7 (5.7%) interrupted treatment due to adverse effects, 2 developed TB, 2 died, and 2 moved away. Treatment completion was associated with having acquired HIV infection through heterosexual sex as compared to intravenous drug use (OR:4.6; 95% CI:1.4-14.7) and with having taken rifampin and pyrazinamide for 2 months as compared to isoniazid for 9 months (OR:8.3; 95% CI:2.7-24.9). CONCLUSIONS A minority of HIV-infected patients eligible for TLTBI actually starts and completes a course of treatment. Obstacles to successful implementation of this intervention need to be addressed.

An Open-Label, Noncomparative, Multicenter Study to Evaluate Efficacy and Safety of NASHA/Dx Gel as a Bulking Agent for the Treatment of Fecal Incontinence

Fecal incontinence (FI) is the involuntary loss of rectal contents through the anal canal. Reports of its prevalence vary from 1-21%. Studies, have demonstrated a positive effect on FI symptoms with injectable bulking agents. This study evaluated the safety and efficacy of NASHA/Dx gel in the treatment of FI. One hundred fifteen eligible patients suffering from FI received 4 injections of 1 mL NASHA/Dx gel. Primary efficacy was based on data from 86 patients that completed the study. This study demonstrated a ≥50% reduction from baseline in the number of FI episodes in 57.1% of patients at 6 months, and 64.0% at 12 months. Significant improvements (P < .001) were also noted in total number of both solid and loose FI episodes, FI free days, CCFIS, and FIQL scores in all 4 domains. The majority of the treatment related AEs (94.9%) were mild or moderate intensity, and (98.7%) of AEs resolved spontaneously, or following treatment, without sequelae. Results of this study indicate NASHA/Dx gel was efficacious in the treatment of FI. Treatment effect was significant both in reduction of number of FI episodes and disease specific quality of life at 6 months and lasted up to 12 months after treatment.

The anticancer drug tamoxifen is active against Trypanosoma cruzi in vitro but ineffective in the treatment of the acute phase of Chagas disease in mice

The activity of the antineoplastic drug tamoxifen was evaluated against Trypanosoma cruzi. In vitro activity was determined against epimastigote, trypomastigote and amastigote forms of CL14, Y and Y benznidazole resistant T. cruzi strains. Regardless of the strain used, the drug was active against all life-cycle stages of the parasite with a half maximal effective concentration ranging from 0.7-17.9 µM. Two experimental models of acute Chagas disease were used to evaluate the in vivo efficacy of treatment with tamoxifen. No differences in parasitemia and mortality were observed between control mock-treated and tamoxifen-treated mice.

Prevention and treatment of protein energy wasting in chronic kidney disease patients: a consensus statement by the International Society of Renal Nutrition and Metabolism.

Protein energy wasting (PEW) is common in patients with chronic kidney disease (CKD) and is associated with adverse clinical outcomes, especially in individuals receiving maintenance dialysis therapy. A multitude of factors can affect the nutritional and metabolic status of CKD patients requiring a combination of therapeutic maneuvers to prevent or reverse protein and energy depletion. These include optimizing dietary nutrient intake, appropriate treatment of metabolic disturbances such as metabolic acidosis, systemic inflammation, and hormonal deficiencies, and prescribing optimized dialytic regimens. In patients where oral dietary intake from regular meals cannot maintain adequate nutritional status, nutritional supplementation, administered orally, enterally, or parenterally, is shown to be effective in replenishing protein and energy stores. In clinical practice, the advantages of oral nutritional supplements include proven efficacy, safety, and compliance. Anabolic strategies such as anabolic steroids, growth hormone, and exercise, in combination with nutritional supplementation or alone, have been shown to improve protein stores and represent potential additional approaches for the treatment of PEW. Appetite stimulants, anti-inflammatory interventions, and newer anabolic agents are emerging as novel therapies. While numerous epidemiological data suggest that an improvement in biomarkers of nutritional status is associated with improved survival, there are no large randomized clinical trials that have tested the effectiveness of nutritional interventions on mortality and morbidity.

Granulocyte colony-stimulating factor in the treatment of high-risk febrile neutropenia: a multicenter randomized trial.

BACKGROUND Granulocyte colony-stimulating factors (G-CSFs) have been shown to help prevent febrile neutropenia in certain subgroups of cancer patients undergoing chemotherapy, but their role in treating febrile neutropenia is controversial. The purpose of our study was to evaluate-in a prospective multicenter randomized clinical trial-the efficacy of adding G-CSF to broad-spectrum antibiotic treatment of patients with solid tumors and high-risk febrile neutropenia. METHODS A total of 210 patients with solid tumors treated with conventional-dose chemotherapy who presented with fever and grade IV neutropenia were considered to be eligible for the trial. They met at least one of the following high-risk criteria: profound neutropenia (absolute neutrophil count <100/mm(3)), short latency from previous chemotherapy cycle (<10 days), sepsis or clinically documented infection at presentation, severe comorbidity, performance status of 3-4 (Eastern Cooperative Oncology Group scale), or prior inpatient status. Eligible patients were randomly assigned to receive the antibiotics ceftazidime and amikacin, with or without G-CSF (5 microg/kg per day). The primary study end point was the duration of hospitalization. All P values were two-sided. RESULTS Patients randomly assigned to receive G-CSF had a significantly shorter duration of grade IV neutropenia (median, 2 days versus 3 days; P = 0.0004), antibiotic therapy (median, 5 days versus 6 days; P = 0.013), and hospital stay (median, 5 days versus 7 days; P = 0.015) than patients in the control arm. The incidence of serious medical complications not present at the initial clinical evaluation was 10% in the G-CSF group and 17% in the control group (P = 0.12), including five deaths in each study arm. The median cost of hospital stay and the median overall cost per patient admission were reduced by 17% (P = 0.01) and by 11% (P = 0.07), respectively, in the G-CSF arm compared with the control arm. CONCLUSIONS Adding G-CSF to antibiotic therapy shortens the duration of neutropenia, reduces the duration of antibiotic therapy and hospitalization, and decreases hospital costs in patients with high-risk febrile neutropenia.

Effects of motive-oriented therapeutic relationship in early-phase treatment of borderline personality disorder: a pilot study of a randomized trial.

Motive-oriented therapeutic relationship (MOTR, also called complementary therapeutic relationship) was postulated to be a particularly helpful therapeutic ingredient in the early-phase treatment of patients with personality disorders, in particular borderline personality disorder (BPD). The present pilot study of randomized controlled trial using an add-on design aims to investigate the effects of MOTR in early-phase treatment (up to session 10), with BPD patients on therapeutic alliance, session impact, and outcome. In total, N = 25 patients participated in the study. BPD patients were randomly allocated to a manual-based investigation process in 10 sessions or to the same investigation process infused with MOTR. Adherence ratings were performed and yielded satisfactory results. The results suggested a specific effectiveness of MOTR on the interpersonal problem area, on the quality of the therapeutic alliance and the quality of the therapeutic relationship, as rated by the patient. These results may have important clinical implications for the early-phase treatment of patients presenting with BPD.

A randomized phase II trial of a drug eluting bead in the treatment of hepatocellular carcinoma by transcatheter arterial chemoembolization

Background: Transcatheter arterial chemoembolization (TACE) has been shown to offer a survival benefit for patients with intermediate-stage hepatocellular carcinoma (HCC). A widely accepted TACE regimen includes the administration of a doxorubicin-in-oil emulsion followed by gelatine sponge particles. Recently, a drug-eluting bead (DEB) has been developed to enhance drug delivery to the tumor and reduce its systemic availability. Purpose of this randomized trial was to compare conventional TACE with DEB-TACE for the treatment of intermediate-stage HCC in patients with cirrhosis. Methods: Two hundred and twelve patients (185 males and 27 females; mean age, 67 years) with Child-Pugh A or B liver cirrhosis and large and/or multinodular, unresectable HCC were randomized to receive DEB-TACE (DC Bead; Biocompatibles, UK) uploaded with doxorubicin or conventional TACE with doxorubicin, lipiodol, and gelatin sponge particles. Randomization was stratified according to Child Pugh status (A or B), performance status (ECOG 0 or 1), bilobar disease (yes or no) and prior curative treatment (yes or no). Tumor response at 6 months was the primary study endpoint. An independent, blinded review of magnetic resonance imaging studies was conducted to assess tumor response according to amended RECIST criteria. Results: DEB-TACE with doxorubicin showed a higher rate of complete response, objective response and disease control compared with conventional TACE (27% vs 22%; 52% vs 44%; and 63% vs 52%, respectively; p>0.05). Patients with Child Pugh B, ECOG 1, bilobar disease and recurrence following curative treatment showed a significant increase in objective response (p=0.038) compared to the control. There was a marked reduction in serious liver toxicity in patients treated with DEB-TACE. The rate of doxorubicin related side effects was significantly lower (p=0.0001) in the DEB-TACE group compared with the conventional TACE group. Conclusions: DEB-TACE with doxorubicin is safe and effective in the treatment of intermediate-stage HCC and may offer benefit to patients with more advanced disease.

Effectiveness of the bevacizumab-irinotecan regimen in the treatment of recurrent glioblastoma multiforme: Comparison with other second-line treatments without this regimen.

A retrospective cohort study was conducted to analyse the effectiveness of bevacizumab and irinotecan (BVZ/CPT-11) as a second-line treatment in patients with primary glioblastoma multiforme (GBM) in comparison with a control group that were not administered BVZ/CPT-11 at the first recurrence. The difference in overall survival (OS) between the two groups was used as a predictor of effectiveness. OS was calculated according to prognostic factors and gender. A total of 28 and 32 patients were enrolled in the BVZ/CPT-11 cohort and control group, respectively. The median OS was 17.94 months (95% CI, 14.91-20.96) in the BVZ/CPT-11 treatment cohort and 10.97 months (95% CI, 7.65-14.30) in the control cohort. The results obtained on the effectiveness of BVZ/CPT-11 treatment in patients with primary GBM are consistent with data from previous studies. No significant differences were identified in OS based on prognostic factors; therefore, the latter cannot be used to select patients who would incur the greatest benefits from BVZ/CPT-11 treatment.

Traitement de l'hypertension artérielle chez le sujet obèse [Treatment of hypertension in obese patients].

Prevalence of obesity and hypertension has increased these last decades. Around 60 to 70% of the incidence of hypertension is related to obesity. The relationship between obesity and hypertension is now well established. The sympathetic nervous system and the renin-angiotensin-aldosterone (RAA) system are activated in obese patients, mostly by insulin, and predispose the kidney to reabsorb sodium and water. In obese patients with hypertension, it is recommended to target a blood pressure < 140/90 mmHg. Lifestyle changes (weight loss, physical activity, low-salt diets) are useful to decrease blood pressure but are difficult to maintain in the long-term. When drugs are necessary, drugs that are metabolically neutral should be used, and often need to be combined to other drug classes in order to achieve blood pressure target.

Antiretroviral treatment of adult HIV infection: 2010 recommendations of the International AIDS Society-USA panel.

CONTEXT: Recent data regarding the consequences of untreated human immunodeficiency virus (HIV) infection and the expansion of treatment choices for antiretroviral-naive and antiretroviral-experienced patients warrant an update of the International AIDS Society-USA guidelines for the use of antiretroviral therapy in adults with HIV infection. OBJECTIVES: To provide updated recommendations for management of HIV-infected adults, using antiretroviral drugs and laboratory monitoring tools available in the international, developed-world setting. This report provides guidelines for when to initiate antiretroviral therapy, selection of appropriate initial regimens, patient monitoring, when to change therapy, and what regimens to use when changing. DATA SOURCES AND STUDY SELECTION: A panel with expertise in HIV research and clinical care reviewed relevant data published or presented at selected scientific conferences since the last panel report through April 2010. Data were identified through a PubMed search, review of scientific conference abstracts, and requests to antiretroviral drug manufacturers for updated clinical trials and adverse event data. DATA EXTRACTION AND SYNTHESIS: New evidence was reviewed by the panel. Recommendations were drafted by section writing committees and reviewed and edited by the entire panel. The quality and strength of the evidence were rated and recommendations were made by full panel consensus. CONCLUSIONS: Patient readiness for treatment should be confirmed before initiation of antiretroviral treatment. Therapy is recommended for asymptomatic patients with a CD4 cell count < or = 500/microL, for all symptomatic patients, and those with specific conditions and comorbidities. Therapy should be considered for asymptomatic patients with CD4 cell count > 500/microL. Components of the initial and subsequent regimens must be individualized, particularly in the context of concurrent conditions. Patients receiving antiretroviral treatment should be monitored regularly; treatment failure should be detected and managed early, with the goal of therapy, even in heavily pretreated patients, being HIV-1 RNA suppression below commercially available assay quantification limits.