French multicentre prospective evaluation of radiofrequency ablation in the management of haemorrhoidal disease.

PURPOSE: The aim of this study was to evaluate the efficacy and safety of radiofrequency ablation (RFA) in the management of haemorrhoidal disease with 1 year's follow-up. METHOD: This prospective multicentre study assessed RFA (Rafaelo©) in outpatients with grade II-III haemorrhoids. RFA was performed in the operating room under locoregional or general anaesthesia. Primary endpoint was the evolution of a quality-of-life score adapted to the haemorrhoid pathology (HEMO-FISS-QoL) 3 months after surgery. Secondary endpoints were evolution of symptoms (prolapsus, bleeding, pain, itching, anal discomfort), complications, postoperative pain and medical leave. RESULTS: A total of 129 patients (69% men, median age 49 years) were operated on in 16 French centres. Median HEMO-FISS-QoL score dropped significantly from 17.4/100 to 0/100 (p < 0.0001) at 3 months. At 3 months, the rate of patients reporting bleeding (21% vs. 84%, p < 0.001), prolapse (34% vs. 91.3%, p < 0.001) and anal discomfort (0/10 vs. 5/10, p < 0.0001) decreased significantly. Median medical leave was 4 days [1-14]. Postoperative pain was 4/10, 1/10, 0/10 and 0/10 at weeks 1, 2, 3 and 4. Seven patients (5.4%) were reoperated on by haemorrhoidectomy for relapse, and three for complications. Reported complications were haemorrhage (3), dysuria (3), abscess (2), anal fissure (1), external haemorrhoidal thrombosis (10), pain requiring morphine (11). Degree of satisfaction was high (+ 5 at 3 months on a - 5/+ 5 scale). CONCLUSION: RFA is associated with an improvement in quality of life and symptoms with a good safety profile. As expected for minimally invasive surgery, postoperative pain is minor with short medical leave. CLINICAL TRIAL REGISTRATION AND DATE: Clinical trial NCT04229784 (18/01/2020).

Stochastic heating of free electrons in multiple electromagnetic waves: A simple physical analysis.

It is established that charged particles crossing the interference field of two colliding electromagnetic (EM) waves can behave chaotically, leading to a stochastic heating of the particle distribution. A fine understanding of the stochastic heating process is crucial to the optimization of many physical applications requiring a high EM energy deposition to these charged particles. Predicting key stochastic heating features (particle distribution, chaos threshold) is usually achieved using a heavy Hamiltonian formalism required to model particle dynamics in chaotic regimes. Here, we explore an alternative and more intuitive path, which makes it possible to reduce the equations of motion of particles to rather simple and well-known physical systems such as Kapitza and gravity pendulums. Starting from these simple systems, we first show how to estimate chaos thresholds by deriving a model of the stretching and folding dynamics of the pendulum bob in phase space. Based on this first model, we then derive a random walk model for particle dynamics above the chaos threshold, which can predict major features of stochastic heating for any EM polarization and angle θ_{i}.

Online training on how to diagnose anoperineal lesions of Crohn's disease: Do pictures matter? A nationwide randomized study.

Any gastroenterologist must be trained to properly diagnose anoperineal lesions in patients with Crohn's disease (APLOC). The aim of this study was to establish whether adding pictures would improve teaching effectiveness of the diagnosis of APLOC to French gastroenterology trainees. METHOD: Trainees were asked to answer a first web-based survey consisting of evaluating 12 pictures of APLOC with a closed answer questionnaire. They were then randomized in 2 groups. Group A received an online teaching with typical pictures and APLOC definitions and group B definitions only. Trainees were asked again seven days later to answer a second survey with 12 other pictures of APLOC and 14 experts also answered this survey. Diagnostic scores were expressed in %. The primary endpoint was the comparison of the score of survey 2 between the two groups of trainees. Secondary endpoints were to compare results of survey 2 between trainees of both groups and experts, and assess diagnosis of each lesion. RESULTS: Two hundred fourty eight trainees among 465 answered survey 1, and 195 survey 2. The diagnostic score was 71.9% for groups A and B and 74.6% for experts (differences NS). After training diagnosis of ulceration was 72% for group A and 72.9% for group B, fistulae 85.2% versus 85.8%, erythema 44.1% vs. 55.6%, anoperineal scars 67.5% vs. 65.6%, and abscess 100% (differences NS). CONCLUSION: There was no difference between the two teaching methods. Further research should be performed aiming at improving teaching material and quotation baremes.

Efficacy, Tolerability, and Safety of Low-Volume Bowel Preparations for Patients with Inflammatory Bowel Diseases: The French Multicentre CLEAN Study.

BACKGROUND: Standard high-volume polyethylene glycol [PEG] bowel preparations [PEG-4L] are recommended for patients with inflammatory bowel disease [IBD] undergoing colonoscopy. However, low-volume preparations [≤2 L of active volume] are often used in clinical practice. The aim of this study was to evaluate the efficacy, tolerability, and safety of the various bowel preparations for patients with IBD, including low-volume preparations. METHODS: We conducted a French prospective multicentre observational study over a period of 1 month. Patients aged 18-75 years with IBD with an indication of colonoscopy independent of the study were enrolled. The choice of the preparation was left to the investigators, as per their usual protocol. The patients' characteristics, disease, and colonoscopy characteristics were recorded, and they were given self-reported questionnaires. RESULTS: Twenty-five public and private hospitals enrolled 278 patients. Among them, 46 had a disease flare and 41 had bowel stenoses. Bowel preparations for colonoscopy were as follows: 42% received PEG-2L, 29% received sodium picosulfate [Pico], 15% received PEG-4L, and 14% had other preparations. The preparation did not reach the Boston's score efficacy outcome in the PEG-4L group in 51.2% of the patients [p = 0.0011]. The preparation intake was complete for 59.5% in the PEG-4L group, compared with 82.9% in the PEG-2L group and 93.8% in the Pico group [p < 0.0001]. Tolerability, as assessed by the patients' VAS, was significantly better for both Pico and PEG-2L compared with PEG-4L, and better for Pico compared with PEG-2L [p = 0.008; p = 0.0003]. In multivariate analyses, low-volume preparations were independent factors of efficacy and tolerability. Adverse events occurred in 4.3% of the patients. CONCLUSIONS: Preparations with PEG-2L and Pico were equally safe, with better efficacy and tolerability outcomes compared with PEG-4L preparations. The best efficacy/tolerance/safety profile was achieved with the Pico preparation.

Analytical Predictions of Field and Plasma Dynamics during Nonlinear Weibel-Mediated Flow Collisions.

The formation of collisionless shocks mediated by the ion Weibel instability is addressed theoretically and numerically in the nonrelativistic limit. First, the model developed in C. Ruyer et al., Phys. Plasmas 22, 032102 (2015) for the weakly nonlinear ion Weibel instability in a symmetric two-stream system is shown to be consistent with recent experimental and simulation results. Large-scale kinetic simulations are then performed to clarify the spatiotemporal evolution of the magnetic-field and plasma properties in the subsequent strongly nonlinear phase leading to shock formation. A simple analytical model is proposed which captures the simulation results up to a point close to ion isotropization. Electron screening effects are found important in the instability dynamics, so that numerical simulations using a nonphysical electron mass should be considered with caution.

Optical properties of relativistic plasma mirrors.

The advent of ultrahigh-power femtosecond lasers creates a need for an entirely new class of optical components based on plasmas. The most promising of these are known as plasma mirrors, formed when an intense femtosecond laser ionizes a solid surface. These mirrors specularly reflect the main part of a laser pulse and can be used as active optical elements to manipulate its temporal and spatial properties. Unfortunately, the considerable pressures exerted by the laser can deform the mirror surface, unfavourably affecting the reflected beam and complicating, or even preventing, the use of plasma mirrors at ultrahigh intensities. Here we derive a simple analytical model of the basic physics involved in laser-induced deformation of a plasma mirror. We validate this model numerically and experimentally, and use it to show how such deformation might be mitigated by appropriate control of the laser phase.

[Vaginal flap for rectovaginal fistulae in Crohn's disease]. / Traitement des fistules recto-vaginales de la maladie de Crohn par lambeau d'avancement vaginal.

OBJECTIVES: To evaluate efficacy and functional results (sexual activity) of vaginal flap for rectovaginal fistula in Crohn's disease. PATIENTS AND METHODS: From May 2004 to March 2008, we proposed a vaginal flap in patients who had a rectovaginal fistula in Crohn's disease and for which rectal flap was technically impossible. Monitoring included a clinical examination at 1 month and every 3 months for 1 year, Perianal Disease Activity Index for sexual activity evaluation. Every year and in April 2009 the nursing team during a telephone interview filled a standardized questionnaire. RESULTS: We treated 5 patients. At 6 months, 4 of 5 patients were healed. At 7 months, 1 patient presented a new flare up of CD with reopening of the fistula. The other 3 patients were still healed at a median follow-up of 30.66 months (15 to 59). One patient presented dyspareunia during 3 months. DISCUSSION AND CONCLUSION: Vaginal flap is an effective technique that entails neither prolonged dyspareunia nor fecal incontinence. Stoma is not systematic.

The effect of inactivated Lactobacillus LB fermented culture medium on symptom severity: observational investigation in 297 patients with diarrhea-predominant irritable bowel syndrome.

INTRODUCTION: Little is known about the intensity of symptoms of diarrhea-predominant IBS (IBS-D) or the consequences of the disease on patients' health-related quality of life (HRQOL). This observational investigation assessed the symptoms (abdominal pain, bloating, number of stools per day, and stool consistency), impact on HRQOL, and consequence on anal continence in 297 patients with IBS-D before and after 1 month of probiotic treatment with Lacteol (inactivated Lactobacillus LB plus fermented culture medium). METHODS: Functional assessment using a standardized visual analogue scale in order to quantify abdominal pain, bloating, and quality of life before and after 1 month of treatment with 2 capsules/day of Lacteol. The number of symptomatic days per week, number of stools, consistency of stools, secondary fecal incontinence rate, and potential trigger effect of food were quantified. A χ2 test was used to compare qualitative data and the variance of quantitative criteria was analyzed. RESULTS: The pain score decreased from 4.46±0.15 on a scale of 0-10 before treatment to 2.8±0.14 after treatment (p<0.0001). Bloating decreased from 4.49±0.18 to 2.5±0.15 on a scale of 0-10 (p<0.0001). The HRQOL score, which is inversely correlated with quality of life, decreased from 5.99±0.14 to 3.92±0.16 (p<0.0001). In this cohort study, the fecal incontinence rate secondary to diarrhea was clearly higher than that of the general population: 18% versus a prevalence of 9-10%, according to different studies. The mean number of stools per week decreased from 17.59 to 12.83 after treatment (p<0.0001). Before treatment, 54% of patients had watery stools and 46% had smooth stools; at the end of treatment, only 18.5% of patients still had watery stools, and 34% had normal stools. 52% of patients attributed their symptoms to their diet: 34% to vegetables, 29% to fruit, 15% to milk, 15% to fat, 6% to peppers and spices, and 4% to sugar. CONCLUSION: This observational investigation shed new light on patients with IBS-D, the HRQOL of which is altered by a fecal incontinence rate twice as high as that of the general population. Correlation with diet is confirmed by 1 out of 2 patients reporting poor tolerance of fiber and dairy products. Nutritional management should thus be part of these patients' treatment. Inactivated Lactobacillus LB plus fermented culture medium is a probiotic drug that has been used by physicians for a long time to treat patients with diarrhea. Strongly concentrated, it has no side effects and seems to help these patients. Due to a strong placebo effect in patients with this pathology, however, a controlled study is necessary to confirm this result.

Efficacy of synthetic glue treatment of high crypoglandular fistula-in-ano.

OBJECTIVES: In France, seton drainage followed by fistulotomy is currently the standard treatment for high cryptoglandular fistula-in-ano. Biological or synthetic glues, such as Glubran(®) 2, have been recently proposed for sealing the fistula tract. The purpose of this study is to determine the healing rate with glubran 2 and to assess the functional outcome after cure of fistula-in-ano. PATIENTS AND METHODS: From July 2006 to July 2008, 34 patients (20 males; median age 48.5 years, range 22-55 years) with high cryptoglandular anal fistulas were treated with glubran 2. Patients were seen for physical examination at 1, 3 and 6 months, then interviewed by telephone at 1 and 2 years, and in September 2009. The Fecal incontinence severity index (FISI) score was used to assess continence. RESULTS: The healing rate at 1 month was 67.6% (23 patients); the fistula failed to heal in 11 patients. All 23 patients with a healed fistula remained recurrence-free, with no continence disorders noted, during the median 34-month follow-up period (range 21-43 months). One patient was lost to follow-up after 6 months. CONCLUSION: Glubran 2 provides an effective treatment for high fistula-in-ano, with no change in continence. In future, a randomized comparison of this agent with fibrin glues should be useful.

Phase properties of laser high-order harmonics generated on plasma mirrors.

As a high-intensity laser-pulse reflects on a plasma mirror, high-order harmonics of the incident frequency can be generated in the reflected beam. We present a numerical study of the phase properties of these individual harmonics, and demonstrate experimentally that they can be coherently controlled through the phase of the driving laser field. The harmonic intrinsic phase, resulting from the generation process, is directly related to the coherent sub-laser-cycle dynamics of plasma electrons, and thus constitutes a new experimental probe of these dynamics.

Preliminary results of peripheral transcutaneous neuromodulation in the treatment of idiopathic fecal incontinence.

PURPOSE: Few therapeutic tools are available for treating idiopathic anal incontinence. Sacral neuromodulation appears to be effective in selected patients but requires surgical implantation of a permanent electrical stimulator. The aim of this work was to assess the efficiency of posterior tibial nerve (PTN) transcutaneous electrical nerve stimulation (TENS) in the treatment of anal idiopathic incontinence. METHODS: Ten women were treated by PTN TENS, 20 min a day for 4 weeks. Functional results were evaluated by Wexner's incontinence score and anorectal manometry. RESULTS: Eight of the ten patients showed a 60% mean improvement of their incontinence score after 4 weeks. This improvement remained stable over the 12-week follow-up period. Manometric parameters did not differ before and after stimulation. CONCLUSION: PTN neuromodulation without surgically implanted electrode could represent a safe and low-cost alternative to permanent sacral neuromodulation for idiopathic anal incontinence.

Strong reduction of the degree of spatial coherence of a laser beam propagating through a preformed plasma.

A strong reduction of the spatial coherence of a laser beam after its propagation through a plasma has been measured using a Fresnel biprism interferometer. The laser beam was diffraction limited; the coherence width was reduced from 40 mm in vacuum down to a few mm with the plasma. Numerical results based on a paraxial model exhibit a coherence degree close to the experimental one; they also prove the importance of taking into account the nonlocal transport effects in numerical simulations for such plasma conditions.

[Evaluation of three testing strategies for detection of hepatitis C in a hospital medical consultation and in an HIV testing center]. / Evaluation de trois stratégies de dépistage de l'hépatite C en consultation hospitalière de Médecine générale et dans un Centre de dépistage anonyme et gratuit du virus de l'immunodéficience humaine.

AIMS: Testing for hepatitis C virus (HCV) is recommended. The purpose of this study was to evaluate the efficacy of HCV testing in a medical consultation without an appointment and in an HIV testing center based on three testing strategies: 1997 French Consensus Conference, "Lettre de la Direction Générale de la Santé" (January 1996), and extension to other risk factors. PATIENTS AND METHODS: For 6 months a free blood test was offered to any patient with a risk factor according to the literature. RESULTS: There were 1 736 new patients at the medical consultation and 1 616 at the testing center. The patients were younger at the testing center than at the medical consultation (31.1 vs 43.3 years; P<0.001). Acceptance of screening was better at the testing center (97.8% vs 75.2%; P<0.001). There were more patients exposed to one of the risk factors at the testing center (31.2% vs 13.9%; P<0.001). Tests were more efficient at the testing center: 30 HCV positive patients/1 616 (1.86%) vs 11/1 736 (0.63%, P<0.01). Tests based on the 1997 French Consensus Conference provided detection in 27/30 (90%) of HCV positive patients at the testing center but only 4/11 (36.3%) at the medical consultation (P<0.01). CONCLUSION: Testing was effective in both places but was more efficient at the testing center. Efficacy of the testing strategies differs significantly according to the place of screening. At the testing center, screening can be restricted to patients with a history of intravenous drug use and blood transfusion. At the medical consultation, screening should be extended to other risk factors.

Dose-ranging study of mometasone furoate dry powder inhaler in the treatment of moderate persistent asthma using fluticasone propionate as an active comparator.

BACKGROUND: Mometasone furoate (MF; Schering-Plough, Madison, NJ), is a glucocorticoid with high local potency and low potential systemic availability. OBJECTIVES: To compare the relative efficacy and safety of a new formulation of MF, coupled with a recently designed dry powder inhaler (DPI), in the treatment of patients with moderate persistent asthma. Fluticasone propionate administered by Diskhaler (FP Diskhaler, 250 microg twice a day; Glaxo Wellcome, Research Triangle Park, NC) was used as an active control. DESIGN: A randomized, parallel group, double-blind (for MF-DPI dosage), evaluator-blind (for MF-DPI vs FP) trial. SETTING: Sixty centers in 20 countries. PATIENTS: Seven hundred thirty-three patients with moderate persistent asthma on inhaled corticosteroid treatment. INTERVENTIONS: Discontinuation of previous inhaled corticosteroid and initiation of one of four study treatments: three doses of MF-DPI (100, 200, and 400 microg twice daily) and one of FP (250 microg twice daily >12 weeks). RESULTS: FEV1 (primary efficacy variable) was evaluated as the mean change from baseline to endpoint (last evaluable visit). All dosage groups showed improvement at endpoint. Only 400 microg twice daily of MF-DPI (+0.19 L) was statistically different from 100 microg twice daily of MF-DPI (+0.07 L; P = 0.02). MF-DPI (200 microg twice daily) and FP Diskhaler groups showed similar improvement (+0.16 L). Greater improvement in most secondary variables (forced expiratory flow between 25% and 75% of vital capacity, and morning and evening peak expiratory flows) also resulted from treatment with 200 or 400 microg twice daily of MF-DPI or with FP Diskhaler, compared with 100 microg twice daily of MF-DPI. Overall, a total daily 800-microg dose of MF-DPI conferred no significant additional benefit >400 microg of MF-DPI. The incidence of oral candidiasis was 1%, 7%, 10%, and 10% in the 100, 200, and 400 microg twice daily of MF-DPI and FP groups, respectively. CONCLUSIONS: A total daily dose of 400 microg of MF-DPI provides clinical benefit comparable to that observed with a total daily dose of 500 microg of FP Diskhaler.

Optimisation of HLA-B27 testing by association of flow cytometry and DNA typing.

HLA-B27 typing contributes to the diagnosis of ankylosing spondylitis. The classical technique of microlymphocytotoxicity is costly and can give false-negative results. We have compared 304 samples using two relatively new methods - flow cytometry and PCR-SSP - and evaluated their respective uses in routine analysis. Flow cytometric HLA-B27 testing was performed using three monoclonal anti-B27 antibodies (HLA-ABC-m3, GS145.2 and FD705 clones). Cut-off values were established to differentiate HLA-B27-positive from HLA-B27-negative samples with ROC curves. Although flow cytometric analysis with a reliable monoclonal antibody (mAb) is valuable for HLA screening, none of the HLA-B27 flow cytometry protocols was sufficient on its own to ascertain the HLA phenotype in 100% of samples. Two false negatives were observed with the FD705 mAb and the use of two different monoclonal antibodies did not increase the accuracy of HLA-B27 typing. HLA-B27 typing using molecular biology is a reliable but costly technique. Therefore we suggest that DNA typing could be used as a complementary technique and applied to samples whose HLA-B27 phenotype cannot be determined by flow cytometry. The association of flow cytometry and DNA typing is, in our experience, an economical and reliable approach.

Prognostic factors in patients with Zollinger-Ellison syndrome and multiple endocrine neoplasia type 1. Groupe d'Etude des Néoplasies Endocriniennes Multiples (GENEM and groupe de Recherche et d'Etude du Syndrome de Zollinger-Ellison (GRESZE).

BACKGROUND & AIMS: Risk factors of metachronous liver metastases and death are not well known in patients with the Zollinger-Ellison syndrome and multiple endocrine neoplasia type 1. These factors were retrospectively determined in 77 patients. METHODS: Data chart review was performed. RESULTS: Median follow-up was 102 months (range, 12-366). Surgery was performed on 48 patients, including 9 of the 10 patients with large pancreatic tumors (>/=3 cm). Liver metastases developed in 4 patients (40%) with large pancreatic tumors, in 3 (4.8%) without, and in 1 of the 4 patients with pancreatic tumors of unknown size; all had previously undergone surgery. The only independent factor associated with development of liver metastases identified by multivariate analysis was large pancreatic tumors (risk ratio, 29.0; 95% confidence interval [CI], 3. 2-260.7). Surgery was not selected. The probability of being free of liver metastases in the 63 patients without large pancreatic tumors was 96% (95% CI, 88-100) at 10 and 15 years. Thirteen (16.9%) patients died. The only independent factors of death selected by multivariate analysis were Zollinger-Ellison syndrome diagnosis before 1980 (risk ratio, 8.2; 95% CI, 1.7-40.6) and age at diagnosis (risk ratio/year, 1.08; 95% CI, 1.03-1.14). CONCLUSIONS: Large pancreatic tumors are predictive of the development of metachronous liver metastases, and surgery does not seem to prevent them.

Comparison of measured and calculated X-ray and hot-electron production in short-pulse laser-solid interactions at moderate intensities.

Ultrashort pulse laser-solid interaction experiments with 4x10(16) W/cm(2),120 fs, 45 degrees incidence angle, p-polarized pulses are theoretically analyzed with the help of 1(1/2)-dimensional (1(1/2) D) particle-in-cell (PIC) simulations. The laser impinges upon preformed plasmas with a precisely controlled density-gradient scale-length. PIC electron distribution functions are used as an input to 3D Monte Carlo simulations to interpret measured electron distributions and Kalpha radiation emission. Satisfactory agreement between the experimental and simulation results is obtained for the measured absorption coefficient, the energy distribution of the back-scattered hot electrons, the hot-electron temperature in the bulk of the target, and the Kalpha yield, when the preplasma scale-length is varied.

Landau damping of an electron plasma wave in a plasma with modulated density.

The collisionless Landau damping is analyzed for a homogeneous plasma with a sinusoidal density perturbation. The exact damping values are obtained by numerically solving the kinetic dispersion relation of the electron plasma mode. Quantitative results are provided on the influence of the amplitude and the wave vector of the density modulation. Within a simplified fluid framework, a fit is given to these data.

Predictive factors for late toxicity after endobronchial brachytherapy: a multivariate analysis.

PURPOSE: To determine the predictive factors associated with hemoptysis and radiation bronchitis after endobronchial brachytherapy by univariate and multivariate analyses METHODS AND MATERIALS: One hundred forty-nine patients underwent endobronchial brachytherapy and were divided into three therapeutic groups: group 1: patients treated with palliative intent (n=47); group 2: patients treated with curative intent (small endobronchial tumors without mediastinal or general dissemination: n=73); group 3: patients also receiving external irradiation (n=29). One hundred twelve patients had previously received external irradiation. Brachytherapy was delivered with a dose per fraction ranging from 4 to 7 Gy and a prescription point between 0.5 and 1.5 cm, usually 1 cm from the source center. Two to six fractions were delivered according to the therapeutic group and clinical situation. The influence of the following variables on the incidence of hemoptysis or radiation bronchitis was studied: age, sex, Karnofsky score, therapeutic group, histologic type, endoscopic tumor length, dose per fraction, total brachytherapy dose, total external beam irradiation dose, total dose (brachytherapy dose plus external irradiation dose), volumes of the 100% and 200% isodoses, and volumes of the 7 and 14 Gy isodoses. RESULTS: We observed 11 hemoptyses (7.4%), 10 were lethal. All but one occurred in patients with progressive disease. Two clinical factors were significantly associated with hemoptysis by univariate analysis: palliative group (p=0.009) and endobronchial tumor length (p=0.004). No technical factors seem to be implicated in the occurrence of hemoptysis. Only endobronchial tumor length remained in the multivariate model (p=0.02). Radiation bronchitis was observed in 13 cases (8.7%). By univariate analysis, a good Karnofsky score (p=0.02), curative treatment (p=0.02), and tumor location on trachea and main stem bronchus (p=0.002) were significantly associated with this complication. Two technical factors were also incriminated: the total dose (p=0.04) and the 100% isodose volume (p=0.02). By multivariate analysis, only the tumor location retained statistical significance (p=0.009). CONCLUSION: Hemoptysis is most likely due to disease progression, with the bleeding being facilitated by brachytherapy. Some rare cases could be a direct complication of brachytherapy itself, particularly when tumors are located in the upper lobes. In contrast, radiation bronchitis occurred more frequently in patients with controlled disease, and was significantly influenced by tumor location and technical factors (dose and volumes treated). Technical improvements should increase the therapeutic ratio.