Approche des oedèmes du membre supérieur liés à une occlusion de la veine sous-clavière située en aval d'une fistule artério-veineuse [Approach to upper limb edema secondary to subclavian vein occlusion situated distal to an arteriovenous fistula]

AIM OF THE STUDY: To analyse the course of upper limb edema in patients with an arteriovenous fistula used for dialysis and to analyse the available therapeutic options. STUDY DESIGN: Retrospective study of patients with this type of edema, who were treated in our institution from 1992 to 1996. PATIENTS AND METHODS: Seven consecutive patients with an arterioveinous fistula treated for edema of the upper extremity, were reviewed. The fistula was created at the elbow in 6 patients and at the forearm in 1. The edema appeared immediately after operation in 4 patients and after a delay in 3 patients. Stenosis (3 patients) or occlusion (2 patients) of the subclavian vein was documented in 5 patients who were investigated by angiography. RESULTS: The edema regressed spontaneously in 4 patients because collaterals developed in 3 patients, and the fistula thrombosed in 1 patient. Surgical intervention allowed regression of the edema in the other 3 patients: excessive output of the fistula was reduced in 2 patients and an axillojugular bypass was performed in 1 patient. The fistula remained effective in 6 patients. Another fistula was performed on the contralateral arm in 1 patient. CONCLUSION: Non-operative management is recommended in patients who develop edema immediately after creation of the fistula, because spontaneous regression is likely. Measures aimed at reducing the output of the fistula or enhancing the venous capacities of the arm are required when edema appears at a later stage. The fistula can be saved in the majority of cases.

Role of the stress sigma factor RpoS in GacA/RsmA-controlled secondary metabolism and resistance to oxidative stress in Pseudomonas fluorescens CHA0.

In Pseudomonas fluorescens biocontrol strain CHA0, the two-component system GacS/GacA positively controls the synthesis of extracellular products such as hydrogen cyanide, protease, and 2,4-diacetylphloroglucinol, by upregulating the transcription of small regulatory RNAs which relieve RsmA-mediated translational repression of target genes. The expression of the stress sigma factor sigmaS (RpoS) was controlled positively by GacA and negatively by RsmA. By comparison with the wild-type CHA0, both a gacS and an rpoS null mutant were more sensitive to H2O2 in stationary phase. Overexpression of rpoS or of rsmZ, encoding a small RNA antagonistic to RsmA, restored peroxide resistance to a gacS mutant. By contrast, the rpoS mutant showed a slight increase in the expression of the hcnA (HCN synthase subunit) gene and of the aprA (major exoprotease) gene, whereas overexpression of sigmaS strongly reduced the expression of these genes. These results suggest that in strain CHA0, regulation of exoproduct synthesis does not involve sigmaS as an intermediate in the Gac/Rsm signal transduction pathway whereas sigmaS participates in Gac/Rsm-mediated resistance to oxidative stress.

Correlative light and electron microscopy using immunolabeled sections.

In correlative microscopy, light microscopy provides the overview and orientation of the complex cells and tissue, while electron microscopy offers the detailed localization and correlation of subcellular structures. In this chapter we offer detailed high-quality electron microscopical preparation methods for optimum preservation of the cellular ultrastructure. From such preparations serial thin sections are collected and used for comparative histochemical, immunofluorescence, and immunogold staining.In light microscopy histological stains identify the orientation of the sample and immunofluorescence labeling facilitates to find the region of interest, namely, the labeled cells expressing the macromolecule under investigation. Sections, labeled with immunogold are analyzed by electron microscopy in order to identify the label within the cellular architecture at high resolution.

A peripheral dose calculation model for estimating second cancer risk after breast radiotherapy

AbstractBreast cancer is one of the most common cancers affecting one in eight women during their lives. Survival rates have increased steadily thanks to early diagnosis with mammography screening and more efficient treatment strategies. Post-operative radiation therapy is a standard of care in the management of breast cancer and has been shown to reduce efficiently both local recurrence rate and breast cancer mortality. Radiation therapy is however associated with some late effects for long-term survivors. Radiation-induced secondary cancer is a relatively rare but severe late effect of radiation therapy. Currently, radiotherapy plans are essentially optimized to maximize tumor control and minimize late deterministic effects (tissue reactions) that are mainly associated with high doses (» 1 Gy). With improved cure rates and new radiation therapy technologies, it is also important to evaluate and minimize secondary cancer risks for different treatment techniques. This is a particularly challenging task due to the large uncertainties in the dose-response relationship.In contrast with late deterministic effects, secondary cancers may be associated with much lower doses and therefore out-of-field doses (also called peripheral doses) that are typically inferior to 1 Gy need to be determined accurately. Out-of-field doses result from patient scatter and head scatter from the treatment unit. These doses are particularly challenging to compute and we characterized it by Monte Carlo (MC) calculation. A detailed MC model of the Siemens Primus linear accelerator has been thoroughly validated with measurements. We investigated the accuracy of such a model for retrospective dosimetry in epidemiological studies on secondary cancers. Considering that patients in such large studies could be treated on a variety of machines, we assessed the uncertainty in reconstructed peripheral dose due to the variability of peripheral dose among various linac geometries. For large open fields (> 10x10 cm2), the uncertainty would be less than 50%, but for small fields and wedged fields the uncertainty in reconstructed dose could rise up to a factor of 10. It was concluded that such a model could be used for conventional treatments using large open fields only.The MC model of the Siemens Primus linac was then used to compare out-of-field doses for different treatment techniques in a female whole-body CT-based phantom. Current techniques such as conformai wedged-based radiotherapy and hybrid IMRT were investigated and compared to older two-dimensional radiotherapy techniques. MC doses were also compared to those of a commercial Treatment Planning System (TPS). While the TPS is routinely used to determine the dose to the contralateral breast and the ipsilateral lung which are mostly out of the treatment fields, we have shown that these doses may be highly inaccurate depending on the treatment technique investigated. MC shows that hybrid IMRT is dosimetrically similar to three-dimensional wedge-based radiotherapy within the field, but offers substantially reduced doses to out-of-field healthy organs.Finally, many different approaches to risk estimations extracted from the literature were applied to the calculated MC dose distribution. Absolute risks varied substantially as did the ratio of risk between two treatment techniques, reflecting the large uncertainties involved with current risk models. Despite all these uncertainties, the hybrid IMRT investigated resulted in systematically lower cancer risks than any of the other treatment techniques. More epidemiological studies with accurate dosimetry are required in the future to construct robust risk models. In the meantime, any treatment strategy that reduces out-of-field doses to healthy organs should be investigated. Electron radiotherapy might offer interesting possibilities with this regard.RésuméLe cancer du sein affecte une femme sur huit au cours de sa vie. Grâce au dépistage précoce et à des thérapies de plus en plus efficaces, le taux de guérison a augmenté au cours du temps. La radiothérapie postopératoire joue un rôle important dans le traitement du cancer du sein en réduisant le taux de récidive et la mortalité. Malheureusement, la radiothérapie peut aussi induire des toxicités tardives chez les patients guéris. En particulier, les cancers secondaires radio-induits sont une complication rare mais sévère de la radiothérapie. En routine clinique, les plans de radiothérapie sont essentiellement optimisées pour un contrôle local le plus élevé possible tout en minimisant les réactions tissulaires tardives qui sont essentiellement associées avec des hautes doses (» 1 Gy). Toutefois, avec l'introduction de différentes nouvelles techniques et avec l'augmentation des taux de survie, il devient impératif d'évaluer et de minimiser les risques de cancer secondaire pour différentes techniques de traitement. Une telle évaluation du risque est une tâche ardue étant donné les nombreuses incertitudes liées à la relation dose-risque.Contrairement aux effets tissulaires, les cancers secondaires peuvent aussi être induits par des basses doses dans des organes qui se trouvent hors des champs d'irradiation. Ces organes reçoivent des doses périphériques typiquement inférieures à 1 Gy qui résultent du diffusé du patient et du diffusé de l'accélérateur. Ces doses sont difficiles à calculer précisément, mais les algorithmes Monte Carlo (MC) permettent de les estimer avec une bonne précision. Un modèle MC détaillé de l'accélérateur Primus de Siemens a été élaboré et validé avec des mesures. La précision de ce modèle a également été déterminée pour la reconstruction de dose en épidémiologie. Si on considère que les patients inclus dans de larges cohortes sont traités sur une variété de machines, l'incertitude dans la reconstruction de dose périphérique a été étudiée en fonction de la variabilité de la dose périphérique pour différents types d'accélérateurs. Pour de grands champs (> 10x10 cm ), l'incertitude est inférieure à 50%, mais pour de petits champs et des champs filtrés, l'incertitude de la dose peut monter jusqu'à un facteur 10. En conclusion, un tel modèle ne peut être utilisé que pour les traitements conventionnels utilisant des grands champs.Le modèle MC de l'accélérateur Primus a été utilisé ensuite pour déterminer la dose périphérique pour différentes techniques dans un fantôme corps entier basé sur des coupes CT d'une patiente. Les techniques actuelles utilisant des champs filtrés ou encore l'IMRT hybride ont été étudiées et comparées par rapport aux techniques plus anciennes. Les doses calculées par MC ont été comparées à celles obtenues d'un logiciel de planification commercial (TPS). Alors que le TPS est utilisé en routine pour déterminer la dose au sein contralatéral et au poumon ipsilatéral qui sont principalement hors des faisceaux, nous avons montré que ces doses peuvent être plus ou moins précises selon la technTque étudiée. Les calculs MC montrent que la technique IMRT est dosimétriquement équivalente à celle basée sur des champs filtrés à l'intérieur des champs de traitement, mais offre une réduction importante de la dose aux organes périphériques.Finalement différents modèles de risque ont été étudiés sur la base des distributions de dose calculées par MC. Les risques absolus et le rapport des risques entre deux techniques de traitement varient grandement, ce qui reflète les grandes incertitudes liées aux différents modèles de risque. Malgré ces incertitudes, on a pu montrer que la technique IMRT offrait une réduction du risque systématique par rapport aux autres techniques. En attendant des données épidémiologiques supplémentaires sur la relation dose-risque, toute technique offrant une réduction des doses périphériques aux organes sains mérite d'être étudiée. La radiothérapie avec des électrons offre à ce titre des possibilités intéressantes.

Optic perineuritis secondary to Wegener's granulomatosis.

BACKGROUND: Optic perineuritis (OPN) is an inflammatory condition involving the optic nerve sheath because of a variety of causes. We describe three patients in whom OPN was secondary to Wegener's granulomatosis (WG) and compare the clinical findings in these cases with those of idiopathic OPN. METHODS: This is a retrospective small case series derived from patients with OPN seen in an outpatient neuro-ophthalmology clinic. Medical records and imaging studies of these patients were reviewed. RESULTS: These patients shared clinical similarities with idiopathic OPN including age, sex, symptoms, radiographic findings and steroid responsiveness. However, recurrence of symptoms on lowering the prednisone dose below 40 mg distinguished these patients from those with idiopathic OPN. CONCLUSIONS: Steroid dependency in idiopathic OPN should raise suspicion of WG. Patients with OPN should be specifically questioned regarding pre-existing upper respiratory tract disorders and rheumatic symptoms and laboratory testing should include acute phase reactants, anti-neutrophil cytoplasmic antibodies and tests of renal function.

A protocol for preparing GFP-labeled neurons previously imaged in vivo and in slice preparations for light and electron microscopic analysis.

In vivo imaging of green fluorescent protein (GFP)-labeled neurons in the intact brain is being used increasingly to study neuronal plasticity. However, interpreting the observed changes as modifications in neuronal connectivity needs information about synapses. We show here that axons and dendrites of GFP-labeled neurons imaged previously in the live mouse or in slice preparations using 2-photon laser microscopy can be analyzed using light and electron microscopy, allowing morphological reconstruction of the synapses both on the imaged neurons, as well as those in the surrounding neuropil. We describe how, over a 2-day period, the imaged tissue is fixed, sliced and immuno-labeled to localize the neurons of interest. Once embedded in epoxy resin, the entire neuron can then be drawn in three dimensions (3D) for detailed morphological analysis using light microscopy. Specific dendrites and axons can be further serially thin sectioned, imaged in the electron microscope (EM) and then the ultrastructure analyzed on the serial images.

Value of allogeneic versus autologous stem cell transplantation and chemotherapy in patients with myelodysplastic syndromes and secondary acute myeloid leukemia. Final results of a prospective randomized European Intergroup Trial.

BACKGROUND: Allogeneic stem cell transplantation is usually considered the only curative treatment option for patients with advanced or transformed myelodysplastic syndromes in complete remission, but post-remission chemotherapy and autologous stem cell transplantation are potential alternatives, especially in patients over 45 years old. DESIGN AND METHODS: We evaluated, after intensive anti-leukemic remission-induction chemotherapy, the impact of the availability of an HLA-identical sibling donor on an intention-to treat basis. Additionally, all patients without a sibling donor in complete remission after the first consolidation course were randomized to either autologous peripheral blood stem cell transplantation or a second consolidation course consisting of high-dose cytarabine. RESULTS: The 4-year survival of the 341 evaluable patients was 28%. After achieving complete remission, the 4-year survival rates of patients under 55 years old with or without a donor were 54% and 41%, respectively, with an adjusted hazard ratio of 0.81 (95% confidence interval [95% CI], 0.49-1.35) for survival and of 0.67 (95% CI, 0.42-1.06) for disease-free survival. In patients with intermediate/high risk cytogenetic abnormalities the hazard ratio in multivariate analysis was 0.58 (99% CI, 0.22-1.50) (P=0.14) for survival and 0.46 (99% CI, 0.22-1.50) for disease-free survival (P=0.03). In contrast, in patients with low risk cytogenetic characteristics the hazard ratio for survival was 1.17 (99% CI, 0.40-3.42) and that for disease-free survival was 1.02 (99% CI, 0.40-2.56). The 4-year survival of the 65 patients randomized to autologous peripheral blood stem cell transplantation or a second consolidation course of high-dose cytarabine was 37% and 27%, respectively. The hazard ratio in multivariate analysis was 1.22 (95% CI, 0.65-2.27) for survival and 1.02 (95% CI, 0.56-1.85) for disease-free survival. CONCLUSIONS: Patients with a donor and candidates for allogeneic stem cell transplantation in first complete remission may have a better disease-free survival than those without a donor in case of myelodysplastic syndromes with intermediate/high-risk cytogenetics. Autologous peripheral blood stem cell transplantation does not provide longer survival than intensive chemotherapy.

Clinical benefits of an adherence monitoring program in the management of secondary hyperparathyroidism with cinacalcet: results of a prospective randomized controlled study.

BACKGROUND/AIMS: One of the causes of uncontrolled secondary hyperparathyroidism (sHPT) is patient's poor drug adherence. We evaluated the clinical benefits of an integrated care approach on the control of sHPT by cinacalcet. METHODS: Prospective, randomized, controlled, multicenter, open-label study. Fifty hemodialysis patients on a stable dose of cinacalcet were randomized to an integrated care approach (IC) or usual care approach (UC). In the IC group, cinacalcet adherence was monitored using an electronic system. Results were discussed with the patients in motivational interviews, and drug prescription adapted accordingly. In the UC group, drug adherence was monitored, but results were not available. RESULTS: At six months, 84% of patients in the IC group achieved recommended iPTH targets versus 55% in the UC group (P = 0.04). The mean cinacalcet taking adherence improved by 10.8% in the IC group and declined by 5.3% in the UC group (P = 0.02). Concomitantly, the mean dose of cinacalcet was reduced by 7.2 mg/day in the IC group and increased by 6.4 mg/day in the UC group (P = 0.03). CONCLUSIONS: The use of a drug adherence monitoring program in the management of sHPT in hemodialysis patients receiving cinacalcet improves drug adherence and iPTH control and allows a reduction in the dose of cinacalcet.

Baerveldt shunts in the treatment of glaucoma secondary to anterior uveal melanoma and proton beam radiotherapy.

INTRODUCTION: Melanoma of the iris and ciliary body may be associated with secondary glaucoma. Treatment with proton beam radiotherapy (PBRT) to the anterior segment can also elevate intraocular pressure (IOP), resulting in uncontrolled glaucoma, often requiring enucleation. This is the first prospective study of Baerveldt aqueous shunts in irradiated eyes with anterior uveal melanoma (AUM; affecting the iris or ciliary body). METHODS: Thirty-one eyes with uncontrolled IOP following anterior segment PBRT treatment for AUM were prospectively recruited to undergo Baerveldt shunt implantation. Postoperative examinations were performed on day 1; weeks 1, 3, 6, 9; months 3, 6, 9, 12 and annually thereafter. Surgical success was defined as IOP 21 mm Hg or less and 20% reduction from baseline. All complications were recorded. RESULTS: Mean follow-up was 15.7 months (SD ±8.3 months). Mean interval from irradiation to shunt implantation was 2.5 years. Mean preoperative IOP was 31.0 (±10.3) mm Hg; mean IOP at last visit was 15.0 (±5.0) mm Hg; mean pre-operative glaucoma medications were 3.3 (±1.3); postoperatively 0.7 (±1.3) glaucoma medications. Surgical success rate was 86% using glaucoma medications. Four eyes had minor postoperative complications, none of which were sight threatening. There were no local tumour recurrences or systemic metastases. There were no enucleations caused by ocular hypertension. CONCLUSIONS: Baerveldt shunts were effective in lowering IOP, with few complications, in eyes treated with total anterior segment irradiation for AUM.

In-situ revascularisation for secondary aorto-enteric fistulae: the success of silver-coated Dacron is closely linked to a suitable bowel repair.

OBJECTIVES: The purpose of this study was to assess short- and mid-term results of in-situ revascularisation (ISR) using silver-coated Dacron prostheses and bowel repair for management of secondary aorto-enteric fistulae (SAEF). DESIGN: Single-centre retrospective chart review. MATERIAL AND METHODS: This study includes all the patients treated by ISR using silver-coated Dacron for SAEF between 2006 and 2010. Primary end points were mortality and survival rates. Secondary end points were reinfection-free survival and secondary patency rates. RESULTS: Eighteen male patients with SAEF with a median age of 64 years were operated by ISR using silver-coated Dacron during the study period without operative death. The 30-day mortality was 22% and the in-hospital mortality rate was 39%. Indeed, during hospitalisation, a duodenal leak was observed in four patients including three who died. Four others patients died due to multi-system organ failure. Median follow-up was 16 months (range 1-66). The survival rate at 12 months was 55%. One duodenal leak was observed leading to death. The reinfection-free survival and the secondary patency rates at 12 months were 60% and 89%, respectively. CONCLUSION: In-situ revascularisation with silver-coated Dacron provides acceptable results in terms of mortality. This treatment may be useful for simple vascular reconstruction and allow greater attention to bowel repair that is a determinant in short- and mid-term survival.

Atomic force and electron microscopic-based study of sarcolemmal surface of living cardiomyocytes unveils unexpected mitochondrial shift in heart failure.

Loss of T-tubules (TT), sarcolemmal invaginations of cardiomyocytes (CMs), was recently identified as a general heart failure (HF) hallmark. However, whether TT per se or the overall sarcolemma is altered during HF process is still unknown. In this study, we directly examined sarcolemmal surface topography and physical properties using Atomic Force Microscopy (AFM) in living CMs from healthy and failing mice hearts. We confirmed the presence of highly organized crests and hollows along myofilaments in isolated healthy CMs. Sarcolemma topography was tightly correlated with elasticity, with crests stiffer than hollows and related to the presence of few packed subsarcolemmal mitochondria (SSM) as evidenced by electron microscopy. Three days after myocardial infarction (MI), CMs already exhibit an overall sarcolemma disorganization with general loss of crests topography thus becoming smooth and correlating with a decreased elasticity while interfibrillar mitochondria (IFM), myofilaments alignment and TT network were unaltered. End-stage post-ischemic condition (15days post-MI) exacerbates overall sarcolemma disorganization with, in addition to general loss of crest/hollow periodicity, a significant increase of cell surface stiffness. Strikingly, electron microscopy revealed the total depletion of SSM while some IFM heaps could be visualized beneath the membrane. Accordingly, mitochondrial Ca(2+) studies showed a heterogeneous pattern between SSM and IFM in healthy CMs which disappeared in HF. In vitro, formamide-induced sarcolemmal stress on healthy CMs phenocopied post-ischemic kinetics abnormalities and revealed initial SSM death and crest/hollow disorganization followed by IFM later disarray which moved toward the cell surface and structured heaps correlating with TT loss. This study demonstrates that the loss of crest/hollow organization of CM surface in HF occurs early and precedes disruption of the TT network. It also highlights a general stiffness increased of the CM surface most likely related to atypical IFM heaps while SSM died during HF process. Overall, these results indicate that initial sarcolemmal stress leading to SSM death could underlie subsequent TT disarray and HF setting.

The origin of black colouration in onyx agate from Mali

Natural onyx agate from Mali was investigated in an integrated mineralogical and chemical study to reveal the origin of the unusual black colouration. Detailed studies by polarizing microscopy, scanning electron microscopy and micro-Raman spectroscopy showed that the colour of the dark bands is related to the incorporation of small particles of carbon (low-crystalline graphite) up to 200 nm in size into the cryptocrystalline silica matrix. The dark bands have carbon contents of 1.88 wt.%. The location of the graphite particles is closely related to the primary structural banding in the chalcedony. Cathodoluminescence data shows that the banding is interrupted by small fissures containing secondary hydrothermal quartz. The carbon isotope composition (delta C-13 value of -31.1+/-0.2 parts per thousand) of the carbonaceous material points to an organic precursor. Both the direct hydrothermal formation of graphite from methane under elevated temperature and the graphitization of organic precursors by secondary hydrothermal or metamorphic overprint are possible explanations for the colour of the dark bands. The graphitization of organic precursors results in an intense electron spin resonance line at g(eff) = 2.0026.

Isoelectric focusing of alpha-1 acid glycoprotein (orosomucoid) in immobilized pH-gradients with 8M urea: detection of its desialylated variants using an alkaline phosphatase-linked secondary antibody system.

A method allowing a clear separation of the different variants of desialylated alpha 1-acid glycoprotein (orosomucoid) has been developed using isoelectric focusing in immobilized pH gradients, supplemented with 8 M urea and 2% v/v 2-mercaptoethanol. Immunoblotting with two antibody-steps afforded high sensitivity and permitted the detection of about 700 pg of alpha 1-acid glycoprotein in a 20 microL plasma sample diluted 1:28 672. A one year old bloodstrain, kept at room temperature, could easily be phenotyped.

Small RNAs as regulators of primary and secondary metabolism in Pseudomonas species.

Small RNAs (sRNAs) exert important functions in pseudomonads. Classical sRNAs comprise the 4.5S, 6S, 10Sa and 10Sb RNAs, which are known in enteric bacteria as part of the signal recognition particle, a regulatory component of RNA polymerase, transfer-messenger RNA (tmRNA) and the RNA component of RNase P, respectively. Their homologues in pseudomonads are presumed to have analogous functions. Other sRNAs of pseudomonads generally have little or no sequence similarity with sRNAs of enteric bacteria. Numerous sRNAs repress or activate the translation of target mRNAs by a base-pairing mechanism. Examples of this group in Pseudomonas aeruginosa are the iron-repressible PrrF1 and PrrF2 sRNAs, which repress the translation of genes encoding iron-containing proteins, and PhrS, an anaerobically inducible sRNA, which activates the expression of PqsR, a regulator of the Pseudomonas quinolone signal. Other sRNAs sequester RNA-binding proteins that act as translational repressors. Examples of this group in P. aeruginosa include RsmY and RsmZ, which are central regulatory elements in the GacS/GacA signal transduction pathway, and CrcZ, which is a key regulator in the CbrA/CbrB signal transduction pathway. These pathways largely control the extracellular activities (including virulence traits) and the selection of the energetically most favourable carbon sources, respectively, in pseudomonads.

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).