Influence of social deprivation and remoteness on the likelihood of sphincter amputation for rectal cancer: a high-resolution population-based study.

BACKGROUND: Medical care in rectal cancer is subject to social inequality. According to the last French guidelines, a 1-cm distal margin below the lower pole of the rectal tumor is now considered sufficient. This extends the limits of the current sphincter preservation gold standard. Like for other innovative technics, the dissemination of such technics is often subject to social and geographical inequalities. The objective was to analyze whether sphincter preservation in rectal cancer is subject to social or geographical inequality. METHODS: The odds of sphincter preservation was modeled by logistic regression among the 1453 patients in the Calvados digestive cancer registry between 1 January 1997 and 31 December 2015 by examining some of the variables that could influence it: social inequalities and geographical remoteness, sex, age, and stage. RESULTS: A total of 69.4% of the population received sphincter preservation. Patients in the more deprived quintiles had a significantly higher probability of having sphincter amputation (odds ratio (OR) = 1.469 (1.046-2.064)). This result was no longer significant after adjustment on stage and travel time. There was a dose-effect pattern of geographical remoteness on likelihood of sphincter preservation with a progressive increase in OR between patients living the nearest and the furthest from the reference center (p-trend = 0.0178). CONCLUSION: This study shows that the probability of receiving sphincter preservation is influenced by the social environment and strongly influenced by remoteness. Although management guidelines have had a huge impact on the rates of sphincter preservation, they have not reduced the influence of the social and geographical environment on sphincter preservation.

Significant dose reduction using synchrotron radiation computed tomography: first clinical case and application to high resolution CT exams.

Since the invention of Computed Tomography (CT), many technological advances emerged to improve the image sensitivity and resolution. However, no new source types were developed for clinical use. In this study, for the first time, coherent monochromatic X-rays from a synchrotron radiation source were used to acquire 3D CTs on patients. The aim of this work was to evaluate the clinical potential of the images acquired using Synchrotron Radiation CT (SRCT). SRCTs were acquired using monochromatic X-rays tuned at 80 keV (0.350 × 0.350 × 2 mm3 voxel size). A quantitative image quality comparison study was carried out on phantoms between a state of the art clinical CT and SRCT images. Dedicated iterative algorithms were developed to optimize the image quality and further reduce the delivered dose by a factor of 12 while keeping a better image quality than the one obtained with a clinical CT scanner. We finally show in this paper the very first SRCT results of one patient who received Synchrotron Radiotherapy in an ongoing clinical trial. This demonstrates the potential of the technique in terms of image quality improvement at a reduced radiation dose for inner ear visualization.

A correlational study between signature, writing abilities and decision-making capacity among people with initial cognitive impairment.

BACKGROUND: Some clinical conditions, including dementia, compromise cognitive functions involved in decision-making processes, with repercussions on the ability to subscribe a will. Because of the increasing number of aged people with cognitive impairment there is an acute and growing need for decision-making capacity evidence-based assessment. AIMS: Our study investigates the relationship between writing abilities and cognitive integrity to see if it is possible to make inferences on decision-making capacity through handwriting analysis. We also investigated the relationship between signature ability and cognitive integrity. METHODS: Thirty-six participants with diagnosis of MCI and 38 participants with diagnosis of initial dementia were recruited. For each subject we collected two samples of signature-an actual and a previous one-and an extract of spontaneous writing. Furthermore, we administered a neuropsychological battery to investigate cognitive functions involved in decision-making. RESULTS: We found significant correlations between spontaneous writing indexes and neuropsychological test results. Nonetheless, the index of signature deterioration does not correlate with the level of cognitive decline. DISCUSSION: Our results suggest that a careful analysis of spontaneous writing can be useful to make inferences on decision-making capacity, whereas great caution should be taken in attributing validity to handwritten signature of subjects with MCI or dementia. CONCLUSIONS: The analysis of spontaneous writing can be a reliable aid in cases of retrospective evaluation of cognitive integrity. On the other side, the ability to sign is not an index of cognitive integrity.

[Diagnosis of skin cancer by dermatologists in the French West Indies: a prospective study]. / Étude prospective de l'incidence des cancers cutanés dépistés en pratique dermatologique aux Antilles françaises.

BACKGROUND: The incidence of skin cancer is not well established in the French West Indies, aside from old data concerning cutaneous melanoma. METHOD: A prospective study was performed over a 3-month period in late 2007 in the French West Indies. The number of new cases of histologically confirmed skin cancer was determined using a questionnaire. RESULTS: The rate of participation of dermatologists was 82 %. During the study period, 166 skin cancers were diagnosed in 134 patients (66 women and 68 men: mean age=63.3 years, SD=2.5), including 137 basal cell carcinomas, 12 melanomas, seven squamous cell carcinomas, six Bowen's disease, one B lymphoma and one Paget's disease. The raw incidence of skin cancers detected by dermatologists was calculated as 64.6 cases/100 000 inhabitants/year for basal cell carcinoma, 5.7 cases/100 000 inhabitants/year for melanoma, 3.3 cases/100 000 inhabitants/year for squamous cell carcinoma, and 2.8 cases/100 000 inhabitants/year for Bowen's disease. Seven melanomas (almost exclusively of plantar topography) and seven basal cell carcinomas were diagnosed in patients of phototype V or VI. DISCUSSION: Although lower than in metropolitan France, the number of skin cancers diagnosed by dermatologists in the French West Indies is fairly high. In addition, this study indicates the significant incidence of basal cell carcinomas and melanomas in subjects with phototype V or VI, underreported in the literature. These findings highlight the need to begin longer-term studies and to include skin carcinomas in the cancer registry of the French West Indies in order to better identify their characteristics among the Caribbean population.

X-ray energy optimization in minibeam radiation therapy.

PURPOSE: The purpose of this work is to assess which energy in minibeam radiation therapy provides the best compromise between the deposited dose in the tumor and the sparing of the healthy tissues. METHODS: Monte Carlo simulations (PENELOPE 2006) have been used as a method to calculate the ratio of the peak-to-valley doses (PVDR) in the healthy tissues and in the tumor for different beam energies. The maximization of the ratio of PVDR in the healthy tissues and in the tumor has been used as a criterion. RESULTS: The main result of this work is that, for the parameters being used in preclinical trials (minibeam sizes of 600 microm and 1200 microm center-to-center separation), the optimum beam energy is 375 keV. CONCLUSIONS: The conclusion is that this is the energy of minibeams that should be used in the preclinical studies.

New technology enables high precision multislit collimators for microbeam radiation therapy.

During the past decade microbeam radiation therapy has evolved from preclinical studies to a stage in which clinical trials can be planned, using spatially fractionated, highly collimated and high intensity beams like those generated at the x-ray ID17 beamline of the European Synchrotron Radiation Facility. The production of such microbeams typically between 25 and 100 microm full width at half maximum (FWHM) values and 100-400 microm center-to-center (c-t-c) spacings requires a multislit collimator either with fixed or adjustable microbeam width. The mechanical regularity of such devices is the most important property required to produce an array of identical microbeams. That ensures treatment reproducibility and reliable use of Monte Carlo-based treatment planning systems. New high precision wire cutting techniques allow the fabrication of these collimators made of tungsten carbide. We present a variable slit width collimator as well as a single slit device with a fixed setting of 50 microm FWHM and 400 microm c-t-c, both able to cover irradiation fields of 50 mm width, deemed to meet clinical requirements. Important improvements have reduced the standard deviation of 5.5 microm to less than 1 microm for a nominal FWHM value of 25 microm. The specifications of both devices, the methods used to measure these characteristics, and the results are presented.

Biological equivalent dose studies for dose escalation in the stereotactic synchrotron radiation therapy clinical trials.

Synchrotron radiation is an innovative tool for the treatment of brain tumors. In the stereotactic synchrotron radiation therapy (SSRT) technique a radiation dose enhancement specific to the tumor is obtained. The tumor is loaded with a high atomic number (Z) element and it is irradiated in stereotactic conditions from several entrance angles. The aim of this work was to assess dosimetric properties of the SSRT for preparing clinical trials at the European Synchrotron Radiation Facility (ESRF). To estimate the possible risks, the doses received by the tumor and healthy tissues in the future clinical conditions have been calculated by using Monte Carlo simulations (PENELOPE code). The dose enhancement factors have been determined for different iodine concentrations in the tumor, several tumor positions, tumor sizes, and different beam sizes. A scheme for the dose escalation in the various phases of the clinical trials has been proposed. The biological equivalent doses and the normalized total doses received by the skull have been calculated in order to assure that the tolerance values are not reached.

The radiotherapy clinical trials projects at the ESRF: technical aspects.

The radiotherapy clinical trials projects, both aiming at treating aggressive brain tumors, require several major modifications and new constructions at the ESRF ID17 Biomedical beamline. The application of the Stereotactic Synchrotron Radiation Therapy (SSRT) technique mainly necessitates an upgrade of the existing patient positioning system, which was formerly used for the angiography program. It will allow for accurate positioning, translation and rotation of the patient during the treatment. For the Microbeam Radiation Therapy (MRT) clinical trials project, a new white beam hutch will be constructed to accommodate a dedicated patient positioning system. Consequently, the existing control hutches and the related installations will also be completely refurbished. Furthermore, the foreseen installation of a second X-ray source, which will allow doubling the currently available photon flux at high energies, requires a redesign of most optical components to handle the increased power and power densities. Starting from the current ID17 Biomedical beamline layout, the paper will present an update of the different modification/construction projects, including the general organization and planning.

[Thirty-four years follow-up of a bilateral Mac Kee-Farrar arthroplasty without loosening or osteolysis]. / Absence d'ostéolyse et de descellement d'une arthroplastie bilatérale de Mac Kee-Farrar à 34 ans de recul.

We report the case of a 93-year-old patient with bilateral Mac Kee-Farrar hip arthroplasties implanted 34 years ago. The patient was seen in 2005 for a type B1 periprosthetic fracture on the right prosthesis implanted in 1973. There was no loosening and the fracture was treated by plate fixation. Before the fracture, the Postel-Merle d'Aubigné (PMA) score was 16 on both sides, with a Devane activity score grade 2. At last follow-up, the PMA score was 13 for both hips, with a Devane activity score grade 1. Serum cobalt level was 1.36 microg/L (normal <1 microg/L). This exceptional case is to our knowledge the longest observed with this implant without clinical or radiographic signs of loosening. The serum cobalt level, rarely assayed after more than 30 years, was within the limits accepted for a metal-on-metal hip bilateral arthroplasty. We discuss the causes of failure and success of the Mac Kee-Farrar implant as reported in the literature and remark that long survival of the metal-on-metal bearing can occasionally be observed without signs of wear. Recent works on the metal-on-metal bearing merit attention.

Acoustoelasticity in soft solids: assessment of the nonlinear shear modulus with the acoustic radiation force.

The assessment of viscoelastic properties of soft tissues is enjoying a growing interest in the field of medical imaging as pathologies are often correlated with a local change of stiffness. To date, advanced techniques in that field have been concentrating on the estimation of the second order elastic modulus (mu). In this paper, the nonlinear behavior of quasi-incompressible soft solids is investigated using the supersonic shear imaging technique based on the remote generation of polarized plane shear waves in tissues induced by the acoustic radiation force. Applying a theoretical approach of the strain energy in soft solid [Hamilton et al., J. Acoust. Soc. Am. 116, 41-44 (2004)], it is shown that the well-known acoustoelasticity experiment allowing the recovery of higher order elastic moduli can be greatly simplified. Experimentally, it requires measurements of the local speed of polarized plane shear waves in a statically and uniaxially stressed isotropic medium. These shear wave speed estimates are obtained by imaging the shear wave propagation in soft media with an ultrafast echographic scanner. In this situation, the uniaxial static stress induces anisotropy due to the nonlinear effects and results in a change of shear wave speed. Then the third order elastic modulus (A) is measured in agar-gelatin-based phantoms and polyvinyl alcohol based phantoms.

Automation of sample mounting for macromolecular crystallography.

A standard sample holder and vial for cryocooled macromolecular crystals has been defined for use with robotic sample changers. This SPINE standard sample holder is a modified version, with added features and specifications, of sample holders in common use. In particular, the SPINE standard meets the precision required for automatic sample exchange and includes a cap that is identified by a two-dimensional datamatrix code as well as an optional vial. At the ESRF, the sample holder standard is in use with the EMBL/ESRF/BM14 robotic sample changer (SC3) which is installed on eight beamlines. The SC3 can hold up to 50 crystals stored in five baskets. A datamatrix reader in the SC3 ensures safe management of the sample flow and facilitates fully automatic screening and characterization of samples. Tools for handling and transporting 50 samples in a dry shipping dewar have been developed. In addition to the SC3, the SPINE sample holder is currently compatible with a number of other robotic sample changers.

Axillary recurrence after negative sentinel lymph node biopsy without axillary dissection: a study on 479 breast cancer patients.

AIMS: To determine the axillary recurrence rate in breast cancer patients with negative sentinel lymph nodes (SLN) who did not undergo further axillary lymph node dissection (ALND), and to establish whether this conservative axillary approach leads to an increased recourse to diagnostic axillary biopsy during the follow-up period because of the clinical suspicion of nodal recurrence. METHODS: In 479 patients, operated on for early breast cancer between 1998 and 2002 in five institutions, SLN biopsy was negative and no further axillary surgery was performed. SLN was localized using subdermal injection with 30-50 MBq of 99m-Tc-colloidal albumin. Follow-up controls were performed at 6-monthly intervals. RESULTS: The mean number of SLNs removed was 1.4 per patient. Most patients (90.6%) were given adjuvant systemic therapy, based on the primary tumour characteristics. At a median follow-up of 35.8 months, no clinical axillary recurrence was found. No patient underwent surgical axillary biopsy for suspicious clinical or ultrasonographic findings. CONCLUSIONS: Our results confirm that SLN biopsy without ALND in SLN-negative patients with early breast cancer is not followed by clinically evident axillary recurrence in the short-term.

Belgian legislation and the effect of elective single embryo transfer on IVF outcome.

In order to reduce the number of multiple pregnancies following IVF, the Belgian government agreed to reimburse laboratory expenses for six IVF cycles up to the age of 42 years, in exchange for restriction of the number of embryos replaced. Data on assisted reproduction outcome before and after the introduction of this new legislation were analysed retrospectively in terms of implantation, pregnancy and multiple pregnancy rates. After the introduction of the new law, the percentage of single embryo transfer increased from 14 to 49%. Implantation rates were 25.9 and 23% respectively. There was no difference in the overall pregnancy rate before and after the introduction (36 versus 37%). Twin pregnancies, however, decreased from 19 to 3%. These findings indicate that elective single embryo transfer significantly decreases the twin pregnancy rate without a reduction in the overall pregnancy rate.

Pharmacodynamics of a single low dose of long-acting recombinant follicle-stimulating hormone (FSH-carboxy terminal peptide, corifollitropin alfa) in women with World Health Organization group II anovulatory infertility.

In a double-blind, placebo-controlled, randomized study, 55 anovulatory subjects received a single s.c. injection of placebo (n = 10) or recombinant long-acting FSH [FSH-carboxy terminal peptide (CTP), ORG 36286, corifollitropin alfa; NV Organon, The Netherlands] in doses of 7.5 (n = 13), 15 (n = 10), 30 (n = 11), or 60 microg (n = 11). The injection was given 2 or 3 d after the onset of a spontaneous or progestagen-induced withdrawal bleed. After drug administration, the induced follicular response varied widely among subjects in each dose group. The percentage of subjects with a follicular response (at least one follicle > or = 10.0 mm) increased with the dose (P < 0.01) and was 10, 31, 70, 73, and 82% in the placebo and 7.5-, 15-, 30-, and 60-microg treatment groups, respectively. In responding subjects, the average maximum number of follicles was 4.0, 7.6, 13.4, and 20.0, respectively, which was reached at 6.5, 6.9, 6.6, and 8.2 d after a single dose of 7.5, 15, 30, and 60 microg FSH-CTP, respectively. The dose-response for the number of follicles was statistically significant within the dose range tested (P < 0.01). Peak serum inhibin-B levels were significantly correlated with serum estradiol (E2) levels (r = 0.84, P < 0.01), and peak concentrations of inhibin-B and E2 correlated with the number of follicles observed at the same time point (for both hormones; r = 0.47, P < 0.01). Overall per treatment group, serum E2 and inhibin B concentrations significantly increased only in the two highest FSH-CTP dose groups, reaching peak concentrations at d 3 in the 30-microg group and at d 5 in the 60-microg group. Thereafter these hormone values declined rapidly, returning to baseline within 1 wk after FSH-CTP administration. In total, nine of the 55 treated subjects (16.4%) ovulated after drug administration: one subject in the placebo group, two subjects in the 7.5-microg group, three subjects in the 15-microg group, two in the 30-microg group, and one in the 60-microg group. Three subjects had monofollicular ovulation after placebo (n = 1) and a single dose of 15 microg FSH-CTP (n = 2). In two subjects with too many preovulatory follicles, (multiple) ovulation was prevented by GnRH antagonist administration. Thus, a single low dose of long-acting FSH-CTP was able to induce one or more follicles to grow up to ovulatory sizes, but the anovulatory status was not reversed because the incidence of subsequent (mono)ovulations was low.

[How to prevent saphenous nerve injury. A personal modified technique for the stripping of the long saphenous vein]. / Come prevenire le lesioni del nervo safeno. Una tecnica personale modificata per lo stripping della grande safena.

BACKGROUND: In literature the incidence of paresthesia caused by long stripping (LS) of the saphenous vein (SV) varies widely. Best results have been reported with the invagination technique by Van Der Stricht. However, this technique is associated with a high incidence of vein rupture and incomplete stripping. The aim of this study is to test a personal technique to avoid the SV rupture and to reduce the incidence of saphenous nerve injury. METHODS: Sixty-eight patients underwent LS of the SV from groin to ankle under monolateral spinal anesthesia on a one-day surgery basis using a personal technique combining external and invaginated saphenous stripping. All patients underwent a clinical re-evalutation 1, 3, 6, 12, 24 and 48 months after the operation. RESULTS: No intraoperative complications were recorded. Stripping of the long saphenous vein was complete in all cases without any rupture of the veins. Only one postoperative hematoma of the leg (1.5%) which was naturally reabsorbed, was recorded; four patients (5.9%) had transitory saphenous nerve injury. Permanent saphenous nerve damage was found in only one of 68 patients (1.5%). All the patients were discharged on the day of operation and we did not register any prolonged hospitalization. CONCLUSIONS: The result of our approach was a very low postoperative complication rate (1.5% of permanent neurological damage) without any rupture of the vein.

Lack of cell death enhancement after irradiation with monochromatic synchrotron X rays at the K-shell edge of platinum incorporated in living SQ20B human cells as cis-diamminedichloroplatinum (II).

In this paper we describe the results of experiments using synchrotron radiation to trigger the Auger effect in living human cancer cells treated with a widely used chemotherapy drug: cis-diamminedichloroplatinum (II) (cisplatin). The experiments were carried out at the ID17 beamline of the European Synchrotron Radiation Facility, which produces a high-fluence monochromatic beam that is adjustable from 20 to 80 keV. Cisplatin was chosen as the carrier of platinum atoms in the cells because of its alkylating-like activity and the irradiation was done with monochromatic beams above and below the platinum K-shell edge (78.39 keV). Cell survival curves were comparable with those obtained for the same cells under conventional irradiation conditions. At a low dose of cisplatin (0.1 microM, 48 h), no difference was seen in survival when the cells were irradiated above and below the K-shell edge of platinum. Higher cisplatin concentrations were investigated to enhance the cellular platinum content. The results with 1 microM cisplatin for 12 h showed no difference when the cells were irradiated with beams above or below the platinum K-shell edge with the exception of the higher cell death resulting from drug toxicity. The intracellular content of platinum was significant, as measured macroscopically by inductively coupled plasma mass spectrometry. Its subcellular localization and particularly its presence in the cell nucleus were verified by microscopic synchrotron X-ray fluorescence. This was the first known attempt at K-shell edge photon activation of stable platinum in living cells with a platinum complex used for chemotherapy. Its evident toxicity in these cells leads us to put forth the hypothesis that cisplatin toxicity can mask the enhancement of cell death induced by the irradiation above the K-shell edge. However, K-shell edge photon activation of stable elements provides a powerful technique for the understanding of the biological effects of Auger processes. Further avenues of development are discussed.

First human transvenous coronary angiography at the European Synchrotron Radiation Facility.

The first operation of the European Synchrotron Radiation Facility (ESRF) medical beamline is reported in this paper. The goal of the angiography project is to develop a reduced risk imaging technique, which can be used to follow up patients after coronary intervention. After the intravenous injection of a contrast agent (iodine) two images are produced with monochromatic beams, bracketing the iodine K-edge. The logarithmic subtraction of the two measurements results in an iodine enhanced image, which can be precisely quantified. A research protocol has been designed to evaluate the performances of this method in comparison with the conventional technique. Patients included in the protocol have previously undergone angioplasty. If a re-stenosis is suspected, the patient is imaged both at the ESRF and at the hospital with the conventional technique, within the next few days. This paper reports the results obtained with the first patients. To date, eight patients have been imaged and excellent image quality was obtained.

Research at the European Synchrotron Radiation Facility medical beamline.

The application of synchrotron radiation in medical research has become a mature field of research at synchrotron facilities worldwide. In the relatively short time that synchrotrons have been available to the scientific community, their characteristic beams of UV and X-ray radiation have been applied to virtually all areas of medical science which use ionizing radiation. The ability to tune intense monochromatic beams over wide energy ranges differentiates these sources from standard clinical and research tools. At the European Synchrotron Radiation Facility (Grenoble, France), a major research facility is operational on an advanced wiggler radiation beamport, ID17. The beamport is designed to carry out a broad range of research ranging from cell radiation biology to in vivo human studies. Medical imaging programs at ID17 include transvenous coronary angiography, computed tomography, mammography and bronchography. In addition, a major research program on microbeam radiation therapy is progressing. This paper will present a very brief overview of the beamline and the imaging and therapy programs.

In vivo K-edge imaging with synchrotron radiation.

We present in this paper two imaging techniques using contrast agents assessed with in vivo experiments. Both methods are based on the same physical principle, and were implemented at the European Synchrotron Radiation Facility medical beamline. The first one is intravenous coronary angiography using synchrotron radiation X-rays. This imaging technique has been planned for human studies in the near future. We describe the first experiments that were carried out with pigs at the ESRF. The second imaging mode is computed tomography using synchrotron radiation on rats bearing brain tumors. Owing to synchrotron radiation physical properties, these new imaging methods provide additional information compared to conventional techniques. After infusion of the contrast agent, it is possible to derive from the images the concentration of the contrast agent in the tumor area for the computed tomography and in any visible vessel for the angiography method.