Treatment planning of scanned proton beams in RayStation.

The use of scanned proton beams in external beam radiation therapy has seen a rapid development over the past decade. This technique places new demands on treatment planning, as compared to conventional photon-based radiation therapy. In this article, several proton specific functions as implemented in the treatment planning system RayStation are presented. We will cover algorithms for energy layer and spot selection, basic optimization including the handling of spot weight limits, optimization of the linear energy transfer (LET) distribution, robust optimization including the special case of 4D optimization, proton arc planning, and automatic planning using deep learning. We will further present the Monte Carlo (MC) proton dose engine in RayStation to some detail, from the material interpretation of the CT data, through the beam model parameterization, to the actual MC transport mechanism. Useful tools for plan evaluation, including robustness evaluation, and the versatile scripting interface are also described. The overall aim of the paper is to give an overview of some of the key proton planning functions in RayStation, with example usages, and at the same time provide the details about the underlying algorithms that previously have not been fully publicly available.

The use of a mini-ridge filter with cyclotron-based pencil beam scanning proton therapy.

BACKGROUND: Pencil beam scanning (PBS) proton therapy allows for far superior dose conformality compared with passive scattering techniques. However, one drawback of PBS is that the beam delivery time can be long, particularly when treating superficial disease. Minimizing beam delivery time is important for patient comfort and precision of treatment delivery. Mini-ridge filters (MRF) have been shown to reduce beam delivery time for synchrotron-based PBS. Given that cyclotron systems are widely used in proton therapy it is necessary to investigate the potential clinical benefit of mini-ridge filters in such systems. PURPOSE: To demonstrate the clinical benefit of using a MRF to reduce beam delivery time for patients with large target volumes and superficial disease in cyclotron-based PBS proton therapy. METHODS: A MRF beam model was generated by simulating the effect of a MRF on our clinical beam data assuming a fixed snout position relative to the isocenter. The beam model was validated with a series of measurements. The model was used to optimize treatment plans in a water phantom and on six patient DICOM datasets to further study the effect of the MRF and for comparison with physician-approved clinical treatment plans. Beam delivery time was measured for six plans with and without the MRF to demonstrate the reduction achievable. Plans with and without MRF were reviewed to confirm clinical acceptability by a radiation oncologist. Patient-specific QA measurements were carried out with a two-dimensional ionization chamber array detector for one representative patient's plan optimized with the MRF beam model. RESULTS: Results show good agreement between the simulated beam model and measurements with mean and maximum deviations of 0.06 mm (0.45%) and 0.61 mm (4.9%). The increase in Bragg peak width (FWHM) ranged from 2.7 mm at 226 MeV to 6.1 mm at 70 MeV. The mean and maximum reduction in beam delivery time observed per field was 29.1 s (32.2%) and 79.7 s (55.3%). CONCLUSION: MRFs can be used to reduce treatment time in cyclotron-based PBS proton therapy without sacrificing plan quality. This is particularly beneficial for patients with large targets and superficial disease such as in breast cancer where treatment times are generally long, as well as patients treated with deep inspiration breath hold (DIBH).

Validating a double Gaussian source model for small proton fields in a commercial Monte-Carlo dose calculation engine.

PURPOSE: The primary fluence of a proton pencil beam exiting the accelerator is enveloped by a region of secondaries, commonly called "spray". Although small in magnitude, this spray may affect dose distributions in pencil beam scanning mode e.g., in the calculation of the small field output, if not modelled properly in a treatment planning system (TPS). The purpose of this study was to dosimetrically benchmark the Monte Carlo (MC) dose engine of the RayStation TPS (v.10A) in small proton fields and systematically compare single Gaussian (SG) and double Gaussian (DG) modeling of initial proton fluence providing a more accurate representation of the nozzle spray. METHODS: The initial proton fluence distribution for SG/DG beam modeling was deduced from two-dimensional measurements in air with a scintillation screen with electronic readout. The DG model was either based on direct fits of the two Gaussians to the measured profiles, or by an iterative optimization procedure, which uses the measured profiles to mimic in-air scan-field factor (SF) measurements. To validate the DG beam models SFs, i.e. relative doses to a 10 × 10 cm2 field, were measured in water for three different initial proton energies (100MeV, 160MeV, 226.7MeV) and square field sizes from 1×1cm2 to 10×10cm2 using a small field ionization chamber (IBA CC01) and an IBA ProteusPlus system (universal nozzle). Furthermore, the dose to the center of spherical target volumes (diameters: 1cm to 10cm) was determined using the same small volume ionization chamber (IC). A comprehensive uncertainty analysis was performed, including estimates of influence factors typical for small field dosimetry deduced from a simple two-dimensional analytical model of the relative fluence distribution. Measurements were compared to the predictions of the RayStation TPS. RESULTS: SFs deviated by more than 2% from TPS predictions in all fields <4×4cm2 with a maximum deviation of 5.8% for SG modeling. In contrast, deviations were smaller than 2% for all field-sizes and proton energies when using the directly fitted DG model. The optimized DG model performed similarly except for slightly larger deviations in the 1×1cm2 scan-fields. The uncertainty estimates showed a significant impact of pencil beam size variations (±5%) resulting in up to 5.0% standard uncertainty. The point doses within spherical irradiation volumes deviated from calculations by up to 3.3% for the SG model and 2.0% for the DG model. CONCLUSION: Properly representing nozzle spray in RayStation's MC-based dose engine using a DG beam model was found to reduce the deviation to measurements in small spherical targets to below 2%. A thorough uncertainty analysis shows a similar magnitude for the combined standard uncertainty of such measurements.

Commissioning and validation of a novel commercial TPS for ocular proton therapy.

BACKGROUND: Until today, the majority of ocular proton treatments worldwide were planned with the EYEPLAN treatment planning system (TPS). Recently, the commercial, computed tomography (CT)-based TPS for ocular proton therapy RayOcular was released, which follows the general concepts of model-based treatment planning approach in conjunction with a pencil-beam-type dose algorithm (PBA). PURPOSE: To validate RayOcular with respect to two main features: accurate geometrical representation of the eye model and accuracy of its dose calculation algorithm in combination with an Ion Beam Applications (IBA) eye treatment delivery system. METHODS: Different 3D-printed eye-ball-phantoms were fabricated to test the geometrical representation of the corresponding CT-based model, both in orthogonal 2D images for X-ray image overlay and in fundus view overlaid with a funduscopy. For the latter, the phantom was equipped with a lens matching refraction of the human eye. Funduscopy was acquired in a Zeiss Claus 500 camera. Tantalum clips and fiducials attached to the phantoms were localized in the TPS model, and residual deviations to the actual position in X-ray images for various orientations of the phantom were determined, after the nominal eye orientation was corrected in RayOcular to obtain a best overall fit. In the fundus view, deviations between known and displayed distances were measured. Dose calculation accuracy of the PBA on a 0.2 mm grid was investigated by comparing between measured lateral and depth-dose profiles in water for various combinations of range, modulation, and field-size. Ultimately, the modeling of dose distributions behind wedges was tested. A 1D gamma-test was applied, and the lateral and distal penumbra were further compared. RESULTS: Average residuals between model clips and visible clips/fiducials in orthogonal X-ray images were within 0.3 mm, including different orientations of the phantom. The differences between measured distances on the registered funduscopy image in the RayOcular fundus view and the known ground-truth were within 1 mm up to 10.5 mm distance from the posterior pole. No clear benefit projection of either polar mode or camera mode could be identified, the latter mimicking camera properties. Measured dose distributions were reproduced with gamma-test pass-rates of >95% with 2%/0.3 mm for depth and lateral profiles in the middle of spread-out Bragg-peaks. Distal falloff and lateral penumbra were within 0.2 mm for fields without a wedge. For shallow depths, the agreement was worse, reaching pass-rates down to 80% with 5%/0.3 mm when comparing lateral profiles in air. This is caused by low-energy protons from a scatter source in the IBA system not modeled by RayOcular. Dose distributions modified by wedges were reproduced, matching the wedge-induced broadening of the lateral penumbra to within 0.4 mm for the investigated cases and showing the excess dose within the field due to wedge scatter. CONCLUSION: RayOcular was validated for its use with an IBA single scattering delivery nozzle. Geometric modeling of the eye and representation of 2D projections fulfill clinical requirements. The PBA dose calculation reproduces measured distributions and allows explicit handling of wedges, overcoming approximations of simpler dose calculation algorithms used in other systems.

Technical note: Impact of beam properties for uveal melanoma proton therapy-An in silico planning study.

PURPOSE: To evaluate the impact of beam quality in terms of distal fall-off (DFO, 90%-10%) and lateral penumbra (LP, 80%-20%) of single beam ocular proton therapy (OPT) and to derive resulting ideal requirements for future systems. METHODS: Nine different beam models with DFO varying between 1 and 4 mm and LP between 1 and 4 mm were created. Beam models were incorporated into the RayStation with RayOcular treatment planning system version 10 B (RaySearch Laboratories, Stockholm, Sweden). Each beam model was applied for eight typical clinical cases, covering different sizes and locations of uveal melanoma. Plans with and without an additional wedge were created, resulting in 117 plans with a total prescribed median dose of 60 Gy(RBE) to the clinical target volume. Treatment plans were analyzed in terms of V20-V80 penumbra volume, D1 (dose to 1% of the volume) for optic disc and macula, optic nerve V30 (volume receiving 30 Gy(RBE), i.e., 50% of prescription), as well as average dose to lens and ciliary body. An LP-dependent aperture margin was based on estimated uncertainties, ranging from 1.7 to 4.0 mm. RESULTS: V20-V80 showed a strong influence by LP, while DFO was less relevant. The optic disc D1 reached an extra dose of up to 3000 cGy(RBE), comparing the defined technical limit of DFO = LP = 1 mm with DFO = 3 mm/LP = 4 mm. The latter may result from a pencil-beam scanning (PBS) system with static apertures. Plans employing a wedge showed an improvement for organs at risk sparing. CONCLUSION: Plan quality is strongly influenced by initial beam parameters. The impact of LP is more pronounced when compared to DFO. The latter becomes important in the treatment of posterior tumors near the macula, optic disc or optic nerve. The plan quality achieved by dedicated OPT nozzles in single- or double-scattering design might not be achievable with modified PBS systems.

Clinical validation of a GPU-based Monte Carlo dose engine of a commercial treatment planning system for pencil beam scanning proton therapy.

PURPOSE: To perform the validation of the GPU-based (Graphical Processing Unit based) proton Monte Carlo (MC) dose engine implemented in a commercial TPS (RayStation 10B) and to report final dose calculation times for clinical cases. MATERIALS AND METHODS: 440 patients treated at the Proton Therapy Center of Trento, Italy, between 2018 and 2019 were selected for this study. 636 approved plans with 3361 beams computed with the clinically implemented CPU-MC dose engine (version 4.2 and 4.5), were used for the validation of the new algorithm. For each beam, the dose was recalculated using the new GPU-MC dose engine with the initial CPU computation settings and compared to the original CPU-MC dose. Beam dose difference distributions were studied to ensure that the two dose distributions were equal within the expected fluctuations of the MC statistical uncertainty (s) of each computation. Plan dose distributions were compared with respect to the dosimetric indices D98, D50 and D1 of all ROIs defined as targets. A complete assessment of the computation time as a function of s and dose grid voxel size was done. RESULTS: The median over all mean beam dose differences between CPU- and GPU-MC was -0.01% and the median of the corresponding standard deviations was close to (√2s) both for simulations with an s of 0.5% and 1.0% per beam. This shows that the two dose distributions can be considered equal. All the DVH indices showed an average difference below 0.04%. About half of the plans were computed with 1.0% statistical uncertainty on a 2 mm dose calculation grid, for which the median computation time was 5.2 s. The median computational speed for all plans in the study was 8.4 million protons/second. CONCLUSION: A validation of a clinical MC algorithm running on GPU was performed on a large pool of patients treated with pencil beam scanning proton therapy. We demonstrated that the differences with the previous CPU-based MC were only due to the intrinsic statistical fluctuations of the MC method, which translated to insignificant differences on plan dose level. The significant increase in dose calculation speed is expected to facilitate new clinical workflows.

Experiments and Monte Carlo simulations on multiple Coulomb scattering of protons.

BACKGROUND AND PURPOSE: Monte Carlo simulations as well as analytical computations of proton transport in material media require accurate values of multiple Coulomb scattering (MCS) angles. High-quality experimental data on MCS angles in the energy range for proton therapy are, however, sparse. In this work, MCS modeling in proton transport was evaluated employing an experimental method to measure these angles on a medical proton beamline in clinically relevant materials. Results are compared to Monte Carlo simulations and analytical models. MATERIALS AND METHODS: Aluminum, brass, and lucite (PMMA) scatterers of clinically relevant thicknesses were irradiated with protons at 100, 160, and 220 MeV. Resulting spatial distributions of individual pencil beams were measured with a scintillating screen. The MCS angles were determined by deconvolution and a virtual point source approach. Results were compared to those obtained with the Monte Carlo codes PENH, TOPAS, and RayStation Monte Carlo, as well as the analytical models RayStation Pencil Beam Algorithm and the Molière/Fano/Hanson variant of the Molière theory. RESULTS: Experimental data obtained with the presented methodology agree with previously published results within 6%, with an average deviation of 3%. The combined average uncertainty of the experimental data yielded 1.8%, while the combined maximum uncertainty was below 4%. The obtained Monte Carlo results for PENH, TOPAS, and RayStation deviate on average for all considered energies, materials and thicknesses, by 2.5%, 3.4%, and 2.8% from the experimental data, respectively. For the analytical models, the average deviations amount to 4.5% and 2.9% for the RayStation Pencil Beam Algorithm and the Molière/Fano/Hanson model, respectively. CONCLUSION: The experimental method developed for the present work allowed to measure MCS angles in clinical proton facilities with good accuracy. The presented method permits to extend the database on experimental MCS angles which is rather limited. This work further provides benchmark data for lucite in thicknesses relevant for clinical applications. The data may serve to validate dose engines of treatment planning systems and secondary dose check software. The Monte Carlo and analytical algorithms studied are capable of reproducing MCS data within the required accuracy for clinical applications.

Validation and practical implementation of seated position radiotherapy in a commercial TPS for proton therapy.

PURPOSE: This work aims to validate new 6D couch features and their implementation for seated radiotherapy in RayStation (RS) treatment planning system (TPS). MATERIALS AND METHODS: In RS TPS, new 6D couch features are (i) chair support device, (ii) patient treatment option of "Sitting: face towards the front of the chair", and (iii) patient support pitch and roll capabilities. The validation of pitch and roll was performed by comparing TPS generated DRRs with planar x-rays. Dosimetric tests through measurement by 2D ion chamber array were performed for beams created with varied scanning and treatment orientation and 6D couch rotations. For the implementation of 6D couch features for treatments in a seated position, the TPS and oncology information system (Mosaiq) settings are described for a commercial chair. An end-to-end test using an anthropomorphic phantom was performed to test the complete workflow from simulation to treatment delivery. RESULTS: The 6D couch features were found to have a consistent implementation that met IEC 61712 standard. The DRRs were found to have an acceptable agreement with planar x-rays based on visual inspection. For dose map comparison between measured and calculated, the gamma index analysis for all the beams was >95% at a 3% dose-difference and 3 mm distance-to-agreement tolerances. For an end-to end-testing, the phantom was successfully set up at isocenter in the seated position and treatment was delivered. CONCLUSIONS: Chair-based treatments in a seated position can be implemented in RayStation through the use of newly released 6D couch features.

Validation of the RayStation Monte Carlo dose calculation algorithm using a realistic lung phantom.

PURPOSE: Our purposes are to compare the accuracy of RaySearch's analytical pencil beam (APB) and Monte Carlo (MC) algorithms for clinical proton therapy and to present clinical validation data using a novel animal tissue lung phantom. METHODS: We constructed a realistic lung phantom composed of a rack of lamb resting on a stack of rectangular natural cork slabs simulating lung tissue. The tumor was simulated using 70% lean ground lamb meat inserted in a spherical hole with diameter 40 ± 5 mm carved into the cork slabs. A single-field plan using an anterior beam and a two-field plan using two anterior-oblique beams were delivered to the phantom. Ion chamber array measurements were taken medial and distal to the tumor. Measured doses were compared with calculated RayStation APB and MC calculated doses. RESULTS: Our lung phantom enabled measurements with the MatriXX PT at multiple depths in the phantom. Using the MC calculations, the 3%/3 mm gamma index pass rates, comparing measured with calculated doses, for the distal planes were 74.5% and 85.3% for the APB and 99.1% and 92% for the MC algorithms. The measured data revealed up to 46% and 30% underdosing within the distal regions of the target volume for the single and the two field plans when APB calculations are used. These discrepancies reduced to less than 18% and 7% respectively using the MC calculations. CONCLUSIONS: RaySearch Laboratories' Monte Carlo dose calculation algorithm is superior to the pencil-beam algorithm for lung targets. Clinicians relying on the analytical pencil-beam algorithm should be aware of its pitfalls for this site and verify dose prior to delivery. We conclude that the RayStation MC algorithm is reliable and more accurate than the APB algorithm for lung targets and therefore should be used to plan proton therapy for patients with lung cancer.

Validation of the RayStation Monte Carlo dose calculation algorithm using realistic animal tissue phantoms.

PURPOSE: The aim of this study is to validate the RayStation Monte Carlo (MC) dose algorithm using animal tissue neck phantoms and a water breast phantom. METHODS: Three anthropomorphic phantoms were used in a clinical setting to test the RayStation MC dose algorithm. We used two real animal necks that were cut to a workable shape while frozen and then thawed before being CT scanned. Secondly, we made a patient breast phantom using a breast prosthesis filled with water and placed on a flat surface. Dose distributions in the animal and breast phantoms were measured using the MatriXX PT device. RESULTS: The measured doses to the neck and breast phantoms compared exceptionally well with doses calculated by the analytical pencil beam (APB) and MC algorithms. The comparisons between APB and MC dose calculations and MatriXX PT measurements yielded an average depth difference for best gamma agreement of <1 mm for the neck phantoms. For the breast phantom better average gamma pass rates between measured and calculated dose distributions were observed for the MC than for the APB algorithms. CONCLUSIONS: The MC dose calculations are more accurate than the APB calculations for the static phantoms conditions we evaluated, especially in areas where significant inhomogeneous interfaces are traversed by the beam.

Clinical examination of proton pencil beam scanning on a moving anthropomorphic lung phantom.

The objective of this study was to examine the use of proton pencil beam scanning for the treatment of moving lung tumors. A single-field uniform dose proton pencil beam scanning (PBS) plan was generated for the standard thorax phantom designed by the Imaging and Radiation Oncology Core (IROC) Houston QA Center. Robust optimization, including range and setup uncertainties as well as volumetric repainting, was used for the plan. Patient-specific quality assurance (QA) measurements were performed using both a water tank and a custom heterogeneous QA phantom. A custom moving phantom was used to find the optimal number of volumetric repainting. Both analytical and Monte Carlo (MC) algorithms were used for dose calculation and their accuracies were compared with actual measurements. A single ionization chamber, a 2-dimensional ionization chamber array, thermoluminescent dosimeters (TLDs), and films were used for dose measurements. The optimal number of volumetric repainting was found to be 4 times in our system. The mean dose overestimations on a moving target by analytical and MC algorithms based on a time-averaged computed tomography (CT) image of the phantom were found to be 4.8% and 2.4%, respectively. The mean gamma indexes for analytical and MC algorithms were 91% and 96%, respectively. The MC dose algorithm calculation was found to have a better agreement with measurements compared with the analytical algorithm. When treating moving lung tumors using proton PBS, the techniques of robust optimization, volumetric repainting, and MC dose calculation were found effective. Extra care needs to be taken when an analytical dose calculation algorithm is used.

Dosimetric evaluation of a commercial proton spot scanning Monte-Carlo dose algorithm: comparisons against measurements and simulations.

RaySearch Americas Inc. (NY) has introduced a commercial Monte Carlo dose algorithm (RS-MC) for routine clinical use in proton spot scanning. In this report, we provide a validation of this algorithm against phantom measurements and simulations in the GATE software package. We also compared the performance of the RayStation analytical algorithm (RS-PBA) against the RS-MC algorithm. A beam model (G-MC) for a spot scanning gantry at our proton center was implemented in the GATE software package. The model was validated against measurements in a water phantom and was used for benchmarking the RS-MC. Validation of the RS-MC was performed in a water phantom by measuring depth doses and profiles for three spread-out Bragg peak (SOBP) beams with normal incidence, an SOBP with oblique incidence, and an SOBP with a range shifter and large air gap. The RS-MC was also validated against measurements and simulations in heterogeneous phantoms created by placing lung or bone slabs in a water phantom. Lateral dose profiles near the distal end of the beam were measured with a microDiamond detector and compared to the G-MC simulations, RS-MC and RS-PBA. Finally, the RS-MC and RS-PBA were validated against measured dose distributions in an Alderson-Rando (AR) phantom. Measurements were made using Gafchromic film in the AR phantom and compared to doses using the RS-PBA and RS-MC algorithms. For SOBP depth doses in a water phantom, all three algorithms matched the measurements to within ±3% at all points and a range within 1 mm. The RS-PBA algorithm showed up to a 10% difference in dose at the entrance for the beam with a range shifter and >30 cm air gap, while the RS-MC and G-MC were always within 3% of the measurement. For an oblique beam incident at 45°, the RS-PBA algorithm showed up to 6% local dose differences and broadening of distal fall-off by 5 mm. Both the RS-MC and G-MC accurately predicted the depth dose to within ±3% and distal fall-off to within 2 mm. In an anthropomorphic phantom, the gamma index (dose tolerance = 3%, distance-to-agreement = 3 mm) was greater than 90% for six out of seven planes using the RS-MC, and three out seven for the RS-PBA. The RS-MC algorithm demonstrated improved dosimetric accuracy over the RS-PBA in the presence of homogenous, heterogeneous and anthropomorphic phantoms. The computation performance of the RS-MC was similar to the RS-PBA algorithm. For complex disease sites like breast, head and neck, and lung cancer, the RS-MC algorithm will provide significantly more accurate treatment planning.

Complications after colonoscopy and surgery in a population-based colorectal cancer screening programme.

OBJECTIVES: To report complications after colonoscopy and surgery in patients with neoplasia detected through a population based colorectal cancer (CRC) screening programme in the capital region of Sweden. METHODS: Patients who after a positive FOBT screening result underwent colonoscopy from 1 January 2008 to 30 June 2012 were included. Mortality and complications within 30 days after colonoscopy or subsequent surgery were identified through national registers, and complications were assessed through review of medical charts. Complications were graded using the Clavien-Dindo classification. RESULTS: After 2984 colonoscopies, the complication rate was 1%. The risk of post-polypectomy bleeding was 14/1000. The risk of perforation was 1/1000 after a diagnostic colonoscopy and 2.5/1000 after a colonoscopy with polypectomy. One patient developed a post-polypectomy syndrome. There was one death which was not related to the colonoscopy. After surgery for 37 adenomas and 155 CRCs, the total complication rates were 27% and 50%, respectively. The rate of anastomotic leakage was 13% and 12% after surgery for adenomas and CRC, respectively. There were no deaths after surgery. The overall complication rate after colonoscopy and surgery for adenomas and cancer was 4%. CONCLUSIONS: Overall complication rates were acceptable and mortality low; however, the rate of anastomotic leakage after surgery for both adenomas and CRC was higher than expected.

Predicting lymph node metastases in early rectal cancer.

AIM: In this population-based study, the aim was to investigate risk factors for lymph node metastases and to construct a risk stratification index with relevance for pre-operative planning in T1 and T2 rectal cancers. METHODS: Data were retrieved from The Swedish Rectal Cancer Register, a mandatory, national, prospectively collected data base. All T1 and T2 rectal cancers treated with abdominal resection surgery without neo-adjuvant or adjuvant radio-chemotherapy from 2007 to 2010 were analysed. T-stage, sm-level, histologic differentiation, mucinous tumour type, blood vessel- and perineural infiltration, tumour location (in cm from the anal verge), age and gender were evaluated as potential predictors of lymph node metastases, using uni- and multivariate logistic regression. RESULTS: T2-stage (odds ratio [OR]=2.0), poor differentiation (OR=6.5) and vascular infiltration (OR=4.3) were identified as significant risk-factors for lymph node metastases in the multivariate analysis. The risk stratification index shows the risk for lymph node metastases gradually increasing from 6% to 65% and 11% to 78% in T1 and T2 cancers respectively, when adding the risk factors one by one. CONCLUSION: There is a considerable span in the risk for lymph node metastases between low risk T1 and high risk T2 rectal cancer. Using the risk stratification-model, with the concept of local excision as a macro-biopsy with standby for subsequent immediate radical resection surgery in high-risk cases, could benefit patients by providing the advantages of local excision yet ensuring adequate oncologic outcome.

Localized interaction of single porphyrin molecules with oxygen vacancies on TiO2(110).

Alterations in the electronic structure of adsorbed zinc(II) etioporphyrin I (ZnEtio) through interaction with bridging oxygen vacancies on TiO(2)(110) are studied by scanning tunneling microscopy and spectroscopy at cryogenic temperatures under ultrahigh vacuum (UHV) conditions. Upon lateral manipulation of ZnEtio molecules above surface oxygen vacancies, the highest occupied molecular orbital shifts away from the Fermi level. The magnitude of the shift rapidly decreases with increasing distance of the molecule from the vacancy, indicating a highly localized interaction.

Local insufflation of warm humidified CO2increases open wound and core temperature during open colon surgery: a randomized clinical trial.

BACKGROUND: The open surgical wound is exposed to cold and dry ambient air resulting in heat loss through radiation, evaporation, and convection. Also, general and neuraxial anesthesia decrease the patient's core temperature. Despite routine preventive measures mild intraoperative hypothermia is still common and contributes to postoperative morbidity and mortality. We hypothesized that local insufflation of warm fully humidified CO(2) would increase both the open surgical wound and core temperature. METHODS: Eighty-three patients undergoing open colon surgery were equally and parallelly randomized to either standard warming measures including forced-air warming, warm fluids, and insulation of limbs and head, or to additional local wound insufflation of warm (37°C) humidified (100% relative humidity) CO(2) at a laminar flow (10 L/min) via a gas diffuser. Wound surface and core temperatures were followed with a heat-sensitive infrared camera and a tympanic thermometer. RESULTS: The mean wound area temperature during surgery was 31.3°C in the warm humidified CO(2) group compared with 29.6°C in the control group (P < 0.001, 95% confidence interval [CI], 1.2°C to 2.3°C). Also, the mean wound edge temperature during surgery was 30.1°C compared with 28.5°C in the control group (P < 0.001, 95% CI, 0.2°C to 0.7°C). Mean core temperature before start of surgery was similar with 36.7°C ± 0.5°C in the warm humidified CO(2) group versus 36.6°C ± 0.5°C in the control group (95% CI, 0.4 to -0.1°C). At end of surgery, the 2 groups differed significantly with 36.9 ± 0.5°C in the warm humidified CO(2) group versus 36.3 ± 0.5°C in the control group (P < 0.001, 95% CI, 0.38°C to 0.82°C). Moreover, only 8 patients of 40 in the warm humidified CO(2) group had a core temperature <36.5°C (20%, 95% CI, 7 to 33%), whereas in the control group this was the case in 24 of 39 (62%, 95% CI, 46% to 78%, P = 0.001) patients (difference of the percentages between the groups 42%, 95% CI, 22% to 61%, P < 0.001). With a cutoff at <36.0°C none of the patients in the warm humidified CO(2) group compared with 7 patients (18%, 95% CI, 5% to 31%, P = 0.005) in the control group was hypothermic at end of surgery (difference of the percentages between the groups 18%, 95% CI, 6% to 30%, P = 0.005). The median (25th/75th percentile) operating time was 181.5 (147.5/288) minutes in the warm humidified CO(2) group versus 217 (149/288) minutes in the control group (P = 0.312). Clinical variables did not show any significant differences between the groups. CONCLUSIONS: Insufflation of warm fully humidified CO(2) in an open surgical wound cavity increases surgical wound and core temperatures and helps to maintain normothermia.

Intraoperative local insufflation of warmed humidified CO2 increases open wound and core temperatures: a randomized clinical trial.

BACKGROUND: The open surgical wound is exposed to cold dry ambient air, resulting in substantial heat loss through radiation, evaporation, and convection. At the same time, anesthesia decreases the patient's core temperature. Despite preventive measures, mild intraoperative hypothermia has been associated with postoperative morbidity. We hypothesized that local insufflation of warmed humidified carbon dioxide (CO(2)) would maintain wound and core temperature. METHODS: Eighty patients undergoing open colon surgery were randomized to standard warming measures, or to additional local wound insufflation of warmed (30 °C) humidified (93 % rH) CO(2) via a gas diffuser. Surface temperature of the open abdominal wound was measured with a heat-sensitive infrared camera, and core temperature was measured with an ear thermometer. RESULTS: Mean operative time was 219 ± 104 and 205 ± 85 min in the CO(2) group and the control group, respectively (p = 0.550). Clinical variables did not differ significantly between the groups. The median wound area and wound edge temperatures were 1.2 °C (p < 0.001) and 1.0 °C (p = 0.002) higher in the CO(2) group, respectively, than in the control group. The mean core temperature after intubation was the same (35.9 °C) in both groups, but at end of surgery core temperature in the two groups differed, with a mean of 36.2 ± 0.5 °C in the CO(2) group and a mean of 35.8 ± 0.5 °C in the control group (p = 0.003). CONCLUSIONS: Insufflation of warmed, humidified CO(2) in an open surgical wound cavity prevents intraoperative decrease in surgical wound temperature as well as core temperature.

Bowel obstruction after laparoscopic and open colon resection for cancer: results of 5 years of follow-up in a randomized trial.

BACKGROUND: Postoperative bowel obstruction caused by intra-abdominal adhesions occurs after all types of abdominal surgery. It has been suggested that the laparoscopic technique should reduce the risk for adhesion formation and thus for postoperative bowel obstruction. This study was designed to compare the incidence of bowel obstruction in a randomized trial where laparoscopic and open resection for colon cancer was compared. METHODS: A retrospective analysis was performed, collecting data of episodes of bowel obstruction with or without surgery. Only episodes treated in the hospital where the index surgery took place were included. Data for 786 patients were collected for the 5-year period after cancer surgery. RESULTS: Baseline characteristics for the evaluated laparoscopic (n = 383) and open (n = 403) groups were comparable. The cumulative obstruction percentages at 5 years for the open and laparoscopic groups were 6.5 and 5.1% respectively and did not significantly differ from each other. Tumor stage seemed to influence the risk for bowel obstruction: 2.8% in stage I, 6.6% in stage II, and 7% in stage III, but the differences were not significant. CONCLUSIONS: This analysis does not support the hypothesis that laparoscopy leads to fewer episodes of bowel obstruction compared with open surgery.

Common variants in human CRC genes as low-risk alleles.

The genetic susceptibility to colorectal cancer (CRC) has been estimated to be around 35% and yet high-penetrance germline mutations found so far explain less than 5% of all cases. Much of the remaining variations could be due to the co-inheritance of multiple low penetrant variants. The identification of all the susceptibility alleles could have public health relevance in the near future. To test the hypothesis that what are considered polymorphisms in human CRC genes could constitute low-risk alleles, we selected eight common SNPs for a pilot association study in 1785 cases and 1722 controls. One SNP, rs3219489:G>C (MUTYH Q324H) seemed to confer an increased risk of rectal cancer in homozygous status (OR=1.52; CI=1.06-2.17). When the analysis was restricted to our 'super-controls', healthy individuals with no family history for cancer, also rs1799977:A>G (MLH1 I219V) was associated with an increased risk in both colon and rectum patients with an odds ratio of 1.28 (CI=1.02-1.60) and 1.34 (CI=1.05-1.72), respectively (under the dominant model); while 2 SNPs, rs1800932:A>G (MSH6 P92P) and rs459552:T>A (APC D1822V) seemed to confer a protective effect. The latter, in particular showed an odds ratio of 0.76 (CI=0.60-0.97) among colon patients and 0.73 (CI=0.56-0.95) among rectal patients. In conclusion, our study suggests that common variants in human CRC genes could constitute low-risk alleles.

PepT1 oligopeptide transporter (SLC15A1) gene polymorphism in inflammatory bowel disease.

BACKGROUND: Human polymorphisms affecting gut epithelial barrier and interactions with bacteria predispose to the inflammatory bowel diseases (IBD) Crohn's disease (CD) and ulcerative colitis (UC). The intestinal transporter PepT1, encoded by the SLC15A1 gene, mediates intracellular uptake of bacterial products that can induce inflammation and NF-kappaB activation upon binding to NOD2, a protein often mutated in CD. Hence, we tested SLC15A1 polymorphisms for association with IBD. METHODS: Twelve SLC15A1 single nucleotide polymorphisms (SNPs) were genotyped in 1783 individuals from 2 cohorts of Swedish and Finnish IBD patients and controls. An in vitro system was set up to evaluate the potential impact of SLC15A1 polymorphism on PepT1 transporter function by quantification of NOD2-mediated activation of NF-kappaB. RESULTS: The common allele (C) of a coding polymorphism (rs2297322, Ser117Asn) was associated with CD susceptibility both in Sweden and in Finland, but with genetic effects in opposite directions (risk and protection, respectively). The best evidence of association was found in both populations when the analysis was performed on individuals not carrying NOD2 common risk alleles (Sweden allelic P = 0.0007, OR 1.97, 95% confidence interval [CI] 1.34-2.92; Finland genotype P = 0.0013, OR 0.63, 95% CI 0.44-0.90). The PepT1 variant encoded by the C allele (PepT1-Ser117) was associated with reduced signaling downstream of NOD2 (P < 0.0001 compared to Pept1-Asn117). CONCLUSIONS: A functional polymorphism in the SLC15A1 gene might be of relevance to inflammation and antibacterial responses in IBD. Whether this polymorphism truly contributes to disease susceptibility needs to be further addressed, and should stimulate additional studies in other populations.