Requirements for dose calculation on an active scanned proton beamline for small, shallow fields.

INTRODUCTION: A growing interest in using proton pencil beam scanning in combination with collimators for the treatment of small, shallow targets, such as ocular melanoma or pre-clinical research emerged recently. This study aims at demonstrating that the dose of a synchrotron-based PBS system with a dedicated small, shallow field nozzle can be accurately predicted by a commercial treatment planning system (TPS) following appropriate tuning of both, nozzle and TPS. MATERIALS: A removable extension to the clinical nozzle was developed to modify the beam shape passively. Five circular apertures with diameters between 5 to 34mm, mounted 72cm downstream of a range shifter were used. For each collimator treatment plans with spread-out Bragg peaks (SOBP) with a modulation of 3 to 30mm were measured and calculated with GATE/Geant4 and the research TPS RayStation (RS11B-R). The dose grid, multiple coulomb scattering and block discretization resolution were varied to find the optimal balance between accuracy and performance. RESULTS: For SOBPs deeper than 10mm, the dose in the target agreed within 1% between RS11B-R, GATE/Geant4 and measurements for aperture diameters between 8 to 34mm, but deviated up to 5% for smaller apertures. A plastic taper was introduced reducing scatter contributions to the patient (from the pipe) and improving the dose calculation accuracy of the TPS to a 5% level in the entrance region for large apertures. CONCLUSION: The commercial TPS and GATE/Geant4 can accurately calculate the dose for shallow, small proton fields using a collimator and pencil beam scanning.

Presiones de la vía biliar en pacientes con y sin colelitiasis

Introducción: El reflujo de enzimas pancreáticas hacia la vía biliar extra-hepática y la vesícula biliar es un fenómeno anormal que tiene un rol en la litogénesis y carcinogénesis. Debido a que la presión de la vía biliar depende entre otros factores, de las presiones del esfínter de Oddi. La disfunción de éste se vería reflejada en presiones elevadas de la vía biliar en pacientes con colelitiasis. Objetivo: El objetivo de este estudio es el de medir las presiones de la vía biliar extra-hepática en pacientes con y sin colelitiasis y relacionarlas con la presencia de reflujo pancreáticobiliar. Material y Método: Se diseñó un estudio pros-pectivo de casos y controles. La muestra está constituida por todos los pacientes operados con gastrectomía total por cáncer gástrico estadios I y II durante 30 meses. La medida de resultado primaria fue establecer diferencias en las presiones de la vía biliar entre pacientes con y sin colelitiasis. Resultados: Las presiones de la vía biliar extra-hepática en pacientes con colelitiasis fueron más elevadas (16,9 mmHg) que en los pacientes sin colelitiasis (3,3 mmHg) (p < 0,0001). Estas presiones se correlacionan con la presencia de amilasa y lipasa en la bilis de la vesícula; se encontraron niveles elevados de enzimas pancreáticas en pacientes con colelitiasis (p < 0,0001). Conclusiones: Las presiones de la vía biliar en pacientes con colelitiasis fueron, significativamente, mayores comparadas con las presiones de la vía biliar en pacientes sin colelitiasis. En los pacientes con colelitiasis, la presión elevada de la vía biliar se asocia a la presencia de reflujo pancreáticobiliar.

Background: The reflux of pancreatic enzymes into the bile duct and the gallbladder is an abnormal phenomenon that plays a role in lithogenesis and carcinogenesis. Because the pressure of the common bile duct depends on the pressures of the sphincter of Oddi, its dysfunction would be reflected in an increase in the pressure of the common bile duct in patients with cholelithiasis. Aim: The objective of this study was to measure the pressures of the common bile duct in patients with and without cholelithiasis and to relate them to the presence of pancreatobiliary reflux. Material and Method: A prospective case-control study was designed. The universe was constituted by all patients undergoing total gastrectomy for gastric cancer stages I and II during 30 months. The primary outcome measure was to establish differences between common bile duct pressures in patients with and without cholelithiasis. Results: Common bile duct pressures in patients with gallstones showed a significant elevation (16.9 mmHg) compared to patients without gallstones (3.3 mm Hg) (p < 0.0001). These pressures correlated with the levels of amylase and lipase in gallbladder bile; higher levels were found in patients with gallstones compared to patients without gallstones (p < 0.0001). Conclusions: Common bile duct pressure in patients with cholelithiasis was significantly higher compared to patients without cholelithiasis leading to pancreatobiliary reflux.

Scalable radiotherapy data curation infrastructure for deep-learning based autosegmentation of organs-at-risk: A case study in head and neck cancer.

In this era of patient-centered, outcomes-driven and adaptive radiotherapy, deep learning is now being successfully applied to tackle imaging-related workflow bottlenecks such as autosegmentation and dose planning. These applications typically require supervised learning approaches enabled by relatively large, curated radiotherapy datasets which are highly reflective of the contemporary standard of care. However, little has been previously published describing technical infrastructure, recommendations, methods or standards for radiotherapy dataset curation in a holistic fashion. Our radiation oncology department has recently embarked on a large-scale project in partnership with an external partner to develop deep-learning-based tools to assist with our radiotherapy workflow, beginning with autosegmentation of organs-at-risk. This project will require thousands of carefully curated radiotherapy datasets comprising all body sites we routinely treat with radiotherapy. Given such a large project scope, we have approached the need for dataset curation rigorously, with an aim towards building infrastructure that is compatible with efficiency, automation and scalability. Focusing on our first use-case pertaining to head and neck cancer, we describe our developed infrastructure and novel methods applied to radiotherapy dataset curation, inclusive of personnel and workflow organization, dataset selection, expert organ-at-risk segmentation, quality assurance, patient de-identification, data archival and transfer. Over the course of approximately 13 months, our expert multidisciplinary team generated 490 curated head and neck radiotherapy datasets. This task required approximately 6000 human-expert hours in total (not including planning and infrastructure development time). This infrastructure continues to evolve and will support ongoing and future project efforts.

The dose magnifying glass quality assurance system for daily proton therapy range verification.

Proton therapy has a distinct dosimetric advantage over conventional photon therapy due to its Bragg peak profile. This allows greater accuracy in dose delivery and dose conformation to the target, however it requires greater precision in setup, delivery and for quality assurance (QA) procedures. The AAPM TG 224 report recommends daily range and spot position checks with tolerance on the order of a millimetre. Daily QA systems must therefore be efficient for daily use and be capable of sub-millimetre precision however few suitable commercial systems are available. In this work, a compact, real-time daily QA system is optimised and characterised for proton range verification using an ad-hoc Geant4 simulation. The system is comprised of a monolithic silicon diode array detector embedded in a perspex phantom. The detector is orientated at an angular offset to the incident proton beam to allow range in perspex to be determined for flat proton fields. The accuracy of the system for proton range in perspex measurements was experimentally evaluated over the full range of clinical proton energies. The meanR100,R90andR80ranges measured with the system were accurate within ±0.6 mm of simulated ranges in a perspex phantom for all energies assessed. This system allows real-time read-out of individual detector channels also making it appropriate for temporal beam delivery diagnostics and for spot position monitoring along one axis. The system presented provides a suitable, economical and efficient alternative for daily QA in proton therapy.

Hernia incisional en laparotomía de McBurney: complicaciones de una hernia inusual / Incisional hernia after McBurney incision: complications of an unusual hernia

Resumen Introducción Actualmente, la mayoría de las series que hablan sobre hernia incisional, no mencionan hernias incisionales en laparotomías de McBurney. La incidencia reportada de hernia incisional en esta laparotomía varía entre 0,7% y 2%. Aún más escasas son las publicaciones sobre sus complicaciones. El objetivo del presente reporte de casos es el de discutir el diagnóstico, tratamiento y resultados de dos pacientes operados en nuestra institución por hernia de McBurney complicada. Reporte de Casos: Se describen 2 pacientes femeninos de 68 y 65 años de edad que fueron operadas de urgencia por hernia incisional en laparotomía de McBurney complicada. La evolución postoperatoria fue diferente en ambas y una de ellas falleció. Discusión Se discuten los factores de riesgo para el desarrollo de estas hernias, el diagnóstico y tratamiento. Además, se discute la importancia de la apendicectomía laparoscópica para la prevención de estas hernias. Conclusiones Las complicaciones de la hernia en laparotomía de McBurney, las cuales son severas y potencialmente letales, se diagnostican tardíamente debido al retraso en la presentación y en el diagnóstico. La amplia utilización de la cirugía laparoscópica para la apendicectomía seguramente reducirá aún más la incidencia de este tipo de hernia durante los próximos años.

Introduction Currently, most series over incisional hernia do not mention this hernia occurring in McBurney's laparotomy. The reported incidence for this type of hernia is 0.7% to 2%. Even more scarce are publications regarding its complications. The purpose of this report is to discuss the diagnostic, treatment and outcomes of two patients operated on our institution for complicated McBurney´s hernia. Report of Cases: Two female patients 68 and 65 years-old operated on emergency grounds for complicated incisional hernia over a McBurney´s incision are described. Postoperative evolution was different in both cases and one of them died. Discussion We discuss risk factor for this specific incisional hernia development, its diagnosis and treatment. Besides, the importance of laparoscopic appendectomy was stressed. Conclusions Complicated incisional hernia over McBurney's incision is an infrequent severe clinical condition habitually diagnosed late. The widespread utilization of laparoscopic appendectomy will reduce even more the incidence of this kind of hernia within the next few years.

A Pareto-based beam orientation optimization method for spot scanning intensity-modulated proton therapy.

PURPOSE: To provide a proof of principle of a Pareto-based method to automatically generate optimal intensity-modulated proton therapy (IMPT) plans for various noncoplanar beam orientations. METHODS: A novel multicriteria beam orientation optimization (MCBOO) method was developed to generate Pareto database of optimal plans. The MCBOO method automatically explores the beam orientations and the scalarization parameters of the IMPT plans simultaneously. The MCBOO method is based on multicriteria bilevel optimization (i.e., hierarchical optimization with two nested levels, named the upper and lower level optimization). In MCBOO, the upper level optimization explores the noncoplanar beam orientation space, while the lower level explores the scalarization parameters for a given beam orientation. Differential evolution method was used in both levels, and the Pareto optimal plans were aggregated from the bilevel optimizations to construct the Pareto database. The MCBOO method was implemented on a multinode multi-GPU cluster, and it was tested on three brain tumor patient cases. The Pareto database of the three patients was generated for a set of DVH-based objectives. A statistical analysis was performed between a selected set of MCBOO plans and the manual plan (plan with manually selected beam orientation based on the clinical experience and optimized with the same single plan iterative optimizer used in the MCBOO). The selected set of MCBOO plans consisted of plans that matched the performance of the manual plan [i.e., MCBOO plans that have the same target coverage (within 2%) as the manual plan or better and achieved the same dose (within 2%) or lower to all of the organs at risks (OARs) but one OAR]. Additionally, a dosimetric comparison between of one of the selected MCBOO plans vs the manual plan was conducted. RESULTS: The multicriteria beam orientation optimization algorithm automatically generated Pareto plans for the three noncoplanar brain tumor cases. The MCBOO plans provided an alternative objective trade-offs to the manual plan. The selected MCBOO plans showed a reduction in dose to multiple organs at risk vs the manual plan with a maximum value which ranged between 10.8 and 12.9 Gy for the three patients. The trade-off of the OAR dose reduction resulted in higher dose to no more than one OAR for each of the selected MCBOO plans vs the manual plan. The maximum dose increase in the MCBOO plans over the manual plan ranged from 7.8 to 11.8 Gy. CONCLUSIONS: A novel multicriteria beam orientation optimization method was developed and tested on three IMPT patient cases. The method automatically generates Pareto plans database by exploring the noncoplanar beam orientations. The method was able to identify beam orientations with Pareto optimal plans that are comparable to the manually created plans with varying objective trade-offs.

Perforación traumática aislada de la vesícula biliar: revisión de la literatura actual con reporte de un caso / Isolated gallbladder perforation following blunt abdominal trauma: literature review and case report

Resumen Introducción La lesión de la vesícula biliar secundaria a trauma abdominal cerrado constituye un evento infrecuente de perforación traumática de ella, de presentación tardía. Objetivo Revisar la literatura científica actualmente disponible y además describimos un caso. Materiales y Método Utilizando la plataforma PubMed se buscan las siguientes palabras clave: " Blunt abdominal trauma ". Se seleccionan las series con lesiones de la vesícula biliar: " Traumatic gallbladder rupture". Se seleccionan los reportes de lesiones aisladas de la vesícula biliar: " Isolated gallbladder rupture ". Se seleccionan los reportes de presentación tardía de lesiones aisladas de la vesícula biliar: " Delayed presentation of isolated gallbladder rupture ". Resultados De todas estas publicaciones se seleccionan las que a criterio de los autores son relevantes para el presente caso. Discusión La mayoría de las perforaciones de la vesícula biliar se producen en vesículas sanas de paredes delgadas distendidas por el ayuno o el consumo de alcohol. No existe una presentación clínica clásica. Los estudios imagenológicos son inespecíficos y se llega al diagnóstico definitivo durante la exploración quirúrgica. El tratamiento de esta lesión es la colecistectomía. Conclusiones El diagnóstico no es fácil, pero la resolución es relativamente simple y el pronóstico es bueno. El presente caso ilustra este tipo de lesiones en pacientes con trauma abdominal cerrado.

Introduction Gallbladder injury secondary to blunt abdominal trauma is a rare event. Aim Review the current available scientific literature and describe a case. Materials and Method Using the PubMed platform, the following keywords were searched: "Blunt abdominal trauma". Series with gallbladder lesions were selected: "Traumatic gallbladder rupture". Reports of isolated lesions of the gallbladder were selected: "Isolated gallbladder rupture". Reports of late presentation of isolated lesions of the gallbladder were selected: "Delayed presentation of isolated gallbladder rupture". Of all these publications, those that were relevant to the present case were selected according to the criteria of the authors. Case report A 20 years-old male patient suffered an abdominal trauma two weeks before presentation at our Institution. He underwent an exploratory laparotomy showing bilious content and a gallbladder perforation over the peritoneal wall as an isolated injury. Discussion Most isolated gallbladder perforations occur in healthy gallbladders with thin walls and distended because fasting or alcohol consumption. There are no classical clinical features to diagnose this specific injury and radiologic studies are nonspecific. Definitive diagnosis is often reached during surgery as it was with our patient. Recommended treatment is cholecystectomy. Conclusions This case illustrates this unique kind of gallbladder injury in patients with blunt abdominal trauma. A clear diagnosis is not easy however, the treatment is simple and prognosis is good.

B subset cells in patients with chronic granulomatous disease in a Mexican population.

INTRODUCTION: Chronic granulomatous disease (CGD) is a disorder of phagocyte function, characterized by pyogenic infections and granuloma formation caused by defects in NADPH oxidase complex activity. Although the effect of CGD mainly reflects the phagocytic compartment, B cell responses are also impaired in patients with CGD. MATERIALS AND METHODS: Flow cytometric analysis was performed on peripheral blood samples from 35 CGD patients age-matched with healthy controls (HC). The target cells of our study were the naive (IgD+/CD27-), memory (IgD-/CD27+), and B1a (CD5+) cells. Immunoglobulins (Igs) were also measured. This study was performed in a Latin American cohort. RESULTS: We found significantly higher levels of naive B cells and B1a cells, but lower levels of memory B cells were found in CGD patients compared to HC. There was no significant difference of cell percentages per inheritance type. DISCUSSION: Our findings suggest that the deficiency of NADPH oxidase components can affect the differentiation of naive B cells to memory B cells. Consequently, memory cells will be low, which also influenced the expression of CD27 in memory B cells and as a result, the percentage of naive cells increases. An altered phenotype of B lymphocytes in CGD patients may contribute to the opportunistic infections and autoimmune disorders that are seen in this disease.

Highly efficient and sensitive patient-specific quality assurance for spot-scanned proton therapy.

The purpose of this work was to develop an end-to-end patient-specific quality assurance (QA) technique for spot-scanned proton therapy that is more sensitive and efficient than traditional approaches. The patient-specific methodology relies on independently verifying the accuracy of the delivered proton fluence and the dose calculation in the heterogeneous patient volume. A Monte Carlo dose calculation engine, which was developed in-house, recalculates a planned dose distribution on the patient CT data set to verify the dose distribution represented by the treatment planning system. The plan is then delivered in a pre-treatment setting and logs of spot position and dose monitors, which are integrated into the treatment nozzle, are recorded. A computational routine compares the delivery log to the DICOM spot map used by the Monte Carlo calculation to ensure that the delivered parameters at the machine match the calculated plan. Measurements of dose planes using independent detector arrays, which historically are the standard approach to patient-specific QA, are not performed for every patient. The nozzle-integrated detectors are rigorously validated using independent detectors in regular QA intervals. The measured data are compared to the expected delivery patterns. The dose monitor reading deviations are reported in a histogram, while the spot position discrepancies are plotted vs. spot number to facilitate independent analysis of both random and systematic deviations. Action thresholds are linked to accuracy of the commissioned delivery system. Even when plan delivery is acceptable, the Monte Carlo second check system has identified dose calculation issues which would not have been illuminated using traditional, phantom-based measurement techniques. The efficiency and sensitivity of our patient-specific QA program has been improved by implementing a procedure which independently verifies patient dose calculation accuracy and plan delivery fidelity. Such an approach to QA requires holistic integration and maintenance of patient-specific and patient-independent QA.

Adaptive method for multicriteria optimization of intensity-modulated proton therapy.

PURPOSE: Provide an adaptive multicriteria optimization (MCO) method for intensity-modulated proton therapy (IMPT) utilizing GPU technology. Previously described limitations of MCO such as Pareto approximation and limitation on the number of objectives were addressed. METHODS: The treatment planning process for IMPT must account for multiple objectives, which requires extensive treatment planning resources. Often a large number of objectives (>10) are required. Hence the need for an MCO algorithm that can handle large number of objectives. The novelty of the MCO method presented here lies on the introduction of the adaptive weighting scheme that can generate a well-distributed and dense representation of the Pareto surface for a large number of objectives in an efficient manner. In our approach the generated Pareto surface is constructed for a set of DVH objectives. The MCO algorithm is based on the augmented weighted Chebychev metric (AWCM) method with an adaptive weighting scheme. This scheme uses the differential evolution (DE) method to generate a set of well-distributed Pareto points. The quality of the Pareto points' distribution in the objective space was assessed quantitatively using the Pareto sampling metric. The MCO algorithm was developed to perform multiple parallel searches to achieve a rapid mapping of the Pareto surface, produce clinically deliverable plans, and was implemented on a GPU cluster. The MCO algorithm was tested on two clinical cases with 10 and 18 objectives. For each case one of the MCO-generated plans was selected for comparison with the clinically generated plan. The MCO plan was randomly selected out of the set of MCO plans that had target coverage similar to the clinically generated plan and the same or better sparing of the organs at risk (OAR). Additionally, a validation study of the AWCM method vs the weighted sum method was performed. RESULTS: The adaptive MCO algorithm generated Pareto points on the Pareto hypersurface in a fast (2-3 hr) and efficient manner for 2 cases with 10 and 18 objectives. The MCO algorithm generated a dense and well-distributed set of Pareto points on the objective space, and was able to achieve minimization of the Pareto sampling metric. The selected MCO plan showed an improvement of the DVH objectives in comparison to the clinically optimized plan in both cases. For case one, the MCO plan showed a 48% reduction of the 50% dose to OARs and a 16% reduction of the 1% dose to OARs. For case 2, the MCO plan showed a 72% reduction of the 50% dose to OARs and a 42% reduction of the 1% dose to OARs. The comparison of AWCM to WS showed that the AWCM method has a dosimetric advantage over WS for both patient cases. CONCLUSION: We introduced an adaptive MCO algorithm for IMPT accelerated using GPUs. The algorithm is based on an adaptive method for generating Pareto plans in the objective space. We have shown that the algorithm can provide rapid and efficient mapping of the multicriteria Pareto surface with clinically deliverable plans.

MICRODOSIMETRIC APPLICATIONS IN PROTON AND HEAVY ION THERAPY USING SILICON MICRODOSIMETERS.

Using the CMRP 'bridge' µ+ probe, microdosimetric measurements were undertaken out-of-field using a therapeutic scanning proton pencil beam and in-field using a 12C ion therapy field. These measurements were undertaken at Mayo Clinic, Rochester, USA and at HIMAC, Chiba, Japan, respectively. For a typical proton field used in the treatment of deep-seated tumors, we observed dose-equivalent values ranging from 0.62 to 0.99 mSv/Gy at locations downstream of the distal edge. Lateral measurements at depths close to the entrance and along the SOBP plateau were found to reach maximum values of 3.1 mSv/Gy and 5.3 mSv/Gy at 10 mm from the field edge, respectively, and decreased to ~0.04 mSv/Gy 120 mm from the field edge. The ability to measure the dose-equivalent with high spatial resolution is particularly relevant to healthy tissue dose calculations in hadron therapy treatments. We have also shown qualitatively and quantitively the effects critical organ motion would have in treatment using microdosimetric spectra. Large differences in spectra and RBE10 were observed for treatments where miscalculations of 12C ion range would result in critical structures being irradiated, showing the importance of motion management.

Cumplimiento de analgesia peridural solicitada versus administrada en partos vaginales, durante el periodo 2014-2016 en el Hospital Hernán Henriquez Aravena / Compliance with epidural analgesia requested versus administered in vaginal deliveries, during the period 2014-2016 at the Hospital Hernán Henriquez Aravena

INTRODUCCIÓN: El dolor que se asocia al trabajo de parto (TDP) afecta a todas las mujeres y puede producir alteraciones tanto maternas como fetales, e incluso interferir con el desarrollo normal del proceso. OBJETIVO: Conocer el grado de cumplimiento de solicitud de analgesia peridural en partos vaginales en el servicio de preparto del Hospital Hernán Henríquez Aravena (HHHA) versus la analgesia administrada. MATERIAL Y MÉTODO: Estudio descriptivo retrospectivo, realizado en base a datos del sistema perinatal del servicio de Ginecología y Obstetricia del HHHA, periodo 2014-2016. RESULTADOS: Del total de partos Vaginales entre los años 2014-2016 solo se solicitó Analgesia Peridural en 56.5% de ellos. De las analgesias solicitadas en éste período se administraron un 98%. CONCLUSIÓN: Basado en los registros clínicos, el grado de cumplimiento es cercano al 100% en las analgesias solicitadas. Se observó un incremento anual entre 2014 y 2016 de solicitud de anestesia en procedimientos de parto, y a pesar de esto la eficiencia del hospital no se ha visto afectada. No obstante, se espera que el porcentaje de solicitudes siga en aumento manteniendo el alto nivel de eficiencia. Es pertinente plantear la realización de estudios para extrapolar este resultado a nivel regional y nacional.

INTRODUCTION: Pain associated with labor affects all women and can cause both maternal and fetal alterations and even interfere with the normal development of the process. Objective: to know the degree of compliance with the request for epidural analgesia in vaginal deliveries versus the analgesia administered at the Hernán Henríquez Aravena Hospital (HHHA). Method: Retrospective descriptive study, based on data from the perinatal system of the HHHA Gynecology and Obstetrics Service, period 2014-2016. Results: Of the total number of Vaginal births between 2014-2016 only 56.5% of them were requested for epidural analgesia. Of the analgesia requested in this period, 98% were administered. Conclusion: Based on the clinical records, the degree of compliance is close to 100% in the requested analgesia. There was an annual increase between 2014 and 2016 in the application of anesthesia in childbirth procedures, and despite this, hospital efficiency has not been affected. However, the percentage of applications is expected to continue to increase while maintaining the high level of efficiency. It is pertinent to propose studies to extrapolate this result at regional and national levels.

Sarcoidosis peritoneal: a propósito de un caso / Peritoneal sarcoidosis: about a case

La sarcoidosis es una enfermedad inflamatoria multisistémica, caracterizada por granulomas no caseificados, de etiología desconocida. Dentro de esta, el compromiso seroso es muy infrecuente. Entre los diagnósticos diferenciales a considerar se encuentran patologías neoplásicas, infecciosas e inflamatorias. El tratamiento de la sarcoidosis peritoneal depende del grado, actividad y extensión de la enfermedad. Se presenta el caso de una paciente de 45 años, que consulta por dolor pélvico y aumento de perímetro abdominal de tres meses de evolución.

Sarcoidosis is a multisystemic inflammatory disease characterized by calcified granulomas of unknown etiology. Within this, the serous commitment is rare. Among the differential diagnoses are considered neoplastic, infectious and inflammatory diseases. Treatment of peritoneal sarcoidosis depends on the degree, activity and extent of the disease. We present the case of a 45 years old patient who consulted for pelvic pain and increased abdominal girth of three months of evolution.

A fast GPU-based Monte Carlo simulation of proton transport with detailed modeling of nonelastic interactions.

PURPOSE: Very fast Monte Carlo (MC) simulations of proton transport have been implemented recently on graphics processing units (GPUs). However, these MCs usually use simplified models for nonelastic proton-nucleus interactions. Our primary goal is to build a GPU-based proton transport MC with detailed modeling of elastic and nonelastic proton-nucleus collisions. METHODS: Using the cuda framework, the authors implemented GPU kernels for the following tasks: (1) simulation of beam spots from our possible scanning nozzle configurations, (2) proton propagation through CT geometry, taking into account nuclear elastic scattering, multiple scattering, and energy loss straggling, (3) modeling of the intranuclear cascade stage of nonelastic interactions when they occur, (4) simulation of nuclear evaporation, and (5) statistical error estimates on the dose. To validate our MC, the authors performed (1) secondary particle yield calculations in proton collisions with therapeutically relevant nuclei, (2) dose calculations in homogeneous phantoms, (3) recalculations of complex head and neck treatment plans from a commercially available treatment planning system, and compared with (GEANT)4.9.6p2/TOPAS. RESULTS: Yields, energy, and angular distributions of secondaries from nonelastic collisions on various nuclei are in good agreement with the (GEANT)4.9.6p2 Bertini and Binary cascade models. The 3D-gamma pass rate at 2%-2 mm for treatment plan simulations is typically 98%. The net computational time on a NVIDIA GTX680 card, including all CPU-GPU data transfers, is ∼ 20 s for 1 × 10(7) proton histories. CONCLUSIONS: Our GPU-based MC is the first of its kind to include a detailed nuclear model to handle nonelastic interactions of protons with any nucleus. Dosimetric calculations are in very good agreement with (GEANT)4.9.6p2/TOPAS. Our MC is being integrated into a framework to perform fast routine clinical QA of pencil-beam based treatment plans, and is being used as the dose calculation engine in a clinically applicable MC-based IMPT treatment planning system. The detailed nuclear modeling will allow us to perform very fast linear energy transfer and neutron dose estimates on the GPU.

Stereotactic ablative radiotherapy delivered by image-guided helical tomotherapy for extracranial oligometastases.

PURPOSE: To investigate the outcomes and risk factors of patients treated with stereotactic ablative radiotherapy (SABR) delivered by image-guided helical tomotherapy (HT) for extracranial oligometastases. METHODS: From August 2006 through July 2011, 42 consecutive patients (median age 69 years [range 16-87]) with oligometastases (≤3) received HT to all known cancer sites (lung, n = 28; liver, n = 12; adrenal, n = 2). Prognostic factors were assessed by Cox's proportional hazards regression analysis. RESULTS: A total of 60 lesions were treated with hypofractionated HT (median dose 39 Gy [range 36-72.5]; median dose per fraction 12 Gy [range 5-20]). Complete or partial response was observed in 40 (54 %) patients. With a median follow-up period of 15 months, 1- and 2-year overall survival (OS) was 84 and 63 %, respectively; and 1- and 2-year local control (LC) was 92 and 86 %, respectively. Four patients had pneumonitis Grade ≥2 and two patients had lower gastrointestinal toxicity Grade ≥2. Only the lack of complete/partial response was associated with higher risk of mortality on univariate (HR = 3.8, P = 0.04) and multivariate (HR = 6.6, P = 0.01) analyses. CONCLUSIONS: SABR delivered by image-guided HT is well tolerated and offers adequate LC with low acute morbidity in patients with extracranial oligometastatic disease. We found that the response to HT was the only predictor for OS.

Linac stereotactic radiosurgery for the treatment of small arteriovenous malformations: lower doses can be equally effective.

OBJECTIVE: The purpose of this study was to examine the efficacy and toxicity of treating small arteriovenous malformations (AVMs) (≤3 cm in diameter) with a median marginal applied dose of 14 Gy. METHODS: Two hundred and thirteen patients diagnosed with AVMs were treated between January 1991 and December 2005. Seventy-three percent of the patients had hemorrhaged prior to treatment, 13% had had previous surgery and 19.2% had had previous embolization. The median follow-up duration was 48.1 months. RESULTS: The Kaplan-Meier analysis estimated that the 36-month obliteration rate was 65.5% for patients undergoing their first stereotactic radiosurgery (SRS) and 68.3% for those undergoing repeated SRS. The Kaplan-Meier analysis estimated the 60-month AVMs obliteration rate for the entire cohort to be 82.4%. The median time to AVM obliteration was 40 ± 2.8 months. We found a statistically significant relationship between the time of obliteration and the following factors: site of the AVMs (sites other than brainstem), a higher prescribed dose and a positive history of previous hemorrhage. Thirteen patients (7.6%) experienced toxicities. CONCLUSIONS: SRS was an effective and safe treatment for AVMs ≤3 cm in diameter, with acceptable toxicity.

Mitochondrial inhibitors activate influx of external Ca(2+) in sea urchin sperm.

Sea urchin sperm have a single mitochondrion which, aside from its main ATP generating function, may regulate motility, intracellular Ca(2+) concentration ([Ca(2+)](i)) and possibly the acrosome reaction (AR). We have found that acute application of agents that inhibit mitochondrial function via differing mechanisms (CCCP, a proton gradient uncoupler, antimycin, a respiratory chain inhibitor, oligomycin, a mitochondrial ATPase inhibitor and CGP37157, a Na(+)/Ca(2+) exchange inhibitor) increases [Ca(2+)](i) with at least two differing profiles. These increases depend on the presence of extracellular Ca(2+), which indicates they involve Ca(2+) uptake and not only mitochondrial Ca(2+) release. The plasma membrane permeation pathways activated by the mitochondrial inhibitors are permeable to Mn(2+). Store-operated Ca(2+) channel (SOC) blockers (Ni(2+), SKF96365 and Gd(2+)) and internal-store ATPase inhibitors (thapsigargin and bisphenol) antagonize Ca(2+) influx induced by the mitochondrial inhibitors. The results indicate that the functional status of the sea urchin sperm mitochondrion regulates Ca(2+) entry through SOCs. As neither CCCP nor dicycloexyl carbodiimide (DCCD), another mitochondrial ATPase inhibitor, eliminate the oligomycin induced increase in [Ca(2+)](i), apparently oligomycin also has an extra mitochondrial target.

[Pigmented Paget's disease of the breast]. / Maladie de Paget mammaire pigmentée.

INTRODUCTION: Pigmented Paget's disease of the breast is an uncommon disease. Histology shows intraepidermal pagetoid cells positive for cytokeratin7. We report a difficult case with an atypical clinic presentation as a pigmented lesion and unusual immunohistochemical results such as absence of expression of cytokeratin7 (CK7). OBSERVATION: A 68-year-old woman presented a heterogeneous pigmented lesion on the left nipple extending to the areola, over a period of six years. Histologic study of biopsy showed intraepidermal proliferation of atypical cells positive for melanocytic markers but negative for CK7. The clinicopathological features were consistent with malignant lentigo. Nevertheless, histological study of the whole lesion after complete surgical excision was in favour of mammary Paget's disease, while CK7 remained negative. DISCUSSION: Pigmented Paget's disease of the breast is infrequent, with only a few cases reported in the literature and is suggestive of malignant melanoma or pigmented metastasis of mammary adenocarcinoma. Immunohistochemistry is necessary, especially using CK7 staining, which is usually positive (sensitivity of almost 100%), except in some rare cases such as ours. In these difficult cases, study of a wider panel of antibodies may be necessary for diagnosis.