Improved biomechanical metrics of cerebral vasospasm identified via sensitivity analysis of a 1D cerebral circulation model.

Cerebral vasospasm (CVS) is a life-threatening condition that occurs in a large proportion of those affected by subarachnoid haemorrhage and stroke. CVS manifests itself as the progressive narrowing of intracranial arteries. It is usually diagnosed using Doppler ultrasound, which quantifies blood velocity changes in the affected vessels, but has low sensitivity when CVS affects the peripheral vasculature. The aim of this study was to identify alternative biomarkers that could be used to diagnose CVS. We used a 1D modelling approach to describe the properties of pulse waves that propagate through the cardiovascular system, which allowed the effects of different types of vasospasm on waveforms to be characterised at several locations within a simulated cerebral network. A sensitivity analysis empowered by the use of a Gaussian process statistical emulator was used to identify waveform features that may have strong correlations with vasospasm. We showed that the minimum rate of velocity change can be much more effective than blood velocity for stratifying typical manifestations of vasospasm and its progression. The results and methodology of this study have the potential not only to improve the diagnosis and monitoring of vasospasm, but also to be used in the diagnosis of many other cardiovascular diseases where cardiovascular waves can be decoded to provide disease characterisation.

The Role of Hemodynamics in Intracranial Bifurcation Arteries after Aneurysm Treatment with Flow-Diverter Stents.

BACKGROUND AND PURPOSE: Treatment of intracranial bifurcation aneurysms with flow-diverter stents can lead to caliber changes of the distal vessels in a subacute phase. This study aims to evaluate whether local anatomy and flow disruption induced by flow-diverter stents are associated with vessel caliber changes in intracranial bifurcations. MATERIALS AND METHODS: Radiologic images and demographic data were acquired for 25 patients with bifurcation aneurysms treated with flow-diverter stents. Whisker plots and Mann-Whitney rank sum tests were used to evaluate if anatomic data and caliber changes could be linked. Symmetry/asymmetry were defined as diameter ratio 1 = symmetric and diameter ratio <1 = asymmetric. Computational fluid dynamics was performed on idealized and patient-specific anatomies to evaluate flow changes induced by flow-diverter stents in the jailed vessel. RESULTS: Statistical analysis identified a marked correspondence between asymmetric bifurcation and caliber change. Symmetry ratios were lower for cases showing narrowing or subacute occlusion (medium daughter vessel diameter ratio = 0.59) compared with cases with posttreatment caliber conservation (medium daughter vessel diameter ratio = 0.95). Computational fluid dynamics analysis in idealized and patient-specific anatomies showed that wall shear stress in the jailed vessel was more affected when flow-diverter stents were deployed in asymmetric bifurcations (diameter ratio <0.65) and less affected when deployed in symmetric anatomies (diameter ratio ∼1.00). CONCLUSIONS: Anatomic data analysis showed statistically significant correspondence between caliber changes and bifurcation asymmetry characterized by diameter ratio <0.7 (P < .001). Similarly, computational fluid dynamics results showed the highest impact on hemodynamics when flow-diverter stents are deployed in asymmetric bifurcations (diameter ratio <0.65) with noticeable changes on wall sheer stress fields. Further research and clinical validation are necessary to identify all elements involved in vessel caliber changes after flow-diverter stent procedures.

Hemodynamic Changes Caused by Multiple Stenting in Vertebral Artery Fusiform Aneurysms: A Patient-Specific Computational Fluid Dynamics Study.

BACKGROUND AND PURPOSE: The multiple stent placement technique has largely improved the long-term outcomes of intracranial fusiform aneurysms, but the hemodynamic mechanisms remain unclear. In this study, we analyzed the hemodynamic changes caused by different stent-placement strategies in patient-specific models using the computational fluid dynamics technique, aiming to provide evidence for clinical decision-making. MATERIALS AND METHODS: Ten vertebral artery fusiform aneurysms were included, and their patient-specific computational fluid dynamics models were reconstructed. A fast virtual stent placement technique was used to simulate sequential multiple stent placements (from a single stent to triple stents) in the vertebral artery fusiform aneurysm models. Hemodynamic parameters, including wall shear stress, pressure, oscillatory shear index, relative residence time, and flow pattern, were calculated and compared among groups with different numbers of stents. RESULTS: Virtual stents were deployed in all 10 cases successfully, consistent with the real stent configuration. Wall shear stress decreased progressively by 7.2%, 20.6%, and 25.8% as the number of stents increased. Meanwhile, relative residence time and pressure increased on average by 11.3%, 15.4%, and 45.0% and by 15.7%, 21.5%, and 28.2%. The oscillatory shear index showed no stable variation trend. Flow patterns improved by weakening the intensity of the vortices and displacing the vortex center from the aneurysmal wall. CONCLUSIONS: Stent placement modifies hemodynamic patterns in vertebral artery fusiform aneurysms, which might favor thrombosis formation in the aneurysmal sac. This effect is amplified with the number of stents deployed. However, a potential risk of rupture or recanalization exists and should be considered when planning to use the multiple stent placement technique in vertebral artery fusiform aneurysms.

Wall shear stress at the initiation site of cerebral aneurysms.

Hemodynamics are believed to play an important role in the initiation of cerebral aneurysms. In particular, studies have focused on wall shear stress (WSS), which is a key regulator of vascular biology and pathology. In line with the observation that aneurysms predominantly occur at regions of high WSS, such as bifurcation apices or outer walls of vascular bends, correlations have been found between the aneurysm initiation site and high WSS. The aim of our study was to analyze the WSS field at an aneurysm initiation site that was neither a bifurcation apex nor the outer wall of a vascular bend. Ten cases with aneurysms on the A1 segment of the anterior cerebral artery were analyzed and compared with ten controls. Aneurysms were virtually removed from the vascular models of the cases to mimic the pre-aneurysm geometry. Computational fluid dynamics (CFD) simulations were created to assess the magnitude, gradient, multidirectionality, and pulsatility of the WSS. To aid the inter-subject comparison of hemodynamic variables, we mapped the branch surfaces onto a two-dimensional parametric space. This approach made it possible to view the whole branch at once for qualitative evaluation. It also allowed us to empirically define a patch for quantitative analysis, which was consistent among subjects and encapsulated the aneurysm initiation sites in our dataset. To test the sensitivity of our results, CFD simulations were repeated with a second independent observer virtually removing the aneurysms and with a 20 % higher flow rate at the inlet. We found that branches harboring aneurysms were characterized by high WSS and high WSS gradients. Among all assessed variables, the aneurysm initiation site most consistently coincided with peaks of temporal variation in the WSS magnitude.

Does Arterial Flow Rate Affect the Assessment of Flow-Diverter Stent Performance?

BACKGROUND AND PURPOSE: Our aim was to assess the performance of flow-diverter stents. The pre- and end-of-treatment angiographies are commonly compared. However, the arterial flow rate may change between acquisitions; therefore, a better understanding of its influence on the local intra-aneurysmal hemodynamics before and after flow-diverter stent use is required. MATERIALS AND METHODS: Twenty-five image-based aneurysm models extracted from 3D rotational angiograms were conditioned for computational fluid dynamics simulations. Pulsatile simulations were performed at different arterial flow rates, covering a wide possible range of physiologic flows among 1-5 mL/s. The effect of flow-diverter stents on intra-aneurysmal hemodynamics was numerically simulated with a porous medium model. Spatiotemporal-averaged intra-aneurysmal flow velocity and flow rate were calculated for each case to quantify the hemodynamics after treatment. The short-term flow-diverter stent performance was characterized by the relative velocity reduction inside the aneurysm. RESULTS: Spatiotemporal-averaged intra-aneurysmal flow velocity before and after flow-diverter stent use is linearly proportional to the mean arterial flow rate (minimum R2 > 0.983 of the linear regression models for untreated and stented models). Relative velocity reduction asymptotically decreases with increasing mean arterial flow rate. When the most probable range of arterial flow rate was considered (3-5 mL/s), instead of the wide possible flow range, the mean SD of relative velocity reduction was reduced from 3.6% to 0.48%. CONCLUSIONS: Both intra-aneurysmal aneurysm velocity and flow-diverter stent performance depend on the arterial flow rate. The performance could be considered independent of the arterial flow rates within the most probable range of physiologic flows.

Approximating hemodynamics of cerebral aneurysms with steady flow simulations.

Computational fluid dynamics (CFD) simulations can be employed to gain a better understanding of hemodynamics in cerebral aneurysms and improve diagnosis and treatment. However, introduction of CFD techniques into clinical practice would require faster simulation times. The aim of this study was to evaluate the use of computationally inexpensive steady flow simulations to approximate the aneurysm's wall shear stress (WSS) field. Two experiments were conducted. Experiment 1 compared for two cases the time-averaged (TA), peak systole (PS) and end diastole (ED) WSS field between steady and pulsatile flow simulations. The flow rate waveform imposed at the inlet was varied to account for variations in heart rate, pulsatility index, and TA flow rate. Consistently across all flow rate waveforms, steady flow simulations accurately approximated the TA, but not the PS and ED, WSS field. Following up on experiment 1, experiment 2 tested the result for the TA WSS field in a larger population of 20 cases covering a wide range of aneurysm volumes and shapes. Steady flow simulations approximated the space-averaged WSS with a mean error of 4.3%. WSS fields were locally compared by calculating the absolute error per node of the surface mesh. The coefficient of variation of the root-mean-square error over these nodes was on average 7.1%. In conclusion, steady flow simulations can accurately approximate the TA WSS field of an aneurysm. The fast computation time of 6 min per simulation (on 64 processors) could help facilitate the introduction of CFD into clinical practice.

RADStation3G: a platform for cardiovascular image analysis integrating PACS, 3D+t visualization and grid computing.

RADStation3G is a software platform for cardiovascular image analysis and surgery planning. It provides image visualization and management in 2D, 3D and 3D+t; data storage (images or operational results) in a PACS (using DICOM); and exploitation of patients' data such as images and pathologies. Further, it provides support for computationally expensive processes with grid technology. In this article we first introduce the platform and present a comparison with existing systems, according to the platform's modules (for cardiology, angiology, PACS archived enriched searching and grid computing), and then RADStation3G is described in detail.

Intra-aneurysmal pressure and flow changes induced by flow diverters: relation to aneurysm size and shape.

BACKGROUND AND PURPOSE: Effects of blood flow modification by flow diverters are observed to lead often to aneurysm thrombosis and reverse remodeling. For this process, to further understand the potential roles of intra-aneurysmal blood pressure changes and aneurysm morphologies, 23 patients were studied by numeric simulation. MATERIALS AND METHODS: 3D imaging of aneurysms of different sizes and shapes, all located at the supraclinoid segment of the ICA (n=23), was prepared for CFD simulations. Hemodynamic variables were calculated for conditions before and after virtual FD implantation, reconstituting a vessel wall scaffold across the aneurysm neck. WSS, velocity, residence time, turnover time, and intra-aneurysmal pressure were assessed statistically. RESULTS: After placement of FDs, significant reductions inside the aneurysm were observed for most hemodynamic variables (P<.01) except mean intra-aneurysmal pressures. For minimum/maximum intra-aneurysmal pressure values, small but significant changes were found; however, they were considered too small to be of relevance. CONCLUSIONS: Calculations in 23 cases did not reveal significant intra-aneurysmal mean or peak pressure changes, indicating a minor role of pressure changes in the rare event of secondary ruptures after FD use. Other hemodynamic variables (WSS and velocity) exhibited more significant changes, indicating their role in intra-aneurysmal thrombus formation. Size-dependent, significantly higher reduction in WSS (P=.069) and velocity (P=.013) was observed in small aneurysms compared with larger ones. When it came to shape, there were significantly higher reductions in WSS (P=.055) and velocity (P=.065) and a significantly higher increase in turnover time in fusiform aneurysms compared with saccular aneurysms.

HeMoLab--Hemodynamics Modelling Laboratory: an application for modelling the human cardiovascular system.

In this work we present HeMoLab (Hemodynamics Modeling Laboratory), a computational environment for modeling the Human Cardiovascular System. Its integrates novel computational tools, running from medical image processing to numerical simulation and visualization. As a simulation tool, it allows to accommodate complex physiological and/or pathophysiological (virtual) scenarios aimed to retrieve detailed information from the numerical computations. Such application makes possible to speed up research in the study and analysis of the cardiovascular system and, to provide a virtual laboratory for medical training and education, and specialized Human Resources development. In order to demonstrate the modeling and simulation capabilities of HeMoLab some cases of use are presented.

Deployment of self-expandable stents in aneurysmatic cerebral vessels: comparison of different computational approaches for interventional planning.

In the last few years, there has been a growing focus on faster computational methods to support clinicians in planning stenting procedures. This study investigates the possibility of introducing computational approximations in modelling stent deployment in aneurysmatic cerebral vessels to achieve simulations compatible with the constraints of real clinical workflows. The release of a self-expandable stent in a simplified aneurysmatic vessel was modelled in four different initial positions. Six progressively simplified modelling approaches (based on Finite Element method and Fast Virtual Stenting--FVS) have been used. Comparing accuracy of the results, the final configuration of the stent is more affected by neglecting mechanical properties of materials (FVS) than by adopting 1D instead of 3D stent models. Nevertheless, the differences showed are acceptable compared to those achieved by considering different stent initial positions. Regarding computational costs, simulations involving 1D stent features are the only ones feasible in clinical context.

How do coil configuration and packing density influence intra-aneurysmal hemodynamics?

BACKGROUND AND PURPOSE: Endovascular coiling is a well-established therapy for treating intracranial aneurysms. Nonetheless, postoperative hemodynamic changes induced by this therapy remain not fully understood. The purpose of this work is to assess the influence of coil configuration and packing density on intra-aneurysmal hemodynamics. MATERIALS AND METHODS: Three 3D rotational angiography images of 3 intracranial aneurysms before and after endovascular coiling were used. For each aneurysm, a 3D representation of the vasculature was obtained after the segmentation of the images. Afterward, a virtual coiling technique was used to treat the aneurysm geometries with coil models. The aneurysms were coiled with 5 packing densities, and each was generated by using 3 coil configurations. Computational fluid dynamics analyses were carried out in both untreated and treated aneurysm geometries. Statistical tests were performed to evaluate the relative effect of coil configuration on local hemodynamics. RESULTS: The intra-aneurysmal blood flow velocity and wall shear stress were diminished as packing density increased. Aneurysmal flow velocity was reduced >50% due to the first inserted coils (packing density <12%) but with a high dependency on coil configuration. Nonsignificant differences (P > .01) were found in the hemodynamics due to coil configuration for high packing densities (near 30%). A damping effect was observed on the intra-aneurysmal blood flow waveform after coiling. CONCLUSIONS: Intra-aneurysmal hemodynamics are altered by coils. Coil configuration might reduce its influence on intra-aneurysmal hemodynamics as the packing density increases until an insignificant influence could be achieved for high packing densities.

@neurIST complex information processing toolchain for the integrated management of cerebral aneurysms.

Cerebral aneurysms are a multi-factorial disease with severe consequences. A core part of the European project @neurIST was the physical characterization of aneurysms to find candidate risk factors associated with aneurysm rupture. The project investigated measures based on morphological, haemodynamic and aneurysm wall structure analyses for more than 300 cases of ruptured and unruptured aneurysms, extracting descriptors suitable for statistical studies. This paper deals with the unique challenges associated with this task, and the implemented solutions. The consistency of results required by the subsequent statistical analyses, given the heterogeneous image data sources and multiple human operators, was met by a highly automated toolchain combined with training. A testimonial of the successful automation is the positive evaluation of the toolchain by over 260 clinicians during various hands-on workshops. The specification of the analyses required thorough investigations of modelling and processing choices, discussed in a detailed analysis protocol. Finally, an abstract data model governing the management of the simulation-related data provides a framework for data provenance and supports future use of data and toolchain. This is achieved by enabling the easy modification of the modelling approaches and solution details through abstract problem descriptions, removing the need of repetition of manual processing work.

Patient-specific computational hemodynamics of intracranial aneurysms from 3D rotational angiography and CT angiography: an in vivo reproducibility study.

BACKGROUND AND PURPOSE: Patient-specific simulations of the hemodynamics in intracranial aneurysms can be constructed by using image-based vascular models and CFD techniques. This work evaluates the impact of the choice of imaging technique on these simulations. MATERIALS AND METHODS: Ten aneurysms, imaged with 3DRA and CTA, were analyzed to assess the reproducibility of geometric and hemodynamic variables across the 2 modalities. RESULTS: Compared with 3DRA models, we found that CTA models often had larger aneurysm necks (P = .05) and that most of the smallest vessels (between 0.7 and 1.0 mm in diameter) could not be reconstructed successfully with CTA. With respect to the values measured in the 3DRA models, the flow rate differed by 14.1 ± 2.8% (mean ± SE) just proximal to the aneurysm and 33.9 ± 7.6% at the aneurysm neck. The mean WSS on the aneurysm differed by 44.2 ± 6.0%. Even when normalized to the parent vessel WSS, a difference of 31.4 ± 9.9% remained, with the normalized WSS in most cases being larger in the CTA model (P = .04). Despite these substantial differences, excellent agreement (κ ≥ 0.9) was found for qualitative variables that describe the flow field, such as the structure of the flow pattern and the flow complexity. CONCLUSIONS: Although relatively large differences were found for all evaluated quantitative hemodynamic variables, the main flow characteristics were reproduced across imaging modalities.

AngioLab: integrated technology for patient-specific management of intracranial aneurysms.

AngioLab is a software tool developed within the GIMIAS framework and is part of a more ambitious pipeline for the integrated management of cerebral aneurysms. AngioLab currently includes three plug-ins: angio segmentation, angio morphology and stenting, as well as supports advanced rendering techniques for the visualization of virtual angiographies. In December 2009, 23 clinicians completed an evaluation questionnaire about AngioLab. This activity was part of a teaching course held during the 2(nd) European Society for Minimally Invasive Neurovascular Treatment (ESMINT) Teaching Course held at the Universitat Pompeu Fabra, Barcelona, Spain. The Automated Morphological Analysis (angio morphology plug-in) and the Endovascular Treatment Planning (stenting plug-in) were evaluated. In general, the results provided by these tools were considered as relevant and as an emerging need in their clinical field.

Comparison of steady-state and transient blood flow simulations of intracranial aneurysms.

Hemodynamics play an important role in the pathogenesis of intracranial aneurysms and patient-specific computational hemodynamic simulations could provide valuable information to clinicians. Transient simulations that capture the pulsatility of blood flow are commonly used for research purposes. However, steady-state simulations might provide enough information at a lower computational cost, which could help facilitate the introduction of hemodynamic simulations into clinical practice. In this study, we compared steady-state simulations to transient simulations for two aneurysms. The effect of a change in flow rate waveform was investigated and virtual treatment techniques were employed to compare post-treatment flow reduction predictions. We found that the difference in the time-averaged wall shear stress on the aneurysm was less than 5% and the distribution of wall shear stress was qualitatively assessed to be very similar.

Toward integrated management of cerebral aneurysms.

In the last few years, some of the visionary concepts behind the virtual physiological human began to be demonstrated on various clinical domains, showing great promise for improving healthcare management. In the current work, we provide an overview of image- and biomechanics-based techniques that, when put together, provide a patient-specific pipeline for the management of intracranial aneurysms. The derivation and subsequent integration of morphological, morphodynamic, haemodynamic and structural analyses allow us to extract patient-specific models and information from which diagnostic and prognostic descriptors can be obtained. Linking such new indices with relevant clinical events should bring new insights into the processes behind aneurysm genesis, growth and rupture. The development of techniques for modelling endovascular devices such as stents and coils allows the evaluation of alternative treatment scenarios before the intervention takes place and could also contribute to the understanding and improved design of more effective devices. A key element to facilitate the clinical take-up of all these developments is their comprehensive validation. Although a number of previously published results have shown the accuracy and robustness of individual components, further efforts should be directed to demonstrate the diagnostic and prognostic efficacy of these advanced tools through large-scale clinical trials.

The European contribution to "Sugarbaker's protocol" for the treatment of colorectal peritoneal carcinomatosis.

INTRODUCTION: In 1981, Dr. PH Sugarbaker, challenging oncological orthodoxy, considered carcinomatosis to be a locoregional stage of the disease that was still susceptible to treatment with curative intent. To this end he developed a new therapeutic alternative based on the combined treatment. The macroscopic disease treated by maximum radical oncological cytoreductive surgery (through the peritonectomies described by him), followed by treatment of the residual microscopic disease with the direct intra-abdominal application of intraoperative chemotherapy with locoregional intensification, modulated by hyperthermia and early normothermic postoperative intra-abdominal chemotherapy. Using this new therapeutic regimen, known as "Sugarbaker s Protocol", his group has reported 45% survival rates in carcinomatosis of colorectal origin at 5 years, and, in selected groups of patients, 50% survival rates at 5 years. The scientific community, however, has criticized these results considering that: it is a personal experience, with a not homogenous treatment protocol with developmental modifications over time, that it is a retrospective non-randomized study, and finally that the cytostatics used in his protocol are obsolete. Various European groups have replied to these main criticisms confirming the good results that this new therapeutic alternative offers for patients with carcinomatosis of colorectal origin. The purpose of this article is to present these contributions. MATERIAL AND METHODS: All the articles published in the English language by European groups in the world s medical literature have been reviewed using the Pubmed-MEDLINE database to identify the relevant articles related to the treatment of carcinomatosis of colorectal origin using cytoreduction and intraperitoneal chemotherapy from January 1980 to January 2008. RESULTS: The European contribution during these 25 years in favour of the "Sugarbaker s Protocol" has consisted fundamentally in: a) one multicenter retrospective study; b) two randomized prospective phase III studies; and c) the use of oxaliplatin and irinotecan as new cytostatic agents in the protocols for intraperitoneal chemotherapy. At the same time, two new transcendental European contributions have been made in which the possibility has been considered of combined simultaneous treatment for patients with hepatic metastases and carcinomatosis, and the introduction, as a selection factor, of patients responsive to intravenous induction chemotherapy within the regimen of sandwich treatment (with systemic neoadjuvant and adjuvant chemotherapy) complementary to intraperitoneal chemotherapy. CONCLUSIONS: The results obtained by European groups using "Sugarbaker s protocol" and "Elias protocol" with oxaliplatin compel us to request that these treatments be considered by all professionals involved in the treatment of patients with colorectal carcinomatosis as the best treatment currently available for this condition. Furthermore a randomized, prospective, multicenter study should be carried out to clarify its value and the degree of scientific evidence. A validation of this treatment will change, in the future, the dogmatic consideration of carcinomatosis as an incurable disease stage.

Aportación europea al “protocolo de Sugarbaker” en el tratamiento de la carcinomatosis peritoneal colorrectal / The European contribution to "Sugarbaker's protocol" for the treatment of colorectal peritoneal carcinomatosis

Introducción: el Dr. P. H. Sugarbaker en 1981, desafiando la ortodoxia oncológica, consideró la carcinomatosis como un estadio locorregional de la enfermedad susceptible todavía de tratamiento con intención curativa. Para ello desarrolló una nueva alternativa terapéutica basada en el tratamiento combinado. La enfermedad macroscópica mediante la máxima cirugía citorreductora radical oncológica (merced a las peritonectomías por él descritas), seguido del tratamiento de la enfermedad microscópica residual con la aplicación directa intraabdominal, de quimioterapia de intensificación locorregional, intraoperatoria modulada por hipertermia y de quimioterapia intraabdominal normotérmica postoperatoria precoz. Con este nuevo esquema terapéutico, conocido como "Protocolo de Sugarbaker", su grupo ha publicado supervivencias en carcinomatosis de origen colorrectal de 45% a 5 años y en grupos selectos de pacientes supervivencia de 50% a 5 años. La comunidad científica, sin embargo, ha criticado estos resultados al considerar que: se trata de una experiencia personal, con un protocolo de tratamiento no homogéneo con modificaciones evolutivas en el tiempo, tratarse de un estudio retrospectivo no randomizado, y finalmente considerar que los citostáticos empleados en su protocolo son obsoletos. Diversos grupos europeos han dado respuesta a las principales objeciones, confirmando los buenos resultados que esta nueva alternativa terapéutica ofrece en pacientes con carcinomatosis de origen colorrectal. El objetivo de este trabajo es presentar estas aportaciones. Material y métodos: se han revisado todos los artículos publicados en lengua inglesa por grupos europeos en la literatura médica mundial usando la base de datos Pubmed-MEDLINE para identificar los artículos relevantes relacionados con el tratamiento de la carcinomatosis de origen colorrectal mediante citorreducción y quimioterapia intraperitoneal desde enero de 1980 a enero de 2008...(AU)

Introduction: in 1981, Dr. PH Sugarbaker, challenging oncological orthodoxy, considered carcinomatosis to be a locoregional stage of the disease that was still susceptible to treatment with curative intent. To this end he developed a new therapeutic alternative based on the combined treatment. The macroscopic disease treated by maximum radical oncological cytoreductive surgery (through the peritonectomies described by him), followed by treatment of the residual microscopic disease with the direct intra-abdominal application of intraoperative chemotherapy with locoregional intensification, modulated by hyperthermia and early normothermic postoperative intra-abdominal chemotherapy. Using this new therapeutic regimen, known as "Sugarbaker's Protocol", his group has reported 45% survival rates in carcinomatosis of colorectal origin at 5 years, and, in selected groups of patients, 50% survival rates at 5 years. The scientific community, however, has criticized these results considering that: it is a personal experience, with a not homogenous treatment protocol with developmental modifications over time, that it is a retrospective non-randomized study, and finally that the cytostatics used in his protocol are obsolete. Various European groups have replied to these main criticisms confirming the good results that this new therapeutic alternative offers for patients with carcinomatosis of colorectal origin. The purpose of this article is to present these contributions. Material and methods: all the articles published in the English language by European groups in the world's medical literature have been reviewed using the Pubmed-MEDLINE database to identify the relevant articles related to the treatment of carcinomatosis of colorectal origin using cytoreduction and intraperitoneal chemotherapy from January 1980 to January 2008...(AU)

Peritoneal carcinomatosis of colorectal origin. Current treatment. Review and update.

Colorectal cancer is the most frequent tumor of the digestive tract. The high incidence of abdominal dissemination; the poor prognosis of these patients, with median survival consistently ranging from 5 to 9 months in all studies of peritoneal carcinomatosis from colorectal cancer; the failure of adjuvant systemic chemotherapy treatment with a maximal survival of 18 months despite the development of new cytostatic drugs, and new combinations of use, make it crucial to search for and develop new treatment strategies. We review the principles of Sugarbaker s treatment protocol, which involves the combination of maximum cytoreductive radical oncological surgery for the treatment of all macroscopically disseminated disease with maximum perioperative intraperitoneal intensification chemotherapy to treat residual microscopic disease. We present the results of several scientific papers, all of them phase II studies with more than 10 patients treated, published in the medical literature by the main groups working in this line of treatment, together with the only phase III study reported and published so far, and finally the results of a recently reported retrospective international multicenter study. With this new alternative therapeutic approach, overall mean survival is 40% at 36 months, and 20% at 5 years. Based on these results, this new therapeutic approach is proposed as the treatment of choice for these unfortunate patients.

Carcinomatosis peritoneal de origen colorrectal. Estado actual del tratamiento. Revisión y puesta al día / Peritoneal carcinomatosis of colorectal origin. Current treatment. Review and update

El cáncer colorrectal es el tumor más frecuente del tracto digestivo.La alta incidencia de diseminación abdominal, el pobre pronósticode estos pacientes con una mediana de supervivencia entre5 y 9 meses demostrada repetidamente en todos los estudiosde carcinomatosis peritoneal por cáncer colorrectal, el fracaso delos tratamientos sistémicos adyuvantes con quimioterapia con supervivenciasmáximas de 18 meses independientemente del desarrollode nuevas drogas citostáticas y las nuevas combinaciones oformas de uso, hacen crucial la investigación y el desarrollo denuevas estrategias de tratamiento.Revisamos los principios del protocolo del tratamiento de Sugarbaker,que contempla la combinación de la máxima cirugía radicaloncológica citorreductora para el tratamiento de la enfermedadmacroscópica diseminada con la máxima quimioterapia deintensificación intraperitoneal perioperatoria para el tratamientode la enfermedad microscópica residual.Se presentan los resultados de las publicaciones científicas, detodos los estudios fase II con más de 10 pacientes tratados publicadosen la literatura médica por los principales grupos de trabajoen esta línea de tratamiento, junto con el único estudio fase III publicadohasta el momento, y finalmente los resultados de un recienteestudio multicéntrico internacional retrospectivo.Con esta nueva alternativa terapéutica, la supervivencia mediaa los 36 meses es del 40, y del 20% a los 5 años. Basados en estosresultados, proponemos esta alternativa de tratamiento comoel tratamiento de elección de estos desafortunados pacientes

Colorectal cancer is the most frequent tumor of the digestivetract. The high incidence of abdominal dissemination; the poorprognosis of these patients, with median survival consistentlyranging from 5 to 9 months in all studies of peritoneal carcinomatosisfrom colorectal cancer; the failure of adjuvant systemicchemotherapy treatment with a maximal survival of 18 monthsdespite the development of new cytostatic drugs, and new combinationsof use, make it crucial to search for and develop newtreatment strategies.We review the principles of Sugarbaker´s treatment protocol,which involves the combination of maximum cytoreductive radicaloncological surgery for the treatment of all macroscopically disseminateddisease with maximum perioperative intraperitoneal intensificationchemotherapy to treat residual microscopic disease.We present the results of several scientific papers, all of themphase II studies with more than 10 patients treated, published inthe medical literature by the main groups working in this line oftreatment, together with the only phase III study reported andpublished so far, and finally the results of a recently reported retrospectiveinternational multicenter study. With this new alternativetherapeutic approach, overall mean survival is 40% at 36months, and 20% at 5 years.Based on these results, this new therapeutic approach is proposedas the treatment of choice for these unfortunate patients