The Experts below are selected from a list of 822 Experts worldwide ranked by ideXlab platform
Agnes Francois - One of the best experts on this subject based on the ideXlab platform.
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endothelial hey2 deletion reduces endothelial to mesenchymal transition and mitigates Radiation Proctitis in mice
Scientific Reports, 2017Co-Authors: Elodie Mintet, Fabien Milliat, Jeanchristophe Sabourin, Jeremy Lavigne, Vincent Paget, Georges Tarlet, Valerie Buard, Olivier Guipaud, Marialuisa Iruelaarispe, Agnes FrancoisAbstract:The current study evaluated the role of Hey2 transcription factor in Radiation-induced endothelial-to-mesenchymal transition (EndoMT) and its impact on Radiation-induced tissue damage in mice. Phenotypic modifications of irradiated, Hey2 siRNA- and Hey2 vector plasmid-transfected human umbilical vein endothelial cells (HUVECs) resembling EndoMT were monitored by qPCR, immunocytochemistry and western blots. Subsequently, in mice, a Cre-LoxP strategy for inactivation of Hey2 specifically in the endothelium was used to study the biological consequences. Total body irRadiation and Radiation Proctitis were monitored to investigate the impact of conditional Hey2 deletion on intestinal stem cells and microvascular compartment radiosensitivity, EndoMT and rectal damage severity. We found that EndoMT occurs in irradiated HUVECs with concomitant Hey2 mRNA and protein increase. While Hey2 silencing has no effect on Radiation-induced EndoMT in vitro, Hey2 overexpression is sufficient to induce phenotypic conversion of endothelial cells. In mice, the conditional deletion of Hey2 reduces EndoMT frequency and the severity of rectal tissue damage. Our data indicate that the reduction in mucosal damage occurs through decline in stem/clonogenic epithelial cell loss mediated by microvascular protection. EndoMT is involved in Radiation Proctitis and this study demonstrates that a strategy based on the reduction of EndoMT mitigates intestinal tissue damage.
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mast cells are an essential component of human Radiation Proctitis and contribute to experimental colorectal damage in mice
American Journal of Pathology, 2011Co-Authors: Karl Blirando, Fabien Milliat, Isabelle Martelly, Jeanchristophe Sabourin, Marc Benderitter, Agnes FrancoisAbstract:Radiation Proctitis is characterized by mucosal inflammation followed by adverse chronic tissue remodeling and is associated with substantial morbidity and mortality. Mast cell hyperplasia has been associated with diseases characterized by pathological tissue remodeling and fibrosis. Rectal tissue from patients treated with radiotherapy shows mast cell hyperplasia and activation, suggesting that these cells play a role in the development of Radiation-induced sequelae. To investigate the role of mast cells in Radiation damage, experimental Radiation Proctitis was induced in a mast cell-deficient (W sh /W sh ) mouse model. The colon and rectum of W sh /W sh and wild-type mice were exposed to 27-Gy single-dose irRadiation and studied after 2 and 14 weeks. Irradiated rodent rectum showed mast cell hyperplasia. W sh /W sh mice developed less acute and chronic rectal Radiation damage than their control littermates. Tissue protection was associated with increased tissue neutrophil influx and expression of several inflammatory mediators immediately after Radiation exposure. It was further demonstrated that mast cell chymase, tryptase, and histamine could change human muscularis propria smooth muscle cells into a migrating/proliferating and proinflammatory phenotype. These data show that mast cells have deleterious effects on both acute and chronic Radiation Proctitis, possibly by limiting acute tissue neutrophil influx and by favoring phenotypic orientation of smooth muscle cells, thus making them active participants in the Radiation-induced inflammatory process and dystrophy of the rectal wall.
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Mast cells are an essential component of human Radiation Proctitis and contribute to experimental colorectal damage in mice
American Journal of Pathology, 2011Co-Authors: Karl Blirando, Fabien Milliat, Isabelle Martelly, Marc Benderitter, J.-c. Sabourin, Agnes FrancoisAbstract:Radiation Proctitis is characterized by mucosal inflammation followed by adverse chronic tissue remodeling and is associated with substantial morbidity and mortality. Mast cell hyperplasia has been associated with diseases characterized by pathological tissue remodeling and fibrosis. Rectal tissue from patients treated with radiotherapy shows mast cell hyperplasia and activation, suggesting that these cells play a role in the development of Radiation-induced sequelae. To investigate the role of mast cells in Radiation damage, experimental Radiation Proctitis was induced in a mast cell-deficient (W sh/Wsh) mouse model. The colon and rectum of W sh/Wsh and wild-type mice were exposed to 27-Gy single-dose irRadiation and studied after 2 and 14 weeks. Irradiated rodent rectum showed mast cell hyperplasia. Wsh/Wsh mice developed less acute and chronic rectal Radiation damage than their control littermates. Tissue protection was associated with increased tissue neutrophil influx and expression of several inflammatory mediators immediately after Radiation exposure. It was further demonstrated that mast cell chymase, tryptase, and histamine could change human muscularis propria smooth muscle cells into a migrating/proliferating and proinflammatory phenotype. These data show that mast cells have deleterious effects on both acute and chronic Radiation Proctitis, possibly by limiting acute tissue neutrophil influx and by favoring phenotypic orientation of smooth muscle cells, thus making them active participants in the Radiation-induced inflammatory process and dystrophy of the rectal wall. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
Fabien Milliat - One of the best experts on this subject based on the ideXlab platform.
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endothelial hey2 deletion reduces endothelial to mesenchymal transition and mitigates Radiation Proctitis in mice
Scientific Reports, 2017Co-Authors: Elodie Mintet, Fabien Milliat, Jeanchristophe Sabourin, Jeremy Lavigne, Vincent Paget, Georges Tarlet, Valerie Buard, Olivier Guipaud, Marialuisa Iruelaarispe, Agnes FrancoisAbstract:The current study evaluated the role of Hey2 transcription factor in Radiation-induced endothelial-to-mesenchymal transition (EndoMT) and its impact on Radiation-induced tissue damage in mice. Phenotypic modifications of irradiated, Hey2 siRNA- and Hey2 vector plasmid-transfected human umbilical vein endothelial cells (HUVECs) resembling EndoMT were monitored by qPCR, immunocytochemistry and western blots. Subsequently, in mice, a Cre-LoxP strategy for inactivation of Hey2 specifically in the endothelium was used to study the biological consequences. Total body irRadiation and Radiation Proctitis were monitored to investigate the impact of conditional Hey2 deletion on intestinal stem cells and microvascular compartment radiosensitivity, EndoMT and rectal damage severity. We found that EndoMT occurs in irradiated HUVECs with concomitant Hey2 mRNA and protein increase. While Hey2 silencing has no effect on Radiation-induced EndoMT in vitro, Hey2 overexpression is sufficient to induce phenotypic conversion of endothelial cells. In mice, the conditional deletion of Hey2 reduces EndoMT frequency and the severity of rectal tissue damage. Our data indicate that the reduction in mucosal damage occurs through decline in stem/clonogenic epithelial cell loss mediated by microvascular protection. EndoMT is involved in Radiation Proctitis and this study demonstrates that a strategy based on the reduction of EndoMT mitigates intestinal tissue damage.
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mast cells are an essential component of human Radiation Proctitis and contribute to experimental colorectal damage in mice
American Journal of Pathology, 2011Co-Authors: Karl Blirando, Fabien Milliat, Isabelle Martelly, Jeanchristophe Sabourin, Marc Benderitter, Agnes FrancoisAbstract:Radiation Proctitis is characterized by mucosal inflammation followed by adverse chronic tissue remodeling and is associated with substantial morbidity and mortality. Mast cell hyperplasia has been associated with diseases characterized by pathological tissue remodeling and fibrosis. Rectal tissue from patients treated with radiotherapy shows mast cell hyperplasia and activation, suggesting that these cells play a role in the development of Radiation-induced sequelae. To investigate the role of mast cells in Radiation damage, experimental Radiation Proctitis was induced in a mast cell-deficient (W sh /W sh ) mouse model. The colon and rectum of W sh /W sh and wild-type mice were exposed to 27-Gy single-dose irRadiation and studied after 2 and 14 weeks. Irradiated rodent rectum showed mast cell hyperplasia. W sh /W sh mice developed less acute and chronic rectal Radiation damage than their control littermates. Tissue protection was associated with increased tissue neutrophil influx and expression of several inflammatory mediators immediately after Radiation exposure. It was further demonstrated that mast cell chymase, tryptase, and histamine could change human muscularis propria smooth muscle cells into a migrating/proliferating and proinflammatory phenotype. These data show that mast cells have deleterious effects on both acute and chronic Radiation Proctitis, possibly by limiting acute tissue neutrophil influx and by favoring phenotypic orientation of smooth muscle cells, thus making them active participants in the Radiation-induced inflammatory process and dystrophy of the rectal wall.
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Mast cells are an essential component of human Radiation Proctitis and contribute to experimental colorectal damage in mice
American Journal of Pathology, 2011Co-Authors: Karl Blirando, Fabien Milliat, Isabelle Martelly, Marc Benderitter, J.-c. Sabourin, Agnes FrancoisAbstract:Radiation Proctitis is characterized by mucosal inflammation followed by adverse chronic tissue remodeling and is associated with substantial morbidity and mortality. Mast cell hyperplasia has been associated with diseases characterized by pathological tissue remodeling and fibrosis. Rectal tissue from patients treated with radiotherapy shows mast cell hyperplasia and activation, suggesting that these cells play a role in the development of Radiation-induced sequelae. To investigate the role of mast cells in Radiation damage, experimental Radiation Proctitis was induced in a mast cell-deficient (W sh/Wsh) mouse model. The colon and rectum of W sh/Wsh and wild-type mice were exposed to 27-Gy single-dose irRadiation and studied after 2 and 14 weeks. Irradiated rodent rectum showed mast cell hyperplasia. Wsh/Wsh mice developed less acute and chronic rectal Radiation damage than their control littermates. Tissue protection was associated with increased tissue neutrophil influx and expression of several inflammatory mediators immediately after Radiation exposure. It was further demonstrated that mast cell chymase, tryptase, and histamine could change human muscularis propria smooth muscle cells into a migrating/proliferating and proinflammatory phenotype. These data show that mast cells have deleterious effects on both acute and chronic Radiation Proctitis, possibly by limiting acute tissue neutrophil influx and by favoring phenotypic orientation of smooth muscle cells, thus making them active participants in the Radiation-induced inflammatory process and dystrophy of the rectal wall. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
Joseph Weiner - One of the best experts on this subject based on the ideXlab platform.
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long term results on the efficacy of argon plasma coagulation for patients with chronic Radiation Proctitis after conventionally fractionated dose escalated Radiation therapy for prostate cancer
Practical radiation oncology, 2017Co-Authors: Joseph Weiner, David A Schwartz, Manuel Martinez, Joseph Safdieh, Ayse Aytaman, David SchreiberAbstract:Abstract Purpose This study was designed to assess the efficacy and outcomes of argon plasma coagulation (APC) in the management of chronic Radiation Proctitis after conventionally fractionated, dose-escalated Radiation therapy (≥7560 cGy). Methods and materials We retrospectively reviewed the charts on all patients treated with external beam Radiation therapy (minimum dose, 7560 cGy) for histologically confirmed prostate cancer at our institution from 2003 to 2011. Five hundred patients met these criteria; of these, 35 patients (7.0%) developed Radiation Proctitis necessitating intervention with APC. Indications for APC treatment were either the need for blood transfusions resulting from Proctitis-related anemia or refractory bleeding despite medical management. Results The median follow-up from the completion of Radiation treatment was 78 months (range, 19-129) and the median follow up from the most recent APC treatment was 56 months (range, 3-112). Fifteen men (42.9%) needed blood transfusions because of Proctitis-related anemia. For 19 patients (54.3%), bleeding was controlled after 1 or 2 treatments. Eventual bleeding control was obtained in 30 patients (85.7%). The median number of sessions per patient was 2 (range, 1-13). Post-APC ulceration was noted in 8 cases (22.9%). Two patients (5.7%) developed colovesicular fistulas, with 1 patient dying from this complication. A short interval between treatments (≤35 days) was associated with an increased risk of ulcer or fistula formation. Conclusions APC is an effective treatment for patients with medically refractive Radiation Proctitis after dose-escalated Radiation therapy, frequently controlling bleeding after only one or two sessions. However, rectal ulceration is a common complication, along with a small risk of life-threatening toxicity.
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endoscopic and non endoscopic approaches for the management of Radiation induced rectal bleeding
World Journal of Gastroenterology, 2016Co-Authors: Joseph Weiner, Manuel Martinez, Ayse Aytaman, Andrew T Wong, David Schwartz, David SchreiberAbstract:Pelvic Radiation is a commonly utilized treatment for malignancy of the genitourinary and lower gastrointestinal tract. Radiation Proctitis and the resultant clinical picture varies from asymptomatic to potentially life threatening. Similarly, treatment options also vary greatly, from medical therapy to surgical intervention. Commonly utilized medical therapy includes sucralfate enemas, antibiotics, 5-aminosalicylic acid derivatives, probiotics, antioxidants, short-chain fatty acids, formalin instillation and fractionated hyperbaric oxygen. More invasive treatments include endoscopic-based, focally ablative interventions such as dilation, heater and bipolar cautery, neodymium/yttrium aluminum garnet argon laser, radiofrequency ablation or argon plasma coagulation. Despite its relatively common frequency, there is a dearth of existing literature reporting head-to-head comparisons of the various treatment options via a randomized controlled approach. The purpose of our review was to present the reader a consolidation of the existing evidence-based literature with the goal of highlighting the comparative effectiveness and risks of the various treatment approaches. Finally, we outline a pragmatic approach to the treatment of Radiation Proctitis. In light of the lack of randomized data, our goal is to pursue as least invasive an approach as possible, with escalation of care tailored to the severity of the patient's symptoms. For those cases that are clinically asymptomatic or only mildly symptomatic, observation or medical management can be considered. Once a patient fails such management or symptoms become more severe, invasive procedures such as endoscopically based focal ablation or surgical intervention can be considered. Although not all recommendations are supported by level I evidence, reported case series and single-institutional studies in the literature suggest that successful treatment with cessation of symptoms can be obtained in the majority of cases.
David Schreiber - One of the best experts on this subject based on the ideXlab platform.
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long term results on the efficacy of argon plasma coagulation for patients with chronic Radiation Proctitis after conventionally fractionated dose escalated Radiation therapy for prostate cancer
Practical radiation oncology, 2017Co-Authors: Joseph Weiner, David A Schwartz, Manuel Martinez, Joseph Safdieh, Ayse Aytaman, David SchreiberAbstract:Abstract Purpose This study was designed to assess the efficacy and outcomes of argon plasma coagulation (APC) in the management of chronic Radiation Proctitis after conventionally fractionated, dose-escalated Radiation therapy (≥7560 cGy). Methods and materials We retrospectively reviewed the charts on all patients treated with external beam Radiation therapy (minimum dose, 7560 cGy) for histologically confirmed prostate cancer at our institution from 2003 to 2011. Five hundred patients met these criteria; of these, 35 patients (7.0%) developed Radiation Proctitis necessitating intervention with APC. Indications for APC treatment were either the need for blood transfusions resulting from Proctitis-related anemia or refractory bleeding despite medical management. Results The median follow-up from the completion of Radiation treatment was 78 months (range, 19-129) and the median follow up from the most recent APC treatment was 56 months (range, 3-112). Fifteen men (42.9%) needed blood transfusions because of Proctitis-related anemia. For 19 patients (54.3%), bleeding was controlled after 1 or 2 treatments. Eventual bleeding control was obtained in 30 patients (85.7%). The median number of sessions per patient was 2 (range, 1-13). Post-APC ulceration was noted in 8 cases (22.9%). Two patients (5.7%) developed colovesicular fistulas, with 1 patient dying from this complication. A short interval between treatments (≤35 days) was associated with an increased risk of ulcer or fistula formation. Conclusions APC is an effective treatment for patients with medically refractive Radiation Proctitis after dose-escalated Radiation therapy, frequently controlling bleeding after only one or two sessions. However, rectal ulceration is a common complication, along with a small risk of life-threatening toxicity.
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endoscopic and non endoscopic approaches for the management of Radiation induced rectal bleeding
World Journal of Gastroenterology, 2016Co-Authors: Joseph Weiner, Manuel Martinez, Ayse Aytaman, Andrew T Wong, David Schwartz, David SchreiberAbstract:Pelvic Radiation is a commonly utilized treatment for malignancy of the genitourinary and lower gastrointestinal tract. Radiation Proctitis and the resultant clinical picture varies from asymptomatic to potentially life threatening. Similarly, treatment options also vary greatly, from medical therapy to surgical intervention. Commonly utilized medical therapy includes sucralfate enemas, antibiotics, 5-aminosalicylic acid derivatives, probiotics, antioxidants, short-chain fatty acids, formalin instillation and fractionated hyperbaric oxygen. More invasive treatments include endoscopic-based, focally ablative interventions such as dilation, heater and bipolar cautery, neodymium/yttrium aluminum garnet argon laser, radiofrequency ablation or argon plasma coagulation. Despite its relatively common frequency, there is a dearth of existing literature reporting head-to-head comparisons of the various treatment options via a randomized controlled approach. The purpose of our review was to present the reader a consolidation of the existing evidence-based literature with the goal of highlighting the comparative effectiveness and risks of the various treatment approaches. Finally, we outline a pragmatic approach to the treatment of Radiation Proctitis. In light of the lack of randomized data, our goal is to pursue as least invasive an approach as possible, with escalation of care tailored to the severity of the patient's symptoms. For those cases that are clinically asymptomatic or only mildly symptomatic, observation or medical management can be considered. Once a patient fails such management or symptoms become more severe, invasive procedures such as endoscopically based focal ablation or surgical intervention can be considered. Although not all recommendations are supported by level I evidence, reported case series and single-institutional studies in the literature suggest that successful treatment with cessation of symptoms can be obtained in the majority of cases.
Joe J. Tjandra - One of the best experts on this subject based on the ideXlab platform.
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argon plasma coagulation in chronic Radiation Proctitis
Endoscopy, 2007Co-Authors: A Postgate, Joe J. Tjandra, Brian P Saunders, John J VargoAbstract:Chronic Radiation Proctitis is a relatively common late complication of pelvic irRadiation. The main symptoms are diarrhea, urgency, tenesmus, and rectal bleeding. While mild cases may settle spontaneously over some months, severe hemorrhagic Radiation Proctitis may require repeated blood transfusions and is difficult to treat with medical therapy. Argon plasma coagulation (APC) is a noncontact thermal coagulation technique which can be applied endoscopically. A probe passed through the scope delivers a field of argon gas to the mucosal surface where it is ionized by a high voltage filament, resulting in superficial mucosal heating and coagulation of friable blood vessels. The technique reduces rectal bleeding in 80%-90% of cases, and may improve the other troublesome symptoms of diarrhea and urgency. APC is probably less effective in very severe cases of hemorrhagic Radiation Proctitis; in these cases topical formalin or a combination of APC and topical formalin can be useful. Overall, APC has proved to be a safe and well tolerated technique.
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Argon plasma coagulation is an effective treatment for refractory hemorrhagic Radiation Proctitis
Diseases of the Colon & Rectum, 2001Co-Authors: Joe J. Tjandra, Shomik SenguptaAbstract:INTRODUCTION: Chronic Radiation Proctitis complicating pelvic radiotherapy can be debilitating. It commonly presents with rectal bleeding, which can be difficult to control. Medical management of hemorrhagic Radiation Proctitis is not very successful, although surgery carries high risks. Thus, endoscopic treatments are preferred. The aim of this study is to assess the efficacy of argon plasma coagulation applied endoscopically to treat hemorrhagic Radiation Proctitis that has been refractory to topical formalin therapy. METHODS: Twelve patients who had ongoing bleeding from Radiation Proctitis, after previously failed formalin therapy, underwent endoscopic treatment using argon plasma coagulation. The efficacy of treatment was assessed by grading the frequency and severity of bleeding (0–4, 0 being no bleeding), hemoglobin level, and transfusion requirements. RESULTS: At a median follow-up of 11 months, ten patients (83 percent) had a significant reduction in the severity and frequency of bleeding, with complete cessation in six (50 percent). The presence of coexistent Radiation-induced sigmoiditis in two patients was associated with reduced but persistent bleeding, because of difficulty in targeting the bleeding sites in the sigmoid colon. The median number of treatment sessions per patient was two (range, 1–3), with the number of sessions correlated with the extent of the Proctitis. All patients had an improvement in their hemoglobin level, with the mean increasing from 11.2 to 12.3 g/dl. In the six months before starting therapy, all patients had been taking iron supplements, and four had required blood transfusions (median 3 units, range, 2–6). Iron supplements were ceased four weeks after the completion of therapy in all cases, and no further transfusions were required during the study period. None of the patients experienced any significant side effects or complications. CONCLUSIONS: Argon plasma coagulation is an effective and safe treatment for hemorrhagic Radiation Proctitis that has been refractory to topical formalin therapy.
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chronic Radiation Proctitis
Anz Journal of Surgery, 2001Co-Authors: Peter Tagkalidis, Joe J. TjandraAbstract:Background: Increasing use of Radiation therapy in pelvic malignancy has led to an increase in the incidence of chronic Radiation Proctitis. The commonest presenting complaint is rectal bleeding. Methods: A comprehensive MEDLINE search was undertaken for all articles relating to Radiation Proctitis. Results: The natural history of the disease is poorly documented but improvement is likely in milder forms, with persistence of symptoms in more severe forms. The pathological manifestations of the disease are summarized with particular comparison to acute Radiation Proctitis. The common clinical presentations and the principles of assessing patients with Radiation-induced Proctitis will be reviewed. The present article also reviews current treatment options, with particular reference to newer endoscopic therapies and surgical principles of management. Conclusions: The initial therapy for problematic rectal bleeding related to Radiation-induced Proctitis shoud be endoscopic therapy with argon plasma coagulation or topical formalin therapy. Surgery is reserved as a last resort for resistant rectal bleeding and for complicated Radiation-induced strictures and fistulas.
