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Konopka-Filippow M, Politynska B, Wojtukiewicz AM, Wojtukiewicz MZ. Cancer Pain: Radiotherapy as a Double-Edged Sword. Int J Mol Sci 2025; 26:5223. [PMID: 40508031 PMCID: PMC12154303 DOI: 10.3390/ijms26115223] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2025] [Revised: 05/23/2025] [Accepted: 05/27/2025] [Indexed: 06/16/2025] Open
Abstract
Cancer pain is a common issue for patients, especially in the advanced stages of cancer, and significantly affects the quality of life (QoL), treatment tolerance, and overall treatment outcomes. Pain may be caused by primary tumors, metastases, or as a consequence of the inflammatory reaction of tissues surrounding the tumor following radiotherapy (RT). Effective pain management is crucial, especially with RT being a key method for alleviating cancer pain, particularly in cases of bone and soft tissue metastases. RT provides relief for 60-80% of patients by reducing tumor size and mitigating associated pain. Radiotherapy itself can also induce pain, especially radiation-induced neuropathic pain, which may require further treatment. Despite these potential side effects, RT remains an essential tool in managing cancer pain, though careful management of its toxicities is necessary to improve patient QoL and survival.
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Affiliation(s)
| | - Barbara Politynska
- Department of Psychology and Philosophy, Medical University of Bialystok,15-420 Bialystok, Poland; (B.P.); (A.M.W.)
- Robinson College, University of Cambridge, Cambridge CB3 9AN, UK
| | - Anna M. Wojtukiewicz
- Department of Psychology and Philosophy, Medical University of Bialystok,15-420 Bialystok, Poland; (B.P.); (A.M.W.)
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Zhao Z, He D, Wang J, Xiao Y, Gong L, Tang C, Peng H, Qiu X, Liu R, Zhang T, Li J. Swertiamarin relieves radiation-induced intestinal injury by limiting DNA damage. Mol Cell Biochem 2025; 480:2277-2290. [PMID: 38795212 DOI: 10.1007/s11010-024-05030-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2023] [Accepted: 05/04/2024] [Indexed: 05/27/2024]
Abstract
Radiotherapy is the conventional treatment for pelvic abdominal tumors. However, it can cause some damage to the small intestine and colorectal, which are very sensitive to radiation. Radiation-induced intestinal injury (RIII) affects the prognosis of radiotherapy, causing sequelae of loss of function and long-term damage to patients' quality of life. Swertiamarin is a glycoside that has been reported to prevent a variety of diseases including but not limited to diabetes, hypertension, atherosclerosis, arthritis, malaria, and abdominal ulcers. However, its therapeutic effect and mechanism of action on RIII have not been established. We investigated whether swertiamarin has a protective effect against RIII. In this article, we use irradiator to create cellular and mouse models of radiation damage. Preventive administration of swertiamarin could reduce ROS and superoxide anion levels to mitigate the cellular damage caused by radiation. Swertiamarin also attenuated RIII in mice, as evidenced by longer survival, less weight loss and more complete intestinal barrier. We also found an increase in the relative abundance of primary bile acids in irradiated mice, which was reduced by both FXR agonists and swertiamarin, and a reduction in downstream interferon and inflammatory factors via the cGAS-STING pathway to reduce radiation-induced damage.
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Affiliation(s)
- Zhe Zhao
- The Second Affiliated Hospital of Chengdu Medical College Nuclear Industry 416 Hospital, Chengdu, China
- School of Laboratory Medicine, Chengdu Medical College, Chengdu, China
| | - Dan He
- The Second Affiliated Hospital of Chengdu Medical College Nuclear Industry 416 Hospital, Chengdu, China
| | - Jinyu Wang
- School of Laboratory Medicine, Chengdu Medical College, Chengdu, China
| | - Yu Xiao
- The Second Affiliated Hospital of Chengdu Medical College Nuclear Industry 416 Hospital, Chengdu, China
| | - Lixin Gong
- The Second Affiliated Hospital of Chengdu Medical College Nuclear Industry 416 Hospital, Chengdu, China
| | - Can Tang
- School of Biological Science and Technology, Chengdu Medical College, Chengdu, China
| | - Haibo Peng
- Department of Oncology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, China
| | - Xuemei Qiu
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Research Unit of Oral Carcinogenesis and Management & Chinese Academy of Medical Sciences, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Rui Liu
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Research Unit of Oral Carcinogenesis and Management & Chinese Academy of Medical Sciences, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
| | - Tao Zhang
- The Second Affiliated Hospital of Chengdu Medical College Nuclear Industry 416 Hospital, Chengdu, China.
- School of Biological Science and Technology, Chengdu Medical College, Chengdu, China.
| | - Jingyi Li
- The Second Affiliated Hospital of Chengdu Medical College Nuclear Industry 416 Hospital, Chengdu, China.
- School of Laboratory Medicine, Chengdu Medical College, Chengdu, China.
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Acharya M, Venkidesh BS, Mumbrekar KD. Bacterial supplementation in mitigation of radiation-induced gastrointestinal damage. Life Sci 2024; 353:122921. [PMID: 39032692 DOI: 10.1016/j.lfs.2024.122921] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2024] [Revised: 07/08/2024] [Accepted: 07/17/2024] [Indexed: 07/23/2024]
Abstract
Pelvic irradiation, a crucial treatment for pelvic malignancies, is associated with the risk of gastrointestinal (GI) damage due to the high proliferation rate of epithelial cells. The radiosensitive gastrointestinal tract acts as a dose-limiting organ. High doses of ionizing radiation can cause inflammation and rupture of mucosal barriers and can also lead to intestinal fibrosis. Intestinal damage can cause acute to chronic complications, reducing patients' quality of life. The gut microbiota plays a vital role in maintaining gut health, and any changes in the gut microbial composition can worsen damage, emphasizing the importance of therapies that target and sustain the gut microbiota during radiotherapy. One potential strategy to prevent radiation-induced GI damage is to use bacterial supplements. Research suggests that probiotic supplementation may alleviate radiation-induced gastrointestinal damage, maintaining intestinal morphology and decreasing epithelial injury in cancer patients. The observed protective effects occur through various mechanisms, including antioxidant activities, modulation of the immune response, and preservation of gut barrier function. To optimize probiotic therapies, it is imperative to elucidate these mechanisms. The efficiency of probiotics as radioprotectors is highly dependent on the time and dose of administration, and their interaction with the host immune system is a key facet of their therapeutic potential. This review explores the potential benefits of bacterial supplementation in mitigating radiation-induced GI damage and the underlying mechanism. This highlights the need for further research to establish standardized protocols and refine probiotic supplementation strategies, underscoring the potential for enhancing therapeutic outcomes in patients undergoing pelvic radiotherapy.
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Affiliation(s)
- Meghana Acharya
- Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal 576104, India
| | - Babu Santhi Venkidesh
- Department of Radiation Biology & Toxicology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal 576104, India
| | - Kamalesh Dattaram Mumbrekar
- Department of Radiation Biology & Toxicology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal 576104, India.
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Hauken MA, Velure GK, Müller B, Sekse RJT. Sexual Health and Quality of Life in Cancer Survivors With Pelvic Radiation Injuries. Cancer Nurs 2024; 47:E298-E307. [PMID: 37449715 DOI: 10.1097/ncc.0000000000001259] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/18/2023]
Abstract
BACKGROUND Little knowledge exists on how late radiation tissue injuries (LRTIs) affect sexual health and health-related quality of life (HRQOL) in pelvic cancer survivors. OBJECTIVE To explore sexual health and HRQOL in cancer survivors with pelvic LRTI. METHOD A descriptive cross-sectional study was conducted, including 83 pelvic cancer survivors with LRTI. Data on sexual health, LTRIs, and HRQOL were collected by validated questionnaires, whereas medical variables were collected from medical records. RESULTS Participants' sexual health was severely impaired. Bowel and urinary LRTIs correlated with most of the symptoms of impaired sexual health (Pearson r = -0.241 to -0.376, P < .05-.01). Men and women reported different sexual challenges related to functional and symptomatic variables but not on the gender-neutral aspects of sexual health. Younger survivors, gynecological cancer survivors, or those who received external and internal radiation or additional chemotherapy reported significantly ( P < .05-.001) higher levels of sexual impairment. Participants' HRQOL was impaired. Several dimensions of sexual health correlated significantly ( P < .05-.001) with the functional dimensions of reduced HRQOL. CONCLUSION Cancer survivors with pelvic LRTIs experience severely impaired sexual health across genders, with negative consequences for their HRQOL. IMPLICATIONS FOR PRACTICE Healthcare professionals should include sexual health as an important part of individual patients' health and HRQOL throughout their treatment trajectory and follow-up, by screening sexual health, implementing measures and interventions to promote sexual health, and supporting survivors' coping and health-promoting strategies.
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Affiliation(s)
- May Aasebø Hauken
- Author Affiliations: Centre for Crisis Psychology, Faculty of Psychology, University of Bergen (Drs Hauken, Velure, and Müller); Hyperbaric Medicine Unit, Department of Occupational Medicine (Drs Velure and Müller), and Department of Obstetrics and Gynaecology (Dr Sekse), Haukeland University Hospital; and Faculty of Health Sciences, VID Specialised University (Dr Sekse), Bergen, Norway
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Ouedraogo S, Grosjean M, Brigaud I, Carneiro K, Luchnikov V, Mathieu N, Garric X, Nottelet B, Anselme K, Pieuchot L, Ponche A. Fabrication and characterization of thin self-rolling film for anti-inflammatory drug delivery. Colloids Surf B Biointerfaces 2024; 241:114039. [PMID: 38879896 DOI: 10.1016/j.colsurfb.2024.114039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2024] [Revised: 06/10/2024] [Accepted: 06/12/2024] [Indexed: 06/18/2024]
Abstract
Thin films have been identified as an alternative approach for targeting sensitive site as drug delivery tool. In this work, the preparation of self-rolling thin films to form tubes for wound healing and easy placement (e.g. in the colon via colonoscopy) have been studied. We explored the use of thin films as a protective dressing combined to local release of an anti-inflammatory in order to improve drug efficacy and limit the side effects of the oral route. Non-cytotoxic poly(ethylene) glycol and poly(lactic acid) photo-crosslinkable star copolymers were used for rapid UV crosslinking of bilayered films loaded with prednisolone. The films, crosslinked under UV lamp without the need of photoinitiator, are optimized and compared in terms of water uptake, swelling ratio, final tube diameter and morphology, anti-inflammatory drug loading and release. Our studies showed the spontaneous rolling of bilayer constructs directly after immersion in water. Tubular geometry allows application of the patch through minimally invasive procedures such as colonoscopy. Moreover, the rolled-up bilayers highlighted efficient release of encapsulated drug following Fickian diffusion mechanism. We also confirmed the anti-inflammatory activity of the released anti-inflammatory drug that inhibits the pro-inflammatory cytokine IL-1β in RAW 264.7 macrophages stimulated by Escherichia coli (E. coli).
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Affiliation(s)
- Sidzigui Ouedraogo
- Institut de Science des Matériaux de Mulhouse, Université de Haute-Alsace, CNRS/UHA UMR 7361, Mulhouse, France
| | - Mathilde Grosjean
- Polymer for Health and Biomaterials, IBMM, Université de Montpellier, CNRS, ENSCM, Montpellier, France
| | - Isabelle Brigaud
- Institut de Science des Matériaux de Mulhouse, Université de Haute-Alsace, CNRS/UHA UMR 7361, Mulhouse, France
| | - Katia Carneiro
- Graduate School in Pathological Anatomy and Morphological Sciences, Federal University of Rio de Janeiro, Brazil
| | - Valeriy Luchnikov
- Institut de Science des Matériaux de Mulhouse, Université de Haute-Alsace, CNRS/UHA UMR 7361, Mulhouse, France
| | - Noëlle Mathieu
- Institute for Radioprotection and Nuclear Safety, (IRSN), PSE-SANTE/SERAMED/LRMed, Fontenay-aux-Roses F-92262, France
| | - Xavier Garric
- Polymer for Health and Biomaterials, IBMM, Université de Montpellier, CNRS, ENSCM, Montpellier, France; Department of Pharmacy, Nîmes University Hospital, Nimes, France
| | - Benjamin Nottelet
- Polymer for Health and Biomaterials, IBMM, Université de Montpellier, CNRS, ENSCM, Montpellier, France; Department of Pharmacy, Nîmes University Hospital, Nimes, France
| | - Karine Anselme
- Institut de Science des Matériaux de Mulhouse, Université de Haute-Alsace, CNRS/UHA UMR 7361, Mulhouse, France
| | - Laurent Pieuchot
- Institut de Science des Matériaux de Mulhouse, Université de Haute-Alsace, CNRS/UHA UMR 7361, Mulhouse, France
| | - Arnaud Ponche
- Institut de Science des Matériaux de Mulhouse, Université de Haute-Alsace, CNRS/UHA UMR 7361, Mulhouse, France.
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Weykamp F, Meixner E, Arians N, Hoegen-Saßmannshausen P, Kim JY, Tawk B, Knoll M, Huber P, König L, Sander A, Mokry T, Meinzer C, Schlemmer HP, Jäkel O, Debus J, Hörner-Rieber J. Daily AI-Based Treatment Adaptation under Weekly Offline MR Guidance in Chemoradiotherapy for Cervical Cancer 1: The AIM-C1 Trial. J Clin Med 2024; 13:957. [PMID: 38398270 PMCID: PMC10889253 DOI: 10.3390/jcm13040957] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2023] [Revised: 01/13/2024] [Accepted: 02/06/2024] [Indexed: 02/25/2024] Open
Abstract
(1) Background: External beam radiotherapy (EBRT) and concurrent chemotherapy, followed by brachytherapy (BT), offer a standard of care for patients with locally advanced cervical carcinoma. Conventionally, large safety margins are required to compensate for organ movement, potentially increasing toxicity. Lately, daily high-quality cone beam CT (CBCT)-guided adaptive radiotherapy, aided by artificial intelligence (AI), became clinically available. Thus, online treatment plans can be adapted to the current position of the tumor and the adjacent organs at risk (OAR), while the patient is lying on the treatment couch. We sought to evaluate the potential of this new technology, including a weekly shuttle-based 3T-MRI scan in various treatment positions for tumor evaluation and for decreasing treatment-related side effects. (2) Methods: This is a prospective one-armed phase-II trial consisting of 40 patients with cervical carcinoma (FIGO IB-IIIC1) with an age ≥ 18 years and a Karnofsky performance score ≥ 70%. EBRT (45-50.4 Gy in 25-28 fractions with 55.0-58.8 Gy simultaneous integrated boosts to lymph node metastases) will be accompanied by weekly shuttle-based MRIs. Concurrent platinum-based chemotherapy will be given, followed by 28 Gy of BT (four fractions). The primary endpoint will be the occurrence of overall early bowel and bladder toxicity CTCAE grade 2 or higher (CTCAE v5.0). Secondary outcomes include clinical feasibility, quality of life, and imaging-based response assessment.
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Affiliation(s)
- Fabian Weykamp
- Department of Radiation Oncology, Heidelberg University Hospital, 69120 Heidelberg, Germany (J.H.-R.)
- Heidelberg Institute of Radiation Oncology (HIRO), 69120 Heidelberg, Germany
- National Center for Tumor Diseases (NCT), 69120 Heidelberg, Germany
- Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
| | - Eva Meixner
- Department of Radiation Oncology, Heidelberg University Hospital, 69120 Heidelberg, Germany (J.H.-R.)
- Heidelberg Institute of Radiation Oncology (HIRO), 69120 Heidelberg, Germany
- National Center for Tumor Diseases (NCT), 69120 Heidelberg, Germany
| | - Nathalie Arians
- Department of Radiation Oncology, Heidelberg University Hospital, 69120 Heidelberg, Germany (J.H.-R.)
- Heidelberg Institute of Radiation Oncology (HIRO), 69120 Heidelberg, Germany
- National Center for Tumor Diseases (NCT), 69120 Heidelberg, Germany
| | - Philipp Hoegen-Saßmannshausen
- Department of Radiation Oncology, Heidelberg University Hospital, 69120 Heidelberg, Germany (J.H.-R.)
- Heidelberg Institute of Radiation Oncology (HIRO), 69120 Heidelberg, Germany
- National Center for Tumor Diseases (NCT), 69120 Heidelberg, Germany
- Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
| | - Ji-Young Kim
- Department of Radiation Oncology, Heidelberg University Hospital, 69120 Heidelberg, Germany (J.H.-R.)
- Heidelberg Institute of Radiation Oncology (HIRO), 69120 Heidelberg, Germany
- National Center for Tumor Diseases (NCT), 69120 Heidelberg, Germany
| | - Bouchra Tawk
- Department of Radiation Oncology, Heidelberg University Hospital, 69120 Heidelberg, Germany (J.H.-R.)
- Heidelberg Institute of Radiation Oncology (HIRO), 69120 Heidelberg, Germany
- National Center for Tumor Diseases (NCT), 69120 Heidelberg, Germany
- Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
- Division of Molecular and Translational Radiation Oncology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
| | - Maximilian Knoll
- Department of Radiation Oncology, Heidelberg University Hospital, 69120 Heidelberg, Germany (J.H.-R.)
- Heidelberg Institute of Radiation Oncology (HIRO), 69120 Heidelberg, Germany
- National Center for Tumor Diseases (NCT), 69120 Heidelberg, Germany
- Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
- Division of Molecular and Translational Radiation Oncology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
| | - Peter Huber
- Clinical Cooperation Unit Molecular Radiation Oncology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
| | - Laila König
- Department of Radiation Oncology, Heidelberg University Hospital, 69120 Heidelberg, Germany (J.H.-R.)
- Heidelberg Institute of Radiation Oncology (HIRO), 69120 Heidelberg, Germany
- National Center for Tumor Diseases (NCT), 69120 Heidelberg, Germany
| | - Anja Sander
- Institute of Medical Biometry, University of Heidelberg, 69120 Heidelberg, Germany
| | - Theresa Mokry
- Department of Radiology, Heidelberg University Hospital, 69120 Heidelberg, Germany
- Department of Radiology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
| | - Clara Meinzer
- Department of Radiology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
| | - Heinz-Peter Schlemmer
- Department of Radiology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
| | - Oliver Jäkel
- Division of Medical Physics in Radiation Oncology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
| | - Jürgen Debus
- Department of Radiation Oncology, Heidelberg University Hospital, 69120 Heidelberg, Germany (J.H.-R.)
- Heidelberg Institute of Radiation Oncology (HIRO), 69120 Heidelberg, Germany
- National Center for Tumor Diseases (NCT), 69120 Heidelberg, Germany
- Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
- Heidelberg Ion-Beam Therapy Center (HIT), Department of Radiation Oncology, Heidelberg University Hospital, 69120 Heidelberg, Germany
- German Cancer Consortium (DKTK), Partner Site, 69120 Heidelberg, Germany
| | - Juliane Hörner-Rieber
- Department of Radiation Oncology, Heidelberg University Hospital, 69120 Heidelberg, Germany (J.H.-R.)
- Heidelberg Institute of Radiation Oncology (HIRO), 69120 Heidelberg, Germany
- National Center for Tumor Diseases (NCT), 69120 Heidelberg, Germany
- Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
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Bull C, Morén AT, Skokic V, Wilderäng U, Malipatlolla D, Alevronta E, Dunberger G, Sjöberg F, Bergmark K, Steineck G. Intra-abdominal Surgery and Intestinal Syndromes After Pelvic Radiation Therapy. Adv Radiat Oncol 2024; 9:101303. [PMID: 38260232 PMCID: PMC10801660 DOI: 10.1016/j.adro.2023.101303] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2023] [Accepted: 06/16/2023] [Indexed: 01/24/2024] Open
Abstract
Purpose To determine the effects of intra-abdominal surgery on the intensities of 5 radiation-induced intestinal syndromes in survivors of pelvic cancer. Methods and Materials The analysis included 623 women born in 1927 or later who had survived cancer. They all had received external radiation therapy toward the pelvic area to treat gynecologic cancers. Information from 344 women who did not undergo irradiation, matched for age and residency, was also included. Main outcome measures after the surgical procedures were the intensity scores for 5 radiation-induced intestinal syndromes: urgency-tenesmus syndrome, fecal-leakage syndrome, excessive mucus discharge, excessive gas discharge, and blood discharge. The scores were based on symptom frequencies obtained from patient-reported outcomes and on factor loadings obtained from a previously reported factor analysis. Follow-up was 2 to 15 years after radiation therapy. Results Among survivors of cancer, intra-abdominal surgery increased the intensity of the urgency-tenesmus syndrome, the fecal-leakage syndrome, excessive gas discharge, and blood discharge but had a negligible effect on mucus discharge. Intra-abdominal surgery had an especially negative effect on the urgency-tenesmus syndrome. Although the combination of appendectomy with 1 or more other intra-abdominal surgeries resulted in the highest score for all syndromes, appendectomy alone had weak to no effect. In women who did not undergo irradiation, a similar pattern was seen, albeit with much lower scores. Conclusions We found intra-abdominal surgery to be a risk factor among survivors of gynecologic cancer, increasing the intensity score of 4 out of 5 radiation-induced intestinal syndromes. During radiation therapy, it may be worthwhile to pay extra attention to the dose of unwanted ionizing radiation to the intestines if the patient previously has undergone intra-abdominal surgery.
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Affiliation(s)
- Cecilia Bull
- Division of Clinical Cancer Epidemiology, Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Sweden
| | - Amelie Toft Morén
- Division of Clinical Cancer Epidemiology, Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Sweden
| | - Viktor Skokic
- Division of Clinical Cancer Epidemiology, Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Sweden
- Division of Clinical Cancer Epidemiology, Department of Oncology and Pathology, Karolinska Institute, Stockholm, Sweden
| | - Ulrica Wilderäng
- Division of Clinical Cancer Epidemiology, Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Sweden
| | - Dilip Malipatlolla
- Division of Clinical Cancer Epidemiology, Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Sweden
| | - Eleftheria Alevronta
- Division of Clinical Cancer Epidemiology, Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Sweden
| | - Gail Dunberger
- Department of Health Care Sciences, Marie Cederschiöld University, Stockholm, Sweden
| | - Fei Sjöberg
- Division of Clinical Cancer Epidemiology, Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Sweden
- Department of Infectious Diseases at the Institute of Biomedicine, Sahlgrenska Academy at the University of Gothenburg, Sweden
| | - Karin Bergmark
- Division of Clinical Cancer Epidemiology, Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Sweden
| | - Gunnar Steineck
- Division of Clinical Cancer Epidemiology, Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Sweden
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Krishnamurthy R, Krishnatry R, Rane D, Pawar P, Chakraborty D, Gaikwad U, Ghosh S, Siddiqui A, Datta D, Anup A, Das S, Gudi S, Engineer R. Translation and Pilot Validation of Hindi, Marathi, and Bangla Translation of Quality-of-Life EORTC Radiation Proctitis Module (PRT-20) for Routine Clinical Use. South Asian J Cancer 2024; 13:27-32. [PMID: 38721106 PMCID: PMC11076072 DOI: 10.1055/s-0043-1771442] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/08/2024] Open
Abstract
Rahul Krishnatry The aim of this study was to translate and validate the European Organization for Research and Treatment for Cancer (EORTC) "Radiation Proctitis" (PRT-20) module in Hindi, Marathi, and Bangla languages. The EORTC PRT-20 was translated into Hindi, Marathi, and Bangla using EORTC guidelines. Two separate translators first translated the original questionnaire into the three regional languages, following which a reconciled forward translation was compiled. This reconciled version in each language was then back-translated into English by two other translators. This back-translated version was then compared with the original the EORTC questionnaire for correctness, and the preliminary questionnaires were formed in all three languages. The EORTC translation unit approved the questionnaires. The preliminary questionnaires were administered to 30 patients (10 for each language) diagnosed with rectal or anal canal cancer who had received pelvic radiotherapy and were at risk of developing PRT. None of the patients had seen the questionnaire before. After filling out the questionnaire, each patient was interviewed for difficulty in answering, confusion, understanding, or if any of the questions were upsetting and if patients would have asked the question differently. No changes were suggested for Marathi and Bangla translations. Two modifications were suggested in the Hindi translation, which was then retested in five patients and finalized. All the suggestions were incorporated into the preliminary questionnaires, which were sent back to the EORTC for final approval. After reviewing the entire report of pilot testing for the translated quality-of-life questionaire-PRT-20 in three languages, it was approved by the EORTC translation unit. The translated questionnaires were reliable, with Cronbach α values of 0.767, 0.799, and 0.898 for Hindi, Marathi, and Bangla, respectively. The Hindi, Marathi, and Bangla translations of PRT-20 have been approved by the EORTC and can be used in routine clinical practice.
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Affiliation(s)
- Revathy Krishnamurthy
- Department of Radiation Oncology, Tata Memorial Centre, Mumbai, Maharashtra, India
- Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Rahul Krishnatry
- Department of Radiation Oncology, Tata Memorial Centre, Mumbai, Maharashtra, India
- Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Devankshi Rane
- Department of Radiation Oncology, Tata Memorial Centre, Mumbai, Maharashtra, India
- Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Purva Pawar
- Department of Radiation Oncology, Tata Memorial Centre, Mumbai, Maharashtra, India
- Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Debanjan Chakraborty
- Department of Radiation Oncology, Tata Memorial Centre, Mumbai, Maharashtra, India
- Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Utpal Gaikwad
- Department of Radiation Oncology, Krupamayi Hospital, Aurangabad, Maharashtra, India
| | - Suman Ghosh
- Department of Radiation Oncology, Tata Memorial Centre, Mumbai, Maharashtra, India
- Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Aasma Siddiqui
- Department of Radiation Oncology, Tata Memorial Centre, Mumbai, Maharashtra, India
- Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Debanjali Datta
- Department of Radiation Oncology, Tata Memorial Centre, Mumbai, Maharashtra, India
- Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Akanksha Anup
- Department of Radiation Oncology, Tata Memorial Centre, Mumbai, Maharashtra, India
- Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Sayan Das
- Department of Radiation Oncology, Medica Superspeciality Hospital, Kolkata, West Bengal, India
| | - Shivakumar Gudi
- Department of Radiation Oncology, Tata Memorial Centre, Mumbai, Maharashtra, India
- Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Reena Engineer
- Department of Radiation Oncology, Tata Memorial Centre, Mumbai, Maharashtra, India
- Homi Bhabha National Institute, Mumbai, Maharashtra, India
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Bouges E, Segers C, Leys N, Lebeer S, Zhang J, Mastroleo F. Human Intestinal Organoids and Microphysiological Systems for Modeling Radiotoxicity and Assessing Radioprotective Agents. Cancers (Basel) 2023; 15:5859. [PMID: 38136404 PMCID: PMC10741417 DOI: 10.3390/cancers15245859] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2023] [Revised: 12/08/2023] [Accepted: 12/13/2023] [Indexed: 12/24/2023] Open
Abstract
Radiotherapy is a commonly employed treatment for colorectal cancer, yet its radiotoxicity-related impact on healthy tissues raises significant health concerns. This highlights the need to use radioprotective agents to mitigate these side effects. This review presents the current landscape of human translational radiobiology, outlining the limitations of existing models and proposing engineering solutions. We delve into radiotherapy principles, encompassing mechanisms of radiation-induced cell death and its influence on normal and cancerous colorectal cells. Furthermore, we explore the engineering aspects of microphysiological systems to represent radiotherapy-induced gastrointestinal toxicity and how to include the gut microbiota to study its role in treatment failure and success. This review ultimately highlights the main challenges and future pathways in translational research for pelvic radiotherapy-induced toxicity. This is achieved by developing a humanized in vitro model that mimics radiotherapy treatment conditions. An in vitro model should provide in-depth analyses of host-gut microbiota interactions and a deeper understanding of the underlying biological mechanisms of radioprotective food supplements. Additionally, it would be of great value if these models could produce high-throughput data using patient-derived samples to address the lack of human representability to complete clinical trials and improve patients' quality of life.
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Affiliation(s)
- Eloïse Bouges
- RadioPharma Research, Nuclear Medical Applications, Belgian Nuclear Research Centre (SCK CEN), Boeretang 200, 2400 Mol, Belgium; (E.B.); (C.S.); (N.L.)
- Department of Bioscience Engineering, University of Antwerp, Groenenborgerlaan 171, 2020 Antwerp, Belgium;
- Swammerdam Institute for Life Sciences, Faculty of Science, University of Amsterdam, Science Park 904, 1098 XH Amsterdam, The Netherlands;
| | - Charlotte Segers
- RadioPharma Research, Nuclear Medical Applications, Belgian Nuclear Research Centre (SCK CEN), Boeretang 200, 2400 Mol, Belgium; (E.B.); (C.S.); (N.L.)
| | - Natalie Leys
- RadioPharma Research, Nuclear Medical Applications, Belgian Nuclear Research Centre (SCK CEN), Boeretang 200, 2400 Mol, Belgium; (E.B.); (C.S.); (N.L.)
| | - Sarah Lebeer
- Department of Bioscience Engineering, University of Antwerp, Groenenborgerlaan 171, 2020 Antwerp, Belgium;
| | - Jianbo Zhang
- Swammerdam Institute for Life Sciences, Faculty of Science, University of Amsterdam, Science Park 904, 1098 XH Amsterdam, The Netherlands;
- Tytgat Institute for Liver and Intestinal Research, Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam UMC, Location Academic Medical Center, 1105 BK Amsterdam, The Netherlands
| | - Felice Mastroleo
- RadioPharma Research, Nuclear Medical Applications, Belgian Nuclear Research Centre (SCK CEN), Boeretang 200, 2400 Mol, Belgium; (E.B.); (C.S.); (N.L.)
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Qin Q, Huang B, Wu A, Gao J, Liu X, Cao W, Ma T, Kuang Y, Guo J, Wu Q, Shao B, Guan Q, Yao H, Zhang X, Wang H. Development and Validation of a Post-Radiotherapy Prediction Model for Bowel Dysfunction After Rectal Cancer Resection. Gastroenterology 2023; 165:1430-1442.e14. [PMID: 37625498 DOI: 10.1053/j.gastro.2023.08.022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Revised: 05/22/2023] [Accepted: 08/13/2023] [Indexed: 08/27/2023]
Abstract
BACKGROUND & AIMS The benefit of radiotherapy for rectal cancer is based largely on a balance between a decrease in local recurrence and an increase in bowel dysfunction. Predicting postoperative disability is helpful for recovery plans and early intervention. We aimed to develop and validate a risk model to improve the prediction of major bowel dysfunction after restorative rectal cancer resection with neoadjuvant radiotherapy using perioperative features. METHODS Eligible patients more than 1 year after restorative resection following radiotherapy were invited to complete the low anterior resection syndrome (LARS) score at 3 national hospitals in China. Clinical characteristics and imaging parameters were assessed with machine learning algorithms. The post-radiotherapy LARS prediction model (PORTLARS) was constructed by means of logistic regression on the basis of key factors with proportional weighs. The accuracy of the model for major LARS prediction was internally and externally validated. RESULTS A total of 868 patients reported a mean LARS score of 28.4 after an average time of 4.7 years since surgery. Key predictors for major LARS included the length of distal rectum, anastomotic leakage, proximal colon of neorectum, and pathologic nodal stage. PORTLARS had a favorable area under the curve for predicting major LARS in the internal dataset (0.835; 95% CI, 0.800-0.870, n = 521) and external dataset (0.884; 95% CI, 0.848-0.921, n = 347). The model achieved both sensitivity and specificity >0.83 in the external validation. In addition, PORTLARS outperformed the preoperative LARS score for prediction of major events. CONCLUSIONS PORTLARS could predict major bowel dysfunction after rectal cancer resection following radiotherapy with high accuracy and robustness. It may serve as a useful tool to identify patients who need additional support for long-term dysfunction in the early stage. CLINICALTRIALS gov, number NCT05129215.
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Affiliation(s)
- Qiyuan Qin
- Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Binjie Huang
- Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Aiwen Wu
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing, China; Key Laboratory of Carcinogenesis and Translational Research, Unit III, Gastrointestinal Cancer Center, Peking University Cancer Hospital and Institute, Beijing, China
| | - Jiale Gao
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, China; National Clinical Research Center for Digestive Diseases, Beijing, China
| | - Xinzhi Liu
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing, China; Key Laboratory of Carcinogenesis and Translational Research, Unit III, Gastrointestinal Cancer Center, Peking University Cancer Hospital and Institute, Beijing, China
| | - Wuteng Cao
- Department of Radiology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Tenghui Ma
- Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yingyi Kuang
- Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Jirui Guo
- Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Qian Wu
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Biyan Shao
- Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Qi Guan
- Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Hongwei Yao
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, China; National Clinical Research Center for Digestive Diseases, Beijing, China.
| | - Xiaoyan Zhang
- Department of Radiology, Peking University Cancer Hospital and Institute, Beijing, China; Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education Beijing, Beijing, China.
| | - Hui Wang
- Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
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11
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Wang C, Zhao M, Xie J, Wang H, Gu Z, Sun F. Colon-Targeted Release of Gel Microspheres Loaded with Antioxidative Fullerenol for Relieving Radiation-Induced Colon Injury and Regulating Intestinal Flora. Adv Healthc Mater 2023; 12:e2301758. [PMID: 37657180 DOI: 10.1002/adhm.202301758] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2023] [Revised: 08/15/2023] [Indexed: 09/03/2023]
Abstract
Radiation-induced colitis is a serious clinical problem worldwide. However, the current treatment options for this condition have limited efficacy and can cause side effects. To address this issue, colon-targeted fullerenol@pectin@chitosan gel microspheres (FPCGMs) are developed, which can aggregate on colon tissue for a long time, scavenge free radicals generated in the process of radiation, and regulate intestinal flora to mitigate damage to colonic tissue. First, FPCGMs exhibit acid resistance and colon-targeted release properties, which reduce gastrointestinal exposure and extend the local colonic drug residence time. Second, fullerenol, which has a superior scavenging ability and chemical stability, reduces oxidative stress in colonic epithelial cells. Based on this, it is found that FPCGMs significantly reduce inflammation in colonic tissue, mitigated damage to tight junctions of colonic epithelial cells, and significantly relieved radiation-induced colitis in mice. Moreover, 16S ribosomal DNA (16S rDNA) sequencing results show that the composition of the intestinal flora is optimized after FPCGMs are utilized, indicating that the relative abundance of probiotics increases while harmful bacteria are inhibited. These findings suggest that it is a promising candidate for treating radiation-induced colitis.
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Affiliation(s)
- Chengyan Wang
- Department of Pharmacy, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, 400038, China
| | - Maoru Zhao
- Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience, Institute of High Energy Physics and National Center for Nanoscience and Technology of China, Chinese Academy of Sciences, Beijing, 100049, China
- Center of Materials Science and Optoelectronics Engineering, College of Materials Science and Optoelectronic Technology, University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Jiani Xie
- School of Food and Biological Engineering, Chengdu University, Chengdu, 610106, China
| | - Hongping Wang
- Department of Pharmacy, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, 400038, China
| | - Zhanjun Gu
- Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience, Institute of High Energy Physics and National Center for Nanoscience and Technology of China, Chinese Academy of Sciences, Beijing, 100049, China
- Center of Materials Science and Optoelectronics Engineering, College of Materials Science and Optoelectronic Technology, University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Fengjun Sun
- Department of Pharmacy, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, 400038, China
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12
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He KY, Lei XY, Wu DH, Zhang L, Li JQ, Li QT, Yin WT, Zhao ZL, Liu H, Xiang XY, Zhu LJ, Cui CY, Wang KK, Wang JH, Lv L, Sun QH, Liu GL, Xu ZX, Jian YP. Akkermansia muciniphila protects the intestine from irradiation-induced injury by secretion of propionic acid. Gut Microbes 2023; 15:2293312. [PMID: 38087436 PMCID: PMC10730217 DOI: 10.1080/19490976.2023.2293312] [Citation(s) in RCA: 40] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2023] [Accepted: 12/06/2023] [Indexed: 12/18/2023] Open
Abstract
Intestinal dysbiosis frequently occurs in abdominal radiotherapy and contributes to irradiation (IR)-induced intestinal damage and inflammation. Akkermansia muciniphila (A. muciniphila) is a recently characterized probiotic, which is critical for maintaining the dynamics of the intestinal mucus layer and preserving intestinal microbiota homeostasis. However, the role of A. muciniphila in the alleviation of radiation enteritis remains unknown. In this study, we reported that the abundance of A. muciniphila was markedly reduced in the intestines of mice exposed to abdominal IR and in the feces of patients who received abdominal radiotherapy. Abundance of A. muciniphila in feces of radiotherapy patients was negatively correlated with the duration of diarrhea in patients. Administration of A. muciniphila substantially mitigated IR-induced intestinal damage and prevented mouse death. Analyzing the metabolic products of A. muciniphila revealed that propionic acid, a short-chain fatty acid secreted by the microbe, mediated the radioprotective effect. We further demonstrated that propionic acid bound to G-protein coupled receptor 43 (GRP43) on the surface of intestinal epithelia and increased histone acetylation and hence enhanced the expression of tight junction proteins occludin and ZO-1 and elevated the level of mucins, leading to enhanced integrity of intestinal epithelial barrier and reduced radiation-induced intestinal damage. Metformin, a first-line agent for the treatment of type II diabetes, promoted intestinal epithelial barrier integrity and reduced radiation intestinal damage through increasing the abundance of A. muciniphila. Together, our results demonstrated that A. muciniphila plays a critical role in the reduction of abdominal IR-induced intestinal damage. Application of probiotics or their regulators, such as metformin, could be an effective treatment for the protection of radiation exposure-damaged intestine.
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Affiliation(s)
- Kai-Yue He
- School of Life Sciences, Henan University, Kaifeng, Henan, China
| | - Xin-Yuan Lei
- School of Life Sciences, Henan University, Kaifeng, Henan, China
| | - Dan-Hui Wu
- School of Life Sciences, Henan University, Kaifeng, Henan, China
| | - Lei Zhang
- School of Life Sciences, Henan University, Kaifeng, Henan, China
| | - Jun-Qi Li
- School of Life Sciences, Henan University, Kaifeng, Henan, China
| | - Qiu-Tong Li
- School of Life Sciences, Henan University, Kaifeng, Henan, China
| | - Wei-Tao Yin
- School of Life Sciences, Henan University, Kaifeng, Henan, China
| | - Zi-Long Zhao
- School of Life Sciences, Henan University, Kaifeng, Henan, China
| | - Huai Liu
- School of Life Sciences, Henan University, Kaifeng, Henan, China
| | - Xiong-Yan Xiang
- School of Life Sciences, Henan University, Kaifeng, Henan, China
| | - Ling-Jun Zhu
- School of Life Sciences, Henan University, Kaifeng, Henan, China
| | - Cui-Yun Cui
- Department of Blood Transfusion, Henan Provincial People’s Hospital, Zhengzhou, Henan, China
| | - Ke-Ke Wang
- Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, and The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Jin-Hua Wang
- Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, and The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Lin Lv
- Department of Medical Oncology, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, China
| | - Qian-Hui Sun
- School of Life Sciences, Henan University, Kaifeng, Henan, China
| | - Guo-Long Liu
- Department of Medical Oncology, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, China
| | - Zhi-Xiang Xu
- School of Life Sciences, Henan University, Kaifeng, Henan, China
| | - Yong-Ping Jian
- School of Life Sciences, Henan University, Kaifeng, Henan, China
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Clavo B, Cánovas-Molina A, Ramallo-Fariña Y, Federico M, Rodríguez-Abreu D, Galván S, Ribeiro I, Marques da Silva SC, Navarro M, González-Beltrán D, Díaz-Garrido JA, Cazorla-Rivero S, Rodríguez-Esparragón F, Serrano-Aguilar P. Effects of Ozone Treatment on Health-Related Quality of Life and Toxicity Induced by Radiotherapy and Chemotherapy in Symptomatic Cancer Survivors. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2023; 20:1479. [PMID: 36674232 PMCID: PMC9859304 DOI: 10.3390/ijerph20021479] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/18/2022] [Revised: 01/05/2023] [Accepted: 01/09/2023] [Indexed: 06/17/2023]
Abstract
(1) Background: The continuous improvement in cancer treatment has led to improvement in patients’ survival and a subsequent increase in the number of cancer survivors living with adverse side effects of cancer treatments, sometimes with a high and adverse impact on their health-related quality of life (HRQOL). Side effects of cancer treatments are frequently associated with chronic status of oxidative stress, inflammation, and/or ischemia. The potential for ozone treatment to modulate those processes and improve some of those adverse effects has previously been described. The aim of this study was to evaluate the effect of ozone treatment on the HRQOL and grade of toxicity in symptomatic cancer survivors. (2) Methods: Before and after ozone treatment, we assessed (i) the HRQOL (according to the EQ-5D-5L questionnaire) and (ii) the grade of toxicity (according to the Common Terminology Criteria for Adverse Events of the National Cancer Institute of EEUU (CTCAE v.5.0)) in 26 cancer survivors with chronic side effects of radiotherapy and chemotherapy. (3) Results: There was a significant (p < 0.001) improvement in the EQ-5D-5L index as per the self-reported outcome evaluation of patients’ health status. All the dimensions of the EQ-5D-5L questionnaire (mobility, self-care, activities, pain/discomfort, and anxiety/depression) and the self-evaluation of the health status using the visual analog scale were significantly improved (p < 0.05). The grade of toxicity was also significantly decreased (p < 0.001). (4) Conclusions: In cancer survivors with chronic side effects of cancer treatment, ozone treatment can improve the grade of toxicity and the HRQOL. These results merit additional research. Further studies are ongoing.
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Affiliation(s)
- Bernardino Clavo
- Research Unit, Hospital Universitario de Gran Canaria Dr. Negrín, 35019 Las Palmas de Gran Canaria, Spain
- Chronic Pain Unit, Dr. Negrín University Hospital, 35019 Las Palmas de Gran Canaria, Spain
- Radiation Oncology Department, Hospital Universitario Dr. Negrín, 35019 Las Palmas de Gran Canaria, Spain
- Fundación Canaria Instituto de Investigación Sanitaria de Canarias (FIISC), 35019 Las Palmas de Gran Canaria, Spain
- Universitary Institute for Research in Biomedicine and Health (iUIBS), Molecular and Translational Pharmacology Group, University of Las Palmas de Gran Canaria, 35016 Las Palmas de Gran Canaria, Spain
- Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias, Universidad de La Laguna, 38296 La Laguna, Spain
- CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, 28029 Madrid, Spain
- Spanish Group of Clinical Research in Radiation Oncology (GICOR), 28290 Madrid, Spain
| | - Angeles Cánovas-Molina
- Research Unit, Hospital Universitario de Gran Canaria Dr. Negrín, 35019 Las Palmas de Gran Canaria, Spain
- Chronic Pain Unit, Dr. Negrín University Hospital, 35019 Las Palmas de Gran Canaria, Spain
- Fundación Canaria Instituto de Investigación Sanitaria de Canarias (FIISC), 35019 Las Palmas de Gran Canaria, Spain
| | - Yolanda Ramallo-Fariña
- Fundación Canaria Instituto de Investigación Sanitaria de Canarias (FIISC), 35019 Las Palmas de Gran Canaria, Spain
- Network for Research on Chronicity, Primary Care, and Health Promotion (RICAPPS), Instituto de Salud Carlos III, 28029 Madrid, Spain
- Servicio de Evaluación y Planificación del Servicio Canario de Salud (SESCS), 38109 Santa Cruz de Tenerife, Spain
- Instituto de Tecnologías Biomédicas (ITB), Universidad de la Laguna, 38296 La Laguna, Spain
| | - Mario Federico
- Radiation Oncology Department, Hospital Universitario Dr. Negrín, 35019 Las Palmas de Gran Canaria, Spain
| | - Delvys Rodríguez-Abreu
- Medical Oncology Department, Complejo Hospitalario Universitario Insular Materno-Infantil de Gran Canaria, 35016 Las Palmas de Gran Canaria, Spain
| | - Saray Galván
- Medical Oncology Department, Hospital Universitario de Gran Canaria Dr. Negrín, 35019 Las Palmas de Gran Canaria, Spain
| | - Ivone Ribeiro
- Radiation Oncology Department, Hospital Universitario Dr. Negrín, 35019 Las Palmas de Gran Canaria, Spain
| | - Susana C. Marques da Silva
- Research Unit, Hospital Universitario de Gran Canaria Dr. Negrín, 35019 Las Palmas de Gran Canaria, Spain
- Chronic Pain Unit, Dr. Negrín University Hospital, 35019 Las Palmas de Gran Canaria, Spain
| | - Minerva Navarro
- Chronic Pain Unit, Dr. Negrín University Hospital, 35019 Las Palmas de Gran Canaria, Spain
| | - Damián González-Beltrán
- Research Unit, Hospital Universitario de Gran Canaria Dr. Negrín, 35019 Las Palmas de Gran Canaria, Spain
| | - Juan A. Díaz-Garrido
- Psychiatry Department, Hospital Universitario de Gran Canaria Dr. Negrín, 35019 Las Palmas de Gran Canaria, Spain
| | - Sara Cazorla-Rivero
- Research Unit, Hospital Universitario de Gran Canaria Dr. Negrín, 35019 Las Palmas de Gran Canaria, Spain
- Universidad de La Laguna, 38296 La Laguna, Spain
| | - Francisco Rodríguez-Esparragón
- Research Unit, Hospital Universitario de Gran Canaria Dr. Negrín, 35019 Las Palmas de Gran Canaria, Spain
- Fundación Canaria Instituto de Investigación Sanitaria de Canarias (FIISC), 35019 Las Palmas de Gran Canaria, Spain
- Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias, Universidad de La Laguna, 38296 La Laguna, Spain
- CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Pedro Serrano-Aguilar
- Network for Research on Chronicity, Primary Care, and Health Promotion (RICAPPS), Instituto de Salud Carlos III, 28029 Madrid, Spain
- Servicio de Evaluación y Planificación del Servicio Canario de Salud (SESCS), 38109 Santa Cruz de Tenerife, Spain
- Instituto de Tecnologías Biomédicas (ITB), Universidad de la Laguna, 38296 La Laguna, Spain
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Decreasing the Adverse Effects in Pelvic Radiation Therapy: A Randomized Controlled Trial Evaluating the Use of Probiotics. Adv Radiat Oncol 2022; 8:101089. [PMID: 36483069 PMCID: PMC9723296 DOI: 10.1016/j.adro.2022.101089] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2022] [Accepted: 09/15/2022] [Indexed: 01/19/2023] Open
Abstract
PURPOSE The aim of this randomized controlled trial was to evaluate the potential benefit from 2 probiotic bacteria of the species Lactiplantibacillus plantarum against radiation therapy-induced comorbidities. METHODS AND MATERIALS Women (>18 years of age) scheduled for radiation therapy because of gynecologic cancer were randomly allocated to consume placebo or either low-dose probiotics (1 × 1010 colony-forming unit/capsule twice daily) or high-dose probiotics (5 × 1010 colony-forming unit/capsule twice daily). The intervention started approximately 1 week before the onset of radiation therapy and continued until 2 weeks after completion. During this period the participants were daily filling in a study diary documenting the incidence and severity of symptoms, intake of concomitant medication, and stool consistency. The primary endpoint was the probiotic effect on the mean number of loose stools during radiation therapy. RESULTS Of the 97 randomized women, 75 provided data for the analysis of the results. The mean number of loose stools (sum of Bristol stool type 6 and 7) was not significantly reduced in the probiotic groups, but there was a significant reduction in the mean number of days with >1 loose stool with 15.04 ± 8.92 days in the placebo and 8.65 ± 5.93 days in the high-dose probiotics group (P = .014). The benefit was even more pronounced in the 2 weeks following the end of radiation therapy (P = .005). Moreover, intake of the probiotics resulted in a reduced severity of the symptoms grinding abdominal pain (P = .041) and defecation urgency (P = .08) and a reduced percentage of days with these symptoms (P = .023 and P = .042, respectively), compared with placebo. There were no differences regarding reported adverse events. CONCLUSIONS Intake of the 2 probiotic bacteria was beneficial and reduced many measures or symptoms of the radiation-induced toxicity in women treated for gynecologic cancer.
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Irradiation Induces Tuft Cell Hyperplasia and Myenteric Neuronal Loss in the Absence of Dietary Fiber in a Mouse Model of Pelvic Radiotherapy. GASTROENTEROLOGY INSIGHTS 2022. [DOI: 10.3390/gastroent13010010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023] Open
Abstract
Pelvic radiotherapy is associated with chronic intestinal dysfunction. Dietary approaches, such as fiber enrichment during and after pelvic radiotherapy, have been suggested to prevent or reduce dysfunctions. In the present paper, we aimed to investigate whether a diet rich in fermentable fiber could have a positive effect on radiation-induced intestinal damage, especially focusing on tuft cells and enteric neurons. Male C57BL/6 mice were fed either a purified non-fiber diet or the same purified diet with 5% or 15% oat fiber added, starting two weeks prior to sham-irradiation or irradiation with four fractions of 8 Gray. The animals continued on the diets for 1, 6 or 18 weeks, after which the gross morphology of the colorectum was assessed together with the numbers of enteric neurons, tuft cells and crypt-surface units. The results showed that dietary fiber significantly affected the intestinal morphometrics, both in the short and long-term. The presence of dietary fiber stimulated the re-emergence of crypt-surface unit structures after irradiation. At 18 weeks, the animals fed with the non-fiber diet displayed more myenteric neurons than the animals fed with the dietary fibers, but irradiation resulted in a loss of neurons in the non-fiber fed animals. Irradiation, but not diet, affected the tuft cell numbers, and a significant increase in tuft cells was found 6 and 18 weeks after irradiation. In conclusion, dietary fiber intake has the potential to modify neuronal pathogenesis in the colorectum after irradiation. The long-lasting increase in tuft cells induced by irradiation may reflect an as yet unknown role in the mucosal pathophysiology after pelvic irradiation.
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Symptom burden, psychological distress, and health-related quality of life in cancer survivors with pelvic late radiation tissue injuries. Support Care Cancer 2021; 30:2477-2486. [PMID: 34779920 PMCID: PMC8794896 DOI: 10.1007/s00520-021-06684-x] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2021] [Accepted: 11/04/2021] [Indexed: 12/03/2022]
Abstract
Purpose Curative radiotherapy for cancer may lead to severe late radiation tissue injuries (LRTIs). However, limited knowledge exists about pelvic cancer survivors’ LRTI symptoms, distress, and health-related quality of life (HRQOL). We sought to assess the symptom burden, distress, and HRQOL in survivors with established pelvic LRTIs compared to norm populations and to investigate the relation between these factors. Methods Cancer survivors referred for treatment of established pelvic LRTIs were recruited nationwide. LTRIs were assessed with the Expanded Prostate Cancer Index Composite (EPIC), psychological distress was assessed with the General Health Questionnaire (GHQ-12), and HRQOL was assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORCT-QLQ-C30). Results A total of 107 participants (mean age 64, 53% men) were included. Compared to norms, participants reported more urinary (mean 68.7 vs. 89.5; p = 0.00; d = 1.4) and bowel symptoms (mean 62.5 vs. 92.4; p = 0.00; d = 2.7), increased psychological distress (mean 13.4 vs. 10.3; p = 0.00; d = 0.6), and overall poorer HRQOL (mean 54.9 vs. 71.2; p = 0.00; d = 0.7). Higher symptom burden and higher levels of psychological distress were associated with lower HRQOL (r2 = 46%), but psychological distress did not moderate the influence of symptoms on HRQOL. Conclusion Cancer survivors with established pelvic LRTIs are highly burdened compared to norms. The association of the LRTI-related symptom burden with HRQOL is independent of the level of psychological distress. Both coping and treatment interventions are crucial to promoting long-term health and HRQOL. Trial registration NCT03570229.
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17
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Moussa L, Lapière A, Squiban C, Demarquay C, Milliat F, Mathieu N. BMP Antagonists Secreted by Mesenchymal Stromal Cells Improve Colonic Organoid Formation: Application for the Treatment of Radiation-induced Injury. Cell Transplant 2021; 29:963689720929683. [PMID: 33108903 PMCID: PMC7784604 DOI: 10.1177/0963689720929683] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Radiation therapy is crucial in the therapeutic arsenal to cure cancers; however, non-neoplastic tissues around an abdominopelvic tumor can be damaged by ionizing radiation. In particular, the radio-induced death of highly proliferative stem/progenitor cells of the colonic mucosa could induce severe ulcers. The importance of sequelae for patients with gastrointestinal complications after radiotherapy and the absence of satisfactory management has opened the field to the testing of innovative treatments. The aim of this study was to use adult epithelial cells from the colon, to reduce colonic injuries in an animal model reproducing radiation damage observed in patients. We demonstrated that transplanted in vitro-amplified epithelial cells from colonic organoids (ECO) of C57/Bl6 mice expressing green fluorescent protein implant, proliferate, and differentiate in irradiated mucosa and reduce ulcer size. To improve the therapeutic benefit of ECO-based treatment with clinical translatability, we performed co-injection of ECO with mesenchymal stromal cells (MSCs), cells involved in niche function and widely used in clinical trials. We observed in vivo an improvement of the therapeutic benefit and in vitro analysis highlighted that co-culture of MSCs with ECO increases the number, proliferation, and size of colonic organoids. We also demonstrated, using gene expression analysis and siRNA inhibition, the involvement of bone morphogenetic protein antagonists in MSC-induced organoid formation. This study provides evidence of the potential of ECO to limit late radiation effects on the colon and opens perspectives on combined strategies to improve their amplification abilities and therapeutic effects.
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Affiliation(s)
- Lara Moussa
- Human Health Department, Institut de Radioprotection et de Sûreté Nucléaire (IRSN), PSE-SANTE, SERAMED, LRMed, Fontenay-aux-Roses, France
| | - Alexia Lapière
- Human Health Department, Institut de Radioprotection et de Sûreté Nucléaire (IRSN), PSE-SANTE, SERAMED, LRMed, Fontenay-aux-Roses, France
| | - Claire Squiban
- Human Health Department, Institut de Radioprotection et de Sûreté Nucléaire (IRSN), PSE-SANTE, SERAMED, LRMed, Fontenay-aux-Roses, France
| | - Christelle Demarquay
- Human Health Department, Institut de Radioprotection et de Sûreté Nucléaire (IRSN), PSE-SANTE, SERAMED, LRMed, Fontenay-aux-Roses, France
| | - Fabien Milliat
- Human Health Department, Institut de Radioprotection et de Sûreté Nucléaire (IRSN), PSE-SANTE, SERAMED, LRMed, Fontenay-aux-Roses, France
| | - Noëlle Mathieu
- Human Health Department, Institut de Radioprotection et de Sûreté Nucléaire (IRSN), PSE-SANTE, SERAMED, LRMed, Fontenay-aux-Roses, France
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18
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Dalsania RM, Shah KP, Stotsky-Himelfarb E, Hoffe S, Willingham FF. Management of Long-Term Toxicity From Pelvic Radiation Therapy. Am Soc Clin Oncol Educ Book 2021; 41:1-11. [PMID: 33793314 DOI: 10.1200/edbk_323525] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Pelvic radiation therapy is an integral component in the treatment of various gastrointestinal, gynecologic, and genitourinary cancers. As survival rates from these malignancies improve, the prevalence of toxicity secondary to pelvic radiation has increased. Gastrointestinal toxicities are the most common complications and greatly impact quality of life. Toxicities can present in acute or late stages; although symptoms may be similar during both, the management may differ. Acute toxicities represent an inflammatory reaction in response to the radiation exposure, whereas late toxicities may arise as a result of small vessel disease, ischemia, and fibrosis. Currently, there are no large clinical trials and only limited guidelines on the management of late gastrointestinal radiation toxicities. Therapy is generally approached in a stepwise manner from medical to endoscopic to surgical methods. Several endoscopic therapies, such as the treatment of radiation proctitis with argon plasma coagulation and dilation of radiation bowel strictures, may prevent the need for surgical intervention, which may be associated with high morbidity and mortality. Given that late toxicities can occur years after radiation therapy, they are often difficult to recognize and diagnose. Successful management of late toxicities requires recognition, an understanding of the underlying pathophysiology, and a multidisciplinary approach. More dedicated research could clarify the prevalence of gastrointestinal pelvic radiation toxicities, permit a better understanding of the efficacy and safety profile of current therapies, and allow for the development of novel therapeutic approaches.
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Affiliation(s)
- Raj M Dalsania
- Division of Digestive Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA
| | - Kevin P Shah
- Department of Internal Medicine, Emory University School of Medicine, Atlanta, GA
| | | | | | - Field F Willingham
- Division of Digestive Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA
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19
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Araujo IK, Muñoz-Guglielmetti D, Mollà M. Radiation-induced damage in the lower gastrointestinal tract: Clinical presentation, diagnostic tests and treatment options. Best Pract Res Clin Gastroenterol 2020; 48-49:101707. [PMID: 33317789 DOI: 10.1016/j.bpg.2020.101707] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2020] [Revised: 10/15/2020] [Accepted: 11/05/2020] [Indexed: 01/31/2023]
Abstract
Radiation therapy is an important ally when treating malignant lesions in the pelvic area, but it is not exempt of adverse events. There are some measures that can be taken to reduce the possibility of these effects, but some are non-modifiable factors related to previous treatments, location of the lesions or comorbidities. There is a wide variety of clinical presentations that can be of an acute or chronic onset that go from mild to severe forms or that can have a great impact in the quality of life. Medical available therapies as metronidazole, sucralfate, mesalizine or probiotics, can be of aid although some lack of solid evidence of efficacy. Endoscopic treatment can be performed with argon plasma coagulation, bipolar cautery, radiofrequency, laser therapy or dilation. Hyperbaric therapy can be applied in refractory cases and surgery must be reserved to selected patients due to its high morbidity and mortality.
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Affiliation(s)
- Isis K Araujo
- Endoscopy and Motility Unit, Gastroenterology Department, Hospital Clínic de Barcelona, Barcelona, Spain.
| | | | - Meritxell Mollà
- Radiation Oncology Department, Hospital Clínic de Barcelona, Barcelona, Spain.
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20
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Lapiere A, Geiger M, Robert V, Demarquay C, Auger S, Chadi S, Benadjaoud M, Fernandes G, Milliat F, Langella P, Benderitter M, Chatel JM, Sémont A. Prophylactic Faecalibacterium prausnitzii treatment prevents the acute breakdown of colonic epithelial barrier in a preclinical model of pelvic radiation disease. Gut Microbes 2020; 12:1-15. [PMID: 32985332 PMCID: PMC7524396 DOI: 10.1080/19490976.2020.1812867] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023] Open
Abstract
Every year, millions of people around the world benefit from radiation therapy to treat cancers localized in the pelvic area. Damage to healthy tissue in the radiation field can cause undesirable toxic effects leading to gastrointestinal complications called pelvic radiation disease. A change in the composition and/or function of the microbiota could contribute to radiation-induced gastrointestinal toxicity. In this study, we tested the prophylactic effect of a new generation of probiotic like Faecalibacterium prausnitzii (F. prausnitzii) on acute radiation-induced colonic lesions. Experiments were carried out in a preclinical model of pelvic radiation disease. Rats were locally irradiated at 29 Gray in the colon resulting in colonic epithelial barrier rupture. Three days before the irradiation and up to 3 d after the irradiation, the F. prausnitzii A2-165 strain was administered daily (intragastrically) to test its putative protective effects. Results showed that prophylactic F. prausnitzii treatment limits radiation-induced para-cellular hyperpermeability, as well as the infiltration of neutrophils (MPO+ cells) in the colonic mucosa. Moreover, F. prausnitzii treatment reduced the severity of the morphological change of crypts, but also preserved the pool of Sox-9+ stem/progenitor cells, the proliferating epithelial PCNA+ crypt cells and the Dclk1+/IL-25+ differentiated epithelial tuft cells. The benefit of F. prausnitzii was associated with increased production of IL-18 by colonic crypt epithelial cells. Thus, F. prausnitzii treatment protected the epithelial colonic barrier from colorectal irradiation. New-generation probiotics may be promising prophylactic treatments to reduce acute side effects in patients treated with radiation therapy and may improve their quality of life.
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Affiliation(s)
- Alexia Lapiere
- Department of RAdiobiology and Regenerative MEDicine (SERAMED), Laboratory of MEDical Radiobiology (Lrmed), Institute for Radiological Protection and Nuclear Safety (IRSN), Fontenay-aux-Roses, France
| | - Mallia Geiger
- Department of RAdiobiology and Regenerative MEDicine (SERAMED), Laboratory of MEDical Radiobiology (Lrmed), Institute for Radiological Protection and Nuclear Safety (IRSN), Fontenay-aux-Roses, France
| | - Véronique Robert
- INRAE, AgroParisTech, Micalis Institute, Paris-Saclay University, Jouy-en-Josas, France
| | - Christelle Demarquay
- Department of RAdiobiology and Regenerative MEDicine (SERAMED), Laboratory of MEDical Radiobiology (Lrmed), Institute for Radiological Protection and Nuclear Safety (IRSN), Fontenay-aux-Roses, France
| | - Sandrine Auger
- INRAE, AgroParisTech, Micalis Institute, Paris-Saclay University, Jouy-en-Josas, France
| | - Sead Chadi
- INRAE, AgroParisTech, Micalis Institute, Paris-Saclay University, Jouy-en-Josas, France
| | - Mohamedamine Benadjaoud
- Department of RAdiobiology and Regenerative MEDicine (SERAMED), Institute for Radiological Protection and Nuclear Safety (IRSN), Fontenay-aux-Roses, France
| | - Gabriel Fernandes
- René Rachou Institute, Oswaldo Cruz Foundation, Belo Horizonte, MG, Brazil
| | - Fabien Milliat
- Department of RAdiobiology and Regenerative MEDicine (SERAMED), Laboratory of MEDical Radiobiology (Lrmed), Institute for Radiological Protection and Nuclear Safety (IRSN), Fontenay-aux-Roses, France
| | - Philippe Langella
- INRAE, AgroParisTech, Micalis Institute, Paris-Saclay University, Jouy-en-Josas, France
| | - Marc Benderitter
- Department of RAdiobiology and Regenerative MEDicine (SERAMED), Institute for Radiological Protection and Nuclear Safety (IRSN), Fontenay-aux-Roses, France
| | - Jean-Marc Chatel
- INRAE, AgroParisTech, Micalis Institute, Paris-Saclay University, Jouy-en-Josas, France
| | - Alexandra Sémont
- Department of RAdiobiology and Regenerative MEDicine (SERAMED), Laboratory of MEDical Radiobiology (Lrmed), Institute for Radiological Protection and Nuclear Safety (IRSN), Fontenay-aux-Roses, France,CONTACT : Alexandra Sémont, Department of RAdiobiology and Regenerative MEDicine (SERAMED), Laboratory of MEDical Radiobiology (Lrmed), Institute for Radiological Protection and Nuclear Safety (IRSN), Fontenay-aux-Roses92260, France
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21
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Li Y, Yan H, Zhang Y, Li Q, Yu L, Li Q, Liu C, Xie Y, Chen K, Ye F, Wang K, Chen L, Ding Y. Alterations of the Gut Microbiome Composition and Lipid Metabolic Profile in Radiation Enteritis. Front Cell Infect Microbiol 2020; 10:541178. [PMID: 33194790 PMCID: PMC7609817 DOI: 10.3389/fcimb.2020.541178] [Citation(s) in RCA: 54] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Accepted: 09/28/2020] [Indexed: 12/26/2022] Open
Abstract
Radiation enteritis (RE) is a common complication in cancer patients receiving radiotherapy. Although studies have shown the changes of this disease at clinical, pathological and other levels, the dynamic characteristics of local microbiome and metabolomics are hitherto unknown. We aimed to examine the multi-omics features of the gut microecosystem, determining the functional correlation between microbiome and lipid metabolites during RE activity. By delivering single high-dose irradiation, a RE mouse model was established. High-throughput 16S rDNA sequencing and global lipidomics analysis were performed to examine microbial and lipidomic profile changes in the gut microecosystem. Spearman correlation analysis was used to determine the functional correlation between bacteria and metabolites. Clinical samples were collected to validate the above observations. During RE activity, the intestinal inflammation of the mice was confirmed by typical signs, symptoms, imaging findings and pathological evidences. 16S datasets revealed that localized irradiation dramatically altered the gut microbial composition, resulting in a decrease ratio of Bacteroidetes to Firmicutes. Lipidomics analysis indicated the remarkable lipidomic profile changes in enteric epithelial barrier, determining that glycerophospholipids metabolism was correlated to RE progression with the highest relevance. Spearman correlation analysis identified that five bacteria-metabolite pairs showed the most significant functional correlation in RE, including Alistipes-PC(36:0e), Bacteroides-DG(18:0/20:4), Dubosiella-PC(35:2), Eggerthellaceae-PC(35:6), and Escherichia-Shigella-TG(18:2/18:2/20:4). These observations were partly confirmed in human specimens. Our study provided a comprehensive description of microbiota dysbiosis and lipid metabolic disorders in RE, suggesting strategies to change local microecosystem to relieve radiation injury and maintain homeostasis.
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Affiliation(s)
- Yiyi Li
- Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Hongmei Yan
- Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China.,Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China
| | - Yaowei Zhang
- Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Qingping Li
- Division of Hepatobiliopancreatic Surgery, Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Lu Yu
- Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Qianyu Li
- Medical Imaging Specialty, The First School of Clinical Medicine, Southern Medical University, Guangzhou, China
| | - Cuiting Liu
- Central Laboratory, Southern Medical University, Guangzhou, China
| | - Yuwen Xie
- Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China.,Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Keli Chen
- HuiQiao Medical Center, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Feng Ye
- Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Kai Wang
- Division of Hepatobiliopancreatic Surgery, Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Longhua Chen
- Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Yi Ding
- Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China
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22
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Yuan JH, Song LM, Liu Y, Li MW, Lin Q, Wang R, Zhang CS, Dong J. The Effects of Hyperbaric Oxygen Therapy on Pelvic Radiation Induced Gastrointestinal Complications (Rectal Bleeding, Diarrhea, and Pain): A Meta-Analysis. Front Oncol 2020; 10:390. [PMID: 32328454 PMCID: PMC7160697 DOI: 10.3389/fonc.2020.00390] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2019] [Accepted: 03/04/2020] [Indexed: 12/21/2022] Open
Abstract
Background: Radiotherapy is a routine treatment for pelvic cancer patients. While it had been proven effective, gastrointestinal side effects remain a concern, impairing the quality of life. A few studies focused on the effects of hyperbaric oxygen (HBO) treatment to alleviate radiation-induced gastrointestinal complications. This meta-analysis aimed to critically review and summarize existing literature, assessing the effectiveness of HBO therapy for the treatment of radiation-induced gastrointestinal side effects. Methods: Medical literature search was performed with PubMed, Cochrane Library, and EMBASE up to March 14, 2019. Literatures about HBO treatment upon patients undergoing pelvic cancer (endometrial, cervix, rectum, or prostate cancers) radiotherapy were collected, and the effects of HBO treatment on radiotherapy-induced gastrointestinal complications were evaluated. A random-effects model was used to calculate the pooled effect size. Subgroup analyses were performed to search for sources of heterogeneity. Publication bias was detected with Funnel plots and Egger's test. Results: Three different radiotherapy-related gastrointestinal complications, including rectal bleeding, diarrhea, and pain, were analyzed after screening. It was revealed that the improvement rates were considerable in rectal bleeding (0.81, 95% CI: 0.74-0.89) and diarrhea (0.75, 95% CI: 0.61-0.90) and slightly in pain (0.58, 95% CI: 0.38-0.79). Subgroup analysis revealed factors that significantly influenced the heterogeneity of rectal bleeding, diarrhea, and pain (evaluation criteria, follow-up time, and scoring system, respectively). No significant publication bias was detected. Conclusion: HBO treatment might have the potential to alleviate radiotherapy-related gastrointestinal complications, including rectal bleeding, diarrhea, and pain, but more data are needed for further conclusions. Other symptoms were not further analyzed, as the number of studies was insufficient. More large-scale and prospective studies are needed for better evaluation of HBO's therapeutic values.
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Affiliation(s)
- Jun-hua Yuan
- Department of Special Medicine, School of Basic Medicine, Qingdao University, Qingdao, China
| | - Li-min Song
- Department of Special Medicine, School of Basic Medicine, Qingdao University, Qingdao, China
| | - Yuan Liu
- Department of Special Medicine, School of Basic Medicine, Qingdao University, Qingdao, China
| | - Man-wen Li
- Department of Special Medicine, School of Basic Medicine, Qingdao University, Qingdao, China
| | - Qian Lin
- Department of Special Medicine, School of Basic Medicine, Qingdao University, Qingdao, China
| | - Rui Wang
- Department of Special Medicine, School of Basic Medicine, Qingdao University, Qingdao, China
| | - Cai-shun Zhang
- Department of Special Medicine, School of Basic Medicine, Qingdao University, Qingdao, China
| | - Jing Dong
- Department of Special Medicine, School of Basic Medicine, Qingdao University, Qingdao, China
- Department of Physiology, School of Basic Medicine, Qingdao University, Qingdao, China
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23
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Muschel RJ, Hammond EM, Dewhirst MW. A New Assay to Measure Intestinal Crypt Survival after Irradiation: Challenges and Opportunities. Cancer Res 2020; 80:927-928. [PMID: 32122905 DOI: 10.1158/0008-5472.can-19-4045] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2020] [Accepted: 01/02/2020] [Indexed: 11/16/2022]
Abstract
Radiotherapy is a critical component of many current, curative cancer treatments, yet it is accompanied by unavoidable irradiation of normal tissues. Abdominal and pelvic radiation almost always results in some dose delivered to the bowel with deleterious effects to the small and large intestines. While the likelihood of enteritis is dose dependent, there is also considerable variation between patients in both the extent of symptoms of enteritis as well as their duration. In this article, Martin and colleagues hypothesized that the radiation sensitivity of intestinal organoids could predict the sensitivity of individual patients to enteritis and have taken the first steps to develop such an assay.See related article by Martin et al., p. 1219.
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Affiliation(s)
- Ruth J Muschel
- Oxford Institute for Radiation Oncology, University of Oxford, Oxford, United Kingdom.
| | - Ester M Hammond
- Oxford Institute for Radiation Oncology, University of Oxford, Oxford, United Kingdom
| | - Mark W Dewhirst
- Department of Radiation Oncology, Duke University, Durham, North Carolina
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24
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Shankar A, Patil J, Luther A, Mandrelle K, Chakraborty A, Dubey A, Saini D, Bharat RP, Abrol D, Bharti SJ, Bentrad V. Sexual Dysfunction in Carcinoma Cervix: Assessment in Post Treated Cases by LENTSOMA Scale. Asian Pac J Cancer Prev 2020; 21:349-354. [PMID: 32102510 PMCID: PMC7332127 DOI: 10.31557/apjcp.2020.21.2.349] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2019] [Indexed: 11/25/2022] Open
Abstract
Treatment for cervical cancer consists of hysterectomy, radiotherapy, chemotherapy and targeted therapy in different combination based on stage at presentation. However, late consequences of such radical treatments are known but not many Indian studies have reported it. Quality of life and impact on sexual health has become an important issue in view of long survival of cervical cancer patients. LENTSOMA scale is one such scale validated for scoring radiotherapy related morbidity. However, there is need for a comprehensive scale covering all aspects of physical and psychological disruptions to provide complete recovery and rehabilitation. The study was prospective and patients who were treated for cervical cancer on follow up were included in this study. A total of 85 patients, who were treated with surgery, radiotherapy, chemotherapy alone or in combination, comprising of stage I to stage IV disease, participated in this study. Findings of this study showed that pain during intercourse and altered sexual life were reported by 32.9% and 25.9% patients respectively whereas 24.7% found it problematic and in 22.3% patients, alteration in interest in sex were reported. Vaginal stenosis was seen in 75.29% of patients after treatment with decreased frequency of intercourse after treatment was seen in 16.4 % of patients. Combination of surgery and radiotherapy in cervical cancer patients caused more sexual dysfunction and dissatisfaction, especially in lower age group. Treatment morbidity in term of sexual function was more with advanced stage disease and with the patients on longer follow up. Sexual function is an important aspect of quality of life but there is no single self-report measure in routine clinical follow up use which is brief, easy to complete and incorporates all (physical, psychological, emotional) aspects of sexual health for people affected by cancer.
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Affiliation(s)
- Abhishek Shankar
- Preventive Oncology, Dr BR Ambedkar Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, Delhi, India
| | - Jaineet Patil
- Radiation Oncology, Christian Medical College, Ludhiana, India
| | - Anil Luther
- General Surgery, Christian Medical College, Ludhiana, India
| | - Kavita Mandrelle
- Obstetrics & Gynecology, Christian Medical College, Ludhiana, India
| | | | - Anusha Dubey
- Indian Society of Clinical Oncology, Delhi, India
| | - Deepak Saini
- Indian Society of Clinical Oncology, Delhi, India
| | - Ram Pukar Bharat
- Radiation Oncology, Dr BR Ambedkar Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, Delhi, India
| | - Deepak Abrol
- Radiation Oncology, Government Medical College, Kathua, JK, India
| | - Sachidanand Jee Bharti
- Oncoanaesthesia and Palliative Medicine, Dr BR Ambedkar Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, Delhi, India
| | - Veronika Bentrad
- Department of Tumour Biochemistry & Oncopharmacology, RE Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NASU, Kiev, Ukraine
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25
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Cheng YK, Qin QY, Huang XY, Lan P, Wang L, Gao X, Ma TH. Effect of interval between preoperative radiotherapy and surgery on clinical outcome and radiation proctitis in rectal cancer from FOWARC trial. Cancer Med 2019; 9:912-919. [PMID: 31828956 PMCID: PMC6997091 DOI: 10.1002/cam4.2755] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2019] [Revised: 10/24/2019] [Accepted: 10/28/2019] [Indexed: 12/20/2022] Open
Abstract
Objective The aim of this study was to evaluate the effect of the interval between CRT and surgery on radiation proctitis, the pathologic response, and postoperative morbidity. Methods This was a cohort study from a phase III, randomized controlled trial (FOWARC study, NCT01211210). Data were retrieved from the leading center of the trial. Patients were divided into the short‐interval (≤7 weeks) group and the long‐interval (>7 weeks) group. The rate of radiation proctitis, pathologic complete regression (pCR) and morbidities were calculated for each group. Multivariate analysis was used to verify the impact of interval on radiation proctitis. Results Surgery was performed in 60 patients after an interval of ≤7 weeks and in 97 patients after an interval of >7 weeks. The two groups according to interval were comparable in terms of baseline demographic and clinicotherapeutic characteristics. Radiation proctitis was identified by imaging in 9 (15.0%) patients in short‐interval group and in 31 (32.0%) patients in long‐interval group (P = .018). Multivariate analysis confirmed the correlation between long interval and radiation proctitis (P = .018). The long interval was significantly associated with longer median operation time compared to the short interval (P = .022). The rates of pCR and postoperative complications were not different between two groups. Conclusions A longer interval after CRT may be associated with higher rate of radiation proctitis and longer operation time. Moreover it did not increase the rate of pCR.
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Affiliation(s)
- Yi-Kan Cheng
- Department of Radiation Oncology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Qi-Yuan Qin
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China.,Guangdong Institute of Gastroenterology, Guangzhou, People's Republic of China.,Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China
| | - Xiao-Yan Huang
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China.,Guangdong Institute of Gastroenterology, Guangzhou, People's Republic of China.,Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China
| | - Ping Lan
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China.,Guangdong Institute of Gastroenterology, Guangzhou, People's Republic of China.,Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China
| | - Lei Wang
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China.,Guangdong Institute of Gastroenterology, Guangzhou, People's Republic of China.,Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China
| | - Xiang Gao
- Department of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China
| | - Teng-Hui Ma
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China.,Guangdong Institute of Gastroenterology, Guangzhou, People's Republic of China.,Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China
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26
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Lu L, Li W, Sun C, Kang S, Li J, Luo X, Su Q, Liu B, Qin S. Phycocyanin Ameliorates Radiation-Induced Acute Intestinal Toxicity by Regulating the Effect of the Gut Microbiota on the TLR4/Myd88/NF-κB Pathway. JPEN J Parenter Enteral Nutr 2019; 44:1308-1317. [PMID: 31769063 DOI: 10.1002/jpen.1744] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2019] [Accepted: 10/25/2019] [Indexed: 12/17/2022]
Abstract
BACKGROUND Radiation-induced gastrointestinal syndrome, including nausea, diarrhea, and dehydration, contributes to morbidity and mortality after medical or industrial radiation exposure, which seriously affects patient quality of life after treatment. No safe and effective radiation countermeasure has been approved for clinical therapy. In this study, we aimed to investigate the potential protective effects of phycocyanin (PC) against radiation-induced acute intestinal injury. MATERIALS AND METHODS C57BL/6 mice were orally administered 50 mg/kg PC once per day for 1 month before exposure to total-abdominal x-ray irradiation at a single dose of 12 Gy. The effects of PC on intestinal histopathology and integrity, gut microbiota, lipopolysaccharides (LPS), inflammatory cytokines, and Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (Myd88)/nuclear factor κB (NF-κB) signaling were evaluated. RESULTS Severe histopathological damage, such as intestinal mucosal epithelial cell apoptosis, necrosis, and nuclear rupture, was most clearly observed 24 hours after total-abdominal x-ray irradiation. Intestinal integrity was damaged by irradiation, which manifested in reduced levels of the tight-junction proteins Claudin-1, Occludin, and zonula occludens-1(ZO-1). PC pretreatment significantly ameliorated radiation-induced intestinal injury. PC also modulated the gut microbiota composition, increasing the proportion of beneficial bacteria and decreasing that of harmful bacteria, which in turn lowered LPS levels and suppressed TLR4/Myd88/NF-κB pathway activation. Finally, levels of corresponding inflammatory cytokines, including tumor necrosis factor α and interleukin-6, were also downregulated. CONCLUSION PC protects against mouse intestinal injury from high-dose radiation by regulating the effect of the gut microbiota on the TLR4/Myd88/NF-κB pathway, suggesting PC as a promising natural radiation countermeasure.
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Affiliation(s)
- Lina Lu
- School of Nuclear Science and Technology, Lanzhou University, Lanzhou, Gansu, China.,School of Chemical Engineering, Northwest Minzu University, Lanzhou, Gansu, China
| | - Wenjun Li
- Key Laboratory of Biology and Bioresource Utilization, Yantai Institute of Costal Zone Research, Chinese Academy of Sciences, Yantai, China.,Center for Ocean Mega-Science, Chinese Academy of Sciences, Qingdao, China
| | - Chao Sun
- Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, China
| | - Shuhe Kang
- Key Laboratory of Biology and Bioresource Utilization, Yantai Institute of Costal Zone Research, Chinese Academy of Sciences, Yantai, China
| | - Jia Li
- Key Laboratory of Biology and Bioresource Utilization, Yantai Institute of Costal Zone Research, Chinese Academy of Sciences, Yantai, China
| | - Xingping Luo
- Key Laboratory of Biology and Bioresource Utilization, Yantai Institute of Costal Zone Research, Chinese Academy of Sciences, Yantai, China
| | - Qiong Su
- Key Laboratory of Biology and Bioresource Utilization, Yantai Institute of Costal Zone Research, Chinese Academy of Sciences, Yantai, China
| | - Bin Liu
- School of Nuclear Science and Technology, Lanzhou University, Lanzhou, Gansu, China.,School of Stomatology, Lanzhou University, Lanzhou, Gansu, China
| | - Song Qin
- School of Chemical Engineering, Northwest Minzu University, Lanzhou, Gansu, China.,Center for Ocean Mega-Science, Chinese Academy of Sciences, Qingdao, China
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27
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Malipatlolla DK, Patel P, Sjöberg F, Devarakonda S, Kalm M, Angenete E, Lindskog EB, Grandér R, Persson L, Stringer A, Wilderäng U, Swanpalmer J, Kuhn HG, Steineck G, Bull C. Long-term mucosal injury and repair in a murine model of pelvic radiotherapy. Sci Rep 2019; 9:13803. [PMID: 31551503 PMCID: PMC6760522 DOI: 10.1038/s41598-019-50023-4] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2019] [Accepted: 09/04/2019] [Indexed: 01/02/2023] Open
Abstract
Chronic intestinal injury after pelvic radiotherapy affects countless cancer survivors worldwide. A comprehensive understanding of the long-term injury dynamics is prevented in available animal models. With linear accelerators that are used to treat cancer in patients, we irradiated a small volume encompassing the colorectum in mice with four fractions of 8 Gy per fraction. We then determined the long-term dynamics of mucosal injury, repair, and the duration of inflammation. We show that crypt fission, not cell proliferation, is the main long-term mechanism for rescuing crypt density after irradiation, and provides a potentially wide window for clinical interventions. Persisting macrophage aggregations indicate a chronic mucosal inflammation. A better understanding as to how crypt fission is triggered and why it fails to repair fully the mucosa may help restore bowel health after pelvic radiotherapy. Moreover, anti-inflammatory interventions, even if implemented long after completed radiotherapy, could promote bowel health in pelvic cancer survivors.
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Affiliation(s)
- Dilip K Malipatlolla
- The Division of Clinical Cancer Epidemiology, Department of Oncology at the Institute of Clinical Sciences, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
| | - Piyush Patel
- The Division of Clinical Cancer Epidemiology, Department of Oncology at the Institute of Clinical Sciences, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.,Department of Infectious Diseases at the Institute of Biomedicine, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
| | - Fei Sjöberg
- The Division of Clinical Cancer Epidemiology, Department of Oncology at the Institute of Clinical Sciences, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.,Department of Infectious Diseases at the Institute of Biomedicine, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
| | - Sravani Devarakonda
- The Division of Clinical Cancer Epidemiology, Department of Oncology at the Institute of Clinical Sciences, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
| | - Marie Kalm
- Department of Pharmacology at the Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
| | - Eva Angenete
- The Department of Surgery at the Institute of Clinical Sciences, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
| | - Elinor Bexe Lindskog
- The Department of Surgery at the Institute of Clinical Sciences, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
| | - Rita Grandér
- The Division of Clinical Cancer Epidemiology, Department of Oncology at the Institute of Clinical Sciences, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
| | - Linda Persson
- The Division of Clinical Cancer Epidemiology, Department of Oncology at the Institute of Clinical Sciences, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
| | - Andrea Stringer
- School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, Australia
| | - Ulrica Wilderäng
- The Division of Clinical Cancer Epidemiology, Department of Oncology at the Institute of Clinical Sciences, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
| | - John Swanpalmer
- Department of Radiation Physics at the Institute of Clinical Sciences, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
| | - Hans Georg Kuhn
- Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
| | - Gunnar Steineck
- The Division of Clinical Cancer Epidemiology, Department of Oncology at the Institute of Clinical Sciences, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
| | - Cecilia Bull
- The Division of Clinical Cancer Epidemiology, Department of Oncology at the Institute of Clinical Sciences, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
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28
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Food Supplements to Mitigate Detrimental Effects of Pelvic Radiotherapy. Microorganisms 2019; 7:microorganisms7040097. [PMID: 30987157 PMCID: PMC6518429 DOI: 10.3390/microorganisms7040097] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2019] [Revised: 03/21/2019] [Accepted: 03/28/2019] [Indexed: 12/12/2022] Open
Abstract
Pelvic radiotherapy has been frequently reported to cause acute and late onset gastrointestinal (GI) toxicities associated with significant morbidity and mortality. Although the underlying mechanisms of pelvic radiation-induced GI toxicity are poorly understood, they are known to involve a complex interplay between all cell types comprising the intestinal wall. Furthermore, increasing evidence states that the human gut microbiome plays a role in the development of radiation-induced health damaging effects. Gut microbial dysbiosis leads to diarrhea and fatigue in half of the patients. As a result, reinforcement of the microbiome has become a hot topic in various medical disciplines. To counteract GI radiotoxicities, apart from traditional pharmacological compounds, adjuvant therapies are being developed including food supplements like vitamins, prebiotics, and probiotics. Despite the easy, cheap, safe, and feasible approach to protect patients against acute radiation-induced toxicity, clinical trials have yielded contradictory results. In this review, a detailed overview is given of the various clinical, intestinal manifestations after pelvic irradiation as well as the role of the gut microbiome herein. Furthermore, whilst discussing possible strategies to prevent these symptoms, food supplements are presented as auspicious, prophylactic, and therapeutic options to mitigate acute pelvic radiation-induced GI injury by exploring their molecular mechanisms of action.
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29
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Sung J, Sodhi CP, Voltaggio L, Hou X, Jia H, Zhou Q, Čiháková D, Hackam DJ. The recruitment of extra-intestinal cells to the injured mucosa promotes healing in radiation enteritis and chemical colitis in a mouse parabiosis model. Mucosal Immunol 2019; 12:503-517. [PMID: 30617302 PMCID: PMC6445662 DOI: 10.1038/s41385-018-0123-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2018] [Revised: 11/05/2018] [Accepted: 11/20/2018] [Indexed: 02/04/2023]
Abstract
Mucosal healing occurs through migration and proliferation of cells within injured epithelium, yet these processes may be inadequate for mucosal healing after significant injury where the mucosa is denuded. We hypothesize that extra-intestinal cells can contribute to mucosal healing after injury to the small and large intestine. We generated parabiotic pairs between wild-type and tdTomato mice, which were then subjected to radiation-induced enteritis and 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis. We now show that as compared with singleton mice, mice with a parabiotic partner were protected against intestinal damage as revealed by significantly reduced weight loss, reduced expression of pro-inflammatory cytokines, reduced enterocyte apoptosis, and improved crypt proliferation. Donor cells expressed CD45-, Sca-1+, c-kit+, and CXCR4+ and accumulated around the injured crypts but did not transdifferentiate into epithelia, suggesting that extra-intestinal cells play a paracrine role in the healing response, while parabiotic pairings with Rag1-/- mice showed improved healing, indicating that adaptive immune cells were dispensable for mucosal healing. Strikingly, ablation of the bone marrow of the donor parabionts removed the protective effects. These findings reveal that the recruitment of extra-intestinal, bone marrow-derived cells into the injured intestinal mucosa can promote mucosal healing, suggesting novel therapeutic approaches for severe intestinal disease.
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Affiliation(s)
- J Sung
- Institute of Genetic Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, USA
| | - C P Sodhi
- Division of Pediatric Surgery, Johns Hopkins Children's Center and Department of Surgery, Baltimore, MD, USA
| | - L Voltaggio
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - X Hou
- W. Harry Feinstone Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA
| | - H Jia
- Division of Pediatric Surgery, Johns Hopkins Children's Center and Department of Surgery, Baltimore, MD, USA
| | - Q Zhou
- Division of Pediatric Surgery, Johns Hopkins Children's Center and Department of Surgery, Baltimore, MD, USA
| | - D Čiháková
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - D J Hackam
- Institute of Genetic Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
- Division of Pediatric Surgery, Johns Hopkins Children's Center and Department of Surgery, Baltimore, MD, USA.
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30
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François S, Usunier B, Forgue-Lafitte ME, L'Homme B, Benderitter M, Douay L, Gorin NC, Larsen AK, Chapel A. Mesenchymal Stem Cell Administration Attenuates Colon Cancer Progression by Modulating the Immune Component within the Colorectal Tumor Microenvironment. Stem Cells Transl Med 2018; 8:285-300. [PMID: 3045139 PMCID: PMC6392393 DOI: 10.1002/sctm.18-0117] [Citation(s) in RCA: 59] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2018] [Accepted: 10/07/2018] [Indexed: 12/17/2022] Open
Abstract
We here determine the influence of mesenchymal stem cell (MSC) therapy on the progression of solid tumors. The influence of MSCs was investigated in human colorectal cancer cells as well as in an immunocompetent rat model of colorectal carcinogenesis representative of the human pathology. Treatment with bone marrow (BM)‐derived MSCs significantly reduced both cancer initiation and cancer progression by increasing the number of tumor‐free animals as well as decreasing the number and the size of the tumors by half, thereby extending their lifespan. The attenuation of cancer progression was mediated by the capacity of the MSCs to modulate the immune component. Specifically, in the adenocarcinomas (ADKs) of MSC‐treated rats, the infiltration of CD68+ monocytes/macrophages was 50% less while the presence of CD3+ lymphocytes increased almost twofold. The MSCs reprogrammed the macrophages to become regulatory cells involved in phagocytosis thereby inhibiting the production of proinflammatory cytokines. Furthermore, the MSCs decreased NK (Natural Killer) and rTh17 cell activities, Treg recruitment, the presence of CD8+ lymphocytes and endothelial cells while restoring Th17 cell activity. The expression of miR‐150 and miR‐7 increased up to fivefold indicating a likely role for these miRNAs in the modulation of tumor growth. Importantly, MSC administration limited the damage of healthy tissues and attenuated tumor growth following radiotherapy. Taken together, we here show that that MSCs have durable action on colon cancer development by modulating the immune component of the tumor microenvironment. In addition, we identify two miRNAs associated with the capacity of MSCs to attenuate cancer growth. stem cells translational medicine2019;8:285&300
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Affiliation(s)
- Sabine François
- Radiobiology of Medical Exposure Laboratory (LRMed), Institute for Radiological Protection and Nuclear Safety (IRSN), Fontenay-aux-Roses, France.,Sorbonne Université, Inserm, Centre de Recherche Saint-Antoine, CRSA, F-75012 Paris, France
| | - Benoit Usunier
- Radiobiology of Medical Exposure Laboratory (LRMed), Institute for Radiological Protection and Nuclear Safety (IRSN), Fontenay-aux-Roses, France
| | - Marie-Elisabeth Forgue-Lafitte
- Cancer Biology and Therapeutics, Centre de Recherche Saint-Antoine (CRSA), Institut National de la Santé et de la Recherche Médicale (INSERM) U938, Paris, France.,Institut Universitaire de Cancérologie (IUC), Faculté de Médecine, Sorbonne Université, Paris, France
| | - Bruno L'Homme
- Radiobiology of Medical Exposure Laboratory (LRMed), Institute for Radiological Protection and Nuclear Safety (IRSN), Fontenay-aux-Roses, France
| | - Marc Benderitter
- Radiobiology of Medical Exposure Laboratory (LRMed), Institute for Radiological Protection and Nuclear Safety (IRSN), Fontenay-aux-Roses, France
| | - Luc Douay
- Sorbonne Université, Inserm, Centre de Recherche Saint-Antoine, CRSA, F-75012 Paris, France.,Université Pierre et Marie Curie (UPMC), Sorbonne Universités, Paris, France.,Service d'Hématologie Biologique, Hôpital Saint-Antoine/Armand Trousseau, AP-HP, Paris, France.,Service d'Hématologie Clinique et Thérapie Cellulaire, Hôpital Saint-Antoine, AP-HP, Paris, France
| | - Norbert-Claude Gorin
- Sorbonne Université, Inserm, Centre de Recherche Saint-Antoine, CRSA, F-75012 Paris, France.,Université Pierre et Marie Curie (UPMC), Sorbonne Universités, Paris, France.,Service d'Hématologie Biologique, Hôpital Saint-Antoine/Armand Trousseau, AP-HP, Paris, France.,Service d'Hématologie Clinique et Thérapie Cellulaire, Hôpital Saint-Antoine, AP-HP, Paris, France
| | - Annette K Larsen
- Cancer Biology and Therapeutics, Centre de Recherche Saint-Antoine (CRSA), Institut National de la Santé et de la Recherche Médicale (INSERM) U938, Paris, France.,Institut Universitaire de Cancérologie (IUC), Faculté de Médecine, Sorbonne Université, Paris, France
| | - Alain Chapel
- Radiobiology of Medical Exposure Laboratory (LRMed), Institute for Radiological Protection and Nuclear Safety (IRSN), Fontenay-aux-Roses, France.,Sorbonne Université, Inserm, Centre de Recherche Saint-Antoine, CRSA, F-75012 Paris, France.,Université Pierre et Marie Curie (UPMC), Sorbonne Universités, Paris, France
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31
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Hupkens BJP, Breukink SO, Olde Reuver Of Briel C, Tanis PJ, de Noo ME, van Duijvendijk P, van Westreenen HL, Dekker JWT, Chen TYT, Juul T. Dutch validation of the low anterior resection syndrome score. Colorectal Dis 2018; 20:881-887. [PMID: 29679514 DOI: 10.1111/codi.14228] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2017] [Accepted: 03/26/2018] [Indexed: 12/24/2022]
Abstract
AIM The aim of this study was to validate the Dutch translation of the low anterior resection syndrome (LARS) score in a population of Dutch rectal cancer patients. METHOD Patients who underwent surgery for rectal cancer received the LARS score questionnaire, a single quality of life (QoL) category question and the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire. A subgroup of patients received the LARS score twice to assess the test-retest reliability. RESULTS A total of 165 patients were included in the analysis, identified in six Dutch centres. The response rate was 62.0%. The percentage of patients who reported 'major LARS' was 59.4%. There was a high proportion of patients with a perfect or moderate fit between the QoL category question and the LARS score, showing a good convergent validity. The LARS score was able to discriminate between patients with or without neoadjuvant radiotherapy (P = 0.003), between total and partial mesorectal excision (P = 0.008) and between age groups (P = 0.039). There was a statistically significant association between a higher LARS score and an impaired function on the global QoL subscale and the physical, role, emotional and social functioning subscales of the EORTC QLQ-C30 questionnaire. The test-retest reliability of the LARS score was good, with an interclass correlation coefficient of 0.79. CONCLUSION The good psychometric properties of the Dutch version of the LARS score are comparable overall to the earlier validations in other countries. Therefore, the Dutch translation can be considered to be a valid tool for assessing LARS in Dutch rectal cancer patients.
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Affiliation(s)
- B J P Hupkens
- Department of Surgery, Maastricht University Medical Centre, Maastricht, The Netherlands.,GROW School for Oncology and Developmental Biology, Maastricht, The Netherlands
| | - S O Breukink
- Department of Surgery, Maastricht University Medical Centre, Maastricht, The Netherlands
| | - C Olde Reuver Of Briel
- Dutch Institute for Clinical Auditing, Leiden, The Netherlands.,Medical Research Data Management, Deventer, The Netherlands
| | - P J Tanis
- Department of Surgery, Academic Medical Centre, Amsterdam, The Netherlands
| | - M E de Noo
- Department of Surgery, Deventer Hospital, Deventer, The Netherlands
| | | | | | - J W T Dekker
- Department of Surgery, Reinier de Graaf Hospital, Delft, The Netherlands
| | - T Y T Chen
- Department of Surgery, Aarhus University Hospital, Aarhus, Denmark
| | - T Juul
- Department of Surgery, Aarhus University Hospital, Aarhus, Denmark
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32
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Halkett GKB, Wigley CA, Aoun SM, Portaluri M, Tramacere F, Livi L, Detti B, Arcangeli S, Lund JA, Kristensen A, McFadden N, Grun A, Bydder S, Sackerer I, Greimel E, Spry N. International validation of the EORTC QLQ-PRT20 module for assessment of quality of life symptoms relating to radiation proctitis: a phase IV study. Radiat Oncol 2018; 13:162. [PMID: 30157890 PMCID: PMC6116442 DOI: 10.1186/s13014-018-1107-x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2018] [Accepted: 08/20/2018] [Indexed: 01/02/2023] Open
Abstract
Background Although patients experience radiation proctitis post radiotherapy no internationally tested instruments exist to measure these symptoms. This Phase IV study tested the scale structure, reliability and validity and cross-cultural applicability of the EORTC proctitis module (QLQ-PRT23) in patients who were receiving pelvic radiotherapy. Methods Patients (n = 358) from six countries completed the EORTC QLQ-C30, QLQ-PRT23 and EORTC Quality of Life Group debriefing questions. Clinicians completed the EORTC Radiation Therapy Oncology Group scale. Questionnaires were completed at four time-points. The module’s scale structure was examined and validated using standard psychometric analysis techniques. Results Three items were dropped from the module (QLQ-PRT23 → QLQ-PRT20). Factor analysis identified five factors in the module: bowel control; bloating and gas; emotional function/lifestyle; pain; and leakage. Inter-item correlations were within r = 0.3–0.7. Test-Retest reliability was high. All multi-item scales discriminated between patients showing symptoms and those without symptomology. The module discriminated symptoms from the clinician completed scoring and for age, gender and comorbidities. Conclusion The EORTC QLQ-PRT20 is designed to be used in addition to the EORTC QLQ-C30 to measure quality of life in patients who receive pelvic radiotherapy. The EORTC QLQ-PRT20 is quick to complete, acceptable to patients, has good content validity and high reliability. Trial registration Australian and New Zealand Clinical Trials Registry (ANZCTR) ACTRN12609000972224. Electronic supplementary material The online version of this article (10.1186/s13014-018-1107-x) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Georgia K B Halkett
- School of Nursing, Midwifery and Paramedicine, Curtin University, GPO Box U1987, Perth, WA, 6845, Australia. .,Institute for Health Research, University of Notre Dame, Perth, Western Australia.
| | - Charles Adam Wigley
- Institute for Health Research, University of Notre Dame, Perth, Western Australia
| | - Samar M Aoun
- Institute for Health Research, University of Notre Dame, Perth, Western Australia.,Palliative Care Unit, School of Psychology and Public Health, La Trobe University, Bundoora, VIC, Australia
| | - Maurizio Portaluri
- Radiation Oncology Dept. "A. Perrino" General Hospital, ASL Brindisi, Italy
| | | | | | | | | | - Jo-Asmund Lund
- Cancer Clinic, St. Olavs University Hospital, Trondheim, Norway
| | - Are Kristensen
- Cancer Clinic, St. Olavs University Hospital, Trondheim, Norway
| | - Nathalie McFadden
- Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebec, Canada
| | - Arne Grun
- Charité - University Medicine, Berlin, Germany
| | - Sean Bydder
- Department of Radiation Oncology, Sir Charles Gairdner Hospital, Perth, Western Australia
| | - Irina Sackerer
- Department of Radiation Oncology, Technical University of Munich, Munich, Germany.,Radiation Oncology, Freising and Dachau, Germany
| | | | - Nigel Spry
- Department of Radiation Oncology, Sir Charles Gairdner Hospital, Perth, Western Australia.,Genesis Cancer Care, Joondalup, WA, Australia
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Lemanska A, Dearnaley DP, Jena R, Sydes MR, Faithfull S. Older Age, Early Symptoms and Physical Function are Associated with the Severity of Late Symptom Clusters for Men Undergoing Radiotherapy for Prostate Cancer. Clin Oncol (R Coll Radiol) 2018; 30:334-345. [PMID: 29459102 PMCID: PMC5952898 DOI: 10.1016/j.clon.2018.01.016] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2017] [Revised: 12/15/2017] [Accepted: 12/22/2017] [Indexed: 12/21/2022]
Abstract
AIMS To identify symptom clusters and predisposing factors associated with long-term symptoms and health-related quality of life after radiotherapy in men with prostate cancer. MATERIALS AND METHODS Patient-reported outcomes (PROs) data from the Medical Research Council RT01 radiotherapy with neoadjuvant androgen deprivation therapy trial of 843 patients were used. PROs were collected over 5 years with the University of California, Los Angeles Prostate Cancer Index (UCLA-PCI) and the 36 item Short-Form Health Survey (SF-36). Symptom clusters were explored using hierarchical cluster analysis. The association of treatment dose, baseline patient characteristics and early symptom clusters with the change in severity of PROs over 3 years was investigated with multivariate linear mixed effects models. RESULTS Seven symptom clusters of three or more symptoms were identified. The clusters were stable over time. The longitudinal profiles of symptom clusters showed the onset of acute symptoms during treatment for all symptom clusters and significant recovery by 6 months. Some clusters, such as physical health and sexual function, were adversely affected more than others by androgen deprivation therapy, and were less likely to return to pretreatment levels over time. Older age was significantly associated with decreased long-term physical function, physical health and sexual function (P < 0.001). Both baseline and acute symptom clusters were significant antecedents for impaired function and health-related quality of life at 3 years. CONCLUSIONS Men with poorer physical function and health before or during treatment were more likely to report poorer PROs at year 3. Early assessment using PROs and lifestyle interventions should be used to identify those with higher needs and provide targeted rehabilitation and symptom management.
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Affiliation(s)
- A Lemanska
- School of Health Sciences, Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK.
| | - D P Dearnaley
- Institute of Cancer Research and Royal Marsden NHS Trust, London, UK
| | - R Jena
- Cambridge University Hospitals, Addenbrookes Hospital, Cambridge, UK
| | - M R Sydes
- MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, London, UK
| | - S Faithfull
- School of Health Sciences, Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK
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34
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Nutritional strategies to prevent gastrointestinal toxicity during pelvic radiotherapy. Proc Nutr Soc 2018; 77:357-368. [DOI: 10.1017/s0029665118000101] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
Radiotherapy-induced damage to non-cancerous gastrointestinal mucosa has effects on secretory and absorptive functions and can interfere with normal gastrointestinal physiology. Nutrient absorption and digestion may be compromised. Dietary manipulation is an attractive option with sound rationale for intervention. The aim of this review was to synthesise published evidence for the use of elemental formulae, low or modified fat diets, fibre, lactose restriction and probiotics, prebiotics and synbiotics to protect the bowel from gastrointestinal side effects during long-course, radical pelvic radiotherapy. Thirty original studies (recruiting n 3197 patients) were identified comprising twenty-four randomised controlled trials, four cohort studies and two comparator trials. Endpoints varied and included symptom scales (Inflammatory Bowel Disease Questionnaire, Common Technology Criteria for Adverse Events, Radiation Therapy Oncology Group) and Bristol Stool Scale. Dietary and supplement interventions were employed with many studies using a combination of interventions. Evidence from RCT was weak for elemental, low or modified fat and low-lactose interventions and modestly positive for the manipulation of fibre during radiotherapy. Evidence for probiotics as prophylactic interventional agents was more promising with a number of trials reporting positive results but strength and strains of interventions vary, as do methodologies and endpoints making it difficult to arrive at firm conclusions with several studies lacking statistical power. This consolidated review concludes that there is insufficient high-grade evidence to recommend nutritional intervention during pelvic radiotherapy. Total replacement of diet with elemental formula could be effective in severe toxicity but this is unproven. Probiotics offer promise but cannot be introduced into clinical practice without rigorous safety analysis, not least in immunocompromised patients.
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35
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Doo AR, Shin YS, Yoo S, Park JK. Radiation-induced neuropathic pain successfully treated with systemic lidocaine administration. J Pain Res 2018; 11:545-548. [PMID: 29588612 PMCID: PMC5859894 DOI: 10.2147/jpr.s155070] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Radiation-induced neuropathic pain is a rare but devastating complication following cancer treatment. It is often progressive, refractory to conservative treatment, and sometimes irreversible. The exact mechanism of radiation-induced neuropathic pain is unknown, but it is associated with perineural fibrosis, atrophy, and ischemia. Systemic administration of local anesthetics is known to be effective for various acute and chronic painful diseases, such as neuropathic pain, as well as inflammatory and nociceptive pains. We report a patient with generalized radiation-induced neuropathic pain successfully treated with systemic lidocaine administration.
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Affiliation(s)
- A Ram Doo
- Department of Anesthesiology and Pain Medicine
| | - Yu Seob Shin
- Department of Urology, Chonbuk National University and Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute and Clinical Trial Center of Medical Device of Chonbuk National University, Jeonju, South Korea
| | - Seonwoo Yoo
- Department of Anesthesiology and Pain Medicine
| | - Jong Kwan Park
- Department of Urology, Chonbuk National University and Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute and Clinical Trial Center of Medical Device of Chonbuk National University, Jeonju, South Korea
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Chang P, Zhang B, Shao L, Song W, Shi W, Wang L, Xu T, Li D, Gao X, Qu Y, Dong L, Wang J. Mesenchymal stem cells over-expressing cxcl12 enhance the radioresistance of the small intestine. Cell Death Dis 2018; 9:154. [PMID: 29402989 PMCID: PMC5833479 DOI: 10.1038/s41419-017-0222-1] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2017] [Accepted: 12/07/2017] [Indexed: 12/18/2022]
Abstract
The chemokine C-X-C motif chemokine 12 (CXCL12) greatly impacts various biological processes in mammals, including cell survival, growth and migration. Mesenchymal stem cells (MSCs) are promising tools for carrying foreign genes to treat radiation-induced injuries in the intestinal epithelium. In this study, human adipose-derived MSCs were constructed to over-express the mouse cxcl12 gene to treat such injuries. In vitro, because of the high levels of mouse CXCL12 in conditioned medium produced by mouse cxcl12 gene-modified cells, phosphorylation of Akt at Ser473 and Erk1/2 at Thr202/Thr204 was increased within crypt cells of irradiated organoids compared with unmodified controls. Moreover, intracellular stabilization of β-catenin was achieved after treatment of mouse cxcl12 gene-modified cells with conditioned medium. As a result, survival of crypt cells was maintained and their proliferation was promoted. When delivering mouse cxcl12 gene-modified cells into irradiated BALB/c nude mice, mice were rescued despite the clearance of cells from the host within 1 week. Irradiated mice that received mouse cxcl12 gene-modified MSCs exhibited reduced serum levels of interleukin-1α (IL-1α) and IL-6 as well as elevated levels of CXCL12. Additionally, epithelial recovery from radiation stress was accelerated compared with the irradiated-alone controls. Moreover, mouse cxcl12 gene-modified MSCs were superior to unmodified cells at strengthening host repair responses to radiation stress as well as presenting increased serum CXCL12 levels and decreased serum IL-1α levels. Furthermore, the number of crypt cells that were positive for phosphorylated Akt at Ser473 and phosphorylated Erk1/2 at Thr202/Thr204 increased following treatment with mouse cxcl12 gene-modified MSCs. Thus, cxcl12 gene-modified MSCs confer radioresistance to the intestinal epithelium.
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Affiliation(s)
- Pengyu Chang
- State Key Laboratory of Electroanalytical Chemistry, Chinese Academy of Sciences, 130022, Changchun, China
- Department of Radiation Oncology, First Bethune Hospital of Jilin University, 130021, Changchun, China
| | - Boyin Zhang
- Department of Orthopedics Surgery, China-Japan Union Hospital of Jilin University, 130033, Changchun, China
| | - Lihong Shao
- Department of Radiation Oncology, First Bethune Hospital of Jilin University, 130021, Changchun, China
| | - Wei Song
- Department of Oncology, First Bethune Hospital of Jilin University, 130021, Changchun, China
| | - Weiyan Shi
- Department of Radiation Oncology, First Bethune Hospital of Jilin University, 130021, Changchun, China
| | - Libo Wang
- Department of Radiation Oncology, First Bethune Hospital of Jilin University, 130021, Changchun, China
| | - Tiankai Xu
- Department of Radiation Oncology, First Bethune Hospital of Jilin University, 130021, Changchun, China
| | - Dong Li
- Department of Immunology, College of Basic Medical Sciences, Jilin University, 130021, Changchun, China
- Jilin Province Key Laboratory of Infectious Diseases, Laboratory of Molecular Virology, 130061, Changchun, China
| | - Xiuzhu Gao
- Jilin Province Key Laboratory of Infectious Diseases, Laboratory of Molecular Virology, 130061, Changchun, China
- Department of Hepatology, First Bethune Hospital of Jilin University, Jilin University, 130021, Changchun, China
| | - Yaqin Qu
- Department of Radiation Oncology, First Bethune Hospital of Jilin University, 130021, Changchun, China
| | - Lihua Dong
- Department of Radiation Oncology, First Bethune Hospital of Jilin University, 130021, Changchun, China.
| | - Jin Wang
- State Key Laboratory of Electroanalytical Chemistry, Chinese Academy of Sciences, 130022, Changchun, China.
- Department of Chemistry and Physics, State University of New York at Stony Brook, New York, NY, 11794-3400, USA.
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Moussa L, Usunier B, Demarquay C, Benderitter M, Tamarat R, Sémont A, Mathieu N. Bowel Radiation Injury: Complexity of the Pathophysiology and Promises of Cell and Tissue Engineering. Cell Transplant 2018; 25:1723-1746. [PMID: 27197023 DOI: 10.3727/096368916x691664] [Citation(s) in RCA: 46] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Ionizing radiation is effective to treat malignant pelvic cancers, but the toxicity to surrounding healthy tissue remains a substantial limitation. Early and late side effects not only limit the escalation of the radiation dose to the tumor but may also be life-threatening in some patients. Numerous preclinical studies determined specific mechanisms induced after irradiation in different compartments of the intestine. This review outlines the complexity of the pathogenesis, highlighting the roles of the epithelial barrier in the vascular network, and the inflammatory microenvironment, which together lead to chronic fibrosis. Despite the large number of pharmacological molecules available, the studies presented in this review provide encouraging proof of concept regarding the use of mesenchymal stromal cell (MSC) therapy to treat radiation-induced intestinal damage. The therapeutic efficacy of MSCs has been demonstrated in animal models and in patients, but an enormous number of cells and multiple injections are needed due to their poor engraftment capacity. Moreover, it has been observed that although MSCs have pleiotropic effects, some intestinal compartments are less restored after a high dose of irradiation. Future research should seek to optimize the efficacy of the injected cells, particularly with regard to extending their life span in the irradiated tissue. Moreover, improving the host microenvironment, combining MSCs with other specific regenerative cells, or introducing new tissue engineering strategies could be tested as methods to treat the severe side effects of pelvic radiotherapy.
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Affiliation(s)
- Lara Moussa
- Institut de Radioprotection et de SÛreté Nucléaire (IRSN), PRP-HOM/SRBE/LR2I, Fontenay-aux-Roses, France
| | - Benoît Usunier
- Institut de Radioprotection et de SÛreté Nucléaire (IRSN), PRP-HOM/SRBE/LR2I, Fontenay-aux-Roses, France
| | - Christelle Demarquay
- Institut de Radioprotection et de SÛreté Nucléaire (IRSN), PRP-HOM/SRBE/LR2I, Fontenay-aux-Roses, France
| | - Marc Benderitter
- Institut de Radioprotection et de SÛreté Nucléaire (IRSN), PRP-HOM/SRBE/LR2I, Fontenay-aux-Roses, France
| | - Radia Tamarat
- Institut de Radioprotection et de SÛreté Nucléaire (IRSN), PRP-HOM/SRBE/LR2I, Fontenay-aux-Roses, France
| | - Alexandra Sémont
- Institut de Radioprotection et de SÛreté Nucléaire (IRSN), PRP-HOM/SRBE/LR2I, Fontenay-aux-Roses, France
| | - Noëlle Mathieu
- Institut de Radioprotection et de SÛreté Nucléaire (IRSN), PRP-HOM/SRBE/LR2I, Fontenay-aux-Roses, France
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What pelvic radiation disease symptoms are experienced by patients receiving external beam radiotherapy and a high-dose-rate brachytherapy boost for prostate cancer? J Contemp Brachytherapy 2017; 9:393-402. [PMID: 29204159 PMCID: PMC5705828 DOI: 10.5114/jcb.2017.70731] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2017] [Accepted: 08/12/2017] [Indexed: 01/28/2023] Open
Abstract
Purpose Research describing proctitis or pelvic radiation disease symptoms of prostate cancer patients one year after external beam radiotherapy (EBRT) plus high-dose-rate (HDR) brachytherapy is limited. This study aimed to assess prostate cancer patients’ pelvic radiation disease symptoms from baseline to 12 months post-radiotherapy. Material and methods Men with prostate cancer referred for EBRT and HDR brachytherapy were recruited. Patients’ age, diagnosis, staging, PSA, past medical history, and treatment were recorded. Pelvic radiation disease symptoms were assessed via the Phase III EORTC proctitis module. Patients completed questionnaires before radiotherapy (baseline) and at one, three, six, and 12 months afterwards. To assess acute toxicity, symptoms one month after radiotherapy were compared with baseline. To assess post-treatment recovery, symptoms at three, six, and 12 months post radiotherapy were compared with one month. Symptom changes over time were assessed with linear mixed effect models. Results Two hundred and sixty-six patients were recruited. Mean scores were below 2 at all time-points. The proportion of patients experiencing symptoms were also calculated. Linear mixed effect models showed that time-point, age, and T-stage were associated with some pelvic radiation disease symptoms. Conclusions Patients receiving EBRT plus HDR brachytherapy to the prostate experienced mild pelvic radiation disease symptoms. Determining the proportion of patients with symptoms provided the most meaningful data.
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Quality of Life in Rectal Cancer Patients After Chemoradiation: Watch-and-Wait Policy Versus Standard Resection - A Matched-Controlled Study. Dis Colon Rectum 2017; 60:1032-1040. [PMID: 28891846 DOI: 10.1097/dcr.0000000000000862] [Citation(s) in RCA: 184] [Impact Index Per Article: 23.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Fifteen to twenty percent of patients with locally advanced rectal cancer have a clinical complete response after chemoradiation therapy. These patients can be offered nonoperative organ-preserving treatment, the so-called watch-and-wait policy. The main goal of this watch-and-wait policy is an anticipated improved quality of life and functional outcome in comparison with a total mesorectal excision, while maintaining a good oncological outcome. OBJECTIVE The aim of this study was to compare the quality of life of watch-and-wait patients with a matched-controlled group of patients who underwent chemoradiation and surgery (total mesorectal excision group). DESIGN This was a matched controlled study. SETTINGS This study was conducted at multiple centers. PATIENTS The study population consisted of 2 groups: 41 patients after a watch-and-wait policy and 41 matched patients after chemoradiation and surgery. Patients were matched on sex, age, tumor stage, and tumor height. All patients were disease free at the moment of recruitment after a minimal follow-up of 2 years. MAIN OUTCOME MEASURES Quality of life was measured by validated questionnaires covering general quality of life (Short Form 36, European Organization for Research and Treatment of Cancer QLQ-C30), disease-specific total mesorectal excision (European Organization for Research and Treatment of Cancer QLQ-CR38), defecation problems (Vaizey and low anterior resection syndrome scores), sexual problems (International Index of Erectile Function and Female Sexual Function Index), and urinary dysfunction (International Prostate Symptom Score). RESULTS The watch-and-wait group showed better physical and cognitive function, better physical and emotional roles, and better global health status compared with the total mesorectal excision group. The watch-and-wait patients showed fewer problems with defecation and sexual and urinary tract function. LIMITATIONS This study only focused on watch-and-wait patients who achieved a sustained complete response for 2 years. In addition, this is a study with a limited number of patients and with quality-of-life measurements on nonpredefined and variable intervals after surgery. CONCLUSIONS After a successful watch-and-wait approach, the quality of life was better than after chemoradiation and surgery on several domains. However, chemoradiation therapy on its own is not without long-term side effects, because one-third of the watch-and-wait patients experienced major low anterior resection syndrome symptoms, compared with 66.7% of the patients in the total mesorectal excision group. See Video Abstract at http://links.lww.com/DCR/A395.
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Bonet M, Cayetano L, Núñez M, Jovell-Fernández E, Aguilar A, Ribas Y. Assessment of acute bowel function after radiotherapy for prostate cancer: Is it accurate enough? Clin Transl Oncol 2017; 20:576-583. [PMID: 28900813 DOI: 10.1007/s12094-017-1749-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2017] [Accepted: 09/01/2017] [Indexed: 11/25/2022]
Abstract
BACKGROUND AND PURPOSE Pelvic radiotherapy for prostate cancer can be associated with bowel toxicity, which may have a significant impact on quality of life. Our aim was to assess the adequacy of the tools currently used to assess bowel symptoms after radiotherapy, including physician and patient reported outcomes. This sub-study on acute toxicity was part of a prospective trial assessing long-term bowel dysfunction. MATERIALS AND METHODS Between February 2013 and July 2015, 75 patients with prostate cancer who received radiotherapy completed the LENT/SOMA and the EPIC questionnaires baseline and 2 weeks after the treatment. The Bristol stool scale and two additional questions on faecal urgency were added. Physicians assessed toxicity using Common Terminology Criteria for Adverse Events v.4.0. Agreement between patients and clinicians was assessed using the Cohen's κ coefficient. RESULTS Acute toxicity during radiotherapy was very low. The pattern of overall bowel bother was similar before and after treatment. Faecal urgency significantly increased after radiotherapy compared to baseline but was only detected by the additional questions and not by the physicians or the patient-reported outcomes (PRO) questionnaires. Correlation between physician and PRO was poor for most symptoms. CONCLUSION Bowel symptoms such as urgency may remain undetected by usual tools to assess toxicity after radiotherapy. Assessment of bowel toxicity should be reappraised in order to identify those patients who may have symptoms with an impact on their quality of life.
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Affiliation(s)
- M Bonet
- Department of Radiation Oncology, Consorci Sanitari de Terrassa, Terrassa, Spain.
- Department of Radiation Oncology, Hospital Universitari Sant Joan de Reus, Avda. del Dr. Josep Laporte, 2, 43201, Reus, Spain.
| | - L Cayetano
- Department of Surgery, Consorci Sanitari de Terrassa, Terrassa, Spain
| | - M Núñez
- Department of Radiation Oncology, Consorci Sanitari de Terrassa, Terrassa, Spain
| | - E Jovell-Fernández
- Department of Epidemiology, Consorci Sanitari de Terrassa, Terrassa, Spain
| | - A Aguilar
- Department of Urology, Consorci Sanitari de Terrassa, Terrassa, Spain
| | - Y Ribas
- Department of Surgery, Consorci Sanitari de Terrassa, Terrassa, Spain
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Muls AC, Klimova K, Andreyev HJN. Clinical decision-making in managing changes in gastrointestinal function following cancer therapies: Is experience enough? Eur J Cancer Care (Engl) 2017; 27. [PMID: 28892252 DOI: 10.1111/ecc.12766] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/03/2017] [Indexed: 02/06/2023]
Abstract
In patients with gastrointestinal (GI) disorders, identical symptoms may occur for many different reasons. This prospective study assessed whether experienced clinicians can predict accurately the underlying diagnosis or diagnoses contributing to specific symptoms based on the history and physical examination. Three clinicians assessed 47 patients referred for management of troublesome GI symptoms identified after treatment for cancer. Investigations were requested following our comprehensive, peer-reviewed algorithm. The clinicians then recorded their predictions as to the results of those investigations. After each patient had completed all their investigations, had received optimal management and had been discharged from the clinic, the predicted diagnoses were compared to those made. The clinicians predicted 92 diagnoses (1.9 per patient). After investigation, a total of 168 unique diagnoses were identified (3.5 per patient). Of the 92 predicted diagnoses, 41 (43%) matched the diagnosis. Of the 168 actual diagnoses identified, only 24% matched the prediction. None of the clinicians predicted the correct combination of diagnoses contributing to bowel symptoms. Clinical acumen alone is inadequate at determining cause for symptoms in patients with GI symptoms developing after cancer therapy.
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Affiliation(s)
- A C Muls
- The GI Unit, The Royal Marsden NHS Foundation Trust, London, UK
| | - K Klimova
- The GI Unit, The Royal Marsden NHS Foundation Trust, London, UK
| | - H J N Andreyev
- The GI Unit, The Royal Marsden NHS Foundation Trust, London, UK
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Toullec A, Buard V, Rannou E, Tarlet G, Guipaud O, Robine S, Iruela-Arispe ML, François A, Milliat F. HIF-1α Deletion in the Endothelium, but Not in the Epithelium, Protects From Radiation-Induced Enteritis. Cell Mol Gastroenterol Hepatol 2017; 5:15-30. [PMID: 29276749 PMCID: PMC5738457 DOI: 10.1016/j.jcmgh.2017.08.001] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2017] [Accepted: 08/08/2017] [Indexed: 12/18/2022]
Abstract
BACKGROUND & AIMS Radiation therapy in the pelvic area is associated with side effects that impact the quality of life of cancer survivors. Interestingly, the gastrointestinal tract is able to adapt to significant changes in oxygen availability, suggesting that mechanisms related to hypoxia sensing help preserve tissue integrity in this organ. However, hypoxia-inducible factor (HIF)-dependent responses to radiation-induced gut toxicity are unknown. Radiation-induced intestinal toxicity is a complex process involving multiple cellular compartments. Here, we investigated whether epithelial or endothelial tissue-specific HIF-1α deletion could affect acute intestinal response to radiation. METHODS Using constitutive and inducible epithelial or endothelial tissue-specific HIF-1α deletion, we evaluated the consequences of epithelial or endothelial HIF-1α deletion on radiation-induced enteritis after localized irradiation. Survival, radiation-induced tissue injury, molecular inflammatory profile, tissue hypoxia, and vascular injury were monitored. RESULTS Surprisingly, epithelium-specific HIF-1α deletion does not alter radiation-induced intestinal injury. However, irradiated VECad-Cre+/-HIF-1αFL/FL mice present with lower radiation-induced damage, showed a preserved vasculature, reduced hypoxia, and reduced proinflammatory response compared with irradiated HIF-1αFL/FL mice. CONCLUSIONS We demonstrate in vivo that HIF-1α impacts radiation-induced enteritis and that this role differs according to the targeted cell type. Our work provides a new role for HIF-1α and endothelium-dependent mechanisms driving inflammatory processes in gut mucosae. Results presented show that effects on normal tissues have to be taken into account in approaches aiming to modulate hypoxia or hypoxia-related molecular mechanisms.
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Key Words
- EndoMT, endothelial-to-mesenchymal transition
- Endothelium
- HIF, hypoxia-inducible factor
- HIF-1α
- HIF-1αFl/FL, HIF-1α floxed mice
- HIMEC, human intestinal microvascular endothelial cells
- HUVEC, human umbilical vein endothelial cells
- IL, interleukin
- PAI-1, plasminogen activator inhibitor type-1
- PCR, polymerase chain reaction
- ROSA, ROSA26R LacZ reporter mice
- Radiation
- Sham-IR, sham-irradiation
- TBI, total body irradiation
- VECad-Cre, VE-cadherin-Cre mice
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Affiliation(s)
- Aurore Toullec
- Research Laboratory of Radiobiology and Radiopathology, Institute for Radiological Protection and Nuclear Safety, Fontenay-aux-Roses, France
| | - Valérie Buard
- Research Laboratory of Radiobiology and Radiopathology, Institute for Radiological Protection and Nuclear Safety, Fontenay-aux-Roses, France
| | - Emilie Rannou
- Research Laboratory of Radiobiology and Radiopathology, Institute for Radiological Protection and Nuclear Safety, Fontenay-aux-Roses, France
- Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, California
| | - Georges Tarlet
- Research Laboratory of Radiobiology and Radiopathology, Institute for Radiological Protection and Nuclear Safety, Fontenay-aux-Roses, France
| | - Olivier Guipaud
- Research Laboratory of Radiobiology and Radiopathology, Institute for Radiological Protection and Nuclear Safety, Fontenay-aux-Roses, France
| | | | - M. Luisa Iruela-Arispe
- Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, California
| | - Agnès François
- Research Laboratory of Radiobiology and Radiopathology, Institute for Radiological Protection and Nuclear Safety, Fontenay-aux-Roses, France
| | - Fabien Milliat
- Research Laboratory of Radiobiology and Radiopathology, Institute for Radiological Protection and Nuclear Safety, Fontenay-aux-Roses, France
- Correspondence Address correspondence to: Fabien Milliat, PhD, Research Laboratory of Radiobiology and Radiopathology, Institute for Radiological Protection and Nuclear Safety, 92265 Fontenay-aux-Roses, France.Research Laboratory of Radiobiology and RadiopathologyInstitute for Radiological Protection and Nuclear Safety92265 Fontenay-aux-RosesFrance
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Lemanska A, Byford RC, Correa A, Cruickshank C, Dearnaley DP, Griffin C, Hall E, de Lusignan S, Faithfull S. Linking CHHiP prostate cancer RCT with GP records: A study proposal to investigate the effect of co-morbidities and medications on long-term symptoms and radiotherapy-related toxicity. Tech Innov Patient Support Radiat Oncol 2017; 2:5-12. [PMID: 32095558 PMCID: PMC7033766 DOI: 10.1016/j.tipsro.2017.06.001] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2017] [Revised: 05/17/2017] [Accepted: 06/07/2017] [Indexed: 12/25/2022] Open
Abstract
Background Patients receiving cancer treatment often have one or more co-morbid conditions that are treated pharmacologically. Co-morbidities are recorded in clinical trials usually only at baseline. However, co-morbidities evolve and new ones emerge during cancer treatment. The interaction between multi-morbidity and cancer recovery is significant but poorly understood. Purpose To investigate the effect of co-morbidities (e.g. cardiovascular and diabetes) and medications (e.g. statins, antihypertensives, metformin) on radiotherapy-related toxicity and long-term symptoms in order to identify potential risk factors. The possible protective effect of medications such as statins or antihypertensives in reducing radiotherapy-related toxicity will also be explored. Methods Two datasets will be linked. (1) CHHiP (Conventional or Hypofractionated High Dose Intensity Modulated Radiotherapy for Prostate Cancer) randomised control trial. CHHiP contains pelvic symptoms and radiation-related toxicity reported by patients and clinicians. (2) GP (General Practice) data from RCGP RSC (Royal College of General Practitioners Research and Surveillance Centre). The GP records of CHHiP patients will be extracted, including cardiovascular co-morbidities, diabetes and prescription medications. Statistical analysis of the combined dataset will be performed in order to investigate the effect. Conclusions Linking two sources of healthcare data is an exciting area of big healthcare data research. With limited data in clinical trials (not all clinical trials collect information on co-morbidities or medications) and limited lengths of follow-up, linking different sources of information is increasingly needed to investigate long-term outcomes. With increasing pressures to collect detailed information in clinical trials (e.g. co-morbidities, medications), linkage to routinely collected data offers the potential to support efficient conduct of clinical trials.
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Key Words
- ANOVA, analysis of variance
- BNF, British National Formulary
- Big data
- CHHiP
- CHHiP, Conventional or Hypofractionated High Dose Intensity Modulated Radiotherapy for Prostate Cancer
- Data linkage
- EPIC, Expanded Prostate Cancer Index Composite
- FACT-P, Functional Assessment of Cancer Therapy-Prostate
- GEE, Generalized Estimating Equations
- GP, General Practitioner
- ICD10, International Classification of Disease version 10
- ICR, Institute of Cancer Research
- IMRT, Intensity Modulated Radiotherapy
- LENT/SOMA, Late Effects Normal Tissue Toxicity; subjective, objective, management, and analytic
- Late-effects
- PCa, Prostate cancer
- PROs, Patient Reported Outcomes
- QOL, Quality of life
- RCGP RSC
- RCGP, Royal College of General Practitioners
- RCT, Randomised Control Trial
- REC, Research Ethics Committee
- RSC, Research & Surveillance Centre
- RTOG, Radiation Therapy Oncology Group
- Radiotherapy-related side-effects
- SHA2-512, Secure Hash Algorithm 2 with 512 bit hash values
- UCLA-PCI, University of California, Los Angeles Prostate Cancer Index
- UK, United Kingdom
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Affiliation(s)
- Agnieszka Lemanska
- School of Health Sciences, Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK
| | - Rachel C Byford
- Department of Health Care Management and Policy, Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK
| | - Ana Correa
- Department of Health Care Management and Policy, Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK
| | - Clare Cruickshank
- The Institute of Cancer Research - Clinical Trials and Statistics Unit, London, UK
| | - David P Dearnaley
- The Institute of Cancer Research and Royal Marsden NHS Trust, London, UK
| | - Clare Griffin
- The Institute of Cancer Research - Clinical Trials and Statistics Unit, London, UK
| | - Emma Hall
- The Institute of Cancer Research - Clinical Trials and Statistics Unit, London, UK
| | - Simon de Lusignan
- Department of Health Care Management and Policy, Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK
| | - Sara Faithfull
- School of Health Sciences, Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK
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Jordan J, Gage H, Benton B, Lalji A, Norton C, Andreyev HJN. Gastroenterologist and nurse management of symptoms after pelvic radiotherapy for cancer: an economic evaluation of a clinical randomized controlled trial (the ORBIT study). CLINICOECONOMICS AND OUTCOMES RESEARCH 2017; 9:241-249. [PMID: 28496343 PMCID: PMC5417736 DOI: 10.2147/ceor.s122104] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023] Open
Abstract
BACKGROUND Over 20 distressing gastrointestinal symptoms affect many patients after pelvic radiotherapy, but in the United Kingdom few are referred for assessment. Algorithmic-based treatment delivered by either a consultant gastroenterologist or a clinical nurse specialist has been shown in a randomized trial to be statistically and clinically more effective than provision of a self-help booklet. In this study, we assessed cost-effectiveness. METHODS Outcomes were measured at baseline (pre-randomization) and 6 months. Change in quality-adjusted life years (QALYs) was the primary outcome for the economic evaluation; a secondary analysis used change in the bowel subset score of the modified Inflammatory Bowel Disease Questionnaire (IBDQ-B). Intervention costs, British pounds 2013, covered visits with the gastroenterologist or nurse, investigations, medications and treatments. Incremental outcomes and incremental costs were estimated simultaneously using multivariate linear regression. Uncertainty was handled non-parametrically using bootstrap with replacement. RESULTS The mean (SD) cost of treatment was £895 (499) for the nurse and £1101 (567) for the consultant. The nurse was dominated by usual care, which was cheaper and achieved better outcomes. The mean cost per QALY gained from the consultant, compared to usual care, was £250,455; comparing the consultant to the nurse, it was £25,875. Algorithmic care produced better outcomes compared to the booklet only, as reflected in the IBDQ-B results, at a cost of ~£1,000. CONCLUSION Algorithmic treatment of radiation bowel injury by a consultant or a nurse results in significant symptom relief for patients but was not found to be cost-effective according to the National Institute for Health and Care Excellence (NICE) criteria.
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Affiliation(s)
- Jake Jordan
- Surrey Health Economics Centre, School of Economics, University of Surrey, Guildford
| | - Heather Gage
- Surrey Health Economics Centre, School of Economics, University of Surrey, Guildford
| | - Barbara Benton
- Gastrointestinal Unit, Royal Marsden NHS Foundation Trust
| | - Amyn Lalji
- Gastrointestinal Unit, Royal Marsden NHS Foundation Trust
| | - Christine Norton
- Florence Nightingale Faculty of Nursing and Midwifery, King’s College, London, UK
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White ID, Sangha A, Lucas G, Wiseman T. Assessment of sexual difficulties associated with multi-modal treatment for cervical or endometrial cancer: A systematic review of measurement instruments. Gynecol Oncol 2016; 143:664-673. [DOI: 10.1016/j.ygyno.2016.08.332] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2016] [Revised: 08/26/2016] [Accepted: 08/27/2016] [Indexed: 10/21/2022]
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Impact of Preoperative Radiotherapy on Anastomotic Leakage and Stenosis After Rectal Cancer Resection: Post Hoc Analysis of a Randomized Controlled Trial. Dis Colon Rectum 2016; 59:934-42. [PMID: 27602924 DOI: 10.1097/dcr.0000000000000665] [Citation(s) in RCA: 95] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND Evidence regarding the effect of preoperative radiotherapy on anastomotic integrity remains conflicting in rectal cancer surgery. Prospective comparisons with appropriate controls are needed. OBJECTIVE This study aimed to assess the impact of preoperative radiotherapy on anastomotic leakage and stenosis after rectal cancer resection. DESIGN This was a post hoc analysis of a randomized controlled trial (NCT01211210). SETTINGS Data were retrieved from the leading center of the trial, which is a tertiary hospital. PATIENTS The full analysis population of 318 patients was included. INTERVENTIONS Patients were randomly assigned to receive preoperative radiation (50 Gy per 25 fractions) and 5-fluorouracil infusion, alone (arm A) or combined with oxaliplatin (arm B), or preoperative chemotherapy with 5-fluorouracil and oxaliplatin without radiation (arm C). MAIN OUTCOME MEASURES The rates of anastomotic leakage and stenosis were calculated for each treatment arm. Multivariate analysis was used to verify the effect of preoperative radiotherapy. RESULTS The treatment arms were comparable in terms of most baseline characteristics, but more diversions were used in the chemoradiotherapy arms. Anastomotic leakage occurred in 20.2% of patients in arm A, 23.6% of patients in arm B, and 8.5% of patients in arm C (p = 0.007). The corresponding rates of stenosis were 17.0%, 18.9%, and 6.8% (p = 0.02). Multivariate analysis confirmed the correlation between preoperative radiotherapy and clinical leakage (p = 0.02), which was associated with delayed stenosis (p < 0.001). For patients undergoing chemoradiotherapy, radiation proctitis was identified as an independent risk factor for clinical leakage (p = 0.01) and stenosis (p < 0.001). LIMITATIONS The main limitations were discrepancies in stoma creation and chemotherapy regimen among the treatment arms. CONCLUSIONS Preoperative radiotherapy increases the risk of anastomotic leakage and stenosis after rectal cancer resection. Clinical leakage independently contributes to the development of stenosis.
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Kulkarni S, Wang TC, Guha C. Stromal Progenitor Cells in Mitigation of Non-Hematopoietic Radiation Injuries. CURRENT PATHOBIOLOGY REPORTS 2016; 4:221-230. [PMID: 28462013 DOI: 10.1007/s40139-016-0114-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
PURPOSE OF REVIEW Therapeutic exposure to high doses of radiation can severely impair organ function due to ablation of stem cells. Normal tissue injury is a dose-limiting toxicity for radiation therapy (RT). Although advances in the delivery of high precision conformal RT has increased normal tissue sparing, mitigating and therapeutic strategies that could alleviate early and chronic radiation effects are urgently needed in order to deliver curative doses of RT, especially in abdominal, pelvic and thoracic malignancies. Radiation-induced gastrointestinal injury is also a major cause of lethality from accidental or intentional exposure to whole body irradiation in the case of nuclear accidents or terrorism. This review examines the therapeutic options for mitigation of non-hematopoietic radiation injuries. RECENT FINDINGS We have developed stem cell based therapies for the mitigation of acute radiation syndrome (ARS) and radiation-induced gastrointestinal syndrome (RIGS). This is a promising option because of the robustness of standardized isolation and transplantation of stromal cells protocols, and their ability to support and replace radiation-damaged stem cells and stem cell niche. Stromal progenitor cells (SPC) represent a unique multipotent and heterogeneous cell population with regenerative, immunosuppressive, anti-inflammatory, and wound healing properties. SPC are also known to secrete various key cytokines and growth factors such as platelet derived growth factors (PDGF), keratinocyte growth factor (KGF), R-spondins (Rspo), and may consequently exert their regenerative effects via paracrine function. Additionally, secretory vesicles such as exosomes or microparticles can potentially be a cell-free alternative replacing the cell transplant in some cases. SUMMARY This review highlights the beneficial effects of SPC on tissue regeneration with their ability to (a) target the irradiated tissues, (b) recruit host stromal cells, (c) regenerate endothelium and epithelium, (d) and secrete regenerative and immunomodulatory paracrine signals to control inflammation, ulceration, wound healing and fibrosis.
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Affiliation(s)
- Shilpa Kulkarni
- Department of Radiation Oncology, Albert Einstein College of Medicine, NY
| | - Timothy C Wang
- Division of Digestive and Liver Diseases, Department of Medicine, Irving Cancer Research Center, Columbia University, New York, NY 10032, USA
| | - Chandan Guha
- Department of Radiation Oncology, Albert Einstein College of Medicine, NY
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Strup-Perrot C, Vozenin MC, Monceau V, Pouzoulet F, Petit B, Holler V, Perrot S, Desquibert L, Fouquet S, Souquere S, Pierron G, Rousset M, Thenet S, Cardot P, Benderitter M, Deutsch E, Aigueperse J. PrP(c) deficiency and dasatinib protect mouse intestines against radiation injury by inhibiting of c-Src. Radiother Oncol 2016; 120:175-83. [PMID: 27406443 DOI: 10.1016/j.radonc.2016.06.009] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2013] [Revised: 04/13/2016] [Accepted: 06/14/2016] [Indexed: 10/21/2022]
Abstract
BACKGROUND & AIM Despite extensive study of the contribution of cell death and apoptosis to radiation-induced acute intestinal injury, our knowledge of the signaling mechanisms involved in epithelial barrier dysfunction remains inadequate. Because PrP(c) plays a key role in intestinal homeostasis by renewing epithelia, we sought to study its role in epithelial barrier function after irradiation. DESIGN Histology, morphometry and plasma FD-4 levels were used to examine ileal architecture, wound healing, and intestinal leakage in PrP(c)-deficient (KO) and wild-type (WT) mice after total-body irradiation. Impairment of the PrP(c) Src pathway after irradiation was explored by immunofluorescence and confocal microscopy, with Caco-2/Tc7 cells. Lastly, dasatinib treatment was used to switch off the Src pathway in vitro and in vivo. RESULTS The decrease in radiation-induced lethality, improved intestinal wound healing, and reduced intestinal leakage promoted by PrP(c) deficiency demonstrate its involvement in acute intestinal damage. Irradiation of Cacao2/Tc7 cells induced PrP(c) to target the nuclei associated with Src activation. Finally, the protective effect triggered by dasatinib confirmed Src involvement in radiation-induced acute intestinal toxicity. CONCLUSION Our data are the first to show a role for the PrP(c)-Src pathway in acute intestinal response to radiation injury and offer a novel therapeutic opportunity.
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Affiliation(s)
- Carine Strup-Perrot
- Institut de Radioprotection et de Sûreté Nucléaire, PRP-HOM, SRBE, Laboratoire de Recherche sur la Régénération des tissus sains Irradiés, Fontenay-aux-Roses, France
| | - Marie-Catherine Vozenin
- Inserm U1030, Radiotherapie experimentale, Institut Gustave Roussy, Villejuif, France; Laboratoire de Radio-Oncologie, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
| | - Virginie Monceau
- Institut de Radioprotection et de Sûreté Nucléaire, PRP-HOM, SRBE, Laboratoire de Recherche sur la Régénération des tissus sains Irradiés, Fontenay-aux-Roses, France; Inserm U1030, Radiotherapie experimentale, Institut Gustave Roussy, Villejuif, France
| | - Frederic Pouzoulet
- Institut Curie, Translational Research Department, Hopital St Louis, Paris, France
| | - Benoit Petit
- Laboratoire de Radio-Oncologie, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; Service Commun d'Expérimentation Animale, Institut Gustave Roussy, Villejuif, France
| | - Valérie Holler
- Institut de Radioprotection et de Sûreté Nucléaire, PRP-HOM, SRBE, Laboratoire de Recherche sur la Régénération des tissus sains Irradiés, Fontenay-aux-Roses, France
| | - Sébastien Perrot
- Université Paris-Est, Ecole Nationale Vétérinaire d'Alfort, Institut de Recherche Clinique Animale, Maisons-Alfort Cedex, France
| | - Loïc Desquibert
- Université Paris-Est, Ecole Nationale Vétérinaire d'Alfort, Institut de Recherche Clinique Animale, Maisons-Alfort Cedex, France
| | - Stéphane Fouquet
- Stéphane FOUQUET, Centre de Recherche Institut de la Vision, UMR_S968 Inserm/UPMC/CHNO des Quinze-Vingts, Paris, France
| | | | - Gérard Pierron
- CNRS, UMR-8122, Institut Gustave Roussy, Villejuif, France
| | - Monique Rousset
- Centre de Recherche des Cordeliers, Université Pierre et Marie Curie-Paris 6, UMR S 872, France; INSERM, U 872, Paris, France; Université Paris Descartes-Paris 5, UMR S 872, France
| | - Sophie Thenet
- Centre de Recherche des Cordeliers, Université Pierre et Marie Curie-Paris 6, UMR S 872, France; INSERM, U 872, Paris, France; Université Paris Descartes-Paris 5, UMR S 872, France; Ecole Pratique des Hautes Etudes, Laboratoire de Pharmacologie Cellulaire et Moléculaire, Paris, France
| | - Philippe Cardot
- Centre de Recherche des Cordeliers, Université Pierre et Marie Curie-Paris 6, UMR S 872, France; INSERM, U 872, Paris, France; Université Paris Descartes-Paris 5, UMR S 872, France
| | - Marc Benderitter
- Institut de Radioprotection et de Sûreté Nucléaire, PRP-HOM, SRBE, Laboratoire de Recherche sur la Régénération des tissus sains Irradiés, Fontenay-aux-Roses, France
| | - Eric Deutsch
- Inserm U1030, Radiotherapie experimentale, Institut Gustave Roussy, Villejuif, France
| | - Jocelyne Aigueperse
- Institut de Radioprotection et de Sûreté Nucléaire, PRP-HOM, Fontenay-aux-Roses, France
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Persistent visceral allodynia in rats exposed to colorectal irradiation is reversed by mesenchymal stromal cell treatment. Pain 2016; 156:1465-1476. [PMID: 25887464 DOI: 10.1097/j.pain.0000000000000190] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Each year, millions of people worldwide are treated for primary or recurrent pelvic malignancies, involving radiotherapy in almost 50% of cases. Delayed development of visceral complications after radiotherapy is recognized in cancer survivors. Therapeutic doses of radiation may lead to the damage of healthy tissue around the tumor and abdominal pain. Because of the lack of experimental models, the underlying mechanisms of radiation-induced long-lasting visceral pain are still unknown. This makes managing radiation-induced pain difficult, and the therapeutic strategies proposed are mostly inefficient. The aim of our study was to develop an animal model of radiation-induced visceral hypersensitivity to (1) analyze some cellular and molecular mechanisms involved and (2) to test a therapeutic strategy using mesenchymal stromal cells (MSCs). Using a single 27-Grays colorectal irradiation in rats, we showed that such exposure induces a persistent visceral allodynia that is associated with an increased spinal sensitization (enhanced p-ERK neurons), colonic neuroplasticity (as increased density of substance P nerve fibers), and colonic mast cell hyperplasia and hypertrophy. Mast cell stabilization by ketotifen provided evidence of their functional involvement in radiation-induced allodynia. Finally, intravenous injection of 1.5 million MSCs, 4 weeks after irradiation, induced a time-dependent reversion of the visceral allodynia and a reduction of the number of anatomical interactions between mast cells and PGP9.5+ nerve fibers. Moreover, unlike ketotifen, MSC treatment has the key advantage to limit radiation-induced colonic ulceration. This work provides new insights into the potential use of MSCs as cellular therapy in the treatment of pelvic radiation disease.
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van de Wetering FT, Verleye L, Andreyev HJN, Maher J, Vlayen J, Pieters BR, van Tienhoven G, Scholten RJPM, Cochrane Gynaecological, Neuro‐oncology and Orphan Cancer Group. Non-surgical interventions for late rectal problems (proctopathy) of radiotherapy in people who have received radiotherapy to the pelvis. Cochrane Database Syst Rev 2016; 4:CD003455. [PMID: 27111831 PMCID: PMC7173735 DOI: 10.1002/14651858.cd003455.pub2] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND This is an update of a Cochrane review first published in 2002, and previously updated in 2007. Late radiation rectal problems (proctopathy) include bleeding, pain, faecal urgency, and incontinence and may develop after pelvic radiotherapy treatment for cancer. OBJECTIVES To assess the effectiveness and safety of non-surgical interventions for managing late radiation proctopathy. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 11, 2015); MEDLINE (Ovid); EMBASE (Ovid); CANCERCD; Science Citation Index; and CINAHL from inception to November 2015. SELECTION CRITERIA We included randomised controlled trials (RCTs) comparing non-surgical interventions for the management of late radiation proctopathy in people with cancer who have undergone pelvic radiotherapy for cancer. Primary outcomes considered were: episodes of bowel activity, bleeding, pain, tenesmus, urgency, and sphincter dysfunction. DATA COLLECTION AND ANALYSIS Study selection, 'Risk of bias' assessment, and data extraction were performed in duplicate, and any disagreements were resolved by involving a third review author. MAIN RESULTS We identified 1221 unique references and 16 studies including 993 participants that met our inclusion criteria. One study found through the last update was moved to the 'Studies awaiting classification' section. We did not pool outcomes for a meta-analysis due to variation in study characteristics and endpoints across included studies.Since radiation proctopathy is a condition with various symptoms or combinations of symptoms, the studies were heterogeneous in their intended effect. Some studies investigated treatments targeted at bleeding only (group 1), some investigated treatments targeted at a combination of anorectal symptoms, but not a single treatment (group 2). The third group focused on the treatment of the collection of symptoms referred to as pelvic radiation disease. In order to enable some comparison of this heterogeneous collection of studies, we describe the effects in these three groups separately.Nine studies assessed treatments for rectal bleeding and were unclear or at high risk of bias. The only treatments that made a significant difference on primary outcomes were argon plasma coagulation (APC) followed by oral sucralfate versus APC with placebo (endoscopic score 6 to 9 in favour of APC with placebo, risk ratio (RR) 2.26, 95% confidence interval (CI) 1.12 to 4.55; 1 study, 122 participants, low- to moderate-quality evidence); formalin dab treatment (4%) versus sucralfate steroid retention enema (symptom score after treatment graded by the Radiation Proctopathy System Assessments Scale (RPSAS) and sigmoidoscopic score in favour of formalin (P = 0.001, effect not quantified, 1 study, 102 participants, very low- to low-quality evidence), and colonic irrigation plus ciprofloxacin and metronidazole versus formalin application (4%) (bleeding (P = 0.007, effect not quantified), urgency (P = 0.0004, effect not quantified), and diarrhoea (P = 0.007, effect not quantified) in favour of colonic irrigation (1 study, 50 participants, low-quality evidence).Three studies, of unclear and high risk of bias, assessed treatments targeted at something very localised but not a single pathology. We identified no significant differences on our primary outcomes. We graded all studies as very low-quality evidence due to unclear risk of bias and very serious imprecision.Four studies, of unclear and high risk of bias, assessed treatments targeted at more than one symptom yet confined to the anorectal region. Studies that demonstrated an effect on symptoms included: gastroenterologist-led algorithm-based treatment versus usual care (detailed self help booklet) (significant difference in favour of gastroenterologist-led algorithm-based treatment on change in Inflammatory Bowel Disease Questionnaire-Bowel (IBDQ-B) score at six months, mean difference (MD) 5.47, 95% CI 1.14 to 9.81) and nurse-led algorithm-based treatment versus usual care (significant difference in favour of the nurse-led algorithm-based treatment on change in IBDQ-B score at six months, MD 4.12, 95% CI 0.04 to 8.19) (1 study, 218 participants, low-quality evidence); hyperbaric oxygen therapy (at 2.0 atmospheres absolute) versus placebo (improvement of Subjective, Objective, Management, Analytic - Late Effects of Normal Tissue (SOMA-LENT) score in favour of hyperbaric oxygen therapy (HBOT), P = 0.0019) (1 study, 150 participants, moderate-quality evidence, retinol palmitate versus placebo (improvement in RPSAS in favour of retinol palmitate, P = 0.01) (1 study, 19 participants, low-quality evidence) and integrated Chinese traditional plus Western medicine versus Western medicine (grade 0 to 1 radio-proctopathy after treatment in favour of integrated Chinese traditional medicine, RR 2.55, 95% CI 1.30 to 5.02) (1 study, 58 participants, low-quality evidence).The level of evidence for the majority of outcomes was downgraded using GRADE to low or very low, mainly due to imprecision and study limitations. AUTHORS' CONCLUSIONS Although some interventions for late radiation proctopathy look promising (including rectal sucralfate, metronidazole added to an anti-inflammatory regimen, and hyperbaric oxygen therapy), single small studies provide limited evidence. Furthermore, outcomes important to people with cancer, including quality of life (QoL) and long-term effects, were not well recorded. The episodic and variable nature of late radiation proctopathy requires large multi-centre placebo-controlled trials (RCTs) to establish whether treatments are effective. Future studies should address the possibility of associated injury to other gastro-intestinal, urinary, or sexual organs, known as pelvic radiation disease. The interventions, as well as the outcome parameters, should be broader and include those important to people with cancer, such as QoL evaluations.
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Affiliation(s)
- Fleur T van de Wetering
- Julius Center for Health Sciences and Primary Care / University Medical Center UtrechtDutch Cochrane CentrePO Box 85500UtrechtNetherlands3508 GA
| | - Leen Verleye
- Belgian Health Care Knowledge CentreKruidtuinlaan 55BrusselsBelgium1000
| | | | - Jane Maher
- Mount Vernon HospitalDepartment of Radiotherapy and OncologyRickmansworth RoadNorthwoodMiddlesexUKHA6 2RN
| | - Joan Vlayen
- Belgian Health Care Knowledge CentreKruidtuinlaan 55BrusselsBelgium1000
| | - Bradley R Pieters
- Academic Medical Center / University of AmsterdamDepartment of Radiation OncologyMeibergdreef 9AmsterdamNetherlands1105
| | - Geertjan van Tienhoven
- Academic Medical CenterRadiation Oncology and HyperthermiaP.O. Box 22700Meibergdreef 9AmsterdamNetherlands1100 DE
| | - Rob JPM Scholten
- Julius Center for Health Sciences and Primary Care / University Medical Center UtrechtDutch Cochrane CentrePO Box 85500UtrechtNetherlands3508 GA
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