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Pierrard J, Heylen S, Vandermeulen A, Van Ooteghem G. Dealing with rectum motion during radiotherapy: How can we anticipate it? Tech Innov Patient Support Radiat Oncol 2024; 32:100277. [PMID: 39391230 PMCID: PMC11465212 DOI: 10.1016/j.tipsro.2024.100277] [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] [Received: 06/05/2024] [Revised: 09/02/2024] [Accepted: 09/20/2024] [Indexed: 10/12/2024] Open
Abstract
Introduction Intra- and inter-fraction rectum motion is important for pelvic radiotherapy (RT). This study assesses how RT session duration, the presence or the absence of an intra-rectal tumour, and the distance from the anorectal junction (ARJd) impact rectal motion. Materials and methods Analyses used cone-beam computed tomographies (CBCTs) from RT patients treated for rectal and prostate cancer. Three structures were evaluated: (1) the entire rectum in patients without a rectal tumour (RectumProstate); (2) the non-invaded portion (RectumRectum) and (3) the tumour-invaded portion (RectumTumour) in rectal cancer patients.Intrafraction motion was assessed using the Hausdorff distance 95% and the Mean distance-to-agreement between structures delineated on the first CBCT and the 2 subsequent CBCTs within a same RT session. Interfraction motion was quantified by comparing structures delineated on the planning-CT and the first CBCT of each session.Linear mixed model evaluated rectum motion in relation to time, tumour presence, and ARJd, respectively. Results We included 10 patients with and 10 without rectal cancer, collecting 385 CBCTs. A significant correlation (p < 0.05) between rectum motion and RT session duration was found. Intrafraction motion was significantly higher in prostate cancer patients (RectumProstate motion > RectumRectum and RectumTumour, p < 0.01). For interfraction motion, only the mean distance to agreement was significantly higher for RectumProstate (p < 0.05). Motion increased significantly with ARJd for all three structures (p < 0.001). Conclusions Session duration, absence of a tumour, and ARJd are associated with larger intra- and interfraction rectal motion. This highlights the need for tailored RT treatment, including online-adaptive RT, to manage intra- and interfraction variations. Rectal motion should be handled differently for patients with prostate cancer and those with rectal cancer.
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Affiliation(s)
- Julien Pierrard
- UCLouvain, Institut de Recherche Experimentale et Clinique (IREC), Center of Molecular Imaging, Radiotherapy and Oncology (MIRO), Brussels, Belgium
- Department of Radiation Oncology, Cliniques Universitaires Saint-Luc, Brussels, Belgium
| | - Sofie Heylen
- Department of Radiation Oncology, Cliniques Universitaires Saint-Luc, Brussels, Belgium
| | - Ad Vandermeulen
- Department of Radiation Oncology, Cliniques Universitaires Saint-Luc, Brussels, Belgium
| | - Geneviève Van Ooteghem
- UCLouvain, Institut de Recherche Experimentale et Clinique (IREC), Center of Molecular Imaging, Radiotherapy and Oncology (MIRO), Brussels, Belgium
- Department of Radiation Oncology, Cliniques Universitaires Saint-Luc, Brussels, Belgium
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Lynn PB, Cronin C, Rangarajan S, Widmar M. Rectal Cancer and Radiation in Colitis. Clin Colon Rectal Surg 2024; 37:30-36. [PMID: 38188064 PMCID: PMC10769583 DOI: 10.1055/s-0043-1762561] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2024]
Abstract
Inflammatory bowel disease (IBD) is associated with an increased risk of colorectal cancer. When IBD patients develop a rectal cancer, this should be treated with the same oncological principles and guidelines as the general population. Rectal cancer treatment includes surgery, chemotherapy, and radiation therapy (RT). Many IBD patients will require a total proctocolectomy with an ileal-pouch anal anastomosis (IPAA) and others, restoration of intestinal continuity may not be feasible or advisable. The literature is scarce regarding outcomes of IPAA after RT. In the present review, we will summarize the evidence regarding RT toxicity in IBD patients and review surgical strategies and outcomes of IPAA after RT.
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Affiliation(s)
- Patricio B. Lynn
- Division of Colorectal Surgery, Department of General Surgery, New York Presbyterian – Weill-Cornell, New York, New York
| | - Catherine Cronin
- Colorectal Surgery Service, Department of Surgical Oncology, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Sriram Rangarajan
- Colorectal Surgery Service, Department of Surgical Oncology, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Maria Widmar
- Colorectal Surgery Service, Department of Surgical Oncology, Memorial Sloan Kettering Cancer Center, New York, New York
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3
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Wang Y, Su P, Zhuo Z, Jin Y, Zeng R, Wu H, Huang H, Chen H, Li Z, Sha W. Ginsenoside Rk1 attenuates radiation-induced intestinal injury through the PI3K/AKT/mTOR pathway. Biochem Biophys Res Commun 2023; 643:111-120. [PMID: 36592584 DOI: 10.1016/j.bbrc.2022.12.072] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2022] [Revised: 11/30/2022] [Accepted: 12/23/2022] [Indexed: 12/26/2022]
Abstract
Radiation-induced intestinal injury (RIII) frequently occurs during radiotherapy; however, methods for treating RIII are limited. Ginsenoside Rk1 (RK1) is a substance that is derived from ginseng, and it has several biological activities, such as antiapoptotic, antioxidant and anticancer activities. The present study was designed to investigate the potential protective effect of Rk1 on RIII and the potential mechanisms. The results showed that RK1 treatment significantly improved the survival rate of the irradiated rats and markedly ameliorated the structural injury of the intestinal mucosa observed by histology. Treatment with RK1 significantly alleviated radiation-induced intestinal epithelial cell oxidative stress apoptosis. Moreover, RNA-Seq identified 388 differentially expressed genes (DEGs) and showed that the PI3K-AKT pathway might be a key signaling pathway by which RK1 exerts its therapeutic effects on RIII. The western blotting results showed that the p-PI3K, p-AKT and p-mTOR expression levels, which were increased by radiation, were markedly inhibited by Rk1, and these effects were reversed by IGF-1. The present study demonstrates that Rk1 can alleviate RIII and that the mechanism underlying the antiapoptotic effects of RK1 may involve the suppression of the PI3K/Akt/mTOR pathway. This study provides a promising therapeutic agent for RIII.
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Affiliation(s)
- Yilin Wang
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China; Department of Gastroenterology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China; Department of Gastroenterology, The First People's Hospital of Foshan, Foshan, China
| | - Peizhu Su
- Department of Gastroenterology, The First People's Hospital of Foshan, Foshan, China
| | - Zewei Zhuo
- Department of Gastroenterology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Yabin Jin
- Department of Clinical Research Institute, The First People's Hospital of Foshan, Foshan, China
| | - Ruijie Zeng
- Department of Gastroenterology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Huihuan Wu
- Department of Gastroenterology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Huiwen Huang
- Department of Gastroenterology, The First People's Hospital of Foshan, Foshan, China
| | - Hao Chen
- Department of Gastroenterology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
| | - Zhaotao Li
- Department of Gastroenterology, The First People's Hospital of Foshan, Foshan, China.
| | - Weihong Sha
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China; Department of Gastroenterology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
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4
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Wang L, Ding K, Yang D, Zhao X. Management strategies of postoperative gastrointestinal tract dysfunction:a review of 210 cases. Asian J Surg 2021; 45:479-480. [PMID: 34629271 DOI: 10.1016/j.asjsur.2021.08.065] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2021] [Accepted: 08/29/2021] [Indexed: 11/15/2022] Open
Abstract
little study has investigated the postoperative gastrointestinal dysfunction focusing on elderly patients. The study hopes to provide a scientific evidence in evaluation of management strategies of gastrointestinal dysfunction. From January 2018 and January 2021, we selected 210 elderly patiens who was diagnosed with PGID, the patients in the study were divided into two groups, one received the management strategies (GroupⅠ) (n = 100), including drug therapy and traditional chinese medicine treatment. The orther received the general treatment (GroupⅡ) (n = 110)Preoperative examinations (hematology and imaging tests)were should be completed and surgical contraindications were ruled out.
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Affiliation(s)
- Lue Wang
- Department of Intensive Medical, Cangzhou Clinical College of Integrated Traditional Chinese and Western Medicine of Hebei Medical University, Cangzhou, 061000, China
| | - Kaifang Ding
- Department of Intensive Medical, Cangzhou Clinical College of Integrated Traditional Chinese and Western Medicine of Hebei Medical University, Cangzhou, 061000, China
| | - Dongxing Yang
- Department of Intensive Medical, Cangzhou Clinical College of Integrated Traditional Chinese and Western Medicine of Hebei Medical University, Cangzhou, 061000, China
| | - Xuequan Zhao
- Department of Orthopedics, Cangzhou Clinical College of Integrated Traditional Chinese and Western Medicine of Hebei Medical University, Cangzhou, 061000, China.
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5
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White KL, Henson CC, Hann M, Eden M, Burden ST, Lal S, Davidson SE, McLaughlin JT. Randomised clinical trial of a gastrointestinal care bundle to reduce symptoms in patients with pelvic cancer undergoing chemoradiotherapy. BMJ Open Gastroenterol 2021; 7:bmjgast-2020-000432. [PMID: 32771983 PMCID: PMC7418694 DOI: 10.1136/bmjgast-2020-000432] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2020] [Revised: 06/03/2020] [Accepted: 06/07/2020] [Indexed: 11/03/2022] Open
Abstract
OBJECTIVE Pelvic radiotherapy is used to treat 17 000 people in the UK each year. Eight in 10 develop difficult bowel problems during pelvic treatment, especially diarrhoea, urgency and incontinence. Some cannot complete treatment, reducing the chance of cancer cure. Undertaking gastroenterologist-led investigation and management during pelvic radiotherapy has never been evaluated. In this study, we aimed to assess whether patients could successfully receive a novel gastrointestinal (GI) care bundle during chemoradiotherapy (feasibility aim) and would experience reduced symptom severity (clinical impact aim). DESIGN This randomised controlled trial recruited patients with cervical and bladder cancers undergoing radical chemoradiotherapy. Participants were randomised to intervention or control groups. Questionnaire and anthropometric data were collected. All intervention group patients received individualised dietary counselling weekly throughout treatment, and if bowel symptoms developed they were offered rapid-access investigation and treatment for any identified pathology: lactose intolerance, bacterial overgrowth or bile acid malabsorption. RESULTS Feasibility: 50 participants were recruited, 24 were randomised to the intervention group and 26 to the control group. All completed 20 fractions of external beam pelvic radiotherapy. It was possible to perform 57/72 (79%) of proposed intervention tests with no disruption of oncological management. CLINICAL IMPACT All participants developed GI symptoms during radiotherapy. The median symptom score for each group increased from baseline at 6 weeks. This was from 0.156 (0.000-0.333) to 0.600 (0.250-1.286) in the control group, and from 0.00 (0.000-0.300) to 0.402 (0.000-0.667) in the intervention group. CONCLUSION It was feasible to recruit to and deliver a randomised controlled trial of interventions in patients undergoing pelvic chemoradiotherapy. Lower median bowel scores were reported in the intervention group at 6 weeks, with fewer patients experiencing symptoms overall. TRIAL REGISTRATION NUMBER ISRCTN783488.
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Affiliation(s)
- Katherine L White
- Gastroenterology, Manchester Foundation Trust, Wythenshawe Hospital, Manchester, UK.,Manchester Academic Health Sciences Centre, Health Innovation Manchester, Manchester, UK
| | - Caroline C Henson
- Gastroenterology, Manchester Foundation Trust, Wythenshawe Hospital, Manchester, UK.,Manchester Academic Health Sciences Centre, Health Innovation Manchester, Manchester, UK
| | - Mark Hann
- Manchester Academic Health Sciences Centre, Health Innovation Manchester, Manchester, UK.,Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK
| | - Martin Eden
- Manchester Academic Health Sciences Centre, Health Innovation Manchester, Manchester, UK.,Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK
| | - Sorrel T Burden
- Manchester Academic Health Sciences Centre, Health Innovation Manchester, Manchester, UK.,Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.,Salford Royal Foundation Trust, Salford, UK
| | - Simon Lal
- Manchester Academic Health Sciences Centre, Health Innovation Manchester, Manchester, UK.,Salford Royal Foundation Trust, Salford, UK
| | - Susan E Davidson
- Manchester Academic Health Sciences Centre, Health Innovation Manchester, Manchester, UK.,Christie NHS Foundation Trust, Manchester, UK
| | - John T McLaughlin
- Manchester Academic Health Sciences Centre, Health Innovation Manchester, Manchester, UK .,Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.,Salford Royal Foundation Trust, Salford, UK
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Afifi ANAM, Powerski M, Jechorek D, Brunner TB, Weigt J, Venerito M. Radiation-induced damage in the upper gastrointestinal tract: clinical presentation, diagnostic tests and treatment options. Best Pract Res Clin Gastroenterol 2020; 48-49:101711. [PMID: 33317797 DOI: 10.1016/j.bpg.2020.101711] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2020] [Revised: 11/05/2020] [Accepted: 11/09/2020] [Indexed: 01/31/2023]
Abstract
Radiation-induced damage of the upper gastrointestinal (GI) tract results from radiation of GI tumors or structures adjacent to the GI tract. Radiation-induced damages of the upper GI tract may be acute or delayed, and ranges from lack of appetite, mucosal inflammation (i.e. esophagitis, gastritis, duodenitis) to ulcers, which may be complicated by perforation, penetration, bleeding and stenosis. Radiation-related factors as well as individual patient predisposing factors may increase susceptibility to post-radiation damage. High quality evidence for the treatment of radiation-induced GI damage is scarce and the management is often extrapolated from studies on GI lesions of different etiology. Treatment depends on severity and localization of the radiation-induced damage, and ranges from supportive and dietary measures to endoscopic interventions or surgery. Modern radiation techniques may decrease the incidence and severity of the radiation-induced upper gastrointestinal disease.
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Affiliation(s)
- Ahmed N A M Afifi
- Universitätsklinik für Gastroenterologie, Hepatologie und Infektiologie, Germany
| | - Maciej Powerski
- Universitätsklinik für Radiologie und Nuklearmedizin, Germany
| | | | - Thomas B Brunner
- Universitätsklinik für Strahlentherapie, Otto-von-Guericke Universitätsklinikum Magdeburg, Germany
| | - Jochen Weigt
- Universitätsklinik für Gastroenterologie, Hepatologie und Infektiologie, Germany
| | - Marino Venerito
- Universitätsklinik für Gastroenterologie, Hepatologie und Infektiologie, Germany.
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7
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Chronic diarrhoea in an oncology patient - Clinical assessment and decision making. Best Pract Res Clin Gastroenterol 2020; 48-49:101708. [PMID: 33317791 DOI: 10.1016/j.bpg.2020.101708] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2020] [Revised: 10/21/2020] [Accepted: 11/05/2020] [Indexed: 01/31/2023]
Abstract
Cancer survival is improving rapidly due to advances in treatments that will often involve radiotherapy, chemotherapy and novel biological agents in addition to surgery. This comes at the price of living with chronic symptoms, of which diarrhoea is particularly common. There is good evidence that for many patients these symptoms become part of everyday life, their "normality" is adjusted and symptoms are tolerated even when limiting activities severely. Clinicians often fail to appreciate the impact of these problems, as the focus of follow up tends to be on cancer recurrence. However, the rapid identification of patients in significant trouble can lead to earlier diagnosis of treatable pathologies and improvement of patients' symptoms. The aim of this review is to highlight the mechanisms which cause oncology patients to develop diarrhoea and highlight useful investigational and treatment strategies.
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Zvirych VV, Makhmudov DE, Paliiy MI, Ashykhmin AV, Kolesnik OO. BILATERAL AVASCULAR NECROSIS OF SACRAL LATERAL MASSES AFTER A COMPLETE RADIOLOGICAL RESPONSE OF LOCALLY ADVANCED RECTAL CANCER TREATED WITH NEOADJUVANT CHEMORADIATION THERAPY. CASE REPORT. PROBLEMY RADIAT︠S︡IĬNOÏ MEDYT︠S︡YNY TA RADIOBIOLOHIÏ 2020; 24:537-551. [PMID: 31841494 DOI: 10.33145/2304-8336-2019-24-537-551] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/11/2019] [Indexed: 11/10/2022]
Abstract
We present a rare case report of a bilateral avascular necrosis of lateral sacral masses in a patient who developed a sustainable complete clinical and radiological response after chemoradiotherapy for locally advanced rectal cancer. It is shown that despite the standardized and precise planning and fractioning for neoadjuvant chemoradiation therapy for locally advanced rectal cancer, the biological effects of ionizing radiation on critical organs can be va- ried both in time of occurrence and in structure. Evaluating the effect of neoadjuvant chemoradiation therapy, one should take into account the possibility of the development of even very rare effects of ionizing radiation on criti- cal organs and include their early detection in the diagnostic algorithm.
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Affiliation(s)
- V V Zvirych
- National Cancer Institute, 33/43 Lomonosova St., Kyiv, Ukraine
| | - D E Makhmudov
- National Cancer Institute, 33/43 Lomonosova St., Kyiv, Ukraine
| | - M I Paliiy
- National Cancer Institute, 33/43 Lomonosova St., Kyiv, Ukraine
| | - A V Ashykhmin
- National Cancer Institute, 33/43 Lomonosova St., Kyiv, Ukraine
| | - O O Kolesnik
- National Cancer Institute, 33/43 Lomonosova St., Kyiv, Ukraine
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9
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Jahanshahi M, Maleki Dana P, Badehnoosh B, Asemi Z, Hallajzadeh J, Mansournia MA, Yousefi B, Moazzami B, Chaichian S. Anti-tumor activities of probiotics in cervical cancer. J Ovarian Res 2020; 13:68. [PMID: 32527332 PMCID: PMC7291573 DOI: 10.1186/s13048-020-00668-x] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2020] [Accepted: 05/27/2020] [Indexed: 02/06/2023] Open
Abstract
Cervical cancer is considered as an important malignancy among women worldwide. Currently-used treatments of cervical cancer are reported to be cytotoxic for patients. Moreover, these therapies have shown some side effects which can negatively affect the lives of women suffering from this cancer. Therefore, there is need for anti-tumor agents that are less toxic than common therapeutic drugs. Besides, applying agents for preventing or reducing the side effects of cervical cancer therapies can be effective in improving the life quality of cervical cancer patients. Studies have shown that probiotics have several effects on biological processes. One of the most prominent aspects in which probiotics play a role is in the field of cancer. There are multiple studies which have focused on the functions of probiotics in diagnosis, prevention, or treatment of cancer. Besides their direct anti-tumor activities, probiotics can be used as an additional agent for enhancing or modulating other diagnostic and therapeutic methods. Herein, the effects of probiotics on cervical cancer cells are discussed, which may be useful in the prevention and treatment of this cancer. We review the studies concerned with the roles of probiotics in modulating and reducing the gastrointestinal adverse effects caused by cervical cancer therapies. Furthermore, we cover the investigations focusing on the combination of probiotics with other drugs for diagnosis or treatment of cervical cancer.
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Affiliation(s)
- Moghaddaseh Jahanshahi
- Clinical Research Development Center (CRDC), Sayad Shirazi Hospital, Golestan University of Medical Sciences, Gorgan, Iran
| | - Parisa Maleki Dana
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
| | - Bita Badehnoosh
- Department of Gynecology and Obstetrics, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran
| | - Zatollah Asemi
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
| | - Jamal Hallajzadeh
- Department of Biochemistry and Nutrition, Research Center for Evidence-Based Health Management, Maragheh University of Medical Sciences, Maragheh, Iran
| | - Mohammad Ali Mansournia
- Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Bahman Yousefi
- Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Biochemistry, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Bahram Moazzami
- Pars Advanced and Minimally Invasive Medical Manners Research Center, Pars Hospital, Iran University of Medical Sciences, Tehran, Iran
| | - Shahla Chaichian
- Pars Advanced and Minimally Invasive Medical Manners Research Center, Pars Hospital, Iran University of Medical Sciences, Tehran, Iran
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Abstract
PURPOSE OF REVIEW As cancer treatments improve more patients than ever are living for longer with the side effects of these treatments. Radiation enteritis is a heterogenous condition with significant morbidity. The present review aims to provide a broad overview of the condition with particular attention to the diagnosis and management of the condition. RECENT FINDINGS Radiation enteritis appears to be more prevalent than originally thought because of patient underreporting and a lack of clinician awareness. Patient-related and treatment-related risk factors have now been identified and should be modified where possible. Medical and surgical factors have been explored, but manipulation of the gut microbiota offers one of the most exciting recent developments in disease prevention. Diagnosis and treatment are best approached in a systematic fashion with particular attention to the exclusion of recurrent malignancy and other gastrointestinal conditions. Surgery and endoscopy both offer opportunities for management of the complications of radiation enteritis. Experimental therapies offer hope for future management of radiation enteritis but large-scale human trials are needed. SUMMARY Radiation enteritis is an important clinical problem, but awareness is lacking amongst patients and physicians. Clinical guidelines would allow standardised management which may improve the burden of the disease for patients.
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11
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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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Dutta A, Gupta ML, Verma S. Podophyllotoxin and rutin in combination prevents oxidative stress mediated cell death and advances revival of mice gastrointestine following lethal radiation injury. Free Radic Res 2018; 52:103-117. [DOI: 10.1080/10715762.2017.1418982] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Affiliation(s)
- Ajaswrata Dutta
- Division of Radioprotective Drug Development Research, Institute of Nuclear Medicine and Allied Sciences (INMAS) Defence Research and Development Organization (DRDO), Delhi, India
| | - Manju Lata Gupta
- Division of Radioprotective Drug Development Research, Institute of Nuclear Medicine and Allied Sciences (INMAS) Defence Research and Development Organization (DRDO), Delhi, India
| | - Savita Verma
- Division of Radioprotective Drug Development Research, Institute of Nuclear Medicine and Allied Sciences (INMAS) Defence Research and Development Organization (DRDO), Delhi, India
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Wedlake L, Shaw C, McNair H, Lalji A, Mohammed K, Klopper T, Allan L, Tait D, Hawkins M, Somaiah N, Lalondrelle S, Taylor A, VanAs N, Stewart A, Essapen S, Gage H, Whelan K, Andreyev HJN. Randomized controlled trial of dietary fiber for the prevention of radiation-induced gastrointestinal toxicity during pelvic radiotherapy. Am J Clin Nutr 2017; 106:849-857. [PMID: 28679552 DOI: 10.3945/ajcn.116.150565] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2016] [Accepted: 06/08/2017] [Indexed: 11/14/2022] Open
Abstract
Background: Therapeutic radiotherapy is an important treatment of pelvic cancers. Historically, low-fiber diets have been recommended despite a lack of evidence and potentially beneficial mechanisms of fiber.Objective: This randomized controlled trial compared low-, habitual-, and high-fiber diets for the prevention of gastrointestinal toxicity in patients undergoing pelvic radiotherapy.Design: Patients were randomly assigned to low-fiber [≤10 g nonstarch polysaccharide (NSP)/d], habitual-fiber (control), or high-fiber (≥18 g NSP/d) diets and received individualized counseling at the start of radiotherapy to achieve these targets. The primary endpoint was the difference between groups in the change in the Inflammatory Bowel Disease Questionnaire-Bowel Subset (IBDQ-B) score between the starting and nadir (worst) score during treatment. Other measures included macronutrient intake, stool diaries, and fecal short-chain fatty acid concentrations.Results: Patients were randomly assigned to low-fiber (n = 55), habitual-fiber (n = 55), or high-fiber (n = 56) dietary advice. Fiber intakes were significantly different between groups (P < 0.001). The difference between groups in the change in IBDQ-B scores between the start and nadir was not significant (P = 0.093). However, the change in score between the start and end of radiotherapy was smaller in the high-fiber group (mean ± SD: -3.7 ± 12.8) than in the habitual-fiber group (-10.8 ± 13.5; P = 0.011). At 1-y postradiotherapy (n = 126) the difference in IBDQ-B scores between the high-fiber (+0.1 ± 14.5) and the habitual-fiber (-8.4 ± 13.3) groups was significant (P = 0.004). No significant differences were observed in stool frequency or form or in short-chain fatty acid concentrations. Significant reductions in energy, protein, and fat intake occurred in the low- and habitual-fiber groups only.Conclusions: Dietary advice to follow a high-fiber diet during pelvic radiotherapy resulted in reduced gastrointestinal toxicity both acutely and at 1 y compared with habitual-fiber intake. Restrictive, non-evidence-based advice to reduce fiber intake in this setting should be abandoned. This trial was registered at clinicaltrials.gov as NCT 01170299.
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Affiliation(s)
| | | | | | | | | | | | | | - Diana Tait
- Radiotherapy, Breast and Gastrointestinal Unit
| | | | | | | | | | - Nicholas VanAs
- Clinical Oncology, The Royal Marsden NHS Foundation Trust, London, United Kingdom
| | - Alexandra Stewart
- Oncology, The Royal Surrey County Hospital, Guildford, United Kingdom
| | - Sharadah Essapen
- Oncology, The Royal Surrey County Hospital, Guildford, United Kingdom
| | - Heather Gage
- School of Economics, University of Surrey, Guildford, United Kingdom; and
| | - Kevin Whelan
- Diabetes and Nutritional Sciences Division, King's College London, London, United Kingdom
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Kwak YK, Lee SW, Kay CS, Park HH. Intensity-modulated radiotherapy reduces gastrointestinal toxicity in pelvic radiation therapy with moderate dose. PLoS One 2017; 12:e0183339. [PMID: 28846718 PMCID: PMC5573121 DOI: 10.1371/journal.pone.0183339] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2017] [Accepted: 08/02/2017] [Indexed: 12/25/2022] Open
Abstract
This retrospective study was performed to evaluate and compare gastrointestinal (GI) toxicities caused by conventional radiotherapy (cRT) and intensity modulated radiotherapy (IMRT) in 136 cancer patients treated with pelvic radiotherapy (RT) with moderate radiation dose in a single institution. A matched-pair analysis of the two groups was performed; each group included 68 patients. Conventional RT was delivered using the four-field box technique and IMRT was delivered with helical tomotherapy. The median daily dose was 1.8 Gy and the median total dose was 50.4 Gy (range 25.2–56 Gy). Primary end point was GI toxicity during and after RT. Secondary end point was factors that affect toxicity. Patients treated with IMRT had lower incidence of grade ≥ 2 acute GI toxicity compared to the patients treated with cRT (p = 0.003). The difference remained significant in multivariate analysis (p = 0.01). The incidence of chronic GI toxicity was not statistically different between the two groups, but the cRT group had higher incidence of grade 3 chronic GI toxicity. Based on our results, IMRT can reduce GI toxicity compared to cRT in the treatment of pelvic radiotherapy even with moderate radiation dose and this will enhance patients’ quality of life and treatment compliance.
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Affiliation(s)
- Yoo-Kang Kwak
- Department of Radiation Oncology, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Sea-Won Lee
- Department of Radiation Oncology, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Chul Seung Kay
- Department of Radiation Oncology, Incheon St. Mary’s Hospital, College of Medicine, the Catholic University of Korea, Seoul, Republic of Korea
- * E-mail:
| | - Hee Hyun Park
- Department of Radiation Oncology, Incheon St. Mary’s Hospital, College of Medicine, the Catholic University of Korea, Seoul, Republic of Korea
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Anwar M, Ahmad S, Akhtar R, Mahmood A, Mahmood S. Antioxidant Supplementation: A Linchpin in Radiation-Induced Enteritis. Technol Cancer Res Treat 2017; 16:676-691. [PMID: 28532242 PMCID: PMC5762044 DOI: 10.1177/1533034617707598] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023] Open
Abstract
Radiation enteritis is one of the most feared complications of abdominal and pelvic regions. Thus, radiation to abdominal or pelvic malignancies unavoidably injures the intestine. Because of rapid cell turnover, the intestine is highly sensitive to radiation injury, which is the limiting factor in the permissible dosage of irradiation. Bowel injuries such as fistulas, strictures, and chronic malabsorption are potentially life-threatening complications and have an impact on patient quality of life. The incidence of radiation enteritis is increasing because of the current trend of combined chemotherapy and radiation. The consequences of radiation damage to the intestine may result in considerable morbidity and even mortality. The observed effects of ionizing radiation are mediated mainly by oxygen-free radicals that are generated by its action on water and are involved in several steps of signal transduction cascade, leading to apoptosis. The oxyradicals also induce DNA strand breaks and protein oxidation. An important line of defense against free radical damage is the presence of antioxidants. Therefore, administration of antioxidants may ameliorate the radiation-induced damage to the intestine.
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Affiliation(s)
- Mumtaz Anwar
- Department of Experimental Medicine and Biotechnology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Shabeer Ahmad
- Department of Experimental Medicine and Biotechnology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Reyhan Akhtar
- Department of Experimental Medicine and Biotechnology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Akhtar Mahmood
- Department of Biochemistry, Panjab University, Chandigarh, India
| | - Safrun Mahmood
- Department of Experimental Medicine and Biotechnology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
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16
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Abstract
AbstractBackgroundIn those receiving radiotherapy for pelvic cancers, up to 80% develop gastrointestinal symptoms, with dietary interventions recommended to reduce these symptoms. However, research outlining the current dietary support provided to patients undergoing radiotherapy for pelvic cancer is lacking.AimTo identify the gastrointestinal symptoms experienced by those undergoing pelvic radiotherapy and to identify the dietary support provided to these patients.Methods and materialsA service evaluation was undertaken in one NHS Trust hospital whereby patients undergoing radical pelvic radiotherapy during a 15-week recruitment period were invited to complete an anonymous questionnaire. Participants were recruited using purposive sampling and the data were analysed descriptively using SPSS.ResultsIn total, 31 patients responded achieving a response rate of 48%. The most frequent reported gastrointestinal symptoms were gas and flatulence followed by diarrhoea, nausea and abdominal pain. The main dietary changes implemented by the respondents and recommended by health care professionals included reducing fibre intake, reducing certain vegetables, reducing caffeine and increasing water.FindingsThe results illustrate the impact of gastrointestinal side effects on patients’ dietary intake. The results highlight that nutritional guidance need to be standardised, especially for the management of diarrhoea and gas and flatulence as these were the most common occurring side effects. With radiographers most frequently giving nutritional advice they must be provided with guidance to support those undergoing pelvic radiotherapy.
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17
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Goudarzi M, Mak TD, Jacobs JP, Moon BH, Strawn SJ, Braun J, Brenner DJ, Fornace AJ, Li HH. An Integrated Multi-Omic Approach to Assess Radiation Injury on the Host-Microbiome Axis. Radiat Res 2016; 186:219-34. [PMID: 27512828 PMCID: PMC5304359 DOI: 10.1667/rr14306.1] [Citation(s) in RCA: 65] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Medical responders to radiological and nuclear disasters currently lack sufficient high-throughput and minimally invasive biodosimetry tools to assess exposure and injury in the affected populations. For this reason, we have focused on developing robust radiation exposure biomarkers in easily accessible biofluids such as urine, serum and feces. While we have previously reported on urine and serum biomarkers, here we assessed perturbations in the fecal metabolome resulting from exposure to external X radiation in vivo. The gastrointestinal (GI) system is of particular importance in radiation biodosimetry due to its constant cell renewal and sensitivity to radiation-induced injury. While the clinical GI symptoms such as pain, bloating, nausea, vomiting and diarrhea are manifested after radiation exposure, no reliable bioindicator has been identified for radiation-induced gastrointestinal injuries. To this end, we focused on determining a fecal metabolomic signature in X-ray irradiated mice. There is overwhelming evidence that the gut microbiota play an essential role in gut homeostasis and overall health. Because the fecal metabolome is tightly correlated with the composition and diversity of the microorganism in the gut, we also performed fecal 16S rRNA sequencing analysis to determine the changes in the microbial composition postirradiation. We used in-house bioinformatics tools to integrate the 16S rRNA sequencing and metabolomic data, and to elucidate the gut integrated ecosystem and its deviations from a stable host-microbiome state that result from irradiation. The 16S rRNA sequencing results indicated that radiation caused remarkable alterations of the microbiome in feces at the family level. Increased abundance of common members of Lactobacillaceae and Staphylococcaceae families, and decreased abundances of Lachnospiraceae, Ruminococcaceae and Clostridiaceae families were found after 5 and 12 Gy irradiation. The metabolomic data revealed statistically significant changes in the microbial-derived products such as pipecolic acid, glutaconic acid, urobilinogen and homogentisic acid. In addition, significant changes were detected in bile acids such as taurocholic acid and 12-ketodeoxycholic acid. These changes may be associated with the observed shifts in the abundance of intestinal microbes, such as R. gnavus , which can transform bile acids.
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Affiliation(s)
- Maryam Goudarzi
- Department of Biochemistry and Molecular and Cellular Biology, Georgetown University, Washington, DC
| | - Tytus D. Mak
- Mass Spectrometry Data Center, National Institute of Standards and Technology, Gaithersburg, Maryland
| | - Jonathan P. Jacobs
- Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California
| | - Bo-Hyun Moon
- Department of Biochemistry and Molecular and Cellular Biology, Georgetown University, Washington, DC
| | - Steven J. Strawn
- Department of Biochemistry and Molecular and Cellular Biology, Georgetown University, Washington, DC
| | - Jonathan Braun
- Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California
| | - David J. Brenner
- Center for Radiological Research, Columbia University, New York, New York
| | - Albert J. Fornace
- Department of Biochemistry and Molecular and Cellular Biology, Georgetown University, Washington, DC
- Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC
| | - Heng-Hong Li
- Department of Biochemistry and Molecular and Cellular Biology, Georgetown University, Washington, DC
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18
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Li M, Du A, Xu J, Ma Y, Cao H, Yang C, Yang XD, Xing CG, Chen M, Zhu W, Zhang S, Cao J. Neurogenic differentiation factor NeuroD confers protection against radiation-induced intestinal injury in mice. Sci Rep 2016; 6:30180. [PMID: 27436572 PMCID: PMC4951798 DOI: 10.1038/srep30180] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2016] [Accepted: 06/28/2016] [Indexed: 12/12/2022] Open
Abstract
The gastrointestinal tract, especially the small intestine, is particularly sensitive to radiation, and is prone to radiation-induced injury as a result. Neurogenic differentiation factor (NeuroD) is an evolutionarily-conserved basic helix-loop-helix (bHLH) transcription factor. NeuroD contains a protein transduction domain (PTD), which allows it to be exogenously delivered across the membrane of mammalian cells, whereupon its transcription activity can be unleashed. Whether NeuroD has therapeutic effects for radiation-induced injury remains unclear. In the present study, we prepared a NeuroD-EGFP recombinant protein, and explored its protective effects on the survival and intestinal damage induced by ionizing radiation. Our results showed that NeuroD-EGFP could be transduced into small intestine epithelial cells and tissues. NeuroD-EGFP administration significantly increased overall survival of mice exposed to lethal total body irradiation (TBI). This recombinant NeuroD also reduced radiation-induced intestinal mucosal injury and apoptosis, and improved crypt survival. Expression profiling of NeuroD-EGFP-treated mice revealed upregulation of tissue inhibitor of metalloproteinase 1 (TIMP-1), a known inhibitor of apoptosis in mammalian cells. In conclusion, NeuroD confers protection against radiation-induced intestinal injury, and provides a novel therapeutic clinical option for the prevention of intestinal side effects of radiotherapy and the treatment of victims of incidental exposure.
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Affiliation(s)
- Ming Li
- School of Radiation Medicine and Protection, Medical College of Soochow University, Suzhou 215123, China.,Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123, China
| | - Aonan Du
- School of Radiation Medicine and Protection, Medical College of Soochow University, Suzhou 215123, China.,Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123, China
| | - Jing Xu
- School of Radiation Medicine and Protection, Medical College of Soochow University, Suzhou 215123, China.,Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123, China
| | - Yanchao Ma
- School of Radiation Medicine and Protection, Medical College of Soochow University, Suzhou 215123, China.,Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123, China
| | - Han Cao
- School of Radiation Medicine and Protection, Medical College of Soochow University, Suzhou 215123, China.,Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123, China
| | - Chao Yang
- Department of Transfusion Medicine, The General Hospital of the PLA Rocket Force, Beijing 100088, China
| | - Xiao-Dong Yang
- Department of General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China
| | - Chun-Gen Xing
- Department of General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China
| | - Ming Chen
- Zhejiang Key Laboratory of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou 310022, China
| | - Wei Zhu
- School of Radiation Medicine and Protection, Medical College of Soochow University, Suzhou 215123, China.,Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123, China
| | - Shuyu Zhang
- School of Radiation Medicine and Protection, Medical College of Soochow University, Suzhou 215123, China.,Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123, China.,Zhejiang Key Laboratory of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou 310022, China
| | - Jianping Cao
- School of Radiation Medicine and Protection, Medical College of Soochow University, Suzhou 215123, China.,Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123, China
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Abstract
Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract and includes both Crohn's disease and ulcerative colitis. Patients with IBD often present with abdominal pain, diarrhea, and rectal bleeding but may also have a wide variety of other symptoms such as weight loss, fever, nausea, vomiting, and possibly obstruction. Given that the presentation of IBD is not specific, the differential diagnosis is broad and encompasses a wide spectrum of diseases, many of which can mimic and/or even coexist with IBD. It is important for physicians to differentiate symptoms due to refractory IBD from symptoms due to IBD mimics when a patient is not responding to standard IBD treatment. Many of the various IBD mimics include infectious etiologies (viral, bacterial, mycobacterial, fungal, protozoal, and helminthic infections), vascular causes, other immune causes including autoimmune etiologies, drug-induced processes, radiation-induced, and other etiologies such as small intestinal bacterial overgrowth, diverticulitis, and bile acid malabsorption. Thoughtful consideration and evaluation of these potential etiologies through patient history and physical examination, as well as appropriate tests, endoscopic evaluation, and cross-sectional imaging is required to evaluate any patient presenting with symptoms consistent with IBD.
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20
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Kang HJ, Kay CS, Son SH, Kim M, Jo IY, Lee SJ, Lee DH, Suh HJ, Choi YS. Hypofractionated intensity-modulated radiotherapy in patients with localized prostate cancer: a preliminary study. Radiat Oncol J 2016; 34:45-51. [PMID: 27104166 PMCID: PMC4831968 DOI: 10.3857/roj.2016.34.1.45] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2015] [Revised: 02/06/2016] [Accepted: 03/10/2016] [Indexed: 12/04/2022] Open
Abstract
Purpose The aim of this work was to assess the efficacy and tolerability of hypofractionated intensity-modulated radiotherapy (IMRT) in patients with localized prostate cancer. Materials and Methods Thirty-nine patients who received radical hypofractionated IMRT were retrospectively reviewed. Based on a pelvic lymph node involvement risk of 15% as the cutoff value, we decided whether to deliver treatment prostate and seminal vesicle only radiotherapy (PORT) or whole pelvis radiotherapy (WPRT). Sixteen patients (41%) received PORT with prostate receiving 45 Gy in 4.5 Gy per fraction in 2 weeks and the other 23 patients (59%) received WPRT with the prostate receiving 72 Gy in 2.4 Gy per fraction in 6 weeks. The median equivalent dose in 2 Gy fractions to the prostate was 79.9 Gy based on the assumption that the α/β ratio is 1.5 Gy. Results The median follow-up time was 38 months (range, 4 to 101 months). The 3-year biochemical failure-free survival rate was 88.2%. The 3-year clinical failure-free and overall survival rates were 94.5% and 96.3%, respectively. The rates of grade 2 acute genitourinary (GU) and gastrointestinal (GI) toxicities were 20.5% and 12.8%, respectively. None of the patients experienced grade ≥3 acute GU and GI toxicities. The grade 2-3 late GU and GI toxicities were found in 8.1% and 5.4% of patients, respectively. No fatal late toxicity was observed. Conclusion Favorable biochemical control with low rates of toxicity was observed after hypofractionated IMRT, suggesting that our radiotherapy schedule can be an effective treatment option in the treatment of localized prostate cancer.
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Affiliation(s)
- Hye Jin Kang
- Department of Radiation Oncology, Incheon St. Mary's Hospital, The Catholic University of Korea College of Medicine, Incheon, Korea
| | - Chul-Seung Kay
- Department of Radiation Oncology, Incheon St. Mary's Hospital, The Catholic University of Korea College of Medicine, Incheon, Korea
| | - Seok Hyun Son
- Department of Radiation Oncology, Incheon St. Mary's Hospital, The Catholic University of Korea College of Medicine, Incheon, Korea
| | - Myungsoo Kim
- Department of Radiation Oncology, Incheon St. Mary's Hospital, The Catholic University of Korea College of Medicine, Incheon, Korea
| | - In Young Jo
- Department of Radiation Oncology, Incheon St. Mary's Hospital, The Catholic University of Korea College of Medicine, Incheon, Korea
| | - So Jung Lee
- Department of Radiation Oncology, Incheon St. Mary's Hospital, The Catholic University of Korea College of Medicine, Incheon, Korea
| | - Dong Hwan Lee
- Department of Urology, Incheon St. Mary's Hospital, The Catholic University of Korea College of Medicine, Incheon, Korea
| | - Hong Jin Suh
- Department of Urology, Incheon St. Mary's Hospital, The Catholic University of Korea College of Medicine, Incheon, Korea
| | - Yong Sun Choi
- Department of Urology, Incheon St. Mary's Hospital, The Catholic University of Korea College of Medicine, Incheon, Korea
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21
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Sureban SM, May R, Qu D, Chandrakesan P, Weygant N, Ali N, Lightfoot SA, Ding K, Umar S, Schlosser MJ, Houchen CW. Dietary Pectin Increases Intestinal Crypt Stem Cell Survival following Radiation Injury. PLoS One 2015; 10:e0135561. [PMID: 26270561 PMCID: PMC4536042 DOI: 10.1371/journal.pone.0135561] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2015] [Accepted: 07/23/2015] [Indexed: 12/12/2022] Open
Abstract
Gastrointestinal (GI) mucosal damage is a devastating adverse effect of radiation therapy. We have recently reported that expression of Dclk1, a Tuft cell and tumor stem cell (TSC) marker, 24h after high dose total-body gamma-IR (TBI) can be used as a surrogate marker for crypt survival. Dietary pectin has been demonstrated to possess chemopreventive properties, whereas its radioprotective property has not been studied. The aim of this study was to determine the effects of dietary pectin on ionizing radiation (IR)-induced intestinal stem cell (ISC) deletion, crypt and overall survival following lethal TBI. C57BL/6 mice received a 6% pectin diet and 0.5% pectin drinking water (pre-IR mice received pectin one week before TBI until death; post-IR mice received pectin after TBI until death). Animals were exposed to TBI (14 Gy) and euthanized at 24 and 84h post-IR to assess ISC deletion and crypt survival respectively. Animals were also subjected to overall survival studies following TBI. In pre-IR treatment group, we observed a three-fold increase in ISC/crypt survival, a two-fold increase in Dclk1+ stem cells, increased overall survival (median 10d vs. 7d), and increased expression of Dclk1, Msi1, Lgr5, Bmi1, and Notch1 (in small intestine) post-TBI in pectin treated mice compared to controls. We also observed increased survival of mice treated with pectin (post-IR) compared to controls. Dietary pectin is a radioprotective agent; prevents IR-induced deletion of potential reserve ISCs; facilitates crypt regeneration; and ultimately promotes overall survival. Given the anti-cancer activity of pectin, our data support a potential role for dietary pectin as an agent that can be administered to patients receiving radiation therapy to protect against radiation-induces mucositis.
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Affiliation(s)
- Sripathi M. Sureban
- Department of Medicine, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America
- Department of Veterans Affairs Medical Center, Oklahoma City, Oklahoma, United States of America
- The Peggy and Charles Stephenson Cancer Center, Oklahoma City, Oklahoma, United States of America
- * E-mail: (CWH); (SMS)
| | - Randal May
- Department of Medicine, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America
- Department of Veterans Affairs Medical Center, Oklahoma City, Oklahoma, United States of America
| | - Dongfeng Qu
- Department of Medicine, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America
| | - Parthasarathy Chandrakesan
- Department of Medicine, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America
| | - Nathaniel Weygant
- Department of Medicine, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America
| | - Naushad Ali
- Department of Medicine, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America
- The Peggy and Charles Stephenson Cancer Center, Oklahoma City, Oklahoma, United States of America
| | - Stan A. Lightfoot
- Department of Pathology, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America
| | - Kai Ding
- Department of Biostatistics and Epidemiology, College of Public Health, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America
| | - Shahid Umar
- Department of Molecular & Integrative Physiology, The University of Kansas, Kansas City, Kansas, United States of America
| | | | - Courtney W. Houchen
- Department of Medicine, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America
- Department of Veterans Affairs Medical Center, Oklahoma City, Oklahoma, United States of America
- The Peggy and Charles Stephenson Cancer Center, Oklahoma City, Oklahoma, United States of America
- * E-mail: (CWH); (SMS)
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22
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Abstract
Radiation therapy is a widely utilized treatment modality for pelvic malignancies, including prostate cancer, rectal cancer, and cervical cancer. Given its fixed position in the pelvis, the rectum is at a high risk for injury secondary to ionizing radiation. Despite advances made in radiation science, up to 75% of the patients will suffer from acute radiation proctitis and up to 20% may experience chronic symptoms. Symptoms can be variable and include diarrhea, bleeding, incontinence, and fistulization. A multitude of treatment options exist. This article summarizes the latest knowledge relating to radiation proctopathy focusing on the vast array of treatment options.
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Affiliation(s)
- Marc B. Grodsky
- Section of Colon and Rectal Surgery, MedStar Washington Hospital Center, Washington, District of Columbia
| | - Shafik M. Sidani
- Department of Colorectal Surgery, Virginia Hospital Center Physician Group, Arlington, Virginia
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23
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Fahmy HA, Ismail AFM. Gastroprotective effect of kefir on ulcer induced in irradiated rats. JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY 2015; 144:85-93. [PMID: 25728227 DOI: 10.1016/j.jphotobiol.2015.02.009] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/08/2014] [Revised: 02/07/2015] [Accepted: 02/10/2015] [Indexed: 02/07/2023]
Abstract
The current study was designed to investigate the protective effect of kefir milk on ethanol-induced gastric ulcers in γ-irradiated rats. The results of the present study revealed that treatment with γ-irradiation and/or ethanol showed a significant increase in ulcers number, total acidity, peptic, H(+)K(+)ATPase, MMP-2 and MMP-9 activities and MDA level, which were accompanied by a significant decrease in the mucus content, the stomach GSH level, the GSH-Px activity and DNA damage. Pre-treatment with kefir milk exert significant improvement in all the tested parameters. Kefir milk exerts comparable effect to that of the antiulcer drug ranitidine. In conclusion, the present study revealed that oral administration of kefir milk prevents ethanol-induced gastric ulcer in γ-irradiated rats that could attribute to its antioxidant, anti-apoptotic and radio-protective activities.
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Affiliation(s)
- Hanan A Fahmy
- Drug Radiation Research Department, National Centre for Radiation Research and Technology, Atomic Energy Authority, Nasr City, Cairo, Egypt
| | - Amel F M Ismail
- Drug Radiation Research Department, National Centre for Radiation Research and Technology, Atomic Energy Authority, Nasr City, Cairo, Egypt.
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Khayyal MT, Abdel-Naby DH, Abdel-Aziz H, El-Ghazaly MA. A multi-component herbal preparation, STW 5, shows anti-apoptotic effects in radiation induced intestinal mucositis in rats. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2014; 21:1390-1399. [PMID: 25022208 DOI: 10.1016/j.phymed.2014.04.030] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/17/2014] [Revised: 02/25/2014] [Accepted: 04/18/2014] [Indexed: 06/03/2023]
Abstract
PURPOSE Intestinal mucositis is a common adverse effect in patients undergoing radiotherapy and constitutes a treatment-limiting condition. Since no agents are yet known that can adequately guard against its development, the search continues to find safe and effective measures. The present study was intended to investigate whether the herbal preparation, STW 5, could offer a potentially effective agent in this respect. METHODS Intestinal mucositis was induced in rats by exposing them to whole body gamma-irradiation (6 Gy). Rats were treated orally with STW 5 (5 or 10 ml/kg) for five days before and two days after irradiation. One day later, rats were sacrificed and segments of small intestine were examined histologically. Intestinal homogenates and serum samples were used to assess relevant parameters for apoptosis and different markers for inflammation and oxidative stress. RESULTS Exposure to radiation produced dose-dependent extents of intestinal injury associated with apoptotic changes with high radiation levels. Apoptosis was associated with an increase in cytosolic calcium, depletion of mitochondrial cytochrome c, B-cell lymphoma-2 and complex I. Oxidative stress parameters (reduced glutathione, thiobarbituric acid reactive substance and total nitrate/nitrite) were deranged. Inflammation markers (tumor necrosis factor and myeloperoxidase) and indices of intestinal damage (serum diamine oxidase) were increased. STW 5 protected to a large extent against histological changes and counteracted the deranged parameters. CONCLUSION The findings provide experimental evidence for the potential beneficial use of STW5 in protecting against the development of radiation-induced intestinal mucositis and associated changes in tissue biomarkers.
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Affiliation(s)
- Mohamed T Khayyal
- Department of Pharmacology, Faculty of Pharmacy, Cairo University, Egypt.
| | - Doaa H Abdel-Naby
- Department of Drug Radiation Research, National Centre for Radiation Research and Technology, Atomic Energy Authority, Egypt
| | - Heba Abdel-Aziz
- Scientific Department, Steigerwald Arzneimittelwerk GmbH, Darmstadt, Germany
| | - Mona A El-Ghazaly
- Department of Drug Radiation Research, National Centre for Radiation Research and Technology, Atomic Energy Authority, Egypt
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25
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Hauer-Jensen M, Denham JW, Andreyev HJN. Radiation enteropathy--pathogenesis, treatment and prevention. Nat Rev Gastroenterol Hepatol 2014; 11:470-9. [PMID: 24686268 PMCID: PMC4346191 DOI: 10.1038/nrgastro.2014.46] [Citation(s) in RCA: 302] [Impact Index Per Article: 27.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Changes in cancer incidence and mortality have been modest during the past several decades, but the number of cancer survivors has almost tripled during the same period. With an increasing cohort of cancer survivors, efforts to prevent, diagnose and manage adverse effects of cancer therapy, in general, and those of radiation therapy specifically, have intensified. Many cancer survivors have undergone radiation therapy of tumours in the pelvis or abdomen, thus rendering the bowel at risk of injury. In fact, the current prevalence of patients who have long-term radiation-induced intestinal adverse effects exceeds that of IBD. Considerable progress towards reducing toxicity of radiation therapy has been made by the introduction of so-called dose-sculpting treatment techniques, which enable precise delivery of the radiation beam. Moreover, new insights into the underlying pathophysiology have resulted in an improved understanding of mechanisms of radiation-induced bowel toxicity and in development of new diagnostic strategies and management opportunities. This Review discusses the pathogenesis of early and delayed radiation-induced bowel toxicity, presents current management options and outlines priorities for future research. By adding insight into molecular and cellular mechanisms of related bowel disorders, gastroenterologists can substantially strengthen these efforts.
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Affiliation(s)
- Martin Hauer-Jensen
- Surgical Service, Central Arkansas Veterans Healthcare System and Division of Radiation Health, University of Arkansas for Medical Sciences, Little Rock, AR, USA
| | - James W. Denham
- Department of Radiation Oncology, University of Newcastle, Newcastle, NSW, Australia
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Saracino B, Petrongari MG, Marzi S, Bruzzaniti V, Sara G, Arcangeli S, Arcangeli G, Pinnarò P, Giordano C, Ferraro AM, Strigari L. Intensity-modulated pelvic radiation therapy and simultaneous integrated boost to the prostate area in patients with high-risk prostate cancer: a preliminary report of disease control. Cancer Med 2014; 3:1313-21. [PMID: 24976538 PMCID: PMC4302681 DOI: 10.1002/cam4.278] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2014] [Revised: 05/05/2014] [Accepted: 05/06/2014] [Indexed: 11/08/2022] Open
Abstract
The aim of the study was to report the clinical results in patients with high-risk prostate cancer treated with pelvic intensity-modulated radiation therapy (IMRT) and simultaneous integrated boost (SIB) to the prostate area. A total of 110 patients entered our study, 37 patients presented with localized prostate cancer and radiological evidence of node metastases or ≥15% estimated risk of lymph node (LN) involvement, while 73 patients underwent postoperative adjuvant or salvage irradiation for biochemical or residual/recurrent disease, LN metastases, or high risk of harboring nodal metastases. All patients received androgen deprivation therapy (ADT) for 2 years. The median follow-up was 56.5 months. For the whole patient group, the 3- and 5-year freedom from biochemical failure were 82.6% and 74.6%, respectively, with a better outcome in patients treated with radical approach. The 3- and 5-year freedom from local failure were 94.4% and 90.2%, respectively, while the 3- and 5-year distant metastasis-free survival were 87.8% and 81.7%, respectively. For all study patients, the rate of freedom from G2 acute rectal, intestinal, and urinary toxicities was 60%, 77%, and 61%, respectively. There was no G3 acute toxicity, ≥G2 late intestinal toxicity, or G3 late urinary or rectal toxicity. The 3- and 5-year ≥G2 freedom from late rectal toxicity rate were 98% and 95%, respectively, while the 3- and 5-year ≥G2 freedom from late urinary toxicity rate were 95% and 88%, respectively. The study concludes that pelvic IMRT and SIB to the prostatic area in association with 2-year ADT was a well-tolerated technique, providing high disease control in patients with prostate cancer requiring LN treatment.
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Ionizing irradiation induces acute haematopoietic syndrome and gastrointestinal syndrome independently in mice. Nat Commun 2014; 5:3494. [PMID: 24637717 DOI: 10.1038/ncomms4494] [Citation(s) in RCA: 65] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2013] [Accepted: 02/24/2014] [Indexed: 01/17/2023] Open
Abstract
The role of bone marrow (BM) and BM-derived cells in radiation-induced acute gastrointestinal (GI) syndrome is controversial. Here we use bone marrow transplantation (BMT), total body irradiation (TBI) and abdominal irradiation (ABI) models to demonstrate a very limited, if any, role of BM-derived cells in acute GI injury and recovery. Compared with WT BM recipients, mice receiving BM from radiation-resistant PUMA KO mice show no protection from crypt and villus injury or recovery after 15 or 12 Gy TBI, but have a significant survival benefit at 12 Gy TBI. PUMA KO BM significantly protects donor-derived pan-intestinal haematopoietic (CD45+) and endothelial (CD105+) cells after IR. We further show that PUMA KO BM fails to enhance animal survival or crypt regeneration in radiosensitive p21 KO-recipient mice. These findings clearly separate the effects of radiation on the intestinal epithelium from those on the BM and endothelial cells in dose-dependent acute radiation toxicity.
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Muls AC. Acta Oncologica Lecture. Gastrointestinal consequences of cancer treatment and the wider context: a bad gut feeling. Acta Oncol 2014; 53:297-306. [PMID: 24460087 DOI: 10.3109/0284186x.2013.873140] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
BACKGROUND The percentage of people living with a diagnosis of cancer is rising globally. Between 20% and 25% of people treated for cancer experience a consequence of cancer which has an adverse impact on the quality of their life. Gastrointestinal (GI) symptoms are the most common of all consequences of cancer treatment and have the greatest impact on daily activity. PATHOPHYSIOLOGY OF LONG-TERM BOWEL DAMAGE AFTER PELVIC RADIOTHERAPY: Long-term damage to the bowel after radiotherapy is mediated by ischaemic changes and fibrosis. Each fraction of radiotherapy causes a series of repetitive injuries to the intestinal tissue resulting in an altered healing process, which affects the integrity of the repair and changes the architecture of the bowel wall. THE NATURE OF GI SYMPTOMS THAT DEVELOP: Patient-reported outcome measures show that diarrhoea, urgency, increased bowel frequency, tenesmus and flatulence are the five most prevalent GI symptoms with a moderate or severe impact on patients' daily lives after treatment with pelvic radiotherapy. Many patients also experience fatigue, urinary problems and have sexual concerns. SYSTEMATIC ASSESSMENT AND MANAGEMENT: The complex nature of those symptoms warrants systematic assessment and management. The use of a tested algorithm can assist in achieving this. The most common contributing factors to ongoing bowel problems after pelvic radiotherapy are small intestinal bacterial overgrowth, bile acid malabsorption, pancreatic insufficiency, rectal bleeding and its impact on bone health. THE WIDER CONTEXT Symptom burden, socio-psychosocial impact, memory and cognitive function, fatigue, urinary problems and sexual concerns need to be taken into account when thinking about consequences of cancer treatment. CONCLUSION As our understanding of consequences of cancer treatments continues to emerge and encompass a wide variety of specialties, a holistic, multifaceted and multidisciplinary approach is required to manage those consequences long-term.
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Demers M, Dagnault A, Desjardins J. A randomized double-blind controlled trial: impact of probiotics on diarrhea in patients treated with pelvic radiation. Clin Nutr 2013; 33:761-7. [PMID: 24200199 DOI: 10.1016/j.clnu.2013.10.015] [Citation(s) in RCA: 144] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2013] [Revised: 10/18/2013] [Accepted: 10/18/2013] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Radical radiation therapy is commonly used for treatment of pelvic cancer. Up to 80% of patients receiving radiotherapy will develop acute radiation induced diarrhea. The primary aim of this randomized double blind controlled trial is to evaluate the effect of the probiotic Bifilact(®) on moderate and severe treatment-induced diarrhea during pelvic radiation. METHODS Patients with pelvic cancers were treated between 2006 and 2010 at L'Hôtel-Dieu de Québec, University Health Center. Some patients had surgery before pelvic radiotherapy and some received chemotherapy. A total of 246 Patients were randomized between a placebo and either of two regiments of double strain Bifilact(®) probiotics (Lactobacillus acidophilus LAC-361 and Bifidobacterium longum BB-536): a standard dose twice a day (1.3 billion CFU) or a high dose three times a day (10 billion CFU). Patients were trained to record their digestive symptoms daily with a standardized scale and they met a registered dietician and radiation oncologist every week during treatment. The main analysis compared time to first appearance of grade ≥2-3-4 diarrhea using Kaplan-Meier curves as measured by proportion of patients without moderate and severe diarrhea. RESULTS 229 patients were analyzed. The difference between the groups for overall grade 2-3-4 diarrhea was not statistically significant (p = 0.13). However at 60 days, the proportion of patients without moderate and severe diarrhea in the standard dose group (35%) was more than twice as high as that of the placebo group (17%) with a hazard ratio of 0.69 (p = 0.04). In patients who had surgery, the standard probiotics dose group had a better proportion of patients without very severe diarrhea than the placebo group, respectively 97% and 74% (p = 0.03). In all groups, the average number of bowel movements per day during treatment was less than 3 soft stools (p = 0.80) and the median abdominal pain less than 1 based on the National Cancer Institute scale (p = 0.23). CONCLUSION Standard dose of Bifilact(®) may reduce radiation induced grade 2-3-4 diarrhea at the end of the treatment of patients with pelvic cancer. In patients operated on before RT, a standard dose of probiotics may reduce radiation induced grade 4 diarrhea. Nutritional interventions by a registered dietician seemed to reduce global digestive symptoms. TRIAL REGISTRATION clinicaltrials.gov. Identifier NCT01839721.
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Affiliation(s)
- Mimi Demers
- Department of Radio-Oncology, University Health Center, Hôtel Dieu de Québec, Québec, Canada; Department of Clinical Nutrition, University Health Center, Hôtel Dieu de Québec, Québec, Canada.
| | - Anne Dagnault
- Department of Radio-Oncology, University Health Center, Hôtel Dieu de Québec, Québec, Canada
| | - Josée Desjardins
- Department of Radio-Oncology, University Health Center, Hôtel Dieu de Québec, Québec, Canada; Department of Clinical Nutrition, University Health Center, Hôtel Dieu de Québec, Québec, Canada
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Brown LC, Atherton PJ, Neben-Wittich MA, Wender DB, Behrens RJ, Kozelsky TF, Loprinzi CL, Haddock MG, Martenson JA. Assessment of long-term rectal function in patients who received pelvic radiotherapy: a pooled North Central Cancer Treatment Group trial analysis, N09C1. Support Care Cancer 2013; 21:2869-77. [PMID: 23748483 PMCID: PMC3769434 DOI: 10.1007/s00520-013-1853-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2012] [Accepted: 05/16/2013] [Indexed: 12/25/2022]
Abstract
PURPOSE Pelvic radiotherapy (PRT) is known to adversely affect bowel function (BF) and patient well-being. This study characterized long-term BF and evaluated quality of life (QOL) in patients receiving PRT. METHODS Data from 252 patients were compiled from two North Central Cancer Treatment Group prospective studies, which included assessment of BF and QOL by the BF questionnaire (BFQ) and Uniscale QOL at baseline and 12 and 24 months after completion of radiotherapy. BFQ scores (sum of symptoms), Uniscale results, adverse-event incidence, and baseline demographic data were compared via t test, χ (2), Fisher exact, Wilcoxon, and correlation methodologies. RESULTS The total BFQ score was higher than baseline at 12 and 24 months (P < 0.001). More patients had five or more symptoms at 12 months (13 %) and 24 months (10 %) than at baseline (2 %). Symptoms occurring in greater than 20 % of patients at 12 and 24 months were clustering, stool-gas confusion, and urgency. Factors associated with worse BF were female sex, rectal or gynecologic primary tumors, prior anterior resection of the rectum, and 5-fluorouracil chemotherapy. Patients experiencing grade 2 or higher acute toxicity had worse 24-month BF (P values, <.001-.02). Uniscale QOL was not significantly different from baseline at 12 or 24 months, despite worse BFQ scores. CONCLUSIONS PRT was associated with worse long-term BF. Worse BFQ score was not associated with poorer QOL. Further research to characterize the subset of patients at risk of significant decline in BF is warranted.
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Affiliation(s)
- Lindsay C Brown
- Department of Radiation Oncology, Mayo Clinic, 200 First St SW, Rochester, MN, 55905, USA
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Akpolat M, Gulle K, Topcu-Tarladacalisir Y, Safi Oz Z, Bakkal BH, Arasli M, Ozel Turkcu U. Protection by L-carnitine against radiation-induced ileal mucosal injury in the rat: pattern of oxidative stress, apoptosis and cytokines. Int J Radiat Biol 2013; 89:732-740. [PMID: 23510242 DOI: 10.3109/09553002.2013.787176] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
PURPOSE In this study, we tested the effects of L-carnitine (LC) on radiation-induced ileal mucosal damage. MATERIALS AND METHODS Thirty Wistar albino rats were divided into five groups. The control group received physiological saline intraperitoneally (i.p.). Radiation-1 and radiation-2 groups received whole-body X-irradiation of 8.3 Gy as a single dose. These groups were sacrificed at the 6th hour and 4th day after irradiation, respectively. The Radiation-1 + LC and the radiation-2 + LC groups received the same dose irradiation plus a daily dose of 200 mg/kg LC. LC was applied one day before and for four days after irradiation. RESULTS The levels of serum monocyte chemotactic protein-1 (MCP-1) and interferon gamma (IFN-γ) were significantly higher in the radiation groups when compared with the control. Treatment with LC decreased the serum MCP-1 and IFN-γ levels considerably. In the radiations groups, the Chiu score was significantly elevated compared with that of the control group. However, LC administered prior to the irradiation reduced the severity of mucosal damage. The number of apoptotic cells of the ileal crypt in the irradiated rats increased from the 6th hour after irradiation and then decreased at 4th day. CONCLUSIONS Our data demonstrated that LC may be beneficial to radiation enteritis.
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Affiliation(s)
- Meryem Akpolat
- Department of Histology and Embryology, Faculty of Medicine, Bulent Ecevit University, Zonguldak, Turkey.
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Abstract
Radiation enteritis is defined as the loss of absorptive capacity of the intestine following irradiation, which is most commonly seen after radiotherapy for pelvic and abdominal malignancies. It is divided into acute and chronic forms and usually presents with diarrhea and malabsorption. Malnutrition is a common complication of chronic radiation enteritis (CRE). We reviewed the etiology, prevalence, symptoms, diagnosis and management of CRE and CRE with malnutrition in this article. Functional short bowel syndrome as a cause of malnutrition in CRE is also considered. The diagnostic work-up includes serum markers, endoscopy, cross-sectional imaging and the exclusion of alternative diagnoses such as recurrent malignancy. Management options of CRE include dietary manipulation, anti-motility agents, electrolyte correction, probiotics, parenteral nutrition, surgical resection and small bowel transplantation. Treatment may also be required for coexisting conditions including vitamin B12 deficiency, bile acid malabsorption and depression.
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Wedlake LJ, Shaw C, Whelan K, Andreyev HJN. Systematic review: the efficacy of nutritional interventions to counteract acute gastrointestinal toxicity during therapeutic pelvic radiotherapy. Aliment Pharmacol Ther 2013; 37:1046-56. [PMID: 23611411 DOI: 10.1111/apt.12316] [Citation(s) in RCA: 50] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2013] [Revised: 03/12/2012] [Accepted: 03/28/2013] [Indexed: 12/15/2022]
Abstract
BACKGROUND Radiotherapy-induced damage to noncancerous 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 for the prevention and management of symptoms. AIM To synthesise the evidence for the use of elemental formula low- or modified-fat diets, fibre, lactose restriction and probiotics, prebiotics and synbiotics to protect the gastrointestinal tract during pelvic radiotherapy. METHODS Four electronic databases were searched. Randomised controlled trials (RCT), controlled trials (CT) and case series in adult patients receiving radiotherapy for pelvic cancers employing nutritional interventions to reduce gastrointestinal toxicity were included. Methodological quality was assessed using a bespoke tool. RESULTS Twenty-two original studies (2446 patients) were identified. Study quality was highly variable with only 37% scoring ≥10 points (maximum 17: bespoke scale). Few studies assessed compliance with the intervention. End-points varied and included symptom scales (IBDQ, CTC, Bristol Stool and RTOG). Evidence from RCTs was weak for elemental, low- or modified-fat, fibre and low-lactose interventions with 1/4, 3/4, 1/2, 0/1 trials respectively reporting favourable outcomes. Evidence for probiotics as prophylactic interventions was more promising (4/5 favourable), but dose, strains and methodologies varied. CONCLUSIONS There is insufficient high-grade evidence to recommend nutritional intervention during pelvic radiotherapy. Total replacement of diet with elemental formula may be appropriate in severe toxicity. Probiotics offer promise, but cannot be introduced into clinical practice without rigorous safety analysis, not least in immunocompromised patients. The methodological quality of nutritional intervention studies needs to be improved.
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Affiliation(s)
- L J Wedlake
- Department of Nutrition and Dietetics, The Royal Marsden NHS Foundation Trust, Sutton & London, UK
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Shadad AK, Sullivan FJ, Martin JD, Egan LJ. Gastrointestinal radiation injury: Symptoms, risk factors and mechanisms. World J Gastroenterol 2013; 19:185-98. [PMID: 23345941 PMCID: PMC3547560 DOI: 10.3748/wjg.v19.i2.185] [Citation(s) in RCA: 179] [Impact Index Per Article: 14.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2011] [Revised: 03/31/2012] [Accepted: 12/15/2012] [Indexed: 02/06/2023] Open
Abstract
Ionising radiation therapy is a common treatment modality for different types of cancer and its use is expected to increase with advances in screening and early detection of cancer. Radiation injury to the gastrointestinal tract is important factor working against better utility of this important therapeutic modality. Cancer survivors can suffer a wide variety of acute and chronic symptoms following radiotherapy, which significantly reduces their quality of life as well as adding an extra burden to the cost of health care. The accurate diagnosis and treatment of intestinal radiation injury often represents a clinical challenge to practicing physicians in both gastroenterology and oncology. Despite the growing recognition of the problem and some advances in understanding the cellular and molecular mechanisms of radiation injury, relatively little is known about the pathophysiology of gastrointestinal radiation injury or any possible susceptibility factors that could aggravate its severity. The aims of this review are to examine the various clinical manifestations of post-radiation gastrointestinal symptoms, to discuss possible patient and treatment factors implicated in normal gastrointestinal tissue radiosensitivity and to outline different mechanisms of intestinal tissue injury.
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Shadad AK, Sullivan FJ, Martin JD, Egan LJ. Gastrointestinal radiation injury: Prevention and treatment. World J Gastroenterol 2013; 19:199-208. [PMID: 23345942 PMCID: PMC3547575 DOI: 10.3748/wjg.v19.i2.199] [Citation(s) in RCA: 93] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2011] [Revised: 03/31/2012] [Accepted: 04/02/2012] [Indexed: 02/06/2023] Open
Abstract
With the recent advances in detection and treatment of cancer, there is an increasing emphasis on the efficacy and safety aspects of cancer therapy. Radiation therapy is a common treatment for a wide variety of cancers, either alone or in combination with other treatments. Ionising radiation injury to the gastrointestinal tract is a frequent side effect of radiation therapy and a considerable proportion of patients suffer acute or chronic gastrointestinal symptoms as a result. These side effects often cause morbidity and may in some cases lower the efficacy of radiotherapy treatment. Radiation injury to the gastrointestinal tract can be minimised by either of two strategies: technical strategies which aim to physically shift radiation dose away from the normal intestinal tissues, and biological strategies which aim to modulate the normal tissue response to ionising radiation or to increase its resistance to it. Although considerable improvement in the safety of radiotherapy treatment has been achieved through the use of modern optimised planning and delivery techniques, biological techniques may offer additional further promise. Different agents have been used to prevent or minimize the severity of gastrointestinal injury induced by ionising radiation exposure, including biological, chemical and pharmacological agents. In this review we aim to discuss various technical strategies to prevent gastrointestinal injury during cancer radiotherapy, examine the different therapeutic options for acute and chronic gastrointestinal radiation injury and outline some examples of research directions and considerations for prevention at a pre-clinical level.
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Muls AC, Watson L, Shaw C, Andreyev HJN. Managing gastrointestinal symptoms after cancer treatment: a practical approach for gastroenterologists. Frontline Gastroenterol 2013; 4:57-68. [PMID: 28839701 PMCID: PMC5369780 DOI: 10.1136/flgastro-2012-100218] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2012] [Revised: 07/12/2012] [Accepted: 07/12/2012] [Indexed: 02/07/2023] Open
Abstract
The percentage of the population living with a diagnosis of cancer is rising. By 2030, there will be 4 million cancer survivors in the UK. One quarter of cancer survivors are left with physical symptoms, which affect their quality of life. Gastrointestinal (GI) symptoms are the most common of all chronic physical side-effects of cancer treatment and have the greatest impact on daily activity. Cancer therapies induce long-term changes in bowel function due to alterations to specific GI physiological functions. In addition, the psychological effect of a cancer diagnosis, new GI disease or pre-existing underlying conditions, may also contribute to new symptoms. Twenty-three upper GI symptoms have been identified as occurring after pelvic radiotherapy. After upper GI cancer treatment, the most troublesome symptoms include reflux, abdominal pain, indigestion, diarrhoea and fatigue. Often, several symptoms are present simultaneously and women experience more symptoms than men. The symptoms which patients rate as most difficult are urgency, wind, diarrhoea, incontinence, abdominal pain and rectal bleeding. Recent UK Guidance on managing GI symptoms suggests that these symptoms can be treated especially if gastroenterological advice is combined with dietetic and nursing input to optimise investigations and management. However, as different pathological processes can result in identical symptoms; a systematic, 'algorithmic' approach to assess and treat these symptoms is required. This paper aims to illustrate the value of such an approach to investigate and treat the most common GI symptoms that trouble patients. The algorithm allows clinicians to institute a comprehensive medical management plan.
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Affiliation(s)
- Ann C Muls
- The GI unit, Department of Medicine, The Royal Marsden Hospital, London and Sutton, UK
| | - Lorraine Watson
- The Department of Nutrition and Dietetics, The Royal Marsden Hospital, London and Sutton, UK
| | - Clare Shaw
- The Department of Nutrition and Dietetics, The Royal Marsden Hospital, London and Sutton, UK
| | - H Jervoise N Andreyev
- The GI unit, Department of Medicine, The Royal Marsden Hospital, London and Sutton, UK
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Mouiseddine M, François S, Souidi M, Chapel A. Intravenous human mesenchymal stem cells transplantation in NOD/SCID mice preserve liver integrity of irradiation damage. Methods Mol Biol 2012; 826:179-88. [PMID: 22167649 DOI: 10.1007/978-1-61779-468-1_15] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
This work was initiated in an effort to evaluate the potential therapeutic contribution of the infusion of mesenchymal stem cells (MSC) for the correction of liver injuries. We subjected NOD-SCID mice to a 10.5-Gy abdominal irradiation and we tested the biological and histological markers of liver injury in the absence and after infusion of expanded human MSC. Irradiation alone induced a significant elevation of the ALT and AST. Apoptosis in the endothelial layer of vessels was observed. When MSC were infused in mice, a significant decrease of transaminases was measured, and a total disappearance of apoptotic cells. MSC were not found in liver. To explain the protection of liver without MSC engraftment, we hypothesize an indirect action of MSC on the liver via the intestinal tract. Pelvic or total body irradiation induces intestinal absorption defects leading to an alteration of the enterohepatic recirculation of bile acids. This alteration induces an increase in Deoxy Cholic Acid (DCA) which is hepatoxic. In this study, we confirm these results. DCA concentration increased approximately twofold after irradiation but stayed to the baseline level after MSC injection. We propose from our observations that, following irradiation, MSC infusion indirectly corrected liver dysfunction by preventing gut damage. This explanation would be consistent with the absence of MSC engraftment in liver. These results evidenced that MSC treatment of a target organ may have an effect on distant tissues. This observation comes in support to the interest for the use of MSC for cellular therapy in multiple pathologies proposed in the recent years.
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Stewart FA, Akleyev AV, Hauer-Jensen M, Hendry JH, Kleiman NJ, Macvittie TJ, Aleman BM, Edgar AB, Mabuchi K, Muirhead CR, Shore RE, Wallace WH. ICRP publication 118: ICRP statement on tissue reactions and early and late effects of radiation in normal tissues and organs--threshold doses for tissue reactions in a radiation protection context. Ann ICRP 2012; 41:1-322. [PMID: 22925378 DOI: 10.1016/j.icrp.2012.02.001] [Citation(s) in RCA: 858] [Impact Index Per Article: 66.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/03/2023]
Abstract
This report provides a review of early and late effects of radiation in normal tissues and organs with respect to radiation protection. It was instigated following a recommendation in Publication 103 (ICRP, 2007), and it provides updated estimates of 'practical' threshold doses for tissue injury defined at the level of 1% incidence. Estimates are given for morbidity and mortality endpoints in all organ systems following acute, fractionated, or chronic exposure. The organ systems comprise the haematopoietic, immune, reproductive, circulatory, respiratory, musculoskeletal, endocrine, and nervous systems; the digestive and urinary tracts; the skin; and the eye. Particular attention is paid to circulatory disease and cataracts because of recent evidence of higher incidences of injury than expected after lower doses; hence, threshold doses appear to be lower than previously considered. This is largely because of the increasing incidences with increasing times after exposure. In the context of protection, it is the threshold doses for very long follow-up times that are the most relevant for workers and the public; for example, the atomic bomb survivors with 40-50years of follow-up. Radiotherapy data generally apply for shorter follow-up times because of competing causes of death in cancer patients, and hence the risks of radiation-induced circulatory disease at those earlier times are lower. A variety of biological response modifiers have been used to help reduce late reactions in many tissues. These include antioxidants, radical scavengers, inhibitors of apoptosis, anti-inflammatory drugs, angiotensin-converting enzyme inhibitors, growth factors, and cytokines. In many cases, these give dose modification factors of 1.1-1.2, and in a few cases 1.5-2, indicating the potential for increasing threshold doses in known exposure cases. In contrast, there are agents that enhance radiation responses, notably other cytotoxic agents such as antimetabolites, alkylating agents, anti-angiogenic drugs, and antibiotics, as well as genetic and comorbidity factors. Most tissues show a sparing effect of dose fractionation, so that total doses for a given endpoint are higher if the dose is fractionated rather than when given as a single dose. However, for reactions manifesting very late after low total doses, particularly for cataracts and circulatory disease, it appears that the rate of dose delivery does not modify the low incidence. This implies that the injury in these cases and at these low dose levels is caused by single-hit irreparable-type events. For these two tissues, a threshold dose of 0.5Gy is proposed herein for practical purposes, irrespective of the rate of dose delivery, and future studies may elucidate this judgement further.
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López Rodríguez M, Martín Martín M, Cerezo Padellano L, Marín Palomo A, Ibáñez Puebla Y. Gastrointestinal toxicity associated to radiation therapy. Clin Transl Oncol 2010; 12:554-61. [DOI: 10.1007/s12094-010-0553-1] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
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Martin E, Pointreau Y, Roche-Forestier S, Barillot I. [Normal tissue tolerance to external beam radiation therapy: small bowel]. Cancer Radiother 2010; 14:350-3. [PMID: 20598616 DOI: 10.1016/j.canrad.2010.03.013] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2010] [Revised: 02/22/2010] [Accepted: 03/03/2010] [Indexed: 01/12/2023]
Abstract
The small bowel is a hollow organ involved in the transit and absorption of food. In relation to its anatomical location, a significant amount of this organ is exposed in whole or in part to ionizing radiation in external radiotherapy during abdominal or pelvic irradiation either for primary cancers or metastasis. The acute functional changes during external beam radiation are mainly leading to diarrhea, abdominal pain and bloating. The main late side effects of irradiation of the small intestine are chronic diarrhea, malabsorption with steatorrhea, abdominal spasms, intestinal obstruction, bleeding and fistulas. The architecture of the small intestine may be considered as parallel with a significant correlation between the irradiated volume of small bowel and the likelihood of acute toxicity, whatever the dose. The literature analysis recommends to consider the volume of small bowel receiving 15 Gy (threshold of 100 to 200 cm(3)) but also 30 and 50 Gy (thresholds of 35 to 300 cm(3), depending on the level of dose considered). Modern techniques of conformal radiotherapy with modulated intensity will probably have beneficial impact on small bowel toxicity.
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Affiliation(s)
- E Martin
- Département de Radiothérapie, Centre Georges-Francois-Leclerc, 1 Rue du Professeur-Marion, 21079 Dijon cedex, France
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Yeoh EK, Bartholomeusz DL, Holloway RH, Fraser RJ, Botten R, Di Matteo A, Moore JW, Schoeman MN. Disturbed colonic motility contributes to anorectal symptoms and dysfunction after radiotherapy for carcinoma of the prostate. Int J Radiat Oncol Biol Phys 2010; 78:773-80. [PMID: 20153122 DOI: 10.1016/j.ijrobp.2009.08.050] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2009] [Revised: 07/18/2009] [Accepted: 08/24/2009] [Indexed: 11/28/2022]
Abstract
PURPOSE To evaluate the role of colonic motility in the pathogenesis of anorectal symptoms and dysfunction after radiotherapy (RT) for carcinoma of the prostate. PATIENTS AND METHODS Thirty-eight patients, median age 71 (range, 50-81) years with localized prostate carcinoma randomized to one of two radiation dose schedules underwent colonic transit scintigraphy and assessment of anorectal symptoms (questionnaire), anorectal function (manometry), and anal sphincteric morphology (endoanal ultrasound) before and at 1 month and 1 year after RT. RESULTS Whole and distal colonic transit increased 1 month after RT, with faster distal colonic transit only persisting at 1 year. Frequency and urgency of defecation, fecal incontinence, and rectal bleeding increased 1 month after RT and persisted at 1 year. Basal anal pressures remained unchanged, but progressive reductions occurred in anal squeeze pressures and responses to increased intra-abdominal pressure. Rectal compliance decreased progressively in the patients, although no changes in anorectal sensory function ensued. Radiotherapy had no effect on the morphology of the internal and external anal sphincters. Distal colonic retention was weakly related to rectal compliance at 1 month, but both faster colonic transit and reduced rectal compliance were more frequent with increased fecal urgency. At 1 year, a weak inverse relationship existed between colonic half-clearance time and frequency of defecation, although both faster whole-colonic transit and reduced rectal compliance occurred more often with increased stool frequency. CONCLUSION Colonic dysmotility contributes to anorectal dysfunction after RT for carcinoma of the prostate. This has implications for improving the management of anorectal radiation sequelae.
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Affiliation(s)
- Eric K Yeoh
- Department of Radiation Oncology, Royal Adelaide Hospital, Adelaide, SA, Australia.
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Theis V, Sripadam R, Ramani V, Lal S. Chronic Radiation Enteritis. Clin Oncol (R Coll Radiol) 2010; 22:70-83. [DOI: 10.1016/j.clon.2009.10.003] [Citation(s) in RCA: 156] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2009] [Revised: 09/01/2009] [Accepted: 09/22/2009] [Indexed: 02/07/2023]
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Late gastrointestinal complications after pelvic radiotherapy: radiation enteritis. Clin Transl Oncol 2009; 11:539-43. [PMID: 19661029 DOI: 10.1007/s12094-009-0399-6] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
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Wedlake L, Thomas K, McGough C, Andreyev H. Small bowel bacterial overgrowth and lactose intolerance during radical pelvic radiotherapy: An observational study. Eur J Cancer 2008; 44:2212-7. [DOI: 10.1016/j.ejca.2008.07.018] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2008] [Revised: 07/06/2008] [Accepted: 07/11/2008] [Indexed: 01/05/2023]
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Radiation damage to the gastrointestinal tract: mechanisms, diagnosis, and management. Curr Opin Support Palliat Care 2008; 1:23-9. [PMID: 18660720 DOI: 10.1097/spc.0b013e3281108014] [Citation(s) in RCA: 77] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
PURPOSE OF REVIEW To summarize current knowledge about gastrointestinal radiation toxicity, with emphasis on mechanisms and clinical diagnosis and management. RECENT FINDINGS While there has been only modest change in cancer incidence and cancer mortality rates during the past 30 years, the number of cancer survivors has more than doubled. Moreover, the recognition of uncomplicated cancer cure as the ultimate goal in oncology has intensified efforts to prevent, diagnose, and manage side effects of radiation therapy. These efforts have been facilitated by recent insight into the underlying pathophysiology. SUMMARY The risk of injury to the intestine is dose limiting during abdominal and pelvic radiation therapy. Delayed bowel toxicity is difficult to manage and adversely impacts the quality of life of cancer survivors. More than 200,000 patients per year receive abdominal or pelvic radiation therapy, and the estimated number of cancer survivors with postradiation intestinal dysfunction is 1.5-2 million. Worthwhile progress towards reducing toxicity of radiation therapy has been made by dose-sculpting treatment techniques. Approaches derived from an improved understanding of the pathophysiology of bowel injury, however, will result in further advances. This article discusses the mechanisms of radiation-induced bowel toxicity and reviews current principles in diagnosis and management.
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Vistad I, Kristensen GB, Fosså SD, Dahl AA, Mørkrid L. Intestinal malabsorption in long-term survivors of cervical cancer treated with radiotherapy. Int J Radiat Oncol Biol Phys 2008; 73:1141-7. [PMID: 18760883 DOI: 10.1016/j.ijrobp.2008.05.064] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2007] [Revised: 04/15/2008] [Accepted: 05/21/2008] [Indexed: 11/16/2022]
Abstract
PURPOSE The aim of this cross-sectional study is to investigate the associations between pelvic radiotherapy (RT) and markers of intestinal absorption in cervical cancer survivors (CCSs). We compared patient data with normative data from a reference population and explored the associations between cobalamin status and clinically significant diarrhea and depression. METHODS AND MATERIALS Fifty-five CCSs treated with RT in 1994-1999 were included in 2005 in a follow-up questionnaire study exploring physical and psychological symptoms. Blood tests, including serum (S)-vitamin B(12,) S-methylmalonic acid, S-folate, erythrocyte-folate, and plasma homocysteine, were analyzed. Differences in median values between CCSs and reference populations were evaluated by using Wilcoxon tests. Associations between variables were examined by means of multiple regression analyses. RESULTS Median S-vitamin B(12) level was significantly lower and median S-methylmalonic acid level was significantly higher in CCSs compared with the reference population (p < 0.001). Correction for renal function verified a likely cobalamin deficiency in 20% of CCSs (11 of 55). Diarrhea or depression was not significantly related to any of the mentioned markers of cobalamin or folate status. Fifteen percent of CCSs (8 of 55) had subnormal S-calcium values. CONCLUSIONS Significant cobalamin deficiency was observed in 11 (20%) and low calcium level was observed in 8 CCSs (15%) 6-12 years after pelvic RT. Neither diarrhea nor depression was associated with this deficiency. Routine monitoring of S-vitamin B(12) level is recommended, and regular intake of cobalamin should be considered in CCSs treated with RT.
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Affiliation(s)
- Ingvild Vistad
- Department of Gynecology, Sørlandet Hospital HF, Kristiansand, Norway.
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Maher EJ, Denton A. Survivorship, late effects and cancer of the cervix. Clin Oncol (R Coll Radiol) 2008; 20:479-87. [PMID: 18515052 DOI: 10.1016/j.clon.2008.04.009] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2008] [Revised: 04/10/2008] [Accepted: 04/29/2008] [Indexed: 11/17/2022]
Abstract
As the prevention and treatment of cervical cancer improves, there is increasing focus on the months and years after cancer treatment. Of those women living after a diagnosis of cancer, 10% will have a gynaecological malignancy and although the incidence of cervix cancer has dropped over the last 20 years, so has the age at diagnosis, with more than 60% surviving at least 5 years. In a recent report, 63% of 231 064 US survivors of cervix cancer were more than 10 years from diagnosis. More survivors are living long enough to develop chronic treatment-related conditions. The 2007 English Cancer Reform Strategy highlighted the importance of cancer survivorship and uses the US National Coalition for Cancer Survivorship definition-'living through and beyond cancer'. The emerging picture is of populations living after a diagnosis of cancer without active disease, still having similar health and disability profiles to populations with a diagnosis of a chronic illness. This offers new challenges in identifying and meeting their needs.
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Affiliation(s)
- E J Maher
- Mount Vernon Cancer Centre, Mount Vernon Hospital, Rickmansworth Road, Northwood, Middlesex, UK.
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Kim T, Chae G, Chung SS, Sands DR, Speranza JR, Weiss EG, Nogueras JJ, Wexner SD. Faecal incontinence in male patients. Colorectal Dis 2008; 10:124-30. [PMID: 17498204 DOI: 10.1111/j.1463-1318.2007.01266.x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
OBJECTIVE Data concerning faecal incontinence (FI) in men are lacking. The aim of this study was to evaluate the historical aetiology and contrast aetiologies in younger and older men suffering from FI. METHOD After institutional review board approval, a retrospective chart review was undertaken of all patients with FI seen between 1999 and 2005. The data of male patients was further analysed to assess the impact of age and historical aetiology on FI. RESULTS A total of 404 males were included, 203 patients were <70 years of age (group A) and 201 patients were >or=70 years of age (group B). The most common prior diagnosis in group A was perianal sepsis in 23 (11.3%) patients and symptomatic haemorrhoids in 20 (9.9%) patients; in group B it was prostate cancer in 57 (28.4%) patients, symptomatic haemorrhoids in 31 (15.4%) patients and neurological diseases in 18 (9%) patients. The most common prior procedure in group A was restorative proctectomy/proctocolectomy in 32 (15.8%) patients, fistulotomy or haemorrhoidectomy in 21 (10.3%) and 19 (9.4%) patients respectively. In group B, radiation therapy for prostate cancer was utilized in 48 (23.9%) patients and haemorrhoidectomy in 29 (14.4%) patients. Comparing group A and group B relative to diagnosis - perianal sepsis, perineal trauma, congenital disorders, HIV infection and anal cancer were more common in group A, whereas prostate cancer, neurological diseases and colon cancer were significantly more common in group B. CONCLUSION Prostate cancer, symptomatic haemorrhoids, perianal sepsis, rectal cancer and a history of restorative rectal resection were common associations with FI in men. The aetiologies for FI in men vary with age.
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Affiliation(s)
- T Kim
- Department of Colorectal Surgery, Cleveland Clinic Florida, Weston, Florida 33331, USA
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