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Wu Z, Ni C, Ye Z, Xia Z, Li L, Yu Z, Tang S, Lin Y, Zhong W. The efficacy of aminosalicylates in acute radiation enteritis: a systematic review and meta-analysis. Front Pharmacol 2025; 16:1544981. [PMID: 40331201 PMCID: PMC12052727 DOI: 10.3389/fphar.2025.1544981] [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: 12/16/2024] [Accepted: 04/08/2025] [Indexed: 05/08/2025] Open
Abstract
Background and purpose Aminosalicylates have been used for the prevention and treatment of radiation enteritis (RE) for more than 50 years. However, their effectiveness in acute radiation enteritis (ARE) has been controversial. We conducted a meta-analysis to clarify the clinical efficacy of aminosalicylates in controlling the symptoms of ARE. Materials and methods We searched PubMed, Cochrane Library, Embase, and Web of Science for studies published before January 2020. Eligible randomized controlled trials (RCTs) comparing the incidence of diarrhea, abdominal pain, constipation, tenesmus, and hematochezia between the aminosalicylates and control groups were included. Subgroup analyses were conducted based on different drugs and doses. Publication bias was assessed using funnel plots. Results Seven RCTs with 613 patients were included. Aminosalicylates reduced the incidence of mild to moderate diarrhea (P < 0.05), while total diarrhea, severe diarrhea, abdominal pain, hematochezia, tenesmus, and constipation showed no significant differences from the control group. Subgroup analysis showed that sulfasalazine (SASP) reduced mild to moderate diarrhea (P < 0.05), whereas 5-aminosalicylic acid (5-ASA) increased total and severe diarrhea (P < 0.05). Additionally, when aminosalicylate doses exceeded 2 g/d, diarrhea incidence increased (P < 0.05). Conclusion SASP is a safe and effective treatment for mild to moderate diarrhea, while 5-ASA may increase diarrhea incidence in ARE patients. Aminosalicylates at ≤2 g/d are safe for ARE, but higher doses may worsen diarrhea.
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Affiliation(s)
- Zhendong Wu
- Department of Gastroenterology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China
- Department of Gastroenterology, Dongguan Songshan Lake Tungwah Hospital, Dongguan, Guangdong, China
| | - Chuyan Ni
- Department of Gastroenterology, Longgang District People’s Hospital of Shenzhen, Shenzhen, Guangdong, China
| | - Zhen Ye
- Department of Gastroenterology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Zhongsheng Xia
- Department of Gastroenterology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Li Li
- Department of Emergency, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Zhong Yu
- Department of Gastroenterology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Song Tang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, Guangdong, China
| | - Ying Lin
- Department of Gastroenterology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Wa Zhong
- Department of Gastroenterology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China
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Nunes VRT, Vidigal PVT, Pereira MT, Ladeira LCD, Caliari MV, Oliveira FMS, Cesar ALA, Faraco AAG, Barbuto RC, Duval-Araujo I. Evaluation of mesalazine polymeric conjugate in the treatment of actinic proctitis in rats. Acta Cir Bras 2021; 36:e360805. [PMID: 34644773 PMCID: PMC8516428 DOI: 10.1590/acb360805] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2021] [Accepted: 07/24/2021] [Indexed: 11/21/2022] Open
Abstract
Purpose: The present study aimed at testing a new formulation of mesalazine linked to
chondroitin sulfate and its components alone in the treatment of actinic
proctitis in rats. Methods: Forty-seven female Wistar rats were submitted to pelvic radiation and divided
into eight groups: control A, mesalazine A, chondroitin A, and conjugate A,
gavage of the according substance two weeks after irradiation and sacrifice
three weeks after oral treatment; control C, mesalazine C, chondroitin C,
and conjugate C, sacrifice six weeks after oral treatment. The rectum was
submitted to histological characterization for each of the findings:
inflammatory infiltrate, epithelial degeneration, mucosal necrosis, and
fibrosis. Results: The inflammatory infiltrate was more intense in chondroitin A, mesalazine A,
and conjugate C. The collagen deposition was less intense in chondroitin A,
and mesalazine A, and more intense in control C. Conclusions: Mesalazine and chondroitin alone were efficacious in inducing a delayed
inflammatory response, hence reducing the late fibrosis. The conjugate was
able to induce an ever more delayed inflammatory response.
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Rehailia-Blanchard A, He M, Rancoule C, Vallard A, Espenel S, Nivet A, Magné N, Chargari C. Physiopathologie et modulation pharmacologique de l’entérite radique. Cancer Radiother 2019; 23:240-247. [DOI: 10.1016/j.canrad.2018.05.010] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2018] [Revised: 05/07/2018] [Accepted: 05/11/2018] [Indexed: 01/28/2023]
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Valencia J, Velilla C, Urpegui A, Alvarez I, Llorens MA, Coronel P, Polo S, Bascón N, Escó R. The Efficacy of Orgotein in the Treatment of Acute Toxicity Due to Radiotherapy on Head and Neck Tumors. TUMORI JOURNAL 2018; 88:385-9. [PMID: 12487556 DOI: 10.1177/030089160208800507] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Aims and background To assess the efficacy of orgotein in the treatment of acute secondary effects of radiotherapy on head and neck tumors. Material and methods Data were collected on 41 patients who received radiotherapy for tumors of the head and neck. Radiotherapy was the exclusive treatment in 19.5% of cases, with surgery in 24.4%, chemotherapy in 48.8%, and with both in 7.3%. The toxicity requiring use of orgotein was: oropharynx mucositis (26.8%), dysphagia (34.2%), or both (39%), in grade 2 or more according to the RTOG scale. Orgotein (8 mg im) was administered every 48 hrs until radiotherapy was finished. Results The overall response rate was 92.5%; a complete response was obtained in 12 patients (30%) and partial in 25 (62.5%). The reduction in toxicity at the end of radiotherapy was one grade in 18 patients (45%), 2 grades in 16 (40%), 3 in 2 patients (5%), and 4 grades in the only patient with grade 4 acute toxicity. A statistically significant influence was shown in obtaining complete response: laryngeal tumor location (P = 0.037), duration of radiotherapy of more than 53 days (P = 0.002), discontinuation for non-toxic reasons (P = 0.008). Conclusions We consider that orgotein is highly effective in dealing with acute secondary effects of radiotherapy on the head and neck area.
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Affiliation(s)
- Javier Valencia
- Radiotherapeutic Oncology Unit, Hospital Clinico Universitario Lozano Blesa, San Juan Bosco, Zaragoza, Spain
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Yavuz E, Ercan G, Karagulle OO, Bayrak BY, Biricik A, Ercetin C, Gokcek B, Yigitbas H, Kusaslan R, Celik A, Gulcicek OB. Evaluation of prophylactic and therapeutic effects of sildenafil on acute radiation proctitis in rats. Acta Cir Bras 2018; 33:362-374. [DOI: 10.1590/s0102-865020180040000008] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2017] [Accepted: 05/20/2018] [Indexed: 01/27/2023] Open
Affiliation(s)
- Erkan Yavuz
- University of Health Science Bagcilar Training and Research Hospital, Turkey
| | - Gulcin Ercan
- University of Health Science Bagcilar Training and Research Hospital, Turkey
| | | | | | - Aytac Biricik
- University of Health Science Bagcilar Training and Research Hospital, Turkey
| | - Candas Ercetin
- University of Health Science Bagcilar Training and Research Hospital, Turkey
| | - Berk Gokcek
- University of Health Science Okmeydanı Training and Research Hospital, Turkey
| | - Hakan Yigitbas
- University of Health Science Bagcilar Training and Research Hospital, Turkey
| | - Ramazan Kusaslan
- University of Health Science Bagcilar Training and Research Hospital, Turkey
| | - Atilla Celik
- University of Health Science Bagcilar Training and Research Hospital, Turkey
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Lawrie TA, Green JT, Beresford M, Wedlake L, Burden S, Davidson SE, Lal S, Henson CC, Andreyev HJN. Interventions to reduce acute and late adverse gastrointestinal effects of pelvic radiotherapy for primary pelvic cancers. Cochrane Database Syst Rev 2018; 1:CD012529. [PMID: 29360138 PMCID: PMC6491191 DOI: 10.1002/14651858.cd012529.pub2] [Citation(s) in RCA: 49] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND An increasing number of people survive cancer but a significant proportion have gastrointestinal side effects as a result of radiotherapy (RT), which impairs their quality of life (QoL). OBJECTIVES To determine which prophylactic interventions reduce the incidence, severity or both of adverse gastrointestinal effects among adults receiving radiotherapy to treat primary pelvic cancers. SEARCH METHODS We conducted searches of CENTRAL, MEDLINE, and Embase in September 2016 and updated them on 2 November 2017. We also searched clinical trial registries. SELECTION CRITERIA We included randomised controlled trials (RCTs) of interventions to prevent adverse gastrointestinal effects of pelvic radiotherapy among adults receiving radiotherapy to treat primary pelvic cancers, including radiotherapy techniques, other aspects of radiotherapy delivery, pharmacological interventions and non-pharmacological interventions. Studies needed a sample size of 20 or more participants and needed to evaluate gastrointestinal toxicity outcomes. We excluded studies that evaluated dosimetric parameters only. We also excluded trials of interventions to treat acute gastrointestinal symptoms, trials of altered fractionation and dose escalation schedules, and trials of pre- versus postoperative radiotherapy regimens, to restrict the vast scope of the review. DATA COLLECTION AND ANALYSIS We used standard Cochrane methodology. We used the random-effects statistical model for all meta-analyses, and the GRADE system to rate the certainty of the evidence. MAIN RESULTS We included 92 RCTs involving more than 10,000 men and women undergoing pelvic radiotherapy. Trials involved 44 different interventions, including radiotherapy techniques (11 trials, 4 interventions/comparisons), other aspects of radiotherapy delivery (14 trials, 10 interventions), pharmacological interventions (38 trials, 16 interventions), and non-pharmacological interventions (29 trials, 13 interventions). Most studies (79/92) had design limitations. Thirteen studies had a low risk of bias, 50 studies had an unclear risk of bias and 29 studies had a high risk of bias. Main findings include the following:Radiotherapy techniques: Intensity-modulated radiotherapy (IMRT) versus 3D conformal RT (3DCRT) may reduce acute (risk ratio (RR) 0.48, 95% confidence interval (CI) 0.26 to 0.88; participants = 444; studies = 4; I2 = 77%; low-certainty evidence) and late gastrointestinal (GI) toxicity grade 2+ (RR 0.37, 95% CI 0.21 to 0.65; participants = 332; studies = 2; I2 = 0%; low-certainty evidence). Conformal RT (3DCRT or IMRT) versus conventional RT reduces acute GI toxicity grade 2+ (RR 0.57, 95% CI 0.40 to 0.82; participants = 307; studies = 2; I2 = 0%; high-certainty evidence) and probably leads to less late GI toxicity grade 2+ (RR 0.49, 95% CI 0.22 to 1.09; participants = 517; studies = 3; I2 = 44%; moderate-certainty evidence). When brachytherapy (BT) is used instead of external beam radiotherapy (EBRT) in early endometrial cancer, evidence indicates that it reduces acute GI toxicity (grade 2+) (RR 0.02, 95% CI 0.00 to 0.18; participants = 423; studies = 1; high-certainty evidence).Other aspects of radiotherapy delivery: There is probably little or no difference in acute GI toxicity grade 2+ with reduced radiation dose volume (RR 1.21, 95% CI 0.81 to 1.81; participants = 211; studies = 1; moderate-certainty evidence) and maybe no difference in late GI toxicity grade 2+ (RR 1.02, 95% CI 0.15 to 6.97; participants = 107; studies = 1; low-certainty evidence). Evening delivery of RT may reduce acute GI toxicity (diarrhoea) grade 2+ during RT compared with morning delivery of RT (RR 0.51, 95% CI 0.34 to 0.76; participants = 294; studies = 2; I2 = 0%; low-certainty evidence). There may be no difference in acute (RR 2.22, 95% CI 0.62 to 7.93, participants = 110; studies = 1) and late GI toxicity grade 2+ (RR 0.44, 95% CI 0.12 to 1.65; participants = 81; studies = 1) between a bladder volume preparation of 1080 mls and that of 540 mls (low-certainty evidence). Low-certainty evidence on balloon and hydrogel spacers suggests that these interventions for prostate cancer RT may make little or no difference to GI outcomes.Pharmacological interventions: Evidence for any beneficial effects of aminosalicylates, sucralfate, amifostine, corticosteroid enemas, bile acid sequestrants, famotidine and selenium is of a low or very low certainty. However, evidence on certain aminosalicylates (mesalazine, olsalazine), misoprostol suppositories, oral magnesium oxide and octreotide injections suggests that these agents may worsen GI symptoms, such as diarrhoea or rectal bleeding.Non-pharmacological interventions: Low-certainty evidence suggests that protein supplements (RR 0.23, 95% CI 0.07 to 0.74; participants = 74; studies = 1), dietary counselling (RR 0.04, 95% CI 0.00 to 0.60; participants = 74; studies = 1) and probiotics (RR 0.43, 95% CI 0.22 to 0.82; participants = 923; studies = 5; I2 = 91%) may reduce acute RT-related diarrhoea (grade 2+). Dietary counselling may also reduce diarrhoeal symptoms in the long term (at five years, RR 0.05, 95% CI 0.00 to 0.78; participants = 61; studies = 1). Low-certainty evidence from one study (108 participants) suggests that a high-fibre diet may have a beneficial effect on GI symptoms (mean difference (MD) 6.10, 95% CI 1.71 to 10.49) and quality of life (MD 20.50, 95% CI 9.97 to 31.03) at one year. High-certainty evidence indicates that glutamine supplements do not prevent RT-induced diarrhoea. Evidence on various other non-pharmacological interventions, such as green tea tablets, is lacking.Quality of life was rarely and inconsistently reported across included studies, and the available data were seldom adequate for meta-analysis. AUTHORS' CONCLUSIONS Conformal radiotherapy techniques are an improvement on older radiotherapy techniques. IMRT may be better than 3DCRT in terms of GI toxicity, but the evidence to support this is uncertain. There is no high-quality evidence to support the use of any other prophylactic intervention evaluated. However, evidence on some potential interventions shows that they probably have no role to play in reducing RT-related GI toxicity. More RCTs are needed for interventions with limited evidence suggesting potential benefits.
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Affiliation(s)
- Theresa A Lawrie
- Cochrane Gynaecological, Neuro-oncology and Orphan Cancer Group, 1st Floor Education Centre, Royal United Hospital, Combe Park, Bath, UK, BA1 3NG
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Probiotics for prevention of radiation-induced diarrhea: A meta-analysis of randomized controlled trials. PLoS One 2017; 12:e0178870. [PMID: 28575095 PMCID: PMC5456391 DOI: 10.1371/journal.pone.0178870] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2017] [Accepted: 05/19/2017] [Indexed: 02/07/2023] Open
Abstract
Background Radiotherapy is commonly used for abdominal or pelvic cancer, and patients receiving radiotherapy have a high risk developing to an acute radiation-induced diarrhea. Several previous studies have discussed the effect of probiotics on prevention of radiation-induced diarrhea, but the results are still inconsistent. Objective We performed a meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy of probiotic supplementation for prevention the radiation-induced diarrhea. Methods Relevant RCTs studies assessing the effect of probiotic supplementation on clinical outcomes compared with placebo were searched in PubMed, EMBASE, and the Cochrane Library databases (up to March 30 2016). Heterogeneity was assessed with I2 and H2, and publication bias was evaluated using sensitive analysis. Results Six trials, a total of 917 participants (490 participants received prophylactic probiotics and 427 participants received placebo), were included in this meta-analysis. Compared with placebo, probiotics were associated with a lower incidence of radiation-induced diarrhea (RR: 0.55; 95% CI: 0.34–0.88; P = 0.01; I2: 87%; 95% CI: 75%-94%; H2: 2.8; 95% CI: 2.0–4.0). However, there is no significant difference in the anti-diarrheal medication use (RR: 0.68; 95% CI: 0.40–1.14; P = 0.14) or bristol scale on stool form (RR: 0.64; 95% CI: 0.35–1.17; P = 0.14). Conclusion Probiotics may be beneficial to prevent radiation-induced diarrhea in patients who suffered from abdominal or pelvic cancers during radiotherapy period.
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Current Status of Targeted Radioprotection and Radiation Injury Mitigation and Treatment Agents: A Critical Review of the Literature. Int J Radiat Oncol Biol Phys 2017; 98:662-682. [PMID: 28581409 DOI: 10.1016/j.ijrobp.2017.02.211] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2016] [Revised: 02/22/2017] [Accepted: 02/23/2017] [Indexed: 01/17/2023]
Abstract
As more cancer patients survive their disease, concerns about radiation therapy-induced side effects have increased. The concept of radioprotection and radiation injury mitigation and treatment offers the possibility to enhance the therapeutic ratio of radiation therapy by limiting radiation therapy-induced normal tissue injury without compromising its antitumor effect. Advances in the understanding of the underlying mechanisms of radiation toxicity have stimulated radiation oncologists to target these pathways across different organ systems. These generalized radiation injury mechanisms include production of free radicals such as superoxides, activation of inflammatory pathways, and vascular endothelial dysfunction leading to tissue hypoxia. There is a significant body of literature evaluating the effectiveness of various treatments in preventing, mitigating, or treating radiation-induced normal tissue injury. Whereas some reviews have focused on a specific disease site or agent, this critical review focuses on a mechanistic classification of activity and assesses multiple agents across different disease sites. The classification of agents used herein further offers a useful framework to organize the multitude of treatments that have been studied. Many commonly available treatments have demonstrated benefit in prevention, mitigation, and/or treatment of radiation toxicity and warrant further investigation. These drug-based approaches to radioprotection and radiation injury mitigation and treatment represent an important method of making radiation therapy safer.
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van de Wetering FT, Verleye L, Andreyev HJN, Maher J, Vlayen J, Pieters BR, van Tienhoven G, Scholten RJPM, Cochrane Gynaecological, Neuro‐oncology and Orphan Cancer Group. Non-surgical interventions for late rectal problems (proctopathy) of radiotherapy in people who have received radiotherapy to the pelvis. Cochrane Database Syst Rev 2016; 4:CD003455. [PMID: 27111831 PMCID: PMC7173735 DOI: 10.1002/14651858.cd003455.pub2] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND This is an update of a Cochrane review first published in 2002, and previously updated in 2007. Late radiation rectal problems (proctopathy) include bleeding, pain, faecal urgency, and incontinence and may develop after pelvic radiotherapy treatment for cancer. OBJECTIVES To assess the effectiveness and safety of non-surgical interventions for managing late radiation proctopathy. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 11, 2015); MEDLINE (Ovid); EMBASE (Ovid); CANCERCD; Science Citation Index; and CINAHL from inception to November 2015. SELECTION CRITERIA We included randomised controlled trials (RCTs) comparing non-surgical interventions for the management of late radiation proctopathy in people with cancer who have undergone pelvic radiotherapy for cancer. Primary outcomes considered were: episodes of bowel activity, bleeding, pain, tenesmus, urgency, and sphincter dysfunction. DATA COLLECTION AND ANALYSIS Study selection, 'Risk of bias' assessment, and data extraction were performed in duplicate, and any disagreements were resolved by involving a third review author. MAIN RESULTS We identified 1221 unique references and 16 studies including 993 participants that met our inclusion criteria. One study found through the last update was moved to the 'Studies awaiting classification' section. We did not pool outcomes for a meta-analysis due to variation in study characteristics and endpoints across included studies.Since radiation proctopathy is a condition with various symptoms or combinations of symptoms, the studies were heterogeneous in their intended effect. Some studies investigated treatments targeted at bleeding only (group 1), some investigated treatments targeted at a combination of anorectal symptoms, but not a single treatment (group 2). The third group focused on the treatment of the collection of symptoms referred to as pelvic radiation disease. In order to enable some comparison of this heterogeneous collection of studies, we describe the effects in these three groups separately.Nine studies assessed treatments for rectal bleeding and were unclear or at high risk of bias. The only treatments that made a significant difference on primary outcomes were argon plasma coagulation (APC) followed by oral sucralfate versus APC with placebo (endoscopic score 6 to 9 in favour of APC with placebo, risk ratio (RR) 2.26, 95% confidence interval (CI) 1.12 to 4.55; 1 study, 122 participants, low- to moderate-quality evidence); formalin dab treatment (4%) versus sucralfate steroid retention enema (symptom score after treatment graded by the Radiation Proctopathy System Assessments Scale (RPSAS) and sigmoidoscopic score in favour of formalin (P = 0.001, effect not quantified, 1 study, 102 participants, very low- to low-quality evidence), and colonic irrigation plus ciprofloxacin and metronidazole versus formalin application (4%) (bleeding (P = 0.007, effect not quantified), urgency (P = 0.0004, effect not quantified), and diarrhoea (P = 0.007, effect not quantified) in favour of colonic irrigation (1 study, 50 participants, low-quality evidence).Three studies, of unclear and high risk of bias, assessed treatments targeted at something very localised but not a single pathology. We identified no significant differences on our primary outcomes. We graded all studies as very low-quality evidence due to unclear risk of bias and very serious imprecision.Four studies, of unclear and high risk of bias, assessed treatments targeted at more than one symptom yet confined to the anorectal region. Studies that demonstrated an effect on symptoms included: gastroenterologist-led algorithm-based treatment versus usual care (detailed self help booklet) (significant difference in favour of gastroenterologist-led algorithm-based treatment on change in Inflammatory Bowel Disease Questionnaire-Bowel (IBDQ-B) score at six months, mean difference (MD) 5.47, 95% CI 1.14 to 9.81) and nurse-led algorithm-based treatment versus usual care (significant difference in favour of the nurse-led algorithm-based treatment on change in IBDQ-B score at six months, MD 4.12, 95% CI 0.04 to 8.19) (1 study, 218 participants, low-quality evidence); hyperbaric oxygen therapy (at 2.0 atmospheres absolute) versus placebo (improvement of Subjective, Objective, Management, Analytic - Late Effects of Normal Tissue (SOMA-LENT) score in favour of hyperbaric oxygen therapy (HBOT), P = 0.0019) (1 study, 150 participants, moderate-quality evidence, retinol palmitate versus placebo (improvement in RPSAS in favour of retinol palmitate, P = 0.01) (1 study, 19 participants, low-quality evidence) and integrated Chinese traditional plus Western medicine versus Western medicine (grade 0 to 1 radio-proctopathy after treatment in favour of integrated Chinese traditional medicine, RR 2.55, 95% CI 1.30 to 5.02) (1 study, 58 participants, low-quality evidence).The level of evidence for the majority of outcomes was downgraded using GRADE to low or very low, mainly due to imprecision and study limitations. AUTHORS' CONCLUSIONS Although some interventions for late radiation proctopathy look promising (including rectal sucralfate, metronidazole added to an anti-inflammatory regimen, and hyperbaric oxygen therapy), single small studies provide limited evidence. Furthermore, outcomes important to people with cancer, including quality of life (QoL) and long-term effects, were not well recorded. The episodic and variable nature of late radiation proctopathy requires large multi-centre placebo-controlled trials (RCTs) to establish whether treatments are effective. Future studies should address the possibility of associated injury to other gastro-intestinal, urinary, or sexual organs, known as pelvic radiation disease. The interventions, as well as the outcome parameters, should be broader and include those important to people with cancer, such as QoL evaluations.
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Affiliation(s)
- Fleur T van de Wetering
- Julius Center for Health Sciences and Primary Care / University Medical Center UtrechtDutch Cochrane CentrePO Box 85500UtrechtNetherlands3508 GA
| | - Leen Verleye
- Belgian Health Care Knowledge CentreKruidtuinlaan 55BrusselsBelgium1000
| | | | - Jane Maher
- Mount Vernon HospitalDepartment of Radiotherapy and OncologyRickmansworth RoadNorthwoodMiddlesexUKHA6 2RN
| | - Joan Vlayen
- Belgian Health Care Knowledge CentreKruidtuinlaan 55BrusselsBelgium1000
| | - Bradley R Pieters
- Academic Medical Center / University of AmsterdamDepartment of Radiation OncologyMeibergdreef 9AmsterdamNetherlands1105
| | - Geertjan van Tienhoven
- Academic Medical CenterRadiation Oncology and HyperthermiaP.O. Box 22700Meibergdreef 9AmsterdamNetherlands1100 DE
| | - Rob JPM Scholten
- Julius Center for Health Sciences and Primary Care / University Medical Center UtrechtDutch Cochrane CentrePO Box 85500UtrechtNetherlands3508 GA
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Fuccio L, Frazzoni L, Guido A. Prevention of pelvic radiation disease. World J Gastrointest Pharmacol Ther 2015; 6:1-9. [PMID: 25664197 PMCID: PMC4318744 DOI: 10.4292/wjgpt.v6.i1.1] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2014] [Revised: 09/02/2014] [Accepted: 11/10/2014] [Indexed: 02/06/2023] Open
Abstract
Pelvic cancers are among the most frequently diagnosed cancers worldwide. Treatment of patients requires a multidisciplinary approach that frequently includes radiotherapy. Gastrointestinal (GI) radiation-induced toxicity is a major complication and the transient or long-term problems, ranging from mild to very severe, arising in non-cancerous tissues resulting from radiation treatment to a tumor of pelvic origin, are actually called as pelvic radiation disease. The incidence of pelvic radiation disease changes according to the radiation technique, the length of follow up, the assessment method, the type and stage of cancer and several other variables. Notably, even with the most recent radiation techniques, i.e., intensity-modulated radiotherapy, the incidence of radiation-induced GI side effects is overall reduced but still not negligible. In addition, radiation-induced GI side effects can develop even after several decades; therefore, the improvement of patient life expectancy will unavoidably increase the risk of developing radiation-induced complications. Once developed, the management of pelvic radiation disease may be challenging. Therefore, the prevention of radiation-induced toxicity represents a reasonable way to avoid a dramatic drop of the quality of life of these patients. In the current manuscript we provide an updated and practical review on the best available evidences in the field of the prevention of pelvic radiation disease.
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Laterza L, Cecinato P, Guido A, Mussetto A, Fuccio L. Management of radiation-induced rectal bleeding. Curr Gastroenterol Rep 2014; 15:355. [PMID: 24101202 DOI: 10.1007/s11894-013-0355-z] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Pelvic radiation disease is one of the major complication after radiotherapy for pelvic cancers. The most commonly reported symptom is rectal bleeding which affects patients' quality of life. Therapeutic strategies for rectal bleeding are generally ignored and include medical, endoscopic, and hyperbaric oxygen treatments. Most cases of radiation-induced bleeding are mild and self-limiting, and treatment is normally not indicated. In cases of clinically significant bleeding (i.e. anaemia), medical therapies, including stool softeners, sucralfate enemas, and metronidazole, should be considered as first-line treatment options. In cases of failure, endoscopic therapy, mainly represented by argon plasma coagulation and hyperbaric oxygen treatments, are valid and complementary second-line treatment strategies. Although current treatment options are not always supported by high-quality studies, patients should be reassured that treatment options exist and success is achieved in most cases if the patient is referred to a dedicated centre.
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Affiliation(s)
- Liboria Laterza
- Unit of Gastroenterology, Department of Medical and Surgical Sciences, S.Orsola-Malpighi University Hospital, Via Massarenti 9, 40138, Bologna, Italy
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The effect of synbiotics on acute radiation-induced diarrhea and its association with mucosal inflammatory and adaptive responses in rats. Dig Dis Sci 2013; 58:2487-98. [PMID: 23695868 DOI: 10.1007/s10620-013-2700-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2012] [Accepted: 04/24/2013] [Indexed: 01/15/2023]
Abstract
BACKGROUND Previous clinical studies advocated that probiotics beneficially affect acute radiation-induced diarrhea. These encouraging results were attributed to the restoration of the intestinal flora; however, there is lack of evidence if and how probiotics influence the underlying pathophysiological mechanisms. AIMS The present study was conducted to investigate the potential supporting role of a synbiotic preparation (combination of pro- and pre-biotics) on experimentally-induced acute radiation diarrhea from the perspective of mucosal inflammation and histological injury. METHODS Ninety adult Wistar rats were randomly assigned into six groups. Group A (non-irradiated), group B (non-irradiated/synbiotic supplemented), group C (irradiated), and group D (irradiated/synbiotic supplemented) were followed up to a week after the beginning of the experiment. Group E (irradiated) and group F (irradiated/synbiotic supplemented) were followed up for four days. On the last day of the experiments tissues were harvested for structural and molecular assessments. RESULTS Synbiotic administration could not avert the occurrence of diarrhea, but significantly attenuated its severity. This effect was associated with the significant downregulation of neutrophil accumulation and lipid peroxidation during the acute phase. During the subacute phase, synbiotic treatment significantly improved both the histological profile and radiation mucositis. These mechanisms significantly contributed to the rehabilitation of the intestinal absorptive function as further indicated from the significantly reduced weight loss. CONCLUSIONS Given the optimization of the intestinal flora exerted by synbiotics, the resolution of diarrhea relies on the suppression of the "reactive" and the augmentation of "regenerative" components of acute radiation-induced intestinal response.
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Stacey R, Green JT. Nonendoscopic therapies for the management of radiation-induced rectal bleeding. Curr Opin Support Palliat Care 2013; 7:175-82. [DOI: 10.1097/spc.0b013e32835f3e00] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
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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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Fuccio L, Guido A, Andreyev HJN. Management of intestinal complications in patients with pelvic radiation disease. Clin Gastroenterol Hepatol 2012; 10:1326-1334.e4. [PMID: 22858731 DOI: 10.1016/j.cgh.2012.07.017] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2012] [Revised: 06/22/2012] [Accepted: 07/20/2012] [Indexed: 02/07/2023]
Abstract
Gastrointestinal toxicity after radiotherapy for pelvic cancer is a major complication-the most commonly reported symptoms include rectal bleeding, diarrhea, and fecal incontinence, which substantially impair patients' quality of life. Management of these symptoms can be a challenge, although available treatment strategies generally are ignored or underused. Radiation-induced symptoms have multiple mechanisms of pathogenesis; the first step for the correct management is to identify the mechanism that is causing the symptoms. Optimal management requires close liaisons among physicians, gastroenterologists with specialist interests, radiotherapists, oncologists, dieticians, nurses, and surgeons. Patients should be reassured that treatment options (medical, endoscopic, and surgical) exist and are in most cases successful if patients are referred to experts in pelvic radiation disease. However, although new therapeutic approaches are not yet always supported by high-quality trials, research projects are underway to improve management of patients. Clinicians should focus on using proven treatments correctly and avoiding misuse.
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Affiliation(s)
- Lorenzo Fuccio
- Department of Clinical Medicine, S. Orsola-Malpighi Hospital, Bologna, Italy.
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Gibson RJ, Keefe DMK, Lalla RV, Bateman E, Blijlevens N, Fijlstra M, King EE, Stringer AM, van der Velden WJFM, Yazbeck R, Elad S, Bowen JM. Systematic review of agents for the management of gastrointestinal mucositis in cancer patients. Support Care Cancer 2012; 21:313-26. [PMID: 23142924 DOI: 10.1007/s00520-012-1644-z] [Citation(s) in RCA: 143] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2012] [Accepted: 10/29/2012] [Indexed: 12/17/2022]
Abstract
PURPOSE The aim of this study was to review the available literature and define clinical practice guidelines for the use of agents for the prevention and treatment of gastrointestinal mucositis. METHODS A systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO). The body of evidence for each intervention, in each cancer treatment setting, was assigned an evidence level. Based on the evidence level, one of the following three guideline determinations was possible: recommendation, suggestion, and no guideline possible. RESULTS A total of 251 clinical studies across 29 interventions were examined. Panel members were able to make one new evidence-based negative recommendation; two new evidence-based suggestions, and one evidence-based change from previous guidelines. Firstly, the panel recommends against the use of misoprostol suppositories for the prevention of acute radiation-induced proctitis. Secondly, the panel suggests probiotic treatment containing Lactobacillus spp., may be beneficial for prevention of chemotherapy and radiotherapy-induced diarrhea in patients with malignancies of the pelvic region. Thirdly, the panel suggests the use of hyperbaric oxygen as an effective means in treating radiation-induced proctitis. Finally, new evidence has emerged which is in conflict with our previous guideline surrounding the use of systemic glutamine, meaning that the panel is unable to form a guideline. No guideline was possible for any other agent, due to inadequate and/or conflicting evidence. CONCLUSIONS This updated review of the literature has allowed new recommendations and suggestions for clinical practice to be reached. This highlights the importance of regular updates.
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Affiliation(s)
- Rachel J Gibson
- School of Medical Sciences, University of Adelaide, North Terrace, Adelaide 5005, South Australia, Australia.
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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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Seo EH, Kim TO, Kim TG, Joo HR, Park J, Park SH, Yang SY, Moon YS, Park MJ, Ryu DY, Song GA. The efficacy of the combination therapy with oral and topical mesalazine for patients with the first episode of radiation proctitis. Dig Dis Sci 2011; 56:2672-7. [PMID: 21365239 DOI: 10.1007/s10620-011-1637-7] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2010] [Accepted: 02/14/2011] [Indexed: 12/13/2022]
Abstract
BACKGROUND/AIMS Radiation proctitis is a common complication of pelvic radiation for which an optimal treatment remains undetermined. We assessed the efficacy of oral and topical mesalazine combination therapy for patients with naive radiation proctitis. METHODS A total of 23 patients with radiation proctitis were enrolled in the study over a period of 2 years. Three of these patients were excluded due to severe bleeding during the study. Twenty patients (mean age 60.3 years; two males, 18 females) were treated with oral mesalazine (3 × 1 g per day) plus a daily mesalazine suppository (1 g per day at bedtime) for 4 weeks. The efficacy of treatment was assessed according to the Subjective Objective Management Analytic (SOMA) scale for alleviation of clinical symptoms of rectal toxicity and sigmoidoscopic findings. RESULTS The mean bleeding score improved significantly from 2.10 to 1.70 (p = 0.002) with mesalazine treatment. However, scores were not improved for pain (0.30-0.20, p = 0.163), tenesmus (0.50-0.45, p = 0.577), or stool frequency (0.35-0.30, p = 0.577). The improvements in the mean telangiectasia score (1.80-1.45, p = 0.005), bleeding point score (1.60-1.05, p < 0.001), and friable mucosa score (1.35-1.00, p = 0.005) were all statistically significant. No side-effects were noted in any of the patients. CONCLUSIONS The combination of oral and topical mesalazine therapy for radiation proctitis may be a safe and effective treatment for naive radiation proctitis, especially for hemorrhagic proctitis. A large, randomized controlled trial is required to confirm the results of this pilot study.
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Affiliation(s)
- Eun Hee Seo
- Department of Internal Medicine, Haeundae Paik Hospital, Inje University School of Medicine, 1435 Jwa-dong, Haeundae-gu, Busan 612-030, Republic of Korea
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Chitapanarux I, Chitapanarux T, Traisathit P, Kudumpee S, Tharavichitkul E, Lorvidhaya V. Randomized controlled trial of live lactobacillus acidophilus plus bifidobacterium bifidum in prophylaxis of diarrhea during radiotherapy in cervical cancer patients. Radiat Oncol 2010; 5:31. [PMID: 20444243 PMCID: PMC2874795 DOI: 10.1186/1748-717x-5-31] [Citation(s) in RCA: 170] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2009] [Accepted: 05/05/2010] [Indexed: 12/23/2022] Open
Abstract
Background Radiation-induced diarrhea is frequently observed during pelvic radiotherapy. This study was performed to determine the ability of a probiotic containing live lactobacillus acidophilus plus bifidobacterium bifidum to reduce the incidence of radiation-induced diarrhea in locally advanced cervical cancer patients. Methods Patients who were undergoing pelvic radiotherapy concurrent with weekly cisplatin were randomly assigned to a study drug or placebo, in a double-blind study. Diarrhea was graded weekly according the Common Toxicity Criteria (CTC) system. Stool consistency and white and red blood cell count in stool were also assessed. The primary endpoint was to reduce the incidence of diarrhea, defined by a CTC grade 2 or more, and the need for anti-diarrheal medication. Results A total of 63 patients were enrolled. Grade 2 -3 diarrhea was observed in 45% of the placebo group (n = 31) and 9% of the study drug group (n = 32) (p = 0.002). Anti-diarrheal medication use was significantly reduced in the placebo group (p = 0.03). The patients in the study drug group had a significantly improved stool consistency (p < 0.001). Conclusions Live lactobacillus acidophilus plus bifidobacterium bifidum reduced the incidence of radiation-induced diarrhea and the need for anti-diarrheal medication and had a significant benefits on stool consistency.
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Affiliation(s)
- Imjai Chitapanarux
- Department of Radiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
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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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PPARs in Irradiation-Induced Gastrointestinal Toxicity. PPAR Res 2009; 2010:528327. [PMID: 20037741 PMCID: PMC2796461 DOI: 10.1155/2010/528327] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2008] [Revised: 02/06/2009] [Accepted: 11/02/2009] [Indexed: 12/21/2022] Open
Abstract
The use of radiation therapy to treat cancer inevitably involves exposure of normal tissues. Although the benefits of this treatment are well established, many patients experience distressing complications due to injury to normal tissue. These side effects are related to inflammatory processes, and they decrease therapeutic benefit by increasing the overall treatment time. Emerging evidence indicates that PPARs and their ligands are important in the modulation of immune and inflammatory reactions. This paper discusses the effects of abdominal irradiation on PPARs, their role and functions in irradiation toxicity, and the possibility of using their ligands for radioprotection.
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Abstract
Radiation colitis, an insidious, progressive disease of increasing frequency, develops 6 mo to 5 years after regional radiotherapy for malignancy, owing to the deleterious effects of the latter on the colon and the small intestine. When dealing with radiation colitis and its complications, the most conservative modality should be employed because the areas of intestinal injury do not tend to heal. Acute radiation colitis is mostly self-limited, and usually, only supportive management is required. Chronic radiation colitis, a poorly predictable progressive disease, is considered as a precancerous lesion; radiation-associated malignancy has a tendency to be diagnosed at an advanced stage and to bear a dismal prognosis. Therefore, management of chronic radiation colitis remains a major challenge owing to the progressive evolution of the disease, including development of fibrosis, endarteritis, edema, fragility, perforation, partial obstruction, and cancer. Patients are commonly managed conservatively. Surgical intervention is difficult to perform because of the extension of fibrosis and alterations in the gut and mesentery, and should be reserved for intestinal obstruction, perforation, fistulas, and severe bleeding. Owing to the difficulty in managing the complications of acute and chronic radiation colitis, particular attention should be focused onto the prevention strategies. Uncovering the fibrosis mechanisms and the molecular events underlying radiation bowel disease could lead to the introduction of new therapeutic and/or preventive approaches. A variety of novel, mostly experimental, agents have been used mainly as a prophylaxis, and improvements have been made in radiotherapy delivery, including techniques to reduce the amount of exposed intestine in the radiation field, as a critical strategy for prevention.
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Mantena S, Unnikrishnan M, Joshi R, Radha V, Devi PU, Mukherjee T. In vivo radioprotection by 5-aminosalicylic acid. MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS 2008; 650:63-79. [DOI: 10.1016/j.mrgentox.2007.10.005] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/04/2007] [Revised: 10/01/2007] [Accepted: 10/14/2007] [Indexed: 11/25/2022]
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Non-IBD and noninfectious colitis. ACTA ACUST UNITED AC 2008; 5:28-39. [DOI: 10.1038/ncpgasthep1005] [Citation(s) in RCA: 53] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2007] [Accepted: 10/04/2007] [Indexed: 12/25/2022]
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Nakabayashi M, Beard C, Kelly SM, Carr-Locke DL, Oh WK. Treatment of a radiation-induced rectal ulcer with hyperbaric oxygen therapy in a man with prostate cancer. Urol Oncol 2006; 24:503-8. [PMID: 17138131 DOI: 10.1016/j.urolonc.2006.02.002] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2005] [Revised: 02/01/2006] [Accepted: 02/02/2006] [Indexed: 01/05/2023]
Abstract
Late radiation proctopathy is a painful and vexing complication of prostate radiation. We report a case of a 55-year-old man with prostate cancer, and complaints of tenesmus and severe rectal pain after radiation therapy. The patient was diagnosed with a locally advanced Gleason score 8 prostate cancer and an increased prostate-specific antigen of 42.3 ng/ml. His past medical history was notable for a history of bilateral lymph node dissection complicated by Clostridium difficile colitis. He subsequently received 3-dimensional conformal radiation therapy. Seven months after completing therapy, minor rectal bleeding and significant pain developed, requiring increasing doses of opioid analgesics. Fourteen months after 3-dimensional conformal radiation therapy, sigmoidoscopy revealed a single chronic deep ulcer at the anorectal junction. As an alternative to diverting colostomy, the patient underwent a course of hyperbaric oxygen. Within 1 month of completing hyperbaric oxygen treatment, his symptoms completely resolved. Nine months from completion of hyperbaric oxygen therapy, he has had no recurrence of symptoms. Hyperbaric oxygen therapy can be considered a treatment option after failure of standard treatments in patients with severe radiation proctopathy.
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Affiliation(s)
- Mari Nakabayashi
- Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA
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Korkut C, Asoglu O, Aksoy M, Kapran Y, Bilge H, Kiremit-Korkut N, Parlak M. Histopathological comparison of topical therapy modalities for acute radiation proctitis in an experimental rat model. World J Gastroenterol 2006; 12:4879-83. [PMID: 16937473 PMCID: PMC4087625 DOI: 10.3748/wjg.v12.i30.4879] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the prevalent topical therapeutic modalities available for the treatment of acute radiation proctitis compared to formalin.
METHODS: A total of 120 rats were used. Four groups (n = 30) were analyzed with one group for each of the following applied therapy modalities: control, mesalazine, formalin, betamethasone, and misoprostol. A single fraction of 17.5 Gy was delivered to each rat. The rats in control group rats were given saline, and the rats in the other three groups received appropriate enemas twice a day beginning on the first day after the irradiation until the day of euthanasia. On d 5, 10, and 15, ten rats from each group were euthanized and a pathologist who was unaware of treatment assignment examined the rectums using a scoring system.
RESULTS: The histopathologic scores for surface epithelium, glands (crypts) and lamina propria stroma of the rectums reached their maximum level on d 10. The control and formalin groups had the highest and mesalazine had the lowest, respectively on d 10. On the 15th d, mesalazine, betamethasone, and misoprostol had the lowest scores of betamethasone.
CONCLUSION: Mesalazine, betamethasone, and misoprostol are the best topical agents for radiation proctitis and formalin has an inflammatory effect and should not be used.
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Akyurek S, Atahan L, Cengiz M, Sokmensuer C, Haberal I, Yildiz F, Onal C. Effect of ticlopidine in the prevention of radiation enteropathy. Br J Radiol 2006; 79:409-414. [PMID: 16632621 DOI: 10.1259/bjr/16265085] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023] Open
Abstract
Impairment of vascular function is considered to play an important role in chronic radiation enteropathy. In this experimental study, the role of ticlopidine, an inhibitor of ADP-induced platelet aggregation, was investigated in radiation enteropathy. 80 male Wistar albino rats, each weighing 170-200 g, were divided into four groups: (a) radiation alone (n = 20); (b) radiotherapy plus ticlopidine (n = 20); (c) ticlopidine control (n = 20) and (d) control (n = 20). Both radiation groups received 19 Gy radiation to the exteriorized intestinal segments in a single fraction. Ticlopidine or vehicle was administered 12 h after radiotherapy and continued for 1 month. Rats from every group were euthanized randomly at intervals of 6 weeks from 2 weeks to 26 weeks. Histopathological radiation injury was assessed using radiation injury scoring (RIS). Radiation with ticlopidine or radiation alone groups showed significant RIS deterioration compared with controls in all time points studied. Comparison of median RIS of radiotherapy and radiotherapy+ticlopidine groups at the 2nd, 14th and 26th weeks yielded statistically significant RIS in favour of radiotherapy+ticlopidine group (p = 0.05). However, these differences were less pronounced at the 8th and 20th week (p = 0.07). Both radiation groups had poor weight gain when compared with control and ticlopidine groups. The weight gain in radiotherapy+ticlopidine group was significantly superior to only radiation group between 10th and 20th weeks (p = 0.05). This study showed that inhibition of platelet aggregation with ticlopidine might be useful in radiation enteropathy. However, the precise role of antiaggregant therapies on radiation enteropathy should be comprehensively studied before clinical consideration.
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Affiliation(s)
- S Akyurek
- Department of Radiation Oncology, Ankara University School of Medicine, Ankara, Turkey
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Lalla RV, Schubert MM, Bensadoun RJ, Keefe D. Anti-inflammatory agents in the management of alimentary mucositis. Support Care Cancer 2006; 14:558-65. [PMID: 16565821 DOI: 10.1007/s00520-006-0050-9] [Citation(s) in RCA: 47] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2006] [Accepted: 02/21/2006] [Indexed: 01/02/2023]
Abstract
BACKGROUND Alimentary mucositis is a significant complication of cancer therapy, with important clinical and economic implications. MATERIALS AND METHODS In June 2005, the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society for Oral Oncology conducted an evidence-based review of the literature on alimentary mucositis. The goal of this literature review was to update previously published guidelines for the management of mucositis. RESULTS This article reports the findings of the subgroup charged with reviewing the literature related to anti-inflammatory interventions. Considerable preclinical and clinical evidence suggests that the use of anti-inflammatory agents may be a promising approach to reduce the severity of mucositis. However, there was not enough evidence to support any new guidelines advocating the use of any specific anti-inflammatory intervention. CONCLUSION Thus, there is a need for well-designed clinical trials evaluating the use of anti-inflammatory agents in the management of mucositis.
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Affiliation(s)
- Rajesh V Lalla
- Department of Oral Health and Diagnostic Sciences MC1605, University of Connecticut Health Center, 263, Farmington Avenue, Farmington, 06030-1605, USA.
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Rubenstein EB, Peterson DE, Schubert M, Keefe D, McGuire D, Epstein J, Elting LS, Fox PC, Cooksley C, Sonis ST. Clinical practice guidelines for the prevention and treatment of cancer therapy-induced oral and gastrointestinal mucositis. Cancer 2004; 100:2026-46. [PMID: 15108223 DOI: 10.1002/cncr.20163] [Citation(s) in RCA: 491] [Impact Index Per Article: 23.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Oral and gastrointestinal (GI) mucositis can affect up to 100% of patients undergoing high-dose chemotherapy and hematopoietic stem cell transplantation, 80% of patients with malignancies of the head and neck receiving radiotherapy, and a wide range of patients receiving chemotherapy. Alimentary track mucositis increases mortality and morbidity and contributes to rising health care costs. Consequently, the Multinational Association of Supportive Care in Cancer and the International Society for Oral Oncology assembled an expert panel to evaluate the literature and to create evidence-based guidelines for preventing, evaluating, and treating mucositis. METHODS Thirty-six panelists reviewed literature published between January 1966 and May 2002. An initial meeting in January 2002 produced a preliminary draft of guidelines that was reviewed at a second meeting the same year. Thereafter, a writing committee produced a report on mucositis pathogenesis, epidemiology, and scoring (also included in this issue), as well as clinical practice guidelines. RESULTS Panelists created recommendations from higher levels of evidence and suggestions when evidence was of a lower level and there was a consensus regarding the interpretation of the evidence by the panel. Panelists identified gaps in evidence that made it impossible to recommend or not recommend use of specific agents. CONCLUSIONS Oral/GI mucositis is a common side effect of many anticancer therapies. Evidence-based clinical practice guidelines are presented as a benchmark for clinicians to use for routine care of appropriate patients and as a springboard to challenge clinical investigators to conduct high-quality trials geared toward areas in which data are either lacking or conflicting.
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Affiliation(s)
- Edward B Rubenstein
- Department of Palliative Care and Rehabilitation Medicine, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA
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Abstract
OBJECTIVE To review the management of radiotherapy- and chemotherapy-induced gastrointestinal mucositis. DATA SOURCE Articles and research studies. CONCLUSION Gastrointestinal damage is becoming a common dose-limiting toxicity. However, there is only limited research into the mechanism and possible treatment of this toxicity. IMPLICATIONS FOR NURSING PRACTICE It is important to document the frequency and severity of gastrointestinal mucositis, and to alleviate symptoms wherever possible.
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Affiliation(s)
- Dorothy M K Keefe
- Department of Medical Oncology, Royal Adelaide Hospital, South Australia
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Sudheer Kumar M, Unnikrishnan MK, Uma Devi P. Effect of 5-aminosalicylic acid on radiation-induced micronuclei in mouse bone marrow. Mutat Res 2003; 527:7-14. [PMID: 12787909 DOI: 10.1016/s0027-5107(03)00052-6] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
5-Aminosalicylic acid (5ASA), a prescribed drug for ulcerative colitis, is a potent scavenger of oxygen-derived free radicals. The present study was undertaken to ascertain its ability to protect against radiation-induced damage. The drug dose-dependent effect, optimum time of drug administration and radiation dose-dependent effect (0-4 Gy) on in vivo radiation protection against micronuclei induction in polychromatic erythrocytes (PCE) and normochromatic erythrocytes (NCE) were studied in the bone marrow of mice. Intraperitoneal injection of 10-125 mg/kg of the drug 30 min before whole body irradiation with 3 Gy produced a significant reduction in the frequency of micronucleated erythrocytes at 24 h after exposure. The optimum dose for protection without drug toxicity was 25 mg/kg body weight. Injection of 25 mg/kg of the drug 60 or 30 min before or within 15 min after 3 Gy whole body gamma-irradiation resulted in a significant decrease in the radiation-induced PCE and NCE with micronuclei (MPCE and MNCE) and an increase in the ratio of PCE to NCE (P/N), at 24 h post-irradiation. Maximum effect was seen when the drug was administered 30 min before irradiation. Therefore, to study the radiation dose-response, mice were pre-treated with 25 mg/kg of 5ASA 30 min before 1-4 Gy of gamma-irradiation. Radiation increased the MN frequency linearly (r(2)=0.99) with dose. Pre-treatment with 5ASA significantly reduced the MN counts to 40-50% of the radiation (RT) alone values, giving a dose modification factor (DMF) of 2.02 (MPCE) and 2.53 (MNCE). Irradiation resulted in a dose-dependent decline in the P/N ratio at all the doses of radiation studied. 5ASA produced a significant increase in the P/N ratio from that of irradiated controls, at all doses of radiations tested. These results show that 5ASA protect mice against radiation-induced MN formation and mitotic arrest.
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Affiliation(s)
- M Sudheer Kumar
- Department of Pharmacology, College of Pharmaceutical Sciences, Manipal 576119, India
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Delia P, Sansotta G, Frosina P, Pergolizzi S, Santacaterina A, De Renzis C. Trattamento profilattico delia diarrea nei pazienti sottoposti a radioterapia sul distretto pelvico. nostra esperienza. TUMORI JOURNAL 2003. [DOI: 10.1177/030089160308900328] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Affiliation(s)
- P Delia
- Istituto di Scienze Radiologiche, Divisione di Radioterapia Oncologica, Azienda Policlinico Universitario, Messina
| | - G Sansotta
- Istituto di Scienze Radiologiche, Divisione di Radioterapia Oncologica, Azienda Policlinico Universitario, Messina
| | - P Frosina
- Istituto di Scienze Radiologiche, Divisione di Radioterapia Oncologica, Azienda Policlinico Universitario, Messina
| | - S Pergolizzi
- Istituto di Scienze Radiologiche, Divisione di Radioterapia Oncologica, Azienda Policlinico Universitario, Messina
| | - A Santacaterina
- Istituto di Scienze Radiologiche, Divisione di Radioterapia Oncologica, Azienda Policlinico Universitario, Messina
| | - C De Renzis
- Istituto di Scienze Radiologiche, Divisione di Radioterapia Oncologica, Azienda Policlinico Universitario, Messina
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Mechanisms and Modification of the Radiation Response of Gastrointestinal Organs. MEDICAL RADIOLOGY 2003. [DOI: 10.1007/978-3-642-55613-5_5] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
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Minsky BD. Combined modality therapy for rectal cancer. ACTA ACUST UNITED AC 2003; 21:803-16. [PMID: 15338775 DOI: 10.1016/s0921-4410(03)21038-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/30/2023]
Affiliation(s)
- Bruce D Minsky
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA.
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Scolapio JS, Ukleja A, Burnes JU, Kelly DG. Outcome of patients with radiation enteritis treated with home parenteral nutrition. Am J Gastroenterol 2002; 97:662-6. [PMID: 11922561 DOI: 10.1111/j.1572-0241.2002.05546.x] [Citation(s) in RCA: 38] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Intestinal failure requiring either surgery or home parenteral nutrition (HPN) develops in approximately 5% of patients treated with radiation. The aim of the study was to determine survival, duration of HPN, and complications associated with HPN in patients with intestinal failure after radiation therapy. METHODS Fifty-four patients with radiation enteritis who received HPN were studied (39 women and 15 men with a mean age of 57.9 yr). Retrospective data were collected from the patients' medical records dated between 1975 and 1999. The probability of survival was calculated by the Kaplan-Meier method. RESULTS HPN was initiated a median of 20 months (range = 2-432) from the start of radiation therapy. The mean number of intestinal operations for radiation-related complications was 2.2/patient (range = 0-6). The causes of intestinal failure resulting from radiation therapy were intestinal obstruction (27 patients), short bowel (17), malabsorption (five), fistula (three), and dysmotility (two). The mean duration of HPN was 20.4 months (range = 2-108). At last follow-up, 37 patients (68%) were dead, most as a result of recurrent cancer. One patient died of catheter sepsis, and no other deaths were directly related to HPN. The overall estimated 5-yr probability of survival on HPN calculated by Kaplan-Meier analysis was 64%. CONCLUSIONS HPN is a reasonable treatment option in patients with intestinal failure as a result of radiation enteritis. Survival and complications associated with HPN in patients with radiation enteritis seem to be similar to those in other HPN-treated groups.
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Affiliation(s)
- James S Scolapio
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida 32224, USA
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36
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Minsky BD. Management of Locally Unresectable Rectal Cancer. COLORECTAL CANCER 2002. [DOI: 10.1007/978-1-59259-160-2_12] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
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Denton A, Forbes A, Andreyev J, Maher EJ. Non surgical interventions for late radiation proctitis in patients who have received radical radiotherapy to the pelvis. Cochrane Database Syst Rev 2002:CD003455. [PMID: 11869662 DOI: 10.1002/14651858.cd003455] [Citation(s) in RCA: 64] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Chronic radiation proctitis (inflammation of the rectum) may develop after the completion of pelvic radiotherapy. Presently there is no recommended standard management. OBJECTIVES To assess the effects of various non-surgical treatment options for the management of late chronic radiation proctitis. SEARCH STRATEGY We searched the Cochrane Controlled Trials Register, issue 1, 2001, MEDLINE 1966 to 2001, EMBASE 1980 to 2001, CANCERCD 1980 to 2001, Science Citation Index 1991 to 2001, CINAHL 1982 to 2001, as well as sources of grey literature. We also hand searched relevant textbooks and contacted experts in the field. SELECTION CRITERIA Studies (preferentially randomised controlled trials) of interventions for the non-surgical management of late radiation proctitis in patients who have undergone pelvic radiotherapy as part of their cancer treatment. DATA COLLECTION AND ANALYSIS The inclusion criteria were independently applied by two of the reviewers (AD and EJM) and where there was disagreement this was resolved by involving a third reviewer to form a consensus. MAIN RESULTS Six randomised controlled trials were included. None of the trials compared anti-inflammatories with placebo. However rectal sucralfate showed greater clinical improvement for proctitis than anti-inflammatories (odds ratio 14.00, 95% confidence interval 1.46 to 134.26; n=1 study), though no difference was seen for endoscopic improvement (odds ratio 2.74, 95% confidence interval 0.64 to 11.76, n=1 study). The addition of metronidazole to the anti-inflammatory regime also appeared to improve the response rate, as measured by the reduction in rectal bleeding, diarrhoea, erythema and ulceration (n=1 study). Similarly rectal hydrocortisone appeared to be more effective than rectal betamethasone for clinical improvement although no difference was seen in endoscopic improvement (n=1 study). Short chain fatty acid enemas did not appear to be effective compared to placebo (n=2 studies). In the comparison of the heater probe and bipolar electrocautery (n=1 study), there was no discernible difference for severe bleeding after one year, but the heater probe demonstrated a greater increase in the haematocrit and reduced transfusion requirements. REVIEWER'S CONCLUSIONS Late radiation complications are a relatively rare manifestation, with many potential carers and poor diagnostic criteria. Although certain interventions look promising and may be effective (such as rectal sucralfate, adding metronidazole to the anti-inflammatory regime and heater probes), single small studies (even if well conducted) provide insufficient evidence. The episodic and variable nature of late radiation proctitis also requires placebo controlled studies to establish whether particular treatments are effective. Regional or centralised registers of radiation toxicity should be established so that interventions can be administered in the setting of multi-centre trials with specific entry criteria, formal baseline and therapeutic assessments providing standardised outcome data including quality of life evaluations.
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Affiliation(s)
- A Denton
- Centre for Cancer Treatment, Mount Vernon Hospital, Rickmansworth Rd, Northwood, Middlesex, UK, HA6 2RN.
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Kilic D, Ozenirler S, Egehan I, Dursun A. Sulfasalazine decreases acute gastrointestinal complications due to pelvic radiotherapy. Ann Pharmacother 2001; 35:806-10. [PMID: 11485124 DOI: 10.1345/aph.10055] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND Radiation-induced gastrointestinal toxicity is a significant concern for patients who are treated with this modality for pelvic malignancies. Eicosanoids and free radicals are thought to be among the reasons for this effect. Sulfasalazine is an inhibitor of their synthesis in the mucosa. OBJECTlVE: To determine whether sulfasalazine can reduce the radiation-induced acute gastrointestinal complications. METHODS In this prospective, double-blind study, 31 patients receiving pelvic radiotherapy were randomized to receive two sulfasalazine 500-mg tablets twice daily or placebo, administered orally from the first day of irradiation. Patients were evaluated weekly, and gastrointestinal toxicities were graded according to the Late Effect of Normal Tissue-Subjective Objective Management Analytic (LENT-SOMA) toxicity table during pelvic radiotherapy. On the last day of week 5, the subjects were graded endoscopically, and biopsies taken from the rectum were classified histopathologically. RESULTS Groups did not differ in age, gender, tumor site, or irradiation procedure. During radiotherapy, grade 2 or higher gastrointestinal toxicity occurred in 20% (3/15) and 63% (10/16) of the sulfasalazine and placebo groups, respectively. This difference was significant (p = 0.017). No statistically significant differences were found in endoscopic and histopathologic evaluations. CONCLUSIONS Sulfasalazine is effective in decreasing clinically acute gastrointestinal toxicities. Long-term follow-up with the subjects will help to determine the net effect of sulfasalazine on the radiation-induced gastrointestinal injuries.
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Affiliation(s)
- D Kilic
- Faculty of Medicine, Department of Radiation Oncology, Gazi University, Ankara, Turkey.
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Affiliation(s)
- P C O'Brien
- Radiation Oncology Department, Newcastle Mater Hospital, Edith Street, Waratah, NSW 2298 Australia
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Kiliç D, Egehan I, Ozenirler S, Dursun A. Double-blinded, randomized, placebo-controlled study to evaluate the effectiveness of sulphasalazine in preventing acute gastrointestinal complications due to radiotherapy. Radiother Oncol 2000; 57:125-9. [PMID: 11054515 DOI: 10.1016/s0167-8140(00)00254-1] [Citation(s) in RCA: 54] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND PURPOSE Acute radiation-induced diarrhea occurs in approximately 80% of the patients receiving pelvic radiotherapy. It is caused by gastrointestinal irritation and inflammation. Eicosanoids are thought to be one of the mechanisms of this. Sulphasalazine is an inhibitor of their synthesis in the mucosa. This randomized clinical trial was undertaken to evaluate its effect in preventing acute radiation enteritis (ARE). MATERIALS AND METHODS Prospectively, 87 patients receiving pelvic radiotherapy were randomized, in a double-blind fashion. Two tablets twice daily of sulphasalazine (500 mg) or placebo were administered orally. Patients were evaluated weekly according to diarrhea grading for the primary study endpoint and according to late effect of normal tissue-subjective objective management analytic (LENT-SOMA) criteria for the secondary endpoint during irradiation. RESULTS Groups did not differ for age, gender, tumour site or irradiation procedure. Diarrhea occurred in 55 and 86% of the sulphasalazine and placebo groups, respectively (P=0.001). Gastrointestinal toxicity was seen in 80 and 93% of the sulphasalazine and placebo groups according to the maximum LENT-SOMA score (P=0.07). According to the maximum LENT-SOMA score between the two groups, significant differences in favor of sulphasalazine were found for each week. CONCLUSION Sulphasalazine (2 g/day) was found to be effective in decreasing the symptoms of ARE.
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Affiliation(s)
- D Kiliç
- Department of Radiation Oncology, Gazi University Hospital, Ankara 06510, Turkey
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Vernia P, Fracasso PL, Casale V, Villotti G, Marcheggiano A, Stigliano V, Pinnaro P, Bagnardi V, Caprilli R. Topical butyrate for acute radiation proctitis: randomised, crossover trial. Lancet 2000; 356:1232-5. [PMID: 11072942 DOI: 10.1016/s0140-6736(00)02787-2] [Citation(s) in RCA: 87] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND No available therapy has, as yet, proven effective to treat acute radiation proctitis (ARP) following radiation therapy for malignant pelvic disease. We assessed whether sodium butyrate enemas, at a dose of 80 mmol/L (80 mL/24 h), might offer effective treatment for this condition. METHODS 20 patients presenting with ARP after completing a cycle of 35-52 Gy external-beam radiation therapy for pelvic malignant disease, were treated for 3 weeks with topical sodium butyrate and saline enemas according to a randomised, double-blind, crossover protocol. Clinical, endoscopic, and histological findings were assessed at enrollment, at week 3, and then at the end of the study. Data were analysed by two-tailed t test for paired data (continuous variables) and a logistic-regression model with variable multiple response for ordered categorical data. FINDINGS Topical butyrate, but not saline, led to remission of symptoms (clinical score from 8.2 [SE 1.6] to 1.5 [0.7] vs 7.9 [1.8] to 8.1 [3.4]). When the treatment regimen was switched, eight out of nine of the previously placebo-treated patients went into remission, whereas three patients relapsed when switched to saline. The advantage of butyrate over placebo, expressed as CI, odds ratio, and p value was significant for almost all the clinical, endoscopic and histological factors taken into consideration. INTERPRETATION Topical sodium butyrate, unlike other therapeutic regimens used so far, proved effective in the treatment of ARP.
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Affiliation(s)
- P Vernia
- Cattedra di Gastroenterologia 1, Università La Sapienza, Roma, Italy
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Miller AR, Martenson JA, Nelson H, Schleck CD, Ilstrup DM, Gunderson LL, Donohue JH. The incidence and clinical consequences of treatment-related bowel injury. Int J Radiat Oncol Biol Phys 1999; 43:817-25. [PMID: 10098437 DOI: 10.1016/s0360-3016(98)00485-4] [Citation(s) in RCA: 60] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
OBJECTIVE To assess the frequency and clinical features of treatment-induced bowel injury in rectal carcinoma patients receiving perioperative external beam radiotherapy (EBRT). The frequency of and factors associated with treatment-induced intestinal injury have previously not been well quantified for rectal cancer patients. Postoperative adjuvant chemoirradiation is recommended for Stage II and III rectal cancers, making such data of significant interest. METHODS AND MATERIALS The records of 386 consecutive patients undergoing radiotherapy with or without chemotherapy (CT) for rectal carcinoma between 1981-90 were reviewed. Eight-two patients were excluded for receiving nontherapeutic EBRT or modalities other than EBRT. RESULTS Symptomatic acute treatment-related enteritis (within 30 days of EBRT +/- CT) was diagnosed in 13 patients, 3 of whom developed chronic bowel injury. Chronic treatment-related enteritis was identified in 18 patients and reoperation was required in 17 (5% of the 304 patients with complete follow-up). Chronic proctitis was documented in 38 patients, including 3 patients with small bowel injury. The probability of developing treatment-induced bowel injury at 5 years following treatment was 19%. Variables associated with an increased risk of bowel injury using multivariate analysis were transanal excision (p = 0.002), escalating radiation dose (p = 0.005), and increasing age (p = 0.01). Twenty of the affected patients required operative treatment, and 2 deaths resulted from treatment-induced enteritis. CONCLUSION Patients with rectal carcinoma treated with EBRT +/- CT have the risk of developing treatment-induced bowel injury. The pelvic radiation dose should be limited to < or = 5040 cGy unless small bowel can be displaced. Reperitonealization of the pelvis, or other surgical methods of excluding the small intestine should be used whenever possible.
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Affiliation(s)
- A R Miller
- Division of Gastroenterologic and General Surgery, Mayo Clinic and Mayo Foundation, Rochester, MN 55905, USA
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Howarth GS, Fraser R, Frisby CL, Schirmer MB, Yeoh EK. Effects of insulin-like growth factor-I administration on radiation enteritis in rats. Scand J Gastroenterol 1997; 32:1118-1124. [PMID: 9399392 DOI: 10.3109/00365529709002990] [Citation(s) in RCA: 37] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND Acute radiation-induced damage to the small bowel occurs frequently during abdominal radiotherapy. Since the small intestine is selectively responsive to the growth-promoting effects of insulin-like growth factor-I (IGF-I), we investigated the effects of IGF-I administration on mucosal recovery from radiation enteritis in the rat. METHODS Rats received a single 10-Gy dose of total abdominal irradiation followed by implantation of mini-pumps infusing either IGF-I or vehicle for 4 days. After the rats had been killed, gut organs were weighed before light microscopic and biochemical examination. RESULTS Irradiated rats receiving IGF-I lost less body weight than vehicle-treated rats, whereas the wet weights of the stomach, small intestine, and colon were increased by 10%, 19%, and 21%, respectively, and crypt depth was increased in the duodenum, jejunum, and ileum. CONCLUSIONS IGF-I administration after abdominal irradiation increased small-intestinal mass and improved indicators of mucosal integrity, suggesting acceleration of small-intestinal mucosal recovery from radiation injury.
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Affiliation(s)
- G S Howarth
- Child Health Research Institute, North Adelaide, South Australia, Australia
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Resbeut M, Marteau P, Cowen D, Richaud P, Bourdin S, Dubois JB, Mere P, N'Guyen TD. A randomized double blind placebo controlled multicenter study of mesalazine for the prevention of acute radiation enteritis. Radiother Oncol 1997; 44:59-63. [PMID: 9288859 DOI: 10.1016/s0167-8140(97)00064-9] [Citation(s) in RCA: 71] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND AND PURPOSE Symptoms of acute radiation enteritis (ARE), dominated by diarrhea, occur in more than 70% of patients receiving pelvic irradiation. Eicosanoids and free radicals release have been implicated in the pathogenesis. Mesalazine (5-ASA) is a potent inhibitor of their synthesis in the mucosa and could therefore be of some interest in preventing ARE. PATIENTS AND METHODS The study was performed in six radiotherapy units in France who agreed on standardized irradiation procedures. One hundred and fifty-three patients planned for external beam radiotherapy to the pelvis > or = 45 Gy for prostate (n = 97) or uterus (n = 54) cancer were randomized on a double blind basis to receive prophylactic 5-ASA (4 g/day Pentasa) or placebo. Patients with concomitant chemotherapy were excluded. Prostate and uterus cancers were chosen since these centropelvic tumors require a similar radiotherapy protocol during the first step of treatment and involve a comparable volume of small intestine. The symptoms of ARE and their severity were assessed every week during irradiation, and 1 and 3 months after its end. All patients followed a low fiber and low lactose diet. End points were diarrhea, use of antidiarrheal agents, abdominal pain, and body weight. Effficacy was evaluated using intention to treat. RESULTS (means +/- SD) Groups did not differ for age (mean 64 +/- 9 years), sex, tumor site, or irradiation procedure. During irradiation, diarrhea occurred in 69% and 66% of the 5-ASA and placebo groups, respectively (chi2, P = 0.22). Curves of survival without diarrhea did not differ between groups (logrank P = 0.09). Severity of diarrhea did not differ between groups except at d15 where it was significantly more severe in the 5-ASA group (ANOVA P = 0.006). Duration of diarrhea did not differ (22 +/- 15 days in both groups, P = 0.88). Abdominal pain was less frequently reported in the 5-ASA group at d28 (34% vs. 51%, P = 0.048). Use of antidiarrheal agents and body weight did not differ between groups. CONCLUSION Mesalazine 4 g/day did not decrease the symptoms of ARE.
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Affiliation(s)
- M Resbeut
- Centre de Recherche et de Lutte Contre le Cancer, Institut Paoli-Calmettes, Marseille, France
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Martenson JA, Hyland G, Moertel CG, Mailliard JA, O'Fallon JR, Collins RT, Morton RF, Tewfik HH, Moore RL, Frank AR, Urias RE, Deming RL. Olsalazine is contraindicated during pelvic radiation therapy: results of a double-blind, randomized clinical trial. Int J Radiat Oncol Biol Phys 1996; 35:299-303. [PMID: 8635937 DOI: 10.1016/0360-3016(96)00016-8] [Citation(s) in RCA: 55] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
PURPOSE A randomized clinical trial from Great Britain suggested a possible beneficial effect of acetylsalicylate in the prevention of radiation-induced bowel toxicity. Olsalazine is an orally administered drug designed to deliver 5-aminosalicylate to the large bowel with minimal systemic absorption. A randomized clinical trial was undertaken to assess the effectiveness of olsalazine in preventing acute diarrhea in patients receiving pelvic radiation therapy. METHODS AND MATERIALS Patients receiving pelvic radiation therapy were randomized, in double-blind fashion, to olsalazine 250 mg, two capsules twice daily, or an identical appearing placebo, two capsules twice daily. Patients were then evaluated weekly during radiation therapy for the primary study endpoint, diarrhea, as well as rectal bleeding, abdominal cramping, and tenesmus. RESULTS The study was closed early, after entry of 58 evaluable patients, when a preliminary analysis showed excessive diarrhea in patients randomized to olsalazine. The incidence and severity of diarrhea were worse in patients randomized to olsalazine (p = 0.0036). Sixty percent of the patients randomized to olsalazine experienced Grade 3 or 4 diarrhea compared to only 14% randomized to placebo. There was also a trend toward higher incidence and greater severity of abdominal cramping in patients who were randomized to olsalazine (p = 0.084). CONCLUSION Administration of olsalazine during pelvic radiation therapy resulted in an increased incidence and severity of diarrhea. Olsalazine is contraindicated in patients receiving pelvic radiation therapy.
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Kardamakis D, Trask CW, de Bruijn KM. A double-blind comparison study of tropisetron and placebo in the prevention of radiation-induced diarrhoea. Eur J Cancer 1995; 31A:850. [PMID: 7640081 DOI: 10.1016/0959-8049(94)00525-a] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
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Affiliation(s)
- S Cascinu
- Servizio di Oncologia, Ospedali Riunitii-Pesaro, Italy
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