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Bhatia M, Suliman H, Ahmed R, Kostadinov D, Singhal T. Radiation Proctitis: A Review of Pathophysiology and Treatment Strategies. Cureus 2024; 16:e70581. [PMID: 39483948 PMCID: PMC11525059 DOI: 10.7759/cureus.70581] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/30/2024] [Indexed: 11/03/2024] Open
Abstract
Radiotherapy (RT) has become an integral part of cancer treatment worldwide; it aims to arrest the uncontrolled growth of tumor cells by using high-energy rays. Radiation proctitis is a known clinical manifestation after the RT regime for pelvic malignancies. Radiation proctitis can have a variable presentation, and there are a lot of patient-related factors that can affect the eventual outcome. In most instances, it is self-limiting; however, it can become chronic in some cases and can affect the quality of life. Many treatment options are recommended, but there has been no consensus on the treatment protocols for managing this known clinical condition. We have tried to briefly describe its pathogenesis, important factors affecting the outcome, and available treatment strategies.
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Affiliation(s)
- Mohit Bhatia
- Colorectal and General Surgery, Princess Royal University Hospital, King's College Hospital NHS Foundation Trust, London, GBR
| | - Hadeel Suliman
- Colorectal and General Surgery, Princess Royal University Hospital, King's College Hospital NHS Foundation Trust, London, GBR
| | - Rizwan Ahmed
- General Surgery, Princess Royal University Hospital, King's College Hospital NHS Foundation Trust, London, GBR
| | - Danko Kostadinov
- Colorectal and General Surgery, Princess Royal University Hospital, King's College Hospital NHS Foundation Trust, London, GBR
| | - Tarun Singhal
- Colorectal and General Surgery, Princess Royal University Hospital, King's College Hospital NHS Foundation Trust, London, GBR
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Chi MS, Hsieh PH, Huang SH, Hsu HC, Chi KH. Chronic radiation proctitis refractory to steroid enema was successfully treated by metformin and sodium butyrate: a case report. J Med Case Rep 2024; 18:239. [PMID: 38725071 PMCID: PMC11083804 DOI: 10.1186/s13256-024-04551-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2024] [Accepted: 04/17/2024] [Indexed: 05/12/2024] Open
Abstract
BACKGROUND Radiation proctitis (RP) is a significant complication of pelvic radiation. Effective treatments for chronic RP are currently lacking. We report a case where chronic RP was successfully managed by metformin and butyrate (M-B) enema and suppository therapy. CASE PRESENTATION A 70-year-old Asian male was diagnosed with prostate cancer of bilateral lobes, underwent definitive radiotherapy to the prostate of 76 Gy in 38 fractions and six months of androgen deprivation therapy. Despite a stable PSA nadir of 0.2 ng/mL for 10 months post-radiotherapy, he developed intermittent rectal bleeding, and was diagnosed as chronic RP. Symptoms persisted despite two months of oral mesalamine, mesalamine enema and hydrocortisone enema treatment. Transition to daily 2% metformin and butyrate (M-B) enema for one week led to significant improvement, followed by maintenance therapy with daily 2.0% M-B suppository for three weeks, resulting in continued reduction of rectal bleeding. Endoscopic examination and biopsy demonstrated a good therapeutic effect. CONCLUSIONS M-B enema and suppository may be an effective treatment for chronic RP.
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Affiliation(s)
- Mau-Shin Chi
- Department of Radiation Therapy and Oncology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan
- Institute of Veterinary Clinical Science, School of Veterinary Medicine, National Taiwan University, Taipei, Taiwan
| | - Ping-Hsun Hsieh
- Division of Gastroenterology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan
| | - Shu-Han Huang
- Department of Pathology and Laboratory Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan
| | - Ho-Chi Hsu
- Department of General Surgery, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan
| | - Kwan-Hwa Chi
- Department of Radiation Therapy and Oncology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.
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Gao J, Li Y, Chen J, Feng W, Bu J, Lu Z, Wang J. Emodin ameliorates acute radiation proctitis in mice by regulating AKT/MAPK/NF-κB/VEGF pathways. Int Immunopharmacol 2024; 132:111945. [PMID: 38555816 DOI: 10.1016/j.intimp.2024.111945] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2023] [Revised: 03/13/2024] [Accepted: 03/25/2024] [Indexed: 04/02/2024]
Abstract
BACKGROUND Emodin, a natural anthraquinone derivative isolated from the roots of Rheum officinale Baill, has many pharmacological effects including anti-inflammatory, antioxidant, antiviral, antibacterial and anti-cancer. However, little is known about the effect of emodin on acute radiation proctitis (ARP). The present study was conducted to determine its effects and elucidate its mechanisms involving AKT/MAPK/NF-κB/VEGF pathways in ARP mice. METHODS Total 60 C57BL/6 mice were divided randomly into control group, ARP group, AKT inhibitor MK-2206 group, and different doses of emodin groups. ARP mice were induced by 27 Gy of 6 MV X-ray pelvic local irradiation. MK-2206 was given orally for 2 weeks on alternate days. Emodin was administered daily by oral gavage for 2 weeks. Subsequently, all mice were sacrificed on day 15. The rectal tissues were obtained for further tests. The general signs score and the pathological grade were used to evaluate the severity of ARP. The expression of NF-κB, VEGF and AQP1 were determined by immunohistochemistry and western blot. The expression of p-AKT, p-ERK, p-JNK, p-p38, Bcl-2 and Bax were assessed using western blot. RESULTS The worse general signs and damaged tissue structure of ARP mice were profoundly ameliorated by emodin. The expression of p-AKT, p-ERK, NF-κB, VEGF and AQP1 were significantly increased, resulting in the inflammation-induced angiogenesis in ARP mice. However, the expression of p-JNK and p-p38 were decreased, leading to the reduction of apoptosis in ARP mice. Excitedly, emodin reversed these changes, not only inhibited inflammation-induced angiogenesis, but also promoted apoptosis. Notably, the effects of emodin were similar to that of AKT inhibitor MK-2206, suggesting the involvement of AKT signaling in the effect of emodin. CONCLUSION These results suggest that emodin attenuates ARP in mice, and the underlying mechanism might involve inhibition of the AKT/ERK/NF-κB/VEGF pathways and the induction of apoptosis mediated by JNK and p38.
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Affiliation(s)
- Jinsheng Gao
- Department of Preventive Treatment of Disease, Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai, 200137, China
| | - Yousong Li
- Department of Traditional Chinese Medicine, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, 030032, China
| | - Jiaohua Chen
- Department of Health Management, Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai, 200137, China
| | - Wen Feng
- Department of Preventive Treatment of Disease, Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai, 200137, China
| | - Jianchen Bu
- Department of Health Management, Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai, 200137, China
| | - Zixuan Lu
- Department of Emergency, Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai, 200137, China
| | - Jiandong Wang
- Department of General Surgery, Putuo Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, China.
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Zhang H, Zhang Z, Yuan S. Chinese clinical practice guidelines for the prevention and treatment of radiation-induced rectal injury. PRECISION RADIATION ONCOLOGY 2023; 7:237-255. [PMID: 40336868 PMCID: PMC11935203 DOI: 10.1002/pro6.1217] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2023] [Revised: 11/19/2023] [Accepted: 11/20/2023] [Indexed: 05/09/2025] Open
Abstract
Although radiotherapy plays an important role in the treatment of cancer, it may have negative effects in some individuals. Rectal injury is a common adverse effect of abdominal and pelvic radiotherapy. This injury is caused by administering radiation to the abdomen. Appropriate treatment techniques can be determined if doctors have a better understanding of the incidence, risk factors, and clinical symptoms of radiation-induced rectal injuries. Studies on the underlying pathophysiology of radiation-induced rectal injury may aid in the development of effective treatment and prevention strategies. The implementation of efficient preventive measures can improve the quality of life of patients with cancer and make it easier for them to complete their treatment. Therefore, comprehensive and accurate assessments are crucial for developing holistic and individualized treatment plans for patients who have already developed symptoms, with early intervention being a priority.
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Affiliation(s)
- Hui Zhang
- Department of Radiation OncologyFudan University Shanghai Cancer CenterShanghaiChina
| | - Zhen Zhang
- Department of Radiation OncologyFudan University Shanghai Cancer CenterShanghaiChina
- China Anti‐Cancer Association Tumor Support Therapy Committee
- China Anti‐Cancer Association Tumor Radiation Protection Committee
- Chinese Radiation Therapy Oncology Group
| | - Shuanghu Yuan
- China Anti‐Cancer Association Tumor Support Therapy Committee
- China Anti‐Cancer Association Tumor Radiation Protection Committee
- Chinese Radiation Therapy Oncology Group
- Department of RadiologyShandong Cancer HospitalJinanChina
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Ren H, Wu Q, Sun Z, Fang M, Liu J, Luo J. Research progress and treatment of radiation enteritis and gut microbiota. Radiat Oncol J 2023; 41:61-68. [PMID: 37403348 DOI: 10.3857/roj.2023.00346] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2023] [Accepted: 06/01/2023] [Indexed: 07/06/2023] Open
Abstract
Radiation enteritis is a kind of intestinal radiation injury in patients with pelvic and retroperitoneal malignancies after radiotherapy, and its occurrence and development process are very complicated. At present, studies have confirmed that intestinal microecological imbalance is an important factor in the formation of this disease. Abdominal radiation causes changes in the composition of the flora and a decrease in its diversity, which is mainly manifested by a decrease in beneficial bacterial species such as Lactobacilli and Bifidobacteria. Intestinal dysbacteriosis aggravates radiation enteritis, weakens the function of the intestinal epithelial barrier, and promotes the expression of inflammatory factors, thereby aggravating the occurrence of enteritis. Given the role of the microbiome in radiation enteritis, we suggest that the gut microbiota may be a potential biomarker for the disease. Treatment methods such as probiotics, antibiotics, and fecal microbiota transplantation are ways to correct the microbiota and may be an effective way to prevent and treat radiation enteritis. Based on a review of the relevant literature, this paper reviews the mechanism and treatment of intestinal microbes in radiation enteritis.
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Affiliation(s)
- Huiwen Ren
- Department of Radiotherapy, The Affiliated Changzhou Second People's Hospital of Nanjing Medical University, Changzhou Medical Center, Nanjing Medical University, Changzhou, China
- Department of Radiotherapy, Graduate School of Dalian Medical University, Dalian, China
| | - Qi Wu
- Department of Histology and Embryology, Heze Medical College, Heze, China
| | - Zhiqiang Sun
- Department of Radiotherapy, The Affiliated Changzhou Second People's Hospital of Nanjing Medical University, Changzhou Medical Center, Nanjing Medical University, Changzhou, China
| | - Mingming Fang
- Department of Radiotherapy, Changzhou Fourth People's Hospital, Changzhou, China
| | - Jun Liu
- Department of Radiotherapy, Changzhou Fourth People's Hospital, Changzhou, China
| | - Judong Luo
- Department of Radiotherapy, The Affiliated Changzhou Second People's Hospital of Nanjing Medical University, Changzhou Medical Center, Nanjing Medical University, Changzhou, China
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Sharma AK, Prasad A, Kalonia A, Shaw P, Kumar R, Shukla SK. Combined radiation burn injuries: A note. JOURNAL OF RADIOLOGICAL PROTECTION : OFFICIAL JOURNAL OF THE SOCIETY FOR RADIOLOGICAL PROTECTION 2022; 42:043502. [PMID: 36317279 DOI: 10.1088/1361-6498/ac9e61] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/26/2022] [Accepted: 10/28/2022] [Indexed: 06/16/2023]
Abstract
Combined radiation injury occurs when radiation is accompanied by any other form of trauma. The past experiences of Hiroshima, Nagasaki, and Chernobyl have revealed that a large number of victims of such nuclear accidents or attacks suffer from combined radiation injuries. The possibility of a nuclear attack seems very far-fetched, but the destruction that would occur in such an event would be massive, with a huge lossof lives. Therefore, preparedness for the same should be done beforehand. The severity of combined radiation depends upon various factors, such as radiation dose, type, tissues affected, and traumas. The article focuses on combined radiation burn injury (CRBI) which may arise due to the combination of ionising radiation with thermal burns. CRBI can have varied effects on different organs like the hematopoietic, digestive, lymphatic, cardiovascular, and respiratory systems. Some of the most profound lethal effects are hematopoietic dysfunction, gastrointestinal leakage, bacterial translocation to other organ sites, pulmonary fibrosis, and pneumonitis. In this article, we have attempted to accumulate the knowledge of ongoing research on the functioning of different organ systems, which are affected due to CRBI and possible countermeasures to minimize the effects, thus improving survival.
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Affiliation(s)
- Ajay Kumar Sharma
- Institute of Nuclear Medicine & Allied Sciences, Defence Research and Development Organization, Lucknow Road, Timarpur, New Delhi 110054, India
| | - Ayushi Prasad
- Sri Venkateswara College, University of Delhi, Benito Juarez Road, Dhaula Kuan, New Delhi 110021, India
| | - Aman Kalonia
- Institute of Nuclear Medicine & Allied Sciences, Defence Research and Development Organization, Lucknow Road, Timarpur, New Delhi 110054, India
| | - Priyanka Shaw
- Institute of Nuclear Medicine & Allied Sciences, Defence Research and Development Organization, Lucknow Road, Timarpur, New Delhi 110054, India
| | - Rishav Kumar
- Institute of Nuclear Medicine & Allied Sciences, Defence Research and Development Organization, Lucknow Road, Timarpur, New Delhi 110054, India
| | - Sandeep Kumar Shukla
- Institute of Nuclear Medicine & Allied Sciences, Defence Research and Development Organization, Lucknow Road, Timarpur, New Delhi 110054, India
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Steinhauff D, Jensen M, Talbot M, Jia W, Isaacson K, Jedrzkiewicz J, Cappello J, Oottamasathien S, Ghandehari H. Silk-elastinlike copolymers enhance bioaccumulation of semisynthetic glycosaminoglycan ethers for prevention of radiation induced proctitis. J Control Release 2021; 332:503-515. [PMID: 33691185 DOI: 10.1016/j.jconrel.2021.03.001] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Revised: 02/17/2021] [Accepted: 03/01/2021] [Indexed: 12/22/2022]
Abstract
Radiation-induced proctitis (RIP) is a debilitating adverse event that occurs commonly during lower abdominal radiotherapy. The lack of prophylactic treatment strategies leads to diminished patient quality of life, disruption of radiotherapy schedules, and limitation of radiotherapy efficacy due to dose-limiting toxicities. Semisynthetic glycosaminoglycan ethers (SAGE) demonstrate protective effects from RIP. However, low residence time in the rectal tissue limits their utility. We investigated controlled delivery of GM-0111, a SAGE analogue with demonstrated efficacy against RIP, using a series of temperature-responsive polymers to compare how distinct phase change behaviors, mechanical properties and release kinetics influence rectal bioaccumulation. Poly(lactic acid)-co-(glycolic acid)-block-poly(ethylene glycol)-block-poly(lactic acid)-co-(glycolic acid) copolymers underwent macroscopic phase separation, expelling >50% of drug during gelation. Poloxamer compositions released GM-0111 cargo within 1 h, while silk-elastinlike copolymers (SELPs) enabled controlled release over a period of 12 h. Bioaccumulation was evaluated using fluorescence imaging and confocal microscopy. SELP-415K, a SELP analogue with 4 silk units, 15 elastin units, and one elastin unit with lysine residues in the monomer repeats, resulted in the highest rectal bioaccumulation. SELP-415K GM-0111 compositions were then used to provide localized protection from radiation induced tissue damage in a murine model of RIP. Rectal delivery of SAGE using SELP-415K significantly reduced behavioral pain responses, and reduced animal mass loss compared to irradiated controls or treatment with traditional delivery approaches. Histological scoring showed RIP injury was ameliorated for animals treated with GM-0111 delivered by SELP-415K. The enhanced bioaccumulation provided by thermoresponsive SELPs via a liquid to semisolid transition improved rectal delivery of GM-0111 to mice and radioprotection in a RIP model.
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Affiliation(s)
- D Steinhauff
- Department of Biomedical Engineering, University of Utah, Salt Lake City, UT 84112, USA; Utah Center for Nanomedicine, University of Utah, Salt Lake City, UT 84112, USA
| | - M Jensen
- Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USA
| | - M Talbot
- Department of Biomedical Engineering, University of Utah, Salt Lake City, UT 84112, USA; Utah Center for Nanomedicine, University of Utah, Salt Lake City, UT 84112, USA
| | - W Jia
- Utah Center for Nanomedicine, University of Utah, Salt Lake City, UT 84112, USA
| | - K Isaacson
- Department of Biomedical Engineering, University of Utah, Salt Lake City, UT 84112, USA; Utah Center for Nanomedicine, University of Utah, Salt Lake City, UT 84112, USA
| | - J Jedrzkiewicz
- Department of Pathology, University of Utah, Salt Lake City, UT 84112, USA
| | - J Cappello
- Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT 84112, USA
| | - S Oottamasathien
- Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USA; Department of Urology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USA.
| | - H Ghandehari
- Department of Biomedical Engineering, University of Utah, Salt Lake City, UT 84112, USA; Utah Center for Nanomedicine, University of Utah, Salt Lake City, UT 84112, USA; Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT 84112, USA.
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8
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Zimmermann F. Gastrointestinal Toxicity. Radiat Oncol 2020. [DOI: 10.1007/978-3-319-52619-5_108-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
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9
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Lu L, Li W, Chen L, Su Q, Wang Y, Guo Z, Lu Y, Liu B, Qin S. Radiation-induced intestinal damage: latest molecular and clinical developments. Future Oncol 2019; 15:4105-4118. [PMID: 31746639 DOI: 10.2217/fon-2019-0416] [Citation(s) in RCA: 48] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Aim: To systematically review the prophylactic and therapeutic interventions for reducing the incidence or severity of intestinal symptoms among cancer patients receiving radiotherapy. Materials & methods: A literature search was conducted in the PubMed database using various search terms, including 'radiation enteritis', 'radiation enteropathy', 'radiation-induced intestinal disease', 'radiation-induced intestinal damage' and 'radiation mucositis'. The search was limited to in vivo studies, clinical trials and meta-analyses published in English with no limitation on publication date. Other relevant literature was identified based on the reference lists of selected studies. Results: The pathogenesis of acute and chronic radiation-induced intestinal damage as well as the prevention and treatment approaches were reviewed. Conclusion: There is inadequate evidence to strongly support the use of a particular strategy to reduce radiation-induced intestinal damage. More high-quality randomized controlled trials are required for interventions with limited evidence suggestive of potential benefits.
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Affiliation(s)
- Lina Lu
- School of Nuclear Science & Technology, Lanzhou University, Lanzhou 730000, Gansu, PR China.,School of Chemical Engineering, Northwest Minzu University, Lanzhou 730000, Gansu, PR China
| | - Wenjun Li
- Key Laboratory of Biology & Bioresource Utilization, Yantai Institute of Costal Zone Research, Chinese Academy of Sciences, Yantai 264003, PR China.,Center for Ocean Mega-Science, Chinese Academy of Sciences, Qingdao 266071, PR China
| | - Lihua Chen
- School of Chemical Engineering, Northwest Minzu University, Lanzhou 730000, Gansu, PR China
| | - Qiong Su
- School of Chemical Engineering, Northwest Minzu University, Lanzhou 730000, Gansu, PR China
| | - Yanbin Wang
- School of Chemical Engineering, Northwest Minzu University, Lanzhou 730000, Gansu, PR China
| | - Zhong Guo
- Medical College of Northwest Minzu University, Lanzhou 730000, Gansu, PR China
| | - Yongjuan Lu
- School of Chemical Engineering, Northwest Minzu University, Lanzhou 730000, Gansu, PR China
| | - Bin Liu
- School of Nuclear Science & Technology, Lanzhou University, Lanzhou 730000, Gansu, PR China.,School of Stomatology, Lanzhou University, Lanzhou 730000, Gansu, PR China
| | - Song Qin
- Key Laboratory of Biology & Bioresource Utilization, Yantai Institute of Costal Zone Research, Chinese Academy of Sciences, Yantai 264003, PR China.,Center for Ocean Mega-Science, Chinese Academy of Sciences, Qingdao 266071, PR China
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Abstract
RATIONALE Radiation enteritis (RE) is one of the serious complications caused by the radiotherapy and it can occur in any segment of the intestine, including small intestine, colon, and rectum. It can cause a number of serious problems of the intestine, such as chronic ulcers, bleeding, intestinal stenosis, intestinal fistula, and perforation. At present, there is no standard treatment guideline for the RE. PATIENT CONCERNS A 54-year-old male patient received surgery and chemotherapy for rectal cancer and radiofrequency ablation (RFA) for a single metastatic carcinoma of the liver. Three years later, he was diagnosed with recurrent lesion in the rectal anastomotic stoma and was treated with radiotherapy with a total dose of 70 Gy. Following this, he had persistent abdominal pain and diarrhea for 1 year. DIAGNOSES Colonoscopy confirmed a diagnosis of RE. INTERVENTIONS Since intestinal probiotics, intestinal mucosal protectants, antidiarrheal drugs, and other treatments were not effective; the patient was treated by RFA. OUTCOMES Clinical symptoms of the patient were gradually decreased after the RFA. Colonoscopy examination was performed 3 months later and intestinal mucosa was found to have healed well. LESSONS RFA is an effective treatment for patients with RE, and it is expected to be one of the standard treatments for the RE.
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Wu C, Guan L, Yao L, Huang J. Mesalazine suppository for the treatment of refractory ulcerative chronic radiation proctitis. Exp Ther Med 2018; 16:2319-2324. [PMID: 30186474 PMCID: PMC6122487 DOI: 10.3892/etm.2018.6464] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2016] [Accepted: 06/25/2018] [Indexed: 12/21/2022] Open
Abstract
The aim of the present study was to investigate the safety and efficacy of mesalazine suppository in the treatment of refractory ulcerative chronic radiation proctitis (CRP). In total, 10 refractory ulcerative CRP patients who did not respond to previous medical treatments were recruited for the present study and were treated with mesalazine suppository (0.5 g) twice daily for 24 weeks. For each patient, the severity of clinical symptoms and endoscopic appearance was assessed before and after the treatment. For symptom scoring, the reductions in the mean total symptom score (pre- vs. post-treatment, 8.20 vs. 0.90; P<0.01), rectal bleeding score (2.40 vs. 0.30; P<0.01), rectal pain score (2.00 vs. 0.50; P<0.01), stool frequency score (2.00 vs. 0.10; P<0.01) and tenesmus score (1.80 vs. 0.00; P<0.01) were all statistically significant. For mucosal damage scoring, there was a reduction in the mean scores for total scores (9.22 vs. 5.22; P<0.01), telangiectasia (2.78 vs. 1.89; P=0.009), edema (2.89 vs. 1.78; P=0.001) and ulceration (2.44 vs. 0.89; P=0.003). However, statistically reductions in the median symptom scores were not observed for stenosis (0.78 vs. 0.67; P=0.347) and necrosis (0.33 vs. 0.00; P=0.081). Furthermore, no adverse events were observed during and after the treatment. The topical mesalazine suppository may be a safe and effective treatment for CRP, particularly for patients with deep ulcers. Adequately randomized controlled trials are required to confirm the results of the present study.
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Affiliation(s)
- Changliang Wu
- Department of Gastroenterology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530007, P.R. China
| | - Liyu Guan
- Department of Gastroenterology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530007, P.R. China
| | - Li Yao
- Department of Gastroenterology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530007, P.R. China
| | - Jiean Huang
- Department of Gastroenterology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530007, P.R. China
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12
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Zhong W, Weiss HL, Jayswal RD, Hensley PJ, Downes LM, St Clair DK, Chaiswing L. Extracellular redox state shift: A novel approach to target prostate cancer invasion. Free Radic Biol Med 2018; 117:99-109. [PMID: 29421238 PMCID: PMC5845758 DOI: 10.1016/j.freeradbiomed.2018.01.023] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2017] [Revised: 01/18/2018] [Accepted: 01/20/2018] [Indexed: 01/17/2023]
Abstract
AIM Extracellular superoxide dismutase (ECSOD) and the cysteine/glutamate transporter (Cys)/(xCT) are tumor microenvironment (TME) redox state homeostasis regulators. Altered expression of ECSOD and xCT can lead to imbalance of the TME redox state and likely have a profound effect on cancer invasion. In the present study, we investigated whether ECSOD and xCT could be therapeutic targets for prostate cancer (PCa) invasion. RESULTS Immunohistochemistry of tumor microarray PCa tissues (N = 165) with high Gleason scores indicated that xCT protein expression is significantly increased while ECSOD protein expression is significantly decreased. Metastatic PCa indicated ECSOD protein expression is significantly decreased in epithelial area whereas xCT protein expression is significantly increased in stromal area. Furthermore, inhibition of extracellular O2•- by overexpression of ECSOD or alteration of the extracellular Cys/CySS ratio by knockdown of xCT protein inhibited PCa cell invasion. Simultaneous overexpression of ECSOD and knockdown xCT inhibited PCa cell invasion more than overexpression of ECSOD or knockdown of xCT alone. In the co-culturing system, simultaneous overexpression of ECSOD and knockdown of xCT in prostate stromal WPMY-1 cells inhibited PCa cell invasiveness more than overexpression of ECSOD alone. The decrease in PCa invasion correlated with increased of extracellular H2O2 levels. Notably, overexpression of catalase in TME reversed the inhibitory effect of ECSOD on cancer cell invasion. CONCLUSION Impaired ECSOD activity and an upregulated of xCT protein expression may be clinical features of an aggressive PCa, particularly metastatic cancers and/or those with a high Gleason score. Therefore, shifting the extracellular redox state toward an oxidizing status by targeted modulation of ECSOD and xCT, in both cancer and stromal cells, may provide a greater strategy for potential therapeutic interventions of aggressive PCa.
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Affiliation(s)
- Weixiong Zhong
- Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, WI, USA
| | - Heidi L Weiss
- The Markey Biostatistics and Bioinformatics Shared Resource Facility, University of Kentucky, Lexington, USA
| | - Rani D Jayswal
- The Markey Biostatistics and Bioinformatics Shared Resource Facility, University of Kentucky, Lexington, USA
| | | | - Laura M Downes
- College of Medicine, University of Kentucky, Lexington, USA
| | - Daret K St Clair
- Department of Toxicology and Cancer Biology, University of Kentucky, Lexington, USA
| | - Luksana Chaiswing
- Department of Toxicology and Cancer Biology, University of Kentucky, Lexington, USA.
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13
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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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Sahebnasagh A, Ghasemi A, Akbari J, Alipour A, Lashkardoost H, Ala S, Salehifar E. Successful Treatment of Acute Radiation Proctitis with Aloe Vera: A Preliminary Randomized Controlled Clinical Trial. J Altern Complement Med 2017; 23:858-865. [PMID: 28618234 DOI: 10.1089/acm.2017.0047] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023] Open
Abstract
BACKGROUND Acute radiation proctitis (ARP) is a common side-effect that affects up to 50% of patients receiving radiotherapy. The aim of this study was to evaluate the role of a topical preparation of Aloe vera in the treatment of ARP induced by radiotherapy of pelvic area. SUBJECTS AND INTERVENTIONS In this double-blind placebo-controlled trial, 20 consecutive patients with ARP after external-beam radiation therapy (46-72 Gy) of pelvic malignancies were randomized to receive either Aloe vera 3% or placebo ointment, 1 g twice daily for 4 weeks. These patients presented with at least two of the following symptoms: rectal bleeding, abdominal/rectal pain, diarrhea, or fecal urgency. These symptoms were rated by the patients in terms of their severity (grade 0-4) for each of the symptoms mentioned earlier at baseline and then weekly for 4 weeks. A symptom index was calculated by the addition of the scores (16 most symptomatic). Radiation Therapy Oncology Group (RTOG) acute toxicity criteria and psychosocial status of the patients were also recorded weekly. The lifestyle impact of the symptoms was assessed by questionnaire grading from 0 (no effect on daily activity) to 4 (afraid to leave home). RESULTS There was a significant (p < 0.05) improvement in the symptom index (before treatment vs. after treatment with Aloe vera) for diarrhea (median score: 0.67 vs. 0.11), fecal urgency (median score: 0.89 vs. 0.11), clinical presentation total (median score: 4.33 vs. 1.22), RTOG total (median score: 2.89 vs. 0.89), and lifestyle (median score: 1.1 vs. 0.33). Hemorrhage and abdominal/rectal pain did not improve significantly. The odds ratios for advantage of Aloe vera over placebo for "clinical presentation total" and "RTOG total" were 3.97 (1.3-11.9) and 5.9 (1.6-21.6), respectively. CONCLUSION A substantial number of patients with radiation proctitis seem to benefit from therapy with Aloe vera 3% ointment.
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Affiliation(s)
- Adeleh Sahebnasagh
- 1 Department of Clinical Pharmacy, Faculty of Pharmacy, Mazandaran University of Medical Sciences , Sari, Iran
| | - Arash Ghasemi
- 2 Emam Khomeini Hospital, Mazandaran University of Medical Sciences , Sari, Iran
| | - Jafar Akbari
- 3 Pharmaceutical Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences , Sari, Iran
| | - Abbas Alipour
- 4 Faculty of Medicine, Community Medicine Department, Mazandaran University of Medical Sciences , Sari, Iran
| | - Hossein Lashkardoost
- 5 School of Public Health, North Khorasan University of Medical Sciences , Bojnurd, Iran
| | - Shahram Ala
- 3 Pharmaceutical Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences , Sari, Iran
| | - Ebrahim Salehifar
- 6 Gastrointestinal Cancer Research Center, Department of Clinical Pharmacy, Faculty of Pharmacy, Mazandaran University of Medical Sciences , Sari, Iran
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Bansal N, Soni A, Kaur P, Chauhan AK, Kaushal V. Exploring the Management of Radiation Proctitis in Current Clinical Practice. J Clin Diagn Res 2016; 10:XE01-XE06. [PMID: 27504391 DOI: 10.7860/jcdr/2016/17524.7906] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2015] [Accepted: 02/24/2016] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Radiation proctitis is radiation induced rectal mucositis, occurring as a consequence to radiation therapy of the pelvic organs for various pelvic region malignancies. The management of radiation proctitis is extremely challenging as no recommended guidelines are available and limited number of studies are there in the literature involving the various treatment options. AIM The aim of the study is the in-depth review of published literature to see the role of various treatment modalities in the management of radiation proctitis. MATERIALS AND METHODS An integrative review was undertaken within PubMed, MEDLINE, PMC, GOOGLE SEARCH databases and articles published upto February 2015 were reviewed and analysed. A total of 54 studies were included. RESULTS Literature suggests that non surgical therapies are the first line of treatment and surgery is reserved for advanced or refractory cases. Endoscopic therapies form the mainstay of treatment in managing the patients of radiation proctitis. Argon plasma coagulation and laser therapies are preferred. Radiofrequency ablation, cryoablation and mesenchymal stem cell therapy are the upcoming modalities. Medical therapy can be tried alone or in conjunction to endoscopic therapies. In the resistant or refractory cases, surgery can be looked for in the form of diversion or resection with or without anastamosis. CONCLUSION Though, a number of options are available, still a lot can be explored in this field to improve the morbidity in the patients and to confirm the superiority of one treatment over other.
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Affiliation(s)
- Nupur Bansal
- Senior Resident, Department of Radiotherapy, Pt. B.D. Sharma PGIMS , Rohtak, India
| | - Abhishek Soni
- Senior Resident, Department of Radiotherapy, Pt. B.D. Sharma PGIMS , Rohtak, India
| | - Paramjeet Kaur
- Associate Professor, Department of Radiotherapy, Pt. B.D. Sharma PGIMS , Rohtak, India
| | - Ashok Kumar Chauhan
- Senior Professor, Department of Radiotherapy, Pt. B.D. Sharma PGIMS , Rohtak, India
| | - Vivek Kaushal
- Senior Professor, Department of Radiotherapy, Pt. B.D. Sharma PGIMS , Rohtak, India
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16
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Dandin Ö, Akin ML, Balta AZ, Yücel E, Karakaş DÖ, Demirbaş S, Özdemir S, Haholu A. The Efficacy of Probiotic (Lactobacillus rhamnosus GG) and 5-ASA (Aminosalicylic Acid) in the Treatment of Experimental Radiation Proctitis in Rats. Indian J Surg 2015; 77:563-569. [PMID: 26730065 PMCID: PMC4692951 DOI: 10.1007/s12262-013-0923-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2013] [Accepted: 04/24/2013] [Indexed: 01/24/2023] Open
Abstract
The aims of the study are to demonstrate the effect of probiotic use on the healing of radiation proctitis (RP) and evaluate the efficiency of fecal biomarkers at follow-up of the treatment. Thirty-two male/female rats were randomly separated into four groups of eight rats. The first group (control) was not radiated. RP was created by 17.5 Gy single dose rectal irradiation. The second group (RP) was subjected to RP, but not treated. The third group (RP+ASA) was treated with 5-aminosalicylic acid (5-ASA) 250 mg/kg daily by gastric lavage for 14 days after the irradiation, and the forth group (RP+LGG) was treated with Lactobacillus GG (LGG) 25 × 100 million CFU daily. Feces samples were taken at the 7th and 14th day of the treatment for fecal biomarkers. Rectums of the rats were resected at the 14th day by laparotomy. Samples were evaluated both macroscopically and microscopically. RP was achieved both macroscopically and microscopically. Weight loss of RP group is statistically significant (p < 0.005) than other groups. The healing ratio of RP+ASA and RP+LGG groups was significantly better than the RP group (p < 0.005) both macroscopically and microscopically. But there was no significant difference between ASA and LGG groups. Biochemically, fecal calprotectin was found to be more effective than fecal myeloperoxidase and fecal lactoferrin to show the efficacy of treatment of radiation proctitis. The results of our study demonstrate that probiotic is as effective as 5-aminosalicylic in the treatment of radiation proctitis, and fecal calprotectin is a useful biomarker in determining the response to the treatment.
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Affiliation(s)
- Özgür Dandin
- />Department of General Surgery, Bursa Military Hospital, Bursa, Turkey
| | - Mehmet Levhi Akin
- />Department of General Surgery, Haydarpaşa Training Hospital, Gülhane Military Medical Academy, Istanbul, Turkey
| | - Ahmet Ziya Balta
- />Department of General Surgery, Haydarpaşa Training Hospital, Gülhane Military Medical Academy, Istanbul, Turkey
| | - Ergün Yücel
- />Department of General Surgery, Haydarpaşa Training Hospital, Gülhane Military Medical Academy, Istanbul, Turkey
| | | | - Sezai Demirbaş
- />Department of General Surgery, Gülhane Military Medical Academy, Ankara, Turkey
| | - Sevim Özdemir
- />Department of Radiation Oncology, Istanbul University, Istanbul, Turkey
| | - Apdullah Haholu
- />Department of Pathology, Haydarpaşa Training Hospital, Gülhane Military Medical Academy, Istanbul, Turkey
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17
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Systematic Review of the Relationship between Acute and Late Gastrointestinal Toxicity after Radiotherapy for Prostate Cancer. Prostate Cancer 2015; 2015:624736. [PMID: 26697225 PMCID: PMC4677238 DOI: 10.1155/2015/624736] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2015] [Accepted: 11/15/2015] [Indexed: 12/24/2022] Open
Abstract
A small but meaningful percentage of men who are treated with external beam radiation therapy for prostate cancer will develop late gastrointestinal toxicity. While numerous strategies to prevent gastrointestinal injury have been studied, clinical trials concentrating on late toxicity have been difficult to carry out. Identification of subjects at high risk for late gastrointestinal injury could allow toxicity prevention trials to be performed using reasonable sample sizes. Acute radiation therapy toxicity has been shown to predict late toxicity in several organ systems. Late toxicities may occur as a consequential effect of acute injury. In this systematic review of published reports, we found that late gastrointestinal toxicity following prostate radiotherapy seems to be statistically and potentially causally related to acute gastrointestinal morbidity as a consequential effect. We submit that acute gastrointestinal toxicity may be used to identify at-risk patients who may benefit from additional attention for medical interventions and close follow-up to prevent late toxicity. Acute gastrointestinal toxicity could also be explored as a surrogate endpoint for late effects in prospective trials.
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18
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Prevention and Management of Radiation-induced Late Gastrointestinal Toxicity. Clin Oncol (R Coll Radiol) 2015; 27:656-67. [DOI: 10.1016/j.clon.2015.06.010] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2015] [Revised: 05/26/2015] [Accepted: 06/09/2015] [Indexed: 12/18/2022]
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Vanneste BGL, Van De Voorde L, de Ridder RJ, Van Limbergen EJ, Lambin P, van Lin EN. Chronic radiation proctitis: tricks to prevent and treat. Int J Colorectal Dis 2015; 30:1293-303. [PMID: 26198994 PMCID: PMC4575375 DOI: 10.1007/s00384-015-2289-4] [Citation(s) in RCA: 70] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/13/2015] [Indexed: 02/04/2023]
Abstract
OBJECTIVE The purpose of this study was to give an overview of the measures used to prevent chronic radiation proctitis (CRP) and to provide an algorithm for the treatment of CRP. METHODS Medical literature databases including PubMed and Medline were screened and critically analyzed for relevance in the scope of our purpose. RESULTS CRP is a relatively frequent late side effect (5-20%) and mainly dependent on the dose and volume of irradiated rectum. Radiation treatment (RT) techniques to prevent CRP are constantly improving thanks to image-guided RT and intensity-modulated RT. Also, newer techniques like protons and new devices such as rectum spacers and balloons have been developed to spare rectal structures. Biopsies do not contribute to diagnosing CRP and should be avoided because of the risk of severe rectal wall damage, such as necrosis and fistulas. There is no consensus on the optimal treatment of CRP. A variety of possibilities is available and includes topical and oral agents, hyperbaric oxygen therapy, and endoscopic interventions. CONCLUSIONS CRP has a natural history of improving over time, even without treatment. This is important to take into account when considering these treatments: first be conservative (topical and oral agents) and be aware that invasive treatments can be very toxic.
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Affiliation(s)
- Ben G L Vanneste
- Department of Radiation Oncology (MAASTRO Clinic), GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, P.O. Box 3035, 6202 NA, Maastricht, The Netherlands.
| | - Lien Van De Voorde
- Department of Radiation Oncology (MAASTRO Clinic), GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, P.O. Box 3035, 6202 NA, Maastricht, The Netherlands
| | - Rogier J de Ridder
- Department of Gastroenterology, Maastricht University Medical Center, Maastricht, The Netherlands
| | - Evert J Van Limbergen
- Department of Radiation Oncology (MAASTRO Clinic), GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, P.O. Box 3035, 6202 NA, Maastricht, The Netherlands
| | - Philippe Lambin
- Department of Radiation Oncology (MAASTRO Clinic), GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, P.O. Box 3035, 6202 NA, Maastricht, The Netherlands
| | - Emile N van Lin
- Department of Radiation Oncology (MAASTRO Clinic), GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, P.O. Box 3035, 6202 NA, Maastricht, The Netherlands
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20
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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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21
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Viswanathan AN, Lee LJ, Eswara JR, Horowitz NS, Konstantinopoulos PA, Mirabeau-Beale KL, Rose BS, von Keudell AG, Wo JY. Complications of pelvic radiation in patients treated for gynecologic malignancies. Cancer 2014; 120:3870-83. [DOI: 10.1002/cncr.28849] [Citation(s) in RCA: 101] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2014] [Revised: 04/30/2014] [Accepted: 05/01/2014] [Indexed: 01/05/2023]
Affiliation(s)
- Akila N. Viswanathan
- Department of Radiation Oncology; Brigham and Women's Hospital and Dana-Farber Cancer Institute; Boston Massachusetts
| | - Larissa J. Lee
- Department of Radiation Oncology; Brigham and Women's Hospital and Dana-Farber Cancer Institute; Boston Massachusetts
| | - Jairam R. Eswara
- Division of Urology; Washington University School of Medicine; St. Louis Missouri
| | - Neil S. Horowitz
- Division of Gynecologic Oncology; Brigham and Women's Hospital; Boston Massachusetts
| | | | | | - Brent S. Rose
- Harvard Radiation Oncology Residency Program; Boston Massachusetts
| | | | - Jennifer Y. Wo
- Department of Radiation Oncology; Massachusetts General Hospital; Boston Massachusetts
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22
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Radioprotective effect of calcium channel blockers against late rectal bleeding in prostate cancer. Radiol Med 2013; 119:343-7. [PMID: 24311192 DOI: 10.1007/s11547-013-0346-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2012] [Accepted: 01/30/2013] [Indexed: 10/25/2022]
Abstract
OBJECTIVE This study was done to assess the impact of clinical factors and in particular the use of drugs for concomitant illnesses on late radiation-induced rectal bleeding in patients with prostate cancer. MATERIALS AND METHODS Patients with histologically proven prostate adenocarcinoma treated with radical radiotherapy and followed up for at least 6 months were selected. The correlation between late rectal bleeding and a number of factors was investigated by univariate and multivariate analysis. RESULTS A total of 278 patients who underwent radiotherapy at our institution between October 2002 and May 2011 were selected. At univariate analysis, delivery of radiation doses higher than 70 Gy and use of angiotensin-converting enzyme inhibitors were associated with a higher incidence of rectal bleeding. Conversely, patients who used calcium channel blockers had a lower risk (3-year rectal bleeding-free survival 89.8 versus 66.5 %, p = 0.043). At multivariate analysis, use of calcium channel blockers was found to have a protective effect with a hazard ratio of 0.3 (95 % CI 0.12-0.96). Delivery of higher radiation doses was associated with an increased risk of rectal bleeding (hazard ratio 3.02, 95 % CI 1.23-7.38). CONCLUSIONS Use of calcium channel blockers during and after radiotherapy treatment might have a protective effect against late rectal bleeding. If these results are reconfirmed by larger clinical series, calcium channel blockers may be tested as radioprotector agents in clinical trials.
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23
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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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Hou JK, Abudayyeh S, Shaib Y. Treatment of chronic radiation proctitis with cryoablation. Gastrointest Endosc 2011; 73:383-9. [PMID: 21295650 DOI: 10.1016/j.gie.2010.10.044] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2010] [Accepted: 10/25/2010] [Indexed: 12/13/2022]
Abstract
BACKGROUND Chronic radiation proctitis (CRP) is a common problem in patients receiving pelvic radiation. Current therapies have the potential for deep tissue injury with ulcerations, perforation, and fistula formation. Cryospray ablation therapy offers superficial ablation of mucosa and is a potential method to endoscopically treat CRP safely and effectively. OBJECTIVE To determine tolerability of and response to cryotherapy in patients with radiation proctitis. DESIGN Prospective case-series pilot study. SETTING Baylor College of Medicine, Michael E. DeBakey Medical Center, Houston, Texas. PATIENTS Ten patients were prospectively recruited with chronic hemorrhagic radiation proctitis. INTERVENTIONS Endoscopic cryoablation of CRP. MAIN OUTCOME MEASUREMENTS Symptom severity of CRP was obtained by using the Radiation Proctitis Severity Assessment Scale (RPSAS). Endoscopic assessment was obtained using the rectal telangiectasia density grade. The primary endpoint of the study was endoscopic improvement of CRP based on the change in rectal telangiectasia density at 3-month follow-up. Secondary endpoints included symptomatic improvement based on RPSAS and adverse events at 3 months. RESULTS Ten patients with hemorrhagic radiation proctitis were treated with endoscopic cryoablation. Endoscopic severity improved as measured by rectal telangiectasia density from 2.7 to 1.7 (P=.004). Overall subjective clinical scores improved as determined by the Radiation Proctitis Severity Assessment Scale from 27.7 to 13.6 (P=.003). Endoscopic improvement correlated with symptom improvement. LIMITATIONS Nonpowered case series pilot study. CONCLUSIONS Cryoablation improved clinical and endoscopic indices in CRP. Further controlled studies are needed to identify the safety and efficacy of cryoablation for CRP.
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Affiliation(s)
- Jason K Hou
- Baylor College of Medicine, Michael E. Debakey Veterans Affairs Hospital, Houston, TX 77030, USA
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Wierzbicki M, Schaly B, Peters T, Barnett R. Automatic image guidance for prostate IMRT using low dose CBCT. Med Phys 2010; 37:3677-86. [PMID: 20831075 DOI: 10.1118/1.3446800] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022] Open
Abstract
PURPOSE Varian's On-Board Imager is a linac-integrated cone-beam CT (CBCT) system used at the authors' institution to acquire images prior to delivering each fraction of prostate intensity modulated radiotherapy. The images are used to determine a couch shift that realigns the tumor with the position obtained in the planning CT. However, this manual image-guided radiotherapy (IGRT) technique is operator dependent, time consuming, offers limited degrees of freedom, and requires significant imaging dose over the course of treatment. To overcome these problems, the authors propose two fully automatic IGRT techniques that require significantly less imaging dose. METHODS Dose is reduced by lowering the x-ray tube mA s during CBCT acquisition at the cost of increasing image noise. In "forward" IGRT, the CBCT image is automatically registered to the planning CT to obtain the necessary couch shift. The "reverse" technique offers additional degrees of freedom as it involves nonrigid registration of the planning CT to the CBCT. Both techniques were evaluated using images of an anthropomorphic phantom with simulated motion and by retrospectively analyzing data from ten prostate cancer patients. RESULTS IGRT error for the phantom data at 100% relative imaging dose was 8.2 +/- 3.7, 3.5 +/- 1.2,, and 2.1 +/- 0.6 mm for setup only, forward, and reverse techniques, respectively. For patient images acquired at 100% relative imaging dose, the errors were 5.4 +/- 1.7, 5.0 +/- 1.6, 5.0 +/- 2.0, and 4.0 +/- 1.6 mm for setup only, manual forward (performed clinically), automatic forward, and reverse IGRT, respectively. Furthermore, imaging dose could be reduced to 20% without a significant loss in image guidance accuracy. CONCLUSIONS The presented image guidance methods are accurate while requiring only 20% of the standard imaging dose. The combination of low dose, automation, and accuracy enables frequent corrections during treatment, possibly leading to reduced margins and improved treatment outcomes.
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Affiliation(s)
- Marcin Wierzbicki
- Department of Medical Physics, Juravinski Cancer Centre, 699 Concession Street, Hamilton, Ontario L8V 5C2, Canada.
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Abstract
Radiation therapy is commonly utilized as a major component in the treatment of pelvic malignancy. Unfortunately, secondary toxicity to the lower gastrointestinal tract can occur. This most commonly affects the rectum, although injuries to the colon and small intestine are not uncommon. The presentation can be acute or chronic, and different mechanisms are responsible for each. Symptomatology is quite variable but can result in significant compromise for the patient. Numerous preventive and treatment strategies have been applied to this disease process. This article presents a summary of the current knowledge regarding radiation injury to the lower gastrointestinal tract with special emphasis on treatment options for radiation proctitis.
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Affiliation(s)
- Gregory D Kennedy
- Department of Surgery, University of Wisconsin Hospital and Clinics, Madison, Wisconsin 53792-7375, USA
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Abstract
Balsalazide is the newer 5-aminosalicylic acid (5-ASA) prodrug which releases active 5-ASA only into the colon with minimal systemic absorption. The onset of action of this drug is variable, and it may take at least some days to reach clinical effectiveness. Clinical studies found balsalazide faster than mesalazine in the induction of remission, but balsalazide has no benefit compared with mesalazine in preventing relapse in the population selected. However, the high number of pills to take may affect the adherence to the treatment. This 5-ASA prodrug may be effectively used also in patients unable to tolerate other mesalamine compounds for non-hypersensitivity reasons. The costs of balsalazide capsules seem to be lower for the health system, both considering total direct healthcare costs and better outcomes, compared with patients treated with oral mesalazine. Finally, there is also some recent evidence that balsalazide may be effectively used, in combination with probiotics, in treating acute uncomplicated diverticulitis is the colon.
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Affiliation(s)
- Antonio Tursi
- Servizio di Gastroenterologia Territoriale, DSS n 4, ASL BAT, Via Torino, 49, Andria, Italy.
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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: 131] [Impact Index Per Article: 8.7] [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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Safety and efficacy of Qingre Buyi Decoction (清热补益煎剂) in the treatment of acute radiation proctitis: A prospective, randomized and controlled trial. Chin J Integr Med 2009; 15:272-8. [DOI: 10.1007/s11655-009-0272-z] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2008] [Indexed: 01/16/2023]
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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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Huang H, Lu JG, Cao YQ. [Advances in treatment of radiation proctitis]. ZHONG XI YI JIE HE XUE BAO = JOURNAL OF CHINESE INTEGRATIVE MEDICINE 2008; 6:975-978. [PMID: 18782547 DOI: 10.3736/jcim20080921] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/26/2023]
Affiliation(s)
- He Huang
- Department of Anorectal Surgery, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.
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Delia P, Sansotta G, Donato V, Frosina P, Messina G, De Renzis C, Famularo G. Use of probiotics for prevention of radiation-induced diarrhea. World J Gastroenterol 2007; 13:912-5. [PMID: 17352022 PMCID: PMC4065928 DOI: 10.3748/wjg.v13.i6.912] [Citation(s) in RCA: 188] [Impact Index Per Article: 10.4] [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 investigate the efficacy of a high-potency probiotic preparation on prevention of radiation-induced diarrhea in cancer patients.
METHODS: This was a double-blind, placebo-controlled trial. Four hundred and ninety patients who underwent adjuvant postoperative radiation therapy after surgery for sigmoid, rectal, or cervical cancer were assigned to either the high-potency probiotic preparation VSL#3 (one sachet t.i.d.,) or placebo starting from the first day of radiation therapy. Efficacy endpoints were incidence and severity of radiation-induced diarrhea, daily number of bowel movements, and the time from the start of the study to the use of loperamide as rescue medication.
RESULTS: More placebo patients had radiation-induced diarrhea than VSL#3 patients (124 of 239 patients, 51.8%, and 77 of 243 patients, 31.6%; P < 0.001) and more patients given placebo suffered grade 3 or 4 diarrhea compared with VSL#3 recipients (55.4% and 1.4%, P < 0.001). Daily bowel movements were 14.7 ± 6 and 5.1 ± 3 among placebo and VSL#3 recipients (P < 0.05), and the mean time to the use of loperamide was 86 ± 6 h for placebo patients and 122 ± 8 h for VSL#3 patients (P < 0.001).
CONCLUSION: Probiotic lactic acid-producing bacteria are an easy, safe, and feasible approach to protect cancer patients against the risk of radiation-induced diarrhea.
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Affiliation(s)
- P Delia
- Institute of Radiology, Oncologic Radiotherapy Unit, Azienda Ospedaliera Universitaria, Messina, Italy
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Garg AK, Mai WY, McGary JE, Grant WH, Butler EB, Teh BS. Radiation proctopathy in the treatment of prostate cancer. Int J Radiat Oncol Biol Phys 2007; 66:1294-305. [PMID: 17126204 DOI: 10.1016/j.ijrobp.2006.07.1386] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2005] [Revised: 06/13/2006] [Accepted: 07/06/2006] [Indexed: 12/13/2022]
Abstract
PURPOSE To compile and review data on radiation proctopathy in the treatment of prostate cancer with respect to epidemiology, clinical manifestations, pathogenesis, risk factors, and treatment. METHODS Medical literature databases including PubMed and Medline were screened for pertinent reports, and critically analyzed for relevance in the scope of our purpose. RESULTS Rectal toxicity as a complication of radiotherapy has received attention over the past decade, especially with the advent of dose-escalation in prostate cancer treatment. A number of clinical criteria help to define acute and chronic radiation proctopathy, but lack of a unified grading scale makes comparing studies difficult. A variety of risk factors, related to either radiation delivery or patient, are the subject of intense study. Also, a variety of treatment options, including medical therapy, endoscopic treatments, and surgery have shown varied results, but a lack of large randomized trials evaluating their efficacy prevents forming concrete recommendations. CONCLUSION Radiation proctopathy should be an important consideration for the clinician in the treatment of prostate cancer especially with dose escalation. With further study of possible risk factors, the advent of a standardized grading scale, and more randomized trials to evaluate treatments, patients and physicians will be better armed to make appropriate management decisions.
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Affiliation(s)
- Amit K Garg
- Department of Radiation Oncology, MD Anderson Cancer Center, Houston, TX, USA
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