Role of Angiogenesis in Chronic Radiation Proctitis: New Evidence Favoring Inhibition of Angiogenesis Ex Vivo

Wu, Peihuang; Li, Li; Wang, Huaiming; Ma, Tenghui; Wu, Haiyong; Fan, Xinjuan; Yang, Zihuan; Chen, Daici; Wang, Lei

doi:10.1007/s10620-017-4818-1

Cited by 9 publications

(13 citation statements)

References 46 publications

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“…A recent study, on the other hand, suggested a strong role of submucosal microvascular changes leading to onset and progression of CRP[34]. Researchers collected fresh surgical rectal specimens from 30 patients with CRP and 29 patients without CRP that allowed assessment of the entire rectal wall for immunohistochemistry arrays of angiogenic factors.…”

Section: Discussionmentioning

confidence: 99%

“…This study found that angiostatin deposits that reside within rectal vessels are perfused throughout the mucosal-submucosal layer upon radiation damage of the endothelial cells. Angiostatins subsequently suppress microvessel formation, causing vessel stenosis and fibrotic vascular sclerosis, decreasing microvessel density in the submucosal layer[34]. The vascular changes and formation of telangiectasias in the mucosal layer are hypothesized to be compensatory changes in response to the alteration of microvasculature in the submucosal layer.…”

Section: Discussionmentioning

confidence: 99%

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Assessment of chronic radiation proctopathy and radiofrequency ablation treatment follow-up with optical coherence tomography angiography: A pilot study

Ahsen

Liang

Lee

et al. 2019

WJG

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BACKGROUND Chronic radiation proctopathy (CRP) occurs as a result of pelvic radiation therapy and is associated with formation of abnormal vasculature that may lead to persistent rectal bleeding. While incidence is declining due to refinement of radiation delivery techniques, CRP remains one of the major complications of pelvic radiation therapy and significantly affects patient quality of life. Radiofrequency ablation (RFA) is an emerging treatment modality for eradicating abnormal vasculature associated with CRP. However, questions remain regarding CRP pathophysiology and optimal disease management. AIM To study feasibility of optical coherence tomography angiography (OCTA) for investigating subsurface vascular alterations in CRP and response to RFA treatment. METHODS Two patients with normal rectum and 8 patients referred for, or undergoing endoscopic RFA treatment for CRP were imaged with a prototype ultrahigh-speed optical coherence tomography (OCT) system over 15 OCT/colonoscopy visits (2 normal patients, 5 RFA-naïve patients, 8 RFA-follow-up visits). OCT and OCTA was performed by placing the OCT catheter onto the dentate line and rectum without endoscopic guidance. OCTA enabled depth-resolved microvasculature imaging using motion contrast from flowing blood, without requiring injected dyes. OCTA features of normal and abnormal microvasculature were assessed in the mucosa and submucosa. Blinded reading of OCTA images was performed to assess the association of abnormal rectal microvasculature with CRP and RFA treatment, and rectal telangiectasia density endoscopic scoring. RESULTS OCTA/OCT images are intrinsically co-registered and enabled depth-resolved visualization of microvasculature in the mucosa and submucosa. OCTA visualized normal vascular patterns with regular honeycomb patterns vs abnormal vasculature with distorted honeycomb patterns and ectatic/tortuous microvasculature in the rectal mucosa. Normal arterioles and venules < 200 μm in diameter versus abnormal heterogenous enlarged arterioles and venules > 200 μm in diameter were visualized in the rectal submucosa. Abnormal mucosal vasculature occurred in 0 of 2 normal patients and 3 of 5 RFA-naïve patients, while abnormal submucosal vasculature occurred more often, in 1 of 2 normal patients and 5 of 5 RFA-naïve patients. After RFA treatment, vascular abnormalities decreased, with abnormal mucosal vasculature observed in 0 of 8 RFA-follow-up visits and abnormal submucosal vasculature observed in only and 2 of 8 RFA-follow-up visits. CONCLUSION OCTA visualizes depth-resolved microvascular abnormalities in CRP, allowing assessment of superficial features which are endoscopically visible as well as deeper vasculature which cannot be seen endoscopically. OCTA/OCT of the rectum can be performed in conjunction with, or independently from endoscopy. Further studies are warranted to investigate if OC...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Assessment of chronic radiation proctopathy and radiofrequency ablation treatment follow-up with optical coherence tomography angiography: A pilot study

Ahsen

Liang

Lee

et al. 2019

WJG

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“…The RIS system is a popular method for evaluating radiation injury in general [ 14–17 ]. We also used in parallel the expression level and distribution pattern of angiostatin as two parameters to evaluate the severity of radiation-induced damage [ 8 ]. Interestingly, we found that the changes in angiostatin were consistent with the changes in RIS.…”

Section: Discussionmentioning

confidence: 99%

“…Sections with a thickness of 4 µm were sliced from formalin-fixed paraffin-embedded samples and placed on slides for hematoxylin and eosin (HE) and Masson's trichrome stains according to standard protocols. Histopathological assessment of each section was performed by calculating the RIS based on our previous study [ 8 ]. Since all patients enrolled in this study had undergone surgery at approximately 6–8 weeks after irradiation, the pathological changes corresponded to the acute or subacute phase and the basic parameters of the RIS included the following: mucosal ulcerations, mucosal telangiectasia, inflammation, epithelial atypia, submucosal fibrosis, edema, and vascular sclerosis.…”

Section: Methodsmentioning

confidence: 99%

“…Therefore, these two parameters were evaluated to distinguish radiation injury in tissues in this study. All experiments were performed according to the manufacturer’s standard protocols, which we have previously described [ 8 ]. Briefly, anti-human angiostatin K1-3 polyclonal primary antibody (R30129, NSJ Bioreagents, San Diego, CA, USA) was used to evaluate the distributed patterns of angiostatin.…”

Section: Methodsmentioning

confidence: 99%

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To what extent should the intestinal be resected proximally after radiotherapy: hint from a pathological view

Zhong

et al. 2019

Gastroenterology Report

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Background Neoadjuvant chemoradiotherapy (nCRT) is associated with post-operative anastomotic complications in rectal-cancer patients. Anastomosis involving at least one non-irradiated margin reportedly significantly reduces the risk of post-operative anastomotic complications in radiation enteritis. However, the exact scope of radiotherapy on the remaining sigmoid colon remains unknown. Methods We evaluated the radiation damage of proximally resected colorectal segments in 44 patients with rectal cancer, who received nCRT followed by conventional resection (nCRT-C, n = 21) or proximally extended resection (nCRT-E, n = 23). The segments from another 13 patients undergoing neoadjuvant chemotherapy (nCT) were used as control. We dissected these samples at a distance of 2 cm between the two adjacent sections. Radiation damage in proximally resected colorectal segments was evaluated using the radiation injury score (RIS) and the concentration and distribution patterns of angiostatin. Results Compared to those in the nCT group, the nCRT group showed higher RIS, levels of angiostatin, and proportion of diffuse pattern of angiostatin. With increasing distance from the tumor site, these parameters all gradually decreased; and the differences came to be not significant at the site that is over 20 cm from the tumor. The nCRT-E group showed lower RIS (median: 2 vs 4, P = 0.002) and a greater proportion of non-diffuse angiostatin (87% vs 55%, P = 0.039) at the proximal margins compared with the nCRT-C group. Conclusions The severity of the radiation damage of the proximal colon is inversely proportional to the proximal-resection margin length. Little damage was left on the proximal margin that was over 20 cm from the tumor. Removal of an initial length of ≥20 cm from the tumor may be beneficial for rectal-cancer patients after nCRT.

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Gut Microbiota‐Derived 3‐Hydroxybutyrate Blocks GPR43‐Mediated IL6 Signaling to Ameliorate Radiation Proctopathy

Ge,

Chen,

Chen

et al. 2024

Advanced Science

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Radiation proctopathy (RP) is a common complication of radiotherapy for pelvic malignancies with high incidence. RP accompanies by microbial dysbiosis. However, how the gut microbiota affects the disease remains unclear. Here, metabolomics reveals that the fecal and serous concentrations of microbiota‐derived 3‐hydroxybutyrate (3HB) are significantly reduced in RP mice and radiotherapeutic patients. Moreover, the concentration of 3HB is negatively associated with the expression of proinflammatory IL6 that is increased along with the severity of radiation damage. 3HB treatment significantly downregulates IL6 expression and alleviates IL6‐mediated radiation damage. Irradiated cell‐fecal microbiota co‐culture experiments and in vivo assays show that such a radioprotection of 3HB is mediated by GPR43. Microbiome analysis reveals that radiation leads to a distinct bacterial community compared to untreated controls, in which Akkermansia muciniphila is significantly reduced in RP mice and radiotherapeutic patients and is associated with lower 3HB concentration. Gavage of A. muciniphila significantly increases 3HB concentration, downregulates GPR43 and IL6 expression, and ameliorates radiation damage. Collectively, these results demonstrate that the gut microbiota, including A. muciniphila, induce higher concentrations of 3HB to block GPR43‐mediated IL6 signaling, thereby conferring radioprotection. The findings reveal a novel implication of the gut‐immune axis in radiation pathophysiology, with potential therapeutic applications.

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Role of Angiogenesis in Chronic Radiation Proctitis: New Evidence Favoring Inhibition of Angiogenesis Ex Vivo

Cited by 9 publications

References 46 publications

Assessment of chronic radiation proctopathy and radiofrequency ablation treatment follow-up with optical coherence tomography angiography: A pilot study

Assessment of chronic radiation proctopathy and radiofrequency ablation treatment follow-up with optical coherence tomography angiography: A pilot study

To what extent should the intestinal be resected proximally after radiotherapy: hint from a pathological view

Gut Microbiota‐Derived 3‐Hydroxybutyrate Blocks GPR43‐Mediated IL6 Signaling to Ameliorate Radiation Proctopathy

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