Radiation Colitis Research Articles

Selenium Attenuates Radiation Colitis by Regulating cGAS-STING Signaling.

Radiation colitis is one of the most common complications in patients undergoing pelvic radiotherapy and there is no effective treatment in the clinic. Therefore, searching for effective agents for the treatment of radiation colitis is urgently needed. Herein, it is found that the essential element selenium (Se) is protective against radiation colitis through inhibiting X-ray-induced apoptosis, cell cycle arrest, and inflammation with the involvement of balancing the generation of reactive oxygen species after the irradiation. Mechanistically, Se, especially for selenium nanoparticles (SeNPs), induced selenoprotein expression and then functioned to effectively restrain DNA damage response, which reduced X-ray-induced intestinal injury. Additionally, SeNPs treatment also restrained the cyclic GMP-AMP synthas (cGAS)- stimulator of interferon genes (STING)-TBK1-IRF3 signaling pathway cascade, thereby blocking the transcription of inflammatory cytokine gene, IL-6 and TNF-α, and thus alleviating inflammation. Moreover, inducing selenoprotein expression, such as GPX4, with SeNPs in vivo can regulate intestinal microenvironment immunity and gut microbiota to attenuate radiation-induced colitis by inhibiting oxidative stress and maintaining microenvironment immunity homeostasis. Together, these results unravel a previously unidentified modulation role that SeNPs restrained radiation colitis with the involvement of inducing selenoprotein expression but suppressing cGAS-STING-TBK1-IRF3 cascade.

Modern concept of differential diagnosis of colitis: from G.F. Lang to the present day. A review

The aim of the article is to improve the differential diagnosis of specific and nonspecific inflammatory bowel diseases. In Russia, this scientific direction is associated with the name of G.F. Lang, who performed in 1901-1902 the study "On ulcerative inflammation of the large intestine caused by balantidiasis". The etiology of specific colitis is associated with infection with parasites, bacteria and viruses that cause inflammation of the intestinal wall, diarrhea, often with an admixture of mucus, pus and blood. Specific colitis (SC) may be accompanied by fever, abdominal pain, and tenesmus. Bacterial colitis is commonly caused by Salmonella, Shigella, Escherichia coli, Clostridium difficile, Campylobacter jejuni, Yersinia enterocolitica, and Mycobacterium tuberculosis. Viral colitis is caused by rotavirus, adenovirus, cytomegalovirus, and norovirus. Parasitic colitis can be caused by Entamoeba histolytica and balantidia. In gay people, SC can cause sexually transmitted infections: Neisseria gonorrhoeae, Chlamydia trachomatis, and treponema pallidum, affecting the rectum. Stool microscopy, culture, and endoscopy are used to establish the diagnosis. Stool culture helps in the diagnosis of bacterial colitis in 50% of patients, and endoscopic studies reveal only nonspecific pathological changes. Differential diagnosis of SC should be carried out with immune-inflammatory bowel diseases (ulcerative colitis, Crohn's disease, undifferentiated colitis), radiation colitis and other iatrogenic bowel lesions. The principles of diagnosis and therapy of inflammatory bowel diseases associated with various etiological.

A ferroptosis-targeting ceria anchored halloysite as orally drug delivery system for radiation colitis therapy

Radiation colitis is the leading cause of diarrhea and hematochezia in pelvic radiotherapy patients. This work advances the pathogenesis of radiation colitis from the perspective of ferroptosis. An oral Pickering emulsion is stabilized with halloysite clay nanotubes to alleviate radiation colitis by inhibiting ferroptosis. Ceria nanozyme grown in situ on nanotubes can scavenge reactive oxygen species, and deferiprone was loaded into the lumen of nanotubes to relieve iron stress. These two strategies effectively inhibit lipid peroxidation and rescue ferroptosis in the intestinal microenvironment. The clay nanotubes play a critical role as either a medicine to alleviate colitis, a nanocarrier that targets the inflamed colon by electrostatic adsorption, or an interfacial stabilizer for emulsions. This ferroptosis-based strategy was effective in vitro and in vivo, providing a prospective candidate for radiotherapy protection via rational regulation of specific oxidative stress.

Diagnosis and Management of Patients with Radiation Colitis

Radiation colitis (Radiation Proctitis or Proctopathy) is a condition in which injury to the rectal mucosa is induced by radiation therapy to the pelvic organs. Radiation colitis is a condition that progresses and is becoming more common and dangerous—usually occurring 6 months to 5 years following regional radiation. This paper presented the diagnosis and management of patients with radiation colitis. There was a patient who had cervical cancer and was hospitalized every 2-3 months because of red blood chapters and weakness. She did chemotherapy and radiation for one year. The patient also received medical therapy, including rectal administration of sucralfate and oral sulfasalazine. Management of patients with radiation colitis is still a problem. There are no definite and consistent guidelines for the treatment of radiation colitis In this patient's case, medical therapy was recently carried out, including rectal administration of sucralfate and oral sulfasalazine. The patient was planning to undergo surgical therapy, but the patient and family refused. It is necessary to think about endoscopic therapy in patients. Argon plasma coagulation (APC) has become the most widely used first-line endoscopic therapy.

P045 Local administration of extracellular vesicles from adipose-derived stromal cells promote healing in a rat model of radiation colitis – a pilot study

Abstract Background The estimated increase in prevalence of radiation enteropathy associated with a current scarcity of effective treatment options underline the need for the development of new therapies. Extracellular vesicles (EV), which are membrane-bound particles secreted by cells containing proteins, lipids and nucleic acids, have yielded promising preclinical results in various applications in regenerative medicine. Here, we aimed to investigate whether EV from adipose-derived stromal cells (ADSC) may present a therapeutic potential in the context of radiation colitis. Methods EV were produced from primary rat ADSC by exposure to a turbulent flow. Radiation colitis was induced by fractionated irradiation at a dose of 3x10Gy on a colorectal window (3x2cm) in male Sprague-Dawley rats (311-386g) at days 0, 2 and 4; following a pre-established protocol. Treatment was administered at days 11 and 15 through submucosal endoscopic injections of rat ADSC (n=9 rats, 2x106cells per dose), EV (n=9 rats, 1.06x1011 particles per dose), or an equivalent volume of saline (n=10 rats). The rats were sacrificed at day 17. Our primary endpoint was the extent of colonic epithelial injury at histological analysis (Table 1). Secondary endpoints included an endoscopic assessment of the severity of lesions at day 15 (Table 2) and an evaluation of macrophage infiltration in the colonic mucosa by CD68 immunohistochemistry. Comparisons of proportions were performed by the Chi-squared test followed by Fisher’s exact test. Results In the ADSC group, 1 rat died from anaesthesia complications. No other adverse effects were observed. No differences in total body weight evolution were observed between the groups. At day 15, a statistically significant decrease of the proportion of animals with moderate to severe lesions was evidenced by endoscopy in the EV group compared to the saline group (p=0.0031; Figure 1). No differences were observed between the other groups. Histological analysis of the colonic epithelial injury score evidenced a non-significant tendency towards a decreased length of high-grade lesions in the EV group (mean±standard deviation: 9180±3684µm; Figure 2) compared with the saline (11536±2711µm) and ADSC (11636±2815) groups. Similarly, CD68+ macrophage infiltration at the site of colonic mucosal lesions tended to be lower in the EV and ADSC groups compared to the saline group. Conclusion This proof-of-concept study seemed to demonstrate a beneficial effect of locally administered extracellular vesicles for the treatment of radiation colitis in the acute setting. A confirmation study in a larger animal cohort is underway, and further investigations focusing on dose effects or long-term effects on fibrosis are required to complete these preliminary results.

Диарейный синдром в практике врача-терапевта: алгоритм действий

According to the frequency of seeking medical care, diarrhea is one of the most common complaints, being an important health problem. Acute diarrhea, as a rule, is infectious in nature, thus, the scope of diagnostics is aimed at assessing the patient's condition and clarifying the pathogen etiology. Chronic diarrhea has a diverse etiology, which poses a difficult task for the clinician to conduct differential diagnosis. Therefore, most guidelines on the relevant problem suggest the use of medical algorithms aimed at step-by-step exclusion of diseases accompanied by diarrhea: from the most common causes to the more rare ones. First of all, it is necessary to detail complaints, identify the presence of red flags, collect an epidemiological, drug and hereditary history, assess the nutrition habits, dietary preferences of the patient and their possible association with the manifestation of diarrhea. The general examination reveals signs of dehydration and malabsorption, as well as the presence of stigma of the underlying disease. Also, at the first stage, it is advisable to conduct the minimum necessary laboratory and instrumental studies. Subsequently, if there are difficulties in establishing the diagnosis, it is advised to re-assess the clinical picture and prescribe additional examination methods. Alongside this, symptomatic and pathogenetic therapy, dehydration, timely detection and correction of electrolyte disorders should be indicated for all patients with acute and chronic diarrhea at the stage of further examination and diagnosis confirmation. KEYWORDS: acute diarrhea, chronic diarrhea, diagnostic algorithm, celiac disease, intestinal tuberculosis, ischemic colitis, radiation colitis, eosinophilic colitis, microscopic colitis, Whipple disease. FOR CITATION: Livzan M.A., Gaus O.V., Gavrilenko D.A. Diarrheal syndrome in the practice of a general practitioner: medical algorithm. Russian Medical Inquiry. 2023;7(5):300–309 (in Russ.). DOI: 10.32364/2587-6821-2023-7-5-8.

S1082 Endoscopic Ultrasound-Guided Superior Hypogastric Plexus Neurolysis: An Update on a Unique Technique for the Management of Pelvic Pain

Introduction: The superior hypogastric plexus is a paired structure located anterior to the sacral promontory, in close proximity to the bifurcation of common iliac vessels. It mediates painful visceral stimuli from most of the pelvic structures. Superior hypogastric plexus neurolysis (SHPN) is a well-recognized treatment for pelvic pain resulting from cancer of sigmoid colon, rectum, prostate, bladder, cervix, and uterus. It is also used to manage pain resulting from benign conditions such as endometriosis, pelvic inflammatory disease, and radiation colitis. The conventional approach used by pain experts is difficult and requires CT guidance. The purpose of this study was to test the hypothesis that endoscopic ultrasound (EUS)-guided SHPN is technically feasible. Methods: Patients with severe pelvic pain due to cancer were eligible for the study. Consecutive patients with pelvic pain secondary to cancer were offered to participate in the study. Pain was graded before and after the procedure and weekly thereafter, by using a visual analog scale graded from 1 to 10. A linear scope was introduced into the rectum and advanced until iliac vessels were identified. In 10 patients, the sacral promontory was identified with fluoroscopy. A 22-gauge needle was passed in the space posterior to the rectum and 10 mL of bupivacaine injected, followed by 10 mL absolute alcohol. In one patient, internal iliac vessels were identified by using EUS and the injections were given anterior to the periosteum; fluoroscopy was not used. Results: SHPN was performed in 11 patients with pelvic pain due to cancer. The procedure was completed successfully in all patients. The mean pain score was 9 before the procedure and 3 after (Table). No complications were encountered. The mean procedure time was 20 minutes. Conclusion: Our study reveals that EUS-guided SHPN is technically feasible. The iliac vessels are well seen by this approach, thus making hemorrhage an unlikely complication. Table 1. - Patient's Clinical profile and Pre-Visual analogue scale and Post-Visual analogue scale scores Number Diagnosis Pre-VAS Post-VAS Duration of Relief (weeks) 1 Rectal Cancer 10 3 6 2 Rectal Cancer 9 2 14 3 Rectal Cancer 8 3 12 4 Prostate Cancer 9 4 6 5 Rectal Cancer 10 2 12 6 Cervix Cancer 9 3 16 7 Sigmoid Cancer 9 5 8 8 Uterine Cancer 8 3 10 9 Rectal Cancer 9 4 24 10 Rectal Cancer 10 2 18 11 Anal Cancer* 10 3 16 *Superior Hypogastric and Ganglion Impar Neurolysis.VAS = Visual analogue scale.

Red dichromatic imaging is useful in argon plasma coagulation of sigmoid radiation colitis.

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SPAR: A randomized placebo-controlled phase 2 trial of simvastatin in addition to standard chemotherapy and radiation in preoperative treatment for rectal cancer: An AGITG clinical trial.

TPS3646 Background: In retrospective studies statin use during preoperative chemo-radiation (pCRT) for rectal cancer is associated with improved overall survival, pathological tumor response and treatment toxicity. In vivo preclinical studies show that statins radiosensitize cancer cells, with improved tumor control and reduced radiation-induced gastrointestinal (GI) and skin toxicities. A prospective randomized trial is justified to confirm these clinically important benefits. Tumor regression following pCRT has strong prognostic significance, as assessed radiologically (MRI-based tumor regression grading [mrTRG]) prior to, or pathologically (pathTRG) following, surgery. Using mrTRG after each treatment phase in total neoadjuvant therapy (TNT) programs could assess incremental tumor regression and optimize patient management including surgery. Methods: Design: This double-blind phase 2 trial is recruiting 222 patients planned to receive long-course fluoropyrimidine-based pCRT for rectal adenocarcinoma at 17 sites in New Zealand and Australia. Patients are randomized to simvastatin 40mg or placebo daily for 90 days, starting 1 week prior to pCRT, with minimization for major prognostic variables. Pelvic MRI at baseline and 6-8 weeks after pCRT will assess mrTRG. A protocol amendment allows TNT using consolidation chemotherapy after pCRT; MRI timing is unchanged. Primary objective: comparison of rates of grades 1-2 mrTRG following pCRT with simvastatin or placebo, considering mrTRG in 4 ordered categories (1, 2, 3, 4-5). Secondary objectives: comparison of rates of grades 1-2 pathTRG in resected tumors; incidence of > grade 2 acute GI and non-GI adverse events (AE); incidence of late GI AE; compliance with intended pCRT and trial medication; proportion of patients undergoing surgical resection post-pCRT; 3-year local recurrence rate, disease-free and cancer-specific survival; and pathological scores for radiation colitis. Tertiary and correlative objectives: association between mrTRG and pathTRG grouping; inter-observer scoring agreement on mrTRG and pathTRG; comparison of the association between tumor CD3+ and/or CD8+ T-cell infiltrates in diagnostic biopsies and pathTRG; intensity and distribution of subsets of infiltrating T-cells in irradiated resected normal and malignant tissue; and the effect of simvastatin on markers of systemic inflammation (modified Glasgow prognostic score and the neutrophil-lymphocyte ratio). Eligibility criteria exclude statin use within 6 weeks prior to trial entry, patients intolerant of statins, and planned use of oxaliplatin or biological agents during pCRT. Trial recruitment commenced April 2018 and 95 of 222 patients have been recruited as at 21 January 2022. Clinical trial information: ACTRN12617001087347.

MP08-12 GUANYLATE CYCLASE-C AGONIST IW-3300 ATTENUATES CHRONIC COLONIC AND BLADDER HYPERSENSITIVITY IN A RAT MODEL OF PELVIC RADIATION INJURY

INTRODUCTION AND OBJECTIVE:Radiotherapy for pelvic cancers can lead to radiation-induced visceral organ injuries that develop into persistent chronic radiation proctitis, colitis, and cystitis. One...

Identifying Bleeding Etiologies by Endoscopy Affected Outcomes in 10,342 Cases With Hematochezia: CODE BLUE-J Study.

INTRODUCTION:The bleeding source of hematochezia is unknown without performing colonoscopy. We sought to identify whether colonoscopy is a risk-stratifying tool to identify etiology and predict outcomes and whether presenting symptoms can differentiate the etiologies in patients with hematochezia.METHODS:This multicenter retrospective cohort study conducted at 49 hospitals across Japan analyzed 10,342 patients admitted for outpatient-onset acute hematochezia.RESULTS:Patients were mostly elderly population, and 29.5% had hemodynamic instability. Computed tomography was performed in 69.1% and colonoscopy in 87.7%. Diagnostic yield of colonoscopy reached 94.9%, most frequently diverticular bleeding. Thirty-day rebleeding rates were significantly higher with diverticulosis and small bowel bleeding than with other etiologies. In-hospital mortality was significantly higher with angioectasia, malignancy, rectal ulcer, and upper gastrointestinal bleeding. Colonoscopic treatment rates were significantly higher with diverticulosis, radiation colitis, angioectasia, rectal ulcer, and postendoscopy bleeding. More interventional radiology procedures were needed for diverticulosis and small bowel bleeding. Etiologies with favorable outcomes and low procedure rates were ischemic colitis and infectious colitis. Higher rates of painless hematochezia at presentation were significantly associated with multiple diseases, such as rectal ulcer, hemorrhoids, angioectasia, radiation colitis, and diverticulosis. The same was true in cases of hematochezia with diarrhea, fever, and hemodynamic instability.DISCUSSION:This nationwide data set of acute hematochezia highlights the importance of colonoscopy in accurately detecting bleeding etiologies that stratify patients at high or low risk of adverse outcomes and those who will likely require more procedures. Predicting different bleeding etiologies based on initial presentation would be challenging.

PO-1140: Role of Functional Imaging in evaluation of Radiation Colitis

PO-1140: Role of Functional Imaging in evaluation of Radiation Colitis

S1746 An Unusual Case of Metastasis to Colon From Primary Breast Cancer With Subtle Colonoscopy Findings

INTRODUCTION: Breast cancer is the most common malignancy in women all over the world. Distant metastasis is by far the most common cause of death. It is common for breast cancers to metastasize to bone, liver and lung. Metastasis to the GI tract especially colon is very rare and can mimick primary colon cancer vs colitis with variable colonoscopy findings. CASE DESCRIPTION/METHODS: A 72 years old female was diagnosed with estrogen receptor-positive, well-differentiated, invasive mammary cancer in 2013. She underwent a localized lumpectomy with sentinel lymph node dissection. Her disease was stage 1A(pT1c pN0(i-) pMX). She received adjuvant radiation, tamoxifen and an aromatase inhibitor. Five years later, she was diagnosed with widespread metastatic disease to the axial and appendicular skeleton. She got palliative radiation and 10 cycles of Fulvestrant chemotherapy. A restaging CT scan 6 months later showed colonic wall thickening at the hepatic flexure. A colonoscopy showed normal colon with a subtle decrease in the mucosal vascular pattern at the hepatic flexure, biopsies were taken and pathology revealed expansion of the lamina propria by metastatic adenocarcinoma. The specimen was reviewed alongside the previous biopsy of the T9 vertebral lesion and showed similar histologic features, compatible with metastases from the patient's known breast primary. In addition, CK7 was positive and CK20 was negative. In the subsequent 8 months, she received 8 cycles of chemotherapy but developed worsening abdominal pain, inability to tolerate diet and an interval CT scan showed progression of colonic wall thickening in ascending colon and proximal transverse colon. Shortly after, she passed away from her widespread metastatic disease. DISCUSSION: The incidence of breast cancer metastasizing to GI tract is 3.4-4.5%, according to one study, 92% of it involves stomach. Metastasis from primary breast cancer to the colon is extremely rare. Usually liver, bone and lungs are the most common sites of metastasis. Presentation is variable and symptoms include abdominal pain, weight loss, bowel obstruction, anemia and GI bleed. Certain markers such as CK7 can be used to differentiate between primary GI cancers and metastasis from breast cancer. Diagnosis can be challenging as these colonic lesions can mimic other diseases such as IBD, radiation colitis and primary GI cancers. Colonoscopy findings can be variable and as in this case, even minimal changes in background of known malignancy warrants a biopsy for early diagnosis.Figure 1.: Decreased mucosal vascular pattern at the hepatic flexure.

Ulcerative colitis that developed during radiotherapy for prostate cancer, deteriorated rapidly and required emergency surgery

BackgroundAlthough there are reports linking ulcerative colitis (UC) to prostate cancer (PC), those reports are of PC patients who were previously diagnosed with UC. There are no reports of the development of UC during radiotherapy. Here we describe the first case of a patient who developed UC during radiotherapy for PC. The UC progressed rapidly and required emergency surgery.Case presentationA 61-year-old Japanese man underwent a prostate biopsy at another hospital due to a high prostate-specific antigen level and was diagnosed with PC. Goserelin and bicalutamide treatment was initiated in 2019, and intensity-modulated radiotherapy (total of 60 Gy/20 Fr) was administered in 2020. Diarrhea began during the radiotherapy and bleeding began post-radiotherapy. He was admitted to another hospital 14 days after the end of the radiotherapy, and colonoscopy revealed a deep ulcer in the colon, which led to the suspicion of UC. He was transferred to our hospital, and colonoscopy showed a widespread map-like ulcer, pseudopolyposis, and very easy bleeding in the colon. We diagnosed severe UC, and it worsened rapidly with uncontrollable bleeding, which we considered an indication for surgery. Emergency surgery (a total colectomy and ileostomy creation) was performed. The specimens confirmed an extensively spreading ulcer throughout the colon. The pathological report was UC in the active phase. The postoperative course was good.ConclusionsWhen a patient exhibits diarrhea while undergoing radiotherapy for PC, clinicians should be aware of the possibility of UC in addition to radiation colitis, and colonoscopy should be considered.

Acute Radiation Colitis after Preoperative Short-Course Radiotherapy for Rectal Cancer: A Morphological, Immunohistochemical and Genetic Study.

Simple SummaryRadiotherapy is the standard treatment for locally advanced rectal cancer with a high risk of local recurrence, if treated with surgery alone. The two regimens accepted are preoperative long-course radiotherapy with concomitant chemotherapy and preoperative short-course radiotherapy. The aim of our retrospective study is to provide a comprehensive morphological description of radiation-induced changes in rectal cancer specimens. We compared 2 groups of 95 rectal cancer patients treated preoperatively with either short-course (45 patients) or long-course radiotherapy (50 patients). Interestingly, in the non-neoplastic mucosa we identified features closely mimicking dysplasia/pre-neoplasia only in the group treated with short-course radiotherapy. Pathologists awareness of radiation-induced abnormalities is essential, as the misinterpretation may lead to patient’s overtreatment. In our study, next generation sequencing analysis supported the morphological concept that short-course radiotherapy-induced abnormalities do not represent true dysplasia, as somatic mutations were not identified in “dysplastic-like” tissues.Preoperative radiotherapy is a widely accepted treatment procedure in rectal cancer. Radiation-induced changes in the tumor are well described, whereas less attention has been given to the non-neoplastic mucosa. Our aim is to provide a detailed analysis of the morphological features present in non-neoplastic mucosa that pathologists need to be familiar with, in order to avoid misdiagnosis, when evaluating rectal cancer specimens of patients preoperatively treated with radiotherapy, especially with short-course regimen. We compared 2 groups of 95 rectal cancer patients treated preoperatively with either short-course (45 patients) or long-course radiotherapy (50 patients). Depending on the type of protocol, different histopathological features, in terms of inflammation, glandular abnormalities and endocrine differentiation were seen in the non-neoplastic mucosa within the irradiated volume. Of note, features mimicking dysplasia, such as crypt distortion, nuclear and cytoplasmic atypia of glandular epithelium, were identified only in the short-course group. DNA mutation analysis, using a panel of 56 genes frequently mutated in cancer, and p53 immunostaining were performed on both tumor and radiation-damaged mucosa in a subset of short course cases. Somatic mutations were identified only in tumors, supporting the concept that tissues with radiation-induced “dysplastic-like” features are not genetically transformed. Pathologists should be aware of the characteristic morphological changes induced by radiation. The presence of features simulating dysplasia in the group treated with short-course radiotherapy may lead to serious diagnostic mistakes, if erroneously interpreted. Next generation sequencing (NGS) analysis further validated the morphological concept that radiation-induced abnormalities do not represent pre-neoplastic lesions.

Basics of vascular damage and progress of diagnosis and treatment in radiation intestinal injury

Radiation intestinal injury is one of the most common complications after abdominal pelvic radiotherapy, which seriously affects the quality of life for patients. According to the site of occurrence, it is divided into radiation enteritis, colitis and proctitis. The pathological characteristics of radiation intestinal injury mainly include interstitial fibrosis, mucosal edema, ulcers, and inflammatory cell infiltration, and significant vascular lesions as well. It showed telangiectasia and hemorrhage under endoscopy. Under ultrasound examination, it showed diffusive thickening of the intestinal wall and increased blood flow signals. In addition, it also has other features such as increased thickness of the distal sigmoid colon and rectal wall, and increased width of the presacral space. The key factors in the incidence and development of radiation intestinal injury include angiostatin, PDGF, CXCL16, etc. The mechanisms to be clarified include abnormally heightened angiostatin through which signal pathways specifically affect vascular endothelial cells and inhibit angiogenesis and vascular homeostasis, how CXCL16 expressed by macrophages interacting with receptor promotes the transformation of fibroblasts and vascular smooth muscle cells into myofibroblasts, etc. Therapy targeted on basics of vascular damage will be a promising field of radiation intestinal injury research.

Multi-slice spiral CT evaluation of chronic radiation colitis and rectitis.

The aim of the present study was to retrospectively analyse the multi-slice spiral CT (MSCT) findings of radiation colitis and rectitis (RC&R). A total of 23 cases of RC&R detected by helical CT were included. The CT findings and clinical and endoscopy data of the patients were reviewed. The primary tumours included cancers of the cervix (n=17), rectum (n=4), ovaries (n=1) and bladder (n=1). The total dose of radiation per patient was 46-60 Gy (mean, 49.7 Gy) delivered over 5 weeks. The CT manifestations included different degrees of increased thickness of the intestinal wall (n=20, 87.0%), with a maximum thickness of 16.6 mm. On enhanced CT, the target sign was observed (n=16, 69.9%), with an obviously enhanced mucosa and/or serosa and the following changes observed: Oedema and increased density of the mesentery (n=15, 65.2%); increased density of the subcutaneous fat, and blurred and oedematous pelvic wall muscles (n=4, 17.4%), with the obturator internus and levator ani muscles being most commonly affected; narrowed intestinal lumen (n=3, 13.0%); and a small amount of ascitic fluid (n=2, 8.7%) located in the paracolic sulci and bladder or Douglas pouch. The 23 patients underwent colonoscopy and were diagnosed with RC&R. The major manifestations included telangiectasia and mucosal hyperaemia (n=21, 91.3%). MSCT of chronic RC&R (CRC&R) was associated with certain characteristic findings, which, combined with a medical history of radiotherapy and the clinical manifestations, may prove to be of value in the diagnosis of CRC&R.

Pharmacological and clinical feature of rebamipide: new therapeutic targets

Rebamipide is a cytoprotector developed in Japan where it has been successfully used for the treatment of stomach diseases for 30 years. Initially discovered effects of the drug included the induction of prostaglandins and the elimination of free oxygen radicals. Recent studies discovered new therapeutic targets of the drug, its new forms that made possible using rebamipid for the treatment of such diseases as NSAID enteropathy, ulcerative colitis, radiation colitis, pouchitis, enteropathy with impaired membrane digestion. It is used in endoscopy, ophthalmology, chemotherapy, rheumatology. The aim of this review is to present current information about the pharmacological and clinical feature of rebamipide and to study its therapeutic potential.

Feasibility and safety of self-expandable metal stent in nonmalignant disease of the lower gastrointestinal tract.

In recent years, self-expandable metal stents (SEMSs) have been employed to treat benign gastrointestinal strictures secondary to several conditions: Acute diverticulitis, radiation colitis, inflammatory bowel disease (IBD), and postanastomotic leakages and stenosis. Other applications include endometriosis and fistulas of the lower gastrointestinal tract. Although it may be technically feasible to proceed to stenting in the aforementioned benign diseases of the lower gastrointestinal tract, the outcome has been reported to be poor. In fact, in some settings (such as complicated diverticulitis and postsurgical anastomotic strictures), stenting seems to have a limited evidence-based benefit as a bridge to surgery, while in other settings (such as endometriosis, IBD, radiation colitis, etc.), even society guidelines are not able to guide the endoscopist through decisional algorithms for SEMS placement. The aim of this narrative paper is to review the scientific evidence regarding the use of SEMSs in nonmalignant diseases of the lower gastrointestinal tract, both in adult and pediatric settings.

SPAR \u2013 a randomised, placebo-controlled phase II trial of simvastatin in addition to standard chemotherapy and radiation in preoperative treatment for rectal cancer: an AGITG clinical trial

BackgroundRetrospective studies show improved outcomes in colorectal cancer patients if taking statins, including overall survival, pathological response of rectal cancer to preoperative chemoradiotherapy (pCRT), and reduced acute and late toxicities of pelvic radiation. Major tumour regression following pCRT has strong prognostic significance and can be assessed in vivo using MRI-based tumour regression grading (mrTRG) or after surgery using pathological TRG (pathTRG).MethodsA double-blind phase 2 trial will randomise 222 patients planned to receive long-course fluoropyrimidine-based pCRT for rectal adenocarcinoma at 18+ sites in New Zealand and Australia. Patients will receive simvastatin 40 mg or placebo daily for 90 days starting 1 week prior to standard pCRT. Pelvic MRI 6 weeks after pCRT will assess mrTRG grading prior to surgery. The primary objective is rates of favourable (grades 1–2) mrTRG following pCRT with simvastatin compared to placebo, considering mrTRG in 4 ordered categories (1, 2, 3, 4–5). Secondary objectives include comparison of: rates of favourable pathTRG in resected tumours; incidence of toxicity; compliance with intended pCRT and trial medication; proportion of patients undergoing surgical resection; cancer outcomes and pathological scores for radiation colitis. Tertiary objectives include: association between mrTRG and pathTRG grouping; inter-observer agreement on mrTRG scoring and pathTRG scoring; studies of T-cell infiltrates in diagnostic biopsies and irradiated resected normal and malignant tissue; and the effect of simvastatin on markers of systemic inflammation (modified Glasgow prognostic score and the neutrophil-lymphocyte ratio). Trial recruitment commenced April 2018.DiscussionWhen completed this study will be able to observe meaningful differences in measurable tumour outcome parameters and/or toxicity from simvastatin. A positive result will require a larger RCT to confirm and validate the merit of statins in the preoperative management of rectal cancer. Such a finding could also lead to studies of statins in conjunction with chemoradiation in a range of other malignancies, as well as further exploration of possible mechanisms of action and interaction of statins with both radiation and chemotherapy. The translational substudies undertaken with this trial will provisionally explore some of these possible mechanisms, and the tissue and data can be made available for further investigations.Trial registrationANZ Clinical Trials Register ACTRN12617001087347.(www.anzctr.org.au, registered 26/7/2017)Protocol Version: 1.1 (June 2017).