Acute Radiation Proctitis Research Articles

Rectal Epithelial Stem Cell Kinetics in Acute Radiation Proctitis

The intestinal tract is a typical radiosensitive tissue, and radiation rectal injury is a severe side effect that limits the prescribed dose in radiotherapy of the abdominal and pelvic region. Understanding the post-irradiation kinetics of Lgr5-positive stem cells is crucial in comprehending this adverse process. In this study, we utilized Lgr5-EGFP knock-in mice expressing EGFP and LGR5 antibody fluorescence staining of wild-type mice. At the state of radiation injury, the qPCR analysis showed a significant decrease in the expression level of Lgr5 in the rectal epithelial tissue. The dose-response relationship analysis showed that at low to moderate doses up to 10 gray (Gy), Lgr5-clustered populations were observed at the base of the crypt, whereas at sublethal doses (20 Gy and 29 Gy), the cells exhibited a dot-like scatter pattern, termed Lgr5-dotted populations. During recovery, 30 days post-irradiation, Lgr5-clustered populations gradually re-emerged while Lgr5-dotted populations declined, implying that some of the Lgr5-dotted stem cell populations re-clustered, aiding regenerations. Based on statistical analysis of the dose-response relationship using wild-type mice, the threshold dose for destroying these stem cell structures is 18 Gy. These findings may help set doses in mouse abdominal irradiation experiments for radiation intestinal injury and for understanding the histological process of injury development.

Emodin ameliorates acute radiation proctitis in mice by regulating AKT/MAPK/NF-κB/VEGF pathways

BackgroundEmodin, 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. MethodsTotal 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. ResultsThe 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. ConclusionThese 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.

P183 Therapeutic Effects of Curcumin and Ginsenoside Combination in a Animal Model of Radiation Proctitis

Abstract Background Although various preventive and therapeutic modalities have been proposed to manage radiation-induced proctitis, there are no universally accepted preventive measures for effective treatment. This study aimed to investigate using an animal model whether the combination of curcumin and ginsenoside could be an effective treatment or preventive agent for progressive rectal inflammation caused by radiation. Methods C57BL/6 mice were exposed to gamma irradiation at 27 Gy (3 Gy/min) in the lower abdominal (rectal) region, establishing an animal model with acute radiation proctitis. A combination hydrogel containing 5 mM curcumin and 1 mM ginsenoside Rh1 was prepared and administered into the inflammed rectum of the murine model. This administration was repeated every 2 to 3 days after radiation exposure for a total of 6 times. Two weeks after radiation exposure, the mice were sacrificed to obtain the irradiated tissue samples. The histological and molecular evaluations were performed using H&E staining, Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) analysis, Proliferating Cell Nuclear Antigen (PCNA) staining, immunohistochemistry, and qPCR. Results The murine group treated with the combination hydrogel of curcumin and ginsenoside showed significant restoration of the damaged rectal mucosa induced by radiation, including recovery of the mucosal layer and villi, mitigation of epithelial loss, and repair of crypt damage, compared to control group. Additionally, at the cellular level, a comparative analysis of apoptosis and proliferation within the tissues through TUNEL and PCNA staining demonstrated the combination hydrogel not only significantly inhibited cell death but also significantly increased cell proliferation. The gene expression of inflammatory cytokines in rectal tissue, including IL-6 and IFN-γ was significantly decreased in the treatment group. The infiltration of immune cells including T cells (CD4) and macrophages (CD68), which are important components in the pathogenesis of radiation proctitis, as shown by immunohistochemistry of tissue samples, was significantly reduced in the treatment group compared to the control group. Conclusion These promising results suggest that the combination of curcumin and ginsenosides has therapeutic potential for the management of radiation proctitis and provide valuable insights into new therapeutic strategies in clinical applications.

Correlation analysis of treatment positions and body mass index on acute radiation enteritis for cervical cancer patients underwent volumetric modulated arc therapy

PurposeTo investigate the correlation of the incidence of acute radiation-induced enteritis with the factors of patient treatment position and body mass index (BMI) in cervical cancer patient treated with the volumetric modulated arc therapy (VMAT) radiotherapy. Methods96 patients with cervical cancer underwent VMAT were divided into two groups based on the BMI of the patients: the underweight (<24 kg/m2) group and the overweight (≥24 kg/m2) group. According to the treatment position during radiotherapy, all patients were divided into two groups: supine position and prone position subgroups. All the patients were further divided into four groups: Group I (prone position with underweight (n = 23)), Group II (prone position with overweight (n = 20)), group III (supine position with underweight (n = 40)) and Group IV (supine with overweight (n = 13)). The treatment volumes and normal tissues (e.g., small intestine and rectum) were delineated and confirmed by two senior radiation oncologists. Then, the treatment plans were produced and optimized by the experienced medical physicists. The correlation between the incidence of acute radiation enteritis and the dose volume measurements of the small intestine and rectum was analyzed. ResultsBinary logistic analysis showed that the dose parameter of V40 of the rectal was a risk factor for radiation proctitis (p = 0.003), and the univariate receiver operating characteristic (ROC) analysis showed a high area under curve AUC of 0.927 of this parameters for prediction of radiation proctitis. Using the nonparametric Kruskal Wallis test, the treatment position was found to be an important factor in distinguishing radiation enteritis above grade II (p = 0.003), whereas the BMI showed no significant role in predicting radiation enteritis above grade II, and there was no interaction effect between treatment position and BMI (p = 0.224). Using stratified Chi-square test, it was found that treatment position and BMI were not high-risk factors for acute radiation proctitis above grade II (P > 0.05). ConclusionFor obese cervical cancer patients underwent VAMT radiotherapy, the prone position was recommended during the beam irradiation, which can significantly reduce the radiation dose to the small intestine. To reduce the incidence of radiation proctitis, it is recommended that the V40 of rectal should be less than 45% as possible through optimizing the treatment plan.

Ginsenoside Rg3 treats acute radiation proctitis through the TLR4/MyD88/NF-κB pathway and regulation of intestinal flora.

This study aimed to investigate the protective effect of ginsenoside Rg3 (GRg3) against acute radiation proctitis (ARP) in rats. Wistar rats were randomly divided into control, model, dexamethasone-positive, GRg3 low-dose, GRg3 medium-dose, and GRg3 high-dose groups. The ARP rat model was established by a single 22-Gy irradiation of 6 MV) X-rays. The distribution and function of intestinal flora were detected using 16S rRNA high-throughput sequencing, rectal tissue was observed by hematoxylin and eosin (H&E) staining, the expression of interleukin 1β (IL-1β) and IL-10 inflammatory factors was detected by ELISA, and mRNA and protein expression of toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) were detected by RT-qPCR and Western blotting, respectively. GRg3 improved the symptoms of ARP in rats in a dose-dependent manner. The species distribution of intestinal flora in GRg3 rats was significantly different from that in ARP rats. These differences were more significant in the high-dose group, where the numbers of Ruminococcus, Lactobacillus, and other beneficial bacteria were significantly increased, whereas those of Escherichia, Alloprevotella, and other harmful bacteria were decreased. In addition, GRg3 was closely related to amino acid metabolism. After GRg3 treatment, the mRNA and protein expression of TLR4, MyD88, and NF-κB in rectal tissue was significantly down-regulated, and the level of downstream inflammatory factor IL-1β decreased, whereas that of IL-10 increased. Our study indicated GRg3 as a new compound for the treatment of ARP by inhibiting the TLR4/MyD88/NF-κB pathway, down-regulating the expression of proinflammatory factors, thus effectively regulating intestinal flora and reducing inflammatory reactions.

Effects of hyaluronic acid and chondroitin sulfate on acute radiation proctitis in rats.

This study was designed to investigate the prophylactic and therapeutic effects of hyaluronic acid and chondroitin sulfate combination (HA/CS) on a model of acute radiation proctitis. Rats were divided into five groups: SHAM; irradiation (IR) + saline (1 mL for 5th and 10th day); IR + HA/CS (1 mL for 5th and 10th day). A single fraction of 17.5 Gy was delivered to each rat. HA/CS was administered rectally each day after irradiation. Each rat was observed daily for signs of proctitis. Irradiated rats were euthanized on days 5 and 10. The mucosal changes were evaluated macroscopically and pathologically. According to the clinical findings, five rats in the irradiation + saline group showed grade 3-4 symptoms on the 10th day. No significant difference in the macroscopic finding scores on the 5th day was observed between the irradiation + saline and irradiation + HA/CS groups. In the pathological examination, radiation-induced mucosal damage was the most prominent finding 10 days after irradiation in saline-treated rats. On the 10th day, the irradiation + HA/CS group showed mild inflammation and slight crypt changes, which corresponded to grade 1-2 pathological findings. We think that HA/CS used in radiation cystitis can be beneficial for radiation proctitis.

Novel mechanisms underlying inhibition of inflammation-induced angiogenesis by dexamethasone and gentamicin via PI3K/AKT/NF-κB/VEGF pathways in acute radiation proctitis

Acute radiation proctitis (ARP) is one of the most common complications of pelvic radiotherapy attributed to radiation exposure. The mechanisms of ARP are related to inflammation, angiogenesis, and so on. In this study we evaluated the effect of dexamethasone (DXM) combined with gentamicin (GM) enema on ARP mice, and explored its possible mechanisms by transcriptome sequencing, western blot and immunohistochemistry. C57BL/6 mice were randomly divided into 3 groups: healthy control group, ARP model group, and DXM + GM enema treatment group. ARP mice were established by using a single 6 MV X-ray dose of 27 Gy pelvic local irradiation. Transcriptome sequencing results showed that 979 genes were co-upregulated and 445 genes were co-downregulated in ARP mice compared to healthy mice. According to gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis, we firstly found that PI3K/AKT/NF-κB/VEGF pathways were mostly correlated with the inflammation-induced angiogenesis in ARP mice. PI3K/AKT pathway leads to the activation of NF-κB, which promotes the transcription of VEGF and Bcl-2. Interestingly, symptoms and pathological changes of ARP mice were ameliorated by DXM + GM enema treatment. DXM + GM enema inhibited inflammation by downregulating NF-κB and upregulating AQP3, as well as inhibited angiogenesis by downregulating VEGF and AQP1 in ARP mice. Moreover, DXM + GM enema induced apoptosis by increasing Bax and suppressing Bcl-2. The novel mechanisms may be related to the downregulation of PI3K/AKT/NF-κB/VEGF pathways.

S1800 A Case of Metastatic Prostate Cancer Masquerading as Radiation Proctitis on Colonoscopy

Introduction: CDX2 is a homeobox transcription factor that regulates development, and differentiation of epithelial cells. It is traditionally associated with benign or malignant tumors of intestinal origin but has also been reported in cases of prostate tumors. Therefore, without a known primary cancer, a CDX2 positive biopsy does not exclude extra-intestinal primary malignancy especially in patients with non-specific clinical findings. Case Description/Methods: Here, we report a case of an 84-year-old male with long-standing history of low-grade, recurrent, prostate cancer who presented to the clinic with obstipation and rising prostate-specific antigen (PSA) levels. He was previously treated with radiation therapy 20 years ago followed by brachytherapy and Bicalutamide, and was on biannual Leuprolide at the time of exam. Due to a firm rectal mass palpated on digital rectal exam, a CT scan was obtained and showed circumferential thickening of the distal rectum. Colonoscopy revealed friable and edematous mucosa, whose appearance was suggestive of acute radiation proctitis but was inconsistent with the chronicity of radiation therapy. Therefore, rectal biopsies were taken and showed positive immunostaining for AE1, AE3, NKX3.1, CDX2, PSA, and prostatic specific acid phosphatase (PSAP). CK7 and CK20 were negative. Patient was subsequently started on Enzalutamide which led to a decline in PSA. Due to worsening obstipation and partial rectal obstruction, the patient had to undergo diverting colostomy placement. Discussion: Metastatic tumors to the large intestine are relatively rare compared to primary intestinal neoplasms. The prostate gland is one of the most common sites of origin for secondary colorectal adenocarcinoma. The presence of CDX2, NKX3.1, PSA, and PSAP, and the absence of CK7 and CK20 leads us towards the origin of the secondary tumor as prostate. In medical literature, besides primary gastrointestinal tumors, CDX2 has been infrequently shown to be positive in both benign and malignant prostate specimens. In the latter, it has been more frequently found to be from primary rather than metastatic disease which is contrary to our case. This case represents an exception where the presence of CDX2 was unable to exclude a non-gastrointestinal primary tumor. This case also provides clinicians with insight to arrive at the correct diagnosis and treatment, and help differentiate between similar presentations such as primary colorectal carcinoma, secondary neoplasm of colon, and radiation proctitis.Figure 1.: Left: Endoscopic image of colonoscopy showed an edematous area concerning for radiation proctitis prior to biopsies. Center: Medium power view of hematoxylin and eosin stained section showing neoplastic cells expanding the lamina propria. Right: The neoplastic cells are positive for pancytokeratin (AE1/AE3), NKX3.1 and PSAP, confirming metastatic carcinoma consistent with prostate primary.

Effects of Huaihuasan and baitouweng formular on rats with acute radiation proctitis and its mechanism

Objective: To investigate the effects of huaihuasan and baitouweng formular on acute radiation proctitis (ARP) in rats. Methods: Forty clean grade SD rats were randomly divided into control group, model group, mesalazine group and formula group. Except the control group, all the other three groups received 6 MV-20 GY dose of X-ray irradiation in the pelvic cavity, and the rat model of acute radiation proctitis was established. The rats were given daily gavage intervention with the corresponding drugs after mold formation. According to the adult clinical equivalent dose (body surface area), the control group and the model group were given 10 ml/kg saline daily, the Mesalazine group was treated with Mesalazine solution at the dose of 0.27 g/kg, and the Formular group was given (0.91 g/kg) respectively for 14 days. All rats were killed on the 14th day after administration. To evaluate the general situation of the rats, HE staining was used to observe the pathological changes in the rectal tissues of the rats. The contents of intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1) were detected by Elisa, and the expression of NF-κb P65 in the tissues were detected by Western blot. Results: Compared with the model group, in the mesalazine group and the formular group, the clinical symptoms and intestinal mucosal healing of rats were improved significantly, the expression level of NF-κB P65 protein in the rectal tissues and the serum contents of ICAM-1 and VCAM-1 were decreased with statistically significant differences (P＜0.05). Conclusion: Huaihuasan and baitouweng formular can reduce NF-κB, ICAM-1 and VCAM-1 to improve symptoms and rectal mucosal injury in ARP rats.

Aloe vera for Prevention of Acute Radiation Proctitis in Colorectal Cancer a Preliminary Randomized, Placebo-Controlled Clinical Trial.

To examine the preventive effects of Aloe vera in colorectal cancer patients undergoing radiotherapy. Twenty colorectal cancer patients, who received radiation, were randomized to receive Aloe vera 3% or placebo ointment, 1g twice daily for 6weeks. At weekly visits, acute radiation proctitis (ARP) was evaluated by Radiation Therapy Oncology Group and clinical presentation criteria as the primary endpoint. We also evaluated secondary endpoints of quality of life, psychosocial status, by applying Hospital Anxiety-Depression (HAD) Scale and laboratory measures of quantitative measurement of C-reactive protein (CRP) as a marker for systemic inflammation. There was a significant improvement in the symptom index (before treatment vs. after treatment with Aloe vera) for diarrhea (p=0.029, median score: 0.5 vs. 0.001). The overall primary and secondary outcomes favored Aloe group, while the measures of toxicity did not achieve a statistical significant difference. The lifestyle score improved significantly with A. vera (p=004), and they also had a lower depression score in HAD scale (p=0.008). Furthermore, quantitative CRP decreased significantly during the course of treatment with Aloe vera. The use of topical formulation of Aloe vera 3% diminishes the severity of ARP in colorectal cancer patients.

Efficacy and safety of berberine in the prophylactic treatment of acute radiation proctitis in postoperative patients with cervical cancer: a randomized controlled study*

Abstract Objective The aiom of this study was to study the efficacy and safety of berberine as a prophylactic treatment of acute radiation proctitis in postoperative patients with cervical cancer. Methods A total of 120 postoperative patients with cervical cancer were enrolled between July 2016 and October 2019, and randomly divided into a treatment group (berberine 300 mg three times a day, n = 60) and a control group (receiving vitamin C tablets, 100 mg three times a day; n = 60) using the random number table method. All patients received pelvic intensity-modulated radiation therapy (IMRT) and concurrent sensitizing chemotherapy weekly. The difference in the percentage of irradiation volume to the rectum and small intestine as well as the incidence, onset time, severity, and duration of acute radiation proctitis and cystitis during radiotherapy were compared between the two groups. The completion rate, completion time, number of chemotherapy sessions, and quality of life during radiotherapy were also compared. Results There were no statistical differences in age, FIGO stage, pathological type, complications, high-risk factors, and rectum and small intestine irradiation dose distribution (V20, V30, V40, and V50) between the two groups (P &gt; 0.05). No acute radiation proctitis of grade 3 or above occurred in the two groups. There was no significant difference in the incidence of acute radiation cystitis, grade 2 acute radiation proctitis, completion rate of IMRT, and frequency of sensitization chemotherapy between the two groups. After prophylactic treatment with berberine, the incidence of grade 1 acute radiation proctitis, occurrence of grade 1 radiation proctitis, and completion time of radiotherapy in the treatment group were significantly lower than those in the control group (P &lt; 0.05). The SF-36 score of the treatment group after radiotherapy was 67.53 ± 4.21, which was significantly better than that of the control group (64.90 ± 6.32; P &lt; 0.05). The incidence of grade 3-4 neutropenia in the treatment group was 10% and lower than that in the control group (31.7%, P = 0.003). No adverse reactions related to berberine were observed. Conclusion Prophylactic prescription with oral berberine can reduce the incidence, onset time, and duration of grade 1 acute radiation proctitis, and improve the quality of life of postoperative patients with cervical cancer receiving concurrent chemoradiotherapy.

Research progress on the prevention and treatment of radiation-induced intestinal injury by the genus Lactobacillus

Acute radiation-induced intestinal injury is the common complication in patients following abdominal and pelvic radiotherapy. However, no effective clinical prevention and treatment interventions are available. As the probiotics and symbiotic bacteria, many species of the genus Lactobacillus are normally present in the gastrointestinal tract and beneficial for the intestinal health. Preclinical studies have reported that the genus Lactobacillus can prevent and treat acute radiation-induced intestinal injury by protecting crypt stem cells, maintaining intestinal barrier and exerting the antioxidant effect, etc. Clinical trials have prompted that oral administration of adequate complex probiotics containing Lactobacillus spp.at one week before radiotherapy contributes to preventing radiation-induced diarrhea. In addition, oral intake of the genus Lactobacillus has the tendency to treat radiation-induced diarrhea and mitigate acute radiation proctitis. At present, no relevant adverse events have been reported. Key words: Genus Lactobacillus; Aacute radiation-induced intestinal injury; Research progress

Changrui enema inhibits inflammation-induced angiogenesis in acute radiation proctitis by regulating NF-κB and VEGF.

Purpose Changrui enema, a traditional Chinese medicine prescription, is used as a supplementary treatment for acute radiation proctitis (ARP). Herein we explored the inhibition effects of Changrui enema on NF-κB and VEGF in ARP mice.Methods A total of 120 C57BL/6 mice were divided randomly into normal mice group, ARP mice group, western medicine enema group (dexamethasone combined with gentamicin), and Changrui enema group. ARP mice were established by pelvic local irradiation. The expression of IL-1β, NF-κB, VEGF, AQP1, AQP3, p-ERK1/2 and p-JNK was determined by immunohistochemistry or western blot.Results The study firstly found that Changrui enema alleviated ARP mice. The expression of IL-1β, NF-κB, VEGF, AQP1 and p-ERK1/2 was increased in ARP mice, and was reserved by Changrui enema. However, the expression of AQP3 and p-JNK was decreased in ARP mice, and was up-regulated by Changrui enema.Conclusions Changrui enema is an effective treatment with fewer side effects for ARP. The mechanism of Changrui enema may be related to the inhibition of inflammation-induced angiogenesis. Changrui enema inhibits IL-1β and NF-κB expression as well as VEGF expression. Interestingly, AQP1 promotes angiogenesis, while AQP3 inhibits inflammation. Changrui enema probably inhibits AQP1 expression by down-regulating p-ERK1/2, and improves AQP3 expression by up-regulating p-JNK.

Efficacy of sucralfate ointment in the prevention of acute proctitis in cancer patients: A randomized controlled clinical trial.

Background:Acute radiation proctitis (ARP) is a usual adverse effect in patients undergoing pelvic radiotherapy. The symptoms include diarrhea, rectal blood or mucus discharge, fecal urgency and tenesmus with pain. Sucralfate, an aluminum-based salt of sucrose octasulfate, is a cytoprotective agent that forms a coating barrier at injured sites by adhering to mucoproteins. It has been used in topical management of a wide variety of local lesion. This study was designed to evaluate the preventive effect of rectal sucralfate on acute radiotherapy induced proctitis.Methods:Seven percent sucralfate ointment was prepared for topical use. Drug quantification, chemical stability and microbial limit tests were performed carefully. In this randomized double blind placebo controlled trial, fifty-seven patients with pelvic malignancies undergoing radiotherapy were allocated to receive either 1 g of sucralfate or 1 g of placebo, given as a twice daily ointment, one day before and during radiotherapy for six weeks. The eligible patients were evaluated based on RTOG acute toxicity criteria and the following ARP symptoms weekly: rectal hemorrhage, diarrhea, rectal pain, and fecal urgency. The influence of symptoms on lifestyle was also recorded weekly.Results:Acute proctitis was significantly less prevalent in patients in the sucralfate group. The incidence of rectal bleeding (P=0.003), diarrhea (P=0.002), rectal pain (P=<0.001) and fecal urgency (P=0.002) was significantly less common in the sucralfate group. No statistical significant difference was observed for radiotherapy induced cystitis in the placebo and sucralfate groups (P=0.27).Conclusion:This study suggests that sucralfate7% ointment reduces the incidence of symptoms associated with acute radiation proctitis.

Experimental study of ginsenoside Rg3 in the treatment of acute radiation proctitis in rat models

Objective To evaluate the efficacy of ginsenoside Rg3(GRg3) in the treatment of acute radiation proctitis in rat models. Methods On the 7th day after 21.5 Gy irradiation, 100 rats were divided into the control group (normal saline, n=20), GRg3 group (gavage of 20 mg/kg, 40 mg/kg and 80 mg/kg GRg3, n=20 for each dose) and Smecta mixture enema group (n=20). After 2 weeks, all rats were anesthetized with chloral hydrate (3 ml/kg) and approximately 5 ml of blood sample was collected from the abdominal aorta prior to sacrifice. The rectal tissues were taken and prepared for detection of Bax and NF-κB contents and HE staining to observe the pathological changes of the rectal tissues. After the blood samples were centrifuged, the supernatants were collected for ELISA to detect the serum levels of IL-2, IL-6, TNF-α and MPO in each group. Results In the GRg3 group, the serum inflammatory cytokines, serum MPO concentration and the concentration of Bax and NF-κB in the intestinal tissues of rats were decreased along with the increasing dose of GRg3. These parameters in the high-dose GRg3 group were significantly lower than those in the saline group (all P 0.05), suggesting that GRg3 exerted good therapeutic effect on acute radiation proctitis in rat models. Conclusions GRg3 can significantly reduce the concentration of inflammatory cytokines, Bax and NF-κB in the intestinal tissues of rat models with acute radiation proctitis, which is more efficacious than the normal saline. GRg3 can be used to treat acute radiation proctitis in rat models. Key words: Ginsenoside Rg3; Acute radiation proctitis; Rat

Efficacy of Synbiotics to Reduce Symptoms and Rectal Inflammatory Response in Acute Radiation Proctitis: A Randomized, Double-Blind, Placebo-Controlled Pilot Trial

Purpose: Evaluate whether the daily intake of synbiotics improves symptoms and rectal/systemic inflammatory response in patients with radiation-induced acute proctitis.Methods and Materials: Twenty patients who underwent three-dimensional conformal radiotherapy for prostate cancer were randomized to intake either a synbiotic powder containing Lactobacillus reuteri (108 CFU) and soluble fiber (4.3 g) or placebo. EORTC QLQ-PRT23 questionnaire was applied before the beginning of radiotherapy and after the fifth, sixth, and seventh weeks of treatment, and the sum of both the complete (proctitis symptoms plus quality of life) and partial (proctitis symptoms) scores were compared. Fecal calprotectin was measured at Day 0 and in the fourth week of treatment, and serum C-reactive protein/albumin ratio were measured in the fourth week of treatment.Results: Both the complete and partial questionnaire score (median and range) were higher in the fifth and sixth weeks in the placebo group; there was a higher increase in fecal calprotectin in the placebo group and no difference comparing CRP/albumin ratio.Conclusions: Synbiotics reduce proctitis symptoms and improve quality of life by preventing rectal inflammation during radiotherapy for prostate cancer.

The effect of the combination of Malva sylvestris L. and Althaea digitata Boiss. on prevention of acute radiation proctitis in patients with prostate cancer

The effect of a combination of Malva sylvestris and Althaea digitata flower powder in prevention of acute radiation proctitis was assessed in patients undergoing radiation therapy (RT) for prostate cancer. This double-blind randomized controlled study was conducted at three centers in Iran. Before starting RT, patients (N = 65) received a 4 g packet of flower powder or placebo to use 3 times a day as an infusion from the first day of RT and for five consecutive weeks including the three weeks of RT. They were visited by a physician 3 times during this period. Acute morbidity was classified according to the Radiation Therapy Oncology Group (RTOG) criteria. Severity of proctitis symptoms was assessed by Visual Analog Scale (VAS) with 10 points. Non-statistical significant differences were observed between the groups in relation to RTOG grade criteria (grade 0: drug 22.8% (N = 8), placebo 10% (N = 3), difference 12.8%; grade 1: drug 65.8%, placebo 64.4%, difference 1.4%; grade 2: drug 11.4% (N = 8), placebo 26.6% (N = 4), difference 15.2%. (P = .059))According to VAS, the most common complaint was anal burning and diarrhea in the flower powder group showing a significant decrease in these symptoms at the end of the study as compared to the placebo; flower powder (1.56 ± 1.07) vs placebo (3.82 ± 1.67) for burning (P < .05) and flower powder (1.06 ± 0.58) vs placebo (1.95 ± 0.79) for diarrhea (P = .046). The flower powder prevented anal discomfort and diarrhea induced by prostate radiotherapy, although there were no significant differences between the two groups in RTOG. No serious side effects were reported, so the combination could be suggested for patients who cannot tolerate symptoms of proctitis after further studies.

Impact of Various Prognostic Factors on Overall Survival, Disease-Free Survival and Patterns of Failure in Carcinoma Cervix: A Tertiary Care Centre Experience from South India

As per GLOBACON 2012, the incidence of cervical cancer is 22.9% with a mortality rate of 54.9% ( http://globocan.iarc.fr , 2010). As the disease affects relatively younger population, high fatality rate impacts family and society in a disastrous way. Cervical carcinoma has a relatively poor prognosis due to advanced stage at presentation. We retrospectively analysed the treated cases of carcinoma cervix to know the impact of various prognostic factors on survival and patterns of failure in our hospital. All cases treated from 2010 to 2015 (total 920 pts) who completed curative treatment in a tertiary care hospital were analysed to evaluate overall survival, disease-free survival, factors impacting survival, patterns of failure, factors affecting failure, mortality, and treatment-related toxicity. OS and DFS were calculated with Kaplan–Meier method, and log-rank test was used to identify the difference between groups. Failure factors were correlated with logistic regression, and toxicity was expressed in percentage. Univariate and multivariate analyses were performed. Pre treatment staging, lymphadenopathy, imaging used for diagnosis, hemoglobin levels extent of vagina involved and during treatment usage of concurrent chemotherapy, dose of radiation used, development of neutropenia and aftercompletion of treatment type of response had shown significant impact on DFS and OS. The presence of lymphadenopathy, increasing involvement of vagina, low pretreatment haemoglobin levels, and not receiving chemotherapy had increased risk of failure, while pretreatment evaluation with CT or MRI decreased the risk of failure. Para-aortic nodes (28%) were the commonest among distant failures. Acute bowel toxicity and radiation proctitis were commonly seen. Presentation in locally advanced stage decreases survival; hence, detection in early stages by population-based screening programmes is needed. Pretreatment imaging with MRI/CT improves staging and thereby improves survival. There is no impact of 2D versus 3D CRT planning; hence, in high-case-load centres, 2D planning may be used. Follow-up at regular intervals with imaging may aid in earlier identification of failures with better salvage and improved survival.

Evaluation of prophylactic and therapeutic effects of ruscogenin on acute radiation proctitis: an experimental rat model.

PurposeRadiation proctitis (RP) is inflammation and damage to the rectum, manifested secondary to ionizing radiation utilized for treatment. In this study, we evaluated the anti-inflammatory therapeutical and protective effects of ruscogenin in a model of acute RP.MethodsThirty-two Sprague-Dawley rats were divided into 4 groups (n = 8) as sham, control, treatment, and prophylaxis groups. Prophylaxis group and treatment group were dosed ruscogenin by oral gavage for 14 days pre- and postradiation. At the end of the 28th day, all subjects were sacrificed.ResultsHistopathological analysis showed a significant increase in cryptitis abscess, cryptitis and reactive atypia, and depth of lymphocytic infiltration of the control group, compared to the other groups (P < 0.05), while treatment and prophylaxis groups showed significant decreases (P < 0.05). Immunohistochemical analysis indicated that immunoreactivity were significantly higher in control group (P < 0.05, P < 0.001, and P < 0.01, respectively), but vice versa for treatment and prophylaxis groups. There was not any significant difference for fibroblast growth factor 2 immunoreactivity. The epithelium of control rectums indicated an increase in TNF-α immunoreactivity while other groups had significant decrease (P < 0.01). Electron microscopical findings were parallel to light microscopy.ConclusionIn this study, ruscogenin was observed to be effective on prophylaxis or treatment of acute RP. Although there are various reports on the treatment of the rectum damaged by acute RP in the literature, this could be the first study since there is no research indicating the ultrastructural effect of ruscogenin.

Successful Treatment of Acute Radiation Proctitis with Aloe Vera: A Preliminary Randomized Controlled Clinical Trial.

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. 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). 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. A substantial number of patients with radiation proctitis seem to benefit from therapy with Aloe vera 3% ointment.