Qingchang suppositry induced remission in patients with mild-to-moderate ulcerative proctitis: a multicenter, prospective, randomized, parallel-controlled clinical trial.

OBJECTIVE: To evaluate the efficacy and safety of Qingchang suppository (, QCS), a preparation of Chinese herbal medicine, in the induction of remission in patients with mild-to-moderate ulcerative proctitis (UP). METHODS: We performed a multicenter, prospective, randomized, parallel-controlled trial to evaluate the efficacy of QCS induction therapy in 140 adult patients with mild-to-moderate UP and TCM syndrome of dampness-heat in large intestine. The patients were randomized to receive QCS (study group) or Salicylazosulfapyridine (SASP) suppository (control group) one piece each time, twice a day, per anum for 12 weeks. Mayo score and main symptoms score were evaluated at weeks 0, 2, 4, 8 and 12, rectosigmoidscopy was taken at weeks 0, 4, 8 and 12, Geboes score, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and safety indexes were assessed at weeks 0 and 12. The primary efficacy endpoint is clinical remission rate, the secondary efficacy endpoints are clinical response rate, mucosa healing rate, Geboes score, the remission rates of the main symptoms, the median day to the remission of the symptom, etc. RESULTS: There were no statistical difference in the clinical remission rates, the clinical response rates, the mucosa healing rates, Geboes score, ESR and CRP between the two groups. The remission rates of tenesmus and anal burning sensation of the study group were significantly higher than those of the control group (76.5% vs 25.0%, P = 0.009; 74.51% vs 29.63%, P = 0.003). The median day to the remission of purulent bloody stool of the study group was significantly less than that of control group [11 (1, 64) vs 19 (2, 67), P = 0.007]. The patients receiving QCS had a significantly higher mucosa healing rate at week 4 than the patients receiving SASP suppository (71.42% vs 52.85%, P = 0.023). No adverse event occurred in the study group while the adverse events incidence of the control group was 5.7% (P = 0.049). CONCLUSIONS: QCS could induce the remission of UP as effectively and safely as SASP suppository, and was superior to SASP suppository in relieving the symptoms of tenesmus, anal burning sensation and purulent bloody stool and the time to reach mucosa healing.

Temporary diverting stoma in therapy-refractory luminal colonic Crohn's disease: an alternative to immediate colorectal resection?

AIM: Creation of a diverting stoma in patients with Crohn's disease (CD) can counteract luminal inflammation. The clinical utility of a diverting stoma with the prospect of restoration of gastrointestinal continuity warrants further investigation. The aim of this work was to evaluate the long-term effects of creation of a diverting stoma on the disease course in patients with luminal colonic CD. METHOD: In this retrospective, multicentre cohort study we investigated the disease course of patients who received a diverting stoma in the biological era. Clinical characteristics, medication use and surgical course were assessed at the time of creation of the diverting stoma and during follow-up. The primary outcome was the rate of successful and lasting reestablishment of gastrointestinal continuity. RESULTS: Thirty six patients with refractory luminal CD from four institutions underwent creation of a diverting stoma. Of the overall cohort, 20 (56%) patients had their gastrointestinal continuity reestablished after initial stoma creation and 14 (39%) who had their stoma reversed remained stoma-free during a median of 3.3 years follow-up (interquartile range 2.1-6.1 years). Absence of stoma reversal was associated with the presence of proctitis (p = 0.02). Colorectal resection after creation of a diverting stoma was performed in 28 (78%) patients, with 7 (19%) having a less extensive resection and 6 (17%) having a more extensive resection compared with the surgical plan before stoma creation. CONCLUSION: A diverting stoma could potentially be an alternative to immediate definitive stoma placement in specific populations consisting of patients with luminal colonic CD, especially in the absence of proctitis.

Hyperbaric oxygen treatment for late radiation-induced tissue toxicity in treated gynaecological cancer patients: a systematic review.

PURPOSE: The aim of this study was to investigate the result of hyperbaric oxygen therapy (HBOT) in women with treated gynaecological malignancies who suffer from late radiation-induced tissue toxicity (LRITT). Moreover, which symptoms of LRITT benefit most from HBOT was evaluated as well. MATERIAL AND METHODS: An online literature search was conducted using PubMed; Embase and the Cochrane Library. Studies were included if the study examined gynaecological cancer patients who had been treated with radiotherapy, who suffered from LRITT and who subsequently received HBOT. In addition, the outcome measures were based on examining the effects of HBOT. RESULTS: Twenty-one articles were included. The study investigating proctitis reported an improvement and three out of four studies investigating cystitis reported decreased complaints in women treated for gynaecological malignancies. In addition, all studies reported improvement in patients with wound complications and fifty percent of the studies reported better Patient Reported Outcome Measurements (PROMS) in women with gynaecological malignancies. Finally, all studies, except one related to pelvic malignancies reported reduced prevalence of symptoms for cystitis and proctitis and all studies reported better PROMS. However, only eleven studies reported p-values, nine of which were significant. CONCLUSION: This study demonstrated that HBOT has a positive effect in women with gynaecological LRITT. Within the included patient group, gynaecological cancer patients with wound complications seem to benefit most from this treatment compared to other late side effects of LRITT.

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.

The role of hyperbaric oxygen therapy in the treatment of radiation lesions.

INTRODUCTION: Cancer remains one of the leading causes of death worldwide, with 50-60% of patients requiring radiotherapy during the course of treatment. Patients' survival rate has increased significantly, with an inevitable increase in the number of patients experiencing side effects from cancer therapy. One such effect is late radiation injuries in which hyperbaric oxygen therapy appears as complementary treatment. With this work we intend to divulge the results of applying hyperbaric oxygen therapy among patients presenting radiation lesions in our Hyperbaric Medicine Unit. MATERIALS AND METHODS: Retrospective analysis of clinical records of patients with radiation lesions treated at the Hyperbaric Medicine Unit assessed by the scale Late Effects of Normal Tissues-Subjective, Objective, Management, Analytical (LENT-SOMA) before and after treatment, between October 2014 and September 2019 were included. Demographic characteristics, primary tumor site, subjective assessment of the LENT-SOMA scale before and after treatment were collected and a comparative analysis (Students t test) was done. RESULTS: 88 patients included: 33 with radiation cystitis, 20 with radiation proctitis, 13 with osteoradionecrosis of the mandible and 22 with radiation enteritis. In all groups, there was a significant decrease (p < 0.005) in the subjective parameter of the LENT-SOMA scale. DISCUSSION: Late radiation lesions have a major influence on patients' quality of life. In our study hyperbaric oxygen therapy presents as an effective therapy after the failure of conventional treatments. CONCLUSION: Hyperbaric oxygen therapy is an effective complementary therapy in the treatment of refractory radiation lesions.

Establishing a rabbit model of perianal fistulizing Crohn's disease.

BACKGROUND: Crohn's disease (CD) is a chronic nonspecific intestinal inflammatory disease. The aetiology and pathogenesis of CD are still unclear. Anal fistula is the main complication of CD and is a difficult problem to solve at present. The main limitation of developing new therapies is bound up with the short of preclinical security and effectiveness data. Therefore, an ideal animal model is needed to establish persistent anal fistula and an inflamed rectal mucosa. AIM: To improve the induction method of colitis and establish a reliable and reproducible perianal fistulizing Crohn's disease animal model to evaluate new treatment strategies. METHODS: Twenty male New Zealand rabbits underwent rectal enema with different doses of 2,4,6-trinitrobenzene sulfonic acid to induce proctitis. Group A was treated with an improved equal interval small dose increasing method. The dosage of group B was constant. Seven days later, the rabbits underwent surgical creation of a transsphincteric fistula. Then, three rabbits were randomly selected from each group every 7 d to remove the seton from the fistula. The rabbits were examined by endoscopy every 7 days, and biopsy forceps were used to obtain tissue samples from the obvious colon lesions for histological analysis. The disease activity index (DAI), colonoscopy and histological scores were recorded. Perianal endoscopic ultrasonography (EUS) was used to evaluate the healing of fistulas. RESULTS: Except for the DAI score, the colonoscopy and histological scores in group A were significantly higher than those in group B (P < 0.05). In the ideal model rabbit group, on the 7th day after the removal of the seton, all animals had persistent lumens on EUS imaging, showing continuous full-thickness high signals. Histological inspection of the fistula showed acute and chronic inflammation, fibrosis, epithelialization and peripheral proctitis of the adjoining rectum. CONCLUSION: The improved method of CD colitis induction successfully established a rabbit perianal fistula CD preclinical model, which was confirmed by endoscopy and pathology.

Efficacy of Pharmacological Agents for Ulcerative Proctitis: A Systematic Literature Review.

BACKGROUND: Ulcerative proctitis is a common and often highly symptomatic form of inflammatory bowel disease. We performed a systematic review to assess the efficacy of different therapies in the management of patients with ulcerative proctitis. METHODS: We identified randomized controlled trials in adults with ulcerative proctitis treated with oral or topical therapies for induction of response or remission, or prevention of relapse. RESULTS: A total of 32 randomized controlled trials were included [27 induction/2839 participants, five maintenance/334 participants]. Follow-up varied from 3 to 8 weeks for induction, and from 6 to 24 months for maintenance of remission. 5-Aminosalicylic acid [5-ASA] suppository was the most frequently evaluated treatment [14/32, 43.7%], followed by steroid enema [7/32, 21.9%]. Topical 5-ASA demonstrated effectiveness for induction of clinical response or remission and prevention of relapse in several studies. Combined topical steroids and 5-ASA was more effective than topical 5-ASA or topical steroids alone to induce response [100% of patients for combination vs 70% for beclomethasone alone and 76% for 5-ASA alone]. One observational study suggested azathioprine may be effective in patients with ulcerative proctitis. Only two cohort studies evaluated the efficacy of tumour necrosis factor inhibitors in ulcerative proctitis. Small molecules, anti-integrins and anti-interleukin therapies have not been evaluated in isolated ulcerative proctitis. CONCLUSION: The role of topical 5-ASA as a treatment for ulcerative proctitis has been confirmed in this systematic literature review, for induction and maintenance of remission. Future trials are needed to investigate the efficacy of more recent and upcoming drug classes in patients with ulcerative proctitis.

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

OBJECTIVE: To examine the preventive effects of Aloe vera in colorectal cancer patients undergoing radiotherapy. MATERIAL AND METHOD: Twenty colorectal cancer patients, who received radiation, were randomized to receive Aloe vera 3% or placebo ointment, 1 g twice daily for 6 weeks. 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. RESULTS: 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. CONCLUSION: The use of topical formulation of Aloe vera 3% diminishes the severity of ARP in colorectal cancer patients.

Hyperbaric oxygen therapy as a complementary treatment for radiation proctitis: Useless or useful? - A literature review.

Radiotherapy (RT) is the backbone of multimodality treatment of more than half of cancer cases. Despite new modern RT techniques, late complications may occur such as radiation proctitis (RP). The natural history of RP is unpredictable. Minor symptoms may resolve spontaneously or require conservative treatment. On the other hand, for similar and uncomplicated clinical contexts, symptoms may persist and can even be refractory to the progressive increase in treatment measures. Over the last decades, an enormous therapeutic armamentarium has been considered in RP, including hyperbaric oxygen therapy (HBOT). Currently, the evidence regarding the impact of HBOT on RP and its benefits is conflicting. Additional prospective and randomised studies are necessary to validate HBOT's effectiveness in the 'real world' clinical practice. This article reviewed the relevant literature on pathophysiology, clinical presentation, different classifications and discuss RP management including a proposal for a therapeutic algorithm with a focus on HBOT.

Functional recovery by colon organoid transplantation in a mouse model of radiation proctitis.

Radiation proctitis is the collateral damage that occurs to healthy cells during radiation treatment of pelvic malignancies. Conservative treatment of radiation proctitis can mitigate inflammatory symptoms, but, to date, no therapeutic options are available for direct recovery of the damaged colonic epithelium. The present study assessed the ability of colon organoid-based regeneration to treat radiation proctitis. Radiation proctitis was induced in mice by irradiating their recta, followed by enema-based transplantation of mouse colon organoids. The transplanted colon organoids were found to successfully engraft onto the damaged rectal mucosa of the irradiated mice, reconstituting epithelial structure and integrity. Lgr5+ stem cells were shown to be pivotal to colon organoid mediated regeneration. Endoscopic examination showed the efficacy of localized transplantation of colon organoids with fibrin glue to irradiated sites. These findings provide useful insights into the use of colon organoid-based regenerative therapy for the treatment of radiation proctitis.

How Much Daily Image-guided Volumetric Modulated Arc Therapy Is Useful for Proctitis Prevention With Respect to Static Intensity Modulated Radiotherapy Supported by Topical Medications Among Localized Prostate Cancer Patients?

BACKGROUND/AIM: To evaluate if topical support therapy during static-intensity modulated radiotherapy (sIMRT) course is able to equal the characteristic minimum risk for radiation proctitis of Image-guided volumetric modulated arc therapy (IG-VMAT) treatment among localized prostate cancer patients. PATIENTS AND METHODS: Rectal toxicity data of the above patients were retrospectively collected throughout three different clinical periods at our Radiotherapy Deparment: from October 2011 to December 2012, prostate cancer patients were treated with sIMRT and in advance supported by means of daily topical corticosteroids; from January 2013 to November 2016, topical corticosteroids were replaced by daily hyaluronic acid enemas; from December 2016 to May 2018 eligible patients were treated with newly introduced IG-VMAT supported by only on-demand topical corticosteroids. RESULTS: Among 359 eligible patients, IG-VMAT was proven generally more effective than sIMRT supported by topical medications in terms of proctitis reduction, although without clinical and practical relevance. CONCLUSION: Topical medications might have a role in radiation proctitis prevention.

Stereotactic Body Radiation Therapy for Intermediate-risk Prostate Cancer With VMAT and Real-time Electromagnetic Tracking: A Phase II Study.

OBJECTIVES: Stereotactic body radiation treatment represents an intriguing therapeutic option for patients with early-stage prostate cancer. In this phase II study, stereotactic body radiation treatment was delivered by volumetric modulated arc therapy with flattening filter free beams and was gated using real-time electromagnetic transponder system to maximize precision of radiotherapy and, potentially, to reduce toxicities. MATERIALS AND METHODS: Patients affected by histologically proven prostate adenocarcinoma and National Comprehensive Cancer Network (NCCN) intermediate class of risk were enrolled in this phase II study. Beacon transponders were positioned transrectally within the prostate parenchyma 7 to 10 days before simulation computed tomography scan. The radiotherapy schedule was 38 Gy in 4 fractions delivered every other day. Toxicity assessment was performed according to Common Terminology Criteria for Adverse Events (CTCAE), v4.0. RESULTS: Thirty-six patients were enrolled in this study. Median initial prostate-specific antigen was 7.0 ng/mL (range: 2.3 to 14.0 ng/mL). Median nadir-prostate-specific antigen after treatment was 0.2 ng/mL (range: 0.006 to 4.8 ng/mL). A genitourinary acute toxicity was observed in 21 patients (dysuria grade [G] 1: 41.7%, G2: 16.7%). Gastrointestinal acute toxicity was found in 9 patients (proctitis G1: 19.4%, G2: 5.6%). Late toxicity was mild (genitourinary toxicity G1: 30.6%; G2: 8.3%; gastrointestinal toxicity G1: 13.9%; G2: 19.4%). At a median follow-up time of 41 months, 3 biochemical recurrences were observed (2 local recurrences, 1 distant metastasis). Three-year biochemical recurrence-free survival was 89.8% (International Society of Urologic Pathology Grade Group 2: 100%, Grade Group 3: 77.1%, P=0.042). CONCLUSION: Ultrahypofractionated radiotherapy, delivered with flattening filter free-volumetric modulated arc therapy and gated by electromagnetic transponders, is a valid option for intermediate-risk prostate cancer.

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-1ß, 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-1ß, 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-1ß 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.

Prevention of acute radiation-induced Proctitis by Aloe vera: a prospective randomized, double-blind, placebo controlled clinical trial in Pelvic Cancer patients.

BACKGROUND: Acute radiation-induced proctitis (ARP) is the most common side effect following radiotherapy for malignant pelvic disease. This study evaluated the efficacy of Aloe vera ointment in prevention of ARP. METHODS: Forty-two patients receiving external-beam radiotherapy (RT) for pelvic malignancies were randomized to receive either Aloe vera 3% or placebo topical ointment during radiotherapy for 6 weeks. These patients were evaluated based on the severity (grade 0-4) of the following symptoms weekly: rectal bleeding, abdominal/rectal pain, diarrhea, or fecal urgency. RTOG acute toxicity criteria and psychosocial status of the patients were also recorded weekly. Lifestyle impact of the symptoms, and quantitative measurement of C-reactive protein (CRP), an indicator of systemic inflammation, were also measured. RESULTS: The results of present study demonstrated a significant preventive effect for Aloe vera in occurrence of symptom index for diarrhea (p < 0.001), rectal bleeding (p < 0.001), and fecal urgency (p = 0.001). The median lifestyle score improved significantly with Aloe vera during RT (p < 0.001). Intervention patients had a significant lower burden of systemic inflammation as the values for quantitative CRP decreased significantly over 6 weeks of follow-up (p = 0.009). CONCLUSION: This study showed that Aloe vera topical ointment was effective in prevention of symptoms of ARP in patients undergoing RT for pelvic cancers. TRIAL REGISTRATION: IRCT201606042027N6. Registration date: 2016-09-04.

Treatment and outcomes of patients with chronic radiation proctitis. A single-center experience and review of the literature.

Chronic radiation proctitis is a frequent complication after radiotherapy for pelvic malignancies. It is reported that 1 to 5% of patients develop chronic radiation proctitis even with recent advances in external radiotherapy. Hematochezia, mucus discharge, urgency and tenesmus are common symptoms and they can vary in severity but bleeding is often the most debilitating to the patient. Different options are reported for treatment of this condition that always should keep in differential diagnosis in patients with history of pelvic radiotherapy. Treatments range from easy, with topic administration of formalina, to expensive and requiring specialized equipment such as hyperbaric oxygen therapy. Surgery is reserved to patients with failure of conservative treatments due to the high risk of leakage and high morbidity up to 60%. KEY WORDS: Argon beam, Bleeding, Formalin, Radiation, Proctitis, Sucralfate enema.

Effect of interval between preoperative radiotherapy and surgery on clinical outcome and radiation proctitis in rectal cancer from FOWARC trial.

OBJECTIVE: The aim of this study was to evaluate the effect of the interval between CRT and surgery on radiation proctitis, the pathologic response, and postoperative morbidity. METHODS: This was a cohort study from a phase III, randomized controlled trial (FOWARC study, NCT01211210). Data were retrieved from the leading center of the trial. Patients were divided into the short-interval (≤7 weeks) group and the long-interval (>7 weeks) group. The rate of radiation proctitis, pathologic complete regression (pCR) and morbidities were calculated for each group. Multivariate analysis was used to verify the impact of interval on radiation proctitis. RESULTS: Surgery was performed in 60 patients after an interval of ≤7 weeks and in 97 patients after an interval of >7 weeks. The two groups according to interval were comparable in terms of baseline demographic and clinicotherapeutic characteristics. Radiation proctitis was identified by imaging in 9 (15.0%) patients in short-interval group and in 31 (32.0%) patients in long-interval group (P = .018). Multivariate analysis confirmed the correlation between long interval and radiation proctitis (P = .018). The long interval was significantly associated with longer median operation time compared to the short interval (P = .022). The rates of pCR and postoperative complications were not different between two groups. CONCLUSIONS: A longer interval after CRT may be associated with higher rate of radiation proctitis and longer operation time. Moreover it did not increase the rate of pCR.

Preclinical Model of Perianal Fistulizing Crohn's Disease.

BACKGROUND: Fistulizing anoperineal lesions (FAPLs) are common and severe complications of Crohn's disease (CD), exposing patients to the risk of anal sphincter alteration and permanent stoma. Due to the limited efficacy of current treatments, identifying new local therapies is mandatory. However, testing new treatments is currently limited because no relevant preclinical model of Crohn's-like FAPL is available. Thus, a reliable and reproducible experimental model of FAPLs is needed to assess new therapeutic strategies. METHODS: Twenty-one rats received a rectal enema of 2,4,6-trinitrobenzensulfonic acid (TNBS) to induce proctitis. Seven days later, a transsphincteric fistula tract was created with a surgical thread, instilled with TNBS twice a week until its removal at day 7 (group 1), day 14 (group 2), or day 28 (group 3). In each rat, pelvic MRI was performed just before and 7 days after thread removal. Rats were sacrificed 7 days after thread removal for pathological assessment of the fistula tract. RESULTS: The optimal preclinical model was obtained in group 3. In this group, 7 days after thread removal, all animals (9 of 9) had a persistent fistula tract visible on MRI with T2-hypersignal (normalized T2 signal intensity: 2.36 ± 0.39 arbitrary units [a.u.] [2.08-2.81]) and elevation of the apparent diffusion coefficient (1.33 ± 0.16 10-3 millimeter squared per seconds [1.18-1.49]). The pathological examination of the fistula tract revealed acute and chronic inflammation, granulations, fibrosis, epithelialization, and proctitis in the adjacent rectum. CONCLUSIONS: This reproducible preclinical model could be used to assess the effectiveness of innovative treatments in perianal fistulizing CD.

Recommendations of the Crohn's Disease and Ulcerative Colitis Spanish Working Group (GETECCU) for the treatment of perianal fistulas of Crohn's disease. / Recomendaciones del Grupo Español de Trabajo de Enfermedad de Crohn y Colitis Ulcerosa (GETECCU) para el tratamiento de las fístulas perianales de la enfermedad de Crohn.

Recommendations are advice that is given and considered to be beneficial; however, they are still suggestions and are therefore open to different interpretations. In this sense, the final objective of the review has been to try to homogenize, with the evidence available, the approach to the diagnosis and medical/surgical treatment of one of the most complex manifestations of Crohn's disease, such as simple and complex perianal fistulas.

Development of an Indigo Naturalis Suppository for Topical Induction Therapy in Patients with Ulcerative Colitis.

BACKGROUND: Indigo naturalis (IN) consists of ligands for the aryl hydrocarbon receptor and exhibits anti-inflammatory effects. Previously, we demonstrated that an 8-week treatment with oral IN is effective in inducing a clinical response in patients with ulcerative colitis (UC). Some UC patients with proctitis are refractory to topical mesalamine or corticosteroids and therefore require an alternative topical treatment. OBJECTIVES: We aimed to prospectively evaluate the safety and efficacy of IN suppositories in UC patients. METHOD: We performed an open-label, single-center, prospective pilot study from February 2018 to October 2018. A total of 10 patients with active UC, who had moderate to severe inflammation from the rectum to the sigmoid colon, were enrolled. The patients received a daily dose of 50 mg IN suppository for 4 weeks. The primary endpoint was safety at week 4. RESULTS: Although 1 patient experienced anal pain, no serious adverse events were observed. At week 4, the rates of clinical remission and mucosal healing were 30 and 40%, respectively. Mayo rectal bleeding subscores significantly improved after treatment (1.80 ± 0.13 vs. 0.90 ± 0.28; p = 0.009). Approximately 80% of the patients with a baseline Mayo endoscopic subscore in the rectum (r-MES) of 2 achieved mucosal healing, but those with a baseline r-MES of 3 did not. CONCLUSIONS: We found that 4 weeks of IN suppository can be tolerated by UC patients, but its efficacy was limited by the severity of the disease. Further investigation will be needed in order to confirm the optimum dose of IN suppository for patients with UC.