Chronic radiation proctitis refractory to steroid enema was successfully treated by metformin and sodium butyrate: a case report.

BACKGROUND: Radiation proctitis (RP) is a significant complication of pelvic radiation. Effective treatments for chronic RP are currently lacking. We report a case where chronic RP was successfully managed by metformin and butyrate (M-B) enema and suppository therapy. CASE PRESENTATION: A 70-year-old Asian male was diagnosed with prostate cancer of bilateral lobes, underwent definitive radiotherapy to the prostate of 76 Gy in 38 fractions and six months of androgen deprivation therapy. Despite a stable PSA nadir of 0.2 ng/mL for 10 months post-radiotherapy, he developed intermittent rectal bleeding, and was diagnosed as chronic RP. Symptoms persisted despite two months of oral mesalamine, mesalamine enema and hydrocortisone enema treatment. Transition to daily 2% metformin and butyrate (M-B) enema for one week led to significant improvement, followed by maintenance therapy with daily 2.0% M-B suppository for three weeks, resulting in continued reduction of rectal bleeding. Endoscopic examination and biopsy demonstrated a good therapeutic effect. CONCLUSIONS: M-B enema and suppository may be an effective treatment for chronic RP.

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

BACKGROUND: Emodin, a natural anthraquinone derivative isolated from the roots of Rheum officinale Baill, has many pharmacological effects including anti-inflammatory, antioxidant, antiviral, antibacterial and anti-cancer. However, little is known about the effect of emodin on acute radiation proctitis (ARP). The present study was conducted to determine its effects and elucidate its mechanisms involving AKT/MAPK/NF-κB/VEGF pathways in ARP mice. METHODS: Total 60 C57BL/6 mice were divided randomly into control group, ARP group, AKT inhibitor MK-2206 group, and different doses of emodin groups. ARP mice were induced by 27 Gy of 6 MV X-ray pelvic local irradiation. MK-2206 was given orally for 2 weeks on alternate days. Emodin was administered daily by oral gavage for 2 weeks. Subsequently, all mice were sacrificed on day 15. The rectal tissues were obtained for further tests. The general signs score and the pathological grade were used to evaluate the severity of ARP. The expression of NF-κB, VEGF and AQP1 were determined by immunohistochemistry and western blot. The expression of p-AKT, p-ERK, p-JNK, p-p38, Bcl-2 and Bax were assessed using western blot. RESULTS: The worse general signs and damaged tissue structure of ARP mice were profoundly ameliorated by emodin. The expression of p-AKT, p-ERK, NF-κB, VEGF and AQP1 were significantly increased, resulting in the inflammation-induced angiogenesis in ARP mice. However, the expression of p-JNK and p-p38 were decreased, leading to the reduction of apoptosis in ARP mice. Excitedly, emodin reversed these changes, not only inhibited inflammation-induced angiogenesis, but also promoted apoptosis. Notably, the effects of emodin were similar to that of AKT inhibitor MK-2206, suggesting the involvement of AKT signaling in the effect of emodin. CONCLUSION: These results suggest that emodin attenuates ARP in mice, and the underlying mechanism might involve inhibition of the AKT/ERK/NF-κB/VEGF pathways and the induction of apoptosis mediated by JNK and p38.

Anal Monkeypox Disease: Description of 65 Cases.

BACKGROUND: Monkeypox is a zoonosis endemic in Africa caused by 3 orthopoxvirus clades. Knowledge of the disease is limited, but a worldwide outbreak involving a new route of transmission was declared in April 2022. OBJECTIVE: This study aimed to describe anal symptoms and outcomes in patients infected with Monkeypox virus presenting to an emergency proctology unit in Paris. DESIGN: This was an observational study. SETTING: We reported anal symptoms of all consecutive patients with monkeypox anal infection in a single proctology center between June 16, 2022, and July 26, 2022. Association with sexually transmitted infections and outcomes were also recorded. PATIENTS: Sixty-five men with a mean age of 39.6 (19.9-64.6) years with confirmed monkeypox anal infection were included in the study. MAIN OUTCOME MEASURES: Anal symptoms and their severity were clinically assessed. A favorable outcome consisted of a complete resolution of clinical manifestation. RESULTS: Sexual transmission was reported in 51 patients (78.4%), among whom 63 (97%) were men who have sex with men. Twenty-eight (43%) were living with HIV, and 24 (36.9%) were taking tenofovir/emtricitabine for HIV preexposure prophylaxis. Anal symptoms appeared first in 36 patients (55.4%) and skin rash or other general symptoms in 22 patients (33.8%). Incubation time was 6.9 (1-26) days. Symptoms included painful perianal (n = 42 patients; 64.6%), anal (n = 28, 43%), and rectal (n = 25; 38.4%) ulcerations and perianal vesicles (n = 24; 36.9%). Proctitis was observed in 49 patients (75.4%). It was mild in 20 (40.8%) and intense in 29 (59.2%), and severe proctitis mimicking high intersphincteric suppuration was found in 4 (8.2%). Fifteen patients (23.1%) had concurrent sexually transmitted infection and 3 were hospitalized. Complete symptom resolution occurred within 12 days. LIMITATIONS: We performed a single-center study during a short period of time. CONCLUSIONS: Proctological symptoms are frequent in the current outbreak of monkeypox disease, probably linked to the route of transmission. Rectal ulcerations mimicking high intersphincteric suppuration should be recognized to avoid unnecessary surgery. See Video Abstract . ENFERMEDAD ANAL DE LA VIRUELA DEL MONO DESCRIPCIN DE CASOS: ANTECEDENTES:La viruela del simio mono es una zoonosis endémica en África causada por tres clados de orthopoxvirus. El conocimiento de la enfermedad es limitado, pero en abril de 2022 se declaró un brote mundial que implica una nueva vía de transmisión.OBJETIVO:Describir los síntomas anales y los resultados en pacientes que sufren de infección por Monkeypox que asistieron a una unidad de proctología de emergencia en París.DISEÑO:Un estudio observacional.ESCENARIO:Informamos los síntomas anales de todos los pacientes consecutivos con infección anal por viruela del mono en un solo centro de proctología entre el 16/6/2022 y el 26/7/2022. También se registró la asociación con infecciones de transmisión sexual (ITS) y el resultado.PACIENTES:Sesenta y cinco hombres de 39,6 [19,9-64,6] años con infección anal confirmada.PRINCIPALES MEDIDAS DE RESULTADO:Los síntomas anales y su gravedad se evaluaron clínicamente. Un resultado favorable consistió en una resolución completa de la manifestación clínica.RESULTADOS:La transmisión sexual se informó en 51 (78,4%) pacientes, de los cuales 63 (97%) eran hombres que tuvieron sexo con hombres. Veintiocho (43%) vivían con el VIH y 24 (36,9%) tomaban Emtricitabina/Tenofovir para profilaxis previa por exposición al VIH. Los síntomas anales aparecieron primero en 36 (55,4%) pacientes y la erupción cutánea u otros síntomas generales en 22 (33,8%). El tiempo de incubación fue de 6,9 [1-26] días. Los síntomas incluyeron ulceraciones perianales dolorosas (n = 42 pacientes, 64,6%), anales (n = 28, 43%), rectales (n = 25, 38,4%) y vesículas perianales (n = 24, 36,9%). Se observó proctitis en 49 (75,4%) pacientes. Fue leve en 20 (40,8%) e intensa en 29 (59,2%) y proctitis severa simulando supuración interesfinteriana alta en 4 (8,2%). Quince (23,1%) pacientes presentaban ITS concurrentes y 3 fueron hospitalizados. La resolución completa de los síntomas ocurrió dentro de los 12 días.LIMITACIONES:Estudio de un solo centro y durante corto período de tiempo.CONCLUSIÓN:Los síntomas proctológicos son frecuentes en el brote actual de la enfermedad de la viruela del mono, probablemente relacionados con la vía de transmisión. Las ulceraciones rectales que simulan una supuración interesfinteriana alta deben reconocerse para evitar una cirugía innecesaria. (Traducción-Dr. Fidel Ruiz Healy ).

Tofacitinib for Patients with Anti-TNF Refractory Ulcerative Proctitis: A Multicentre Cohort Study from the GETAID.

BACKGROUND: Although ulcerative proctitis [UP] can dramatically impair quality of life, treatment efficacy has been poorly investigated in UP as it was historically excluded from phase 2/3 randomised controlled trials in ulcerative colitis. Our aim was to assess the effectiveness and safety of tofacitinib for the treatment of UP. METHODS: We conducted a retrospective, multicentre study in 17 GETAID centres, including consecutive patients with UP treated with tofacitinib. The primary endpoint was steroid-free remission between Week 8 and Week 14, defined as a partial Mayo score of 2 [and no individual subscore above 1]. Secondary outcomes included clinical response and steroid-free remission after induction and at 1 year. RESULTS: All the 35 enrolled patients previously received anti-tumour necrosis factor [TNF] therapy and 88.6% were exposed to at least two lines of biologics. At baseline, the median partial Mayo score was 7 (intequartile range [IQR] [5.5-7]). After induction [W8-W14], 42.9% and 60.0% of patients achieved steroid-free remission and clinical response, respectively. At 1 year, the steroid-free clinical remission and clinical response rates were 39.4% and 45.5%, respectively, and 51.2% [17/33] were still receiving tofacitinib treatment. Survival without tofacitinib withdrawal was estimated at 50.4% (95% confidence interval [CI] [35.5-71.6]) at 1 year. Only a lower partial Mayo at baseline was independently associated with remission at induction (0dds ratio [OR] = 0.56 for an increase of 1, (95% CI [0.33-0.95], p = 0.03). Five [14.3%] adverse events were reported, with one leading to treatment withdrawal [septic shock secondary to cholecystitis]. CONCLUSION: Tofacitinib may offer a therapeutic option for patients with refractory UP.

Comparative efficacy of oral drugs for chronic radiation proctitis - a systematic review.

BACKGROUND: Chronic radiation proctitis (CRP) is a long-term complication of pelvic radiotherapy that manifests as rectal bleeding, diarrhoea, fistula formation and obstruction. Treatments such as endoscopic argon plasma coagulation, hyperbaric oxygen therapy and rectal topical formalin have imposed a significant medical burden on CRP patients. In contrast, oral therapies offer a more accessible and acceptable option for managing CRP. Here, we conducted a systematic review of the efficacy of oral treatments for CRP to assess their potential as an effective and convenient treatment option for this condition. METHODS: We searched the Cochrane Central Register of Controlled Trials, PubMed, Web of Science, China National Knowledge Infrastructure and Chinese VIP in February 2021. We included post-radiotherapy participants with CRP that compared oral medicine alone or in combination with other treatments versus control treatments. The primary outcomes were bleeding, diarrhoea and symptom score. Heterogeneity between studies was checked using Cochrane Q test statistics and I2 test statistics. The Cochrane risk-of-bias tool was used to assess the quality of the included studies. RESULTS: We included 10 randomised controlled trials (RCTs) and 1 retrospective study with 898 participants. Three placebo-controlled trials evaluated the effects of oral sucralfate on CRP, with meta-analysis showing no significant different with placebo arm. Four trials on TCM demonstrated significant improvement of symptoms, especially for the 3 trials on oral TCM drinks. Retinyl palmitate and high-fibre diet were found to reduce rectal bleeding. The combination of oral pentoxifylline and tocopherol did not significantly change the process of CRP. CONCLUSIONS: Our study implies that oral TCM drinks, retinyl palmitate and a high-fiber diet showed significant improvement in CRP symptoms, but not with the combination of oral pentoxifylline and tocopherol. Further multicentre, larger-scale RCTs are needed to confirm the efficacy and safety of these treatments and optimize treatment strategies, ultimately improving the quality of life for patients with CRP.

Argon plasma coagulation therapy in hemorrhagic radiation proctitis following pelvic radiation in gynecological malignancies.

Introduction: Chronic radiation proctitis is a common chronic complication of malignant pelvic diseases after pelvic radiation therapy. Although, the incidence has decreased after advent of intensity-modulated radiotherapy due to better control of radiation dose to rectum. In the era of conventional two-field radiotherapy to pelvis, this was a common complication usually presenting after 1-2 years of treatment completion. Rectal bleeding caused by radiation proctitis is difficult to manage. Argon plasma coagulation (APC) is an electrocoagulation technique that appears to be an effective and low-cost alternative to the use of lasers in gastrointestinal endoscopy. The aim of this study was to evaluate the efficacy of APC, as well as patients' tolerance of the procedure, in the treatment of bleeding radiation-induced proctitis. Materials and Methods: Between January 2015 and August 2017, 29 patients of cancer cervix treated with definite radiotherapy both external and brachytherapy who suffered from rectal bleeding due to radiation proctitis were included for treatment with argon plasma laser (APC). Twenty-three patients suffered from anemia, 16 of whom required blood transfusion. APC was performed, applying the no-touch spotting technique at an electrical power of 40 Watt and an argon gas flow of 1.5-2.0 l/min. Pulse duration was <0.5 s. Treatment sessions were carried out at intervals of 3 weeks. Subjects received 2-4 treatment sessions. Results: Twenty-eight out of 29 patients were accessible for effects and results. APC led to persistent clinical and endoscopic remission of rectal bleeding after a median of three sessions. No adverse effects were encountered after initial treatment. All the patients were in complete remission. Conclusions: APC is an effective, safe, and well-tolerated treatment for rectal bleeding caused by chronic radiation proctitis. It should be considered as a first-line therapy for radiation proctitis.

Anorectal Manifestations of Treatment-Refractory Monkeypox Requiring Surgical Intervention.

Anorectal manifestations of monkeypox are increasingly being recognized as a potentially serious complication. We present the case of an HIV-positive, tecovirimat-treated male presenting with monkeypox virus-associated severe proctitis with associated perianal pathology. Despite the use of antiviral agents and intravenous vaccinia immune globulin, the monkeypox-associated perianal lesions evolved into abscesses, requiring incision and drainage. This report highlights a multidisciplinary approach involving surgery for anorectal complications of monkeypox virus-associated proctitis and perianal lesions. Surgery may offer immediate relief and reduce the potential long-term morbidity associated with severe monkeypox virus-associated rectal and perianal manifestations refractory to available medical countermeasures.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: We think that HA/CS used in radiation cystitis can be beneficial for radiation proctitis.

Regorafenib-Induced Radiation Recall Presenting as Acute Blood Loss Anemia With Rectal Bleeding and Severe Proctitis.

Radiation recall is a rare inflammatory reaction that occurs in an area that was subjected to prior irradiation that is usually triggered by certain drugs or chemotherapy agents. This reaction is drug-specific for each individual and occurs in about 6% to 9% of the patients receiving chemotherapy after radiation therapy. We report a case of radiation recall-induced severe proctitis which is thought to be triggered by administration of regorafenib for stage IV rectal adenocarcinoma with lung metastases. We present a 65-year-old female patient who was initially diagnosed with stage III T4N1M0 rectal adenocarcinoma that was treated with neoadjuvant concurrent chemoradiotherapy, followed by low anterior resection. The tumor was pathologically staged a ypT3 yN1 with a partial response to the treatment. After the surgery, the patient was found to have lung nodules consistent with metastatic disease, when she was treated initially with folinic acid, fluorouracil, and oxaliplatin, plus bevacizumab. The patient had further disease progression with metastases in her lungs despite treatment with several chemotherapy agents. She was started on regorafenib, an oral vascular endothelial growth factor inhibitor, as a fourth line of therapy. However, in a month after initiation of oral regorafenib, and 9 months after the prior radiation treatment, the patient presented to the emergency room with a complaint of bright red blood per rectum. She was diagnosed with severe radiation proctitis that was treated therapeutically with argon plasma coagulation. This particular case serves as a reminder that although infrequent and rare, radiation recall may result in an inflammatory reaction in an organ such as rectum. To the best of our knowledge, this regorafenib-induced severe proctitis secondary to radiation recall has not been reported in the literature before.

Systematic review of therapies for refractory ulcerative proctitis.

Patients with ulcerative proctitis have favorable long-term outcomes but are typically excluded from ulcerative colitis clinical trials. Refractory proctitis presents a management conundrum for gastroenterologists, and there remains a lack of clarity as to the best therapeutic strategy. This study aimed to undertake a systematic review of studies assessing the clinical efficacy and safety of therapies for refractory proctitis. PubMed, Embase, Cochrane Library, and MEDLINE databases were searched without restriction from inception to October 27, 2022. Both interventional and noninterventional studies examining efficacy of therapeutic modalities for the induction and/or maintenance of remission in refractory proctitis were included. Included studies were grouped by therapeutic modalities as follows: (i) immunomodulators, (ii) monoclonal antibodies, (iii) topical calcineurin inhibitors, (iv) other topical therapies, and (v) appendicectomy. The search strategy identified 3301 studies, of which 13 met eligibility criteria for inclusion. Clinical remission rates for systemic therapies ranged from 20-26% for azathioprine to 50-69% for tumor necrosis factor-α inhibitor therapies. The use of systemic therapies for proctitis raised safety concerns, with 22-37% of patients discontinuing therapies due to adverse effects across four retrospective cohort studies. Prospective clinical trials of topically applied tacrolimus demonstrated clinical remission rates of 42-46%, with a favorable safety profile. Substantial heterogeneity in study design precluded meta-analysis. Refractory ulcerative proctitis remains a neglected entity, with a dearth of prospective clinical trials to guide therapeutic decision-making. Current evidence supports a role for topically administered tacrolimus.

CMV proctitis: a rare disease presentation in a young and immunocompetent man.

A young adult man presented to an outlying emergency department with a sore throat, fever and chills. Upon failure of symptomatic management and a course of amoxicillin, he developed rectal pain and loose stools. Despite outpatient doxycycline treatment for presumed chlamydial proctitis, he developed worsening rectal pain and bloody stools. Results on abdominal and pelvic CT were consistent with proctitis. His symptoms worsened despite added metronidazole for bacterial proctitis. Workup revealed an elevated erythrocyte sedimentation rate, C reactive protein and calprotectin, suggestive of a diagnosis of inflammatory bowel disease (IBD). A colonoscopy revealed proximal tightness of the rectum, and pathology reported features suggestive of IBD. He was treated with prednisone and mesalamine. However, immunostaining positive for cytomegalovirus (CMV) confirmed a diagnosis of tissue-invasive CMV proctitis. This was further supported by serological testing for CMV consistent with a diagnosis of CMV proctitis preceded by a primary CMV infection of the pharynx.

Tacrolimus (FK506) for induction of remission in corticosteroid-refractory ulcerative colitis.

BACKGROUND: There are a limited number of treatment options for people with corticosteroid-refractory ulcerative colitis. Animal models of inflammatory bowel disease and uncontrolled studies in humans suggest that tacrolimus may be an effective treatment for ulcerative colitis. OBJECTIVES: To evaluate the efficacy and safety of tacrolimus for induction of remission in people with corticosteroid-refractory ulcerative colitis. SEARCH METHODS: We searched the Cochrane Gut group specialised register, CENTRAL, MEDLINE (PubMed), Embase, Clinicaltrials.gov and WHO ICTRP from inception to October 2021 to identify relevant randomised controlled trials (RCT). SELECTION CRITERIA: Two review authors independently selected potentially relevant studies to determine eligibility based on the prespecified criteria. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and analysed them using Review Manager Web. The primary outcomes were induction of remission and clinical improvement, as defined by the studies and expressed as a percentage of the participants randomised (intention-to-treat analysis). MAIN RESULTS: This review included five RCTs with 347 participants who had active ulcerative colitis or ulcerative proctitis. The duration of intervention varied between two weeks and eight weeks. Tacrolimus versus placebo Tacrolimus (oral and rectal) may be superior in achieving clinical remission compared to placebo (oral and rectal) (14/87 participants with tacrolimus versus 1/61 participants with placebo; risk ratio (RR) 3.76, 95% confidence interval (CI) 1.03 to 13.73; 3 studies). These results are of low certainty due to imprecision and risk of bias. Tacrolimus (oral and rectal) may be superior for clinical improvement compared to placebo (oral and rectal) (45/87 participants with tacrolimus versus 7/61 participants with placebo; RR 4.47, 95% CI 2.15 to 9.29; 3 studies). These results are of low certainty due to imprecision and risk of bias. The evidence is very uncertain about the effects of tacrolimus (oral and rectal) on serious adverse events compared to placebo (oral and rectal) (2/87 participants with tacrolimus versus 0/61 participants with placebo; RR 2.44, 95% CI 0.12 to 48.77; 3 studies). These results are of very low certainty due to high imprecision and risk of bias. Tacrolimus versus ciclosporin One study compared oral tacrolimus to intravenous ciclosporin, with an intervention lasting two weeks and 113 randomised participants. The evidence is very uncertain about the effect of tacrolimus on achievement of clinical remission compared to ciclosporin (15/33 participants with tacrolimus versus 24/80 participants with ciclosporin; RR 1.52, 95% CI 0.92 to 2.50). The results are of very low certainty due to risk of bias and high imprecision. The evidence is very uncertain about the effect of tacrolimus on clinical improvement compared to intravenous ciclosporin (23/33 participants with tacrolimus versus 62/80 participants with ciclosporin; RR 0.90, 95% CI 0.70 to 1.16). The results are of very low certainty due to risk of bias and imprecision. Tacrolimus versus beclometasone One study compared tacrolimus suppositories with beclometasone suppositories in an intervention lasting four weeks with 88 randomised participants. There may be little to no difference in achievement of clinical remission (16/44 participants with tacrolimus versus 15/44 participants with beclometasone; RR 1.07, 95% CI 0.60 to 1.88). The results are of low certainty due to high imprecision. There may be little to no difference in clinical improvement when comparing tacrolimus suppositories to beclometasone suppositories (22/44 participants with tacrolimus versus 22/44 with beclometasone; RR 1.00, 95% CI 0.66 to 1.52). The results are of low certainty due to high imprecision. There may be little to no difference in serious adverse events when comparing tacrolimus suppositories to beclometasone suppositories (1/44 participants with tacrolimus versus 0/44 with beclometasone; RR 3.00, 95% CI 0.13 to 71.70). These results are of low certainty due to high imprecision. There may be little to no difference in total adverse events when comparing tacrolimus suppositories to beclometasone suppositories (21/44 participants with tacrolimus versus 14/44 participants with beclometasone; RR 1.50, 95% CI 0.88 to 2.55). These results are of low certainty due to high imprecision. No secondary outcomes were reported for people requiring rescue medication or to undergo surgery. AUTHORS' CONCLUSIONS: There is low-certainty evidence that tacrolimus may be superior to placebo for achievement of clinical remission and clinical improvement in corticosteroid-refractory colitis or corticosteroid-refractory proctitis. The evidence is very uncertain about the effect of tacrolimus compared to ciclosporin for achievement of clinical remission or clinical improvement. There may be no difference between tacrolimus and beclometasone for inducing clinical remission or clinical improvement. The cohorts studied to date were small, with missing data sets, offered short follow-up and the clinical endpoints used were not in line with those suggested by regulatory bodies. Therefore, no clinical practice conclusions can be made. This review highlights the need for further research that targets the relevant clinical questions, uses appropriate trial methodology and reports key findings in a systematic manner that facilitates future integration of findings with current evidence to better inform clinicians and patients. Future studies need to be adequately powered and of pertinent duration so as to capture the efficacy and effectiveness of tacrolimus in the medium to long term. Well-structured efficacy studies need to be followed up by long-term phase 4 extensions to provide key outputs and inform in a real-world setting.

IOIBD Recommendations for Clinical Trials in Ulcerative Proctitis: The PROCTRIAL Consensus.

BACKGROUND & AIMS: Clinical trials evaluating biologics and small molecules in patients with ulcerative colitis are predominantly excluding ulcerative proctitis. The objective of the Definition and endpoints for ulcerative PROCtitis in clinical TRIALs initiative was to develop consensus statements for definitions, inclusion criteria, and endpoints for the evaluation of ulcerative proctitis in adults. METHODS: Thirty-five international experts held a consensus meeting to define ulcerative proctitis, and the endpoints to use in clinical trials. Based on a systematic review of the literature, statements were generated, discussed, and approved by the working group participants using a modified Delphi method. Consensus was defined as at least 75% agreement among voters. RESULTS: The group agreed that the diagnosis of ulcerative proctitis should be made by ileocolonoscopy and confirmed by histopathology, with the exclusion of infections, drug-induced causes, radiation, trauma, and Crohn's disease. Ulcerative proctitis was defined as macroscopic extent of lesions limited to 15 cm distance from the anal verge in adults. Primary and secondary endpoints were identified to capture response of ulcerative proctitis to therapy. A combined clinical and endoscopic primary endpoint for the evaluation of ulcerative proctitis disease activity was proposed. Secondary endpoints that should be evaluated include endoscopic remission, histologic remission, mucosal healing, histologic endoscopic mucosal improvement, disability, fecal incontinence, urgency, constipation, and health-related quality of life. CONCLUSIONS: In response to the need for guidance on the design of clinical trials in patients with ulcerative proctitis, the Definition and end points for ulcerative PROCtitis in clinical TRIALs consensus provides recommendations on the definition and endpoints for ulcerative proctitis clinical trials.

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.

Cytomegalovirus proctitis in non-human immunodeficiency virus infected patients: A case report and literature review.

Cytomegalovirus (CMV) infection is associated with significant morbidity and mortality in both immunocompetent and immunocompromised patients. CMV is a ubiquitous Herpesviridae virus with a wide spectrum of pathologies in humans. Immunocompetent patients generally develop a benign, self-limited mononucleosis-like syndrome, whereas gastrointestinal tissue-invasive disease is more frequently seen in immunocompromised. The clinical manifestations of CMV colitis or proctitis are demarcated by bloody diarrhea, ulcerations, ulcero-infiltrative changes, and pseudomembranous formation on colonoscopy. Gastrointestinal CMV infections complicated with deep rectal ulcer and fistula formation are rare in patients with systemic lupus erythematosus. Ganciclovir is also the gold standard therapy for CMV colitis or proctitis.

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

Objectives: This study aimed to investigate the protective effect of ginsenoside Rg3 (GRg3) against acute radiation proctitis (ARP) in rats. Methods: 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 1ß (IL-1ß) 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. Results: 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-1ß decreased, whereas that of IL-10 increased. Conclusion: 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.

Proctitis y enfermedad perianal de causa infecciosa: una mirada más allá de la enfermedad inflamatoria intestinal / Infectious proctitis and perianal disease: a gaze beyond inflammatory bowel disease

Resumen La proctitis infecciosa secundaria a una enfermedad de transmisión sexual ha aumentado en incidencia y deben ser consideradas especial-mente en varones homosexuales o bisexuales con síntomas rectales. Presentamos un paciente con una proctitis y enfermedad perianal por Chlamydia trachomatis que podría haber sido diagnosticado con otra enfermedad ano-rectal como es la enfermedad inflamatoria intestinal, si la historia clínica no hubiese sido considerada. Un alto nivel de sospecha es necesario para evitar un diagnóstico incorrecto, retrasar el tratamiento antimicrobiano y el desarrollo de complicaciones.

Abstract Infectious proctitis by sexually transmitted diseases are increasing in incidence and should be considered in homosexual patients with rectal symptoms. In this case, we show a patient with proctitis and perianal disease caused by Chlamydia trachomatis that could be diagnosed as another anorectal disease such as inflammatory bowel disease if the clinical history is not taken into account. A high level of suspicion is crucial, in order to avoid an incorrect diagnosis, delayed antibiotic therapy and the development of complications.

Evaluation of mesalazine polymeric conjugate in the treatment of actinic proctitis in rats.

PURPOSE: The present study aimed at testing a new formulation of mesalazine linked to chondroitin sulfate and its components alone in the treatment of actinic proctitis in rats. METHODS: Forty-seven female Wistar rats were submitted to pelvic radiation and divided into eight groups: control A, mesalazine A, chondroitin A, and conjugate A, gavage of the according substance two weeks after irradiation and sacrifice three weeks after oral treatment; control C, mesalazine C, chondroitin C, and conjugate C, sacrifice six weeks after oral treatment. The rectum was submitted to histological characterization for each of the findings: inflammatory infiltrate, epithelial degeneration, mucosal necrosis, and fibrosis. RESULTS: The inflammatory infiltrate was more intense in chondroitin A, mesalazine A, and conjugate C. The collagen deposition was less intense in chondroitin A, and mesalazine A, and more intense in control C. CONCLUSIONS: Mesalazine and chondroitin alone were efficacious in inducing a delayed inflammatory response, hence reducing the late fibrosis. The conjugate was able to induce an ever more delayed inflammatory response.