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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.

A 72 year-old man was referred to our hospital for a detailed examination of a recurrent rectal polyp. He had past histories of surgery and radiation therapy for prostate cancer at the age of 66 and endoscopic excision of a rectal polyp at the age of 70. Colonoscopy revealed a semi-pedunculated lesion surrounded by friable mucosa, which was positive under positron-emission tomography-computed tomography. Histopathological examination of the endoscopically excised polyp revealed proliferation of atypical cells, characterized by strong pleomorphic or spindle morphology, which was immunohistochemically compatible with undifferentiated pleomorphic sarcoma. We diagnosed this case as sarcoma presumably associated with radiation proctitis., (© 2024. The Author(s).)

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.

Purpose: There are no effective treatment methods with which to control complications of radiation proctitis with fistula or recurrent bleeding following radiation treatment for prostate, cervical, or rectal cancer. Mesenchymal stem cells (MSCs) can induce immune modification, resulting in tissue repair and regeneration. Therefore, we used a rat model of radiation-induced proctitis and observed the effects of using human placenta-derived (PD) and adipose tissue-derived (AD) MSCs., Materials and Methods: Female Sprague Dawley rats were irradiated at the pelvic area with 25 Gy. We injected 1×10 6 cells of human PD-MSCs, human AD-MSCs, human foreskin fibroblasts, and control media into the rectal submucosa following irradiation. We sacrificed rats for pathologic evaluation., Results: Fibrosis on the rectum was reduced in both MSC groups, compared to the control group. Mucosal Ki-67 indices of both MSC injected groups were higher than those in the control group. Although caspase-3 positive cells in the mucosa gradually increased and decreased in the control group, those in both MSC injected groups increased rapidly and decreased thereafter., Conclusion: We demonstrated the effects of regional MSC injection treatment for radiation-induced proctitis in rats. MSC injection reduced fibrosis and increased proliferation in rat mucosa. Human AD-MSCs and PD-MSCs had similar effectiveness., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2023.)

Introduction: Since 2003, a progressive increase in sexually transmitted infections (STI), presented as proctitis, has been described in homosexual men. In 2013 Arnold et al. described microscopic features that enable pathologists to formulate a histological diagnosis of STI related proctitis. The aim of this study is to identify the presence of Chlamydia trachomatis by immunohistochemistry in a group of patients with male to male sexual activity and pathology compatible with STI proctitis., Methods: Cross-sectional study. The study included 54 patients with risky sexual activity and histopathology compatible with STI-proctitis according to Arnold´s recommendations. The Chlamydia trachomatis identification was carried out retrospectively on paraffin blocks using mouse monoclonal antibodies from Santa Cruz biotechnology., Results: all patients were young men with male to male sexual activity, 69% were positive for HIV. The most common endoscopic presentation was rectal ulcer (61%). Basal lymphoplasmacytic inflammation and mild crypt distortion were the most common histological findings. The immunohistochemical study identified positivity for Chlamydia trachomatis in 40% (18 of 45 tested) of STI proctitis cases., Discussion: The epidemiological and endoscopic characteristics of the patients studied are similar to those previously reported. In accordance with Arnold et al., the most common histological findings were (a) mild distortion of the crypts; (b) dense and basal lymphoplasmacytic infiltrate and (c) scarcity of eosinophils. The positivity of chlamydia trachomatis in immunohistochemistry was lower than others studies that used PCR for this purpose. We did not find similar published studies to compare our results., Conclusions: In summary, 54 cases of patients with STI related proctitis are presented, all of them with distinctive histological characteristics and third of the cases tested positive by IHC for Chlamydia trachomatis., (© 2022. The Author(s).)

A Japanese male in his 50s was presented to our hospital with the chief complaint of positive fecal immunochemical test. He had a history of hypertension. He underwent colonoscopy and was diagnosed with sigmoid colon cancer. He also underwent laparoscopic sigmoid colectomy with D3 lymph node dissection for sigmoid colon cancer. The inferior mesenteric artery and inferior mesenteric vein were amputated at the root of the vessels. The patient received adjuvant chemotherapy and was recurrence-free. Eleven months after the surgery, lower abdominal pain during defecation appeared. Contrast-enhanced computed tomography (CT) and colonoscopy showed marked rectal mucosal edema and increased fatty tissue density (dirty fat sign) around the anorectal side of the anastomosis. Intestinal blood flow was maintained. There were many fine blood vessels around the rectal wall, and the amputated distal part of the superior rectal artery was retrogradely contrasted. Amputated superior rectal artery and superior rectal vein were dilated than before. Colonoscopy revealed mucosal redness, edema, and easy bleeding on the anorectal side of the anastomosis. Abdominal contrast-enhanced 3D-CT showed increased arterial blood flow and increased fine blood vessels around the rectal wall. It suggested the presence of an arteriovenous fistula and venous congestion. Conservative treatment with total parenteral nutrition and prednisolone infusion did not improve the patient's condition, and a colostomy was performed. After colostomy, the pain improved, and the CT scan of the abdomen showed improvement in arterial blood flow and venous congestion. Colostomy was closed after 10 months. There has been no relapse since the closure of the colostomy. There are few reports on ischemic proctitis on the anorectal side of the anastomosis after colon cancer resection due to impaired venous blood flow.

Aims: Recent studies from multiple global regions have reported a resurgence of lymphogranuloma venereum (LGV) proctitis, which is caused by Chlamydia trachomatis (CT). LGV proctitis is histologically indistinguishable from other forms of sexually transmitted proctitis and is difficult to differentiate from inflammatory bowel disease. While immunohistochemical stains are available for syphilis, there is no commonly available stain for the tissue identification of CT., Materials and Methods: From 200 positive CT nucleic acid tests (NAT) from anorectal swabs, we identified 12 patients with biopsies collected from the distal colorectum or anus within 90 days of the positive NAT. We collected basic demographic information and tabulated clinical and histological findings. We examined the performance of a novel RNA in-situ hybridisation (ISH) stain targeting CT 23s rRNA on these 12 cases and 10 controls from the anorectum., Results: All 12 patients were male; nine were HIV+, two had concurrent gonococcal infection, one had concurrent syphilis and one had cytomegalovirus co-infection. The majority of biopsies (11 of 12) showed mild or moderate acute inflammation, had a prominent lymphoplasmacytic infiltrate (eight of 11) and lacked marked crypt distortion (10 of 10). The RNA ISH stain was positive in 10 of 12 cases (sensitivity 83%). One case showed equivocal staining. No controls showed definitive positive staining (specificity 100%). One had equivocal staining., Conclusion: Our series showed that anorectal LGV had similar histological findings to those of prior STI proctitis series predominantly comprised of syphilis. The novel RNA ISH stain was sensitive and specific and may show utility in differentiating types of STI proctitis., (© 2020 John Wiley & Sons Ltd.)

Objectives: We explored the association between nucleic acid amplification testing (NAAT) and rectal microscopy/proctoscopy findings and correlates of rectal STIs among 150 gay and bisexual men (GBM) diagnosed with proctitis at the Sydney Sexual Health Centre from March 2016 to October 2017., Methods: From case files, we analysed risk behaviours, microscopy, proctoscopy and NAAT results for rectal STIs ( Chlamydia trachomatis , Neisseria gonorrhoeae , Mycoplasma genitalium , herpes simplex virus type 1/2, lymphogranuloma venereum and syphilis). χ 2 test assessed the association between microscopy/proctoscopy findings and NAAT results. Linear regression assessed the association between NAAT positivity and correlates of rectal STIs., Results: The mean age was 32.5 (9.8) years, 43% (65/150) were taking pre-exposure prophylaxis, 17% (26/150) were HIV positive and 24% (36/147) had multiple rectal STIs.Among GBM with documented proctoscopy findings (n=113), 58% (65/113) had discharge, 36% (41/113) had anorectal erythema and 25% (28/113) had bleeding. A quarter of GBM (28/113) had negative proctoscopy findings.Discharge found on proctoscopy (p=0.001), positive HIV status (p=0.030) and time since last receptive anal intercourse (p=0.028) were independently associated with NAAT positivity for any rectal STI. Discharge had a positive likelihood ratio of 1.6 (95% CI 1.0 to 2.4).Among those with documented microscopy findings (n=69), 59% (41/69) and 41% (28/69) were NAAT positive and negative, respectively. Among NAAT-positive GBM, 27 (66%) had polymorphonuclear cells (PMNs) (mean number of PMNs, 10 (SD 9) cells per oil immersion field), 1 (2%) had Gram-negative intracellular diplococci and 11 (27%) had negative findings. There was no significant association between microscopy findings and NAAT results (p=0.651) or the number of rectal STI (p=0.279)., Conclusion: Microscopy does not reliably provide information necessary to tailor the management of GBM diagnosed with proctitis. Discharge found during proctoscopy may identify GBM with rectal STI. Services should consider recommendations to perform these investigations., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Various methods have been used for treatment of hemorrhagic radiation proctitis (HRP) with variable results. Currently, the preferred treatment is formalin application or endoscopic therapy with argon plasma coagulation. Recently, a novel therapy with colonic water irrigation and oral antibiotics showed promising results and more effective compared to 4% formalin application for HRP. The study objective is to compare the effect of water irrigation and oral antibiotics versus 4% formalin application in improving per rectal bleeding due to HRP and related symptoms such as diarrhoea, tenesmus, stool frequency, stool urgency and endoscopic findings., Methods: We conducted a study on 34 patients with HRP and randomly assigned the patients to two treatment arm groups (n=17). The formalin group underwent 4% formalin dab and another session 4 weeks later. The irrigation group self-administered daily rectal irrigation at home for 8 weeks and consumed oral metronidazole and ciprofloxacin during the first one week. We measured the patients' symptoms and endoscopic findings before and after total of 8 weeks of treatment in both groups., Results: Our study showed that HRP patients had reduced per rectal bleeding (p = 0.003) in formalin group, whereas irrigation group showed reduced diarrhoea (p=0.018) and tenesmus (p=0.024) symptoms. The comparison between the two treatment arms showed that irrigation technique was better than formalin technique for tenesmus (p=0.043) symptom only., Conclusion: This novel treatment showed benefit in treating HRP. It could be a new treatment option which is safe and conveniently self-administered at home or used as a combination with other therapies to improve the treatment outcome for HRP., .

Introduction: Long-term outcomes of patients with ulcerative proctitis (UP) have been poorly investigated, since these patients are excluded from participation in randomized controlled clinical trials., Objective: The aim of this study was to investigate the prognostic and therapeutic long-term outcomes of patients with UP., Methods: A retrospective study of patients with UP followed at our referral centre between 1 January 1998 and 1 January 2019 was performed. Treatment success was defined as clinical response (significant improvement in UP-related symptoms) and endoscopic response (mayo endoscopic sub-score of 0 or 1) if available at last follow-up., Results: From a total of 1561 patients with ulcerative colitis, 118 patients with UP were identified. A total of 36 (31%) patients were refractory to rectal and oral therapy with 5-ASA and corticosteroids, necessitating azathioprine as monotherapy in 19 (16%) patients and/or biological therapies in 33 (28%) patients. After a median follow-up of 71 months (interquartile range 29-149 months), treatment success was observed in 103/118 (87%) UP patients and in 25/36 (69%) patients with refractory UP. Clinical response rates were significantly higher for refractory UP patients treated with biologicals (23/33; 70%) compared to ones treated with azathioprine (2/19; 11%; p   =  0.001)., Conclusion: Good clinical outcomes were recorded in UP, with treatment success in 87% of patients. Nevertheless, 28% needed escalation to biologicals. Long-term outcome in patients on biologicals was superior to azathioprine.

Rationale: There are many treatments for chronic hemorrhagic radiation colorectal inflammation, but only a few treatments are supported by high-quality research evidence. Studies have shown that the occurrence and development of radiation proctitis are closely associated with the intestinal flora. Animal studies have indicated that faecal microbiota transplantation (FMT) can improve radiation enteropathy in a mouse model., Patient Concerns: A 45-year-old female patient suffered from recurrent hematochezia and diarrhea for half a year after radiotherapy and underwent recurrent transfusion treatments. Colonoscopy showed obvious congestion of the sigmoid colon and rectal mucosa, a smooth surface, and bleeding that was easily induced by touch, which are consistent with radiation proctitis. The pathological findings revealed chronic mucosal inflammation. The magnetic resonance imaging examination of the pelvic cavity with a plain scan and enhancement showed changes after radiotherapy and chemotherapy, and no obvious tumor recurrence or metastasis was found. The laboratory examinations excluded pathogen infection., Diagnoses: Based on the history and examinations, the final diagnosis of this patient was chronic hemorrhagic radiation proctitis., Interventions: The patient was treated with a total of 4 individual courses of FMT., Outcomes: After the six-month follow-up, her hematochezia, abdominal pain and diarrhea were relieved. Furthermore, 16S rRNA sequencing of the feces showed that the intestinal bacterial composition of the patient obviously changed after FMT and became similar to that of the donors., Lessons: This case report shows that FMT can relieve the symptoms of hematochezia and diarrhea by changing the bacterial community structure in patients with chronic hemorrhagic radiation proctitis.

Purpose: The impact of acute histopathological changes (HC) of the rectum on development of late clinical proctitis (LCP) after external radiotherapy (RT) for prostate cancer is poorly explored and was the primary end point of this prospective study., Methods: In 70 patients, 15 HC of early rectal biopsies after RT were identified, whereby RT was conventional 2D RT in 41 cases and conformational 3D RT in 29. Associations of HC in anterior and posterior rectal walls (ARW, PRW) with LCP, acute endoscopic (AEP) and acute clinical proctitis (ACP) were statistically evaluated considering as explicative variables the patient general characteristics and the HC., Results: The mean patients' follow-up was 123.5 months (24-209). The median prostatic dose was 72 Gy (2 Gy/fraction). For the 41 and 29 patients the ARW and PRW doses were 64 and 49 Gy vs. 63 and 50 Gy, respectively. The incidence of LCP ≥ grade 2 at 10 years was 12.9%. The univariate (p = 0.02) and Kaplan-Meyer methods (p = 0.007) showed that the gland (or crypts) loss in the ARW was significantly associated with LCP. AEP and ACP occurred in 14.3 and 55.7% of cases. At multivariate level AEP significantly correlated with hemorrhoids (p = 0.014) and neutrophilia in ARW (p = 0.042)., Conclusions: Early after RT, substantial gland loss in ARW is predictive of LCP. To reduce this complication with conventional fractionation, we suggest keeping the mean dose to ARW ≤48-52 Gy.

We analyzed the main properties of autologous adipose-derived stromal vascular fraction (SVF) used for the treatment of radiation-induced lesions in the rectum. No statistically significant correlation between the main characteristics of the cell product (cell number, viability) and patient's age or donor area were revealed. The stages and peculiarities of histological changes in the regenerating tissue after injection of autologous adipose tissue cells were analyzed. Morphological changes at the stages of granulation, early and complete epithelialization, and tissue maturation were described.

Purpose: This phase II study evaluated the utility of magnetic resonance imaging (MRI) and positron emission tomography for planning radiation and brachytherapy in patients with postsurgical recurrence of cervical cancer., Methods and Materials: The study (NCT01391065) recruited patients with residual or recurrent disease after hysterectomy. Patients underwent baseline T2 weighted (T2W) MRI, 18 F-flouro-deoxyglucose ( 18 F-FDG), 18 F-flouro thymidine ( 18 F-FLT) and 18 F-flouromisonidazole ( 18 F-F Miso) positron emission tomography (PET) and received external radiation (50 Gy/25 fractions for 5 weeks) and weekly cisplatin (40 mg/m 2 ). MRI was performed at brachytherapy and used for delineation of clinical target volume (CTV). Patients with parametrial disease at baseline received interstitial brachytherapy (16-20 Gy/4-5 fractions) and those with vaginal disease received intracavitary brachytherapy (12-14 Gy/2-4 fractions). Kaplan-Meier analysis was performed to evaluate locoregional relapse, disease free survival, and overall survival. Common Toxicity Criteria for adverse event reporting (CTCAE) v4.1 was used for toxicity scoring and European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questtionaire Core 30 (QLQC-30) and Cx 24 for quality-of-life reporting., Results: Between January 2011 and February 2016, 60 patients were included, of which 50 received study treatment. The mean gross tumor volume on T2 W MR was 20 (IQR 3.6-90) cc. The metabolic tumor volume was 15 (interquartile range [IQR] 2.1-56.1) cc. The median FLT volume was 10 (IQR 0-48) cc. A total of 8 patients had 18- F F Miso uptake. The median CTV at brachytherapy was 38 (12-85) cc. The median CTVD90 and D 98 was 71 (53-74) and 74 (53-74) Gy. At a median follow-up of 60 (5-93) months, the 5-year local control, disease free survival, and overall survival were 84%, 73%, and 74.5%, respectively. Grade III and IV proctitis and cystitis were observed in 4% and 2% of patients. On multivariate analysis baseline tumor volume, on T2 W MR impacted disease free (91% vs 65%, P = .03) and overall survival (96% vs 77%, P = .06)., Conclusions: Image-guided assisted radiation and brachytherapy are associated with good to excellent local control and survival in patients with vaginal recurrences of cervical cancer., (Copyright © 2019 Elsevier Inc. All rights reserved.)

We present the case of a woman infected with the HIV type 1, controlled with highly active antiretroviral therapy. In the meantime, she developed a severe perianal disease, with complex fistulae and chronic anal fissures. After developing a severe chronic diarrhea, a total ileocolonoscopy with biopsies was performed, showing multiple ileal and segmental colonic erosions. Histology favoured a Crohn's disease diagnosis. Despite the limited experience of anti-tumour necrosis factor agents in the HIV-infected population, infliximab was started in this patient, due to her severe and symptomatic Crohn's disease, with a controlled HIV infection. No side effects were reported and her bowel movements and perianal disease improved right after induction regimen with infliximab. 1 year after starting this therapy she is in clinical and endoscopic remission. The CD4+ T-cell count remained stable, the HIV-RNA undetectable and no opportunistic infections were reported during follow-up period. Data concerning the use of anti-tumour necrosis factor drugs is limited in patients with both inflammatory bowel disease and HIV infection. Only three cases of Crohn's disease and concomitant HIV infection treated with infliximab were reported in the literature. This case report might help future decisions in patients with a similar clinical situation.

The incidence of syphilis is increasing. Syphilitic proctitis involving the rectal mucosa often presents with pain on defecation, rectal bleeding, or ulceration. We present a case of asymptomatic syphilitic proctitis diagnosed upon a routine screening colonoscopy.

Background: Chronic radiation proctitis (CRP) is a complication which occurs in 1%-5% of patients who undergo radiotherapy for pelvic malignancies. Although a wide range of therapeutic modalities are available, there is no literature to date showing any particularly appropriate therapeutic modality for each disease stage. Argon plasma coagulation (APC) is currently recommended as the first-choice treatment for hemorrhagic CRP, however, its indication based on long-term follow-up is still unclear. On the hypothesis that the long-term efficacy and safety of APC are not fully understood, we reviewed APC treatment for patients with hemorrhagic CRP from a single center., Aim: To assess the long-term efficacy and safety of APC for hemorrhagic CRP., Methods: This is a retrospective study of consecutive patients treated with APC for hemorrhagic CRP from January 2013 to October 2017. Demographics, clinical variables, and typical endoscopic features were recorded independently. Success was defined as either cessation of bleeding or only occasional traces of bloody stools with no further treatments for at least 12 mo after the last APC treatment. We performed univariate and multivariate analyses to identify factors associated with success and risk factors for fistulas., Results: Forty-five patients with a median follow-up period of 24 mo (range: 12-67 mo) were enrolled. Fifteen (33.3%) patients required blood transfusion before APC. Successful treatment with APC was achieved in 31 (68.9%) patients. The mean number of APC sessions was 1.3 (1-3). Multivariate analysis showed that APC failure was independently associated with telangiectasias present on more than 50% of the surface area [odds ratio (OR) = 6.53, 95% confidence interval (CI): 1.09-39.19, P = 0.04] and ulcerated area greater than 1 cm 2 (OR = 8.15, 95%CI: 1.63-40.88, P = 0.01). Six (13.3%) patients had severe complications involving rectal fistulation. The only factor significantly associated with severe complications was ulcerated area greater than 1 cm 2 ( P = 0.035)., Conclusion: The long-term efficacy of APC for hemorrhagic CRP is uncertain in patients with telangiectasias present on > 50% of the surface area and ulceration > 1 cm 2 ., Competing Interests: Conflict-of-interest statement: All authors declare no conflicts of interest related to this article.

Background & Aims: Studies of non-celiac gluten or wheat sensitivity (NCGWS) have increased but there are no biomarkers of this disorder. We aimed to evaluate histologic features of colon and rectal tissues from patients with NCGWS., Methods: We performed a prospective study of 78 patients (66 female; mean age, 36.4 years) diagnosed with NCGWS by double-blind wheat challenge at 2 tertiary care centers in Italy, from January 2015 through September 2016. Data were also collected from 55 patients wither either celiac disease or self-reported NCGWS but negative results from the wheat-challenge test (non-NCGWS controls). Duodenal and rectal biopsies were collected and analyzed by immunohistochemistry to quantify intra-epithelial CD3 + T cells, lamina propria CD45 + cells, CD4 + and CD8 + T cells, mast cells, and eosinophils and to determine the presence and size of lymphoid nodules in patients with NCGWS vs patients with celiac disease or non-NCGWS controls., Results: Duodenal tissues from patients with NCGWS had significantly higher numbers of intra-epithelial CD3 + T cells, lamina propria CD45 + cells, and eosinophils than duodenal tissues from non-NCGWS controls. Duodenal tissues from patients with NCGWS and dyspepsia had a higher number of lamina propria eosinophils than patients with NCGWS without upper digestive tract symptoms. Rectal mucosa from patients with NCGWS had a larger number of enlarged lymphoid follicles, intra-epithelial CD3 + T cells, lamina propria CD45 + cells, and eosinophils than rectal mucosa from non-NCGWS controls. Duodenal and rectal mucosal tissues from patients with celiac disease had more immunocytes (CD45 + cells, CD3 + cells, and eosinophils) than tissues from patients with NCGWS or non-NCGWS controls., Conclusions: We identified markers of inflammation, including increased numbers of eosinophils, in duodenal and rectal mucosa from patients with NCGWS. NCGWS might therefore involve inflammation of the entire intestinal tract. Eosinophils could serve as a biomarker for NCGWS and be involved in its pathogenesis. Clinicaltrials.gov: NCT01762579., (Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Cow's milk protein allergy/intolerance (CMPA/CMPI) is a common entity in the pediatric population with a nonspecific presentation ranging from gastrointestinal symptoms to systemic manifestations. Most infants with CMPI are term, and symptoms often appear in the week following the introduction of cow's milk-based formula. There is typically a significant delay in the onset of milk allergy in premature infants compared to full term. We report a rare case of a premature neonate who presented with symptoms of CMPA within the first 2 days of life.

Objective: To assess the cost-effectiveness of three testing strategies with or without light microscopic Gram-stained smear (GSS) evaluation for the detection of anogenital gonorrhoea among men who have sex with men (MSM) at the Amsterdam STI clinic using a healthcare payer perspective., Methods: Three testing strategies for MSM were compared: (1) GSS in symptomatic MSM only (currently practised strategy), (2) no GSS and (3) GSS in symptomatic and asymptomatic MSM. The three testing protocols include testing with nucleic acid amplification test to verify the GSS results in (1) and (3), or as the only test in (2). A transmission model was employed to calculate the influence of the testing strategies on the prevalence of anogenital gonorrhoea over 10 years. An economic model combined cost data on medical consultations, tests and treatment and utility data to estimate the number of epididymitis cases and quality-adjusted life years (QALY) associated with gonorrhoea. Incremental cost-effectiveness ratios (ICERs) for the testing scenarios were estimated. Uncertainty and sensitivity analyses were performed., Results: No GSS testing compared with GSS in symptomatic MSM only (current strategy) resulted in nine extra epididymitis cases (95% uncertainty interval (UI): 2-22), 72 QALYs lost (95% UI: 59-187) and €7300 additional costs (95% UI: -€185 000 (i.e.cost-saving) to €407 000) over 10 years. GSS testing in both symptomatic and asymptomatic MSM compared with GSS in symptomatic MSM only resulted in one prevented epididymitis case (95% UI: 0-2), 1.1 QALY gained (95% UI: 0.1-3.3), €148 000 additional costs (95% UI: €86 000 to-€217 000) and an ICER of €177 000 (95% UI: €67 000-to €705 000) per QALY gained over 10 years. The results were robust in sensitivity analyses., Conclusions: GSS for symptomatic MSM only is cost-effective compared with no GSS for MSM and with GSS for both symptomatic and asymptomatic MSM., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Patients with refractory inflammatory bowel disease (IBD) might require a subtotal colectomy with construction of an ileostomy. Due to the risk of nerve damage and pelvic sepsis, the diverted rectum is often left in situ. Evidence on long-term complications of this rectal stump is limited, particularly in patients with Crohn's disease (CD). In addition to the risk of development of neoplasia, diversion proctitis is a frequently reported rectal stump associated complication. Surprisingly, clear recommendations concerning rectal stump surveillance and timing of proctectomy are lacking., Methods: Through the use of a pathology database and a review of medical records, we established a cohort of IBD patients with a diverted rectum. Among these patients, long-term complications of the rectal stump were identified. Main endpoint was advanced neoplasia (carcinoma or high-grade dysplasia [HGD]) in the rectal stump. Risk factors for advanced neoplasia were identified using Cox regression modeling. In the second, prospective part of the study, a questionnaire was sent out to 165 patients with either a rectal stump in situ or who had undergone a proctectomy, in order to identify differences in patient-reported outcome measures associated with the excision of the rectal stump., Results: From 530 patients with IBD and a (temporal) diversion of the rectum, we included 250 patients in whom the rectal stump was left in situ for more than 12 months. The majority of patients was female (61%) and had Crohn's disease (67%). On follow-up (median 8 years), 8 carcinomas, 2 cases of high-grade dysplasia, and 7 cases of low-grade dysplasia were found with incidence rates of 3.9 and 8.5 per 1000 patient-years of follow-up for cancer and all neoplasia, respectively. The 8 cases of rectal stump cancer (RSC) were diagnosed after a median of 15 years after colectomy. A history of colorectal neoplasia was associated with advanced rectal stump neoplasia. Out of 191 patients with endoscopic follow-up, rectal stump inflammation occurred in 161 (88.5%) patients. Results of the questionnaire did not show a significant difference in quality of life between patients with and patients without a rectal stump, although the latter group reported significantly more sexual and urinary symptoms than patients with a rectal stump in situ. The majority of rectal stump patients reported rectal blood loss, but 65.5% of them were not or barely limited in daily life by their rectal stumprelated problems., Conclusion: Rectal stump cancer has a low incidence rate, with patients with a history of colonic neoplasia carrying the highest risk of developing this severe complication. We observed no significant differences in quality of life between rectal stump and postproctectomy patients, but proctectomy surgery is associated with sexual and urinary complications.

Chronic inflammation in the colorectum, a significant contributor to colorectal carcinogenesis, can be triggered by the activation of proinflammatory signaling pathways such as those initiated by Toll-like receptors (TLR) and nuclear factor κB (NF-κB). Although experimental evidence supports calcium and vitamin D potentially modifying these proinflammatory pathways in the colorectum, human data in these regards are scarce. We investigated supplemental calcium (1,200 mg daily) and/or vitamin D 3 (1,000 IU daily) effects on inflammatory signaling pathway-related biomarkers in a subset of 105 participants from a colorectal adenoma recurrence chemoprevention clinical trial. We assessed expression of TLR4 and TLR5, which recognize the bacterial components lipopolysaccharides and flagellin, respectively, and phospho-IKKα/β (pIKKα/β), a biomarker of inflammation, in the normal-appearing rectal crypt epithelium and stroma using standardized, automated immunohistochemistry and quantitative image analysis. Following 1 year of treatment, TLR4, TLR5, and pIKKα/β expression in the rectal mucosa did not statistically significantly change with vitamin D or calcium supplementation, taken alone or in combination. Several baseline participant characteristics, including body mass index, history of sessile serrated adenomas, high red/processed meat intake, and high levels of rectal epithelial cell proliferation (as measured by MIB-1/Ki-67), were associated with higher baseline expression of TLRs or pIKKα/β. Our findings suggest that vitamin D and calcium may have no substantial effect on the investigated biomarkers. However, several modifiable lifestyle factors may be associated with TLRs and pIKKα/β expression in the normal rectal mucosa, supporting their future investigation as potentially treatable, preneoplastic risk factors for colorectal neoplasms. Cancer Prev Res; 11(11); 707-16. ©2018 AACR ., (©2018 American Association for Cancer Research.)

Lymphogranuloma venereum (LGV) is caused by L1, L2 and L3 serovars of Chlamydia trachomatis. The anorectal syndrome caused by LGV is often misdiagnosed as inflammatory bowel disease and may rarely lead to stricture formation. Recurrent stricture formation, despite adequate LGV treatment, has not to our knowledge, previously been reported.

Lymphoid follicular proctitis (LFP) is an uncommon inflammatory disease that is characterized by rectal bleeding, congested and granular mucosa without ulceration and abnormal and coalescing hyperplastic lymphoid follicles without acute inflammatory changes. The lesions are usually confined to the rectal mucosa. LFP therapy is not well defined. Herein, we present a case of LFP that was resolved with a rapid administration of mesalazine enemas. A 35-year-old male was admitted to our hospital due to intermittent rectal bleeding associated with stools. Total colonoscopy revealed nodular mucosa with top pinpoint-like ulcers from the rectum to the border between the sigmoid flexure and the rectum. The nodules congested together on the lower rectal segment and occupied 2/3 of the rectal lumina. Endoscopic submucosal dissection was performed in order to obtain more specimens for histologic examination, which revealed marked lymphoid follicular hyperplasia with prominent germinal centers and a conserved mantle zone. Treatment was started with mesalazine enemas of 4 g q.d. and the patient was asymptomatic after three days. All the lesions disappeared two months later. Mesalazine enemas could be a promising and effective therapeutic option for LFP therapy.

Aim: The aim of this study was to assess the expression of vascular endothelial growth factor (VEGF) as a key proangiogenic factor and determine whether there is any correlation between its expression and clinical symptoms or endoscopic changes in patients with chronic radiation proctitis (ChRP)., Method: Fifty patients who had all undergone radiotherapy for prostate, cervical or uterine cancer were included in the study (37 women, 13 men). There was a control group of 20 patients (9 women, 11 men). The Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC) scoring system was used for grading the severity of the proctitis. Endoscopic scoring of late rectal mucosal damage was performed using Gilinsky's classification. Serum levels of VEGF were analysed by the enzyme-linked immunosorbent assay method., Results: Most patients presented with Grade 1 symptoms. Endoscopic assessment showed that most patients had Grade 1 late rectal mucosal damage. The predominant endoscopic finding was the presence of telangiectasia. Assessment of VEGF correlation between the control group and the degrees of endoscopic changes showed statistically significant differences for all three degrees (P < 0.0001, P = 0.0251 and P = 0.0005, respectively). Due to the small numbers of patients with Grades 2 and 3 symptoms using the RTOG/EORTC scoring system, they were grouped with Grades 1 and 4 respectively forming two groups for statistical purposes. VEGF expression differed significantly between controls and group I and between controls and group II (P = 0.0001, P = 0.0009, respectively)., Conclusion: A significant increase in VEGF expression was found to correlate with clinical symptoms and endoscopic rectal mucosa changes in patients with ChRP, suggesting that it may play an important role in pathological angiogenesis., (Colorectal Disease © 2017 The Association of Coloproctology of Great Britain and Ireland.)

Purpose: To investigate the prophylactic and therapeutical effects of sildenafil in a model of acute radiation proctitis (ARP)., Methods: All experimental procedures of this study was examined by histopathological, immunohistochemical and transmission electron microscopic analysis., Results: Our histopathological evaluations indicated significant increases in lesion severity, cryptic apsis, cryptitis, cryptic distortion, reactive atypia and infiltration depth of the control (proctitis) group. While the prophylaxis group and the treatment group had significantly lower scores. High-dose group showed similar results as prophylaxis group. Histopathological findings of the prophylaxis group was more significant than the treatment group. Immunoreactivities of IL-1β, FGF-2, TNF- α and HIF-1α increased in the control group especially in the epithelial and cryptic regions. On the contrary, sildenafil application caused significant decreases of inflammatory markers in all treatment groups, specifically better results in the prophylaxis group., Conclusion: The sildenafil has anti-inflammatory effects on ARP, as well as protective effects against ARP and the protective effect of sildenafil surpasses its therapeutic effect histopathologically.

Background: Ulcerative proctitis, one of the disease types of ulcerative colitis, is considered one of the initial manifestations of ulcerative colitis. Prevention of aggravation of ulcerative proctitis is important for improving the prognosis of ulcerative colitis. Here we reviewed the epidemiology, diagnosis, and management of ulcerative proctitis., Summary: The number of patients with ulcerative proctitis is increasing. Disease extension occurs in many patients with ulcerative proctitis. Differential diagnosis from other chronic proctitis is important and should be performed based on the clinical history and endoscopical and histological features. Mesalazine suppository has been the first-line therapy for patients with ulcerative proctitis because of its high effectiveness and safety. Topical treatment of ulcerative proctitis, particularly using mesalazine suppository has been underused in clinical practice. Key Messages: Mesalazine suppositories are more effective than dose intensification of oral mesalazine for relapsed patients with maintenance dose of oral mesalazine. However, low adherence to rectal mesalazine has hindered remission in patients with ulcerative proctitis., (© 2018 S. Karger AG, Basel.)

The current study evaluated the role of Hey2 transcription factor in radiation-induced endothelial-to-mesenchymal transition (EndoMT) and its impact on radiation-induced tissue damage in mice. Phenotypic modifications of irradiated, Hey2 siRNA- and Hey2 vector plasmid-transfected human umbilical vein endothelial cells (HUVECs) resembling EndoMT were monitored by qPCR, immunocytochemistry and western blots. Subsequently, in mice, a Cre-LoxP strategy for inactivation of Hey2 specifically in the endothelium was used to study the biological consequences. Total body irradiation and radiation proctitis were monitored to investigate the impact of conditional Hey2 deletion on intestinal stem cells and microvascular compartment radiosensitivity, EndoMT and rectal damage severity. We found that EndoMT occurs in irradiated HUVECs with concomitant Hey2 mRNA and protein increase. While Hey2 silencing has no effect on radiation-induced EndoMT in vitro, Hey2 overexpression is sufficient to induce phenotypic conversion of endothelial cells. In mice, the conditional deletion of Hey2 reduces EndoMT frequency and the severity of rectal tissue damage. Our data indicate that the reduction in mucosal damage occurs through decline in stem/clonogenic epithelial cell loss mediated by microvascular protection. EndoMT is involved in radiation proctitis and this study demonstrates that a strategy based on the reduction of EndoMT mitigates intestinal tissue damage.

These 5 cases of atypical inflammatory lymphogranula venereum (LGV) serovar L2b presenting initially with edema and persistent painful ulceration illustrate that clinical manifestations of LGV in the current outbreak in men who have sex with men reflect the influence of both the serovars virulence and the host immune system and are not confined to proctitis. L2b serovar could have a particular high virulence profile, and the need for awareness of LGV as a cause of genital ulceration is crucial.

Purpose: Multiple features have been described for assessing inflammation in Crohn's disease (CD) in MR enterography, but have not been validated in perianal magnetic resonance imaging (MRI). Retrospectively, we studied which MRI features are valuable in assessing proctitis., Materials and Methods: CD patients (≥18 years) who underwent colonoscopy (reference standard) and perianal fistula MRI within 8 weeks were included. Seventeen MRI features were blindly scored by three observers and correlated to endoscopy (regression analysis). Reproducibility (multirater kappa, intraclass correlation coefficient) was determined for all three observer pairs. MRI features were considered relevant when significantly correlated to endoscopy for ≥2 observers, and reproducibility was ≥0.40 for ≥2 observer pairs., Results: Perianal MRI of 58 CD patients were included. Wall thickness, rectal mural fat, creeping fat, and size of mesorectal lymph nodes showed a significant correlation with endoscopy for ≥2 observers (p = 0.000-0.023, p = 0.011-0.172, p = 0.007-0.011 and p = 0.000-0.005, respectively) with a kappa/intraclass correlation coefficient of ≥0.60 for ≥2 observer pairs. Perimural T2 signal and perimural enhancement significantly correlated to endoscopy (all p values ≤0.05) for all three observers and the reproducibility was ≥0.40 for ≥2 observer pairs. Mural T2 signal and degree and pattern of T1 enhancement showed significant correlation to endoscopy for two observers, but with poor to moderate reproducibility., Conclusion: Wall thickness, mural fat, and mesorectal features (perimural T2 signal, perimural enhancement, creeping fat, and size of mesorectal lymph nodes) had significant correlation to endoscopy and were reproducible in diagnosing proctitis. Some established luminal features in MRE were considered not useful., Competing Interests: Compliance with ethical standards Funding This study received no funding. For none of the authors of this manuscript any financial interest is applicable. Disclosures Professor J. Stoker is a consultant for Robarts. Dr.C.Y. Ponsioen has received unconditional grants from Takeda, served as a consultant for Takeda and Abbvie, and received speaker’s fees from Takeda, MSD, Ferring, Dr. Falk, and Abbvie. All other authors, C.J. Tutein Nolthenius, S. Bipat, B. Mearadji, S. Spijkerboer, and A.D. Montauban van Swijndregt, have nothing to disclose. Informed consent The requirement for review by the Medical Ethical Committee or informed consent was waived because of the retrospective nature of this study with pre-existing data.

Aim: Ulcerative colitis (UC) is considered to be a disease of continuous mucosal inflammation extending proximally from the rectum. However, appendiceal orifice inflammation (AOI) is a skip lesion with segments of continuous involvement from the rectum. The aim of this study was to examine the clinical characteristics and clinical course, particularly focused on proximal extension, of UC in patients with AOI., Method: A retrospective evaluation of patients with UC who underwent total colonoscopy at the Department of Surgical Oncology, The University of Tokyo, from 2004 to 2014. The degree of AOI was graded endoscopically as follows: 0 (no inflammation); 1 (slight oedema); 2 (moderate inflammation); and 3 (marked inflammation). A total of 189 patient records were reviewed retrospectively. The presence of AOI was analysed with regard to the clinical information of each patient, and its association with proximal extension of proctitis or left-sided colitis was evaluated., Results: Of 189 patients with UC who underwent total colonoscopy at our institution, 92 were diagnosed with pancolitis, 50 with left-sided colitis and 47 with proctitis. Endoscopic findings of AOI were observed in 26 patients, including 11 (12.0%) with pancolitis, six (12.0%) with left-sided colitis and nine (19.1%) with proctitis. During follow up, proximal extension of the disease occurred in all nine patients with proctitis AOI., Conclusion: AOI is more frequently observed in patients with proctitis. Our results showed correlations between AOI and subsequent proximal extension of mucosal inflammation in patients with proctitis., (Colorectal Disease © 2016 The Association of Coloproctology of Great Britain and Ireland.)

Background: Since 2003, outbreaks of lymphogranuloma venereum (LGV) with anorectal syndrome have been increasingly recognized in many Western countries. All of them have been classified as LGV serovar L2b, mainly occurring in human immunodeficiency virus (HIV)-infected men who have had sex with men (MSM). We describe a series of 26 diagnosed cases of LGV proctitis in downtown Madrid, Spain, in 2014, after implementing routine diagnostic procedures for this disease in symptomatic MSM., Methods: We conducted an observational study of patients with symptomatic proctitis attending an outpatient infectious diseases clinic in Madrid, Spain during calendar year 2014. Clinical, epidemiological, laboratory, and therapeutic data were gathered and analyzed., Results: Twenty-six patients were included in the analysis. All were MSM, and 24 of them were HIV-positive. All patients reported having acute proctitis symptoms including tenesmus (85%), pain (88%), constipation (62%), or anal discharge (96%). Proctoscopy showed mucopurulent exudate (25 patients [96%]), and rectal bleeding, with mucosal erythema and/or oedema in all cases. Rectal swabs were obtained from all patients, and LGV serovar L2 was confirmed in all of them. The cure rate was 100% after standard treatments with doxycycline 100 mg twice per day for 3 weeks. Simultaneous rectal infections with other sexually transmitted pathogens (gonorrhoea, herpes simplex virus, Mycoplasma genitalium) and systemic sexually transmitted diseases (STDs) (syphilis, acute HIV, and hepatitis C infections) were also documented in 12 patients (46%), but these co-infections did not appear to influence the clinical manifestations of LGV., Conclusions: Anorectal LGV is a common cause of acute proctitis and proctocolitis among HIV-infected MSM who practice unprotected anal sex, and it is frequently associated with other rectal STDs. The implementation of routine screening and prompt diagnosis of these rectal infections should be mandatory in all clinical settings attended by HIV and STD patients.

Case 1: Following 2 years of rectal blood loss, a 31-year-old male was diagnosed with ulcerative pancolitis in 1978. Initial treatment consisted of both topical and systemic 5-aminosalicylic acids [5-ASAs], and remission was achieved. In both 1984 and 1986 he was hospitalised due to exacerbations necessitating treatment with intravenous corticosteroids. The following years went well, without disease activity, under treatment with 5-ASA. In 1997, at the age of 50 years, a surveillance colonoscopy showed a stenotic process with a macroscopic irregularity in the sigmoid region. Histology revealed at least high-grade dysplasia [HGD] and signs of an invasive growth pattern which could indicate colorectal cancer [CRC]. The patient underwent restorative proctocolectomy with ileal pouch-anal anastomosis [IPAA]. Histology of the resection specimen confirmed active inflammation in the colon and rectum and a carcinoma in situ was identified in the sigmoid colon without invasive growth. This patient did not have significant comorbidities-for example primary sclerosing cholangitis [PSC]-and the CRC family history was negative. What pouch surveillance strategy should be recommended?, Case 2: A 34-year-old man presented at our inflammatory bowel disease [IBD] centre with ulcerative proctitis. Ten years later, after an initially mild disease course, his disease progressed to a pancolitis. An 11-year period with multiple exacerbations [on average every 2 year, including hospitalisation] followed and treatment consisted of topical and systemic 5-ASAs with intermittent corticosteroids. In 1998, at the age of 65 years, a two-stage restorative proctocolectomy with IPAA was performed due to disease activity refractory to systemic corticosteroids. The colectomy specimen confirmed the diagnosis of ulcerative pancolitis without evidence for colorectal dysplasia or carcinoma. Other than steroid-induced diabetes mellitus, this patient had no comorbidities. His father died from CRC at unknown age. What pouch surveillance strategy should be recommended?, (Copyright © 2016 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Purpose: To determine whether participants taking angiotensin-converting enzyme inhibitors (ACEIs) and treated with radical radiation therapy with neoadjuvant/adjuvant hormone therapy have less incidence, severity, and duration of radiation proctitis., Methods and Materials: A propensity score analysis of 817 patients who underwent radical radiation therapy with neoadjuvant or adjuvant hormone therapy as primary line management in a cohort study during 2009 to 2013 was conducted. Patients were stratified as follows: group 1, hypertensive patients taking ACEIs (as a study group); group 2, nonhypertensive patients not taking ACEIs; and group 3, hypertensive patients not taking ACEIs (both as control groups). The incidence, severity, and duration of proctitis were the main outcome. χ(2) tests, Mann-Whitney U tests, analysis of variance, risk ratio (RR), confidence interval (CI), Kaplan-Meier plots, and log-rank tests were used., Results: The mean age of the participants was 68.91 years, with a follow-up time of 3.38 years. Based on disease and age-matched comparison, there was a statistically significant difference of proctitis grading between the 3 groups: χ(2) (8, n=308) = 72.52, P<.001. The Mann-Whitney U test indicated that grades of proctitis were significantly lower in hypertensive patients taking ACEIs than in nonhypertensive patients not taking ACEIs and hypertensive patients not taking ACEIs (P<.001). The risk ratio (RR) of proctitis in hypertensive patients taking ACEIs was significantly lower than in hypertensive patients not taking ACEIs (RR 0.40, 95% CI 0.30-0.53, P<.001) and in nonhypertensive patients not taking ACEIs (RR 0.58, 95% CI 0.44-0.77, P<.001). Time to event analysis revealed that hypertensive patients taking ACEIs were significantly different from the control groups (P<.0001). Furthermore, hypertensive patients taking ACEIs had significantly faster resolution of proctitis (P<.0001)., Conclusion: Patients who were taking ACEIs were significantly less likely to have high-grade proctitis after radical radiation therapy with neoadjuvant or adjuvant hormone therapy (P<.001). The intake of ACEIs was significantly associated with a reduced risk of radiation-induced proctitis and also with acceleration of its resolution., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: A temporary stoma is often created to protect a distal anastomosis in colorectal surgery. Short-chain fatty acids, mainly butyrate, are the major fuel source for the epithelium and their absence in the diverted tract may produce mucosal atrophy and inflammation., Aims: To investigate whether the administration of sodium butyrate enemas (Naburen(©), Promefarm, Italy) could prevent mucosal inflammation and atrophy and affect gene expression profiles after ileo/colostomy., Methods: We performed a randomized, double-blind, placebo-controlled clinical trial, in patients with enterostomy performed for inflammatory bowel disease, colorectal cancer or diverticulitis. Twenty patients were randomly allocated to receive 30ml of sodium butyrate 600mmol/L (group A) or saline (group B), b.i.d. for 30 days., Results: In group A endoscopic scores were significantly improved (p<0.01) while mucosal atrophy was reduced or unchanged; in group B mucosal atrophy was increased in 42.8% of patients. Despite the high dose of butyrate used, no short-chain fatty acids were detectable by gas chromatography-mass spectrometry in colorectal biopsies. Group A patients showed up-regulation of genes associated with mucosal repair such as Wnt signalling, cytoskeleton regulation and bone morphogenetic protein-antagonists., Conclusion: Butyrate enemas may prevent the atrophy of the diverted colon/rectum, thus improving the recovery of tissue integrity., (Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Introduction: In children treated surgically for first-time perianal abscesses, discovery and excision of concomitant fistulas may also be warranted., Aim: To evaluate children of varying age after incision and drainage of first-time perianal abscesses, examining recurrences rates with and without search for a fistula., Method: A retrospective review was conducted, analyzing children (ages 0-15 years) treated for first-time perianal abscesses at a tertiary pediatric surgical center, with a minimum follow-up of 6 months., Results: A total of 104 patients subjected to 112 treatments for first-time perianal abscesses were eligible. Surgical procedures constituted 84 (75%) of treatments, searching for fistulas in 49 (58%). In 34 (69%), fistulas were confirmed and treated. In the surgically treated subset, the recurrence rate was higher if no attempt was made to exclude a fistula (46%), as opposed to confirmed absence of a fistula (27%) or concurrent fistulotomy (9%; p = 0.02). Younger patients showed a higher recurrence rate (12/26; 46%), compared with older counterparts (11/58; 19%) (p = 0.002)., Conclusion: In children surgically treated for first-time perianal abscess, recurrence rates appear to be lowered by locating and treating coexisting fistulas.

Background Aims: Mesenchymal stromal cells (MSCs) have been reported to be a promising cell source in cell therapy, and large amounts of MSCs can easily be isolated from human amnion. Therapeutic irradiation for intra-pelvic cancer often causes radiation proctitis; however, there is currently no effective treatment. We therefore investigated the effect of transplantation of human amnion-derived MSCs (AMSCs) in rats with radiation proctitis., Methods: Amnion was obtained at cesarean delivery, and AMSCs were isolated and expanded. Sprague-Dawley rats were γ-irradiated (5 Gy/d) at the rectum for 5 days. On day 5, AMSCs (1 × 10(6) cells) were intravenously transplanted. Rats were killed on day 8. Histological analyses were performed, and messenger RNA expression of inflammatory mediators was measured. In vitro, after γ-irradiation of rat intestinal epithelial cells (IEC-6), the cells were cultured with AMSC-conditioned medium (CM). The effect of AMSC-CM was evaluated by measurement of caspase-3/7 activity, p53 transcription activity and quantitative reverse-transcription-polymerase chain reaction for p53-target genes., Results: Histological examination demonstrated that epithelial injury and infiltration of inflammatory cells in the rectum were significantly suppressed by transplantation of AMSCs. In vitro, the cell injury in IEC-6 cells induced by γ-irradiation was inhibited by AMSC-CM, which also inhibited the upregulation of p53 transcription activity, caspase-3/7 activity and p21 expression., Conclusions: Transplantation of AMSCs improved radiation proctitis, possibly through inhibition of cell injury and inflammatory reactions. AMSC transplantation should be considered as a new treatment for radiation proctitis., (Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

The endothelial-to-mesenchymal transition (EndoMT) is a crucial cellular process during heart development necessary to the formation of cardiac valves. This embryonic process reappears in several pathological situations, such as vascular injury or organ fibrosis of various etiologies, as a mediator of extracellular matrix-producing cells. Because radiation induces both vascular damage and fibrosis, we investigated whether radiation exposure induces EndoMT in primary human intestinal microvascular endothelial cells (HIMECs) and whether EndoMT contributes to radiation-induced rectal damage in humans and in a preclinical model of radiation proctitis in mice. Irradiated HIMECs show phenotypic hallmarks of radiation-induced endothelial cell activation in vitro. Moreover, HIMECs undergo changes in molecular expression pattern compatible with EndoMT, with up-regulation of mesenchymal markers and down-regulation of endothelial markers via transforming growth factor/Smad pathway activation. In vivo, EndoMT readily occurs in the human rectum after radiation therapy for rectal adenocarcinoma. Finally, EndoMT was observed in rectal mucosal and submucosal microvessels in a preclinical model of radiation proctitis in Tie2-green fluorescent protein reporter-expressing mice all along radiation proctitis development, also associated with transforming growth factor/Smad pathway activation. In conclusion, radiation-induced cell activation and tissue inflammation constitute a setting that fosters the phenotypic conversion of endothelial cells into mesenchymal cells. Therefore, EndoMT is identified as a potential participant in radiation-induced gut damage and may represent an interesting therapeutic target in cases of radiation-induced pelvic disease., (Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

In our series of 366 patients who received intensity-modulated radiation therapy (IMRT) for prostate cancer, radiation proctitis developed in 24 patients. We examined the endoscopic evidence and clinical characteristics of radiation proctitis in these patients. The onset time was 2-29 months after treatment, with bloody bowel discharge being the most common symptom (22 cases). Colonoscopy revealed that the lesions tended to be concentrated on the rectal right anterior wall. Severity, according to the Tada classification, was 0b or Ia in 70.8% of all cases. The incidence of radiation proctitis decreased, and the clinical and endoscopic findings showed only mild radiation proctitis after IMRT.