Resistencia antibiótica y aspectos clínicos de Neisseria gonorrhoeae anorrectal en un hospital de CABA, Argentina / Antimicrobial resistance and clinical aspects in anorectal Neisseria gonorrhoeae in a hospital in CABA, Argentina

La infección por Neisseria gonorrhoeae (NG) es considerada de alta prioridad en salud pública, por su capacidad para desarrollar resistencia a la mayoría de los antibióticos empleados para tratarla. La presentación anorrectal suele ser asintomática y frecuente en hombres que tienen sexo con hombres (HSH). En Argentina, se recomienda terapia antibiótica dual (ceftriaxona+azitromicina/doxiciclina) como primera línea empírica. Este estudio observacional y retrospectivo se realizó para evaluar el porcentaje de positividad de NG anorrectal, el perfil de sensibilidad a penicilina, tetraciclina, ciprofloxacina, ceftriaxona, cefixima y azitromicina, así como los aspectos clínicos-epidemiológicos de los pacientes atendidos entre 20/10/2015 y 20/03/2020 en consultorios coloproctológicos de un hospital público. Se detectaron 55/436 hisopados rectales positivos para NG (13%). El 95% era HSH y 71%, VIH+. En 18/55 NG fue la única infección. Las co-infecciones más frecuentes: HPV (38%) y C. trachomatis (35%). La sensibilidad a cefalosporinas de espectro extendido (CEE) y a azitromicina fueron 100% y 98%, respectivamente. Se observó la emergencia local de los primeros cinco aislamientos de NG anorrectal con sensibilidad reducida (SR) a CEE, el primer aislamiento con categoría no-sensible a azitromicina y otro con SR a azitromicina concomitantemente con SR a CEE. Aunque el uso de terapia empírica dual sigue siendo adecuado para nuestra institución, se observó la emergencia de aislamientos con SR y NS a las drogas de primera línea, evidenciando la importancia de la vigilancia epidemiológica a nivel local para definir los tratamientos empíricos.

Neisseria gonorrhoeae (NG) infection is considered a high public health priority because of its ability to develop resistance to most of the antibiotics used to treat it.The anorectal presentation is generally asymptomatic and frequent in men who have sex with men (MSM). In Argentina, dual therapy (ceftriaxone+azithromycin/doxycycline) is recommended as first line empiric therapy.This observational and retrospective study was conducted to evaluate the percentage of anorectal NG positivity, the susceptibility profile to penicillin, tetracycline, ciprofloxacin, ceftriaxone, cefixime and azithromycin, as well as the clinical-epidemiological aspects of patients attended between 20/10/2015 and 20/03/2020 in coloproctology of a public hospital.We detected 55/436 positive rectal swabs for NG (13%). 95% were MSM and 71% were PLHIV. In 18/55 NG was the only infection. The most frequent co-infections: HPV (38%) and C. trachomatis (35%).Susceptibility to extended-spectrum cephalosporins (ESCs) and azithromycin was 100% and 98%, respectively. Local emergence of the first five anorectal NG isolates with decreased susceptibility (DS) to ESCs, the first isolate with nonsusceptible category to azithromycin and another with DS to azithromycin concomitantly with DS to ESCs were observed.Although the use of dual empirical therapy continues to be adequate for our institution, the emergence of isolates with DS and NS to first-line drugs was observed, evidencing the importance of epidemiological surveillance at the local level to define empirical treatments

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.

Effects of Mesenchymal Stem Cells Treatment on Radiation-Induced Proctitis in Rats.

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 1×106 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.

[A case of ischemic proctitis caused by impaired venous blood flow 11 months after surgery for sigmoid colon cancer].

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.

A Randomized Controlled Trial of Novel Treatment for Hemorrhagic Radiation Proctitis.

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.
.

Multi-donor multi-course faecal microbiota transplantation relieves the symptoms of chronic hemorrhagic radiation proctitis: A case report.

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.

Long-term outcomes of patients with ulcerative proctitis: Analysis from a large referral centre cohort.

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.

Evaluation of Stromal Vascular Fraction Properties and Histological Changes of Regenerating Tissue during Healing of Radiation-Induced Lesions in the Rectum.

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.

Association between acute histopathological changes of rectal walls and late radiation proctitis following radiotherapy for prostate cancer.

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.

Proctitis in gay and bisexual men. Are microscopy and proctoscopy worthwhile?

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). χ2 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.

MRI- and PET-Guided Interstitial Brachytherapy for Postsurgical Vaginal Recurrences of Cervical Cancer: Results of Phase II Study.

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, 18F-flouro-deoxyglucose (18F-FDG), 18F-flouro thymidine (18F-FLT) and 18F-flouromisonidazole (18F-F Miso) positron emission tomography (PET) and received external radiation (50 Gy/25 fractions for 5 weeks) and weekly cisplatin (40 mg/m2). 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.

Successful treatment of severe perianal Crohn's disease with infliximab in an HIV-positive patient.

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.

Efficacy and complications of argon plasma coagulation for hemorrhagic chronic radiation proctitis.

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 cm2 (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 cm2 (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 cm2.

Malignant and Nonmalignant Complications of the Rectal Stump in Patients with Inflammatory Bowel Disease.

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.

Duodenal and Rectal Mucosa Inflammation in Patients With Non-celiac Wheat Sensitivity.

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.

Early Onset Allergic Proctitis in a Preterm Neonate-A Case Report and Review of the Literature.

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.

A Case of Asymptomatic Syphilitic Proctitis.

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.

Effects of Supplemental Calcium and Vitamin D on Expression of Toll-Like Receptors and Phospho-IKKα/ß in the Normal Rectal Mucosa of Colorectal Adenoma Patients.

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 D3 (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/ß (pIKKα/ß), 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/ß 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/ß. 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/ß 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.

Effects of mesalazine enemas on lymphoid follicular proctitis.

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.