Severe Rectal Bleeding Research Articles

Case report: atypical presentation of mpox with massive hematochezia and prolonged viral shedding despite tecovirimat treatment

BackgroundThe outbreak of mpox that occurred between 2022 and 2023 is primarily being transmitted through sexual contact. As of now, there is no consensus on the recommended duration of isolation to prevent sexual transmission of the virus. Moreover, this particular mpox outbreak has presented with distinct complications in comparison to previous occurrences. In this report, we present a case involving severe rectal bleeding from an ulcer in a mpox patient with a history of engaging in receptive sexual contact.Case presentationA 30-year-old Korean man presented at the hospital with complaints of fever, multiple skin lesions, and anal pain. Monkeypox virus polymerase chain reaction (PCR) results were positive for skin lesions on the penis and wrist. The patient received a 12-day course of tecovirimat due to anal symptoms and perianal skin lesions. Following isolation for 12 days and after all skin scabs had naturally fallen off, with no new skin lesions emerging for a consecutive 48 hours—conforming to the criteria of the Korean Disease Control and Prevention Agency—the patient was discharged. However, 1 day after discharge, the patient returned to the hospital due to hematochezia. His hemoglobin level had significantly dropped from 14.0 g/dL to 8.2 g/dL. Sigmoidoscopy unveiled a sizable rectal ulceration with exposed blood vessels, prompting the application of hemostasis through metal clipping. Subsequent monkeypox virus real-time PCR conducted on rectal tissue and swabs yielded positive results (with cycle threshold values of 28.48 and 31.23, respectively). An abdominal CT scan exposed a perirectal abscess, for which ampicillin-sulbactam was administered.ConclusionThis case underscores the importance of monitoring for bleeding complications and confirming the resolution of rectal lesions before discharging patients from isolation, particularly in cases where patients have a history of engaging in receptive sexual contact with men or are presenting with anal symptoms.

Current status and future outlook of ultrasound treatment for prostate cancer.

Radical prostatectomy and radiation therapy are the standard treatment options for localized prostate cancer (PC). However, radical prostatectomy may cause the deterioration of urinary and sexual function, and radiation-induced hemorrhagic cystitis and severe rectal bleeding are risk factors for fatal conditions in patients after radiation therapy. With the recent development of magnetic resonance imaging (MRI) for the localization of clinically significant PC (csPC) and treatment modalities, "focal therapy", which cures csPC while preserving anatomical structures related to urinary and sexual functions, has become a minimally invasive treatment for localized PC. Based on the clinical results of transrectal high-intensity focused ultrasound (HIFU) for localized PC in the whole gland and focal therapy, HIFU is considered an attractive treatment option for focal therapy. Recently, the short-term clinical results of transurethral high-intensity directional ultrasound (HIDU) have been reported. With the resolution of some issues, HIDU may be commonly used for PC treatment similar to HIFU. Because HIFU and HIDU have limitations regarding the treatment of patients with large prostate calcifications and large prostate volumes, the proper use of these modalities will enable the treatment of any target area in the prostate. To establish a standard treatment strategy for localized PC, pair-matched and historically controlled studies are required to verify the oncological and functional outcomes of ultrasound treatment for patients with localized PC.

PSOR2 Presentation Time: 11:35 AM: Effect of SpaceOAR on Patient-Reported Rectal Bleeding Following External Beam Radiation Therapy and Cs-131 Prostate Brachytherapy Boost

<h3>Purpose</h3> To evaluate long-term patient reported rectal bleeding in patients with prostate cancer treated at our institution with and without SpaceOAR following external beam radiation therapy and Cesium-131 (131Cs) prostate LDR brachytherapy boost. <h3>Materials and Methods</h3> We started routinely offering SpaceOAR to patients treated with external beam radiation therapy and 131Cs prostate LDR brachytherapy boost from 2016 with goal of potentially reducing rectal toxicity, including late rectal bleeding. We analyzed patients treated with and without SpaceOAR with at least 6 months of follow-up, with treatment from January 2007 to February 2021. Patients were asked to fill out Expanded Prostate Cancer Index Composite (EPIC) QOL questionnaire pre-treatment and at each scheduled follow-up appointment. The EPIC questionnaire included the following categories related to rectal bleeding and bother from rectal bleeding. Rectal bleeding occurring more than "rarely" was deemed clinically significant and severe rectal bleeding was defined as occurring "usually" or "always". Clinically significant bother from rectal bleeding was defined as considering bleeding to be more than a "very small problem." Severe bother from rectal bleeding was defined as being a "moderate" or "big" problem. Univariate Cox regression was performed to assess for impact of SpaceOAR on incidence of clinically significant rectal bleeding, with censorship at maximum follow-up. <h3>Results</h3> 317 patients were included in the analysis, all of whom were treated with a combination of external beam radiation therapy and LDR brachytherapy boost. 172 patients (54.3%) had intermediate-risk prostate cancer, while 145 patients (45.7%) had high-risk disease. 157 patients (49.5%) received androgen deprivation therapy, while 160 patients (50.5%) did not. 87 patients (27.4%) underwent prostate LDR brachytherapy boost with SpaceOAR inserted in the operating room following completion of prostate seed implant, with remaining 230 patients (72.5%) treated without SpaceOAR. Median follow-up for patients who received SpaceOAR was 18 months (IQR 12-30 months), whereas median follow-up for patients who did not receive SpaceOAR was 54 months (IQR 36-72 months). Incidence of acute clinically significant rectal bleeding, occurring before 6 months, was 3.9% in the cohort treated without SpaceOAR and 3.4% in the cohort treated with SpaceOAR. Incidence of late clinically significant rectal bleeding was 19.6% without SpaceOAR and 0% with SpaceOAR. For patients who developed late clinically significant rectal bleeding, median time to development was 18 months (IQR 9-24 months). Prevalence of late clinically significant rectal bleeding at last follow-up was 3.5% without SpaceOAR. Incidence and prevalence of late severe rectal bleeding without SpaceOAR was 4.7% and 1.3%, respectively. Incidence of late clinically significant bother from rectal bleeding was 20% without SpaceOAR and 0% with SpaceOAR. Prevalence of late clinically significant bother from rectal bleeding at last follow-up was 4.3% without SpaceOAR. Incidence and prevalence of late severe bother from rectal bleeding without SpaceOAR was 10.9% and 2.2%, respectively. On univariate analysis, SpaceOAR utilization was significantly associated with reduction in incidence of clinically significant rectal bleeding (p=0.035, hazard ratio 0.033; 95% confidence interval 0.001-0.784). <h3>Conclusions</h3> Overall prevalence of late rectal bleeding following 131Cs LDR prostate brachytherapy at last follow-up was less than 5%. SpaceOAR was associated with lower incidence of clinically significant rectal bleeding occurring at 6 months post-treatment or later as assessed by the EPIC questionnaire. Given the lower median follow-up in the SpaceOAR group, additional follow-up is warranted to determine whether this reduction is maintained long-term.

S698 Bleeding Complications From Fecal Management Systems in the COVID Era: A Single Center Experience

Introduction: Fecal Management Systems (FMS) have become common practice in hospitalized patients with severe diarrhea, or pressure wounds. These devices allow diversion of stool away from the body in an enclosed system. Contraindications to FMS placement include hemorrhoids, anal strictures, rectal mucosal impairment and device use for greater than 29 days. Although FMS are generally safe and effective, severe rectal bleeding has been reported in a small number of studies and case reports though characteristics not well-defined. The goal of this study was to investigate patient characteristics with FMS use and subsequent development of severe bleeding complications. Methods: We reviewed endoscopy reports for rectal ulcerations and identified 16 patients who developed severe rectal bleeding from FMS at a large medical center from August 1, 2019 to August 1, 2021. Severe rectal bleeding was defined as requirement of blood transfusion, endoscopy or embolization. Demographics, medications, and hospitalization characteristics were extracted from the medical record. Mean, standard deviation, and percentages were calculated for variables of interest. Results: Patients who bled with FMS had prolonged hospitalizations (mean 67.4 days), and 50% (8/16) died during hospitalization (Table). 43.8% (7/16) had COVID-19 infection, and 75% (12/16) were cared for in intensive care units. 18.8% (3/16) were on antiplatelets, and 50% were on anticoagulation. 93.8% (15/16) of patients who bled with FMS required blood transfusion, receiving 6.1±6.3 units of blood during their hospital admission. 81.3% (13/16) required endoscopy, 12.5% (2/16) required second endoscopy for hemostasis, and 6.3% (1/16) required embolization by Interventional Radiology. Of note, 18.8% (3/16) patients had hemorrhoids, 18.8% (3/16) had FMS for longer than 29 days, and only 37.5% (6/16) had an order for a rectal tube placed. No severe bleeding complications occurred in the 10 months prior to COVID-19 pandemic. (Figure) Conclusion: FMS has clinical utility but carries risks of severe bleeding complications. It remains unclear how COVID-19 impacted rates of these complications as baseline utilization could not be assessed in our center. Careful attention to hemorrhoids, FMS placement > 29 days, and other relative contraindications like coagulopathy is important to improve patient safety. Interventions should be developed to ensure safe, appropriate FMS placement and timely removal of FMS to avoid adverse events.Figure 1.: Total number of fecal management system (FMS) severe bleeding complications from August 1, 2019-August 1, 2021. Table 1. - Characteristics of patients undergoing sigmoidoscopy or colonoscopy for bleeding from rectal tubes (n =16) Variable N (%) or mean (SD) Length of hospitalization (days) 67.4 (30.6) Death during hospitalization 8 (50.0) Hospitalization in intensive care unit (ICU) 13 (81.3) Age (years) 63.4 (14.9) Male sex 13 (81.3) RaceWhite or CaucasianBlack or African-AmericanAsian 8 (50.0)6 (37.5)2 (12.5) Body mass index 26.9 (6.7) History of hemorrhoids 3 (18.8) Immobility 12 (75.0) Mechanical ventilation 11 (68.8) Aspirin use 10 (62.5) Antiplatelet use 3 (18.8) Anticoagulant use 8 (50.0) NSAID use 2 (12.5) Bowel regimen use 12 (75.0) Vasopressor use 9 (56.3) COVID-19 diagnosis 7 (43.8) Rectal tube order placement 6 (37.5) Duration of rectal tube use (days) 18.5 (14.5) Rectal tube placement >29 days 3 (18.8) Receipt of blood transfusion 15 (93.8) Number of blood transfusions 6.1 (6.3)

S2654 Severe Rectal Bleeding due to Foreign Body Ingestion

Introduction: Foreign body ingestion is often seen in children and the elderly. Food particles such as chicken or fish bones are the most often ingested foreign bodies; however, most patients do not recall ingestion. Clinically, most foreign bodies pass through the GI tract without issue, however, complications occur in roughly 1% of cases. Complications of foreign body ingestion include bleeding, bowel obstruction, and perforation. We present a case of a 95-year-old female presenting with bright red blood per rectum found to have foreign body impaction with ulceration in the rectosigmoid region. Case Description/Methods: A 95-year-old female with past medical history of diverticulosis and GERD presented with a complaint of rectal bleeding. She had experienced 7 episodes of voluminous bright red blood per rectum with diffuse crampy abdominal pain. She had no history of previous GI bleeds. Her most recent colonoscopy was 25 years prior with diverticulosis only. DRE was positive for bloody stool and her hemoglobin was 10g/dL with a baseline of approximately 13. CT scan showed rectosigmoid wall thickening consistent with inflammation, diverticula and a metallic-like object in the proximal sigmoid colon (Figurea). The patient was started on piperacillin-tazobactam and prepared for flexible sigmoidoscopy occurring next morning. Endoscopy revealed areas of multiple diverticula, surrounding ulceration and bleeding in the rectosigmoid colon (Figureb); cold biopsy was taken of the ulceration. A foreign body was found in the sigmoid colon (Figurec) and was successfully removed with a Roth Net. The foreign body appeared to be swallowed chicken bone. Biopsy showed cellular debris and colonic mucosa with acute and chronic inflammation. Pathology identified the object as a bone fragment. Discussion: The differential diagnosis of gastrointestinal bleeding is broad, but rarely is foreign body obstruction in the rectosigmoid region considered. The object must traverse 25 feet of small bowel prior to ulcerating the colon. The most common sites of complication occur at the ileocecal and rectosigmoid regions due to luminal narrowing and anatomic angulation. If complication occurs, 10-20% of foreign bodies can be removed endoscopically; 1% or less require surgical intervention. Intestinal strictures, cancer, diverticular disease, and hernias increase risk of complications after foreign body ingestion. Diverticulosis was the only identifiable risk factor in our patient case making it a unique clinical presentation.Figure 1.: Images from left to right (1a) foreign body as seen on admission CT (1b) sigmoid colon ulceration with diverticula seen proximal (1c) foreign body as seen on approach.

Patient-related risk factors for late rectal bleeding after hypofractionated radiotherapy for localized prostate cancer: a single-center retrospective study

BackgroundSeveral studies have reported patient-related risk factors for late rectal bleeding following conventionally fractionated radiotherapy for prostate cancer. We investigated patient-related risk factors for late rectal bleeding after hypofractionated radiotherapy.MethodsA total of 231 patients with local or locally advanced prostate cancer treated with hypofractionated radiotherapy (70 or 67.2 Gy in 28 fractions) were evaluated retrospectively. All patients received intensity-modulated radiotherapy with daily image guidance. The relationships between late rectal bleeding and risk factors like diabetes, hypertension, cirrhosis, and anticoagulant use were analyzed.ResultsDuring a median follow-up of 23 months, the crude rates of grade ≥ 1, grade ≥ 2, and grade ≥ 3 late rectal bleeding were 23.8%, 16.9%, and 9.5%, respectively. Cirrhosis and anticoagulant use predicted an increased risk of grade ≥ 3 rectal bleeding in multivariable analyses (hazard ratio [HR] 14.37, 95% confidence interval [CI] 3.09–66.87, P = 0.001, and HR 2.93, 95% CI 1.14–7.55, P = 0.026, respectively). The non-anticoagulant group had a significantly superior 5-year freedom from grade ≥ 3 bleeding compared to the anticoagulant group in a propensity-weighted log-rank analysis (88.0% vs. 76.7%, P = 0.041). A receiver operating characteristic curve analysis revealed that rectal bleeding was minimized in the anticoagulant group if the equivalent dose at fractionation of 2 Gy (EQD2) V77 Gy of the rectum was < 4.5% or if the EQD2 V8.2 Gy was < 71.0%.ConclusionsPatients taking anticoagulants or those with cirrhosis had a significantly higher risk of severe late rectal bleeding than other patients after hypofractionated radiotherapy for prostate cancer in the present study. The bleeding risk could be lowered by minimizing hotspots in patients taking anticoagulants.

An Unusual Case of Rectal Bleed in an Section Adolescent: Solitary Rectal Ulcer Syndrome Mimicking Rectosigmoid Malignancy

Solitary Rectal Ulcer Syndrome (SRUS) is an uncommon rectal disorder. Severe rectal bleeding, anaemia and a mass on evaluation are a rare presentation of SRUS, and can pose as an endoscopic challenge in differentiating from other causes of rectal bleeding. The incidence of SRUS is 1 in 100,000 people per year. Hence, a high degree of suspicion and timely diagnosis is necessary. The present case case is about a 17-year-old female who presented with rectal bleeding. Physical evaluation revealed a large polypoidal rectal mass mimicking malignancy which later turned out to be SRUS. The patient improved with medical management. On outpatient follow-up, she had no complaints after a month and follow-up lower endoscopy and imaging later revealed complete healing within three months. Although uncommon, SRUS should be considered as a potential cause of lower gastrointestinal bleeding after sinister causes have been ruled out.

Sangrado Tardio Luego de Tratamiento con Macroligadura Elástica de Hemorroides

Objetivo: Presentar el caso infrecuente de sangrado tardío posterior al tratamiento con macroligadura elástica de hemorroides, tratamiento propuesto por A. Reis Neto.Caso Clínico: Mujer de 26 años con tratamiento de hemorroides con macroligadura elástica. A los 28 días es admitida en urgencia por proctorragia abundante sin signos de shock hipovolémico. Laboratorio: Hematocrito27%, Hemoglobina 8,9 mg/dl. Se realiza colonoscopia evidenciando la cicatriz de macroligadura con signos de coágulo desprendido sin sangrado activo. Se decide conducta expectante con tratamiento de la hipovolemia incial y anemia. Evoluciona sin resangrado con control endoscópico a los 60 y 180 (sin sangrado y excelentes resultados.Discusión: La macroligadura es una técnica alternativa para el tratamiento de hemorroides con excelentes resultados anatómicos y funcionales. Presenta menor dolor postoperatorio, bajo índice de complicaciones (ninguna severa o propia del método). No existen comunicaciones sobre sangrado tardío grave tanto en ligaduras convencionales como macroligadura.Conclusiones: Se presenta el primer caso comunicado a la fecha de un sangrado tardío en macroligaduras que fue resuelto en forma conservadora.

Administration of the vasopressin analog desmopressin for the management of bleeding in rectal cancer patients: results of a phase I/II trial

SummaryPurpose The vasopressin analog desmopressin (dDAVP) is known to increase plasma levels of hemostatic factors, and preclinical studies in colorectal cancer models have demonstrated that it hampers tumor vascularization and metastatic progression. We evaluated safety and preliminary efficacy of dDAVP in rectal cancer patients with bleeding, before receiving specific oncologic treatment with surgery, chemotherapy and/or radiotherapy. Methods Patients with rectal cancer having moderate or severe rectal bleeding were enrolled in an open-label, dose-finding trial. Intravenous infusions of dDAVP were administered during two consecutive days in doses from 0.25 to 2.0 µg/kg, using single or twice daily regimen. Bleeding was graded using a score based on the Chutkan scale and tumor perfusion was evaluated by dynamic contrast-enhanced magnetic resonance imaging. Results The trial accrued a total of 32 patients. Dose-limiting toxicity occurred in patients receiving 1 µg/kg or higher. The most prominent treatment-related severe adverse event was hyponatremia. Most patients receiving the maximum tolerated dose of 0.5 µg/kg showed at least a partial hemostatic response and 58% developed a complete response with absence of bleeding at day 4 and/or at the last follow-up at day 14. Tumor perfusion was decreased in two-thirds of patients after dDAVP treatment. Conclusions dDAVP appeared as a promising hemostatic agent in rectal cancer patients with bleeding. Randomized clinical trials to confirm its effectiveness are warranted.Clinical trial registrationwww.clinicaltrials.gov NCT01623206

P065 CHARACTERIZATION OF EARLY CLINICAL AND PHARMACOKINETIC RESPONSE PROFILES OF VEDOLIZUMAB: AN INTERIM ANALYSIS OF ENTERPRET, A PHASE 4 CLINICAL STUDY

Abstract Introduction Vedolizumab (VDZ), a gut-selective antibody that binds specifically to integrin α4β7, is approved for treatment of adults with moderate-to-severe ulcerative colitis (UC). An association between VDZ levels and clinical remission during induction therapy at Week (Wk) 6 was observed in pivotal trial data; the majority of nonresponders at Wk 6 had VDZ levels &amp;lt;40 μg/mL, and those with VDZ clearance &amp;gt;0.14 L/d had reduced efficacy outcomes (Osterman MT, et al. Aliment Pharmacol Ther. 2019). In the ongoing randomized controlled trial (ENTERPRET), we are evaluating whether dose escalation starting at Wk 6 in clinical nonresponders with high VDZ clearance (level &amp;lt;50 μg/mL) at Wk 5 leads to improved outcomes at Wk 30. This is an interim analysis of ENTERPRET in which baseline predictors of response at Wk 6 were investigated. Methods Adults with moderately to severely active UC received VDZ 300 mg IV on Day 1 and Wk 2. At Wk 5, VDZ concentration in serum was measured; clinical response was assessed at Wk 6 based on partial Mayo score (reduction in partial Mayo score ≥2 points and ≥25% from baseline [Day 1] with an accompanying decrease in rectal bleeding subscore ≥1 point or absolute rectal bleeding score ≤1 point). Descriptive analysis was used for these interim data, including baseline characteristics in responder and nonresponder groups. Results A total of 117 patients (mean age 41.2 years, 40.2% female) were analyzed; 112 were classified as a responder (n=55) or nonresponder (n=57) based on Wk 6 response. At baseline, mean disease duration was higher in nonresponders than responders (9.5 vs 7.1 years), with 47.4% of nonresponders having disease duration ≥7 years compared with 38.2% of responders. Endoscopic activity score was higher in nonresponders vs responders (49.1% vs 36.4% had severely active disease [Mayo endoscopic subscore=3]). 63.2% of nonresponders had a high stool frequency at baseline (Mayo subscore=3) compared with 49.1% of responders. 63.6% of responders had more severe rectal bleeding scores (Mayo subscore of 2–3) compared with 45.6% of nonresponders. More responders (67.3%) were anti-TNF–naïve at baseline than nonresponders (52.6%). At Wk 6, change in mean (SD) partial Mayo score from baseline was -4.2 (1.65) for responders and -0.2 (0.96) for nonresponders. Wk 5 mean VDZ serum concentrations were numerically lower in nonresponders (31.5 [SD=12.8] vs 40.3 [SD=15.3] μg/mL in responders). There were no unexpected treatment-emergent adverse events in either group. Conclusion Interim data from ENTERPRET show Wk 6 responders had higher VDZ serum concentrations at Wk 5 than nonresponders. Although current results are consistent with the hypothesis that lower response to VDZ at Wk 6 correlates with lower drug exposure, we await the final results of ENTERPRET to better understand the exposure-response relationship of VDZ.

Severe rectal bleeding caused by a small polypoid lobular capillary hemangioma.

Severe rectal bleeding caused by a small polypoid lobular capillary hemangioma.

3055 Solitary Rectal Ulcer Syndrome: A Rare Cause of Hematochezia

INTRODUCTION: Solitary rectal ulcer syndrome (SRUS) is an uncommon rectal disorder that may result in severe rectal bleeding. The term solitary rectal ulcer syndrome is a misnomer. Endoscopic findings in patients with SRUS can range from mucosal erythema alone to single or multiple ulcers and polypoid mass lesions. Here, we present a rare case of severe hematochezia occurring secondary to a solitary rectal ulcer. CASE DESCRIPTION/METHODS: The patient is a 37 year-old male with a medical history of alcohol abuse who presented to our emergency department complaining of three episodes of hematochezia accompanied by dizziness and lightheadedness that began the night prior. Notable workup in the emergency department included a complete blood count (CBC) showing a hemoglobin of 12.5 gm/dL. A fecal occult blood test was also done which returned positive. This was followed by a repeat CBC showing an acute drop in the hemoglobin to 9.8 gm/dL. The gastroenterology service was then consulted and performed a colonoscopy. This was done and showed a large cratered ulcer about two centimeters in size and a non-bleeding visible vessel noted approximately five centimeters from the anal verge (Figure 1). These were treated with BiCAP cautery and the three hemostatic clips. Biopsies were not taken given the high risk of bleeding and emergent nature of the procedure. After the procedure the patient remained hemodynamically stable with no further drops in hemoglobin. He was then discharged with follow up appointments for repeat colonoscopy. DISCUSSION: SRUS is an oftentimes-misdiagnosed condition. The prevalence of SRUS is not clear, but has an estimated incidence of 1 in 100,000 people per year. Its diagnosis can usually be accomplished through a combination of symptomatology, endoscopy, sigmoidoscopy, and the histologic finding of fibromuscular obliteration of the lamina propria. The pathogenesis if SRUS is not well known, but various factors contribute to its development. This includes straining, self-induced trauma, paradoxical contraction of puborectalis muscle and rectal prolapse, and intussusception. Treatment of SRUS is based on the symptoms and severity. Asymptomatic patient treatment options include dietary modification, patient education, and behavioral modification. Endoscopic treatment can be applied to control bleeding and allows the clinician to obtain a biopsy specimen. Surgical treatment is recommended for those who have full thickness and rectal prolapse.

Ten New Cases of Hermansky-Pudlak Syndrome in the Iberian Peninsula: Identification of Novel Genetic Variants in HPS3, HPS4, HPS6 and DTNBP1 Associated with Significant Clinical Complications

IntroductionHermansky-Pudlak syndrome (HPS) is an inherited platelet disorder characterized by bleeding diathesis, oculocutaneous albinism (OCA) and, sometimes, serious clinical complicationssuch as immunodeficiency, granulomatous colitis, and/or pulmonary fibrosis. Heterogeneous clinical symptoms and a large number of possible genetic culprits (10 HPS genes, >120 exons) complicate an unequivocal diagnosis of HPS. This study aimed to assess the clinical and platelet phenotype in ten patients with suspected HPS, and to identify the underlying genetic defects.MethodsTen patients from six families (F1 and F3 were Spanish, F2 was Turkish and F4, F5 and F6 were Portuguese) presenting with OCA (confirmed by skin biopsy) and bleeding diathesiswere included. Bleeding was evaluated by ISTH-BAT score. Phenotyping included, in patients with fresh blood samples available, platelet aggregation and ATP release, flow cytometry (FC), 14C-serotonin uptake and whole-mount electron microscopy (EM). Patients DNA was analyzed using two different targeted panels by high throughput sequencing (HTS). Sequence variants classification was performed according to ACMP recommendations.ResultsPatient characteristics are summarized in table 1. In F1, that had no history of consanguinity, there were two affected sisters. Patients 1 (P1) had several episodes of gastrointestinal bleeding (GI), which was attributed to granulomatous colitis. F2 is a consanguineous Turkish family, were P3 had severe rectal bleeding, requiring colectomy combined with ileostomy surgery. Pathological examination of the colon was reported as non-granulomatous colitis. Her older sister (P4) had exhibited dyspnea and shortness according to diffuse bilateral pulmonary fibrosis (BPF) diagnosis. In F3, P5 had been referred with acute GI bleeding secondary to angiodysplasia. In the non-consanguineous F4, HPS was first confirmed in P6, who showed blonde hair, nystagmus and low visual acuity; his older sister was diagnosed with HPS later, at the age of 56 years old (P7), because her OCA was masked using dark brown hair-coloring products. In P8, born from a non-consanguineous family (F5), HPS was suspected early in life, four months of age, upon recognition of OCA, nystagmus, deep visual deficiency and exotropia with compensatory torticollis. Lastly, in the consanguineous Portuguese family (F6), the two affected children (P9 and P10) had also showed a horizontal and torsional nystagmus and reduced visual activity. P10 also suffered from epilepsy and mild development delay. In phenotyping studies, the Spanish patients (P1, P2, P5) showed impaired platelet aggregation to mild agonists and reduced platelet dense granules by FC and EM. No platelet studies could be performed in F2. In Portuguese patients (F4, F5 and F6), the ATP release studies demonstrated a dense granule deficiency (Table 1). Molecular diagnosis was achieved, as a first-line approach, by means of HTS gene panels that revealed: a) F1 (P1 & P2) a homozygous deletion c.2054delC (p.P685L fs17*) in exon 13 of the HPS4, which had been previously reported in one Asian patient who showed BPF; b) F2 (P3 & P4): anovel missense homozygousvariant c.272T>C (p.L91P) in exon 4 of the HPS4. Remarkably, the phenotype of the two Turkish sisters was different, with one having had severe GI bleeding requiring colectomy, and the other had developed BPF. C) F3 (P5): a novel heterozygous variant c.2464C>T (p.R822*) in exon 13 of the HPS3 was detected; d) F4 (P6 & P7) and F5 (P8): here a nonsense variant c.307C>T (p.Q103*) was identified in exon 5 of the DTNBP1, which was previously reported in a Portuguese patient. E) F6 (P9 & P10): these patients carried a novel five base pair duplication in the single exon of HPS6, c.60_64dup (p.L22R fs*33).ConclusionsThis study reports 10 new HPS patients, which demonstrates the heterogeneous nature of this syndrome and the complex phenotype-genotype correlations. The novel HTStechnology has facilitated the molecular diagnosis of HPS in these patients. Among the underlying molecular pathology, we identified a novel p.L91P variant in HPS4 that is associated with a severe clinical phenotype.FundingGerencia Regional de Salud (GRS 1647/A/17), Fundación Séneca (19873/GERM/15), Instituto de Salud Carlos III (ISCIII, PI17/01966, PI17/01311,CB15/00055), Grupo de trabajo SETH and Instituto de Investigación Biomédica de Salamanca (IBSAL, IBY17/00006). [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Leech Infestation Presenting as Severe Rectal Bleeding

ABSTRACTLeech or Hirudinea is a major parasite in rural India. Normally, the leech attacks the skin and exposed areas. An 18‑year‑old child presented with bleeding per rectum for 1 day along with giddiness. A history revealed that while the boy was working in a field, had acrawling sensation in the perianal area. After admission, the patient was resuscitated with crystalloids and a limited colonoscopy revealed a rectal ulcer with a leech head attached to its base. The hooklets were removed using foreign body removal forceps and injection Adrenaline at 1:10,000 dilutions was injected in 1 ml aliquots into four quadrant to achieve hemostasis. There was no postprocedure complication. Leech infestation can present with exsanguinating acute severe lower gastrointestinal bleed.

The Use of Octreotide in Refractory Gastrointestinal Bleeding Due to Crohnʼs Disease

A 36 year male with history of Crohn's disease complicated by anal stricture and anorectal fistula presented to the emergency department with one day of severe rectal bleeding. His Crohn's disease was diagnosed at age six and he underwent a left hemicolectomy at age 14. He had been treated with mesalamine, adalimumab, infliximab with 6-mercaptopurine in the past, and was currently being treated with vedolizumab. On presentation to the emergency room he was tachycardic. His abdomen was mildly distended with decreased bowel sounds. His labs were significant for leukocytosis (WBC 16.9) and anemia (Hemoglobin 10.8 g/dL). A CT scan showed nonspecific colitis and narrowing of the mid descending colon. He was treated with intravenous levofloxacin and metronidazole and after unremarkable stool cultures, intravenous methylprednisolone was added. He continued to have hematochezia and his hemoglobin continued to drop (7.4 g/dL, followed by 6.9 g/dL). He was transferred to the medical intensive care unit and was transfused four units of packed red blood cells. He was then started on intravenous octreotide 50 mcg/hr. After starting octreotide no further episodes of bleeding occurred. Repeat hemoglobin was 11.1 g/dL and remained stable. Colonoscopy was performed which showed skip areas of ulceration including the rectum and ileocecal valve. The intravenous octreotide was continued for a total of 72 hours. The patient was discharged home and has had no further episodes of bleeding. Octreotide is an analog of somatostatin. It is known to decrease splanchnic blood flow, and it may have a local vasoconstrictive effect. For these reasons it is a Class 1, Level A recommendation for patients with esophageal variceal bleeding (1). The effect of octreotide on other types of gastrointestinal bleeding is less clear. Andrews et al reported a patient with severe hematochezia due to CMV colitis who continued to bleed despite ganciclovir, but stopped bleeding after initiation of octreotide (2). Our case is the first reported use of octreotide to control lower gastrointestinal bleeding due to severe Crohn's colitis. Considering its safety profile, octreotide may be considered in patients with refractory lower gastrointestinal bleeding. Further randomized control trials are warranted.

PO-0873: Modelling severe late rectal bleeding in a large pooled population of prostate cancer patients

PO-0873: Modelling severe late rectal bleeding in a large pooled population of prostate cancer patients

Modeling severe late rectal bleeding: Results on a large pooled population of prostate cancer patients.

82 Background: To develop a model for grade 3 (G3) late rectal bleeding (LRB) after radical radiotherapy (RT) for prostate cancer, in a pooled population from 2 large prospective trials: Airopros0102 (Fellin RO2014) and TROG 03.04 RADAR (Ebert IJROBP2015). Methods: Both trials included patients (pts) treated with 3DCRT at 66-80Gy, conventional fractionation. Planning data were available for all pts, G3 LRB was prospectively scored using the SOMA/LENT, with a minimum follow-up of 3 years. Rectal dose-volume histograms were reduced to Equivalent Uniform Dose (EUD) calculated with volume parameter n derived by 3 studies: n=0.06 (Rancati RO2004), n=0.05 (Rancati RO2011) and n=0.018 (Defraene IJROBP2011). EUD was inserted into multivariable logistic regression (MVL) together with clinical and treatment features. Irradiation of seminal vesicles (SV), irradiation of pelvic nodes, hormonal therapy, hypertension, previous abdominal surgery (SURG), use of anticoagulants, diabetes, cardiovascular diseases and presence of acute toxicity were considered as potential dose-modifying factors. Goodness of fit was evaluated with Hosmer Lemeshow test (HL), calibration through calibration slope and AUC was used for discrimination power. Results: 1,337 pts were available: 708 RADAR and 669 Airopros. G3 LRB was scored in 95 pts (7.1%): 62 RADAR and 33 Airopros. EUD calculated with n=0.05 was the best dosimetric predictor for G3 LRB. A 4-variable MVL model was fitted including EUD (OR=1.07 p=0.16), SV (OR=4.75 p&lt;0.001), SURG (OR=2.30 p=0.02) and cardiovascular disease (OR=1.42 p=0.18). AUC=0.63, calibration slope=0.99 (R^2=0.89), p for HL=0.43. Inclusion of acute toxicity (OR=2.34 p&lt;0.001) slightly improved AUC (0.65), confirming a possible role of consequential injury. Conclusions: EUD with n=0.05 was predictive of G3 LRB in this pooled population, confirming the importance of sparing the rectum from high doses. Irradiation of seminal vesicles together with the presence of cardiovascular disease and previous abdominal surgery were relevant dose-modifying factors highly impacting the incidence of G3 LRB. The study was funded by: AIRC IG16087, Fondazione Monzino, NHMRC (300705, 455521, 1006447)

Predictors of prostate cancer in ultrasound-guided transperineal saturation biopsy in Turkish men with multiple prior negative biopsies.

Transperineal prostate biopsy (STPB) is associated with an improved cancer detection rate and an increase in anterior and apical prostate cancers compared to standard transrectal biopsy. A total of 48 men with at least two sets of prior prostate biopsies underwent transrectal ultrasound-guided STPB. Prostate rebiopsy indications were serum prostate-specific antigen (PSA) levels greater than 2.5 ng/mL and/or abnormal digital rectal examination and/or presence of high-grade prostatic intraepithelial neoplasia (HGPIN; ≥2 cores) or atypical small acinar proliferation (ASAP) at previous biopsies. The procedure was performed at dorsal lithotomy position under general anesthesia using a perineal 0.5 cm brachytherapy template attached to the transrectal ultrasound probe. Specimens from each zone were sent separately for pathological examination. Mean PSA level at STPB was 15.9 ng/mL (range 4.03 to 59.57). An average of 54.5 cores was obtained. Prostate adenocarcinoma was detected in 15 of 48 (31%) patients. Mean percentage of malignant cores was 11.9%. Multivariate logistic regression analysis revealed that age and presence of ASAP or HGPIN at previous biopsies were independent predictors of prostate cancer (p&lt;0.05). No major complications, including sepsis and severe urinary or rectal bleeding, were observed in any of the patients. Five patients (10%) developed acute urinary retention after the procedure requiring urethral catheterization. Considerable number of patients with negative multiple biopsies were diagnosed with prostate cancer. STPB is a well-tolerated procedure with minimal morbidity, which can be considered for the diagnosis of prostate cancer in patients with previous negative biopsies.

L13a-dependent translational control in macrophages limits the pathogenesis of colitis.

Sustained inflammation from infiltrated immune cells plays a pivotal role in the pathogenesis of ulcerative colitis (UC). Previously, we established the role of ribosomal protein L13a in the regulation of an inflammation-responsive post-transcriptional operon in myeloid cells. However, the role of this protein as a molecular cue to control the severity of colitis is not known. Here, we examined whether L13a-dependent translational control in macrophages could serve as an endogenous defense against colitis. The administration of dextran sodium sulfate induced experimental colitis in myeloid-specific L13a-knockout (KO) and control mice. Pathological scoring and injury to the colon mucosa evaluated the severity of colitis. The steady-state levels of several pro-inflammatory cytokines and chemokines were determined through ELISA and polyribosome profile analysis. Rapid weight loss, severe rectal bleeding, shortening of the colon, and significantly reduced survival rate were observed in the KO mice. Histopathological analysis of the colons of KO mice showed a severe disruption of epithelial crypts with immune cell infiltrates. Elevated levels of several inflammatory cytokines and chemokines and abrogation of their naturally imposed translational silencing were observed in the colons of the KO mice. Higher serum levels of several pro-inflammatory cytokines and the release of gut bacteria and endotoxins into the blood streams of KO mice were detected, suggesting the amplification of the inflammatory response to septicemia. Taken together, these results reveal an essential role for L13a in the endogenous protection against UC and demonstrate the potential for new therapeutic opportunities through the deliberate promotion of this mechanism.

Rectal bleeding after radiation therapy for endometrial cancer

Background and purposeThe goals of this study were to determine the rate and risk factors of rectal bleeding (RB) after external beam radiotherapy and vaginal brachytherapy (EBRT +VB), and to compare these data to previously unreported RB rates from PORTEC-2 patients receiving EBRT or VB alone. Materials and methodsRetrospective chart review identified 212 endometrial cancer patients receiving adjuvant EBRT+VB between 2006 and 2013. Patient-reported RB data were also obtained from PORTEC-2 patients randomized to EBRT (n=166) or VB (n=182). The two populations were compared using an RB scale of symptom severity. ResultsAfter a median 35months, 17.9% of EBRT+VB patients (n=38) experienced any RB with 1.9% (n=4) having bleeding requiring intervention. Age ⩽70years was the only predictor of RB (OR 2.8; 95% CI 1.1–8.7; p=0.027). Rates of patient-reported RB after EBRT were similar with 15.0% (n=25) having any RB and 0.6% (n=1) having “very much” bleeding. On regression analysis, any EBRT (either EBRT alone or EBRT+VB) increased the risk of RB compared to those who received VB alone (OR 3.0; p=0.0028; 95% CI 1.4–6.7). The rates of more severe RB were low and did not significantly differ between treatments. ConclusionsSignificant RB is rare after radiation. EBRT has higher rates of rectal bleeding than VB. The addition of VB to EBRT does not significantly alter bleeding rates.