Hemostatic spray powder TC-325 in the primary endoscopic treatment of peptic ulcer-related bleeding: multicenter international registry.

BACKGROUND: Upper gastrointestinal bleeding (UGIB) is a leading cause of morbidity and is associated with a 2 % - 17 % mortality rate in the UK and USA. Bleeding peptic ulcers account for 50 % of UGIB cases. Endoscopic intervention in a timely manner can improve outcomes. Hemostatic spray is an endoscopic hemostatic powder for GI bleeding. This multicenter registry was created to collect data prospectively on the immediate endoscopic hemostasis of GI bleeding in patients with peptic ulcer disease when hemostatic spray is applied as endoscopic monotherapy, dual therapy, or rescue therapy. METHODS: Data were collected prospectively (January 2016 - March 2019) from 14 centers in the UK, France, Germany, and the USA. The application of hemostatic spray was decided upon at the endoscopist's discretion. RESULTS: 202 patients with UGIB secondary to peptic ulcers were recruited. Immediate hemostasis was achieved in 178/202 patients (88 %), 26/154 (17 %) experienced rebleeding, 21/175 (12 %) died within 7 days, and 38/175 (22 %) died within 30 days (all-cause mortality). Combination therapy of hemostatic spray with other endoscopic modalities had an associated lower 30-day mortality (16 %, P < 0.05) compared with monotherapy or rescue therapy. There were high immediate hemostasis rates across all peptic ulcer disease Forrest classifications. CONCLUSIONS: This is the largest case series of outcomes of peptic ulcer bleeding treated with hemostatic spray, with high immediate hemostasis rates for bleeding peptic ulcers.

Hemostatic powder TC-325 treatment of malignancy-related upper gastrointestinal bleeds: International registry outcomes.

BACKGROUND AND AIM: Upper gastrointestinal tumors account for 5% of upper gastrointestinal bleeds. These patients are challenging to treat due to the diffuse nature of the neoplastic bleeding lesions, high rebleeding rates, and significant transfusion requirements. TC-325 (Cook Medical, North Carolina, USA) is a hemostatic powder for gastrointestinal bleeding. The aim of this study was to examine the outcomes of upper gastrointestinal bleeds secondary to tumors treated with Hemospray therapy. METHODS: Data were prospectively collected on the use of Hemospray from 17 centers. Hemospray was used during emergency endoscopy for upper gastrointestinal bleeds secondary to tumors at the discretion of the endoscopist as a monotherapy, dual therapy with standard hemostatic techniques, or rescue therapy. RESULTS: One hundred and five patients with upper gastrointestinal bleeds secondary to tumors were recruited. The median Blatchford score at baseline was 10 (interquartile range [IQR], 7-12). The median Rockall score was 8 (IQR, 7-9). Immediate hemostasis was achieved in 102/105 (97%) patients, 15% of patients had a 30-day rebleed, 20% of patients died within 30 days (all-cause mortality). There was a significant improvement in transfusion requirements following treatment (P < 0.001) when comparing the number of units transfused 3 weeks before and after treatment. The mean reduction was one unit per patient. CONCLUSIONS: Hemospray achieved high rates of immediate hemostasis, with comparable rebleed rates following treatment of tumor-related upper gastrointestinal bleeds. Hemospray helped in improving transfusion requirements in these patients. This allows for patient stabilization and bridges towards definitive surgery or radiotherapy to treat the underlying tumor.

Outcomes from an international multicenter registry of patients with acute gastrointestinal bleeding undergoing endoscopic treatment with Hemospray.

BACKGROUND AND AIM: Acute gastrointestinal bleeding carries poor outcomes unless prompt endoscopic hemostasis is achieved. Mortality in these patients remains significant. Hemospray is a novel intervention that creates a mechanical barrier over bleeding sites. We report the largest dataset of patient outcomes after treatment with Hemospray from an international multicenter registry. PATIENTS AND METHODS: Prospective data (Jan 2016-May 2018) from 12 centers across Europe were collected. Immediate hemostasis was defined as endoscopic cessation of bleeding within 5 min after application of Hemospray. Rebleeding was defined as subsequent drop in hemoglobin, hematemesis, persistent melena with hemodynamic compromise post-therapy. RESULTS: Three hundred and fourteen cases were recruited worldwide (231 males, 83 females). Median pretreatment Blatchford score was 11 (IQR: 8-14) and median complete Rockall score (RS) was 7 (IQR: 6-8) for all patients. Peptic ulcer disease (PUD) was the most common pathology (167/314 = 53%) and Forrest Ib the most common bleed type in PUD (100/167 = 60%). 281 patients (89.5%) achieved immediate hemostasis after successful endoscopic therapy with Hemospray. Rebleeding occurred in 29 (10.3%) of the 281 patients who achieved immediate hemostasis. Seven-day and 30-day all-cause mortality were 11.5% (36/314) and 20.1% (63/314), respectively (lower than the predicted rates as per the RS). Similar hemostasis rates were noted in the Hemospray monotherapy (92.4%), combination therapy (88.7%) and rescue therapy (85.5%) groups. CONCLUSIONS: These data show high rates of immediate hemostasis overall and in all subgroups. Rebleeding and mortality rates were in keeping/lower than predicted rates.

Hemospray® (hemostatic powder TC-325) as monotherapy for acute gastrointestinal bleeding: a multicenter prospective study.

Background: Hemostatic powders are used as second-line treatment in acute gastrointestinal (GI) bleeding (AGIB). Increasing evidence supports the use of TC-325 as monotherapy in specific scenarios. This prospective, multicenter study evaluated the performance of TC-325 as monotherapy for AGIB. Methods: Eighteen centers across Europe and USA contributed to a registry between 2016 and 2022. Adults with AGIB were eligible, unless TC-325 was part of combined hemostasis. The primary endpoint was immediate hemostasis. Secondary outcomes were rebleeding and mortality. Associations with risk factors were investigated (statistical significance at P≤0.05). Results: One hundred ninety patients were included (age 51-81 years, male: female 2:1), with peptic ulcer (n=48), upper GI malignancy (n=79), post-endoscopic treatment hemorrhage (n=37), and lower GI lesions (n=26). The primary outcome was recorded in 96.3% (95% confidence interval [CI]: 92.6-98.5) with rebleeding in 17.4% (95%CI 11.9-24.1); 9.9% (95%CI 5.8-15.6) died within 7 days, and 21.7% (95%CI 15.6-28.9) within 30 days. Regarding peptic ulcer, immediate hemostasis was achieved in 88% (95%CI 75-95), while 26% (95%CI 13-43) rebled. Higher ASA score was associated with mortality (OR 23.5, 95%CI 1.60-345; P=0.02). Immediate hemostasis was achieved in 100% of cases with malignancy and post-intervention bleeding, with rebleeding in 17% and 3.1%, respectively. Twenty-six patients received TC-325 for lower GI bleeding, and in all but one the primary outcome was achieved. Conclusions: TC-325 monotherapy is safe and effective, especially in malignancy or post-endoscopic intervention bleeding. In patients with peptic ulcer, it could be helpful when the primary treatment is unfeasible, as bridge to definite therapy.

Retrospective comparison of G-EYE balloon-colonoscopy with standard colonoscopy for increased adenoma detection rate and reduced polyp removal time.

Background and study aims The newly introduced G-EYE colonoscope (G-EYE) employs a balloon, installed at the bending section of a standard colonoscope (SC), for increasing adenoma detection and stabilizing the colonoscope tip during intervention. This retrospective work explores the effect of introducing G-EYE into an SC endoscopy room, in terms of adenoma detection and polyp removal time. Patients and methods This was a single-center, retrospective study. Historical data from patients who underwent colonoscopy prior to, and following, introduction of G-EYE into a particular endoscopy room were collected and analyzed to determine adenoma detection rate (ADR), adenoma per patient (APP), and polyp removal time (PRT), in each of the SC and G-EYE groups. Results Records of 1362 patients who underwent SC and 1433 subsequent patients who underwent G-EYE colonoscopy in the same endoscopy unit by the same endoscopists were analyzed. Following G-EYE introduction, overall ADR increased by 37.5 % ( P  < 0.0001) from 39.2 % to 53.9 %, the serrated adenoma rate increased by 47.3 % from 27.9 % to 41.1 % ( P  < 0.0001), and the APP increased by 50.6 % from 0.79 to 1.19 ( P  < 0.0001). The number of advanced adenomas increased by 32.7 %, from 19.6 % to 26.0 % of all adenomas ( P  < 0.0001). With G-EYE, average PRT was reduced overall by 29.5 % ( P  < 0.0001), and particularly for endoscopic mucosal resection (EMR) by 37.5 % for polyps measuring ≥ 5 mm to ≤ 20 mm ( P  < 0.0001) and by 29.4 % for large polyps > 20 mm ( P  < 0.0001). Conclusions Introduction of G-EYE to an SC endoscopy room yielded considerable increase in ADR and notable reduction in PRT, particularly with the EMR technique. G-EYE balloon colonoscopy might increase the effectiveness of colorectal cancer screening and surveillance colonoscopy, and can shorten the time of endoscopic intervention.

Outcomes of Hemospray therapy in the treatment of intraprocedural upper gastrointestinal bleeding post-endoscopic therapy.

INTRODUCTION: With increasing advances in minimally invasive endoscopic therapies and endoscopic resection techniques for luminal disease, there is an increased risk of post-procedure bleeding. This can contribute to significant burden on patient's quality of life and health resources when reintervention is required. Hemospray (Cook Medical, North Carolina, USA) is a novel haemostatic powder licensed for gastrointestinal bleeding. The aim of this single-arm, prospective, non-randomised multicentre international study is to look at outcomes in patients with upper gastrointestinal bleeds following elective endoscopic therapy treated with Hemospray to achieve haemostasis. METHODS: Data was prospectively collected on the use of Hemospray from 16 centres (January 2016-November 2019). Hemospray was used during the presence of progressive intraprocedural bleeding post-endoscopic therapy as a monotherapy, dual therapy with standard haemostatic techniques or rescue therapy once standard methods had failed. Haemostasis was defined as the cessation of bleeding within 5 min of the application of Hemospray. Re-bleeding was defined as a sustained drop in haemoglobin (>2 g/l), haematemesis or melaena with haemodynamic instability after the index endoscopy. RESULTS: A total of 73 patients were analysed with bleeding post-endoscopic therapy. The median Blatchford score at baseline was five (interquartile range 0-9). The median Rockall score was six (interquartile range 5-7). Immediate haemostasis following the application of Hemospray was achieved in 73/73 (100%) of patients. Two out of 57 (4%) had a re-bleed post-Hemospray, one was following oesophageal endoscopic mucosal resection and the other post-duodenal endoscopic mucosal resection. Both patients had a repeat endoscopy and therapy within 24 h. Re-bleeding data was missing for 16 patients, and mortality data was missing for 14 patients. There were no adverse events recorded in association with the use of Hemospray. CONCLUSION: Hemospray is safe and effective in achieving immediate haemostasis following uncontrolled and progressive intraprocedural blood loss post-endoscopic therapy, with a low re-bleed rate.

Endoscopic and angiographic management of lower gastrointestinal bleeding: Review of the published literature.

Lower gastrointestinal bleeding is common and occurs often in elderly patients. In rare cases it is associated with hemorrhagic shock. A large number of such bleedings, which are often caused by colon diverticula, subside spontaneously. Alternatively they can be treated by endoscopic procedures successfully. Given the aging population of our society, the rising incidence of lower gastrointestinal tract bleeding and new anticoagulant therapies, some of the bleedings tend to be severe. Colonoscopy is the established standard procedure for the diagnosis and treatment of lower gastrointestinal bleeding. However, a small number of patients experience re-bleeding or shock; their bleeding does not resolve spontaneously and cannot be treated successfully by endoscopic procedures. In such patients, interventional radiology is very useful for the detection of bleeding and the achievement of hemostasis. Against this background we performed a literature search using PubMed to identify all relevant studies focused on the endoscopic and radiological management of lower gastrointestinal bleeding and present recent conclusions on the subject.

A guide to multimodal endoscopy imaging for gastrointestinal malignancy - an early indicator.

Multimodality imaging is an essential aspect of endoscopic surveillance for the detection of neoplastic lesions, such as dysplasia or intramucosal cancer, because it improves the efficacy of endoscopic surveillance and therapeutic procedures in the gastrointestinal tract. This approach reveals mucosal abnormalities that cannot be detected by standard endoscopy. Currently, these imaging techniques are divided into those for primary detection and those for targeted imaging and characterization, the latter being used to visualize areas of interest in detail and permit histological evaluation. This Review outlines the use of virtual chromoendoscopy, narrow-band imaging, autofluorescence imaging, optical coherence tomography, confocal endomicroscopy and volumetric laser endomicroscopy as new imaging techniques for diagnostic investigation of the gastrointestinal tract. Insights into use of multimodal endoscopic imaging for early disease detection, in particular for pre-malignant lesions, in the oesophagus, stomach and colon are described.

[Rare gastroenterologic finding as a cause of hypochromic microcytic anemia]. / Seltener gastroenterologischer Befund als Ursache für eine hypochrome mikrozytäre Anämie.

CASE HISTORY: A 66-year-old woman suffering from skin paleness and weakness presented an increasing hypochromic, microcytic anemia. Diagnostic: In an ambulant setting a capsule endoscopy of the small intestine was carried out because of multiple polyps of the colon (colonoscopy) in addition to non-invasive (Hämoccult-Test) and invasive (gastroscopy) diagnostic. The patient was then admitted to hospital to clarify a suspicious ulcer of the small bowl. According to biopsies taken via balloon enteroscopy, an adenocarcinoma of the small intestine was diagnosed. THERAPY AND CLINICAL COURSE: After staging and exploratory laparotomy, histology findings showed an advanced tumour stage. A palliative chemotherapy, analogue to colon cancer treatment, was conducted. CONCLUSION: Small bowel diagnostics should be carried out if the aetiology of an anemia is not certain with an existing polyposis of the colon. Individuals with personal or family history of cumulative colorectal adenomas should undergo assessment for an adenomatous polyposis syndrom.

[Response to Terlipressin and albumin is associated with improved outcome in patients with cirrhosis and hepatorenal syndrome]. / Leberzirrhose und hepatorenales Syndrom: Das Ansprechen auf Terlipressin und Albumin ist mit besserem Überleben assoziiert.

BACKGROUND AND AIM: Hepatorenal syndrome (HRS) is a severe but potentially reversible complication in patients with cirrhosis. Untreated it is associated with a poor prognosis. Several randomized controlled trials (RCT) demonstrated that treatment with terlipressin and albumin improves renal function. However the effect on overall survival is unclear. Aim of the study was to gain further insight into the effect of terlipressin treatment in patients with HRS on renal function, overall survival and survival without liver transplantation or renal replacement. METHODS: All patients presenting with HRS and treated with terlipressin in our tertiary referral liver and transplantation center between April 2013 and April 2014 were included. Clinically relevant parameters such as response to therapy, overall survival and transplant- and renal-replacement-free-survival were prospectively investigated. RESULTS: Overall 57 patients were prospectively followed over a median of 65 days. In the majority of patients cirrhosis was in an advanced stage (Child-Pugh C: 46; 81%). Median cumulative terlipressin dosage and treatment duration were 20 mg and 5 days, respectively. Complete or partial response to terlipressin with recovery from HRS was observed in 20 and 3 out of 57 patients (51%; 5%). Median overall survival was significantly better in patients with response to terlipressin than in patients with non-response (167 vs. 27 days; p > 0.0001), as well as median survival free of liver transplantation and renal-replacement-therapy (81 vs. 4 days; p > 0.0001). In uni- and multivariate analysis, non-response was associated with a high baseline serum-bilirubin-concentration. CONCLUSION: Terlipressin in combination with albumin is effective in the majority of patients with HRS. Response to therapy is associated with improved survival.

Acute gastrointestinal bleeding - a new approach to clinical and endoscopic management.

Overt or occult gastrointestinal bleeding is a frequently observed condition in routine gastroenterological practice. Occult gastrointestinal bleeding is usually a purely incidental finding, based on the discovery of iron deficiency anemia in the laboratory or blood in stool (a positive Hemoccult test). However, overt bleeding accompanied by the clinical features of tarry stool, hematemesis, or hematochezia may be a life-threatening condition, calling for immediate emergency management. In contrast to traumatology, algorithms of emergency and intensive medicine are not sufficiently validated yet for acute life-threatening bleeding. The purpose of this review was to present all established and new endoscopic hemostasis techniques and to evaluate their efficacy, as well as to provide the treating endoscopist with practical advice on how he/she could incorporate these procedures into acute medical management. The recommendations are based on inspection of the study results in the recent published literature, as well as emergency medicine algorithms in traumatology.

Beyond standard image-enhanced endoscopy confocal endomicroscopy.

Endomicroscopy is a new imaging tool for gastrointestinal endoscopy. In vivo histology becomes possible at subcellular resolution during ongoing colonoscopy. Panchromoendoscopy with targeted biopsies has become the method of choice for surveillance of patients with inflammatory bowel disease. Endomicroscopy can be added after chromoendoscopy to clarify whether standard biopsies are needed. This smart biopsy concept can increase the diagnostic yield of intraepithelial neoplasia and substantially reduce the need for biopsies. Clinical acceptance is increasing because of a multitude of positive studies about the diagnostic value of endomicroscopy. Smart biopsies, functional imaging, and molecular imaging may represent the future for endomicroscopy.

Selection of higher order regression models in the analysis of multi-factorial transcription data.

INTRODUCTION: Many studies examine gene expression data that has been obtained under the influence of multiple factors, such as genetic background, environmental conditions, or exposure to diseases. The interplay of multiple factors may lead to effect modification and confounding. Higher order linear regression models can account for these effects. We present a new methodology for linear model selection and apply it to microarray data of bone marrow-derived macrophages. This experiment investigates the influence of three variable factors: the genetic background of the mice from which the macrophages were obtained, Yersinia enterocolitica infection (two strains, and a mock control), and treatment/non-treatment with interferon-γ. RESULTS: We set up four different linear regression models in a hierarchical order. We introduce the eruption plot as a new practical tool for model selection complementary to global testing. It visually compares the size and significance of effect estimates between two nested models. Using this methodology we were able to select the most appropriate model by keeping only relevant factors showing additional explanatory power. Application to experimental data allowed us to qualify the interaction of factors as either neutral (no interaction), alleviating (co-occurring effects are weaker than expected from the single effects), or aggravating (stronger than expected). We find a biologically meaningful gene cluster of putative C2TA target genes that appear to be co-regulated with MHC class II genes. CONCLUSIONS: We introduced the eruption plot as a tool for visual model comparison to identify relevant higher order interactions in the analysis of expression data obtained under the influence of multiple factors. We conclude that model selection in higher order linear regression models should generally be performed for the analysis of multi-factorial microarray data.

Pro12Ala polymorphism of the peroxisome proliferator-activated receptor γ2 in patients with fatty liver diseases.

AIM: To test the occurrence of the Pro12Ala mutation of the peroxisome proliferator-activated receptor-γ (PPARγ)2-gene in patients with non-alcoholic fatty liver disease (NAFLD) or alcoholic fatty liver disease (AFLD). METHODS: DNA from a total of 622 specimens including 259 blood samples of healthy blood donors and 363 histologically categorized liver biopsies of patients with NAFLD (n = 263) and AFLD (n = 100) were analyzed by Real-time polymerase chain reaction using allele-specific probes. RESULTS: In the NAFLD and the AFLD collective, 3% of the patients showed homozygous occurrence of the Ala12 PPARγ2-allele, differing from only 1.5% cases in the healthy population. In NAFLD patients, a high incidence of the Ala12 mutant was not associated with the progression of fatty liver disease. However, we observed a significantly higher risk (odds ratio = 2.50, CI: 1.05-5.90, P = 0.028) in AFLD patients carrying the mutated Ala12 allele to develop inflammatory alterations. The linkage of the malfunctioning Ala12-positive PPARγ2 isoform to an increased risk in patients with AFLD to develop severe steatohepatitis and fibrosis indicates a more prominent anti-inflammatory impact of PPARγ2 in progression of AFLD than of NAFLD. CONCLUSION: In AFLD patients, the Pro12Ala single nuclear polymorphism should be studied more extensively in order to serve as a novel candidate in biomarker screening for improved prognosis.