PuraStat in gastrointestinal bleeding: results of a prospective multicentre observational pilot study.

BACKGROUND: A recently developed haemostatic peptide gel for endoscopic application has been introduced to improve the management of gastrointestinal bleeding. The aim of this pilot study was to evaluate the feasibility, safety, efficacy and indication profiles of PuraStat in a clinical setting. METHODS: In this prospective observational multicentre pilot study, patients with acute non-variceal gastrointestinal bleeding (upper and lower) were included. Primary and secondary application of PuraStat was evaluated. Haemoglobin, prothrombin time, platelets and transfusion behaviour were documented before and after haemostasis. The efficacy of PuraStat was assessed during the procedure, at 3 days and 1 week after application. RESULTS: 111 patients with acute gastrointestinal bleeding were recruited into the study. 70 percent (78/111) of the patients had upper gastrointestinal bleeding and 30% (33/111) had lower gastrointestinal bleeding. After primary application of PuraStat, initial haemostatic success was achieved in 94% of patients (74/79, 95% CI 88-99%), and in 75% of the patients when used as a secondary haemostatic product, following failure of established techniques (24/32, 95% CI 59-91%). The therapeutic success rates (absence of rebleeding) after 3 and 7 days were 91% and 87% after primary use, and 87% and 81% in all study patients. Overall rebleeding rate at 30 day follow-up was 16% (18/111). In the 5 patients who finally required surgery (4.5%), PuraStat allowed temporary haemostasis and stabilisation. CONCLUSIONS: PuraStat expanded the therapeutic toolbox available for an effective treatment of gastrointestinal bleeding sources. It could be safely applied and administered without complications as a primary or secondary therapy. PuraStat may additionally serve as a bridge to surgery in order to achieve temporary haemostasis in case of refractory severe bleeding, possibly playing a role in preventing immediate emergency surgery.

[Long-term response in advanced pancreatic adenocarcinoma - a case report and literature review]. / Langzeitremission bei einem Patienten mit metastasiertem Adenokarzinom des Pankreas: Aktuelle Therapiemöglichkeiten und neue Therapiealgorithmen mit Hilfe des Molekularen Tumorboards.

BACKGROUND: Pancreatic cancer is still considered one of the most aggressive types of cancer and is associated with a very poor prognosis although there have been improvements in diagnostics and chemotherapy regimes in recent years. A cure can only be achieved through complete resection which is only possible when diagnosed at a very early stage, though this is rarely the case. We report on a patient with stage IV adenocarcinoma of the pancreas in which several therapeutically actionable mutations could be detected and discuss new options of targeted therapies. CASE REPORT: A patient in his 50s was diagnosed with metastatic adenocarcinoma of the pancreas. The patient showed an excellent response to platinum-based chemotherapy with FOLFIRINOX. When a germline mutation in the BRCA-2 gene could be identified, he took part in the POLO-study receiving a maintenance therapy with the PARP-Inhibitor Olaparib. Due to a relapse, 2nd and 3rd line chemotherapy regimens were applied with Gemcitabine combined with Nab-Paclitaxel and later with Erlotinib. Although an activating mutation in the KRAS-gene could be detected as well, the patient rejected further experimental treatment. CONCLUSION: Identifying predictive factors and specific targetable mutations in patients with advanced pancreatic cancer is needed to be able to apply more individual and specific therapies in order to improve outcomes.

Diagnostic and therapeutic single-operator cholangiopancreatoscopy with SpyGlassDS™: results of a multicenter retrospective cohort study.

BACKGROUND AND AIMS: The aim of the study was to evaluate the usefulness and diagnostic and therapeutic outcome of the single-operator cholangiopancreatoscopy (SOC) with SpyGlassDS™. METHODS: In a retrospective multicenter study between November 2015 and January 2017, SpyGlassDS™ procedures were analyzed in participating centers. Indications, accuracy of SOC-guided biopsies, management of large bile duct stones, and complications were analyzed. Follow-up was 4 months. RESULTS: Two hundred and six patients out of 250 examinations were evaluated. Indications were biliary stones (n = 132), bile duct stenosis (n = 93), stones and stenosis combined (n = 24), and bile duct leakage (n = 1). Of the 117 cases which were suspicious of malignancy, in 99 cases the lesion could be stratified into benign (n = 55) or malignant (n = 44) indicating a sensitivity of 95.5% and a specificity of 94.5% for the indication tumor. SOC-guided biopsies revealed a sensitivity of 57.7% with a specificity of 100%. In 107 examinations, biliary stones were visualized and could be completely removed in 91.1% with a need of three procedures (range 1-6) to achieve final stone clearance. In 75 cases, lithotripsy was performed and was successful in 71 cases (95%). Four out of 45 patients (8.9%) underwent cholecystectomy with surgical bile duct revision as a final therapy. Adverse Event (AE) occurred in 33/250 patients (13.2%) and Serious Adverse Event (SAE) occurred in 1/250 patients (0.4%). Cholangitis was 1% (n = 102) after peri-interventional administration of antibiotics and 12.8% (n = 148) without antibiotic prophylaxis (p < 0.001). CONCLUSIONS: SOC with SpyGlassDS™ became a new standard for the diagnosis of indefinite biliary lesions and therapy of large bile duct stones. The diagnostic yield of SOC-guided biopsies facilitated a definite diagnosis in most cases and should be improved by standardized biopsy protocols. SOC-guided interventions allowed removal of large biliary stones by SOC-guided lithotripsy. The complication rate of 13.2% can be considerably reduced by use of a single-shot antibiotic treatment.

EndoClot Polysaccharide Hemostatic System in Nonvariceal Gastrointestinal Bleeding: Results of a Prospective Multicenter Observational Pilot Study.

BACKGROUND AND STUDY AIMS: Hemostatic powders have been introduced to improve the management of gastrointestinal (GI) bleeding and to extend the variety of tools available for emergency endoscopy. The aim of the present pilot study was to evaluate the indication profiles and the short-term outcome of EndoClot. PATIENTS, MATERIALS AND METHODS: In a prospective observational pilot study patients with acute nonvariceal GI bleeding were included. Primary or secondary application of EndoClot was assessed. Hemoglobin, prothrombine time and platelets were documented before and after hemostasis. The efficacy of EndoClot was assessed 72 hours and 1 week after application. RESULTS: Seventy patients with acute GI bleeding were recruited into the study. Eighty-three percent (58/70) of the patients had upper and 17% (12/70) had lower GI bleeding. In the upper GI tract treatment success was achieved in 64% (30/47, 95% confidence interval, 50%-76%) after primary use and in all patients, when used after established techniques had failed (95% confidence interval, 70%-100%). In lower GI bleeding hemostasis was achieved in 83% of cases (10/12, 95% confidence interval 54%-97%). Rebleeding occurred in 11% (8/70), in 10% EndoClot served as a bridge to surgery (7/70). CONCLUSIONS: EndoClot expanded the therapeutic options in the management of GI bleeding. It was applicable as a monotherapy or in combination with other techniques from oozing bleeding type or lower. It was most effective in diffuse or extensive bleeding activity or when access to the bleeding vessel was difficult. EndoClot can be applied as a bridge to surgery when classical methods of hemostasis have failed.

Acute HIV infection induces mucosal infiltration with CD4+ and CD8+ T cells, epithelial apoptosis, and a mucosal barrier defect.

BACKGROUND & AIMS: A barrier defect of the intestinal mucosa is thought to affect the progression of human immunodeficiency virus (HIV) infection. It is not clear whether the mucosal barrier impairment already is present in acute infection and what mechanisms cause this defect. We analyzed T-cell subsets, epithelial apoptosis, and barrier function of the duodenal mucosa in patients with acute HIV infection. METHODS: Mucosal T-cell subsets, epithelial apoptosis, and barrier function were assessed by immunohistochemistry, immunofluorescence, flow cytometry, and impedance spectroscopy in duodenal samples from 8 patients with early acute infection, 8 patients with chronic infection, and 9 HIV-negative individuals (controls). One patient was analyzed serially, before and during acute infection. RESULTS: Compared with controls, densities of mucosal CD8+ and, surprisingly, of mucosal CD4+ T cells too, increased in patients with acute infection. Most mucosal CD4+ T cells had an activated effector memory phenotype (CD45RA-CD45RO+CD62L-CD40L+CD38+) and did not proliferate. Perforin-expressing mucosal CD8+ T cells also were increased in acutely infected patients; their frequency correlated with epithelial apoptosis. The epithelial barrier was impaired significantly in patients with acute HIV infection. The patient analyzed serially developed increased densities of mucosal CD4+ and CD8+ T cells, increased apoptosis of epithelial cells, and mucosal barrier impairment during acute infection. CONCLUSIONS: Before depleting CD4+ T cells, acute HIV infection induces infiltration of the mucosa with activated effector memory CD4+ and CD8+ T cells. The HIV-induced barrier defect of the intestinal mucosa is evident already in acute infection; it might arise from increased epithelial apoptosis, induced by perforin-positive mucosal cytotoxic T cells.

[A young man with chronic diarrhea and epigastric pain]. / Junger Mann mit chronischer Diarrhö und Oberbauchschmerzen.

CASE REPORT: A 26-year-old man was admitted to hospital with a 6-month history of diarrhea and abdominal pain. Before admission, upper and lower gastrointestinal endoscopy had shown a mild erosive duodenitis and the patient was started on a proton pump inhibitor. Physical examination and laboratory tests on admission were not constructive. In addition, repeated gastrointestinal endoscopy, cross-sectional imaging and neuroendocrine markers did not point to a specific etiology. Therefore, as a provocation test, the proton pump inhibitor therapy was discontinued. Discontinuation resulted in a progression of the patient's symptoms and an endoscopic detection of duodenal ulcers. Except for the normal serum gastrin levels, this constellation was suggestive of a gastrinoma, so that further investigations were initiated. Subsequently, the diagnosis could be confirmed and the gastrinoma located. After successful pancreaticoduodenectomy, the patient was symptom-free. CONCLUSION: As part of a systematic investigation on chronic diarrhea, the work-up for neuroendocrine causes can play an important role. In this context, it should be kept in mind that some gastrinoma patients present without an elevation of serum gastrin levels. Regardless of a negative gastrin test, a typical symptom constellation should therefore prompt further investigations.

Disorders of intestinal secretion and absorption.

The gastrointestinal tract possesses a huge epithelial surface area and performs many different tasks. Amongst them are the digestive and absorptive functions. Disorders of intestinal absorption and secretion comprise a variety of different diseases, e.g. coeliac disease, lactase deficiency or Whipple's disease. In principle, impaired small intestinal function can occur with or without morphological alterations of the intestinal mucosa. Therefore, in the work up of a malabsorptive syndrome an early small intestinal biopsy is encouraged in conjunction with breath tests and stool analysis to guide further management. In addition, there is an array of functional tests, the clinical availability of which becomes more and more limited. In any case, early diagnosis of the underlying pathophysiology is most important, in order to initiate proper therapy. In this chapter, diagnostic procedure of malabsorption is discussed with special attention to specific disease like coeliac disease, Whipple's disease, giardiasis and short bowel syndrome. Furthermore, bacterial overgrowth, carbohydrate malabsorption and specific nutrient malabsorption (e.g. for iron or vitamins) and protein-losing enteropathy are presented with obligatory and optional tests as used in the clinical setting.

Mucosal but not peripheral FOXP3+ regulatory T cells are highly increased in untreated HIV infection and normalize after suppressive HAART.

Recent evidence indicates that regulatory T cells (T(regs)) play an important role in HIV infection. However, although the gastrointestinal mucosa is a key compartment in HIV disease, no data on mucosal T(regs) in HIV infection are available. In this study, we compared the frequency of T(regs) in duodenal mucosa and peripheral blood (PB) of 13 treatment-naive and 13 suppressively treated HIV-infected patients with that of 6 patients with norovirus infection and 12 healthy controls. T(regs) were quantified by immunohistochemistry (CD3/FOXP3) and further characterized (CD25, CTLA-4, GITR) by immunohistochemistry, immunofluorescence, and fluorescence-activated cell sorting (FACS). Both the frequency and the absolute count of mucosal T(regs) were highly increased in untreated HIV patients but were normal in treated HIV patients. In contrast, in peripheral blood of HIV patients, the absolute number of T(regs) was not increased, and their frequency was only slightly elevated. In norovirus infection, frequency of mucosal T(regs) in the CD4+ T-cell subset was not elevated. The high increase in count and frequency of mucosal T(regs) seems to be a characteristic feature of untreated HIV infection, suggesting a significant contribution of T(regs) to the pathogenesis of HIV disease. Their role may be 2-edged: attenuating HIV-induced immune hyperactivation while suppressing the immune response to HIV and mucosal pathogens.