Combined Gastric and Colorectal Cancer Screening—A New Strategy

Background: Our aim was to evaluate the feasibility of a serological assessment of gastric cancer risk in patients undergoing colonoscopy in countries with low-to-moderate incidence rates. Methods: Serum samples were prospectively collected from 453 patients (>50 years old) undergoing colonoscopies. Of these, 279 (61.6%) also underwent gastroscopy to correlate the results for serum pepsinogen I and II (sPG-I and sPG-II), sPG-I/II ratio, and anti-H. pylori antibodies with gastric histopathology findings (graded according to the updated Sydney classification and the Operative Link of Gastritis Assessment (OLGA) and the Operative Link for Gastric Intestinal Metaplasia assessment (OLGIM) systems). Results: H. pylori was found in 85 patients (30.5%). Chronic atrophic gastritis was diagnosed in 89 (31.9%) patients. High-risk OLGA (III-IV) stages were present in 24 patients, and high-risk OLGIM stages were present in 14 patients. There was an inverse correlation of sPG-I with the degree of atrophy and intestinal metaplasia (IM), as well as with the respective OLGA (r = -0.425; p < 0.001) and OLGIM (r = -0.303; p < 0.001) stages. A pathological sPG-I result was associated with a relative risk (RR) of 12.2 (95% confidence interval: 6.29-23.54; p < 0.001) for gastric preneoplastic changes. Conclusions: The assessment of serum pepsinogen allows the identification of patients at increased risk of gastric cancer. A prevention strategy of combining a screening colonoscopy with a serological screening for preneoplastic gastric changes should be considered in the general population

COVID-19 und Lebererkrankungen

Bis zu 53 % der PatientInnen mit Coronavirus Disease 2019 (COVID-19) weisen eine hepatische Beteiligung auf. Durch die Expression der Hauptzielstruktur für „severe acute respiratory syndrome coronavirus type 2“ (SARS-CoV-2), des Angiotensin-converting-Enzym-2(ACE2)-Rezeptors, auch auf Cholangiozyten, sinusoidalen Endothelzellen und Hepatozyten kann es zu einer direkten Schädigung der Leber kommen. Ferner spielt eine indirekte (nicht durch Rezeptoren vermittelte) Schädigung der Leber im Rahmen von COVID-19 durch eine schwere systemische Inflammation mit Zytokinsturm, hepatischen Thrombosen und einer systemischen Hypoxie eine wichtige Rolle. Bei COVID-19 gelten Leberwerte als wichtige Prädiktoren für die Prognose der PatientInnen. Wichtig ist es hierbei Differenzialdiagnosen für die Leberwerterhöhung, wie andere Virusinfektionen, medikamentös-toxisch induzierte Leberschädigung sowie autoimmune, metabolische und andere Lebererkrankungen, abzuklären. Von hoher klinischer Relevanz für die Behandlung kritisch kranker PatientInnen auf der Intensivstation ist das Krankheitsbild der „secondary sclerosing cholangitis in critically ill patients“ (SSC-CIP). Hierfür sind unter anderem hochdosierte Katecholamine, eine Beatmung mit hohem positivem endexspiratorischem Druck (PEEP) und die extrakorporale Membranoxygenierung (ECMO) Risikofaktoren. Eine frühe Diagnose dieser Erkrankung und Behandlung mittels interventioneller endoskopischer retrograder Cholangiographie (ERC) ist hierbei von entscheidender Bedeutung. Auch sollte eine Lebertransplantation evaluiert werden. Bei einer COVID-19-Erkrankung treten Fälle mit SSC, sog. COVID-SSC, auf. Die COVID-SSC und die SSC-CIP sind im klinischen Phänotyp, Risikofaktoren, Prognose und transplantatfreien Überleben vergleichbar. PatientInnen mit vorbestehender Lebererkrankung haben kein erhöhtes Risiko für eine Infektion mit SARS-CoV‑2, erkranken jedoch schwerer an COVID-19 als PatientInnen ohne Lebervorerkrankungen. Bei PatientInnen mit einer vorbestehenden Leberzirrhose kann eine SARS-CoV-2-Infektion ein akut-auf-chronisches Leberversagen (ACLF) induzieren. Hierbei handelt es sich um ein Krankheitsbild mit einer sehr hohen Mortalität, das im Rahmen einer intensivmedizinischen Behandlung therapiert werden muss. ---------------------------------------------------- In patients with coronavirus disease 2019 (COVID-19), hepatic involvement occurs in up to 53% of all cases. Via the primary target for severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), the angiotensin-converting enzyme 2 (ACE2) receptor, expressed on cholangiocytes, sinusoidal endothelial cells, and hepatocytes, direct damage to the liver may occur. Furthermore, indirect (= not receptor-mediated) damage to the liver plays a crucial role in the context of COVID-19 due to severe systemic inflammation with cytokine storm, hepatic thrombosis, and systemic hypoxia. In COVID-19, liver enzymes are considered significant predictors of outcome. Thus, it is essential to rule out other causes of liver enzyme elevation, such as other viral infections, drug-induced liver injury, and metabolic, autoimmune and other liver diseases. Secondary sclerosing cholangitis in critically ill patients (SSC-CIP) is highly relevant in treating critically ill patients in the intensive care unit (ICU). Risk factors for SSC-CIP include high doses of catecholamines, high positive end-expiratory pressure (PEEP), and extracorporeal membrane oxygenation (ECMO) therapy. Early recognition of this disease and treatment by endoscopic retrograde cholangiography (ERC) is crucial. Furthermore, liver transplantation should be evaluated. Some patients with COVID-19 are diagnosed with SSC, which is termed COVID-19-associated SSC. COVID-19-associated SSC and SSC-CIP are comparable with regard to clinical phenotype, risk factors, prognosis, and graft-free survival. Patients with pre-existing liver disease are not at increased risk for infection with SARS-CoV‑2 but show more severe clinical courses of COVID-19 than patients without pre-existing liver disease. Patients with pre-existing liver cirrhosis may develop acute-on-chronic liver failure (ACLF) upon infection with SARS-CoV‑2. ACLF has a high mortality rate, which must be treated in the ICU

Inflammatory Myofibroblastic Tumor of the Pancreatic Head: An Unusual Cause of Recurrent Acute Pancreatitis – Case Presentation of a Palliative Approach after Failed Resection and Review of the Literature

Inflammatory myofibroblastic tumors (IMTs) are a rare cause of echo-poor pancreatic head enlargement. Histologically, IMTs are characterized by spindle-shaped myofibroblasts or fibroblasts accompanied by a mixed immune cell infiltration. The most common localizations of IMTs have been reported in lung, mesentery and omentum, especially in children and young adults. IMTs show infiltrating growth, multilocular appearance and also metastasis have been reported. Curative resection is the only therapeutic option so far. In the palliative situation, evident data and clear guidelines for this rare tumor entity are missing. We report on a 44-year-old male with an unresectable IMT of the pancreatic head causing recurrent episodes of acute pancreatitis that resulted in a chronic obstructive course of the disease. The patient entered a palliative therapeutic regimen including radiation therapy and antiinflammatory medication. In a regular follow-up of 12 months, he presented with stable disease after initial progression. This case of local progressive IMT of the pancreatic head was managed with a palliative therapeutic regimen and is discussed based on the current literature

Diagnostic Accuracy and Therapeutic Efficacy of Digital Single-Operator Cholangioscopy for Biliary Lesions and Stenosis

Background/Aims: Digital single-operator cholangioscopy (dSOC) has revolutionized bile duct visualization. Interventions like electrohydraulic or laser lithotripsy, inspection of suspicious areas, and targeted biopsies have become possible quick and easy. One main indication for dSOC remains the evaluation of indeterminate biliary strictures. Objective and Methods: We analyzed 180 consecutive dSOCs procedures performed in a high-volume tertiary center to evaluate sensitivity, specificity as well as positive and negative predictive values (PPV and NPV) for indeterminate strictures. Furthermore, technical success and complications were analyzed. Results: In 92–97%, the region of interest was reached and successfully visualized. In 83–100%, targeted biopsies were obtained from the suspicious area. Only the distal bile duct was less successful with only 84 and 62%, respectively. In general, dSOC procedures were safe. Cholangitis was the main complication. Regarding the diagnostic accuracy of dSOC of indeterminate biliary strictures, we found a sensitivity of 0.87 and specificity of 0.88, over all. Within the whole cohort, the investigators’ assessment directly after dSOC had a PPV of 0.63 and a NPV of 0.97. In patients with biliary lesions or stenosis suspicious for malignancy, the dSOC-based visual diagnosis revealed a very high diagnostic accuracy with sensitivity and specificity of 1.0 (95% CI 0.86–1.0) and 0.76 (95% CI 0.56–0.9) with a PPV of 0.77 (95% CI 0.59–0.9) and a high NPV of 1.0 (95% CI 0.85–1.0). Conclusions: Our study demonstrates that dSOC has a high diagnostic accuracy as well as a favorable safety profile. Therefore, dSOC should be discussed as standard of care during endoscopic retrograde cholangiography for indeterminate biliary lesions

Serum Chemerin Does Not Differentiate Colorectal Liver Metastases from Hepatocellular Carcinoma

The chemoattractant adipokine chemerin is related to the metabolic syndrome, which is a risk factor for different cancers. Recent studies provide evidence that chemerin is an important molecule in colorectal cancer (CRC) and hepatocellular carcinoma (HCC). Serum chemerin is high in CRC patients and low in HCC patients and may serve as a differential diagnostic marker for HCC and liver metastases from CRC. To this end, serum chemerin was measured in 36 patients with CRC metastases, 32 patients with HCC and 49 non-tumor patients by ELISA. Chemerin serum protein levels were, however, similar in the three cohorts. Serum chemerin was higher in hypertensive than normotensive tumor patients but not controls. Cancer patients with hypercholesterolemia or hyperuricemia also had increased serum chemerin. When patients with these comorbidities were excluded from the calculation, chemerin was higher in CRC than HCC patients but did not differ from controls. Chemerin did not correlate with the tumor markers carcinoembryonic antigen, carbohydrate antigen 19-9 and alpha-fetoprotein in both cohorts and was not changed with tumor-node-metastasis stage in HCC. Chemerin was not associated with hepatic fat, liver inflammation and fibrosis. To conclude, systemic chemerin did not discriminate between CRC metastases and HCC. Comorbidities among tumor patients were linked with elevated systemic chemerin

Insights in Molecular Therapies for Hepatocellular Carcinoma

We conducted a comprehensive review of the current literature of published data and clinical trials (MEDLINE), as well as published congress contributions and active recruiting clinical trials on targeted therapies in hepatocellular carcinoma. Combinations of different agents and medical therapy along with radiological interventions were analyzed for the setting of advanced HCC. Those settings were also analyzed in combination with adjuvant situations after resection or radiological treatments. We summarized the current knowledge for each therapeutic setting and combination that currently is or has been under clinical evaluation. We further discuss the results in the background of current treatment guidelines. In addition, we review the pathophysiological mechanisms and pathways for each of these investigated targets and drugs to further elucidate the molecular background and underlying mechanisms of action. Established and recommended targeted treatment options that already exist for patients are considered for systemic treatment: atezolizumab/bevacizumab, durvalumab/tremelimumab, sorafenib, lenvatinib, cabozantinib, regorafenib, and ramucirumab. Combination treatment for systemic treatment and local ablative treatment or transarterial chemoembolization and adjuvant and neoadjuvant treatment strategies are under clinical investigation

Case Report: Simultaneously Induced Neutropenia and Hemolysis After a Single Metamizole Dose

Background and objective Metamizole is a non-opioid ampyrone sulfonate compound with potent analgesic, antipyretic, and spasmolytic effects. Agranulocytosis is a rare life-threatening complication of metamizole. Case Here, we present the case of a 62-year-old patient who developed agranulocytosis as well as hemolysis after a single administration of metamizole. Conclusion This case illustrates the inherent allergic potential of metamizole and its effects on different hematopoietic cell types

Unraveling the Role of Reactive Oxygen Species in T Lymphocyte Signaling

Reactive oxygen species (ROS) are central to inter- and intracellular signaling. Their localized and transient effects are due to their short half-life, especially when generated in controlled amounts. Upon T cell receptor (TCR) activation, regulated ROS signaling is primarily initiated by complexes I and III of the electron transport chain (ETC). Subsequent ROS production triggers the activation of nicotinamide adenine dinucleotide phosphate oxidase 2 (NADPH oxidase 2), prolonging the oxidative signal. This signal then engages kinase signaling cascades such as the mitogen-activated protein kinase (MAPK) pathway and increases the activity of REDOX-sensitive transcription factors such as nuclear factor-kappa B (NF-κB) and activator protein-1 (AP-1). To limit ROS overproduction and prevent oxidative stress, nuclear factor erythroid 2-related factor 2 (Nrf2) and antioxidant proteins such as superoxide dismutases (SODs) finely regulate signal intensity and are capable of terminating the oxidative signal when needed. Thus, oxidative signals, such as T cell activation, are well-controlled and critical for cellular communication

Pathogenesis and Current Treatment Strategies of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the most frequent liver cancer with high lethality and low five-year survival rates leading to a substantial worldwide burden for healthcare systems. HCC initiation and progression are favored by different etiological risk factors including hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, non-/and alcoholic fatty liver disease (N/AFLD), and tobacco smoking. In molecular pathogenesis, endogenous alteration in genetics (TP53, TERT, CTNNB1, etc.), epigenetics (DNA-methylation, miRNA, lncRNA, etc.), and dysregulation of key signaling pathways (Wnt/β-catenin, JAK/STAT, etc.) strongly contribute to the development of HCC. The multitude and complexity of different pathomechanisms also reflect the difficulties in tailored medical therapy of HCC. Treatment options for HCC are strictly dependent on tumor staging and liver function, which are structured by the updated Barcelona Clinic Liver Cancer classification system. Surgical resection, local ablative techniques, and liver transplantation are valid and curative therapeutic options for early tumor stages. For multifocal and metastatic diseases, systemic therapy is recommended. While Sorafenib had been the standalone HCC first-line therapy for decades, recent developments had led to the approval of new treatment options as first-line as well as second-line treatment. Anti-PD-L1 directed combination therapies either with anti-VEGF directed agents or with anti-CTLA-4 active substances have been implemented as the new treatment standard in the first-line setting. However, data from clinical trials indicate different responses on specific therapeutic regimens depending on the underlying pathogenesis of hepatocellular cancer. Therefore, histopathological examinations have been re-emphasized by current international clinical guidelines in addition to the standardized radiological diagnosis using contrast-enhanced cross-sectional imaging. In this review, we emphasize the current knowledge on molecular pathogenesis of hepatocellular carcinoma. On this occasion, the treatment sequences for early and advanced tumor stages according to the recently updated Barcelona Clinic Liver Cancer classification system and the current algorithm of systemic therapy (first-, second-, and third-line treatment) are summarized. Furthermore, we discuss novel precautional and pre-therapeutic approaches including therapeutic vaccination, adoptive cell transfer, locoregional therapy enhancement, and non-coding RNA-based therapy as promising treatment options. These novel treatments may prolong overall survival rates in regard with quality of life and liver function as mainstay of HCC therapy

High-resolution Visualization of Intestinal Microcirculation using Ultra-microangiography in Patients with Inflammatory Bowel Disease: A Pilot Study

Background & Aims: Ultra-microangiography (UMA) is a novel Doppler technique with optimized wall filtering that provides high sensitivity to low-velocity blood flows and optimized visualization of microcirculation. The aim of this pilot study was to compare intestinal vascularization assessed by color Doppler signals (CDS) and UMA. Methods: We investigated intestinal vascularization using UMA and CDS in 13 patients with confirmed inflammatory bowel disease (IBD). A cohort of 28 patients without structural bowel disease served as the control. Results: Microcirculation and dysregulated microcirculation in patients without and with inflammatory bowel disease can be visualized and quantified using UMA. In 83 % of IBD patients and 76% of non-IBD patients, a high resolution of intestinal perfusion could be achieved using UMA. Conclusions: To the best of our knowledge, this is the first study to investigate intestinal vascularization using UMA in patients with and without structural bowel disease. Quantification and visualization of intestinal vascularization should be further investigated in prospective studies and could help guide our therapy of patients with IBD