Akute Gefäßerkrankungen in der Gastroenterologie

Zusammenfassung: Vaskulär-gastroenterologische Notfälle zählen zu den häufigen Krankheitsbildern auf internistischen und chirurgischen Notfallstationen. Die klinischen Konsequenzen reichen von trivialen bis zu lebensbedrohlichen Situationen. Nur eine frühzeitige Erkennung der Symptomenkomplexe und die Anwendung der adäquaten diagnostischen Mittel führen zur korrekten Diagnosestellung mit nachfolgend - möglicherweise lebensrettender - Therapie. Um die hohen Mortalitätsraten der akuten Mesenterialischämien (50%), aortoenterischen Fisteln (30-40%), Aneurysmen viszeraler Arterien (10-100%) sowie des Budd-Chiari-Syndroms weiter senken zu können, gewinnen neue Strategien mit endovaskulärem Therapieansatz zunehmend an Bedeutung und ersetzen teilweise über viele Jahrzehnte etablierte Diagnose- und Therapiealgorithmen. Diese Übersichtsarbeit soll einen Überblick über aktuelle Diagnostik- und Therapiekonzepte häufiger vaskulär-gastroenterologischer Notfälle verschaffe

Evaluation of quality indicators following implementation of total mesorectal excision in primarily resected rectal cancer changed future management

Background and aims: We evaluated the outcome of primarily resected rectal cancer patients immediately after the implementation of total meserectal excision (TME) based on potential quality indicators. Patients and methods: Following initial teaching of two staff surgeons (PMS and AHH) by RJ Heald, 164 consecutive patients were analyzed. The following quality indicators were evaluated: (a) frequency of local recurrence, (b) number of resected lymph nodes, (c) selection of operative technique depending on tumor localization, (d) use of a protective loop ileostomy, and (e) frequency and type of adjuvant therapy. Results: Local recurrence rate was 8.5% after a minimum follow-up of 5years. An increasing pT category (p < 0.02) and the presence of lymph node metastases (pN+, p < 0.05) were significantly associated with local recurrence rates. The number of resected lymph nodes was significantly associated with nodal metastases rate (p < 0.02). Patients with distal third rectal cancer underwent significantly more often an abdominoperineal amputation (p < 0.0001). Clinical course, but not the rate of anastomotic leakage (9.5%) itself was influenced by using a protective loop ileostomy. Forty-two (29.7%) patients received adjuvant therapy; however, local recurrence rate was higher in patients with adjuvant chemo-/radiotherapy (14.2% vs. 6.1%). Conclusions: The local recurrence rate of 8.5% demonstrates that through consequent implementation of TME excellent onclogical results can be achieved. The number of resected lymph nodes significantly influenced the pN category. The primary construction of a protective loop ileostomy after TME became standard. Neoadjuvant chemoradiation was systematically introduced in order to improve local tumor control and prevent abdominoperineal amputations. No conclusions can be drawn concerning adjuvant therap

COX-2 mRNA Expression is Significantly Increased in Acid-exposed Compared to Nonexposed Squamous Epithelium in Gastroesophageal Reflux Disease

Background: Little is known about the role of cyclooxygenase (COX)-2 in gastroesophageal reflux disease (GERD) and the development of Barrett's metaplasia. The objectives of this study were to further analyze COX-2 mRNA expression in patients with GERD compared to Barrett's esophagus (BE) and Barrett's cancer (BC). Methods: Tissue samples from 110 patients with GERD (n = 43), BE (n = 20), and BC (n = 47) were obtained in routine upper GI endoscopy. Expression levels of COX-2 were measured by quantitative real-time reverse trancriptase polymerase chain reaction (RT-PCR). Also, 24-h pH monitoring was performed in all patients of the GERD study group and the DeMeester composite score was used to match COX-2 mRNA expression with the severity of acid exposure in the lower esophagus. Results: COX-2 mRNA is progressively upregulated within the metaplasia-dysplasia-adenocarcinoma (MDA) sequence (p = 0.001). COX-2 levels of the squamous epithelium in the distal esophagus from patients with GERD and a pathologic mean DeMeester score (>14.72) were significantly higher than in patients with normal DeMeester scores (p = 0.01). Conclusion: In summary our findings suggest that alterations in COX-2 mRNA expression occur independently of endoscopic or histologic signs of GERD in the acid-exposed squamous epithelium of the distal esophagus. However, this early COX-2 increase in GERD is further upregulated within the MDA sequence for yet unknown reason

Analytical Solution for the Deformation of a Cylinder under Tidal Gravitational Forces

Quite a few future high precision space missions for testing Special and General Relativity will use optical resonators which are used for laser frequency stabilization. These devices are used for carrying out tests of the isotropy of light (Michelson-Morley experiment) and of the universality of the gravitational redshift. As the resonator frequency not only depends on the speed of light but also on the resonator length, the quality of these measurements is very sensitive to elastic deformations of the optical resonator itself. As a consequence, a detailed knowledge about the deformations of the cavity is necessary. Therefore in this article we investigate the modeling of optical resonators in a space environment. Usually for simulation issues the Finite Element Method (FEM) is applied in order to investigate the influence of disturbances on the resonator measurements. However, for a careful control of the numerical quality of FEM simulations a comparison with an analytical solution of a simplified resonator model is beneficial. In this article we present an analytical solution for the problem of an elastic, isotropic, homogeneous free-flying cylinder in space under the influence of a tidal gravitational force. The solution is gained by solving the linear equations of elasticity for special boundary conditions. The applicability of using FEM codes for these simulations shall be verified through the comparison of the analytical solution with the results gained within the FEM code.Comment: 23 pages, 3 figure

Dendritic Cell and T Cell Crosstalk in Liver Fibrogenesis and Hepatocarcinogenesis: Implications for Prevention and Therapy of Liver Cancer

Liver fibrosis is a chronic, highly prevalent disease that may progress to cirrhosis and substantially increases the risk for development of hepatocellular carcinoma (HCC). Fibrotic livers are characterized by an inflammatory microenvironment that is composed of various immunologically active cells, including liver-resident populations (e.g., Kupffer cells, hepatic stellate cells and sinusoidal endothelium) and infiltrating leukocytes (e.g., monocytes, monocyte-derived macrophages, neutrophils and lymphocytes). While inflammatory injury drives both fibrogenesis and carcinogenesis, the tolerogenic microenvironment of the liver conveys immunosuppressive effects that encourage tumor growth. An insufficient crosstalk between dendritic cells (DCs), the professional antigen presenting cells, and T cells, the efficient anti-tumor effector cells, is one of the main mechanisms of HCC tumor tolerance. The meticulous analysis of patient samples and mouse models of fibrosis-HCC provided in-depth insights into molecular mechanisms of immune interactions in liver cancer. The therapeutic modulation of this multifaceted immunological response, e.g., by inhibiting immune checkpoint molecules, in situ vaccination, oncolytic viruses or combinations thereof, is a rapidly evolving field that holds the potential to improve the outcome of patients with HCC. This review aims to highlight the current understanding of DC-T cell interactions in fibrogenesis and hepatocarcinogenesis and to illustrate the potentials and pitfalls of therapeutic clinical translation

Wirtsfaktoren in primären Tumoren der Leber und Gallenwege: Einfluss auf kurative Therapieansätze

Primärer Leberkrebs – hepatozelluläres (HCC) und cholangiozelluläres Karzinom (CCA) - ist die Tumorerkrankung, die nach dem Lungenkarzinom für den Verlust der meisten Lebensjahre weltweit verantwortlich gemacht wird. Unter einem Drittel der Patienten kann kurativen Therapien, wie der Leberresektion zugeführt werden, aber ihr Outcome ist durch eine hohe perioperative Morbidität und Mortalität sowie hohe Rezidivraten limitiert, sodass ein hoher Bedarf besteht, präoperativ PatientInnen besser zu stratifizieren. In dieser Habilitationsschrift wurden prognostische Parameter für primäre Lebertumoren nach einer Leberteilresektion in kurativer Intention untersucht. Hierbei lag ein Fokus auf dem selteneren, und gerade in Europäischen Kollektiven unterrepräsentiertem, Cholangiokarzinom. Bisherige prognostische Parameter haben einen starken Fokus auf Tumor-Parameter, wie Genmutationen und pathologische Kriterien gelegt. Einzelnukleotidpolymorphismen können sich sowohl auf Prozesse der Wirtszellen, als auch auf die Interaktion des Wirtes mit dem Tumor auswirken, zum Beispiel in Bereichen der Immunologie und Neoangiogenese. Hierbei fanden wir für IL-1b, IL-8, und den IL-8 Rezeptor, Polymorphismen, die hochgradig mit der onkologischen und allgemeinen Prognose assoziiert war. Somit kann die Analyse von Genopymorphismen die Abschätzung onkologischer Outcomes auch für das CCA unterstützen. Im zweiten Teil dieser Arbeit wurde anhand präoperativer Computertomographie (CT)-Bilder die Körperzusammensetzung basierend auf dem Muskel-und Fettkompartiment. Wichtige Erkenntnisse hierbei waren, dass während isolierte konventionelle Parameter wie die Sarkopenie oder die viszerale oder subkutane Fettleibigkeit keinen isolierten prognostischen Stellenwert hatten, hatten Patient*innen mit Sarkopener Obesität ein dramatisch verkürztes Überleben. Somit konnten unsere Daten eine – gerade im Kontext der weltweiten Übergewichtsepidemie immer prävalenter werdende – Hochrisikogruppe aufzeigen, die bei konventioneller klinischer Betrachtung durch BMI nicht aufgefallen wäre. Zusammenfassend konnte diese Arbeit angeborene als auch akquirierte Wirtfaktoren als prognostisch relevant für das chirurgisch therapierte Cholangiokarzinom herausstellen. Unsere Ergebnisse können dank ihrer präoperativen Erhebbarkeit (Einzelnukleotidpolymorphismen aus peripherem Blut, body composition aus präoperativen CT Bildern) prognostisch unterstützend wirken und in Zukunft helfen, vulnerable Patient*innengruppen aufzeigen

A let-7 microRNA-binding site polymorphism in 3′-untranslated region of KRAS gene predicts response in wild-type KRAS patients with metastatic colorectal cancer treated with cetuximab monotherapy

Purpose: Recent studies have found that KRAS mutations predict resistance to monoclonal antibodies targeting the epidermal growth factor receptor in metastatic colorectal cancer (mCRC). A polymorphism in a let-7 microRNA complementary site (lcs6) in the KRAS 3′ untranslated region (UTR) is associated with an increased cancer risk in non-small-cell lung cancer and reduced overall survival (OS) in oral cancers. We tested the hypothesis whether this polymorphism may be associated with clinical outcome in KRAS wild-type (KRASwt) mCRC patients treated with cetuximab monotherapy. Patients and methods: The presence of KRAS let-7 lcs6 polymorphism was evaluated in 130 mCRC patients who were enrolled in a phase II study of cetuximab monotherapy (IMCL-0144). Genomic DNA was extracted from dissected formalin-fixed paraffin-embedded tumor tissue, KRAS mutation status and polymorphism were assessed using direct sequencing and PCR restriction fragment length polymorphism technique. Results: KRAS let-7 lcs6 polymorphism was found to be related to object response rate (ORR) in mCRC patients whose tumors had KRASwt. The 12 KRASwt patients harboring at least a variant G allele (TG or GG) had a 42% ORR compared with a 9% ORR in 55 KRASwt patients with let-7 lcs6 TT genotype (P = 0.02, Fisher's exact test). KRASwt patients with TG/GG genotypes had trend of longer median progression-free survival (3.9 versus 1.3 months) and OS (10.7 versus 6.4 months) compared to those with TT genotypes. Conclusions: These results are the first to indicate that the KRAS 3'UTR polymorphism may predict for cetuximab responsiveness in KRASwt mCRC patients, which warrants validation in other clinical trial

Genetic polymorphisms in interleukin-1β (rs1143634) and interleukin-8 (rs4073) are associated with survival after resection of intrahepatic cholangiocarcinoma

Intrahepatic cholangiocarcinoma (iCCA) is a rare, understudied primary hepatic malignancy with dismal outcomes. Aiming to identify prognostically relevant single-nucleotide polymorphisms, we analyzed 11 genetic variants with a role in tumor-promoting inflammation (VEGF, EGF, EGFR, IL-1B, IL-6, CXCL8 (IL-8), IL-10, CXCR1, HIF1A and PTGS2 (COX-2) genes) and their association with disease-free (DFS) and overall survival (OS) in patients undergoing curative-intent surgery for iCCA. Genomic DNA was isolated from 112 patients (64 female, 48 male) with iCCA. Germline polymorphisms were analyzed with polymerase chain reaction-restriction fragment length polymorphism protocols. The IL-1B +3954 C/C (73/112, hazard ratio (HR) = 1.735, p = 0.012) and the IL-8 -251 T/A or A/A (53/112 and 16/112, HR = 2.001 and 1.1777, p = 0.026) genotypes were associated with shorter OS in univariable and multivariable analysis. The IL-1B +3954 polymorphism was also associated with shorter DFS (HR = 1.983, p = 0.012), but this effect was not sustained in the multivariable model. A genetic risk model of 0, 1 and 2 unfavorable alleles was established and confirmed in multivariable analysis. This study supports the prognostic role of the IL-1B C+3954T and the IL-8 T-251A variant as outcome markers in iCCA patients, identifying patient subgroups at higher risk for dismal clinical outcomes

Ueber das Verhalten der Netzhautgefässe bei Sclerose der Hornarterien und der übrigen Theile des Aortensystems : Inaugural-Dissertation zur Erlangung des Grades eines Doctors der Medicin / verfasst und mit Bewilligung Einer Hochverordneten Medicinischen Facultät der Kaiserlichen Universität zu Jurjew zur öffentlichen Vertheidigung bestimmt von Mark Lurje, Arzt

http://tartu.ester.ee/record=b2286933~S1*es

The prognostic impact of preoperative body composition in perihilar and intrahepatic cholangiocarcinoma

Cholangiocarcinoma (CCA) is a rare but highly aggressive malignancy of the biliary system. Although it is amenable to surgical resection in early disease, outcomes are frequently dismal. Here, we investigated the prevalence of body composition (BC) alterations and their prognostic role for surgical patients with intrahepatic (iCCA) and perihilar (pCCA) disease. Patients undergoing curative-intent surgery for iCCA or pCCA between 2010 and 2019 at University Hospital Aachen were included. Axial computed tomography images were retrospectively assessed with a segmentation tool (3D Slicer) at the level of the third lumbar vertebra to determine lumbar skeletal muscle (SM) index, mean SM radiation attenuation, and visceral fat area. The related BC pathologies sarcopenia, myosteatosis, visceral obesity, and sarcopenic obesity were determined using previously described cutoffs. A total of 189 patients (86 with iCCA, 103 with pCCA) were included. Alterations of BC were highly prevalent in iCCA and pCCA, respectively: sarcopenia, 33% (28/86) and 39% (40/103); myosteatosis, 66% (57/86) and 66% (68/103); visceral obesity, 56% (48/86) and 67% (69/103); sarcopenic obesity, 11% (9/86) and 17% (17/103). Sarcopenia and myosteatosis did not have a significant prognostic role for disease-free survival (DFS) and overall survival (OS). Patients with iCCA with sarcopenic obesity (n = 9) had significantly shorter OS than patients without sarcopenic obesity (n = 7; log-rank p = 0.002; median OS, 11 months and 31 months; 1-year mortality, 55.6% [5/9] and 22% [17/77]; 5-year mortality, 88.9% [8/9] and 61% [47/77], respectively). In multivariable analysis, only tumor-related risk factors remained prognostic for DFS and OS. Sarcopenic obesity may affect clinical outcomes after curative-intent surgery for iCCA, indicating that imaging-based analysis of BC may hold prognostic value for long-term survival and could aid preoperative patient selection