Background Increasing knowledge about the genomic changes underpinning cancer development and growth has led to a rapidly expanding number of individualized therapies that specifically target these changes in a patient's tumor. Here we present a case report of a patient with metastatic esophageal carcinoma whose tumor harbored NTRK1 gene amplification and who received targeted systemic therapy with larotrectinib. At initial diagnosis, the patient presented with tumor obstruction of the middle esophagus, simultaneous liver and lung metastases, UICC IV and WHO performance status 3. Materials and Methods The solid tumor genomic profiling test FoundationOne CDx (F1CDx) was used to detect clinically relevant genomic alterations that, in turn, might identify a targeted therapeutic approach if suggested by the findings. The patient was then treated with larotrectinib and had subsequent follow-up biopsies. Results Simultaneous biopsies of the primary tumor and liver lesions identified a metastatic squamous cell esophageal carcinoma. Comprehensive genomic profiling obtained from liver metastases identified numerous genomic alterations including amplification of NTRK1. Owing to the reduced performance status of the patient, chemotherapy could not be applied and was denied. Although larotrectinib is only approved for the treatment of cancers with NTRK gene fusions, treatment was started and led to a shrinkage of the primary tumor as well as the liver and lung metastases within 6 weeks according to RECIST criteria accompanied by tumor marker decrease. The NTRK1 gene amplification was below the limit of detection in a subsequent liver biopsy. Conclusion The use of comprehensive genomic profiling, specifically F1CDx, enabled the selection of a targeted therapy that led to a rapid reduction of the tumor and its metastases according to RECIST criteria. This case suggests that larotrectinib is not only effective in NTRK fusions but may be efficacious in cases with gene amplification. Key Points Advances in precision medicine have revolutionized the treatment of cancer and have allowed oncologists to perform more individualized therapy. This case shows that larotrectinib could also be effective in cases of NTRK amplification of cancer. Today, there is only limited knowledge about NTRK alterations in squamous epithelial carcinoma of the esophagus. Longitudinal tumor sequencing during the course of the disease may allow for the detection of a molecular genetic cause once the tumor progresses. Additional actionable gene alterations may then be identified, which may provide the rationale for a therapy switch.

Hintergrund/Einleitung: Die Beurteilung des Dünndarmes mit der Videokapselendoskopie (VE) ist ein neues Verfahren, das teuer und zeitaufwendig ist. Ihr Stellenwert in der klinischen Routine ist noch offen.

Einleitung: Die palliative Standardtherapie der tumorbedingten symptomatischen Duodenalstenose ist bisher die operative Gastroenterostomie, die die meist stark reduzierten Patienten zusätzlich belastet. Als nichtoperative Alternative wird zunehmend häufiger die endoskopische Metallstenteinlage ins Duodenum vorgenommen.

10 Jahre nach Erscheinen der Erstauflage gibt das Endoskopiezentrum des Augsburger Klinikums unter der Leitung von Prof. Helmut Messmann die überarbeitete 2. Auflage des „Lehratlas der Koloskopie“ heraus. Strukturelle Voraussetzungen, wie die räumlich-technische Ausstattung und die Gerätetechnik, führen in das Thema ein. Die Ausführungen zum normalen Untersuchungsablauf und zu Normalbefunden geben mit Kombinationen aus Bildern und Grafiken hilfreiche Informationen gerade auch für Anfänger.

Hintergrund: Die untere gastrointestinale Blutung (GIB) stellt bei Patienten auf der Intensivstation ein seltenes Ereignis dar. Im Gegensatz zur oberen GIB, deren hohe Mortalität bei Intensivpatienten bekannt ist, liegen zur unteren GIB nur wenige Daten vor.

Hintergrund: Die endoskop. Mukosaresektion (EMR) ist in der Therapie prä- bzw. frühmaligner Läsionen im GI-Trakt etabliert. Bei großen Läsionen muss die EMR oft als piecemeal-Resektion oder inkomplett erfolgen (mit dann erhöhtem Rezidivrisko und Problemen bei der Beurteilung einer R0-Situation). Besonders bei großflächigen Läsionen können diese Probleme durch die ESD verbessert werden.

We report on three patients with severe gastrointestinal bleeding arising from aortoenteric fistula. Two patients presented with a secondary aortoduodenal fistula. In the first case bleeding occurred 8 months after aortobifemoral graft implantation. In the second patient aortobiliacal graft implantation was performed 22 years before. In the third case the aortoenteric fistula was primary and was caused by an abdominal aortic aneurysm without prior vascular intervention. In the first case diagnosis was made by urgent endoscopy visualizing ongoing bleeding from the duodenal fistula. In the two other patients urgent endoscopy and CT as well could not demonstrate the bleeding source. Aortoenteric fistula was diagnosed endoscopically during severe rebleeding some hours later. Two patients underwent surgery with implantation of an axillobifemoral bypass; the third patient declined further intervention and died. The course shows that aortoduodenal fistula can present with severe but intermittent gastrointestinal bleeding making the diagnosis in the non-bleeding interval difficult. In patients with severe gastrointestinal bleeding and a history of aortic disease (aneurysm, prior aortic graft repair or stenting) an aortoduodenal fistula should be suspected and the indication for surgical intervention should be considered early in spite of negative results of endoscopy and CT.

Hintergrund: Ulzera ventriculi erweisen sich in bis zu 5% histologisch als maligne. Neue endoskopische Verfahren (Autofluoreszenzendoskopie und narrow band imaging) stellen vielversprechende Ansätze dar, benigne und maligne Läsionen möglicherweise bereits in vivo differenzieren zu können (“virtual biopsy“).

Einleitung: Die mikroskopische Vergrößerungsmöglichkeit des neu entwickelten Endo-Zytoskopie-Systems erlaubt die Beurteilung von Zellverbänden und mukosalen Gewebestrukturen in vivo während der Endoskopie des oberen und unteren Gastrointestinaltraktes.

We report on three patients with severe gastrointestinal bleeding arising from aortoenteric fistula. Two patients presented with a secondary aortoduodenal fistula. In the first case bleeding occurred 8 months after aortobifemoral graft implantation. In the second patient aortobiiliacal graft implantation was performed 22 years before. In the third case the aortoenteric fistula was primary and was caused by an abdominal aortic aneurysm without prior vascular intervention. In the first case diagnosis was made by urgent endoscopy visualizing ongoing bleeding from the duodenal fistula. In the two other patients urgent endoscopy and CT as well could not demonstrate the bleeding source. Aortoenteric fistula was diagnosed endoscopically during severe rebleeding some hours later. Two patients underwent surgery with implantation of an axillobifemoral bypass; the third patient declined further intervention and died. The course shows that aortoduodenal fistula can present with severe but intermittent gastrointestinal bleeding making the diagnosis in the non-bleeding interval difficult. In patients with severe gastrointestinal bleeding and a history of aortic disease (aneurysm, prior aortic graft repair or stenting) an aortoduodenal fistula should be suspected and the indication for surgical intervention should be considered early in spite of negative results of endoscopy and CT.

Despite benign endoscopic appearance up to 5% of gastric ulcers are shown to be malignant in histology. Recently autofluorescence and narrow band imaging have been developed as new endoscopic techniques to differentiate benign from malignant lesions in vivo (“virtual biopsy”). Aim: To evaluate the diagnostic value of AF and NBI in the differentiation of benign and malignant gastric ulcers. Methods: We examined 25 ulcers of unknown histology in 23 patients prospectively with AF and NBI (XGIF-Q240FZ; prototype, Olympus); additionally biopsies were taken. Images were recorded and evaluated by an experienced endoscopist at the end of the study. AF images were classified as “normal AF” (green appearance) or “abnormal AF” (violet appearance) for the base and margin of the ulcer. NBI patterns were classified as “regular” and “irregular” for the base and margin of the ulcer. The findings were correlated with histology. Results: Histologic examination revealed peptic ulcers (n = 20), adenocarcinoma (n = 3), signet ring cell carcinoma (n = 1) and lymphoma (n = 1). AF was found to be “abnormal” in each ulcer base but only in the ulcer margin of the ulcers showing adenocarcinoma. A “regular” NBI pattern could be seen in the margin of all benign ulcers but also in the signet ring cell carcinoma an the lymphoma. NBI findings were classified “irregular” in the ulcer base of all adenocarcinomas and also in the signet ring cell carcinoma. Benign ulcers but also the lymphoma showed “regular” NBI patterns in the base. Conclusions: AF and NBI findings can be helpful in the differentiation of benign and malignant gastric ulcers in vivo. Abnormal autofluoresecence in the ulcer margin and irregular NBI patterns in the ulcer ground are highly suggestive of malignancy. The sensitivity of such findings is limited. Tabled 1 Prediction of malignancy of gastric ulcers Sensitivity Specificity positive predictive value negative predictive value abnormal AF in ulcer margin 60% 100% 100% 90,9% irregular NBI in ulcer base 80% 100% 100% 95,2% abnormal AF in margin and irregular NBI in base 60% 100% 100% 90,9% Open table in a new tab

Zur palliativen Therapie von tumorbedingten symptomatischen Obstruktionen im Dünndarm und Kolon wird zunehmend häufiger eine endoskopische Metallstenteinlage vorgenommen. Bewährt hat sich hier der Wallstent, allerdings sind das TTS-Applikationsbesteck und die relativ traumatischen Stentenden nicht optimal. Wir berichten über unsere Erfahrungen mit einem verbesserten Wallstent (WallFlex™ Enteral, BostonScientific)

Das Einwachsen der inneren Halteplatte bei lange liegender PEG (sog. buried bumper-Syndrom) ist eine Komplikation im Langzeitverlauf, die als Folge eines Pflegefehlers (zu straffe Fixierung mit mangelnder Mobilisierung der PEG beim Verbandswechsel) auftritt. In der Folge kommt es zum Funktionsverlust der PEG und zu lokalen Infektionen, so dass die PEG entfernt und neu angelegt werden muss. Wir untersuchten Häufigkeit, Management und Folgen dieser Komplikation an unserem Zentrum.

Hintergrund: Für operable gastrointestinale Stromatumoren (GIST) stellt die primäre Resektion die Methode der Wahl dar; im Gegensatz zu primär nicht resektablen Tumoren ist eine neoadjuvante Therapie nicht etabliert. Wir berichten über einen Patienten mit einem großen GIST-Tumor des Rektums. Nach neoadjuvanter Therapie mit Imatinib konnte eine deutliche Größenreduktion des Tumors erreicht und hiermit eine kontinenzerhaltende Resektion ermöglicht werden.

The buried bumper syndrome (overgrowth of the internal bumper by gastric mucosa) is a long-term complication of PEG. It often leads to loss of function of the PEG and to local complications like local infection and pain, which in turn results in the need to remove and replace the PEG. We analyzed the frequency, management and consequences of this syndrome in our tertiary care center. Methods: Retrospective analysis of all patients with buried bumper syndrome in our center since 1998. Results: Since 1998 31 pts. with buried bumper syndrome were observed. Regarding the average number of about 230 inserted PEGs per year this results in a mean frequency of 1.9%/year. However, there was a substantial rise of the frequency over time (from 0.8% in 1998 to 3.6% in 2004). Buried bumper syndrome was detected due to local infection in 17 pts. (55%), due to loss of function of PEG in 11 pts. (35%) and due to inability to move the PEG in 3 pts. (10%). The removal of PEG was performed endoscopically using a needle knife in 14 pts. (35%), transcutaneously with the Staritz-method in 4 pts. (13%) and surgically in 8 pts. (26%). In 5 pts. (16%) the buried bumper was left in place because of high OP-risk after a median number of 2 (1-3) unsuccessful endoscopic removal attempts and a new PEG was inserted next to the old PEG. The median number of sessions needed for endoscopic removal was 2 (1-3), while transcutaneous removal was possible in one session in all patients. Surgical removal was preceded by a mean of 1 (1-2) unsuccessful endoscopic removal attempts. Removal of buried bumpers was accompanied by complications in 9 pts. (29%): Bleeding during endoscopic removal procedures in 6 pts., severe local infection after surgical removal in 1 pt. and 2 disconnected bumpers which had to be left in place in 2. All these complications could be managed without serious consequences for the pts. Since the method of transcutaneous removal was introduced in 2004 no surgical removal was needed up to now. Conclusion: The buried bumper syndrome is a still rare, but increasing and relevant complication in the long term after PEG insertion. Therapy is often complex, time consuming and associated with a high number of complications, but in the majority of pts. non-surgical management is possible.

Hintergrund: Das kürzlich entwickelte Endozytoskopie-System (ECS) ist eine spezielle Form der Vergrösserungsendoskopie, mit der sich die Oberfläche der Mukosa bis zu 1000-fach vergrössern lässt. Dieses System erlaubt eine in-vivo Darstellung und Beobachtung zellulärer Strukturen der gastrointestinalen Mukosa nach Färbung der Schleimhaut.. Ziel: Evaluierung des Potentials des ECS bezüglich der on-line Detektion neoplastischer Veränderungen im Ösophagus, Magen und Kolon im Vergleich zur Histologie als derzeitigem Goldstandard. Methodik: 48 Patienten (37M/ 11W; 37–86Jahre) mit neoplastischen Läsionen im Ösophagus, Magen und Kolon wurden eingeschlossen und einer ÖGD oder Koloskopie unterzogen. Nach Durchführung einer Methylenblau-Färbung (1%) mittels Sprühkatheter wurde normale Mukosa und die neoplastische Veränderung mit zwei Zytoskopie-Sonden (450- und 1000-fache Vergrösserung) untersucht. Das Vergrösserungsbild wurde mehrere Minuten kontinuierlich beobachtet und auf CD aufgezeichnet. Dann wurden Biopsien der normalen und pathologischen Schleimhaut an der mittels Zytoskopie untersuchten Stelle entnommen. Die Gewebeproben und Videosequenzen wurden durch zwei verschiedene Pathologen verblindet untersucht. Ergebnisse: 15 Pt. mit neoplastischen Läsionen im Ösophagus (Plattenepithelkarzinom: n=10, Barrettkarzinom: n=3, Barrettösophagus: n=2), 17 Pt. mit Läsionen im Magen (Magenkarzinom: n=16, GIST-Tumor: n=1) und 16 Pt. mit Läsionen im Kolon (KRK: n=3, adenomatöse Polypen: n=13) wurden untersucht. Die Ergebnisse der Beurteilung neoplastischer Läsionen mittels ECS im Vergleich zur Histologie als Goldstandard sind in Tabelle 1 wiedergegeben. Schlussfolgerung: Erste Erfahrungen mit dem ECS zeigen eine Sensitivität von bis zu 80% für neoplastische Läsionen im Ösophagus und Kolon. Die Sensitivität maligner Läsionen im Magen fällt wegen dessen sekretorischer Komponente niedriger aus. Die ECS-Ergebnisse können durch eine grössere Erfahrung der Pathologen in der Beurteilung von ECS-Sequenzen noch verbessert werden.

Up to now radical esophageal resection is considered as the gold standard for treatment in high-grade intraepithelial neoplasia (HGIN) and early adenocarcinoma (EC) in Barrett's esophagus (BE). Aim: of this prospective observational study was to assess the role of local endoscopic therapy of HGIN and EC in Barrett's esophagus. Methods: From January 2002 up to now, HGIN and/or EC was diagnosed in 21 patients (18M/4F; 44-83 yrs) with BE by chromoendoscopy with biopsies of the four quadrants and of suspicious lesions; endosonography was used for further staging. Local endoscopic therapy was performed by endoscopic mucosal resection (EMR, “suck-and-cut” technique) and/or photodynamic therapy (PDT) with photofrin® (2 mg/kg i.v.) as photosensitizer. Results: 6 HGIN, 8 EC (4 T1m and 4 T1sm) and 2 HGIN+EC were histologically confirmed in 16 pts with LSBE. In 5 pts with SSBE, 1 HGIN and 4 EC (2 T1m and 2 T1sm) were diagnosed histologically. EMR was performed in 15 pts, PDT in one patient and the combination of EMR and PDT in 5 pts. After EMR, in 6 patients submucosal invasion of the EC was diagnosed; 4 of them were treated by surgery, 1 patient with BE not suitable for PDT or surgery died 18 months later from other causes and 1 patient with BE not suitable for surgery was treated by additional PDT. Complete local remission was achieved in 67% (14/21). Mortality occured in 1 patient, he died from pulmonary embolism. Major complication was seen in 3 patients: 1 perforation and 2 pts with bleeding after EMR were treated endoscopically. The minor complication rate was 9% including stricture after EMR (2) and EMR + PDT (1) and sunburn (1) after PDT. During an average follow-up period of 10,6 (1-21) months, a relapse rate of 9% was observed (2/21). Conclusions: Following this data with good local results, endoscopic therapy of HGIN and mucosal EC in BE could replace esophagectomy as the treatment of choice, but further long-term results will be necessary. EMR alone or in combination with PDT will be the treatment of choice.

The Rockall score is one of the best known scoring system which was developed to predict recurrent hemorrhage and mortality in patients with acute upper gastrointestinal bleeding. However, until now scoring systems are not widely accepted in daily clinical use. Aim: Of the study was a retrospective evaluation of the Rockall score to analyse its use in the prediction of rebleeding and mortality in patients presenting with signs of upper gastrointestinal hemorrhage (e.g. hematemesis) in our emergency unit. Methods: 237 patients (95 female/142 male; 22-95 years, median age 72 years) with a history or clinical signs of an upper gastrointestinal bleeding were registered in our emergency unit in a 12-month period (from 6/03 to 6/04). All patients were examined by oesophagogastroduodenoscopy within 12 hours after admission. The Rockall score includes 3 nonendoscopic (age, shock, and comorbidity) and 2 endoscopic variables (endoscopic diagnosis and presence or absence of endoscopic stigmata of recent hemorrhage), which were analysed for each patient retrospectively. Results: Conclusion: We find a very good reliability of the Rockall score in identifying patients with a low risk for complications of upper gastrointestinal bleeding such as rebleeding or death. The Rockall score is a useful parameter to manage patients with non-variceal upper gastrointestinal bleeding as in– or outpatients.

Hintergrund: Der Rockall-Score [1] ist einer der bekanntesten Scoresysteme, die zur Vorhersage von Blutungsrezidiven und Mortalität bei Patienten mit akuter oberer gastrointestinaler Blutung entwickelt wurden. Jedoch konnten sich solche Scoresysteme bisher nicht in der klinischen Routine durchsetzen.