Maria Burian

Protein expression profiling in esophageal adenocarcinoma patients indicates association of heat-shock protein 27 expression and chemotherapy response.

Purpose: To identify pretherapeutic predictive biomarkers in tumor biopsies of patients with locally advanced esophageal adenocarcinomas treated with neoadjuvant chemotherapy, we used an explorative proteomic approach to correlate pretherapeutic protein expression profiles with tumor response to neoadjuvant chemotherapy. Experimental Design: Thirty-four patients with locally advanced esophageal adenocarcinomas who received neoadjuvant platin/5-fluorouracil–based chemotherapy before surgical resection were enrolled in this study. Response to chemotherapy was determined (a) by the amount of decline of [18F]fluorodeoxyglucose tumor uptake 2 weeks after the start of chemotherapy measured by positron emission tomography and (b) by histopathologic evaluation of tumor regression after surgical resection. Explorative quantitative and qualitative protein expression analysis was done through a quantitative differential protein expression analysis that used dual-isotope radioactive labeling of protein extracts. Selected identified biomarkers were validated by immunohistochemistry and quantitative real time reverse transcription-PCR. Results: Proteomic analysis revealed four cellular stress response–associated proteins [heat-shock protein (HSP) 27, HSP60, glucose-regulated protein (GRP) 94, GRP78] and a number of cytoskeletal proteins whose pretherapeutic abundance was significantly different (P < 0.001) between responders and nonresponders. Immunohistochemistry and gene expression analysis confirmed these data, showing a significant association between low HSP27 expression and nonresponse to neoadjuvant chemotherapy (P = 0.049 and P = 0.032, respectively). Conclusions: Albeit preliminary, our encouraging data suggest that protein expression profiling may distinguish cancers with a different response to chemotherapy. Our results suggest that response to chemotherapy may be related to a different activation of stress response and inflammatory biology in general. Moreover, the potential of HSPs and GRPs as biomarkers of chemotherapy response warrants further validation.

Sentinel node detection in Barrett's and cardia cancer.

Because of surveillance strategies in patients with known Barretts esophagus, more patients with high-grade dysplasia or early cancer in the distal esophagus and at the esophagogastric junction are identified. The need for and extent of lymphadenectomy in such patients are controversial. The technique of sentinel lymph node dissection (SLND) to diagnose early lymphatic spread is applied increasingly in tumors of the gastrointestinal tract. The poorly defined lymphatic drainage of the esophagogastric junction has so far prevented many investigators from performing SLND in tumors of this anatomic region. We report the first results of SLND in Barretts and cardia cancer. The preliminary experience indicates that the method is, even in this anatomical area, feasible and yields good results in early tumors. In advanced tumors, the method lacks sensitivity. Mapping should be done with blue dye and a radiocolloid. The concept of sentinel lymph node mapping and detection thus may open the door to individualized therapy for patients with high-grade dysplasia in a Barretts esophagus or with early Barretts and cardia cancer.

Loss of endothelial thrombomodulin predicts response to steroid therapy and survival in acute intestinal graft-versus-host disease

Steroid-refractory graft-versus-host disease causes significant morbidity and mortality after allogeneic stem cell transplantation. The pathomechanism of steroid resistance is currently not understood, but it has been suggested that endothelial cell dysfunction plays a role. Endothelial thrombomodulin was quantified along with histological markers of epithelial damage and cytotoxic T cells in colon biopsies from 51 allografted patients, and retrospectively correlated with response to steroids and survival. Loss of endothelial thrombomodulin was the strongest predictor of response to steroids (P=0.02) and nonrelapse mortality (P=0.01) in multivariate analyses adjusting for T-cell infiltrates, histological grading, vessel density, disease status, donor type, and conditioning therapy. Our data provide evidence that at disease onset, loss of endothelial thrombomodulin expression rather than excessive T-cell infiltration associates with steroid-refractory graft-versus-host disease and mortality. Prospective histological investigations are now warranted to improve diagnosis and prognostication of this core complication of stem cell transplantation.

Set of instruments for innovative, safe and sterile sigmoid access for natural-orifice transluminal endoscopic surgery.

Abstract One of the current main challenges in transluminal surgery is in obtaining sterile and secure access to the peritoneal cavity. Since the transgastric approach has not fulfilled these requirements up to now, a new transcolonic surgical approach was developed to achieve these objectives and enhance the potential of transluminal surgery. A new set of instruments comprising an endoscopic trocar, a flexible obturator and a modified transanal endoscopic microsurgery device was designed to permit sterile sigmoid access for transcolonic surgery. The set of instruments has already been successfully tested in an experimental in vivo survival study that confirmed safety and sterility as objectives during surgical intervention. The suitability of the instruments for use in the human anatomy was confirmed by a cadaveric study. Zusammenfassung Eine der Hauptherausforderungen in der heutigen transluminalen Chirurgie ist die Herstellung eines sterilen und sicheren Zugangs zur Bauchhöhle. Da die transgastrische Entrierung des Abdomens diese Anforderungen bis heute nicht hinreichend erfüllt hat, wird der neue Ansatz einer transkolischen Penetration eingeführt, um die definierte Zielsetzung zu erfüllen und die Potenziale der transluminalen Chirurgie zu erweitern. Ein neues Instrumentenset bestehend aus einem endoskopischen Trokar, einem flexiblen Obturator und einem modifizierten transanalen endoskopischen Mikrochirurgiegerät wurden entwickelt, um einen sterilen sigmoidalen Zugang für die transkolische Chirurgie zu ermöglichen. Das Instrumentenset konnte in einer experimentellen In-vivo-Studie erfolgreich getestet werden. Sicherheit und Sterilität, als wichtige Zielsetzungen, konnten während des ganzen chirurgischen Eingriffs gewährleistet werden. Die Tauglichkeit für den Einsatz in der menschlichen Anatomie wurde durch eine zusätzliche Leichenstudie bestätigt.

Zur Methodik des Sentinel Lymph Node Mapping

ZusammenfassungDas Sentinel-Lymphknoten-Mapping (sentinel: der Wächter) ist ein diagnostisches Verfahren, mit dessen Hilfe eine recht genaue Aussage über den Nodalstatus eines Tumorpatienten zu treffen ist und dies ohne die Morbidität der radikalen Lymphadenektomie. Es basiert auf der Annahme, dass es für jeden Tumor einen oder mehrere Lymphknoten gibt, die als erste von Metastasen befallen werden. Nach histopathologischer Untersuchung dieser Sentinel-Lymphknoten kann der Lymphknotenstatus des tumorabhängigen Lymphabflusses zuverlässig vorhergesagt werden. Es hat sich in diesem Zusammenhang bei bisher allen untersuchten Entitäten gezeigt, dass auch die Lymphknotenmetastasierung per continuitatem erfolgt und nicht „de principe“ in allen Kompartimenten besteht. So wurde beim Mamma- und beim Magenkarzinom bewiesen, das es sog. Skip-Metastasen (das Überspringen von Kompartimenten) kaum gibt.Die Hauptziele des Sentinel Lymph Node Mapping sind also die Verbesserung des Stagings durch Detektion der Lymphknoten, die mit höchster Wahrscheinlichkeit als erste Lymphknotenmetastasen entwickeln und zudem die Reduktion der Morbidität durch Individualisierung der Indikation zur radikalen Lymphadenektomie.AbstractSentinel lymph node mapping is used as a diagnostic method in order to increase staging accuracy without the well-known morbidities of radical lymphadenectomy. The sentinel node is defined as the first node to receive lymphatic drainage from a primary tumor. The sentinel node concept postulates that if the first draining node is negative for metastasis, the remaining lymph nodes in the nodal basin can be spared. Thus one can predict the status of the nodal basin with high accuracy. It also shows that lymphatic spread seems to follow certain rules that do not concern the whole lymphatic basin. Skip metastases were proven to be rare in breast and gastric cancer. The main issue in sentinel lymph node mapping remains the improvement of staging accuracy for detection of lymph nodes most likely to develop metastasis as well as reducing morbidity by planning lymphadenectomies individually for each tumor and each patient.

Seltene Ursache einer fulminanten Säureverätzung des Ösophagus

Peptic ulcer due to Zollinger-Ellison syndrome is a rare entity. In this case report a 55-year-old man had a medical history of esophageal reflux, vomiting, and diarrhea for 10 years. Despite continuous medication with a proton pump inhibitor, no complete recovery from symptoms was achieved. A diagnosis of gastrinoma was at first not considered. After discontinuation of the proton pump inhibitor for only a few days, the strong stimulation of the gastrinoma led to fulminant hydrochloric acid burn of the distal esophagus with iatrogenic or spontaneous perforation at the esophagogastral junction. We describe the operative treatment as a two-stage reconstruction with colon interposition and resection of the primary tumor in the duodenum.

Zur Methodik des Sentinel Lymph Node Mapping@@@Methods of sentinel lymph node mapping

ZusammenfassungDas Sentinel-Lymphknoten-Mapping (sentinel: der Wächter) ist ein diagnostisches Verfahren, mit dessen Hilfe eine recht genaue Aussage über den Nodalstatus eines Tumorpatienten zu treffen ist und dies ohne die Morbidität der radikalen Lymphadenektomie. Es basiert auf der Annahme, dass es für jeden Tumor einen oder mehrere Lymphknoten gibt, die als erste von Metastasen befallen werden. Nach histopathologischer Untersuchung dieser Sentinel-Lymphknoten kann der Lymphknotenstatus des tumorabhängigen Lymphabflusses zuverlässig vorhergesagt werden. Es hat sich in diesem Zusammenhang bei bisher allen untersuchten Entitäten gezeigt, dass auch die Lymphknotenmetastasierung per continuitatem erfolgt und nicht „de principe“ in allen Kompartimenten besteht. So wurde beim Mamma- und beim Magenkarzinom bewiesen, das es sog. Skip-Metastasen (das Überspringen von Kompartimenten) kaum gibt.Die Hauptziele des Sentinel Lymph Node Mapping sind also die Verbesserung des Stagings durch Detektion der Lymphknoten, die mit höchster Wahrscheinlichkeit als erste Lymphknotenmetastasen entwickeln und zudem die Reduktion der Morbidität durch Individualisierung der Indikation zur radikalen Lymphadenektomie.AbstractSentinel lymph node mapping is used as a diagnostic method in order to increase staging accuracy without the well-known morbidities of radical lymphadenectomy. The sentinel node is defined as the first node to receive lymphatic drainage from a primary tumor. The sentinel node concept postulates that if the first draining node is negative for metastasis, the remaining lymph nodes in the nodal basin can be spared. Thus one can predict the status of the nodal basin with high accuracy. It also shows that lymphatic spread seems to follow certain rules that do not concern the whole lymphatic basin. Skip metastases were proven to be rare in breast and gastric cancer. The main issue in sentinel lymph node mapping remains the improvement of staging accuracy for detection of lymph nodes most likely to develop metastasis as well as reducing morbidity by planning lymphadenectomies individually for each tumor and each patient.

A new endoscopic/laparoscopic interdisciplinary training and education (ELITE) system for NOTES

For endoluminal and laparoscopic training and education, sufficient training models are available. Neither of these, however, are suitable for NOTES. We developed a new simulation model including a highly immersive endoluminal and intraabdominal environment to perform both combined laparoscopic/endoscopic rendezvous procedures as well as NOTES interventions. Material and methods: The anatomical mockup of a human trunc including the head and stumps of the arms and legs contains the entire gastrointestinal tract. The stumps of the legs are fixed in lithotomy position to provide access to the anus. Flab valves are integrated into the esophagus and the rectum to retain the insufflated gas. The abdominal cavity – based upon a former CLA prototype (Coburger Lehrmittelanstalt, Coburg, Germany) is gas-tight with an extendable abdominal wall. Transmural insertion of Veress needles or trocars is possible without gas loss. The texture of the GI-tract and of the gallbladder can be mechanically dissected and approximated by standard flexible instruments. Results: The comprehensive spectrum of current translumenal endoscopic surgery could successfully be performed via the transgastric or transsigmoid (ISSA) approach. Since no electrocautery can be applied, dissecting with scissors was required. Reliable closure of canalicular structures could be achieved by clips and stapling devices. Conclusion: The newly created simulation model for NOTES appears to be useful for training and education of NOTES procedures. The only restriction is that electrocautery cannot be applied. Supported in part by Bavarian Research Foundation Keywords: NOTES, Training, Simulation, Hybrid Procedures, Laparoscopy

Seltene Ursache einer fulminanten Säureverätzung des Ösophagus@@@Rare occurrence of fulminant acid burn of the esophagus

Peptic ulcer due to Zollinger-Ellison syndrome is a rare entity. In this case report a 55-year-old man had a medical history of esophageal reflux, vomiting, and diarrhea for 10 years. Despite continuous medication with a proton pump inhibitor, no complete recovery from symptoms was achieved. A diagnosis of gastrinoma was at first not considered. After discontinuation of the proton pump inhibitor for only a few days, the strong stimulation of the gastrinoma led to fulminant hydrochloric acid burn of the distal esophagus with iatrogenic or spontaneous perforation at the esophagogastral junction. We describe the operative treatment as a two-stage reconstruction with colon interposition and resection of the primary tumor in the duodenum.

Rare occurrence of fulminant acid burn of the esophagus

Peptic ulcer due to Zollinger-Ellison syndrome is a rare entity. In this case report a 55-year-old man had a medical history of esophageal reflux, vomiting, and diarrhea for 10 years. Despite continuous medication with a proton pump inhibitor, no complete recovery from symptoms was achieved. A diagnosis of gastrinoma was at first not considered. After discontinuation of the proton pump inhibitor for only a few days, the strong stimulation of the gastrinoma led to fulminant hydrochloric acid burn of the distal esophagus with iatrogenic or spontaneous perforation at the esophagogastral junction. We describe the operative treatment as a two-stage reconstruction with colon interposition and resection of the primary tumor in the duodenum.