Showing papers by "J. R. Siewert published in 2000"

Cancer of the esophagogastric junction

Abstract: In the Western world, there has been an alarming rise in the incidence and prevalence of adenocarcinoma arising at the esophagogastric junction during recent decades. Epidemiological, clinical and pathological data support a sub-classification of adenocarcinomas arising in the vicinity of the esophagogastric junction (AEG) into adenocarcinoma of the distal esophagus (Type I), true carcinoma of the cardia (Type II) and subcardial carcinoma (Type III). While most, if not all, adenocarcinomas of the distal esophagus arise from areas with specialized intestinal metaplasia, which develop as a consequence of chronic gastroesophageal reflux, the etiology and pathogenesis of true carcinoma of the gastric cardia and subcardial gastric cancer is not clear at present. Although a subgroup of true carcinomas of the gastric cardia may also develop within short segments of intestinal metaplasia at the esophagogastric junction, a causal relation between these tumors and gastroesophageal reflux has been difficult to establish. Irrespective of the etiology, a complete removal of the primary tumor and its lymphatic drainage has to be the primary goal of any surgical approach to adenocarcinoma of the esophagogastric junction. Our experience in the management of more than 1000 such patients during the past 18 years suggests that an individualized therapeutic strategy oriented by tumor type and stage results in survival rates superior to those reported with a more indiscriminate approach. This individualized strategy prescribes a transmediastinal esophagectomy with lymphadenectomy in the lower posterior mediastinum and along the celiac axis for Type I tumors, extended total gastrectomy with transhiatal resection of the distal esophagus and D2 lymphadenectomy for Type II and Type III tumors, a limited resection of the esophagogastric junction and distal esophagus with interposition of a pedicled jejunal segment for uT1N0 tumors, and neoadjuvant chemotherapy followed by resection for uT3/T4 tumors. Extensive preoperative staging is essential to allow correct selection of the appropriate therapeutic strategy using this tailored approach.

Malignant progression in Barrett's esophagus: pathology and molecular biology.

Abstract: Due to its increasing incidence, esophageal adenocarcinoma and its precursor lesions have received increasing attention in recent years. The histopathologic steps in the process of malignant progression in Barrett’s esophagus are well described and include the following: (a) metaplasia of the normal esophageal squamous epithelium to a specialized intestinal glandular epithelium, (b) development of dysplasia (classified histologically as low and high grade), and (c) development of adenocarcinoma characterized by invasive and metastatic potential. Intestinal metaplasia can be identified by the presence of goblet cells, the detection of which can be aided by finding mucin stained by Alcian blue at low pH. Despite this well-characterized sequence, the timing of the development of dysplasia and the subsequent transition to carcinoma and the risk of development of carcinoma in low-and high-grade dysplasia are not precisely known. In addition, there are problems in the identification of dysplasia, including sampling error and interobserver discrepancies among pathologists. A better understanding of the mechanisms of these events would allow early identification and elimination of high-risk lesions before adenocarcinoma with its attendant poor prognosis were able to develop. In order to better understand this process and to potentially identify early markers of malignant transformation, a variety of molecular studies have been carried out in recent years on adenocarcinoma and its precursor lesions in Barrett’s esophagus. On the phenotypic level, increased expression and changes in pattern of expression of proliferation marker (Mib-1) Ki-67 antigen, overexpression of p53 protein, overexpression of growth factors such as epidermal growth factor (EGF), c-erbB2, and transforming growth factor (TGF)-a, decreased and abnormal expression of the cell adhesion molecule E-cadherin, and, in carcinomas, increased expression of serine proteases have all been described. A new area of interest is the family of rab proteins, which play an important role in maintaining cell polarity in the gastrointestinal tract. Increased expression of one of these proteins, rab ll, has been described in low-grade, but not high-grade dysplasia. In cytogenetic studies, an increased S-phase fraction, followed by an increased tetraploid (4N) fraction and then aneuploidy, has been described. So far, the specific genes which have been most thoroughly investigated have been p53, APC, p16, and the sites of probable tumor suppressor genes, including 3p (FHIT), 13q, and 18q. With only a few exceptions (i.e., rabll expression, and possibly mutations of FHIT), the numerous molecular abnormalities which have been described occur late in malignant progression, which means that the best marker which presently exists to identify high-risk lesions in Barrett’s esophagus is the histologic identification of dysplasia in endoscopic biopsies, especially high-grade dysplasia. We are presently beginning studies using laser microdissection and competitive genomic hybridization (CGH), which could help to identify new chromosomal areas that might contain genes that are crucial in the early phases of malignant progression in Barrett’s esophagus. In the future, identification of such early molecular events which predispose to carcinoma development will allow more precise and earlier risk assessment for individual patients, therefore enabling more effective therapy.

Risk analysis in esophageal surgery.

Abstract: The postoperative mortality after esophagectomy still remains a major factor influencing the prognosis of esophageal cancer and largely depends on the patient’s preoperative physiological status.

Comparison of loss of heterozygosity and microsatellite instability in adenocarcinomas of the distal esophagus and proximal stomach.

Abstract: Adenocarcinoma of the gastroesophageal junction is rapidly rising in incidence. It has been proposed that these tumors be classified as three different types: distal esophageal (AEG I), cardia (AEG II), and subcardia (AEG III). Using comparative genomic hybridization (CGH) analysis, one recent study reported that the 14q chromosomal arm showed a significantly higher rate of deletion in esophageal than in cardia adenocarcinoma. Using a microsatellite analysis technique, we analyzed this area and regions in the vicinity of the APC, DCC, and p53 genes. Tumor and normal tissues were microdissected from 54 cases (27 AEG I and 27 AEG III). DNA was extracted and then amplified using seven fluorescent-labeled microsatellite markers, one pair each on 5q, 18q, and 17p and four on 14q. The results were analyzed for loss of heterozygosity (LOH) and microsatellite instability (MSI). LOH varied from 20% to 30% at each locus except for the 17p locus, where it was slightly above 50% in both groups. No significant differences in LOH or MSI were found between the esophageal and gastric tumors, including the 14q chromosomal arm. These results fail to confirm the finding that abnormalities on the 14q chromosomal arm distinguish between distal esophageal and proximal gastric tumors.

Individualized surgical strategies for cancer of the esophagogastric junction.

Abstract: Due to their borderline location between the stomach and esophagus the optimal surgical strategy for patients with adenocarcinoma of the esophagogastric junction is controversial. Irrespective of the surgical approach a complete removal of the primary tumor and its lymphatic drainage has to be the primary goal of surgical treatment of such tumors. Based on the experience with surgical resection of more than 1000 patients with adenocarcinoma of the esophagogastric junction we recommend an individualized surgical strategy guided by tumor stage and topographic location of the tumor center or tumor mass. This requires detailed preoperative staging and classification of tumors arising in the vicinity of the esophagogastric junction into adenocarcinoma of the distal esophagus (AEG Type I Tumors), true carcinoma of the gastric cardia (AEG Type II Tumors) and subcardial gastric carcinoma infiltrating the esophagogastric junction (AEG Type III Tumors). In patients with Type I Tumors transthoracic esophagectomy offers no survival benefit over radical transmediastinal esophagectomy, but is associated with higher morbidity. In patients with Type II or Type III tumors an extended total gastrectomy results in equal or superior survival and less postoperative mortality than a more extended esophagogastrectomy. In patients with early tumors, staged as uT1 on preoperative endosonography, a limited resection of the proximal stomach, cardia and distal esophagus with interposition of a pedicled isoperistaltic jejunal segment allows a complete tumor removal with adequate lymphadenectomy and offers excellent functional results. Multimodal treatment protocols with neoadjuvant chemotherapy or combined radiochemotherapy followed by surgical resection appear to markedly improve the prognosis in patients with locally advanced tumors who respond to preoperative treatment. With this tailored approach extensive preoperative staging becomes mandatory for an adequate selection of the appropriate therapeutic concept.

Fibrovascular esophageal polyp as a diagnostic challenge.

Abstract: Fibrovascular polyps are rare benign esophageal tumors that usually arise from the proximal third of the esophagus. We present the case of a 48-year-old man with a history of dysphagia and 7-kg weight loss over a period of 2 months. A barium swallow showed a distended esophagus with a tumor extending from the upper esophageal sphincter to the cardia. On a thoracic computed tomographic scan, a homogeneous intramural mass with a density of 22 Hounsfield units was seen, which extended throughout the entire esophagus. Fiberoptic endoscopy confirmed the presence an intramural tumor beginning at the upper esophageal sphincter and reaching to the cardia. The tumor was completely covered with mucosa, except for an ulcerated area at its distal end, which herniated into the stomach. On endoscopic ultrasound, the tumor appeared to grow submucosally and to respect the muscularis propria. Endoscopic biopsies from the ulcerated distal aspect of the tumor suggested a leiomyoma. None of the imaging modalities used revealed evidence of a polyp or intraluminal esophageal tumor. Rather, a potentially malignant extensive intramural tumor was suspected, and an esophagectomy was performed. Only at the time of removal of the specimen did it become evident that the tumor mass was located intraluminally with a pedicle in the region of the upper esophageal sphincter. The final pathological diagnosis was a giant fibrovascular polyp of the esophagus.

Malignant Degeneration of Barrett’s Esophagus: Clinical Point of View

Abstract: The incidence of adenocarcinoma of the distal esophagus is increasing at an alarming rate. Intestinal metaplasia in the distal esophagus, i.e. Barrett’s esophagus, has been identified as the single most important risk factor for these tumors. Barrett’s esophagus develops as a consequence of chronic mucosal injury in up to 10% of patients with long-lasting gastroesophageal reflux disease. Experimental and clinical data indicate that adenocarcinoma of the distal esophagus is a direct consequence of mixed (i.e., acid and bile) reflux into the esophagus. Interestingly, Helicobacter pylori infection of the stomach appears to exert a protective effect against the development of esophageal adenocarcinoma. Neither aggressive medical acid suppression nor antireflux surgery can induce a predictable regression of Barrett’s esophagus or exert a protective effect against its malignant degeneration. Endoscopic ablation of Barrett’s esophagus, although appealing, currently constitutes a potentially dangerous procedure without proven benefit for the patient. Since the development of Barrett’s adenocarcinoma follows a multistep process from metaplasia through increasingly severe grades of dysplasia, close endoscopic surveillance with extensive biopsies currently remains the only means to identify patients at risk for malignant degeneration and detect esophageal adenocarcinoma at an early and curable stage.

Image processing in esophageal scintigraphy: topography of transit times.

Abstract: In the investigation of esophageal transport, the knowledge provided by scintigraphy is mostly based upon the extraction as well as representation of the information obtained. Recently, new tools have been developed for use in computer-based image processing which have made visualization and quantitation of esophageal bolus transport possible through depiction of the 'topography of transit times'. Data extracted from the images obtained in multiple swallowing studies from a single healthy volunteer as well as in patients suffering from gastroesophageal reflux disease (GERD) and from Barrett's esophagus are compressed, filtered and depicted in quantifiable concise plots or multidimensional images. Profile plots demonstrated a considerable increase in local transit times along the esophagus superimposed, however, by a distinctive pattern of local delays. Above the level of the lower esophageal sphincter (LES), the bolus accumulates in a functional ampulla. Subprocesses of bolus transit through the LES, disclosed by spatiotemporal enhancement, allow for the differentiation between mass transit of the bolus and closure of the LES which was considerably retarded in the case of the patient with Barrett's esophagus. The image-processing tools developed for topographic visualization of transit times for esophageal bolus transport have greatly improved the extraction and quantifiable depiction of information obtained by scintigraphy. This can be used for definition of pathognomonic indices.

Complications and pitfalls of open and laparoscopic antireflux surgery

Abstract: Background: With the introduction of the laparoscopic approach, antireflux surgery has recently experienced a renaissance as an effective and minimally invasive alternative to life long medical treatment in patients with gastroesophageal reflux disease. Antireflux surgery, whether performed via the traditional open or new laparoscopic approach, is, however, not devoid of complications and failures. Methods: The current literature on open and laparoscopic antireflux surgery was reviewed with focus on complications, side effects and failures. Results: Independent of the surgical approach, complications occur in up to 12 % of patients. Up to 15 % of patients who had an antireflux operation will experience some form of recurrent, persistent or new symptoms. An analysis of failed antireflux procedures shows that technical errors during the initial procedure and wrong patient selection account for the vast majority of the failures. The management of patients with a failed antireflux procedure requires an individual therapeutic approach based on the presenting symptoms, the results of function tests, and the intraoperative findings. The surgeon caring for patients with failed antireflux procedures should be intimately acquainted with the whole spectrum of revisional, resective, and reconstructive procedures of the stomach, cardia, and esophagus. Conclusions: A profound understanding of the pathophysiology of gastroesophageal reflux disease, a careful selection of patients, a meticulous attention to the technical details of the procedure and an appreciation of the potential sources of failure are therefore the key to successful antireflux surgery. In this respect the selection of the surgical access, i.e. laparoscopic or via laparotomy, appears of minor importance.

[New therapy approaches in tumors of the upper gastrointestinal tract (esophagus, stomach)].

Abstract: Trotz zahlreicher Phase II und Phase III-Studien ist der Stellenwert der neoadjuvanten Therapie in der Behandlung von Patienten mit Oesophagus- und Magencarcinomen noch nicht eindeutig definiert. Dieses begrundet sich nicht zuletzt aus den unterschiedlichen Eingangskriterien und Stagingmodalitaten der verschiedenen Studien. Bei der Therapie des Oesophaguscarcinoms hat sich fur die neoadjuvante Chemotherapie nach mehreren Phase III-Studien kein Vorteil ergeben. Sie sollte nur im Rahmen von innovativen Studienprotokollen durchgefuhrt werden. Es ist jedoch belegt, das beim Oesophaguscarcinom die kombinierte Radio-Chemotherapie der alleinigen Strahlentherapie uberlegen ist. Fur die kombinierte Radio-Chemotherapie, verglichen mit der alleinigen Chirurgie, deutet sich ein Vorteil fur die Vorbehandlung an. Bei lokal-fortgeschrittenen Plattenepithelcarcinomen des Oesophagus eroffnet die Radio-Chemotherapie 30–60 % der Patienten die Moglichkeit auf eine R0-Resektion, dies aber mit deutlich erhohter postoperativer Morbiditat und Letalitat. Die neoadjuvante Chemotherapie ist beim Magencarcinom noch ein experimenteller Ansatz, die Wirksamkeit wird in einer laufen Studie der EORTC (European Organisation for Research and Treatment of Cancer) zur Zeit getestet. Ein Schwerpunkt in der klinischen Forschung im Rahmen multimodaler Konzepte ist die pratherapeutische Erfassung der Patienten, die auf die neoadjuvante Therapie ansprechen. Erste Ergebnisse zeigen, das mit Hilfe molekularbiologischer Parameter eine „Response-Predicition“ moglich sein konnte. Mit der PET mit 18-FDG scheint ein fruhzeitiges Erfassen des Response unter laufender Therapie, nach ca. 1 Woche, moglich zu sein. Neue Therapeutika wie monoklonale Antikorper zum Einsatz in der adjuvanten Therapie, die beim Magencarcinom einen neuen Stellenwert erhalten hat, befinden sich in Phase I-Studien.

Ischemic spinal cord syndrome after transthoracic esophagectomy: two cases of a rare neurologic complication.

Abstract: Anterior spinal artery syndrome (ASAS) is a rare complication after surgery of the thoracic or abdominal aorta. The sulco commissuralis syndrome represents a partial or incomplete ASAS. We report two cases of ischemic spinal cord syndromes after transthoracic esophagectomy. This represents a prevalence of this syndrome of 0.2% in more than 1000 consecutive esophagectomies performed at our institution. Patient 1 developed an ASAS on the first day after esophagectomy. Patient 2 showed the pathognomonic clinical signs associated with sulco commissuralis syndrome after an asymptomatic window. In both patients, the extent of the neurologic symptoms initially improved but then remained unchanged for the rest of the follow-up of 9 and 12 months. Although the prognosis of neurologic syndromes resulting from spinal cord infarction is poor, preoperative tests to identify patients at risk appear not to be justified because of the very low incidence of these syndromes after esophagectomy and the poor sensitivity and specificity of currently available diagnostic modalities. However, the possibility of ischemic spinal cord syndrome should be kept in mind when patients present with neurologic symptoms after esophagectomy.

Erweiterte Diagnostische Laparoskopie (EDL)

Abstract: Grundlagen: Die sogenannte erweiterte diagnostische Laparoskopie (EDL) ist ein minimal-invasiver chirurgischer Eingriff, der die Exploration des gesamten Bauchraumes ermoglicht und somit das pratherapeutische Staging bei malignen Erkrankungen erheblich verbessern kann.

Interventionelle oder operative Therapie aus chirurgischer Sicht

Abstract: In einer prospektiven Analyse wurden bei 174/3346 Pat. (5,2%) nach grosen viszeralchirurgischen Eingriffen intraabdominelle Abszesse mit PAD versorgt. Bei 149/174 Pat. (85,6%) war die PAD als alleinige Therapiemasnahme erfolgreich. 25/174 Pat. (14,4%) musten sekundar operiert werden. Punktionsbedingte Komplikationen traten bei 8/174 Pat. (4,6%) auf. Die punktionsbedingte Mortalitat war 0,6% (1/174 Pat.). In der eigenen Erfahrung ist das interventionelle Vorgehen mit PAD heute die Therapie der Wahl wegen der hohen Erfolgsrate, niedrigen Komplikationsrate oder geringeren Invasivitat. Eine operative Therapie ist weiterhin erforderlich: primar bei der generalisierten Peritonitis und Abszessen ausgehend von einer grosen Insuffizienz/Fistel und sekundar bei Versagen der PAD; d. h. keine klinische Besserung trotz PAD-Kontrolle/Korrektur (≤48 h) und Persistieren der Abszeshohle (2–3 Wochen).

Endoskopisch-laparoskopische Eingriffe am Kolon

Abstract: SummaryA combined endocavitary (laparoscopic) and endoluminal (coloscopic) approach allows to compensate methodologic restrictions of both procedures. With this procedure local excisions of the colonic wall in localised, (still) benign lesions are feasible. Combined procedures were applied in 33 patients with colonic lesions. The conversion rate was 9%. In 2 cases anastomotic fistulae were seen, which could be treated conservatively. The postoperative time of hospitalisation was 10 days. In patients with uncomplicated local excisions this time period was markedly shorter than in patients with segmental resection of the colon (9 versus 11 days). The simultaneous colonoscopy during laparoscopic procedures of the colon is valuable in cases of local excision of localised benign lesions. In cases where the findings a priori imply a laparoscopic segment resection, intraoperative colonoscopy is not necessary in the first place. Copyright © 2000 S. Karger GmbH, Freiburg