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J R Siewert

Publications and source records attributed to J R Siewert.

At least 55 records · Page 3Linked to original sources
PubMed2004

[Anastomotic leaks in the upper gastrointestinal tract].

Anastomotic leaks are still among the most common severe postoperative complications and account for the majority of postoperative deaths after esophagectomy and gastrectomy. Every disturbance of the normal postoperative course should trigger surgeons to consider an underlying anastomotic leak and initiate a specific diagnostic workup. This includes direct endoscopic inspection of the anastomosis to evaluate the vitality of the anastomosed organs and the size of the leak. Adequate external drainage of the leak and prevention of further contamination are the primary therapeutic goals. Selection of therapy is guided by the available modalities for sufficiently draining the leak and avoiding sepsis. The spectrum of therapeutic options ranges from simple opening of the neck incision in cervical esophageal anastomoses, interventional placement of drains, to endoscopic intervention with closure of the fistula or placement of stents, and reoperation with exclusion, diversion, or discontinuity resection.

Anastomosis, Surgical↗
PubMed2004

Responders benefit from neoadjuvant radiochemotherapy in esophageal squamous cell carcinoma: results of a prospective phase-II trial.

BACKGROUND: We present the results of a prospective phase-II-study of neoadjuvant combined radiochemotherapy followed by surgical resection in patients with histological proven locally advanced squamous cell carcinoma of the esophagus located at or above the level of the tracheal bifurcation. METHODOLOGY: Between February 1995 and March 2000 a total of 76 patients with esophageal squamous cell carcinoma (uT3/4N0/+-categories) received simultaneous combined neoadjuvant radiochemotherapy consisting of a continuous intravenous infusion of 5-fluorouracil (300 mg/m2/day) 7 day per week concurrently with conventional fractioned external beam radiation therapy (2 Gy/day), five fractions per week up to a total dose of 30 Gy. RESULTS: Radiochemotherapy related acute severe toxicity rate (CTC-grade-III) occurred in 34 patients, two patients died. Sixty-four patients underwent surgery with a complete resection in 48 patients. Three patients died during a 90-day post-operative course. The histopathological workup revealed no viable residual tumour cells in eight patients (ypCR) and according to the modified criteria of Mandard in 26 patients a histopathological response. Twenty-two of these patients underwent a R0-resection. The median follow-up time was 5.4 years with an overall median survival time of 20.6 months. The median survival in the 26 responders was 32.3 months versus 19.5 months in 38 non-responders (p=0.03). CONCLUSIONS: Patients with locally advanced squamous cell carcinoma of the esophagus, who respond to preoperative neoadjuvant combined radiochemotherapy, seem to have more benefit from subsequent resection than non-responding patients.

Adult↗
PubMed2004

Malignant degeneration of Barrett's esophagus: the role of the Ki-67 proliferation fraction, expression of E-cadherin and p53.

Barrett's columnar epithelium with dysplasia is the most important risk factor for adenocarcinoma of the distal esophagus. The molecular mechanisms responsible for progression of columnar metaplasia to dysplasia and invasive carcinoma are mostly unknown. We investigated expression of the tumor suppressor gene p53, E-cadherin expression and cell proliferation in the metaplasia-dysplasia-carcinoma sequence of esophageal adenocarcinoma. In 24 patients with R0-resected adenocarcinomas of the distal esophagus we evaluated the expression of E-cadherin (antibody HECD-1), mutated p53 (antibody DO1) and cell proliferation (antibody MiB1) by immunohistochemistry in sections of adenocarcinoma, columnar metaplasia, with and without dysplasia, and in squamous epithelium of the esophagus. No p53 immunoreactivity was seen in sections of normal squamous epithelium or columnar metaplasia. Fifty per cent of invasive adenocarcinomas stained positive for mutated p53. The p53 expression correlated with the T-category (P = 0.048) and the N-category (P = 0.024). There was a significant decrease in the expression of E-cadherin from columnar metaplasia to dysplasia and to esophageal adenocarcinoma (P < 0.0001). Expression of E-cadherin in columnar metaplasia without dysplasia was similar to that seen in normal squamous epithelium of the esophagus. The Ki-67 proliferation fraction increased significantly from normal squamous epithelium to columnar metaplasia to dysplasia and to invasive carcinoma (P < 0.001), with a marked expansion of the proliferative component. There was no correlation between cell proliferation, E-cadherin expression and the tumor stage. In contrast to the alterations in the p53 expression, a decreased E-cadherin expression and the expansion of the proliferative component represent an early phenomenon in the malignant degeneration of Barrett's esophagus. This might aid in the early detection of esophageal adenocarcinoma.

Adenocarcinoma↗
PubMed2004

[Prediction of response to neoadjuvant chemotherapy in Barrett's carcinoma by quantitative gene expression analysis].

The potential of gene expression profiles to predict the response to neoadjuvant chemotherapy in patients with advanced adenocarcinoma of the esophagus was analyzed. Paraffin-embedded endoscopic esophageal tumor biopsies of 38 patients with advanced esophageal adenocarcinoma (Barrett's adenocarcinoma) were included. All patients underwent two cycles of cisplatin and fluorouracil (5-FU) therapy with or without additional paclitaxel (taxol) followed by abdominothoracal esophagectomy. RNA expression levels of 5-FU-metabolism associated genes thymidylate synthase (TS), thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD), methylenetetrahydrofolate reductase (MTHFR), MAP7, ELF3, as well as of platinum and taxane associated related genes caldesmon, excision cross-complementing genes (ERCC1 and ERCC4) HER2-neu, DNA damage-inducible gene 45 (GADD45) and multidrug resistance genes (MDR1, MRP1) were determined using real-time RT-PCR. Expression levels were correlated with the histopathological response to chemotherapy assessed in surgically resected specimens. Responding patients showed significantly higher pretherapeutic expression levels of MTHFR (p = 0.012), Caldesmon (p = 0.016), MRP1 (p = 0.007) and MDR1 (p = 0.025). In addition, patients with high pretherapeutic MTHFR and MRP1 levels had a survival benefit after surgery (p = 0.013 and p = 0.015, respectively). Additionally, intratumoral heterogeneity of gene expression of selected genes (TP, DPD, MTHFR, HER2-neu, Caldesmon, ERCC4, MRP1) was additionally verified in 9 untreated Barrett's adenocarcinoma by examination of 5 distinct tumor areas and was observed in 12.7% (5.6%-23.5%, CI 95%) of all cases analyzed. Our results indicate that determination of mRNA levels of a few genes may be useful for the prediction of the success of neoadjuvant chemotherapy in individual cancer patients with advanced adenocarcinoma of the esophagus.

Adenocarcinoma↗
PubMed2003

The influence of periarterial papaverine application on intraoperative renal function and blood flow during laparoscopic donor nephrectomy in a pig model.

BACKGROUND: The transplantation of live donor kidneys harvested laparoscopically is associated with a higher incidence of delayed graft function than the transplantation of grafts harvested via the open technique. The delay is believed to be due to a decrease in renal blood flow during laparoscopic donor nephrectomy (LDN). The aim of this study was to evaluate whether renal function and blood perfusion can be enhanced by the periarterial application of papaverine during LDN. METHODS: Renal function and blood flow were studied in a porcine model that included a total of 24 pigs (20-30 kg). In 12 of the pigs, urine output and creatinine clearance were determined as measures of renal function. In the other 12 pigs, renal blood flow was determined using fluorescent-labeled microspheres. In each group, the pigs were randomized into two subgroups, one with and one without a perivascular injection of 50 mg papaverine. RESULTS: As compared to the controls, the animals receiving papaverine had a significantly higher urine output (3.1 +/- 1.6 vs 0.9 +/- 0.45 ml/h/kg; p = 0.02), superior creatinine clearance (2.22 +/- 0.5 vs 0.95 +/- 0.1 ml/min/kg; p = 0.038), and enhanced renal blood flow (4.9 +/- 2.2 vs 2.1 +/- 0.8 ml/min/g; p = 0.008). CONCLUSIONS: When applied to the tissue surrounding the renal artery, papaverine substantially improves renal function and blood flow during laparoscopic live kidney donation. Whether graft optimization during kidney procurement also translates into improved posttransplantation function remains to be established.

Animals↗
PubMed2003

[Carcinoma of the oesophagogastric junction and Barrett's esophagus: an almost clear oncologic model?].

From a clinical and biological point of view, the term "adenocarcinoma of the esophagogastric junction" (AEG) encompasses several distinct tumor entities. The topographic anatomic classification into adenocarcinoma of the distal esophagus (AEG I), true carcinoma of the cardia (AEG II), and subcardiac gastric cancer (AEG III) also reflects differences regarding the pathogenesis of these tumors and is increasingly accepted worldwide. Associated Barrett's esophagus, which usually develops as a consequence of chronic gastroesophageal reflux, can be documented in practically all patients with AEG I tumors and constitutes the most important precancerous lesion. A metaplasia-dysplasia-carcinoma sequence has been confirmed for these tumors. Barrett's esophagus is thus considered a model for studies on carcinogenesis and the prevention of esophageal adenocarcinoma. Its pathogenetic role in AEG II and III tumors must, however, be discussed differently. Our own experience shows that pathogenetic mechanisms similar to those in AEG I tumors may be present in up to 30% of tumors classified as AEG II. The majority of AEG II tumors, however, show morphologic, biologic and pathogenetic similarities with AEG III tumors and proximal gastric cancer.

Adenocarcinoma↗
PubMed2003

The 'angiogenic switch' in the progression from Barrett's metaplasia to esophageal adenocarcinoma.

AIMS: We investigated VEGF expression and neovascularisation in the metaplasia-dysplasia-carcinoma sequence of Barrett's esophagus and 47 shades of adenocarcinoma. METHOD: Slides of 27 cases of Barrett's metaplasia and high grade dysplasia were immunostained for VEGF, CD 31 and alpha-sm actin to discriminate between mature and immature vessels. VEGF stained slides were quantitatively evaluated measuring optical density with a computer based program. The neovascularisation coefficient was estimated with an interactive analytic computer program. RESULTS: The median VEGF expression increased from metaplasia to advanced carcinoma. VEGF expression and the neovascularisation coefficient reached statistical significance between Barrett's metaplasia and high grade dysplasia (p<0.001), but were not statistically different between high grade dysplasia and microinvasive carcinoma (p=0.421; p=0.146). Comparing microinvasive to advanced carcinoma the difference was significant for both parameters (p<0.001). CONCLUSIONS: Based on a quantitative computer based evaluation program, the present study suggests, that an angiogenic switch might exist and that it is an early event in the metaplasia-dysplasia-carcinoma sequence of Barrett's carcinoma. The neovascularisation phase in Barrett's carcinoma may precede tumour growth.

Adenocarcinoma↗
PubMed2003

Delayed aortic rupture after radiochemotherapy and esophagectomy for esophageal cancer.

Spontaneous rupture of major vessels is a known though rare complication in treatment of patients with esophageal cancer, but its pathophysiology is not very well understood. We herein report about the sudden death of a 42-year-old man due to spontaneous aortic rupture, 11 days after transthoracic esophagectomy. Because of a locally advanced squamous cell carcinoma of the distal esophagus, which was considered irresectable at the time of presentation, the patient had received one course of chemotherapy followed by synchronous chemoradiation (60 Gy, 5-fluorouracil and cisplatin) prior to surgery. We discuss the patho-anatomic findings of the postmortem examination concerning alterations of the aortic wall and the potential correlations with aggressive radiochemotherapy protocols.

Adult↗
PubMed2002

Comparison of two density gradient centrifugation systems for the enrichment of disseminated tumor cells in blood.

BACKGROUND: The detection of disseminated tumor cells in peripheral blood is limited by the presence of very few tumor cells within a large number of blood cells. Therefore, tumor cell detection calls for enrichment systems with effective depletion of blood cells and high tumor cell recovery. METHODS: We compared the new density gradient centrifugation method OncoQuick with the standard method of Ficoll. The enriched cell fractions were quantified. Tumor cell spiking experiments examined the recovery of tumor cells as detected by immunocytochemistry and cytokeratin-20 reverse transcriptase-polymerase chain reaction (RT-PCR). Clinical application of OncoQuick was evaluated in 37 peripheral blood samples of patients with gastrointestinal carcinomas. RESULTS: The depletion of mononuclear cells (MNCs) in the enriched cell fraction after OncoQuick centrifugation was 632-fold, with an average cell number of 9.5 x 10(4), compared with Ficoll, with a depletion factor of 3.8 and a mean number of 1.6 x 10(7) MNCs. The mean tumor cell recovery rates were 87% for OncoQuick and 84% for Ficoll. The increased depletion of MNCs with OncoQuick centrifugation further simplified immunocytochemical evaluation by reducing the number of cytospins and increasing the tumor cell density. Due to the reduced number of co-enriched MNCs by OncoQuick, the blood volume, which could be analyzed in one RT-PCR reaction, was increased up to 30 ml. Examination of peripheral blood samples from 37 patients with gastrointestinal tumors showed a cytokeratin-20 detection rate of 30% and a significant correlation with the presence of distant metastases (P < 0.02). CONCLUSIONS: OncoQuick significantly reduced the co-enriched number of MNCs, with a high tumor cell recovery rate. Processing blood from tumor patients with OncoQuick increased the chance of detecting circulating tumor cells.

Cell Count↗
PubMed2002

Pneumatosis cystoides intestinalis coli.

The rare case of a 63-year-old male diagnosed with pneumatosis cystoides intestinalis coli is presented and discussed. The patient was found to have an unsymptomatic pneumoperitoneum on plain chest x-ray. The results of a contrast enema, computed tomography scan, and laparoscopy are presented. The patient had an uneventful hospital course without any specific therapy. Causes and possible therapeutic options are discussed.

Diagnosis, Differential↗
PubMed2002

[Necessary prerequisites for the function of an oncological competence center. Information technology, documentation of findings and telecommunication].

INTRODUCTION: The organisation of an interdisciplinary cancer center, especially the establishment of a daily tumorboard requires adequate hardware and intelligent software, which is not available in most hospitals and described here with concepts, realisation and first clinical results. MATERIALS AND METHODS: Based on a TCP/IP network and several inhomogeneous department subsystems we developed an intranet-based oncological documentation- and conference software (oncofile), which can be easily operated and administered in a web browser. Common digital media can be imported and the concept allows for paperless organisation of the daily tumor board. The expert decisions are documented online during tumor board runtime together with selected clinical images and the consensus of the decisionmakers. Local therapeutic guidelines as well as trial information can be accessed over the intranet, and interfaces for internet- and telecommunication are used for second opinion and integration of external expertise. RESULTS: Between 10/99 and 2/2002 3298 presentations of 2438 cases were made in the daily tumor board. 74% of the patients had a curative oncological treatment concept, and 24% of the patients received neoadjuvant treatment. 49% of the patients were scheduled for primary resection. Six patients can be effectively handled in a 30 minute tumorboard. CONCLUSION: The establishment of a daily tumorboard is possible by help of intranet-technology, a central database with web clients and moderate hardware investments. The composition of the patient cohort as well as all decisions ever made to a particular patient are transparent at all times. Prospective quality control studies are under way.

Cancer Care Facilities↗