Biomedical subjects

M Feith

Publications and source records attributed to M Feith.

At least 19 recordsLinked to original sources

PubMed2006

The prognostic impact of O6-Methylguanine-DNA Methyltransferase (MGMT) promotor hypermethylation in esophageal adenocarcinoma.

Promotor hypermethylation is a common event in human cancer. O6-Methylguanine-DNA Methyltransferase (MGMT) is a gene involved in DNA repair, which is methylated in a variety of cancer types. In colorectal cancer and lung cancer, hypermethylation of MGMT has been correlated with p53 mutation. In the present study, 132 samples of esophageal adenocarcinoma and 58 samples of normal esophageal tissue were investigated for MGMT hypermethylation status by methylation-specific real-time PCR and results were correlated to clinicopathological parameters, patient's survival, p53 mutation and expression of p53 protein and MGMT protein. In the carcinomas, hypermethylation of MGMT was found in 63.6% of cases and loss of MGMT protein expression in 48.5% of cases. Furthermore, MGMT hypermethylation was found in 5.7% of normal esophageal smooth muscle tissue, in 20.0% of esophageal squamous epithelium and in 61.5% of nonneoplastic Barrett's mucosa. In the carcinomas, hypermethylation of the MGMT gene was correlated with loss MGMT protein expression (p < 0.0001) and with high tumor differentiation (p = 0.0079). In contrast, no correlation between MGMT hypermethylation, Lauren's classification, WHO classification, tumor size, gender, age, pT category and pN category, and p53 status was found. Neither MGMT hypermethylation nor loss of MGMT protein expression was correlated with patient's survival. In conclusion, MGMT hypermethylation in esophageal adenocarcinoma is a frequent event that is associated with loss of MGMT protein expression but not with patient's outcome.

Adenocarcinoma↗

PubMed2006

[Limited surgical resection versus local endoscopic therapy of early cancers of the esophagogastric junction].

BACKGROUND: Adenocarcinomas of the esophagogastric junction (especially Barrett's cancers) are increasingly diagnosed at early stages. The current standard treatment - radical resection with extensive lymphadenectomy - has been challenged. Limited resection or endoscopic mucosal ablation have been proposed as less invasive alternatives. METHODS: Available data regarding limited surgical resections and endoscopic interventional procedures are evaluated with respect to short- and long-term results (mortality, morbidity, oncologic adequacy, quality of life). RESULTS: Limited resection of the esophagogastric junction has been proven as safe (low morbidity and mortality) and oncologically adequate procedure (low rate of recurrence/excellent long-term survival) with good quality of life. The procedure meets the oncological requirements (R0-resection, complete resection of potentially tumor-infiltrated lymph nodes and the entire precancerous Barrett's esophagus). Reconstruction with interposition of a pedicled isoperistaltic jejunal loop prevents reflux and is crucial for achieving good postoperative quality of life. In contrast, endoscopic mucosal resection (EMR) carries the risk of high recurrence rates (at least 30 %). This has to be regarded as an effect of the frequent incomplete resection, multicentric tumor growth, the persistence of precancerous Barrett's mucosa and persistence of gastroesophageal reflux. Consequently, from the oncological view point, EMR is only suited for unicentric mucosal tumors (T1a) in short segments of Barrett's esophagus. Reliable preoperative identification of such tumors is, however, currently not possible. CONCLUSION: For adequately selected patients with early Barrett's cancer, limited resection of the esophagogastric junction is an appropriate procedure. Endoscopic mucosa resection (EMR) might gain importance as staging tool.

Adenocarcinoma↗

PubMed2006

Prognostic significance of expression patterns of c-erbB-2, p53, p16INK4A, p27KIP1, cyclin D1 and epidermal growth factor receptor in oesophageal adenocarcinoma: a tissue microarray study.

AIMS: To correlate immunohistochemical expression patterns and prognosis in oesophageal adenocarcinoma. METHODS: The expression of c-erbB-2, p53, p16INK4A, p27KIP1, cyclin D1 and epidermal growth factor receptor (EGFR) was studied in a series of 137 primarily resected oesophageal adenocarcinoma samples. The expression analysis on protein level was performed on routine paraffin wax-embedded material, with immunohistochemical staining of the samples, assembled on a tissue microarray. The results were correlated with clinicopathological features (pT, pN and G) and survival. RESULTS: 22 (16%) tumours showed an overexpression of the c-erbB-2 oncoprotein. Expression of EGFR was observed in 72 (55%) cases, accumulation of p53 in 68 (52%) cases and of cyclin D1 in 102 (77%) cases. Loss of p16INK4A expression was observed in 101 (76%) cases and low expression of p27KIP1 in 91 (71%) cases. Expression of these proteins did not correlate with tumour stage, grade, Lauren's or World Health Organization classification or lymph node status. On univariate survival analysis, more advanced tumour stage (p = 0.002), lymph node involvement (p = 0.003), high tumour grade (p = 0.017) and lack of EGFR expression (p = 0.034) were found to be associated with poorer survival. On multiple regression analysis, only tumour stage (p = 0.03) and lymph node involvement (p = 0.004) were shown to have an association with the survival of the patient. CONCLUSION: The immunohistochemical expression of c-erbB-2 oncoprotein, cylin D1, p16INK4A, p27KIP1, p53 and EGFR in most oesophageal adenocarcinomas suggests their implication in the pathogenesis of this entity. None of the molecular markers assessed, however, was of prognostic value. Identification of any marker superior to or even approaching the prognostic value of conventional histopathological markers (pT and pN) was therefore not possible.

Adenocarcinoma↗

PubMed2005

Preferred location for the development of esophageal adenocarcinoma within a segment of intestinal metaplasia.

BACKGROUND: Barrett's metaplasia is the predominant precursor for the development of esophageal adenocarcinoma. This precancerous lesion has become the focus of various surveillance programs aimed at detecting earlier and therefore potentially curable lesions. However, sampling error by missing invasive cancer lesions is a common problem. This study aimed to identify preferred locations within a segment of Barrett's mucosa for the development of esophageal adenocarcinoma. METHODS: The study group consisted of 213 patients with histologically proven esophageal adenocarcinoma. Of those, there were 134 cases of early cancer and 79 cases of locally advanced lesions. These patients received neoadjuvant chemotherapy. The frequency of intestinal metaplasia and the location of the tumor occurrence within the segment of intestinal metaplasia were assessed. RESULTS: Intestinal metaplasia was found in 83% of the early lesions and in 98% of the advanced tumors after neoadjuvant chemotherapy. In 82.2% of the cases, the tumor was located at the distal margin of the intestinal metaplasia in patients with early tumor manifestations. The remaining tumor mass after neoadjuvant therapy also was located predominantly at the distal margin of the segment of intestinal metaplasia (85% of the cases). CONCLUSIONS: The results demonstrate that almost all adenocarcinomas of the esophagus are based on the development of a segment of intestinal metaplasia. The distal margin of Barrett's mucosa seems to be the most vulnerable location for the development of invasive cancer.

Adenocarcinoma↗

PubMed2005

Surgery for early stage esophageal adenocarcinoma.

Current treatment recommendations for early esophageal adenocarcinoma range from radical esophagectomy with extensive lymphadenectomy, limited surgical resection with/without regional lymphadenectomy to endoscopic mucosectomy or ablation. A comparison of treatment associated morbidity, tumor recurrence rates, and functional outcome suggests that none of these alternatives can be universally recommended. Rather, an individualized strategy should be employed based on depth of tumor penetration into the mucosa/submucosa, presence of lymph node metastases, multicentricity of tumor growth, length of the underlying Barrett mucosa and comorbidity of the affected patient. Endoscopic mucosectomy may suffice for an isolated focus of high-grade neoplasia or mucosal cancer, provided the neoplasia and underlying Barrett mucosa can be removed completely. Surgical resection is the treatment of choice for tumors invading the submucosa, multicentric tumors and recurrence after endoscopic mucosectomy. The extent of surgical resection must be guided by the length of the Barrett mucosa. In most instances a complete tumor resection and removal of the entire Barrett mucosa can be achieved by a limited transabdominal approach, and therefore subtotal esophagectomy may not be necessary. Application of the sentinel node technology may in the future allow to limit systematic lymphadenectomy to the rather small subgroup of patients who in fact have lymph node metastases.

Adenocarcinoma↗

PubMed2005

[Esophagectomy as therapeutic principle for squamous cell esophageal cancer].

The fatalistic approach towards surgical therapy of esophageal squamous cell cancer has been replaced in recent years by a more differentiated view. This was triggered by the establishment of individualized therapeutic modalities based on tumor stage, tumor location, general patient status, and comorbidity. Despite advances in nonsurgical therapy of squamous cell esophageal cancer, esophagectomy remains the central therapeutic modality. Primary subtotal en-bloc esophagectomy with lymphadenectomy is the only curative option with a high likelihood of success for resectable tumors (uT1-3 categories) located below the level of the tracheal bifurcation and for early more proximal tumors. In patients with locally advanced tumors at or above the level of the tracheal bifurcation, surgical resection can still cure those who respond to neoadjuvant radiochemotherapy. Preoperative "conditioning" of risk patients, surgical safety strategies in risk situations, and standardization of both the operative procedure and the perioperative management have resulted in a marked reduction of the previously substantial postoperative mortality to below 3% in experienced centers. In our own experience of 900 esophagectomies for squamous cell esophageal cancer, the 5-year survival rate rose from about 20% to more than 50% in the last two decades. Esophagectomy thus has become a safe operation and remains the only therapeutic option offering cure for a substantial proportion of patients with squamous cell cancer of the esophagus.

Adenocarcinoma↗

PubMed2005

Surgical strategies for early esophageal adenocarcinoma.

The need for extensive surgical resection for early-stage esophageal adenocarcinoma has been challenged by the increasing frequency of early detection in patients with Barrett's esophagus undergoing surveillance endoscopy. Limited endoscopic or surgical procedures are promoted as alternatives to radical esophagectomy and lymphadenectomy in such patients. Currently available data show that limited surgical resection of the distal esophagus with regional lymphadenectomy and interposition of an isoperistaltic jejunal segment is a safe and oncologically adequate procedure in this situation and provides good quality of life. This is in contrast to endoscopic ablation or endoscopic mucosal resection, which are associated with high tumour recurrence rates and persistence of premalignant Barrett esophagus. New technologies for accurate prediction of the presence and pattern of lymphatic spread-e.g. sentinel node techniques and artificial neural networks-may allow a further reduction of the invasiveness of surgical resection without compromising cure rates.

Adenocarcinoma↗

PubMed2005

COX2 expression, angiogenesis, proliferation and survival in Barrett's cancer.

OBJECTIVES: To examine COX2 expression and its relation to angiogenesis, Ki67 and Bcl2 expression in Barrett's cancer. METHODS: Specimens from 48 R0-resected Barrett's adenocarcinoma were immunostained for cyclooxygenase 2 (COX2), CD 31 and alpha-sm actin to discriminate between mature and immature vessels, Mib-1 and Bcl2. COX2 staining, angiogenesis, Ki67 expression and Bcl2 expression were also measured. RESULTS: COX2 expression was increased in 25 of 48 cases. There was no significant correlation between COX2 expression and age, sex and tumor differentiation. A significant association was found between lymph node positive cases and elevated COX2 expression (p=0.008). The percentage of Ki67 positive cancer cells was 43.8% (range 15.4-67.5%) in the low COX2 group and 57.8% (range 12.0-84.6%) in the high COX2 group. The difference was statistically significant (p=0.046). The median neovascularisation coefficient in the low COX2 group was 11.68 (range 8.22-43.64) and 25.47 (range 8-38.3) in the high COX2 group. The difference was statistically significant (p=0.012). A significant difference in survival was observed between patients in the COX2 low category when compared with the COX2 high category (log-rank test p=0.013). CONCLUSIONS: Elevated COX2 expression is associated with lymph-node metastases and reduced survival in Barrett's cancer. This appears to be related to the induction of angiogenesis and proliferation.

Barrett Esophagus↗

PubMed2004

[Sentinel lymph node mapping in gastric and esophageal carcinomas].

During the last 5 years, the concept of sentinel lymph nodes has been investigated in a variety of solid tumors. Despite the multidirectional and complex lymphatic drainage of the stomach, early gastric cancer has been shown to be a suitable model for sentinel lymph node mapping. In contrast, sentinel lymph node mapping of esophageal cancer is compromised by the anatomic location of the esophagus and its lymphatic drainage in the closed space of the mediastinum. The technique and clinical application of sentinel lymph node mapping thus differ between esophageal and gastric cancer. Reliable detection of sentinel lymph nodes in the mediastinum requires radioisotope labelling, while blue dye and radioisotope labelling are both feasible for gastric cancer. In patients with early gastric cancer, laparoscopic resection with sentinel node negative status is already under investigation in clinical trials. In esophageal cancer, sentinel node mapping is still considered an experimental technique. Preliminary data, however, indicate that it may be reliable and feasible in patients with early adenocarcinoma of the distal esophagus.

Adenocarcinoma↗

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 '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↗

PubMed2002

Preoperative chemotherapy unmasks underlying Barrett's mucosa in patients with adenocarcinoma of the distal esophagus.

BACKGROUND: Intestinal metaplasia of the distal esophagus frequently cannot be detected in patients with esophageal adenocarcinoma. It has therefore been questioned whether Barrett's esophagus is the primary precursor lesion of such lesions. We hypothesized that the underlying Barrett's mucosa may be masked by tumor overgrowth in the majority of these patients. METHODS: The pretherapeutic endoscopy and biopsy records of 79 patients with locally advanced esophageal adenocarcinoma who had undergone preoperative chemotherapy were reviewed and compared to findings on restaging endoscopy/biopsy and subsequent resection and histopathologic analysis of the resected specimen. RESULTS: Pretherapeutic endoscopy and biopsy showed associated Barrett's esophagus in 59/79 patients, whereas there was no evidence of associated intestinal metaplasia in 20/79 patients on extensive biopsies. Following neoadjuvant chemotherapy, Barrett's mucosa was unmasked and later documented by biopsy or histopathologic assessment of the resected specimen in 18 of the latter 20 patients. This resulted in an overall association of Barrett's mucosa with adenocarcinoma in the distal esophagus of 97.4% CONCLUSION: Underlying Barrett's mucosa is frequently masked by tumor overgrowth in patients with locally advanced adenocarcinoma of the distal esophagus.

Adenocarcinoma↗

PubMed2002

Cervical esophageal perforation with severe mediastinitis due to an impacted dental prosthesis.

We herein report about a case of perforation of the cervical esophagus by an artificial denture, which had been swallowed by the patient after a horse-related-injury. Impactation of the foreign body at the level of the upper esophageal sphincter was followed by its penetration through the esophageal wall, causing severe infection of the cervical soft tissue, mediastinitis and sepsis. We discuss the well-known phenomena of prosthesis ingestion and frequently delayed diagnosis, as well as our treatment strategy of cervical esophageal perforation with placement of a T-tube into the cervical esophagus and mediastinal drainage.

Dental Prosthesis↗

PubMed2002

A scintigraphic study of local oesophageal bolus transit: differences between patients with Barrett's oesophagus and healthy controls.

BACKGROUND: In Barrett's patients, functional disorders of oesophageal motility are currently measured by oesophageal manometry. Yet abnormalities of oesophageal volume transport in the critical regions of the upper oesophageal sphincter (UOS) and lower oesophageal sphincter (LOS) cannot be determined using these methods. AIMS: To further characterise the activity of the sphincter regions, we developed a quantitative method for differentiation of oesophageal volume transport in Barrett's patients and healthy controls. METHODS: We used a new technique of processing scintigraphic images, with data analysis based on a new concept of relative local transit time. Twelve patients with Barrett's oesophagus and 11 healthy volunteers were examined using alimentary scintigraphy after a semisolid test meal in a multiple swallow test. In individual scintigraphic images of five swallows we studied: (1) overall oesophageal clearance and (2) the topographic profile of the relative local transit time obtained by image conversion to a two dimensional line graph. This profile was reconstructed by assembling constituent Gauss bands, allocating their integrals to five oesophageal regions according to their band position. RESULTS: (1) Overall oesophageal clearance was not significantly different between the two groups. (2) In comparison with healthy volunteers, relative regional transit times of all 12 Barrett's patients were significantly increased in the hypopharyngeal region and decreased in the region of the distal oesophagus. The extent of the decrease in the region of the distal oesophagus showed a close correlation with the length of Barrett's metaplasia. CONCLUSION: Improvement in image processing allows alimentary scintigraphy to describe different regional patterns of oesophageal volume transport. Local oesophageal bolus transit is markedly abnormal in Barrett's patients without alteration in clearance. The presence of metaplasia itself implies a negative impact on both sphincter functions. These findings substantiate the diagnostic value of refined oesophageal scintigraphy.

Adult↗

PubMed2002

[Lymph node excision in invasive Barrett carcinoma].

Similar to squamous cell esophageal cancer, the lymph node status constitutes the major prognostic factor after complete tumor resection (R0-resection) in patients with adenocarcinoma of the distal esophagus (the so-called Barrett's cancer). Lymphatic spread in patients with Barrett's cancer, however, appears to follow certain rules. Lymphatic spread is closely correlated to the pT-category of the primary tumor, starts only after infiltration of the submucosa und is initially limited to the regional lymph nodes. Distant lymph node metastases are almost exclusively found in patients with multiple positive regional nodes, skipping of regional lymph nodes is rare. These observations set the stage for tailored lymphadenectomy-strategies based on the, sentinel-lymphadenectomy' concept.

Adenocarcinoma↗

PubMed2001

Quality of life before and after laparoscopic Nissen fundoplication.

BACKGROUND: Gastroesophageal reflux disease (GERD) is a common disorder in the Western world. The acute disease can usually be managed by medical therapy. To prevent relapse, many patients require lifelong medication. In these patients, laparoscopic antireflux surgery offers a good alternative. The aim of this study was to evaluate the postoperative results and compare pre- and postoperative quality of life after laparoscopic Nissen fundoplication. METHODS: Clinical investigations, including esophageal manometry, pH monitoring, and endoscopy, and a previously validated Quality of Life Index, were performed before and a median of 41 month after antireflux surgery in 75 patients. RESULTS: After laparoscopic Nissen fundoplication, the percentage of total time with pH <4 decreased from 10.4% to 3.2% on 24-h pH monitoring. The mean pressure of the lower esophageal sphincter improved from 8.1 to 12.3 mmHg. Esophagitis healed in 63 of 66 patients in whom it was present prior to surgery. The overall Quality of Life Index improved significantly from 86 +/- 16 to 116 +/- 16. CONCLUSION: Laparoscopic fundoplication provides effective and durable relief of reflux in patients with GERD. The Quality of Life Index showed significant improvement after surgery.

Adult↗

PubMed2001

[Distal esophageal resection and jejunum interposition for early Barrett carcinoma].

Distal esophageal resection and jejunum interposition for early Barrett carcinoma. Limited resection with regional lymphadenectomy and jejunal interposition is safe, prevents gastroesophageal reflux and is associated with good quality of life. The procedure represents an oncologically adequate and thus attractive limited surgical alternative to radical esophagectomy or endoscopic resection and ablation techniques in patients with high grade dysplasia or T1 adenocarcinoma in Barrett's esophagus.

Adenocarcinoma↗