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Biomedical subjects

S P Mönig

Publications and source records attributed to S P Mönig.

At least 19 recordsLinked to original sources

[Ulcer surgery - what remains?].

Ulcer surgery today concentrates on the complications of chronic ulcer disease, especially ulcer perforation and endoscopically uncontrollable ulcer bleeding. In this case the laparoscopic or open closure of the gastroduodenal defect or local hemostasis of the bleeding ulcer by laparotomy are the main aims of surgery. Elective operations due to recurrent gastric or duodenal ulcers have become rare. An indication for gastric ulcer resistant to conservative therapy could be persisting suspicion of malignancy whereas in duodenal ulcer gastric outlet obstruction represents a reason for surgery. If these indications are confirmed the classic procedures of gastric resection like Billroth I and Billroth II are performed whereas vagotomy is no longer used. Altogether ulcer surgery has become very safe although it is practiced quite rarely.

Gastrectomy↗

Lewis(y) antigen (CD174) and apoptosis in gastric and colorectal carcinomas: correlations with clinical and prognostic parameters.

Lewis(y) (Le(y)), also designated CD174, represents a carbohydrate blood group antigen which is strongly expressed in neoplastic gastrointestinal tissues. Previous reports indicated an association between Le(y) expression and apoptosis. Therefore, we tried to elucidate its clinicopathological relevance in a series of 160 gastric and 215 colorectal carcinomas by immunohistochemical detection of Le(y) and visualization of apoptotic cells applying the in-situ-end labelling (ISEL) method, followed by semiquantitative scoring of the specimens. In both gastric as well as colorectal carcinomas, between 40 and 50% of the cases were Le(y) reactive. Signet-ring cell carcinomas of the stomach exhibited a significantly stronger Le(y) expression compared to other tumor types. In colorectal cancers, Le(y) was associated with increased tumor staging, showing the strongest positivity in stage IV. Further correlations with clinicopathological variables or prognosis were not observed. On the other hand, the amount of apoptotic cells was significantly reduced in mucinous adenocarcinomas of the colorectum compared to non-mucinous carcinomas. Scoring of apoptotic cells did not result in any other clinicopathologically relevant correlations. In addition, a significant association between Le(y) antigen expression and apoptosis score could not be established. Therefore, the hypothesis of a functional relationship between these two aspects of gastrointestinal tumor biology is not confirmed by our data.

Adenocarcinoma↗

Quality-assured Efficient Engineering of Feedforward Neural Networks (QUEEN) -- pretherapeutic estimation of lymph node status in patients with gastric carcinoma.

OBJECTIVES: Lymph node metastasis (LNM) is an important prognostic indicator in patients with gastric carcinoma. However, the methods that have been established for preoperative diagnosis of LNM show insufficient accuracy. METHODS: This study describes the use of the Quality Assured Efficient Engineering of Feedforward Neural Networks with Supervised Learning (QUEEN) technique to attempt optimization of the preoperative diagnosis of lymph node metastasis in patients with gastric carcinoma. The results were compared with the Maruyama Diagnostic System (MDS) for preoperative prediction of LNM, established at the National Cancer Center in Tokyo. RESULTS: QUEEN is able to extract predictive variables from a case-based database. The combination of a development method, a special type of neural network and the corresponding encoding yielded an accuracy of 72.73%, which is notably higher than that of the MDS. Our system produced a nearly ten per cent higher sensitivity and around eighteen per cent higher specificity than MDS. CONCLUSION: Our results show that QUEEN is a reasonable method for the development of ANNs. We used the QUEEN system for prediction of LNM in gastric cancer. This system may allow more meaningful preoperative planning by gastric surgeons.

Germany↗

[Regression of oesophageal carcinomas after neoadjuvant radiochemotherapy: criteria of the histopathological evaluation].

Following surgical resection locally advanced oesophageal carcinomas exhibit a bad prognosis and therefore neoadjuvant therapeutic strategies were developed. Because success of therapy is associated with the extent of tumor regression in this context, the introduction of objective histopathological criteria seems to be very important. This study included 67 patients with oesophageal carcinomas (cT2-cT4 cNx cM0) that were treated with a cisplatin- and 5-fluorouracil-containing simultaneous radiochemotherapy. In 43 patients squamous cell, in 24 cases adenocarcinomas were diagnosed. After completion of therapy, a surgical resection and a histopathological examination of the tissue specimens were performed. The extent of tumor regression was histologically evaluated and therapy-induced alterations were graded semiquantitatively. Thereby, a significantly favorable prognosis was observed in the group of patients that showed a regression of carcinomas of 90% or more. Additionally, the extent of a resorptive-histiocytic reaction, giant cells and lymphocytic infiltrates correlated with the grade of regression. These results underline the importance of an exact examination and histomorphological evaluation of the response for the assessment of survival probability after neoadjuvant radiochemotherapy of oesophageal carcinomas.

Antineoplastic Combined Chemotherapy Protocols↗

[Prognostic relevance of biological and molecular markers in oncology. Criteria for planning and interpreting studies].

Experts on different specialties (surgery, pathology, molecular biology and medical statistics) discussed the evaluation of prognostic factors during a workshop. The most important results presented are: (1) the prognostic relevance of new biological or molecular markers must be evaluated in a phase-III prognostic study. To establish such a marker in the UICC-TNM-classification in at least two different centers, two multivariate analyses according to defined criteria are necessary; (2) the standards of laboratory methods have to be defined, e.g.,which method to apply for RNA-analysis,which materials to used, etc; (3) intensive data analysis should be done before using methods of multivariate analysis. The criteria for the presentation of survival curves are given in detail; (4) in multivariate analysis, the Cox proportional hazard regression for survival outcomes is discussed with explanations and examples of the terms relative risk, odds-ratio, hazard and relative hazard. The arrangement and interpretation of a good prognostic study should be performed as an interdisciplinary approach.

Biomarkers, Tumor↗

Immunoreactivity of cytokeratins (CK7, CK20) and mucin peptide core antigens (MUC1, MUC2, MUC5AC) in adenocarcinomas, normal and metaplastic tissues of the distal oesophagus, oesophago-gastric junction and proximal stomach.

AIMS: Adenocarcinomas of the distal oesophagus and especially the oesophago-gastric junction have shown an increasing incidence during the last decade. Definition of subgroups according to different sites of development, histogenesis or aetiology may prove to be valuable for clinical diagnosis and treatment. Previous studies have shown differences in cytokeratin patterns between Barrett's metaplasia of the oesophagus and intestinal metaplasia in the stomach. The aim of our study was to investigate whether the expression of certain cytokeratins (CK7, CK20) and mucins (MUC1, MUC2, MUC5AC) exhibit clear-cut patterns, thus allowing a subclassification of adenocarcinomas of the oesophago-gastric junction. The possibility of a relationship between antigen expression and the presence or absence of Barrett's metaplastic epithelium was also studied. METHODS AND RESULTS: CK7, CK20, MUC1, MUC2 and MUC5AC were visualized in six adenocarcinomas of the distal oesophagus, 29 adenocarcinomas of the oesophago-gastric junction and eight adenocarcinomas of the proximal stomach. CK7, CK20 and MUC1 were strongly expressed in the great majority of all neoplasms under study, whereas MUC2 and MUC5AC were absent or only faintly detectable. CK20 exhibited a significantly stronger expression in poorly differentiated tumours (G3) and MUC1 immunoreactivity correlated with tubular and papillary versus signet-ring cell histopathology. Other statistically significant correlations between antigens and histopathological features (pTNM stage, grading, histopathological subtype, presence/absence of Barrett's epithelium) were not observed. CONCLUSIONS: According to our results, most adenocarcinomas of the oesophago-gastric junction show a CK7+, CK20+, MUC1+ phenotype irrespective of the presence or absence of Barrett's epithelium. The immunohistochemical data suggest a similar histogenesis of these tumours.

Adenocarcinoma↗

[Does Charlson-comorbidity index correlate with short-term outcome in patients with gastric cancer?].

OBJECTIVES: Because of the high prevalence of coexisting medical conditions in patients with gastrointestinal cancer, clinical investigators often need to adjust for comorbidity when assessing the effect of comorbidity on patient outcome. Comorbidity in cancer has been shown to be a major determinant in treatment selection and survival. However, none of the comorbidity studies in patients with gastric cancer reported in the literature have been performed using the Charlson comorbidity index. The purpose of this study was to examine the applicability of the CCI and usefulness of the CCI as a predictor in patients with gastric cancer and to examine whether it correlates with short- term outcome in these patients. METHOD: Study design was a prospective study. The study population was drawn from our department and included 139 patients who underwent curative treatment of gastric cancer between 1.1.1997 and 31.12.2001. All patients were staged by the CCI for comorbidity and divided into three groups based on the comorbidity severity staging. Group 1 included patients with no comorbidity, group 2 included those with low-level comorbidity and group 3 those with severe comorbidity. Outcomes were compared based on these divisions performing uni- and multivariate analysis. RESULTS: 35 patients (25.2 %) had no, 55 (39.6 %) low and 39 (35.2 %) severe comorbidity. 28.8 % of patients showed no or mild, 14.4 % moderate and 14.4 % of patients severe postoperative complications and 5.8 % died in hospital postoperatively. 30-day-mortality was 3.6 % (n = 5). There was no statistical significant correlation between CCI and occurrence of postoperative complications, severity of postoperative course and postoperative stay in hospital. In multivariate analysis only age was an independent factor for postoperative course. CONCLUSION: The method of classifying comorbidity by CCI provides a simple, readily applicable and valid method of estimating risk of death from comorbid disease for use in longitudinal studies and in outcomes research from administrative databases. In gastric cancer, however, the CCI was found not to be a valid prognostic indicator.

Adult↗

Frequency of nodal metastases to the upper mediastinum in Barrett's cancer.

BACKGROUND: In Barrett's cancer, the frequency of lymph node metastases to the middle and upper mediastinum has rarely been analyzed because it requires a complete mediastinal lymphadenectomy. METHODS: Fifty-one patients with esophageal adenocarcinoma underwent transthoracic en-bloc esophagectomy with two-field lymph node dissection. A meticulous work-up of the resected specimen allowed a specific assignment of each single lymph node to defined groups of the abdominal and mediastinal compartment. Histopathology classified the lymph nodes as metastatic or nonmetastatic. RESULTS: A total of 1706 lymph nodes were resected, with a mean of 33.5 lymph nodes per patient (range, 13-74). Of 51 patients, 28 (54.9%) were classified as pN1; 7 (25%) of 28 pN1 patients had nodal metastases at the level of the tracheal bifurcation (3 of 28 patients) or in the upper mediastinum (5 of 28 patients). In all 28 pN1 patients, the abdominal compartment was involved. The distribution of nodal metastases demonstrated that the main lymphatic spread occurred close to the primary tumor, along the lesser curvature and the left gastric artery. CONCLUSIONS: Adenocarcinomas of the distal esophagus have a bidirectional lymphatic spread to the mediastinum and the abdomen. Two-field lymphadenectomy seems to be an adequate surgical approach for this tumor entity to achieve a complete nodal clearance.

Adenocarcinoma↗

[Adenocarcinoma of the stomach with heterotopic ossification. Case report and discussion of the pathogenesis].

Heterotopic ossification of gastric adenocarcinomas is very rarely observed in humans. In rats such lesions could be induced by ingestion of nitroso compounds. We describe the case of a 70-year-old patient with an extended, initially spleen-infiltrating tubular adenocarcinoma of the stomach with a mucinous component, heterotopic ossifications and pronounced regressive alterations after neoadjuvant chemotherapy. Various speculations regarding the pathogenesis of heterotopic ossifications in gastrointestinal adenocarcinomas are discussed.

Adenocarcinoma↗

Comparative evaluation of the prognostic value of MUC1, MUC2, sialyl-Lewis(a) and sialyl-Lewis(x) antigens in colorectal adenocarcinoma.

AIMS: The significance of MUC1, MUC2 and sialylated Lewis blood group antigens as prognostic markers in colorectal adenocarcinoma was investigated in a large series of patients because previous investigations revealed inconsistent results due to unrelated tumour samples from different patient groups and methodological differences. METHODS AND RESULTS: Tissues from 243 patients with colorectal adenocarcinoma were stained immunohistochemically. MUC1 showed a strong immunoreactivity (in more than 35% of the tumour area) in 32.5%, MUC2 in 51.0%, sialyl-Lewis(x) in 67.9% and sialyl-Lewis(a) in 73.7% of the cases, respectively. MUC1 immunoreactivity displayed a significant correlation with tumour progression as reflected by advancing pTNM staging and poor differentiation. MUC2 expression was significantly stronger in mucinous adenocarcinomas. Sialyl-Lewis(x) immunostaining correlated with the extent of lymph node metastasis as well as low cytological differentiation. According to univariate and multivariate analysis (P < 0.0001) only MUC1 reactivity represented a marker of worse survival probability, opposed to the sialylated Lewis antigens that did not exert a predictive value. CONCLUSIONS: According to our data, MUC1 and sialyl-Lewis(x) immunoreactivity exhibit statistically significant correlations with established markers of tumour progression. However, only MUC1 presents as an independent prognostic factor of colorectal adenocarcinoma.

Adenocarcinoma↗

Preoperative lymph-node staging in gastrointestinal cancer--correlation between size and tumor stage.

Our data suggest that lymph-node size is not a reliable indicator for lymph-node metastasis in gastric, esophageal, and colon cancer. Despite a significant difference in diameter of metastatic and non-metastatic nodes, the accurate evaluation of lymph-node metastasis in gastro-intestinal carcinoma cannot be determined by nodal size, because the majority of counted lymph nodes is ?5 mm and the frequency of small lymph-node metastases is high. Therefore imaging techniques using the size as criterion of nodal infiltration can not exactly assess the nodal status of patients with gastro-intestinal carcinomas. For rational lymphadenectomy, the value of sentinel node biopsy in gastro-intestinal cancer is now discussed. At the moment it is too early to apply sentinel node biopsy in order to reduce the extent of lymphadenectomy in these carcinomas [11]. Recent interest has focused on PET scanning in the detection of lymph-node metastases. PET represents a potentially ideal imaging modality for malignancy. It allows a quick and simultaneous assessment of both local and distant sites and, as a result of avid uptake of the glucose moiety, may potentially identify small tumor loads. There are only limited experience in detecting lymph-node metastases in gastro-intestinal carcinoma and the results of the published reports are controversially discussed [12, 13]. Our data demonstrate a high frequency of small lymph-node metastases in gastro-intestinal carcinoma and suggest that a careful histological search for small lymph-node metastases should be undertaken to avoid false-negative lymph-node staging. These results emphasize that a reliable pathological staging of gastro-intestinal cancer must be based on a standardized systematic lymphadenectomy because lymph-node sampling based on lymph-node size is not sufficient.

Gastrointestinal Neoplasms↗

Immunoreactivity of Lewis blood group and mucin peptide core antigens: correlations with grade of dysplasia and malignant transformation in the colorectal adenoma-carcinoma sequence.

Previous studies on the immunoreactivity of various mucin peptide and carbohydrate antigens in neoplastic colorectal tissues led to at least in part contradictory results. Therefore, we investigated a series of 42 adenomas and 44 carcinomas applying monoclonal antibodies (mabs) directed against Lewis blood group antigens (sialyl-Le(a), Le(x), sialyl-Le(x), Le(y)) as well as mucin peptide cores (MUC1, MUC2 and MUC5AC) by immunohistochemistry. A statistically significant positive correlation between the development of high-grade dysplasia in colorectal adenomas and the immunoreactivity of Le(y) and MUC1 epitopes was observed, whereas MUC2 exhibited a significant negative correlation. The reactivity of the other epitopes did not show an association with the progression of malignant transformation. Colorectal carcinomas were subdivided according to their histopathological subtype. The immunohistochemical staining resulted in a significantly stronger MUC2 reactivity of mucinous vs. tubular adenocarcinomas. Immunoreactivity of the MUC1-specific mab, which does not react with the fully glycosylated peptide core, showed a statistically non-significant inverse tendency, whereas all carbohydrate antigens displayed a strong expression in both tumor subtypes. Furthermore, correlations between mucin peptide and carbohydrate epitope labelling were evaluated. Progression of the adenoma-carcinoma sequence was accompanied by an increase of Le(y) as well as MUC1 antigen and an increase of all Lewis antigens compared to MUC2 immunoreactivity. On the other hand, mucinous carcinomas exhibited an inverse pattern. In conclusion, these results demonstrate that Le(y) and MUC1 immunoreactivity correlate with malignant transformation in the colorectum, whereas MUC2 represents a marker for low-grade dysplasia and the subtype of mucinous carcinomas.

Adenoma↗

Splenectomy in proximal gastric cancer: frequency of lymph node metastasis to the splenic hilus.

BACKGROUND AND OBJECTIVES: The indication for splenectomy in proximal gastric cancer remains controversial. Splenectomy is performed because of possible lymph node metastasis of the splenic hilus or infiltration/metastasis of the spleen. The purpose of this study was to investigate the frequency of lymph node metastasis to the splenic hilus and metastasis to the spleen in proximal gastric carcinomas. METHODS: In a morphologic study, the frequency of lymph node metastasis to the splenic hilus in 112 patients with proximal gastric cancer was investigated with particular emphasis on its correlation with established clinicopathological characteristics and classifications. Seventy-seven gastrectomy specimens were obtained from men and 35 from women. Patients ranged in age from 20 to 89 years (median 60 years). All patients underwent a potential curative resection (RO resection) with total gastrectomy and pancreas-preserving splenectomy. None of the patients had been treated preoperatively with cytotoxic drugs or radiation. RESULTS: A mean number of three lymph nodes (range 0-8) in the splenic hilus was found in each specimen. The incidence of lymph node metastasis of the splenic hilus was 9.8% (n=11). Lymph node metastasis was only observed in advanced proximal gastric cancer (UICC IIIb/IV) located at the greater curvature and in Borrmann type III/IV cancer with advanced lymph node metastasis. An infiltration of the spleen was seen only in two cases with advanced stages of gastric carcinoma (stage IV). CONCLUSIONS: Based on our data lymph node metastasis to the splenic hilus is rarely observed in proximal gastric cancer and only found in advanced cancer (UICC IIIb/IV) especially in tumors of the greater curvature and of Borrmann type IV cancer.

Female↗

Lesser curvature lymph node metastases with esophageal squamous cell carcinoma: implications for gastroplasty.

The creation of a gastric tube after subtotal esophagectomy includes resection of the lesser curvature and abdominal lymph nodes. The fundus rotation gastroplasty has been recently proposed as an alternative technique of reconstruction that preserves the vascular arcade of the lesser curvature. This study investigates the number of resected and metastatic lymph nodes associated with abdominal lymphadenectomy to assess the oncologic radicality of fundus rotation gastroplasty. In this prospective clinical trial a two-field lymphadenectomy was performed in 39 patients with squamous cell carcinoma of the esophagus. The abdominal lymphadenectomy included partial resection of compartment I (lymph node groups 1, 2, and 3) and compartment II (lymph node groups 7, 8, 9, and 11). A meticulous workup of the specimen allowed an exact classification of specific lymph node groups and their metastatic status. After two-field lymphadenectomy a total of 1170 lymph nodes (average 30.0) including 690 abdominal lymph nodes with an average of 17.7 per patient were resected. Metastatic disease was found in 27 of 39 patients (pN1 69.2%), with metastatic growth in 116 of 867 resected lymph nodes (13.4%). Of the 27 pN1 patients, 21 had abdominal lymph node metastases. Metastatic lymph nodes at the lesser curvature (groups 1, 3, and 7) were detected in 11.7%, 16.7%, and 29.7% of the resected lymph nodes, respectively. Of the 21 patients (85.7%) with abdominal lymph node metastases, 18 had positive lymph nodes at the lesser curvature. Squamous cell carcinoma of the esophagus is associated with a high rate of lymph node metastases at the lesser curvature and the left gastric artery. Therefore preservation of the lesser curvature and the left gastric artery for gastroplasty reduces the radicality regarding lymph node metastases.

Adult↗

Expression of MMP-2 is associated with progression and lymph node metastasis of gastric carcinoma.

AIMS: One important step in tumour invasion is the penetration of the basement membrane. Matrix metalloproteinases (MMPs) play a key role in the migration of normal and malignant cells through the basement membrane. The aim of this study was to investigate correlations between matrix metalloproteinase 2 (MMP-2) immunoreactivity and currently used classification systems and possible relationships between lymph node metastasis and MMP-2 expression. METHODS AND RESULTS: This prospective study analysed specimens obtained from 114 gastric cancer patients (mean age 64 years; range 33-86 years) who underwent gastrectomy with extended lymphadenectomy. All specimens were categorized according to UICC classification, WHO classification, tumour differentiation, Laurén classification, Ming classification and Goseki classification. Formalin-fixed paraffin-embedded tumour specimens were stained using an avidin-biotin complex peroxidase assay. MMP-2 expression in the tumour epithelium was studied by immunohistochemistry with semiquantitative (score 0-3) evaluation. The MMP-2 staining pattern was positive (score 1-3) in 93 (81.6%) specimens and negative (score 0) in 21 (18.4%) samples. No significant correlations were found between MMP-2 expression and other variables such as age, tumour differentiation, WHO, Lauren, Goseki, and Ming classifications. In contrast, the intensity of MMP-2 staining in tumour cells correlated significantly with depth of tumour infiltration (T-stage), lymph node metastasis (N-stage), distant metastasis (M-stage), and UICC stage. CONCLUSIONS: Expression of MMP-2 is strongly associated with tumour progression and lymph node metastasis in gastric cancer. Therefore MMP-2 staining may be clinically useful as predictor of tumour progression, especially for lymph node metastasis.

Adult↗