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Biomedical subjects

R Busch

Publications and source records attributed to R Busch.

At least 73 records · Page 4Linked to original sources
PubMed1995

Preoperative chemotherapy for stage III-IV gastric carcinoma: feasibility, response and outcome after complete resection.

Despite extensive resection and systematic lymphadenectomy the prognosis of patients with locally advanced gastric carcinoma remains poor. The effect of preoperative outpatient chemotherapy with etoposide, doxorubicin and cisplatin was evaluated prospectively in 30 patients who had been shown by preoperative staging (including endosonography and surgical laparoscopy) to have gastric carcinoma stages IIIA, IIIB or IV. Haematological side-effects were common and necessitated hospitalization in 13 of 30 patients. Complete clinical response to neoadjuvant therapy was observed in eight of 27 evaluable patients. Resection was performed in 27 of 30 patients, with complete macroscopic and microscopic tumour removal in 24. There were no deaths and no major morbidity following operation. On multivariate analysis complete clinical response (P < 0.01) and complete tumour resection (P < 0.01) were the major independent predictors of long-term survival after neoadjuvant chemotherapy. Actuarial survival after complete tumour removal was superior with neoadjuvant therapy compared with results in an age-, sex- and tumour stage-matched control population who had primary resection (P = 0.07). Recurrence occurred in 17 of 23 evaluable patients who had complete tumour removal, with relapse in the tumour bed or area of lymphatic drainage in 11. These data show that neoadjuvant therapy in patients with locally advanced gastric carcinoma is feasible and appears to increase the rate of complete tumour removal. More powerful and less toxic regimens are, however, required to improve the response rate and to delay or avoid recurrence after neoadjuvant chemotherapy.

Adult↗
PubMed1995

Poor loading of major histocompatibility complex class II molecules with endogenously synthesized short peptides in the absence of invariant chain.

In normal antigen-presenting cells, newly synthesized major histocompatibility complex (MHC) class II molecules associate with the invariant chain (Ii) glycoprotein in the endoplasmic reticulum (ER). They are loaded with peptides only after proteolytic removal of the Ii in post-Golgi endocytic vesicles. Since the Ii inhibits peptide binding to MHC class II molecules, this association could protect MHC class II molecules from being loaded with endogenous peptides early after biosynthesis. If this were an important function of the Ii in vivo, MHC class II molecules synthesized in cells lacking the Ii should be loaded efficiently with short endogenous peptides in the ER; such peptides are known to be present there due to TAP-mediated import from the cytosol. To examine this possibility, we have studied peptide loading in HeLa transfectants expressing murine H-2Ak MHC class II molecules either alone or together with an excess of Ii. Endogenous peptides could readily be extracted from conformationally intact Ak alpha beta dimers of biosynthetically labeled Ii+ cells, whereas peptide loading was greatly (> 95%) diminished in the absence of Ii. Significant amounts of sodium dodecyl sulfate-(SDS) stable 55-kDa peptide: Ak complexes were only found in the Ii+ transfectants. In the absence of Ii, the MHC class II molecules instead formed stable complexes with long (20 and 50 kDa) polypeptides. Known Ak-binding peptides bound stably to Ak molecules on Ii- cells, could be co-purified with them, and were resistant to release in SDS, suggesting that poor recovery of endogenous peptides was not due to decreased stability of Ak:peptide complexes in the absence of Ii. We conclude that protection of MHC class II molecules from endogenous short peptides does not appear to be a quantitatively important function of the Ii molecule, because peptide loading is inefficient in its absence.

Antigens, Differentiation, B-Lymphocyte↗
PubMed1995

[Superior mesenteric artery syndrome after surgical correction of severe dorso-lumbar deformities. Authors' experience].

The authors report two cases of superior mesenteric artery syndrome observed in 22 operations for severe spinal deformities. Medical, dietary and postural treatment enabled the situation to be resolved in one case; whereas an intestinal derotation according to Strong-Valdoni was successfully performed in the other. The various surgical alternatives are discussed.

Child↗
PubMed1995

Urinary excretion of proteolyzed alpha1-antitrypsin: specificity, quantitation, and relation to therapy response in patients with acute myeloid leukemia.

During remission induction chemotherapy, a 41-kDa cleavage product of alpha1-antitrypsin (alpha1-AT41) can be found in the urine of patients with acute myeloid leukemia. By using immunoblotting with antibodies against this protein, 27 patients with acute myeloid leukemia were screened for the excretion of this fragment and the amount of alpha1-AT41 compared with treatment response assessed by therapy-induced cytoreduction in the bone marrow and time to reach remission. Patients with acute lymphoblastic leukemia, malignant lymphomas, and solid tumors receiving chemotherapy, patients with nonmalignant diseases like sepsis and kidney dysfunction, and healthy subjects were probed to evaluate the specificity of this phenomenon. In 74% of the acute myeloid leukemia patients, the truncated inhibitor was detected. Mean concentration of peak excretion was found to be 6.7 microgram/mg creatinine (range, 1.1-41 microgram/mg). Among the patients treated with induction chemotherapy, those who responded completely (<5% residual marrow blast cells) exhibited significantly higher alpha1-AT41 concentrations than the nonresponders (P < 0.03). Patients who showed a partial response (6-25% residual blasts) excreted intermediate values of the protein. The probability of median time to reach remission was 40 days in patients excreting the truncated inhibitor in measurable amounts compared to 100 days in patients negative for alpha1-AT41 (P < 0.02). The 41-kDa fragment was also found in one of 10 patients with acute lymphoblastic leukemia and in 3 of 18 lymphoma patients but not in those with solid tumors, infections, or kidney disease or in healthy individuals.

Adult↗
PubMed1994

Ratio of invaded to removed lymph nodes as a predictor of survival in squamous cell carcinoma of the oesophagus.

Prognostic factors that may alter the indications for primary surgical resection or that can be influenced by the extent of the procedure were analysed in a homogeneous group of 186 patients with squamous cell carcinoma of the oesophagus. All patients underwent standardized en bloc oesophagectomy and lymph node dissection with prospective documentation of the histopathological findings; follow-up was complete. Multivariate analysis identified the Union Internacional Contra la Cancrum R category (i.e. the presence of residual tumour after resection) as the most important independent prognostic factor (P < 0.001) followed by the ratio of invaded to removed lymph nodes (P < 0.001). These data suggest that only patients in whom R0 resection can be anticipated based on preoperative assessment should undergo primary resection for oesophageal cancer. Extended lymphadenectomy may improve survival in patients with a limited number of invaded mediastinal nodes.

Carcinoma, Squamous Cell↗
PubMed1994

[Risk of surgical therapy of stomach cancer in Germany. Results of the German 1992 Stomach Cancer Study. German Stomach Cancer Study Group ('92)].

The German Gastric Cancer Study (GGCS '92) permits a representative pictures of the current situation in surgery for gastric carcinoma at university centers in Germany. The analysis of frequency of resection, complication rate and mortality provides a quality measure for anybody who performs surgical therapy for gastric carcinoma. The results of multivariate analyses will have therapeutic consequences.

Cause of Death↗
PubMed1994

[Non-Hodgkin's lymphoma of the stomach, surgical therapy and prognosis].

In a retrospective study, clinical and histopathologic factors of 41 patients with a primary gastric non-Hodgkin lymphoma were analysed. All patients underwent gastric resection: total gastrectomy in 44%, subtotal in 34% and extended gastric resection in 22% of the patients. In 27% of the cases gastric resection was part of a multimodal therapy. While RO resection was achieved in 80% of the cases, the overall 5-year survival rate was 74%. In a multivariate analysis using the Cox model R0-resection independently improved prognosis, whereas extended gastric resection was associated with a poorer survival rate. As R0-resection should be the aim of every oncologic surgery, preoperative identification of the R0-resectable cases by extended patient evaluation is of great importance.

Combined Modality Therapy↗
PubMed1993

Prognostic factors in gastric carcinoma. Results of the German Gastric Carcinoma Study 1992.

BACKGROUND: The impact of patient- and tumor-dependent factors and the postoperative course on the prognosis of patients who underwent resection for gastric carcinoma between 1986 and 1989 were analyzed in a prospective multicenter observation study. METHODS: Resection techniques, the extent of lymph node dissection, and the histopathologic assessment of the specimen were standardized at all participating centers. A total of 1654 patients were enrolled. Follow-up is complete for 99.2% of the patients, with a median follow-up time of 48 months. Prognostic factors were assessed by multivariate analysis. RESULTS: In the total patient population there was an independent prognostic effect of nodal status, a International Union Against Cancer (UICC)-R0 resection, distant metastases, the pT category, three or more risk factors on preoperative risk analysis, and the presence of postoperative complications. Multivariate analysis in the subgroup of patients who had a UICC-R0 resection confirmed the nodal status as the major independent prognostic factor. CONCLUSION: These data suggest that the prognosis of patients who undergo gastrectomy for gastric carcinoma may be improved by a complete resection of the primary tumor and its lymphatic drainage, resulting in a UICC-R0 resection. In addition, a detailed preoperative risk analysis and identification of high-risk patients and meticulous attention to the technical details of the surgical procedure to reduce the frequency of postoperative complications may improve the prognosis.

Adult↗
PubMed1993

Epitope-specific enhancement of antigen presentation by invariant chain.

The MHC class II-associated invariant chain (Ii) is involved in the intracellular sorting of class II molecules to the endocytic pathway where peptides from processed exogenous antigens are bound, and thereby Ii is thought to enhance antigen presentation. Here we demonstrate that presentation of only one out of five epitopes of a given antigen is augmented by Ii. We have compared the presentation of five different epitopes derived from hen egg white lysozyme (HEL) to Ak-restricted T hybridomas by rat-2 fibroblasts transfected with A alpha k and A beta k (RKK) and RKK cells supertransfected with the mouse invariant chain (RKKI). Only the presentation of the HEL epitope 46-61 was enhanced whereas the presentation of the HEL epitopes 25-43, 34-45, 112-124, and 116-129 was unchanged or even slightly diminished in RKKI cells. The presentation of the epitopes 25-43 and 34-45 was virtually insensitive to the lysosomotropic reagent chloroquine. Brefeldin A (BFA), which inhibits protein egress from the endoplasmic reticulum, blocked the presentation of all epitopes tested in RKKI cells. In contrast, in Ii-negative RKK cells only the presentation of the epitope HEL(46-61) was inhibited by BFA and the presentation of the epitopes 25-43 and 34-45 was only slightly impaired. These findings suggest that Ii may target class II molecules to selected endosomal subcompartments involved in the processing of different peptides derived from an endocytosed antigen. As a result, the enhancement of the class II-restricted presentation in Ii expressing cells appears to be epitope specific rather than antigen specific.

Animals↗
PubMed1993

[The epidemiology of stomach carcinoma from the surgical viewpoint. The results of the German Stomach Carcinoma Study 1992. The German Stomach Carcinoma Study Group].

In a prospective multi-centre study data were collected on 1,999 patients (1273 men, 726 women; mean age 62.3 [19-99] years) with gastric carcinoma, admitted to one of 19 surgical departments in Germany between 1.4. 1986 to 30. 6. 1989. Previously treated patients as well as those with synchronous or metachronous tumours and carcinoma of the gastric stump had been excluded. The resection rate for gastric carcinoma was 82.7%, i.e. resection was no longer possible because of the advanced tumour stage in nearly 20%. The tumour was located in the upper third of the stomach in 30%, the antrum in 26.3%. An intestinal type of growth was present in 51.9%. An early carcinoma was diagnosed in 16.9% of operated patients; it had already metastasized to regional lymph nodes in 16.5%. Nearly 70% of patients with resectable tumours had metastases to the regional lymph-nodes, with distant metastases in 30%. An advanced tumour stage (UICC stage IIIB or IV) was present in 43%. Exclusively surgical treatment is not effective in these cases.

Adult↗
PubMed1993

Prognostic relevance of systematic lymph node dissection in gastric carcinoma. German Gastric Carcinoma Study Group.

In a prospective multicentre study of 2394 patients with gastric carcinoma the prognostic relevance of systematic lymph node dissection was evaluated. Of 1654 patients undergoing resection, 558 had a standard lymph node dissection, defined as fewer than 26 nodes in the specimen, and 1096 underwent radical lymphadenectomy, i.e. 26 or more nodes in the specimen. Radical dissection significantly improved the survival rate in patients with Union Internacional Contra la Cancrum (UICC) stages II and IIIA tumours. Multivariate analysis identified radical dissection as an independent prognostic factor in the subgroups of patients with UICC tumour stages II and IIA. Radical dissection conferred no survival advantage in patients with pN2 tumours. There was no significant difference in morbidity and mortality rates between radical and standard lymph node dissection. Radical lymphadenectomy improves survival in patients with UICC gastric cancer stages II and IIIA, and should be the recommended treatment for such patients.

Female↗
PubMed1993

Inhibitory effects on in vitro cell growth of human urothelial tumor cell lines under the combined administration of hematopoietic growth factors and clinically relevant antineoplastic agents.

In five of eight human transitional carcinoma cell (TCC) lines a proliferative response has been reported during exposure to interleukin-3 (IL-3), granulocyte-macrophage colony stimulating factor (GM-CSF) and granulocyte colony stimulating factor (G-CSF). To elucidate possible growth-modulating effects of these factors combined with clinically relevant antineoplastic agents, cells of the human TCC lines EJ28 and T24 were exposed to methotrexate (MTX), vinblastine (VBL), doxorubicin (DXR) and cisplating (CDDP) with and without single or continuous exposure to IL-3, GM-CSF and G-CSF at concentrations of 1-100 ng/ml. Compared with cells exposed only to chemotherapy, significant inhibitory effects occurred as a result of continuous exposure to IL-3 or GM-CSF at the highest activities with CDDP and MTX in the T24 and EJ28 lines; continuous G-CSF administration (100 ng/ml) in combination with MTX led to significant growth inhibition in the EJ28 line. In contrast, no significant growth modulation was found on combined administration of DXR or VBL with any one of the three colony stimulating factors tested.

Antineoplastic Agents↗
PubMed1993

Expression of the proliferating cell nuclear antigen in the different types of Hodgkin's disease.

Thirty-eight cases of Hodgkin's disease (HD, lymphocyte-predominant, n = 10; nodular sclerosis, n = 10; mixed cellularity, n = 10; lymphocyte depletion, n = 8) were investigated with the antibody PC10 directed against the proliferating cell nuclear antigen (PCNA) with B- and T-cell markers using a double-staining technique in paraffin-embedded material. It could be shown that nearly all (95-97%) Hodgkin's and Reed-Sternberg (HRS) cells and their variants were PCNA-positive regardless of the type of HD. There was only a low number of PCNA-positive lymphocytes (2.8-3.4%) in all types mostly consisting of MT1-positive T lymphocytes. In contrast to the other types, lymphocyte-predominant type showed a relatively high percentage (5%) of Leu-7-positive lymphocytes. The high percentage of PCNA-positive HRS cells correlates with their malignant nature, and might be another example of dysregulated expression of PCNA.

Antigens, Differentiation↗
PubMed1993

[Prognostic factors in primary gastric non-Hodgkin's lymphoma--results of uni- and multivariate analysis].

Retrospectively analyzed data of 41 patients with primary gastric non-Hodgkin lymphoma which were all treated by gastric resection are presented with regard to their histopathologic and clinical findings. 87% of the patients were distributed on stage EI and EII (51% high-grade and 49% low-grade lymphoma). R0 resection was achieved in 80% of our cases and in 27% of the cases gastric resection was part of a multimodal therapy. The median follow up of the living patients was 42 months, the overall 5-year survival rate 74%. Tumor stage, extent of surgical resection, histologic grade, tumor site, R0-resection and tumor size showed a significant prognostic influence on survival. The question whether R0 resectable cases benefit from an adjuvant therapy must be answered by further randomized studies.

Adult↗
PubMed1992

Expression of HER-2/neu in renal-cell carcinoma. Correlation with histologic subtypes and differentiation.

Twenty-four renal-cell carcinomas (RCC) and corresponding non-neoplastic kidney tissue were examined for amplification and expression of the HER-2/neu gene. Gene amplification was examined by slot-blot analysis, mRNA expression by in situ hybridization and Northern blot analysis, and protein expression by immunohistochemistry. Northern-blot analysis revealed lower expression of HER-2/neu mRNA in clear-cell (p less than 0.001) and compact (p less than 0.001) tumor subtypes, while chromophilic, chromophobic and tubulo-papillary subtypes did not show significant differences in HER-2/neu gene expression, as compared with non-neoplastic kidney tissues. HER-2/neu gene expression was not significantly associated with tumor stage. Low differentiation (G3) was associated with lower HER-2/neu gene expression, but the number of G3 cases was too small for statistical analysis. HER-2/neu gene amplification was not found in any of the tumors. The results of in situ hybridization and immunohistochemistry generally agreed with those of Northern-blot analysis. We conclude that HER-2/neu gene expression correlates with Thoenes' classification of RCC and may be inversely related to tumor differentiation; it is probably not involved in progression of RCC, in contrast to carcinomas of other locations (e.g. breast, ovary).

Blotting, Northern↗
PubMed1992

[Prognostic factors in diffuse peritonitis].

In order to evaluate their prognostic relevance for survival 46 variables were submitted to univariate as well as multivariate analysis in a group of 184 patients with diffuse peritonitis. In the univariate analysis a significant correlation with the outcome was found for the following parameters: age greater than or equal to 70 years, preexisting hepatic or cardiac disease, no eradication of the primary source of infection at first laparotomy for peritonitis, cardiovascular instability, respiratory failure, hyperbilirubinemia, thrombocytopenia, elevated serum creatinine and diminished creatinine clearance at the beginning and proof of pseudomonas aeruginosa in the peritoneal exsudate and of candida albicans in the blood culture during the course of the peritonitis. In the multivariate analysis the surgical eradication of the primary source of infection at the first laparotomy for peritonitis, serum creatinine at the beginning of peritonitis, age greater than or equal to 70 years and a preexisting hepatic disease proved to be the independent variables with significant prognostic relevance for survival of the patients.

Aged↗