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Biomedical subjects

M Peiper

Publications and source records attributed to M Peiper.

At least 19 recordsLinked to original sources

Expression of HER2/neu does not correlate with survival in soft tissue sarcoma.

BACKGROUND: The expression of HER2/neu has been identified as a prognostic factor in several malignant diseases. However, only sparse data exist correlating HER2/neu expression in soft tissue sarcoma with subsequent tumor progression or recurrence. The purpose of this study was to investigate the clinical significance of HER2/neu in adult soft tissue sarcoma (STS). METHODS: Tumor specimens of patients with STS were evaluated regarding HER2/neu expression using immunohistochemistry. The significance of the proposed prognostic indicators was evaluated in relation to survival and local recurrence. RESULTS: Of 62 analyzed specimens, 43 tumors were HER2/neu negative compared to 19 HER2/neu positive tumors. Kaplan-Meier analysis indicated no difference in survival according to HER2/neu expression (p = 0.31, log-rank test = 1.10). Variables that were predictive of longer survival included better resection quality (R0, p < 0.01) and smaller tumor size (T1, p = 0.02). CONCLUSION: HER2/neu expression does not correlate with prognosis of soft tissue sarcomas. Its evaluation for tumor prognosis as well as for the identification for adjuvant therapeutic strategies does not appear warranted at this point.

Adult↗

[The Internet as a source for information retrieval. Example: soft tissue sarcoma].

INTRODUCTION: Due to increasing availability, easier access, and rapid growth of information, the Internet has become an important source of medical information. We analyzed the value of Internet sites and the content of their medical information for physicians and patients using the example "soft tissue sarcoma." METHODS: Sixteen German and English Internet search engines were used to evaluate the retrieved internet sites regarding their target group, publisher, contents, and topicality. RESULTS: The majority of retrieved websites were in English compared to significantly fewer in German. The content of information was more valuable for patients and physicians on the English websites compared to the German ones. Even if many of the evaluated websites originated from medical organizations or universities, the amount of information was limited and often not up to date. CONCLUSION: Information on the web is widespread, but for special queries too limited and difficult to identify. An improvement of available websites is needed, especially those maintained by universities and nonprofit medical organizations. The retrieval software should be optimized to ease identification of information, which should be validated by a recognized standard.

Humans↗

[Laparoscopic splenectomy for idiopathic thrombocytopenia].

BACKGROUND AND OBJECTIVE: Splenectomy is of great benefit for patients with idiopathic thrombocytopenia (ITP), when medical therapy has failed. It was the aim of this retrospective study to evaluate the results of laparoscopic splenectomy. PATIENTS AND METHODS: All patients with ITP, who had a laparoscopic splenectomy between 1992 and 1999, were included in this study. RESULTS: 53 patients with an average age of 41.8 years had a laparoscopic splenectomy: 48 of these operations were finished laparoscopically, while conversion to the open technique was necessary in five patients. The mean operation time was 95 minutes. In the last 38 cases it was 76 minutes. There were no deaths and no reoperations were necessary. The average postoperative hospital stay was 3.9 days. After a mean follow-up of 24 (1-75) months thrombocytopenia recurred in eight patients, of whom five received medical therapy. CONCLUSION: Splenectomy can be easily performed laparoscopically in patients with ITP and has a low morbidity. The results of therapy of ITP are good. Because of the quick convalescence the patients' comfort is better than with the conventional operation.

Adolescent↗

[Current diagnosis and therapy of soft tissue sarcomas in the adult].

Soft tissue sarcomas embrace a wide variety of rare tumours. This often means excision without wide margins, and the unexpected malignancy leads to diversity of postoperative treatment. As a rule all lesions of a soft tissue tumour should be biopsied if persisting for more than 6 weeks. The extent of the biopsy is determined by the tumour characteristics, but should not aggravate later resection of a malignant tumour. Preoperative diagnostic studies should be standardised and include MNR, while the tumour is characterised according to the recent edition of the UICC GTNM system. The primary tumour should be excised in a limb-sparing way with wide margins, if necessary including the neighbouring fascia. Local recurrence should be approached aggressively like primary tumours, with curative intention. In cases of distant metastases, which usually occur in the lungs, a grading-associated approach is necessary. In G3 metastases chemotherapy should be administered before the surgical intervention. Radiation therapy is saved for patients in whom the tumour cannot be resected with wide margins or is larger than 10 cm maximum diameter. In the light of current knowledge, radiation therapy should be given as an adjuvant for patients whose tumour was resected without wide margins and for tumours larger than 10 cm in diameter. The use of palliative chemotherapy is still controversial and identification of new prognostic markers for patient selection is necessary. Since most patients with soft tissue sarcoma die from distant metastases and not the primary or locally recurrent tumour, the need for effective chemotherapy in an adjuvant setting is obvious. Controlled studies with as many enrolled patients as possible are necessary if valid data are to be collected. The management of soft tissue sarcoma patients is in principle multidisciplinary and should be confined to specialised centres.

Humans↗

Pancreatic cancer cells can evade immune surveillance via nonfunctional Fas (APO-1/CD95) receptors and aberrant expression of functional Fas ligand.

BACKGROUND: The Fas (APO-1/CD95) receptor/Fas ligand (FasR/FasL) system plays a key role in immune surveillance. We investigated the possibility of a tumor escape mechanism involving the FasR/FasL system in pancreatic cancer cells. METHODS: Fourteen pancreatic cancer cell lines and 3 pancreatic cancer surgical specimens were studied for their expression of FasR and FasL by flow cytometry, immunoblotting, and immunohistochemistry, FasR function was tested with an anti-FasR antibody. FasL function was assessed by coculture assays using pancreatic cancer cells and FasR-sensitive Jurkat T-cells. RESULTS: FasR was expressed in normal pancreas, in 14 of 14 pancreatic cancer cell lines, and in 3 of 3 surgical specimens. However, only 1 of 14 cancer cell lines expressed functional FasR when grown in monolayer, although 3 additional cell lines displayed functional FasR when cultured in suspension. Normal pancreas did not express FasL, whereas 14 of 14 cancer cell lines and 3 of 3 surgical specimens expressed FasL. FasL expressed by pancreatic cancer cells mediated killing of Jurkat T-cells in coculture assays (P < .005). CONCLUSIONS: These data suggest that pancreatic cancer cells have 2 potential mechanisms of evading Fas-mediated immune surveillance. A nonfunctional FasR renders them resistant to Fas-mediated apoptosis. The aberrant expression of functional FasL allows them to "counterattack" activated Fas-sensitive T-cells. Alone or in unison, these tumor escape mechanisms may contribute to the malignant and often rapid course of pancreatic cancer disease.

Apoptosis↗

Rupture of the spleen associated with Enterobacter cloacae.

A 58-year-old male, with abdominal pain but no signs of sepsis, was admitted as a medical emergency. During hospitalization, spontaneous splenic rupture was diagnosed and splenectomy successfully performed. A smear revealed presence of Enterobacter cloacae on the splenic surface; histopathology demonstrated granulocytous infiltration of the spleen.

Enterobacter cloacae↗

Stromal sarcoma of the stomach--a report of 20 surgically treated patients.

BACKGROUND: Twenty patients with gastric stromal sarcomas underwent surgery at the University Hospital of Hamburg-Eppendorf from 1979 to 1995. Symptoms were nonspecific. Exact preoperative diagnosis was difficult because of submucosal tumor growth. Operations varied from excision of the gastric wall to extended gastrectomy (pancreas, spleen, partial liver resection). RESULTS: In 16 cases, tumor could be resected with wide margins (R0). In four cases, tumor was found at the resection line (R1). After a median follow-up of 69 months, 12 patients with R0 resections (including tumors with poor differentiation or infiltration of surrounding organs) lived tumor free, and two died due to other causes. All four patients with R1 resections died because of tumor disease within 40 months. All patients had a mean survival time of 59 months and a 5-year-survival rate of 69%. CONCLUSIONS: Our series shows that not all gastric malignancies have a dismal prognosis, but that gastric stromal sarcomas have a favorable follow-up if resected with wide margins at initial surgery.

Adult↗

Survival in patients with primary soft-tissue sarcomas treated within 6 years.

Since 1988, treatment strategies for our sarcoma patients have been determined by the same team and operations performed by one surgeon. The aim of this study was to analyse prognostic data on local recurrence and survival of 101 consecutive patients who presented in our institution with the primary tumour manifestation. After a median follow-up of 35 months, the local recurrence rate was 13.5%, the mean survival time was 68 months and the 5-year survival rate was 83%. Besides positive lymph nodes (only 3 patients) the quality of resection significantly influenced local recurrences (P < 0.05). Univariate predictors of mortality were tumour grade (P < 0.01), tumour size (P < 0.05), distant metastases (P < 0.01), and resection quality (P < 0.01). Multivariate predictors of mortality consisted of grade (P < 0.0001), positive lymph nodes (P < 0.001) and resection quality (P < 0.01). In this homogeneous group of patients, excellent recurrence and survival rates could be achieved. An optimized surgical treatment not only reduces the rate of local recurrences but also augments survival time.

Adolescent↗

[Secondary resection of soft tissue sarcomas within the scope of a multimodality therapy concept].

We treated 95 patients with primary soft tissue sarcoma of the extremities or trunk between 1988 and 1995, who were operated on initially elsewhere and their tumors were supposed to be excised completely. We performed a primary re-excision in all patients and found residual tumor in 46%. After a median follow-up of 61 months, 16 patients developed a local recurrence and 6 patients died due to the tumor disease. Primary re-excision is therefore indicated in most cases where the histology report of an assumed benign tumor reveals malignancy.

Adolescent↗

Human pancreatic cancer cells (MPanc-96) recognized by autologous tumor-infiltrating lymphocytes after in vitro as well as in vivo tumor expansion.

A human tumor line designated MPanc-96 has been established from a poorly differentiated primary pancreatic adenocarcinoma. MPanc-96 has a doubling time of 27 hr and grows as a confluent monolayer in various culture media. Cytogenetic analysis of in vitro-cultured tumor cells revealed a large number of clonal chromosomal aberrations, confirming their neoplastic origin. MPanc-96 grows in SCID mice when injected s.c. Xenografts established from the tumor line had a similar histology as the primary tumor. Tumor-infiltrating lymphocytes (TILs) were isolated from the primary tumor, and cytotoxic T lymphocytes (CTLs) were generated after activation on immobilized anti-CD3 monoclonal antibody (MAb) for 48 hr, expansion in low-dose IL-2 and repeated stimulation with irradiated MPanc-96 tumor cells. The generated CTLs lysed fresh autologous tumor cells as well as in vitro and in vivo expanded tumor cells from passages 9-53, suggesting that one or more tumor-associated antigens (TAAs) are stably expressed. CTLs lysed tumor cells in an HLA-class I-restricted fashion but showed no significant cytotoxicity against autologous fibroblasts, several allogeneic pancreatic cancer cell lines or K562. Our findings may be significant for the design of an animal model for studying the mechanisms of immunotherapy in human pancreatic cancer or for the identification of TAAs in pancreatic cancer.

Adenocarcinoma↗

The HER2/neu-derived peptide p654-662 is a tumor-associated antigen in human pancreatic cancer recognized by cytotoxic T lymphocytes.

The protooncogene HER2/neu encodes a 185-kDa transmembrane protein with extensive homology to the epidermal growth factor receptor. It is overexpressed in several human cancers of epithelial origin, such as pancreatic cancer. Previously, we demonstrated that cytotoxic T lymphocytes (CTL) derived from breast, ovarian, and non-small cell lung cancer recognized a peptide derived from HER2/neu. To evaluate whether this HLA-A2-binding peptide is a tumor-associated antigen (TAA) in pancreatic cancer, the ability of HER2/neu-reactive CTL to lyse human pancreatic carcinoma cells was tested. CTL were generated from tumor-associated T lymphocytes from HLA-A2+ HER2/neu+ breast and ovarian cancer patients. All CTL recognized autologous and allogeneic HER2/ neu+ tumor cells in an HLA-A2-restricted fashion. Furthermore, all CTL recognized p654-662 (GP2) derived from HER2/neu. These CTL also recognized HER2/neu+ pancreatic cancer cells in an HLA-A2-restricted fashion. HER2/neu+ HLA-A2- pancreatic cancer were not or only poorly lysed. Repeated stimulation of HLA-A2+ PBL from pancreatic cancer patients using the HER2/neu-derived peptide resulted in specific recognition of this peptide and, more importantly, HER2/neu+ pancreatic tumors in an HLA-A2-restricted fashion. Autologous HLA-A2+ fibroblasts or HLA-A2+ malignant melanoma cells were not recognized. HLA-A2- peptide-stimulated T lymphocytes showed no significant cytotoxicity. These results demonstrate that this HER2/neu-derived peptide is a shared TAA among several adenocarcinomas including pancreatic carcinoma, suggesting a common mechanism of recognition of these human tumors by T lymphocytes. The identification of the HER2/neu-derived peptide GP2 as a TAA in pancreatic cancer provides an opportunity for the design of novel immunotherapy and vaccine strategies.

Adenocarcinoma↗

Chondrosarcoma of the thumb arising from a solitary enchondroma.

Secondary chondrosarcoma of the bone of the hand arising from a solitary enchondroma is a rare entity, with only 16 published cases in the literature. We report the clinicopathologic findings of a new case arising from a preexisting solitary enchondroma. A review of the literature is discussed.

Adult↗

Survival in primary soft tissue sarcoma of the extremities and trunk.

BACKGROUND: Soft tissue sarcomas (STS) of the extremities are rare. The purpose of this study was to identify prognostic risk factors associated with survival in patients with primary extremity and truncal STS. METHODS: Patient, tumor, and pathologic data from 149 consecutive patients with localized primary STS of the extremities and trunk were analyzed using Kaplan-Meier and Cox regression techniques to identify univariate and multivariate risk factors. A subgroup analysis was performed to compare factors predictive of survival in patients who received treatment before (n = 50) and after (n = 99) treatment was standardized in 1988. RESULTS: The 5-year survival rate was 76.5% with an average follow-up of 6 years. Local recurrence occurred in 23% of all patients, 40% before 1988 and 15% after 1988 (P < 0.0001). Risk factors associated with survival included resection quality (R0 vs. R1; P < 0.0001), era of operation (P = 0.002), local recurrence (P < 0.001), UICC stage (P < 0.0001), tumor size (P < 0.001), tumor depth (P = 0.002), regional lymph nodes (P < 0.0001), and histology (P < 0.0001). Multivariate analysis revealed that tumor size, tumor depth, and resection quality were independent risk factors of survival. CONCLUSIONS: These results indicate that management of STS in a specialized institution improves overall survival. Resection quality is the most important risk factor of survival. Therefore, effort should be made during primary treatment of STS to achieve wide, tumor-free resection margins.

Adolescent↗

Laparoscopic treatment of nonparasitic cysts of the liver with omental transposition flap.

BACKGROUND: Between 1991 and November 1994, 18 patients with large, solitary, nonparasitic liver cysts underwent laparoscopic deroofing; the last 13 of them also received an omental transposition flap in addition. METHODS: Using three to four trocars, the cystic contents were first aspirated, and the cyst derooted widely using diathermia. An omental transposition flap was fashioned and stapled into the cyst cavity itself. RESULTS: Postoperative complications included one case of pulmonary atelectasis. Another patient developed a subhepatic bile collection which was aspirated percutaneously. On average, patients were discharged on the 4th (2-14) postoperative day. Follow-up was performed with abdominal ultrasound for 2-43 months (mean 19 months). There were two early cyst recurrences, both in cases without an omental transposition flap (overall recurrence rate, 11%; in patients with omental flap, 0). CONCLUSIONS: Deroofing in combination with an omental transposition flap is a safe and effective therapy for symptomatic solitary liver cysts and can be performed using minimal-access surgical techniques.

Adult↗

Generation of peptide-specific cytotoxic T lymphocytes using allogeneic dendritic cells capable of lysing human pancreatic cancer cells.

BACKGROUND: Dendritic cells (DCs) are potent antigen presenting cells (APCs), able to efficiently induce primary T cell-mediated responses to foreign antigens. In earlier studies we were able to identify a histocompatibility antigen (HLA)-A 2-restricted nine amino acid peptide (GP2, peptide 654-662) from the transmembrane portion of the protooncogene HER2/neu as a tumor-associated antigen (TAA) in human pancreatic cancer. METHODS: Peripheral blood mononuclear cells (PBMCs) of HLA-A2+ and HLA-A2 healthy volunteers were isolated. PBMCs were grown with initial anti-CD3, low-dose interleukin-2 (IL-2), and peptide-pulsed DC stimulation. T-cell lines were analyzed in functional studies. RESULTS: After 4 weeks, T-cell cultures were more than 50% CD8+. All peptide-pulsed T cells significantly lysed APC pulsed with the immunizing antigen in an HLA-A2 restricted fashion. Furthermore, HLA-A2+,HER2/neu+ human pancreatic cancer cells were lysed significantly higher than HLA-A2 HER2/neu+ pancreatic cancer cells. Transfection of an HLA-A2 pancreatic cancer cell line with the HLA-A2 gene resulted in a significantly higher lysis of the transfected cell line compared to the wild type. In HLA-A2+ pancreatic cancer targets, specific lysis was HLA-A2 restricted. CONCLUSION: The ability to use DCs for presentation of either tumor or peptide antigen in an HLA-restricted fashion to stimulate T-cell proliferation, as well as cytotoxicity, demonstrates the potential of this technology for future development of a pancreatic cancer vaccine.

Amino Acid Sequence↗

[Cytotoxic T-lymphocytes and the recognition of tumor antigens--an approach to "preventive tumor vaccination?"].

In spite of modifications of the intra- and postoperative therapeutic strategy as well as new adjuvant protocols, most malignant diseases have a poor prognosis. This demonstrates the need for new approaches in tumor therapy. One alternative is adoptive immunotherapy (AIT). AIT is based on the observation that cytotoxic T-lymphocytes (CTL) may be generated with the ability to lyse autologous tumor cells in vitro and in vivo. Aim of current research activities is to determine specific tumorantigens and the clinical applicability of cell-mediated immunotherapy. The immunobiology of the cell-mediated immune response to cancer with focus on major-histocompatibility complex class I and CD8+ T cells is reviewed. Recent advances in the identification of tumor-associated and tumor-specific antigens were summarized. Previously performed clinical studies were reviewed. We examined the implications that the discovery of these antigens might have on the development of new anticancer vaccines.

Animals↗

[Surgical research and publications in Germany--an analysis of 1984-1994].

The present study analyses a selection of German and American surgical and cancer research journals from the years 1984 and 1994. The aim of the study was to evaluate the amount of publications by German surgeons in these journals. Furthermore, any influence of the impact factor on the publication criteria was analyzed. German surgical journals showed a high percentage increase in the impact factor but are, in absolute numbers, still significantly behind the American journals. In parallel, German surgeons are still the major contributors to German language journals, but increasingly publish in the American ones as well. The impact factor is one of the major selection criteria on to which journal a paper shall be submitted.

Animals↗