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O Thetter

Publications and source records attributed to O Thetter.

At least 37 records · Page 2Linked to original sources

Reduced expression of plakoglobin indicates an unfavorable prognosis in subsets of patients with non-small-cell lung cancer.

PURPOSE: Plakoglobin is thought to play a key role in cadherin-mediated epithelial cell adhesion, because it is a common component of desmosomal and nondesmosomal adherens junctions. Because loss of homotypic cell adhesion is an important early step in invasion and metastasis of solid tumors, we evaluated the frequency and prognostic significance of a deficient expression of plakoglobin in human lung cancer. PATIENTS AND METHODS: At primary surgery, representative specimens of the primary tumor were obtained from 96 consecutive patients with completely resected non-small-cell lung carcinoma (NSCLC) without overt distant metastases. Cryostat sections of these specimens and metastatic lymph nodes were stained with monoclonal antibody (mAb) PG 5.1 against plakoglobin, using an immunoperoxidase technique. Patients were monitored for a median of 39 months (range, 12 to 56) after surgery. RESULTS: Absent or severely reduced expression of plakoglobin (ie, < 30% positive tumor cells) was observed in 39 patients (40.6%). There was no significant correlation to established risk factors, such as the histology, extension, and histologic grade of the primary tumor and metastatic lymph node involvement, or expression of alpha-catenin. Expression of plakoglobin in lymph node metastases ranged from 0% to greater than 60% positive tumor cells. Deficient plakoglobin expression on the primary tumor was significantly correlated to a shortened disease-free and overall survival in patients with adenocarcinomas, pT1-2 tumors, or negative lymph nodes (pN0). In patients with pT1-2 tumors, the independence of this prognostic influence from established risk factors was demonstrated by Cox regression analyses (disease-free survival, P = .002; overall survival, P = .038). CONCLUSION: Deficient expression of plakoglobin appears to be an important event in the progression of NSCLC.

Adult↗

[Simultaneous immunocytochemical detection of tumor cells in lymph nodes and in bone marrow of patients with resectable bronchial carcinomas].

Despite an apparently curative resection more than 50% of patients with non-small cell carcinomas (NSCLC) will relapse after surgery. Therefore, it has to be assumed that in a substantial number of patients a tumor cell dissemination has occurred already at the time of surgery. In a prospective study we analyzed the extend of an early regional tumor cell dissemination into lymph nodes and/or a systemic tumor cell dissemination into the bone marrow in 91 patients with completely resected NSCLC by using sensitive immunocytochemical techniques. A tumor cell dissemination limited to the regional lymph nodes was detected in 14 (15.4%) patients. A systemic dissemination of tumor cells into the bone marrow alone in 10 (11.1%) patients. In 6 patients (6.6%) both body compartments were involved by immunocytochemistry. The detection of a nodal and a systemic tumor cell dissemination was associated with a significantly shortened disease free survival (p = 0.002 and p = 0.05, respectively). A Cox regression analysis demonstrated that the detection of tumor cells by immunocytochemistry is an independent prognostic factor (p = 0.018). In conclusion the detection of disseminated tumor cells by immunocytochemistry is an useful prognostic parameter, which underlines the requirement of a multimodal therapeutic strategy in these patients.

Biopsy↗

[Minimally invasive thoracic surgery--evaluation after 5 years].

A prospective study documented all minimally invasive operations performed in the department of thoracic surgery between 1992 and 1996. The most frequent indications were: lung biopsy (n = 181, 30.9%), coin lesions of unknown origin (n = 179; 30.5%), pneumothoraces (n = 133; 22.7%), pleura effusions (n = 19; 3.2%), and pleura empyema (n = 13; 2.2%). The majority (82.6%) of the minimally invasive procedures were completed without conversion; in 6.0% an extension (< 5 cm) of one of the trocar incisions was necessary and in 11.5% an anterolateral thoracotomy. It is demonstrated that a wide spectrum of thoracic operations can be performed by the minimally invasive approach.

Adolescent↗

[Lymph node documentation and lymphadenectomy in bronchial carcinomas. Results of a survey in Germany].

A number of different mapping systems have been published for the lymph-node staging in lung cancer. The use of a reproducible map is an essential prerequisite for correct determination of the TNM status and comparing the surgical results. In order to evaluate the current status of lymph-node mapping and lymph-node dissection in Germany, we performed a mail survey involving 90 hospitals performing operations for lung cancer. Responses were obtained from 61 (67.7%) hospitals. Currently, the majority of the departments (43%) use the German staging system (according to the Deutsche Gesellschaft für Thorax-, Herz- und Gefässchirurgie/Pneumologie), 23% lymph-node mapping according to Naruke, and 25% an individual description of the resected lymph nodes. The number of resected lymph nodes is reported in 75% of the departments, the quotient of involved/not involved lymph nodes in 33%. Mediastinal lymph-node sampling guided by the intraoperative aspect of lymph nodes is performed in 59% of the departments. A systematic mediastinal "enbloc" resection is accomplished in 41%. The results of this survey represent the current status of lymph-node mapping and lymphadenectomy in lung cancer in Germany and might be useful for the development of a uniform staging system.

Carcinoma, Bronchogenic↗

[Efficacy of minimally invasive thoracic surgery in diagnosis of pulmonary coin lesion].

AIM OF THE STUDY: With only a few exceptions every pulmonary nodule of unknown dignity has to be clarified by biopsy. Aim of the present study was to analyze the usefulness of minimal invasive thoracic surgery in patients with indeterminate pulmonary lesions. METHODS: In the study included were 121 patients (67 male/54 female), who were primarily treated by minimal-invasive surgery during the period 1992-1995. Preoperatively, a single pulmonary nodule was diagnosed in 89 patients. 32 patients had two or more lesions. RESULTS: Using the minimal invasive approach a pulmonary nodule was successfully localized and resected in 83 (68.5%) patients. In 33 patients the operation was classified as diagnostic, in 36 patients benign or inflammatory tumors were completely resected and in 14 patients palliative resections of malignant tumors were performed. Overall, an extension of the operative approach was necessary in 38 (31.5%) of the patients. In 23 patients a "mini-thoracotomy" (< 5 cm) was used to localize the nodule. A standard thoracotomy was performed in 15 patients, mostly because of massive adhesions. CONCLUSIONS: The minimal invasive approach has become a routine procedure in thoracic surgery and is extremely useful in the diagnosis of indeterminate pulmonary nodules.

Adult↗

[Results of minimally invasive surgery in patients with recurrent or persistent primary pneumothorax].

BACKGROUND: The objective of the study was to analyse the efficiency of video-assisted thoracic surgery (VATS) in the treatment of primary spontaneous pneumothorax (PSP) in an initial series of 65 patients. METHODS: From April 1992 to December 1995 47 male and 18 female patients with a median age of 28 years (range 17-53) were treated for persistent (n = 20) or recurrent (n = 45) spontaneous pneumothorax by VATS. In most patients a stapling of bullae using an endostapler was performed followed by parietal pleurectomy or pleural abrasion. Postoperative parameters, like use of analgetics, length of hospital stay and length of drainage were compared with a control group of 57 patients treated by lateral thoracotomy between January 1988 and December 1991. RESULTS: Conversion to lateral thoracotomy was necessary in 6 (9.3%) patients. Postoperative complications occurred in one patient (1.7%) consisting of a persistent air leak for more than 7 days. No second intervention was necessary. There were no operative deaths. 4 recurrences were noted after a median follow-up of 29 months. All recurrences occurred in the first 18 months after surgery. Compared to lateral thoracotomy the treatment by VATS resulted in a significantly shortened hospital stay (mean: 8 vs. 11 days; p < 0.001) and drainage time (mean: 4 vs. 5 days; p < 0.001). The use of opioid analgetics was 3.7 days (mean, range 1-11 days) after VATS and 6.5 days (mean, range 2-20 days) after conventional therapy. CONCLUSIONS: Surgical treatment by VATS is a viable alternative to lateral thoracotomy in patients with recurrent or persisting PSP.

Adolescent↗

[Women in surgery].

Women surgeons are also capable of their job as men surgeons. The part time job imports the balance between surgical career and family goals of a women neverseless respecting economics and efficiency in health care policy. To arrive equal conditions it seems to need a growth of the group of women surgeons and to get more role modells and mentors.

Career Choice↗

[Cost comparison of minimal invasive surgery vs. standard operation exemplified by primary pneumothorax].

In patients with primary spontaneous pneumothorax, the costs for a minimally invasive operation were retrospectively compared with the costs for a standard operation using lateral thoracotomy. The calculations were based on the direct costs for the operation, the expenditures for the in-hospital stay, and the socioeconomic costs in terms of working disability. The results demonstrate that the high expenses for the minimally invasive operation are compensated by the reduction in costs due to a shorter in-hospital stay and a shorter recovery time in patients treated by minimally invasive surgery.

Adult↗

[Perioperative use of noninvasive ventilation].

BACKGROUND AND AIM: Noninvasive mask ventilation is in some cases of respiratory failure the treatment of choice. It is used in cases of acute respiratory failure. We report about perioperative application of noninvasive mask ventilation. PATIENTS AND METHODS: We treated 25 patients with respiratory failure pre- and/or postoperative with noninvasive mask ventilation. RESULTS: The success rate in all patients was 68%, but it was very different in respect to the varying causes of respiratory failure. CONCLUSION: With noninvasive mask ventilation it is possible to avoid in some patients with acute postoperative respiratory failure complications who are referred to intubation. In patients with postoperative decompensation of chronic respiratory failure postoperative treatment becomes easier, in extraordinary cases the method makes surgery possible.

Humans↗

Frequency and prognostic significance of isolated tumour cells in bone marrow of patients with non-small-cell lung cancer without overt metastases.

BACKGROUND: Metastasis is generally looked on as a late event in the natural history of epithelial tumours. However, the poor prognosis of patients with apparently localised lung cancer indicates that micrometastases occur often before diagnosis of the primary tumour. METHODS: At primary surgery, disseminated tumour cells were detected immunocytochemically in bone marrow of 139 patients with non-small-cell lung carcinomas without evidence of distant metastases (pT(1-4)pN(1-2)M(0)). Tumour cells in bone-marrow aspirates were detected with monoclonal antibody CK2 against cytokeratin polypeptide 18. Patients were followed up for a median of 39 months (range 14-52) after surgery. 215 patients without epithelial cancer (ie, with benign epithelial tumours, non-epithelial neoplasms, or inflammatory diseases) acted as controls. FINDINGS: In 83 of 139 (59.7%) patients cytokeratin-positive cells were detected at frequencies of 1 in 100 000 to 1 in 1 000 000. Even without histopathological involvement of lymph nodes (pN(0)), tumour cells were found in 38 of 70 (54.3%) patients. 1 positive cell was found in each of 6 out of 215 controls. Surgical manipulation during primary tumour resection did not affect the frequency of these cells. In Cox's regression analyses, the presence of such cells was a significant and independent predictor for a later clinical relapse in node-negative patients (p=0.028). INTERPRETATION: Early dissemination of isolated tumour cells is a frequent and intrinsic characteristic of non-small-cell lung carcinomas. The finding of these cells may help to decide whether adjuvant systemic therapy is required for the individual patient.

Antibodies, Monoclonal↗

Detection of disseminated lung cancer cells in lymph nodes: impact on staging and prognosis.

BACKGROUND: A major reason for the high incidence of tumor recurrences in patients with apparently resectable non-small cell lung cancer is presumably early tumor cell dissemination, which is clearly underestimated by current staging procedures. METHODS: In this prospective study we assessed the frequency and prognostic significance of early lymphatic tumor cell spread to regional lymph nodes staged as tumor free by conventional histopathology by applying an immunohistochemical assay using monoclonal antibody Ber-Ep4. RESULTS: Ber-Ep4 positive cells were demonstrated in 27 (21.6%) of 125 patients and in 35 (6.2%) of 565 lymph nodes, respectively. Immunohistochemical analysis resulted in an up-staging in 24 of 27 patients. In patients previously staged as having pN0 disease, tumor cells were detected in 11/70 cases (15.7%). Univariate and multivariate survival analysis showed that the detection of minimal nodal tumor cell dissemination was associated with a reduced disease-free survival (log rank test, p = 0.0001; Cox regression model, p = 0.001). CONCLUSIONS: The use of immunohistochemistry enables one to identify many patients with regional tumor cell dissemination at the time of operation. These patients might benefit from an adjuvant therapeutic regimen.

Antibodies, Monoclonal↗

Expression of MHC molecules and ICAM-1 on non-small cell lung carcinomas: association with early lymphatic spread of tumour cells.

Early microdissemination of tumour cells determines the prognosis of patients with apparently localised non-small cell lung cancer (NSCLC). Monoclonal antibodies to epithelial antigens can now be used to detect single carcinoma cells present in mesenchymal secondary organs such as bone marrow or lymph nodes. The present study was designed to obtain insights into the potential role of the immune system in lymphatic and haematogenous microdissemination of NSCLC cells. Using immunohistochemical staining of primary NSCLC, we assessed the expression pattern of molecules mediating an efficient cellular immune response, that is, MHC class I and class II antigens and the intercellular adhesion molecule-1 (ICAM-1). All 58 patients evaluated were staged as free of overt metastases by conventional clinico-pathological screening. Isolated tumour cells in bone marrow or lymph nodes were identified with mAb CK2 to cytokeratin component No. 18 and mAb BerEp-4 to glycoproteins of 34 and 39 kd present on epithelial cells, respectively. MHC class I expression on primary tumours was reduced or absent in 6/10 (60.0%) patients with isolated cancer cells in lymph nodes as compared to 6/33 tumours (18.1%) without such tumour cell dissemination (P = 0.01). MHC class II molecules on primary tumours were detected in 1/10 (10.0%) patients with micrometastases to regional lymph nodes and in 10/33 (30.3%) patients without such a tumour cell spread. None of the 10 patients with nodal microdissemination expressed ICAM-1 on their primary NSCLC, while such expression was detectable in 12/33 (36.4%) patients without this dissemination (P = 0.01). In contrast, the detection of tumour cells in bone marrow was not correlated to the expression of any of these immunoregulatory molecules. Our data suggest that escape caused by deficient expression of MHC class I antigens and ICAM-1 on tumour cells may support homing or survival of disseminated tumour cells in lymphoid tissue.

Adult↗

Mode of spread in the early phase of lymphatic metastasis in non-small-cell lung cancer: significance of nodal micrometastasis.

The impact of lymphatic micrometastases on prognosis of non-small-cell lung cancer has not been clearly established. We therefore prospectively assessed the frequency, mode of mediastinal spread, and prognostic significance of lymphatic micrometastases in lymph nodes of 93 patients with completely resected non-small-cell lung cancer staged as pT1 to pT4 pN0 and pN1 by conventional histopathologic techniques. Frozen tissue sections from 471 lymph nodes that were staged as free of metastases by routine histopathologic examination were screened for micrometastases by the alkaline phosphatase-antialkaline phosphatase immunostaining technique with the monoclonal antibody Ber-Ep-4. Twenty of 73 patients (27.4%) with disease staged as pN0 and nine of 20 patients (45.0%) with disease staged as pN1 had nodal micrometastases. Eight of 17 patients with upper lobe primary tumors and five of 12 patients with lower lobe primary tumors exhibited skip micrometastases. Mean relapse-free survival was significantly increased in patients with pN0 disease without micrometastases (41.1 vs 29 months, p = 0.0081). In patients with pN1 disease, mean relapse-free and cancer-related survivals were also significantly increased if no micrometastases were found (34.8 and 38.2 months vs 18 and 23.5 months, p = 0.0157 and p = 0.0094). Patients with disease staged as pN0 and pN1 with micrometastases revealed no difference in cancer-related survival compared with a control population of patients with disease staged as pN2. The mode of spread was erratic. The prognosis of patients after upstaging of pN0 and pN1 disease according to results of immunohistochemical staining correlated strongly with the prognosis of patients whose disease was staged at the higher stages by conventional histopathologic examination. These findings could represent a new indication for adjuvant therapy, supporting extensive lymph node sampling for staging purposes.

Adult↗

[Limits of surgery in patients with apparently localized bronchial carcinoma (pT1-3, pN0, M0)].

Despite an apparently curative resection, about 30-40% of the patients with pT1-3, pN0, M0 non-small cell carcinomas (NSCLC) will relapse after surgery. Therefore, it has to be assumed that in some patients a tumor cell dissemination has occurred already at the time of surgery. By using sensitive immunocytochemical techniques, the extent of an early regional and/or systemic tumor cell dissemination can be demonstrated. In pN0 patients, an early lymphatic dissemination can be detected in 15.2% of the cases and a systemic spread of tumor cells into the bone marrow in 54.3%. Since systematic mediastinal lymphadenectomy does not significantly improve the long-term prognosis in these patients, a systemic adjuvant therapy should be offered to patients at risk with a stage I NSCLC.

Biomarkers, Tumor↗

[Expression of plakoglobin in bronchial carcinomas: incidence and significance for disease outcome].

Loss of homotypic cell adhesion is an important prerequisite for invasion and metastasis of epithelial tumor cells. The function of E-cadherin, which mediates epithelial cell-cell adhesion, is regulated by a complex of proteins bound to its cytoplasmic tail, including a-, b-, g-catenins and plakoglobin (PG). The present study was designed to assess whether downregulation of plakoglobin expression occurs in human non-small cell lung carcinomas (NSCLC) and whether this change is associated with an unfavorable prognosis. Using immunohistochemistry with monoclonal antibody (mAb) PG 5.1 to PG, absence or severely reduced expression of PG (i.e., less than 30% of positive tumor cells) was observed in 39 of 97 patients (40.2%) with completely resected primary NSCLC (stages T1-3, N1-2, M0). There was no significant correlation to any of the analyzed clinicopathologic factors such as histologic type, grade or size of the primary tumor, and lymph node involvement. After a median observation period of 39 months (12-56 mo.), univariate Kaplan-Meier analysis showed that patients with PG-deficient primaries tended to have a shortened disease-free survival (p = 0.06). This correlation was statistically significant in patients with adenocarcinomas (p = 0.010), locally restricted primary tumors (pT1/2, p = 0.017), and negative lymph nodes (pN0, p = 0.036). Analysis of the overall survival in these subgroups also revealed significant associations between deficient PG expression and poor outcome (p < or = 0.036). Multivariate analysis was performed for the largest subgroup of patients with pT1/2 tumors (n = 66), demonstrating that PG expression was a strong, independent predictor of tumor relapse (p = 0.002). Thus, deficient expression of PG is a frequent, early event in the progression of NSCLC, which appears to predict an unfavorable prognosis in patients at earlier stages of their disease.

Adult↗

[Limits and outcome of curative resection of bronchial carcinoma in advanced age].

In a retrospective study, we analyzed the effect of the age of the patients on long-term results of curative resections for lung cancer. Between 1989 and 1995, 771 patients with resectable lung cancer were recorded in our department. Of these patients, 141 (18.4%) were 70 years or older (median: 73 years, range 70-85). The analysis of long-term survival, including non-cancer-related deaths, demonstrated a poorer prognosis for the older patients. This was, however, mainly due to an increased rate of deaths in patients with advanced tumor stages, while there were no significant differences between younger and older patients with stage I or II lung cancer.

Aged↗