[Prognosis after complete surgical resection for non-small cell lung cancer based on the staging classification]. / Stadienabhängige Prognose nach lokal kompletter Resektion des nicht-kleinzelligen Lungenkarzinoms.

BACKGROUND AND OBJECTIVE: The importance of accurate staging according to the international TNM staging system of non-small cell lung cancer (NSCLC) for patient management and ascertaining individual prognosis cannot be overemphasized. The TNM classification is scheduled to be revised in 2007. In a large single-center collective we investigated the prognosis for patients who had complete resection of a NSCLC. PATIENTS AND METHODS: We retrospectively reviewed hospital records and follow-up data of 2,378 patients operated on between 1996 and 2005 for NSCLC. Complete resection was achieved in 2,083 patients. Systematic hilar and mediastinal lymph node dissection was performed concurrently. Probability of survival was then analysed with the Kaplan-Meier method. The significance of differences between subgroups was calculated using the log-rank test. Odds ratios with 95 % confidence intervals (CI) were calculated for each characteristic. The Cox model was used for multivariate analyses. RESULTS: The 5-year survival for patients after complete resection was 50.7 %. The 5-year survival rates for clinical stages were 72 % for stage IA, 59.8 % for stage IB, not defined for stage IIA, 47,8 % for stage IIB, 45 % for stage IIIA, 38.7 % for stage IIIB, and not defined for stage IV. There were significant differences in survival between stages IIIB and IV (p = 0.013). There was a trend towards significance between patients with IA and IB (p = 0.052). However, there was no significant difference between patients with all the other stages. 5-year survival according to pathological stages was: stage IA 68.5 %; stage IB 66.6 %; stage IIA 55.3 %; stage IIB 49.0 %; stage IIIA 35.8 %; stage IIIB 35.4 %; stage IV not defined. Gender, age and type of histology were found by multivariate analysis to be significant independent prognostic factors for survival. CONCLUSIONS: The TNM and stage grouping classification is valid for defining prognosis and prognosis-related criteria in patients with NSCLC. The difference in prognosis between clinical stages IIIB and IV was significant, but not that between all the other related subgroups. Concordance with histological staging demonstrated the quality of existing clinical staging methods and related strategies. Complete surgical resection, age, gender, histology and stage of the disease significantly influenced long-term survival.

Networking in shared care--first steps towards a shared electronic patient record for cancer patients.

OBJECTIVES: This paper aims at identifying the data protection and security requirements for a cross-institutional EPR. Three possible models and the first steps towards a cross-institutional EPR for the Thoraxklinik Heidelberg and the Department of Clinical Radiology of the University Medical Center of Heidelberg shall be discussed. METHODS: A comprehensive analysis of literature and legal documents supplied information for determining the data protection and security requirements. By means of information system analysis, the technical preconditions in both institutions as well as three possible models towards a cross-institutional EPR were identified. RESULTS: According to the German penal code it is only allowed to reveal patient information to external physicians in cases of so-called "treatment connection". An extension of the written consent, signed by the patient, verifying the patient agreement that his/her patient data will be stored in a cross-institutional EPR is needed. Among the three models that we identified, the model that constitutes of a virtual EPR with distributed data capture in both institutions was favored. By means of SecuRemote software a secure connection between the Thoraxklinik Heidelberg and the Department of Clinical Radiology was established, allowing the physicians to view the complete cross-institutional health information of a jointly treated patient during the weekly consultation on radiotherapy. CONCLUSIONS: Many requirements listed in this paper are requirements for electronic patient records in general. Besides these general requirements there are specific requirements for a cross-institutional EPR. The legal situation in Germany complicates the development and implementation of a cross-institutional EPR. However, we think that the efforts are reasonable, because a cross-institutional EPR will be able to improve the communication between health institutions, medical disciplines and persons involved in shared care processes. It provides them with more complete health information about the jointly treated patients. A cross-institutional EPR is, therefore, expected to improve the quality of patient care.

Using the eXtensible Markup Language (XML) in a regional electronic patient record for patients with malignant diseases.

Communication between different institutions which are responsible for the treatment of the same patient is of outstanding significance, especially in the field of tumor diseases. Regional electronic patient records could support the co-operation of different institutions by providing ac-cess to all necessary information whether it belongs to the own institution or to a partner. The Department of Medical Informatics, University of Heidelberg is performing a project in co-operation with the Thoraxclinic-Heidelberg and the Department of Clinical Radiology, University of Heidelberg with the goal: to define an architectural concept for interlinking the electronic patient record of the two clinical institutions to build a common virtual electronic patient record and carry out an exemplary implementation, to examine composition, structure and content of medical documents for tumor patients with the aim of defining an XML-based markup language allowing summarizing overviews and suitable granularities, and to integrate clinical practice guidelines and other external knowledge with the electronic patient record using XML-technologies to support the physician in the daily decision process. This paper will show, how a regional electronic patient record could be built on an architectural level and describe elementary steps towards a on content-oriented structuring of medical records.

Long-term survival in small cell lung cancer patients is correlated with high interleukin-2 secretion at diagnosis.

PURPOSE: We have previously reported significant impairment of IL-2 secretion in patients with small cell lung cancer (SCLC) at the time of diagnosis. Impairment of IL-2 secretion correlated with reduced survival in SCLC. This new prognostic factor was independent of other factors of prognostic relevance in SCLC. The prognostic value of IL-2 secretion was comparable to the most predominant prognostic factors for survival in SCLC identified so far. We now report long-term survival data from these patients. METHODS: The significance of correlations between single parameters in the test groups was calculated by using linear regression analysis, the Wilcoxon rank sum test, and Fisher's exact test. Using the Kaplan-Meier method, the log-rank test and the Cox regression model, we analyzed the relation of IL-2 secretion in whole blood cell cultures from 52 patients with SCLC at the time of diagnosis to established prognostic factors relevant for survival in SCLC. RESULTS: IL-2 secretion correlates with survival in SCLC. In addition, survival analysis according to tumor response and level of IL-2 secretion at the time of diagnosis demonstrates that long-term survival can only be observed after complete response to chemotherapy and high initial IL-2 secretion. CONCLUSIONS: IL-2 secretion at the time of diagnosis represents an independent prognostic factor for survival in SCLC. Moreover, long-term survival is only observed in patients with complete response upon chemotherapy that showed high IL-2 secretion at diagnosis. Therefore, IL-2 secretion may partially define long-term survival in this disease. These results have to be confirmed in a larger patient population.

Immunochemical analysis of cathepsin B in lung tumours: an independent prognostic factor for squamous cell carcinoma patients.

In order to evaluate the possible role of the proteolytic enzyme cathepsin B (cath B) in human non-small cell lung cancer (NSCLC) we examined cath B concentrations (cath B(C)) and activities (cath B(A)) in homogenates of 127 pairs of lung tumour tissues and corresponding non-tumourous lung parenchyma. Total cath B activity (cath B(AT)) and enzymatic activity of the fraction of cath B, which is stable and active at pH 7.5 (cath B(A7.5)) were determined by a fluorogenic assay using synthetic substrate Z-Arg-Arg-AMC. The immunostaining pattern of cath B was determined in 239 lung tumour tissue sections, showing the presence of the enzyme in tumour cells (cath B(T-I)) and in tumour-associated histiocytes (cath B(H-I)). The median levels of cath B(AT), cath B(A7.5) and cath B(C) were 5.6-, 3.2- and 9.1-fold higher (P < 0.001), respectively, in tumour tissue than in non-tumourous lung parenchyma. Out of 131 tissue sections from patients with squamous cell carcinoma (SCC), 59.5% immunostained positively for cath B, while among the 108 adenocarcinoma (AC) patients 48.2% of tumours showed a positive reaction. There was a strong relationship between the levels of cath B(AT), cath B(A7.5), cath B(C) and cath B(T-I) in the primary tumours and the presence of lymph node metastases. Significant correlation with overall survival was observed for cath B(T-I) and cath B(A7.5) (P < 0.01 and P < 0.05, respectively) in patients suffering from SCC. In these patients positive cath B in tumour cells (cath B(T-I)) and negative cath B in histiocytes (cath B(H-I)) indicated significantly shorter survival rate compared with patients with negative cath B(T-I) and positive cath B(H-I) (P < 0.0001). In contrast, in AC patients, both, positive cath B(T-I) and positive cath B(H-I), indicated poor survival probability (P < 0.014). From these results we conclude that the proteolytic enzyme cath B is an independent prognostic factor for overall survival of patients suffering from SCC of the lung.

Coping, distress, and survival among patients with lung cancer.

BACKGROUND: This study addresses the question of whether coping and emotional state are predictors of survival among patients with lung cancer. The hypotheses were (1) active coping is linked with longer survival time and (2) depressive coping, emotional distress, and depression are linked with shorter survival. METHODS: The study was based on a sample of 103 patients who were investigated after their diagnosis and before the beginning of primary treatment. The psychological variables were assessed by means of self-reports and interviewer ratings. After follow-up of 7 to 8 years, 92 patients had died; survival data were censored for the remaining 11 patients. The prediction of the survival time was performed by the Cox regression, while adjusting for biomedical risk factors (tumor stage, histological classification, and Karnofsky performance status). RESULTS: The self-reported depressive coping (P = .007) and the interviewer-rated emotional distress (P = .04) were significantly associated with shorter survival, independent of the influence of the biomedical prognostic factors. CONCLUSIONS: Both coping and emotional distress had a statistically independent effect on survival among patients with lung cancer. However, the naturalistic design of the study does not allow for any causal interpretation. Thus, the nature of this relationship warrants further investigation.

Sequential hepatic and pulmonary resections for metastatic colorectal cancer.

BACKGROUND: Resection of pulmonary or hepatic colorectal metastases is associated with a 5-year survival rate of 25-40 per cent. This report analyses outcome following sequential resection of colorectal metastases to both organs. METHODS: Seventeen patients with histologically confirmed colorectal adenocarcinoma and resection of liver and lung metastases were identified from a prospective database. RESULTS: The median interval between resection of the primary tumour and first metastasis was 21 (range 0-64) months. The interval between resection of the first and subsequent metastases was 18 (range 1-74) months. No patient died in the postoperative period and there were two perioperative complications. The overall survival rate in 17 patients was 70 per cent at 2 years from resection of metastasis to the second organ, but the disease-free survival rate at 2 years was only 24 per cent. CONCLUSION: Although few long-term survivors were observed in this small series, sequential resection of hepatic and pulmonary metastases is warranted in a highly selected group of patients.

[Treatment strategy in pleural mesothelioma]. / Behandlungsstrategie beim Pleuramesotheliom.

The development of diffuse malignant pleural mesothelioma is associated with exposure to asbestos. The surgical treatment comprises a radical pleuropneumonectomy with resection of the pericardium and diaphragm (P3D) or palliative pleurectomy/decortication of the tumor. The prognosis in general is poor. P3D is most effective in patients with epithelial mesothelioma at an early stage. Complete resection has the best prognosis. Palliative tumor decortication is restricted to symptomatic patients with acceptable performance status. The prognosis of patients after radical resection is not significantly different from patients with pleurectomy/decortication. Preliminary results of multimodal therapy concepts, including additional chemo- and/or radiotherapy, suggest an improvement in survival. Nevertheless, so far treatment has been focused on the palliation of clinical symptoms like pain and dyspnee.

[Do psychological factors modify survival of cancer patients? II: Results of an empirical study with bronchial carcinoma patients]. / Beeinflussen psychologische Faktoren die Uberlebenszeit bei Krebskranken? II: Ergebnisse einer empirischen Untersuchung mit Bronchialkarzinomkranken.

The present prospective test study of hypotheses addressed the question whether psychological factors are predictive of survival time in lung cancer patients. The hypotheses were: Emotional distress, depression and depressive coping are associated with shorter survival; hope and active coping with longer survival. The study was based on a sample of n = 103 patients who were investigated post-diagnosis and before the beginning of primary treatment. Emotional distress and hope were assessed by clinical scales (self-reports and interviewer ratings), depression by the Depression Scale of von Zerssen, depressive coping and active coping by the Freiburg Questionnaire on Coping with illness by Muthny. At follow-up, which took place three to five years later, n = 74 patients had died, for n = 29 patients the survival data are censored. The prediction of the survival time was performed applying multivariate analyses (Kaplan-Meier-method, Cox-Regression), adjusting for biological risk factors (histological classification, stage of the disease, type and amount of treatment, Karnofsky performance status, age). Results were as follows: Active coping and hope were associated with longer survival, emotional distress, depression and depressive coping with shorter survival, respectively. These associations were found consistently across assessment methods. The predictive effects of coping and distress were statistically independent of the influence of the somatic risk factors. The best psychological predictor was the interviewer rating of active coping. Its predictive power equalled that of the Karnofsky performance status. However, there was evidence that the effects of the psychological factors varied somewhat in interaction with treatment modalities. The findings are discussed from a methodological perspective. Possible causal models and mechanisms are presented which could account for interactions of psychological measures and the course of the disease: Thus, it can be conceived that psychological effects were mediated by patients' compliance with medical treatment. In addition, it cannot be ruled out that psychological factors themselves were influenced by the physical status of the patients at the time of entry to the study.

Decrease of interleukin-2 secretion is a new independent prognostic factor associated with poor survival in patients with small-cell lung cancer.

BACKGROUND: We have previously shown that suppression of interleukin-2 (IL-2) secretion was mediated by transforming growth factor (TGF) beta 1 secreted by small-cell lung cancer (SCLC) tumor cells. We have also shown that IL-2 secretion was significantly impaired in patients with SCLC at the time of diagnosis. Reconstitution of cytokine secretion correlated with reduction of tumor load. These data suggested that the immune system was suppressed by the tumor. To address the clinical relevance of cytokine suppression in SCLC, we investigated the correlation of the level of IL-2 secretion with survival. PATIENTS AND METHODS: The significance of correlations between single parameters in the test groups was calculated by using the linear regression analysis, the Wilcoxon rank sum test and the exact test according to Fisher. Using the Kaplan-Meier method, the log-rank test and the Cox-regression model, we analysed the relation of IL-2 secretion in whole blood cell cultures from 52 patients with SCLC at the time of diagnosis to established prognostic factors relevant for survival in SCLC. RESULTS: Impairment of IL-2 secretion significantly correlates to survival in SCLC (P = 0.004). Further univariate and multivariate analysis showed that this prognostic factor is independent from other factors of prognostic relevance in SCLC, namely stage of disease, neurone specific enolase (NSE), lactate dehydrogenase (LDH), age, and sex. More important, the prognostic value of IL-2 secretion is comparable to the most predominant prognostic factors for survival in SCLC identified so far. In the final model of the cox regression analysis, the P-value for IL-2 secretion in relation to stage of disease was 0.012 and 0.019, respectively. CONCLUSIONS: IL-2 secretion at the time of diagnosis represents an independent prognostic factor for survival in SCLC. Although its prognostic value has to be confirmed in a larger group of patients, our results demonstrate that IL-2 secretion may play an important role in diagnosis and treatment of SCLC. Moreover, in contrast to other prognostic factors, impairment of IL-2 secretion may help to understand immunosuppression in SCLC and, thus, important elements of the pathogenesis of this disease.

[Surgical information systems as instruments in quality assurance]. / OP-Informationssysteme als Instrumente zur Qualitätssicherung.

In various aspects, it is important to document medical procedures performed in surgical management. These records have become even more relevant because, in realizing the German health structure law, new forms of remuneration have been established, which are correlated with defined services. This means that data from medical documentation records today "rule" on financial compensation and, consequently, on the total economy of a hospital. Data are to be gathered considering multiple clinical and administrative requests; they have to register all pre-, intra- and postoperative details in their complex correlations; and, they are subject to strictly limited periods of compulsory availability. To meet these demands, data can only be recorded and evaluated by adequate computerized information systems. Starting out from a general data profile in response to questions from inside and outside of the hospitals, general criteria will be presented on what is to be recorded and how data are to be structured by surgery information systems. We will also refer to the interfaces required with information systems of other clinical departments that are part of the overall hospital information system. On this basis, guidelines are set up on how to plan, select, introduce and efficiently run these systems.

[Incomplete resections in bronchial carcinoma: morbidity and prognosis]. / Inkomplette Resektionen bei Bronchialcarcinom: Morbidität und Prognose.

Residual tumor (R1) was proven at the proximal bronchial resection margin in 88 (3.6%) of 2464 cases of lung cancer following lung resection and standard lymph node dissection. Postoperative complications (8%) were: fistula of the bronchial suture line (n = 7), bleeding (n = 2) and heart luxation (n = 1). The in-hospital mortality was 16.6%. Causes of death were: bronchial fistula (n = 7), erosion of the pulmonary artery (n = 4), respiratory failure (n = 1), and empyema (n = 1). Forty-three patients received postoperative radiation therapy. Median survival of all patients following incomplete resection was 16 months, compared to 37 months following complete resection (P < 0.001). Length of survival was independent of tumor stage, histology, site of infiltration and postoperative radiation. In conclusion, in resection for lung cancer clear margins should be verified by intraoperative frozen section. In the case of residual tumor at the bronchial resection margin, wider resection is mandatory in stage I and II if the patient meets the functional criteria. Even in stage III a and III b prognosis is significantly better after complete resection than R1-resection; the difference, however, is smaller than in lower stages.

[Radical surgery and lymph node dissection in bronchial carcinoma]. / Radikalität und Lymphknotendissektion beim Bronchialkarzinom.

Lymphatic spread of bronchial carcinoma can involve each position in the mediastinum. Localisation of the primary tumor has no influence. Metastatic skipping of topographical lymph node positions is not calculable. Therefore, systematic mediastinal lymph node dissection includes all ipsilateral compartments of the mediastinum. It is also possible to reach contralateral sides. In right-sided thoracotomies, the lymph node dissection is standardised. Mobilising the aortic arch and the large vessels also allows from a left-sided approach a complete mediastinal dissection. The surgical technique is described. Perioperative morbidity does not increase. Systematic mediastinal lymph node dissection is the golden standard for the evaluation of an exact pN stage. The stage-related survival rate is significantly improved. Therefore, the systematic mediastinal lymph node dissection should be a standard in the surgical therapy of bronchial carcinoma.

[Surgical therapy of lung metastases. An interdisciplinary responsibility]. / Chirurgische Therapie der Lungenmetastasen. Eine interdisziplinäre Aufgabe.

Surgical therapy of lung metastases is now an established procedure. The operation's purpose is radical, and therefore potentially curative, resection. There are also diagnostic and palliative indications. Median sternotomy is the standard approach as it allows revision of both lungs, which is important even when disease seems to be unilateral. Preoperative staging does not give a reliable idea of the number and extent of metastases. From 1972 to 1991, a total of 843 operations for lung metastases were carried out in 729 patients in the surgical department of the Thorax Clinic in Heidelberg (Rohrbach). The 30-day mortality was 2.9%, and the overall 5-year survival from the date of resection of the metastases was 33%. The best results were achieved in testicular cancer, with a 5-year-survival rate of 67%, and the poorest were observed in melanomas, with only 12% 3-year survival. In addition to the primary tumour, and in some cases depending on it, several other prognostic factors were relevant: radicality, sarcoma vs. carcinoma (carcinoma involved a better prognosis), disease-free interval, type of resection, thoracic lymph node involvement. Multivariate analysis showed that the prognostic influence of the factors varies considerably with the kind of primary tumour. Surgical treatment of lung metastases is part of an interdisciplinary oncological therapeutic concept offering prolongation of survival to most of the patients concerned and even the possibility of cure to some. Even if prolongation of survival is not feasible, an improved quality of life and therefore good palliation are obtained.

Induction chemotherapy with and without recombinant human granulocyte colony-stimulating factor support in locally advanced stage IIIA/B non-small cell lung cancer.

Patients with non-small cell lung cancer (NSCLC) in stage IIIA with more than minimal N2 involvement or in stage IIIB are considered unresectable. Response rates to chemotherapy for these patients are in the range of 40%. Reduction of tumor mass by induction chemotherapy may lead to resectability and to improved survival. We evaluated response rates and determined influence of induction chemotherapy on survival when followed by surgery and radiotherapy in 60 patients with primarily inoperable stage IIIA/IIIB NSCLC. The following cytotoxic regimens were used: cisplatin (100 mg/m2) and vindesine (3 mg/m2); ifosfamide (10 g/m2) and etoposide (360 mg/m2); or a combination of cisplatin (75 mg/m2), ifosfamide (6 g/m2), and etoposide (360 mg/m2). Sixty patients were treated with two to four cycles of these regimens between June 1988 and October 1992. In 40 patients chemotherapy was repeated every 4 weeks. In 20 patients chemotherapy was intensified by interval reduction to 3 weeks with recombinant human granulocyte colony-stimulating factor (r-metHuG-CSF, filgrastim) support. The median patient age was 54 years, and Eastern Cooperative Oncology Group performance status was 0 to 2. Distribution of stages IIIA and IIIB was 21 and 39 in all patients and 5 and 15 in the group treated with r-metHuG-CSF support, respectively. The overall response rate (complete plus partial responses) was 35%. In patients treated with intensified chemotherapy and r-metHuG-CSF support, the response rate was 60%. In 37 patients (61.6%) tumor was resected 4 to 6 weeks after the last cycle of chemotherapy; R0 resection was achieved in 22 patients, R1 in eight patients, and R2 in seven patients. With a follow-up of 4 to 60 months, 1-year survival in patients with tumor regression after chemotherapy and tumor resection was 82.2% versus 35.7% in nonresponders; 2-year survival of responders and nonresponders was 50.9% and 12.8%, respectively; and median survival was 23 months and 9 months, respectively (P < .001). Median survival rates for responders with stage IIIA and IIIB disease were 39 and 17 months, respectively. Median survival after response to chemotherapy and incomplete resection (11 patients) was 17 months, whereas median survival after response to chemotherapy and complete resection (18 patients) has not yet been reached. Only four patients in this group have died with a follow-up of 4 to 60 months. Of 20 patients receiving accelerated chemotherapy with r-metHuG-CSF support, World Health Organization grades 3 and 4 neutropenia occurred in five and eight patients, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Surgery for pulmonary metastases. The Heidelberg experience.

The surgical treatment of pulmonary metastases is now an established technique in the interdisciplinary concept of oncologic therapy. The authors' finding of a 5-year actuarial survival rate of 33% corresponds with the international standard. Unfortunately, data are only rarely provided as to whether the operations were curative or noncurative. The 5-year actuarial survival rate in 76% of the patients with potentially curative macroscopically radical operations was 38% for all organ tumors. For the time being, a series of prognostic factors should be considered in establishing the indication for surgery, and this should help to reduce the risk of undertreatment or overtreatment.

[Surgery for bronchial carcinoma with mediastinal lymph node involvement]. / Chirurgie du carcinome bronchique avec envahissement nodulaire médiastinal.

Or the 3000 patients analyzed in the prospective bronchial carcinoma field study, 1086 were operated between 1984 and 1989. Complete systematic mediastinal lymphadenectomy was performed in 661 patients to assess the PTNM stage as exactly as possible, and to improve prognosis. Lymphadenectomy removes all hylarand mediastinal lymph nodes. Although the operation is technically quite easy on the clearly structured right side, it is more difficult on the left side due to the aortic arch and its branches. The lymph nodes of the upper mediastinum of the left and right side can be completely dissected by mobilizing the aortic arch with the left subclavian artery. In contrast to what is frequently assumed, the histological findings indicate that there is no general pattern of metastatic spread in the lymph nodes. The metastases can leave out varying numbers of lymph nodes craniad as well as caudad. For this reason, the lymph nodes have to be completely resected to ensure a real R0-resection.