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Von vielen Patienten werden Thoraxdrainagen als grose Beeintrachtigung nach videoassistierten thorakoskopischen Operationen (VATS) empfunden. Daher wurde eine prospektiv randomisierte Studie durchgefuhrt, um zu untersuchen, ob bei VATS eine fruhe Drainagenentfernung am Operationstag sinnvoll ist. Dreiundneunzig Patienten erfullten die Einschlusskriterien (VATS-Operationen, u. a. atypische Lungenresektion, ausgedehnte Lunge im postoperativen Rontgenbild) und wiesen keine Ausschlusskriterien auf (Lungenvolumenreduktion, narbige Lungenfibrose, Pneumothorax, Pleuraerguss, Luftfistel). Die Randomisierung fuhrte bei 48 Patienten zur fruhen Thoraxdrainagenentfernung nach 90–120 min. Bei 45 Patienten wurde die Drainage belassen und im Median am 2. postoperativen Tag entfernt. Das Schmerzausmas war nach fruher Drainagenentfernung signifikant niedriger (p=0,03; T-Test), dementsprechend war der mittlere Schmerzmittelbedarf signifikant reduziert. Die Anzahl der postoperativen Rontgenkontrollen war nach fruher Drainagenentfernung signifikant geringer (p=0,0001; T-Test). Die mittlere postoperativ Liegedauer war mit 5,4 gegenuber 6,7 Tagen tendenziell kurzer. Behandlungsbedurftige Komplikationen traten nach fruher Drainagenentfernung nicht auf, jedoch bei 6 Patienten mit konventionellem Vorgehen (p=0,01; Fisher-Test). Die rasche Drainagenentfernung innerhalb 1–2 h nach VATS ist zu empfehlen, es sollte jedoch stets die Indikation gemas der Ein- und Ausschlusskriterien der vorliegenden Studie eingehalten werden. Ob die fruhe Drainagenentfernung auch zu einer Verminderung von chronischen Schmerzen fuhrt, werden die Langzeitergebnisse zeigen.

BACKGROUND A critical look at the effectiveness of medical procedures and therapies is important with the increasing limitations on resources in health care. METHOD The costs for treatment and the quality of life according to the SF-36 were analyzed in a retrospective health economic study on 65 patients who had undergone surgery for primary non-small-cell lung cancer. RESULTS The mean cost for all patients was 7,169 euro per patient. 38.8 % resulted from surgery, 31.6 % were attached to the preoperative phase on the general ward, 11 % postoperatively to the general ward. Intensive care costs accounted for 18.7 %. The cost of each surgical procedure ranged from 4,634 euro for a pneumonectomy to 8,366 euro for a lobectomy with sleeve resection of the bronchus. The most expensive factors were staff, disposable materials, pathological investigations, and radiology services. There was no difference in these proportions with stage of tumor or the surgical procedures undertaken. Quality of life as assessed by the SF-36 questionnaire ranged from 31.82 (physical functioning) to 75.0 (social functioning) one year after the operation. These scores were lower than for those with other chronic diseases. On average, 4.62 quality-adjusted life years were achieved. The cost per QALY was 1,970 euro. The extent of resection and the tumor staging correlates significantly with the mean cost per QALY. CONCLUSION Thoracic surgery is cost intensive. With increasing staging of the tumor, the cost for treatment increased as with increased operation complexity.

Tumors of the diaphragm are rare and caused by there special localisation difficult to diagnose. We describe the case of a 31 year old man with a choristoma of the left diaphragmal crux where the localisation and genesis could only be cleared through lateral thoracotomy. Nor the CT guided puncture or the laparoscopy-although sufficient samples for the pathology could be gained-allowed the right diagnose. The importance of good diagnostic approach to select the right operative procedure-in this case the anterolateral thoracotomy-is described.

Einleitung: Minimal-invasive Techniken haben in der Thoraxchirurgie zu einer Verminderung von unmittelbar postoperativen Schmerzen gefuhrt. Uber die Haufigkeit chronischer postoperativer Beschwerden liegen jedoch nur wenige Beobachtungen vor. Ziel der vorliegenden Untersuchung war es, am Beispiel von Patienten mit Spontanpneumothorax die Haufigkeit von chronischen Beschwerden nach minimal-invasiven Eingriffen zu evaluieren. Methoden: Es wurden 60 Patienten unter Verwendung eines standardisierten Fragebogens befragt und die Haufigkeit, Intensitat und Charakteristik von chronischen Schmerzen und Beschwerden erfast. Die mediane Beobachtungszeit betrug 59 Monate. Mit Hilfe des gleichen Fragebogens wurden weiterhin 27 Patienten nach anterolateraler Thoracotomie bei benignen Grunderkrankungen im Median 24 Monate postoperativ untersucht. Ergebnisse: Nach minimal-invasiver Operation gaben 19 (31,7 %) von 60 Patienten an, unter chronischen Beschwerden zu leiden. Analgeticabedurftige Schmerzen zeigten 2 Patienten (3,3 %). Auf einer visuellen Analogskala (0 = kein Schmerz bis 100 = starkster vorstellbarer Schmerz) bewerteten 17 Patienten die Schmerzintensitat in einem Bereich 50. Uberwiegend wurde der Schmerz als schneidend beschrieben (9/60 Patienten, 15 %). Nach Thoracotomie klagten 14 (51,8 %) Patienten uber chronische Beschwerden, davon 5 (18,5 %) mit Analgeticabedarf. Die mittlere Schmerzintensitat (Analogskala) betrug nach minimal-invasiver Operation 3,6 Punkte, nach Thoracotomie 14,4 Punkte (p = 0,01). Schlusfolgerungen: Auch nach minimal-invasiven thoraxchirurgischen Eingriffen kommen chronische Beschwerden vor. Diese sind aber seltener und weniger belastend als nach Thoracotomie.

BACKGROUND: It became recently evident that isolated tumor cells undetectable by conventional tumor staging are frequently present in bone marrow of patients with apparently localized non-small cell lung cancer (NSCLC). The clinical relevance of this minimal hematogenous tumor cell dissemination is under vigorous debate. METHODS: For tumor cell detection in the bone marrow we used monoclonal antibody CK2 against the epithelial intermediate filament protein cytokeratin 18. The influence of a positive bone marrow finding on clinical outcome was studied in 139 patients with NSCLC postoperatively staged as pT1-4, pN0-2, M0, R0 after a median follow up of 66 months (48-74). FINDINGS: Cytokeratin-18-positive cells in bone marrow were demonstrated in 83 (59.7%) patients at the time of primary surgery and in 6 of 12 representative patients analyzed twice 3-18 months after surgery. In patients without histopathological lymph node metastases (pN0; n = 66) the occurrence of > or = 2 tumor cells in bone marrow at primary surgery was a strong and independent predictor for overall survival (p = 0.007) in univariate analysis. The multivariate analysis showed a 2.8 times increased risk for shorter survival in patients with disseminated tumor cells versus patients without such cells. Four of the six patients with a positive CK status after surgery developed a tumor recurrence 11-44 months after the operation, while in none of the patients with a negative bone marrow at all times intervals showed a tumor relapse. CONCLUSIONS: Minimal residual bone marrow involvement is an independent prognostic factor for overall survival in patients with node-negative NSCLC, which may help to identify patients in need of an adjuvant systemic therapy. The postoperative persistence or re-appearance of tumor cells in bone marrow indicates that these are not only shredded cells but rather represent true micrometastasis.

In view of the high incidence of early distant tumor relapses in apparently completely resected (R0, M0) non-small cell lung cancer (NSCLC), there is a need for an adjuvant therapy. Considering the low tumor burden in these patients, an adjuvant therapy with monoclonal antibodies (i.e., the 17-1A MAb) might be appropriate. The purpose of our study was to test whether the 17-1A antigen is expressed on primary and metastatic NSCLC carcinoma cells. Using immunohistochemistry, the expression of 17-1A was analysed in primary tumors (n = 60) and in lymph node metastases (n = 7) of patients with NSCLC. Additionally, we investigated in 6 patients the expression of 17-1A on disseminated tumor cells in the bone marrow, which were detected by the pan-cytokeratin MAb A45-B/B3 using a double-labeling technique. The 17-1A antigen was homogeneously expressed in 47 (78.3%) out of 60 primary NSCLCs. The expression of 17-1A was independent from the tumor histology, the grade of differentiation, and other clinicopathological parameters (ploidy status, TNM-stage). Lymph node metastases were positive in 4 (57.4%) out of 7 cases. The double-labeling experiments demonstrated that 17-1A is coexpressed on disseminated tumor cells in the bone marrow in 5 (83%) out of 6 patients. The 17-1A antigen is expressed on the majority of primary, metastatic, and disseminated NSCLC cells. Patients with 17-1A-positive tumors might benefit from an adjuvant therapy with MAb 17-1A after completely resected NSCLC.

OBJECTIVE: To evaluate the effectiveness of lymphadenectomy in the treatment of non-small cell lung cancer (NSCLC). SUMMARY BACKGROUND DATA: The extent of lymphadenectomy in the treatment of NSCLC is still a matter of controversy. Although some centers perform mediastinal lymph node sampling (LS) with resection of only suspicious lymph nodes, others recommend a radical, systematic mediastinal lymphadenectomy (LA) to improve survival and to achieve a better staging. METHODS: In a controlled, prospective, randomized clinical trial, the effects of LA on recurrence rates and survival were analyzed, comparing LS and LA in 169 patients with operable NSCLC. RESULTS: After a median follow-up of 47 months, LA did not improve survival in the overall group of patients (hazard ratio: 0.78; 95% confidence interval: 0.47-1.24). Although recurrences rates tended to be reduced among patients who underwent LA, these decreases were not statistically significant (hazard ratio: 0.82; 95% confidence interval: 0.54-1.27). However, analysis of subgroups of patients according to histopathologic lymph node staging revealed that LA appears to prolong relapse-free survival (p = 0.037) with a borderline effect on overall survival (p = 0.058) in patients with limited lymph node involvement (pN1 disease or pN2 disease with involvement of only one lymph node level); in patients with pN0 disease, no survival benefit was observed. CONCLUSIONS: Radical systematic mediastinal lymphadenectomy does not influence disease-free or overall survival in patients with NSCLC and without overt lymph node involvement. However, a small subgroup of patients with limited mediastinal lymph node metastases might benefit from a systematic lymphadenectomy.

The extent of lymphadenectomy in the treatment of non-small cell lung cancer (NSCLC) is still a matter of controversy. While some centers perform mediastinal lymph node sampling (LS) with resection of only suspicious lymph nodes, others recommend a radical, systematic mediastinal lymphadenectomy (LA) in order to improve survival and to achieve a better staging. Herein we report on the impact of LA on intra- and postoperative morbidity and mortality, on tumor staging and on the prognosis of patients with operable NSCLC in a controlled prospective randomized clinical trial comparing LS and LA in a total of 182 patients. Comparison of short-term results revealed a significantly longer operation time in the LA group, but overall-morbidity and mortality were comparable in both groups. However, there were LA-associated complications like prolonged air leak and hemorrhage. Regardless of the type of lymphadenectomy performed, the percentage of patients with pN1 or pN2 disease was very similar in both groups, indicating that systematic radical lymphadenectomy is not an essential prerequisite to determine the N stage of a patient. In contrast, the number of patients detected to have lymph node involvement at multiple levels was significantly increased by LA. In the LS group only 4 out of 23 patients (17.4%) with N2 disease were found to have more than one lymph node level involved, while LA results in the detection of excessive N2 disease in 12 out of 21 patients (57.2%, p=0.007). After a median follow-up of 26.8 months there was no significant influence of LA on local recurrence-free interval, metastasis-free interval, or cancer-related survival. Radical systematic lymphadenectomy is a safe operation and results in a more detailed staging of the N2 region. The prognostic benefit of LA is questionable.

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 resuited 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.

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.

Immunohistochemical detection of the p53 gene product by monoclonal antibodies has been shown to be associated with a poor clinical outcome in carcinomas of the breast and stomach. Because the prognostic relevance of p53 immunostaining in lung cancer is still under debate, we studied the expression pattern and clinical significance of such staining in 73 patients with operable non-small-cell lung cancer. p53 expression was detected on frozen sections with the use of monoclonal antibody p1801, which recognizes both the wild-type and mutant gene product (alkaline phosphatase-anti-alkaline phosphatase method). A tumor was considered p53 positive if more than 1% of the tumor cells were stained. The p53 expression pattern was compared with clinicopathologic parameters, and analysis of follow-up, based on the data of 65 patients, was done by a log rank test (median observation time, 780 days). Nuclear p53 staining was detected in 33 of 73 non-small-cell lung cancers (45.2%). Comparison with clinicopathologic parameters demonstrated that the p53 protein was detected more frequently in younger patients (younger than 50 years, p = 0.014), whereas no correlation was found with sex, tumor differentiation, tumor histologic type, or TNM stage. Surprisingly, follow-up analysis revealed that p53 staining was associated with an increased rate of disease-free survival, especially in patients with early stage tumor disease (p = 0.004) and in male patients (p = 0.023). Counter to previous studies in other solid tumors, immunocytochemical detection of p53 expression does not predict a poor clinical outcome in non-small-cell lung cancer. In early-stage lung cancer it might be associated with an improved disease-free survival, which suggests that the majority of the detected protein inherits the wild-type tumor suppressor function. (J THORAC CARDIOVASC SURG 1995;109:1205-11)

The extent of lymphadenectomy in the treatment of non-small cell lung cancer is still a matter of controversy. While some centers perform mediastinal lymph node sampling with resection of only suspicious lymph nodes, others recommend a radical, systematic mediastinal lymphadenectomy (LA) to improve survival and achieve a better staging. Herein we report on the impact of LA on tumor staging in a controlled, prospective, randomized clinical trial comparing lymph node sampling and LA in a total of 182 patients with operable non-small cell lung cancer. Regardless of the type of lymphadenectomy performed, the percentage of patients with pathologic N1 or N2 (sampling: n = 23, 23.0%; LA: n = 22, 26.8%) disease was very similar in both groups, indicating that systematic radical lymphadenectomy is not an essential prerequisite to determine the N stage of a patient. In contrast, the number of patients detected to have lymph node involvement at multiple levels was significantly increased by LA. In the lymph node sampling group only 4 of 23 patients (17.4%) with N2 disease were found to have more than one lymph node level involved, whereas LA results in the detection of excessive N2 disease in 12 of 21 patients (57.2%; p = 0.007), which was associated with a shorter distant metastases-free (p = 0.021) and overall survival. In conclusion, LA is not essential to determine the N stage of a patient, but results in a more detailed staging of the N2 region, which is of prognostic significance. Therefore, it might be useful to identify patients with a higher risk for tumor relapse.

PURPOSE This prospective study was designed to evaluate the prognostic relevance and biologic characteristics of a minimal lymphatic tumor load in non-small-cell lung cancer (NSCLC). METHODS Frozen-tissue sections from 391 regional lymph nodes of 72 patients with completely resected NSCLCs, who were staged as free of metastases (pT1-3, pN0,M0,R0) by clinical tumor staging procedures and histopathologic examinations, were studied. For tumor-cell detection, we applied the alkaline phosphatase-antialkaline phosphatase (APAAP) immunostaining technique with monoclonal antibody Ber-Ep4 against two glycoproteins of 34 and 49 kd present of the surface and cytoplasm of epithelial cells. RESULTS Individual Ber-Ep4-positive cells were detected in 11 of 72 (15.2%) cancer patients, while positive staining was consistently absent in all sections from control nodes of 24 noncarcinoma patients. No correlation between a positive lymph node finding and either the size or differentiation grade of the primary tumor or the presence of micrometastatic tumor cells in bone marrow assessed by immunocytochemistry with antikeratin monoclonal antibody CK2 was observed. Following a median observation time of 26.0 months (range, 15 to 39), patients with lymph node micrometastases showed a significantly shorter disease-free survival duration than node-negative patients (log-rank test, P = .005). The independence of this prognostic significance was demonstrated by a multivariate analysis (Cox regression model, P = .005). CONCLUSION Our results provide evidence that the presence of single lung carcinoma cells in lymph nodes is an independent indicator of the disseminatory capacity of an individual primary tumor. Immunohistochemical assessment of micrometastases in lymph nodes is recommended for current tumor staging in NSCLC, as it might lead to better stratification of patients for adjuvant therapy.

Major histocompatibility complex (MHC) antigens and adhesion molecules, such as the intercellular adhesion molecule-1 (ICAM-1), appear to play an important role in the immunological recognition and destruction of tumour cells. We, therefore, examined the expression patterns of these proteins on primary tumours of 91 patients with operable non-small cell lung cancer (NSCLC). Applying immunohistochemistry with monoclonal antibody (MAb) W6/32 against a common framework determinant of HLA class I antigens revealed a deficient expression in 33.0% of the cases analysed, while neo-expression of either HLA class II antigens (MAb TAL.1B5) or ICAM-1 (MAb PA3.58-14) was observed in 26.4 or 29.7% of tumours, respectively. Analysis of consecutive tumour specimens indicated that HLA antigens and ICAM-1 were frequently coexpressed. With regard to clinicopathological risk factors, we could demonstrate a preferential expression of those markers in patients with locally restricted and well-differentiated tumours or no lymph node metastases, which was more pronounced in adenocarcinomas than in squamous cell carcinomas. In contrast, the presence versus the absence of HLA antigens and ICAM-1 was not correlated with the rate of tumour recurrence or overall survival in patients with NSCLC. In conclusion, the co-ordinated expression of immunologically relevant cell surface molecules on primary NSCLC is a frequent event that correlates with distinct parameters of favourable prognosis. However, we have no evidence that the immune response facilitated by these molecules can effectively influence the clinical course of the disease.

There is an increasing demand for accurate preoperative and intraoperative staging of bronchial carcinoma with respect to neoadjuvant therapy protocols and parenchyma-sparing operations. This study prospectively evaluated accuracy of computed tomographic scan and surgical assessment for staging of bronchial carcinoma in 108 consecutive patients. The stage of the primary tumor (T stage) was correctly determined in 85% of the patients, and surgical evaluation correctly determined the T stage in 92%. Invasion of major mediastinal structures posed a major problem for computed tomographic scan. On a node-by-node basis, computed tomographic scan predicted involvement of lymph nodes in 81% (sensitivity 29%, specificity 93%, positive predictive value 49%, negative predictive value 85%). The surgeon correctly determined the lymph node status in 69% of lymph nodes (sensitivity 90%, specificity 63%, positive predictive value 39%, negative predictive value 96%). On a patient-by-patient basis, computed tomographic scan correctly predicted the nodal status in 58% of patients. Accuracy of computed tomographic scan and surgical assessment in determination of the lymph node status strongly depended on tumor type and lymph node region (hilar or mediastinal region) studied. This was partly due to the fact that adenocarcinomas exhibited a high proportion of tumor-positive normal-sized lymph nodes, whereas squamous cell carcinomas showed a high proportion of enlarged tumor-free lymph nodes. In conclusion, computed tomographic scan and surgical assessment are sufficiently accurate for determination of the tumor stage but are insufficient in determining the nodal status. (J T horac C ardiovasc S urg 1992;104:413-20)

Pulmonary lymphangioleiomyomatosis is a rare disease that occurs mainly in women of reproductive age. The clinical characteristics include recurrent spontaneous pneumothorax and progressive dyspnea. The features of chest computed tomography are nearly pathognomonic with the detection of bilateral thin-walled cysts.A 32-year-old female presented with sudden-onset right-sided chest pain, which aggravated during inspiration, dyspnea at exertion, and cough. She had a history of bilateral recurrent spontaneous pneumothorax. Physical examination showed reduced pulmonary sounds on the right side. Chest X-ray confirmed the diagnosis of recurrent right-sided pneumothorax. Computed tomography showed multiple bilateral bullae. Video-assisted pleurectomy, bulla resection, and bulla coagulation were performed. The diagnosis of pulmonary lymphangioleiomyomatosis was confirmed by pulmonary biopsy. After pleurectomy, the patient remained symptom-free without recurrent pneumothorax.Pulmonary lymphangioleiomyomatosis is a rare cause of recurrent pneumothorax and should be considered a differential diagnosis, especially in young women with diffuse bilateral bullous emphysema or tuberous sclerosis.

Objectives: So far it has not clearly been demonstrated that systematic mediastinal lymphadenectomy improves survival in patients with non-small cell lung cancer. One explanation might be that in some patients an early spread of tumor cells has occurred which might not be curable by surgical means. To test this hypothesis lymph nodes of patients which were treated either by lymph node sampling or systematic lymphadenectomy were screened for micrometastatic spread of tumor cells and the influence of nodal micrometastases on the efficacy of lymphadenectomy was analyzed. Methods: Lymph nodes from patients (n ¼ 94) which were included in a randomized trial of lymph node sampling (LS, n ¼ 41) versus radical systematic lymphadenectomy (LA, n ¼ 53) were screened by immunohistochemistry for disseminated tumor cells using the antibody Ber-Ep4. The median observation time was longer than 5 years and follow-up data were available from all 94 patients. Kaplan–Meier curves were calculated and tested for statistical significance using the log-rank test. Results: Standard histopathological analysis revealed no lymph node involvement (pN0) in 61 patients, pN1 disease in 13 patients and pN2 disease in 20 patients without significant differences between LA and LS with respect to T-stage, N-stage or age and sex of the patients. By immunohistochemistry a minimal nodal spread of tumor cells was detected in 21 out of 94 patients (LS, n ¼ 10 (24%); LA, n ¼ 11 (21%)). Similar to the entire group of patients also in the subset of patients with nodal micrometastases the type of lymphadenectomy did not significantly influence the longterm survival (P ¼ 0:27 and P ¼ 0:39, respectively). In contrast, in patients with a negative immunohistochemical analysis systematic lymphadenectomy resulted in an improved overall survival (P ¼ 0:044). Conclusions: Our data provide some evidence that systematic lymphadenectomy improves survival in patients without an early locoregional spread of cancer cells. As long as these patients can not be identified preoperatively all patients should undergo a systematic mediastinal lymphadenectomy. q 2002 Elsevier Science B.V. All rights reserved.

Background . Treatment options for patients with microscopic residual disease at the bronchial margin (R1-resection) after resection for non-small cell lung cancer include observation, radiotherapy, reoperation, or even systemic therapy. The present study was performed to identify a parameter that would estimate the prognosis of these patients more precisely to permit a well-founded treatment recommendation for the individual patient. Methods . A total of 1,162 patients with resected nonsmall cell lung cancer were analyzed in this retrospective study. Fifty-four patients (4.6%) had R1-resections at the bronchial margin. Type of residual disease (mucosal, extramucosal, or involvement of the entire bronchial wall) and occurrence of tumor cells in the lymphatic vessels (lymphangiosis carcinomatosa) were recorded as distinct parameters and analyzed by univariate and multivariate analyses (Log rank test; Cox regression model). Results . Lymphangiosis carcinomatosa at the bronchial margin was detected in 22 patients (40.7%) and was associated with a significantly shortened survival (median survival with lymphangiosis carcinomatosa, 13.3 months; without lymphangiosis carcinomatosa, 20.1 months; p = 0.026). Early stage patients (stage I–II) without lymphangiosis carcinomatosa showed a median survival of 49 months. Multivariate analysis revealed that lymphangiosis carcinomatosa at the resection margin is an independent prognostic parameter ( p = 0.038). Even after postoperative radiotherapy the prognosis was still poor if a lymphangiosis carcinomatosa was detected (median survival, 17.1 months). All other parameters (T-stage, N-stage, tumor histology, type of bronchial wall involvement) were not of prognostic significance in R1-resected patients. Conclusions . Lymphangiosis carcinomatosa at the bronchial resection margin predicts a poor prognosis in patients with non-small cell lung cancer. It is more than questionable whether these patients would benefit from local treatment options like radiotherapy.

Objective: Recently, it has been shown that minimal-invasive surgical procedures like operations for spontaneous pneumothorax result in a reduction of pain in the immediate postoperative course. However, little is known on the influence of minimal-invasive thoracic surgery on long term disability. Therefore, we analyzed the incidence of chronic pain in patients after minimal-invasive operation for primary (PSP) or secondary (SSP) spontaneous pneumothorax. Methods: In the study included were 78 patients (PSP: na 59; SSP: na 19; male: 58, female 20) who had been treated at our institution between 1992 and 1995. The median age was 37 years (range: 17‐84). The patients were interviewed by a standardized questionnaire or alternatively by phone or in the outpatient clinic. Complete follow up data were obtained from 60 patients which were further analyzed. Results: After a median follow up of 59 months (range 35‐79) 41 (68.3%) patients were completely free from any complaints. However 19 (31.7%) patients suffered from chronic pain. Two of them (3.3%) required daily oral pain medication. The incidence of chronic complaints was more frequent in patients with pleurectomy (47.1%) as compared to patients with mechanical pleurodesis only (25.6%; Pa 0:107). On a visual analog pain scale (ranging from 0 to 100) five (8.3%) patients described a pain intensity ,10, 12 (20%) patients between 10 and 20 and two (3.3%) patients .50. In the majority of the patients the pain was located in the area of the trocar incisions. Six (10%) patients had a chronic complaints in the ipsilateral shoulder. Conclusions: The incidence of chronic postoperative complaints after minimal-invasive procedures for spontaneous pneumothorax is relatively high. This has to be considered if minimalinvasive procedures are discussed to be an alternative to simple drainage therapy for the first episode of spontaneous pneumothorax. q 2001 Elsevier Science B.V. All rights reserved.

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.

Seit wenigen Jahren stehen sensitive immunzytochemische Verfahren zum Nachweis fruhdisseminierter epithelialer Tumorzellen in Lymphknoten oder im Knochenmark von Patienten mit soliden Tumoren zur Verfugung. Obwohl die simultane Untersuchung beider Regionen wichtige Informationen hinsichtlich der Tumorbiologie und der Relevanz der verschiedenen therapeutischen Ansatze liefern konnte, liegen derartige Untersuchungen bis heute nicht vor. Wir haben daher in einer prospektiven Studie simultan das Ausmas der Tumorzelldisseminierung in die regionaren Lymphknoten und in das Knochenmark bei 91 Patienten mit resektablen Bronchialkarzinomen untersucht.

Summary 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 1000000. 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.

Trotz vermeintlich kurativer Operation erleiden etwa 30–40% der Patienten mit einem pT1–3, pNO, MO-Bronchialkarzinom ein haufig lebensbegrenzendes Tumorrezidiv. Es ist daher anzunehmen, das bei einem Teil dieser Patienten bereits zum Operationszeitpunkt eine Tumorzelldissemination vorliegt. Mit sensitiven immunzyto-chemischen Methoden kann das Ausmas einer fruhen regionalen und/oder systemischen Tumorzelldissemination nachgewiesen werden. So findet sich bei pNO-Patienten in 15,2% der Falle bereits eine fruhe lymphatische Disseminierung und bei 54,3% eine systemische Disseminierung in das Knochenmark. Da eine systematische Lymphadenektomie in dieser Patientengruppe keine wesentliche Prognoseverbesserung erlaubt, sollten die Risikopatienten im Stadium I einer adjuvanten systemischen Therapie unterzogen werden.

BACKGROUND: Pulmonary function is a main factor influencing postoperative morbidity and mortality in thoracic surgery. OBJECTIVE: To determine the significance of surgical trauma on postoperative pulmonary function by comparing the preoperative forced expiratory volume in 1 second with that obtained 14 days after surgery. METHODS: A retrospective study was conducted on 385 consecutive patients undergoing elective thoracic surgery over 3 years. RESULTS: Operative trauma alone effected a reduction of approximately 0.6 L per second in the value of forced expiratory volume in 1 second irrespective of the extent of pulmonary resection. Significant differences in the overall reduction among enucleation, segmental resection, lobectomy, and pneumonectomy were not observed. CONCLUSIONS: The data indicated that the remaining lung tissue was severely compromised throughout the postoperative period and that surgical trauma was the main factor influencing postoperative pulmonary function for at least 2 weeks.

Diffuse parenchymal bleeding and major air leaks still present a challenge to the thoracic surgeon. This study was therefore designed to evaluate efficacy and handling of fibrin-glue-coated collagen fleece, to address these problems. In an experimental part defects were produced in lungs of troll pigs to compare the use of the fleece with infrared coagulation. Immediate airtightness and postoperative adhesions were evaluated. Scores were designed to evaluate quality and extension of the adhesions. In a clinical study parenchymal resection sites were sealed with fibrin-glue-coated collagen fleece in 52 patients. No patient suffered from postoperative bleeding. In three cases air leaks were still present on the third postoperative day, representing a 5.8% failure rate. 92.3% of the patients showed neither postoperative hemorrhage nor prolonged air leaks. A fixed combination of collagen fleece and fibrin glue consequently can be considered as a valuable tool in thoracic surgery.

The value of radical systematic lymphadenectomy in the treatment of bronchial carcinoma is controversial. In a randomized controlled clinical trial, radical lymphadenectomy was compared with conventional node dissection in 182 patients with non-small cell lung cancer. Comparison of short-term results revealed a significantly longer operating time in those undergoing systematic lymphadenectomy, but overall morbidity and mortality rates were comparable between groups. However, there were complications associated with radical lymphadenectomy such as prolonged air leakage and haemorrhage. Interim analysis of results at a median follow-up of 26·8 months showed no significant influence of radical lymphadenectomy on local recurrence-free interlval, metastasis-free interval or cancer-related survival. In conclusion, radical systematic lymphadenectomy is a safe operation that leads to a better staging of non-small cell lung cancer, but its prognostic benefit is questionable.

Lungenkrebs ist die haufigste Ursache der malignom-bedingten Todesfalle in den westlichen Industrielandern mit einer Gesamt-5-Jahresuberlebensrate von etwa 10% [1]. Die meisten Patienten sind zum Zeitpunkt der Diagnosestellung inoperabel und diejenigen mit operablen Primartumoren erleiden haufig ein Tumorrezidiv. Etwa 40% der Patienten, die klinisch und konventionell histopathologisch postoperativ als tumorfrei eingestuft werden (T1-2, N0, M0, R0) zeigen in den ersten zwei postoperativen Jahren eine erneute Tumormanifestation. Man mus daher davon ausgehen, das es bei vielen Patienten bereits zum Zeitpunkt der Diagnosestellung und Operation zu einer Tumorzellaussaat gekommen ist, welche mit den bisherigen Mitteln des Tumorstagings nicht ausreichend erfast wird. Wir haben daher in einer prospektiven Studie das Ausmas und die prognostische Bedeutung einer minimalen Tumorzellabsiedlung in Lymphknoten von 72 Patienten, die klinisch und konventionell histopathologisch ein T1-3, N0, M0, R0 Tumorstadium aufwiesen, untersucht.

The case is reported of a 43-year-old patient with a peripherally located bronchial carcinoid tumor containing large amounts of immunoreactive and bioactive growth-hormone releasing hormone (GHRH). Because no GHRH was found in the peripheral circulation, there was no quantitative or qualitative derangement of growth-hormone secretion. The tumor was excised completely by thoracotomy.

PURPOSE: In recent years, the detection of even a few tumor cells in lymph nodes of patients with surgically resected non–small-cell lung cancer (NSCLC) became possible with immunohistochemical staining procedures. Tumor cells in lymph nodes have been shown to be associated with an increased rate of early recurrence. However, the prognostic significance of this minimal tumor cell spread for overall survival remains unclear. PATIENTS AND METHODS: We used the epithelium-specific monoclonal antibody Ber-EP4, which recognizes the 17-1A antigen (also called EGP40 or Ep-CAM), to discover small tumor cell deposits (≤ three cells) in 565 regional lymph nodes judged as tumor-free by conventional histopathology in patients with NSCLC staged as pT1-4, pN0-2, M0, R0. In a prospective analysis, we studied the influence of the detected tumor cells on the cancer recurrence rate and survival of 117 patients. RESULTS: Ber-EP4-positive cells were found in 27 of 125 patients (21.6%). After an observation period of 64 months, patients with disseminated tumor cells had reduced disease-free survival (P CONCLUSION: The immunohistochemical detection of disseminated tumor cells in lymph nodes of patients with completely resected NSCLC is an independent prognostic factor for overall survival.

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. (J THORAC CARDIOVASC SURG 1996;112:623-30)