[Implementation of new technologies in the DRG system under economic aspects]. / Implementierung neuer Technologien unter ökonomischen Gesichtspunkten im DRG-System.

The implementation of technological innovations in surgery, such as robotic-assisted procedures, novel implants, navigation or modern visualization techniques, pose an economic challenge for institutions, as they are rarely cost-covering per se. In the German diagnosis-related groups (DRG) system, the costs of numerous novel technologies and innovations in surgery are not or not sufficiently covered in the short term and even less in the middle and long term. This review article describes the economic aspects of surgical innovations and outlines possible ways for hospitals to cover costs. A simulated case study illustrates the extent to which the current German DRG tariff system reflects the costs of minimally invasive techniques (laparoscopic, robot-assisted) in the context of an elective sigmoid colon resection with benign indications.

Detection of disseminated tumour cells in mediastinoscopic lymph node biopsies and endobronchial ultrasonography-guided transbronchial needle aspiration in patients with suspected lung cancer.

PURPOSE: Ultrasound-guided transbronchial needle aspiration of mediastinal lymph nodes (EBUS-TBNA) is apparently more accurate for cancer diagnosis than standard transbronchial needle aspiration (TBNA), but it is less sensitive than mediastinoscopy. The detection of disseminated tumour cells in transbronchial needle aspiration and mediastinoscopic biopsies could improve staging and might be helpful concerning indications for neoadjuvant regimen. The goal of this study was to develop a quantitative method for the detection of disseminated tumour cells (DTCs) in lymph node samples from patients with suspected lung cancer. PATIENTS AND METHODS: We compared in a prospective trail EBUS-TBNA (n=58 patients, 86 samples) and mediastinoscopy (n=22 patients, 37 samples) in two largely independent cohorts of lung cancer patients. Eleven patients, 14 samples were analysed using both methods. Patients without evidence of malignant disease were available as controls for EBUS-TBNA (n=20 patients, 28 samples) and mediastinoscopy (n=6 patients, 8 samples). Real-time quantitative mRNA analysis was performed for the cytokeratin 19 (CK19) and MAGE-A genes (MAGE-A 1-6, MAGE-A12) as markers, using a LightCycler 480 instrument. RESULTS: CK19 mRNA expression in EBUS-TBNA samples was detected in 84/86 (98%) and in 28/28 control samples (100%). After mediastinoscopy 16/37 (43%) samples of lung cancer patients were CK19 mRNA positive while controls showed no CK19 mRNA expression (0/8). MAGE-A expression was detectable in 42/86 (49%) EBUS-TBNA samples and in 13/37 (35%) mediastinoscopy samples. MAGE-A expression was detected in EBUS-TBNA controls in 3/28 (11%) and 1/8 (12%) mediastinoscopy controls. High MAGE-A expression correlated with increased tumour stage. CONCLUSION: Since CK19 expression was detected in all EBUS-TBNA samples from the control patients, but not in mediastinoscopy samples, we conclude that CK19 is not suitable as a marker for disseminated tumour cells in samples attained by EBUS-TBNA. One possible explanation is a contamination with epithelial cells from the bronchial tubes. MAGE-A genes are promising markers for disseminated tumour cells in lymph nodes in patients with suspected lung cancer which merit further investigation.

[Multimodal therapy for malignant pleural mesothelioma including extrapleural pneumonectomy]. / Multimodale Therapie des malignen Pleuramesothelioms einschliesslich der Pleuropneumonektomie.

Multimodal therapy including neoadjuvant chemotherapy with subsequent extrapleural pneumonectomy and postoperative radiotherapy has been shown to improve the survival of patients with malignant pleural mesothelioma (MPM) if they are selected carefully. Careful patient selection is required in order to administer aggressive multimodal therapy only to patients who will benefit from such a treatment. To achieve an accurate staging (

[Early chest tube removal after video-assisted thoracoscopic surgery. Results of a prospective randomized study]. / Frühe Drainagenentfernung nach videoassistierten thorakoskopischen Operationen. Ergebnisse einer prospektiv randomisierten Studie.

BACKGROUND: Chest tubes frequently cause postoperative patient discomfort after video-assisted thoracoscopic surgery (VATS). Therefore, a prospective randomized study was conducted to analyze whether early chest tube removal within 2 h postoperatively is justified in VATS. METHODS: Ninety-three patients fulfilled the inclusion criteria (VATS including wedge resection, complete lung extension on postoperative chest roentgenogram) and showed no exclusion criteria (lung volume reduction surgery, extensive pulmonary fibrosis, pneumothorax, pleural effusion, air fistula). Randomization resulted in early chest tube removal in 48 patients and in conventional chest tube management in 45 patients. RESULTS: Pain intensity was significantly reduced after early chest tube removal (P=0.03, t-test). In consequence, the mean analgesic requirement was significantly reduced (P=0.0001, t-test). The number of postoperative chest roentgenograms was significantly reduced after early chest tube removal (P=0.0001, t-test). The mean postoperative length of hospital stay was 5.4 vs 6.7 days (P=0.11, t-test). No postoperative complication occurred after early chest tube removal, while postoperative complications were observed in six patients with conventional chest tube management (P=0.01, Fisher's test). CONCLUSION: Early chest tube removal after video-assisted thoracoscopic wedge resection is recommended. The inclusion and exclusion criteria of this study should be considered for future early chest tube removal. Long-term follow-up will clarify if early chest tube removal also leads to a reduction in chronic pain.

Melanoma associated antigen (MAGE)-A3 expression in Stages I and II non-small cell lung cancer: results of a multi-center study.

OBJECTIVES: Adjuvant immunotherapy is an innovative therapeutic option that might potentially improve outcome of early-stage non-small cell lung cancer. Melanoma associated antigen (MAGE)-A3 is a promising target for immunotherapy because it is exclusively presented on the cell surface of cancer cells and might be associated with an aggressive cancer phenotype. The present study was performed to determine the rate of MAGE-A3 expression in early-stage non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Primary tumor samples from 204 patients with operable clinical Stages I or II NSCLC were collected between March and November 2001. Pathological Stage was determined by the local pathologist in each of the 16 participating institutions. Tissue samples were stored immediately after surgery in a RNA-stabilizing solution and were frozen at -20 degrees C. MAGE-A3 expression was analyzed by detection of MAGE-A3 transcripts using reverse-transcriptase polymerase chain reaction. RESULTS: MAGE-A3 expression was observed in 80 out of the 204 (39.2%) examined Stages I-II primary tumors. Stratification into UICC-Stages showed that 31 out of 105 (29.5%) Stage I non-small cell lung cancers and 49 out of 99 (49.5%) Stage II non-small cell lung cancers expressed MAGE-A3. In comparison to Stage I, the rate of MAGE-A3 positive tumors was significantly increased in Stage II (P=0.004; Chi-square test). CONCLUSION: The MAGE-A3 expression rate showed that a promising proportion of operable patients with early-stage non-small cell lung cancers are possible candidates for trials investigating adjuvant therapy with MAGE-A3 immunization. Currently, a phase two trial of adjuvant MAGE-A3 vaccination is in progress.

[Autotransplantation of at least one parathyroid gland during thyroidectomy in benign thyroid disease minimizes the risk of permanent hypoparathyroidism]. / Simultane Autotransplantation von Nebenschilddrüsengewebe im Rahmen der totalen Thyreoidektomie wegen M. Basedow oder benigner Knotenstruma.

OBJECTIVE: Permanent hypoparathyroidism is a distressing complication of thyroid surgery. The reported incidence varies between 0.4 and 13.8 % and is directly correlated to the extent of thyroidectomy. The aim of this retrospective study was to analyze whether simultaneous autotransplantation of at least one parathyroid gland during total thyroidectomy for benign thyroid disease could reduce the risk of permanent hypoparathyroidism. METHODS: Since 01/1999 all thyroid operations are prospectively recorded. Beside daily postoperative measurement of serum calcium level, iPTH is routinely determined on the third post op day. Patients with complications are followed closely. Postoperative hypoparathyroidism persisting for more than 6 months is defined permanent. RESULTS: Between 01/1999 and 02/2001 146 total thyroidectomies for benign thyroid disease have been performed (81 pat. with Graves disease, 62 with nodular goiter, 3 with thyroiditis de Quervain/Hashimoto). In 37 pat. (25 %) at least one parathyroid gland was simultaneously autotransplanted into the ipsilateral sternocleidomastoid muscle. Group I (no parathyroid autotransplantation, n = 109) and group II (parathyroid autotransplantation, n = 37) were comparable concerning patient age, thyroid disease and lowest post op calcium level (2.07 versus 2.05 mmol/l). The incidence of postoperative symptomatic hypocalcemia (14.7 % versus 21.6 %) and temporary hypoparathyroidism (15.6 % versus 18.9 %) was higher in group II patients (n. s.). Conversely, permanent hypoparathyroidism occurred exclusively in group I patients (2.75 %), patients with parathyroid autotransplantation (group II) did not develop this complication. CONCLUSIONS: Simultaneous autotransplantation of at least one parathyroid gland during total thyroidectomy for benign thyroid disease seems to minimize the risk of permanent hypoparathyroidism. The potential of routine autotransplantation in this setting has to be evaluated. The incidence of postoperative temporary hypocalcemia may be elevated with this policy.

Mediastinal lymphadenectomy in non-small cell lung cancer: effectiveness in patients with or without nodal micrometastases - results of a preliminary study.

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=94) which were included in a randomized trial of lymph node sampling (LS, n=41) versus radical systematic lymphadenectomy (LA, n=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=10 (24%); LA, n=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 long-term survival (P=0.27 and P=0.39, respectively). In contrast, in patients with a negative immunohistochemical analysis systematic lymphadenectomy resulted in an improved overall survival (P=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.

[Chronic diarrhea as a first manifestation of small cell lung cancer. A case report]. / Chronische Diarrhoe als Erstmanifestation eines kleinzelligen Bronchialkarzinoms - Eine Fallbeschreibung.

We report the case of a 57-year-old man presenting with chronic diarrhea for more than three months and a solitary pulmonary nodule of the right upper lobe. After atypical resection, showing a clinical stage I small cell lung cancer (SCLC), a lobectomy combined with a systematic mediastinal lymphadenectomy were performed. The histopathological examination revealed a pT1, pN0, SCLC. Postoperatively, the diarrhea improved for four weeks. The patient developed septic complications after adjuvant chemotherapy and died two months after the diagnosis was established. After exclusion of other causes for chronic diarrhea we suppose that the patient's diarrhea can be considered as an atypical paraneoplastic syndrome of SCLC.

Significance of lymphangiosis carcinomatosa at the bronchial resection margin in patients with non-small cell lung cancer.

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 non-small 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.

[Long-term complaints after minimal invasive thoracic surgery operations and thoracotomy]. / Langzeitbeschwerden nach minimal-invasiven thoraxchirurgischen Operationen und nach Thoracotomie.

BACKGROUND: Minimally invasive techniques are now frequently used in general thoracic surgery. More than 30% of all minimally invasive procedures are operations in patients with spontaneous pneumothorax. Recently, it has been shown that the video-assisted approach compared to the standard anterolateral thoracotomy results in a significant reduction of the early postoperative pain. However, little is known about the influence of video-assisted surgery on long-term complaints. METHODS: We analyzed the frequency and characteristics of chronic complaints in 60 patients after video-assisted operations for spontaneous pneumothorax using a standardized questionnaire. For comparison, 27 patients after anterolateral thoracotomy for benign diseases were interviewed 24 months postoperatively using the same questionnaire. RESULTS: After minimally invasive surgery and a median observation time of 59 months, 19 (31.7%) out of 60 patients suffered from chronic complaints. Two of them (3.3%) required daily oral pain medication. On a visual analog pain scale (ranging from 0 to 100), 17 patients described a pain intensity of < 20 and 2 (3.3%) patients > 50. After thoracotomy 14 (51.8%) out of 27 patients suffered from chronic complaints, 5 (18.5%) of them with regular use of oral pain medications. The mean pain intensity (analog scale) was 3.6 points after minimally invasive operations and 14.4 points after thoracotomy (P = 0.01). CONCLUSIONS: In conclusion, even after minimally invasive thoracic operations some patients suffer from chronic complaints. However, they are less frequent and of lower intensity than after thoracotomy.

Incidence of chronic pain after minimal-invasive surgery for spontaneous pneumothorax.

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: n=59; SSP: n=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%; P=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 minimal-invasive procedures are discussed to be an alternative to simple drainage therapy for the first episode of spontaneous pneumothorax.

Overexpression of matrix metalloproteinase 2 predicts unfavorable outcome in early-stage non-small cell lung cancer.

This prospective study was performed to assess the impact of matrix metalloproteinase (MMP) 2 expression on the clinical course of patients with operable non-small cell lung cancer (NSCLC). Specimens of 193 consecutive patients with completely resected NSCLC were examined for MMP-2 expression by immunohistochemical staining with a polyclonal antibody. Homogeneous immunostaining of cancer cells was considered positive and heterogeneous, or no staining was considered negative concerning overexpression of MMP-2. Four specimens were excluded from further analyses because of unspecific staining. The median follow-up period was 71.5 months (range, 12-120 months). Overexpression of MMP-2 was observed in 64 (33.9%) of 189 patients and did not correlate with clinicopathoiogical parameters. In patients without lymph node involvement (pN0 stage) MMP-2 overexpression was an independent prognostic parameter for unfavorable outcome: Log-rank analysis showed a significant association of MMP-2 overexpression with shortened cancer-related survival (P = 0.04) and disease-free survival (P = 0.03). Multivariate regression analysis confirmed MMP-2 overexpression as predictor of shortened cancer-related survival in NSCLC without lymph node involvement (P = 0.005, relative risk, 2.6). The present study revealed that MMP-2 overexpression predicts a poor prognosis in early-stage NSCLC. Therefore, it might be worth investigating the role of MMP inhibitors as adjuvant therapeutic agents in NSCLC.

The 17-1A antigen is expressed on primary, metastatic and disseminated non-small cell lung carcinoma cells.

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.