Preoperative serum lactate dehydrogenase level as a predictor of major complications following thoracoscopic lobectomy: a propensity-adjusted analysis.

OBJECTIVES: Despite the positive effects of a thoracoscopic approach on improving postoperative outcomes, the risk of major complications following thoracoscopic lobectomy is not negligible. We sought to assess the usefulness of the preoperative determination of serum biomarkers to refine risk stratification in this patient population. METHODS: From 2009 to 2017, 626 patients (285 women, 341 men; median age: 67 years) underwent thoracoscopic lobectomy or anatomical segmentectomy for confirmed or suspected early-stage lung cancer or metastasis at our institution. Preoperative serum biomarkers, including albumin, C-reactive protein, haemoglobin and lactate dehydrogenase (LDH), were examined as predictors of postoperative cardiopulmonary complications using logistic regression analyses followed by causal inference. RESULTS: The 90-day mortality, cardiopulmonary complication and overall morbidity rates were 1.0%, 13.1% and 18.1%, respectively. Although serum albumin, C-reactive protein and haemoglobin were not associated with cardiopulmonary complications in regression analyses, preoperative serum LDH level emerged as an independent morbidity predictor (odds ratio 1.008, 95% confidence interval 1.002-1.013; P = 0.006). The causal inference using the covariate balancing generalized propensity score methodology demonstrated similar results and an approximately positive linear relationship between the odds of cardiopulmonary complications and preoperative serum LDH level. For every 100 U/l increase in preoperative serum LDH, a 2-fold increase in the odds of cardiopulmonary complications was observed. CONCLUSIONS: Our results suggest that the preoperative serum LDH level is an independent predictor of 90-day cardiopulmonary complications following thoracoscopic lobectomy or segmentectomy, even in properly selected patients. Therefore, we recommend incorporating early serum LDH measurements as a readily available method into the risk assessment process prior to major lung resection.

Impact of comorbidity burden on morbidity following thoracoscopic lobectomy: a propensity-matched analysis.

BACKGROUND: Given the positive effect of a thoracoscopic approach on improving postoperative outcomes, it is reasonable to speculate whether an increased comorbidity burden is related to higher morbidity following thoracoscopic lobectomy. We sought to evaluate the impact of comorbidity burden on adverse postoperative outcomes in this patient population. METHODS: A retrospective review of our institutional database included 512 patients undergoing thoracoscopic lobectomy for early-stage non-small cell lung cancer (NSCLC) from 2009 through 2016. Comorbidity burden was assessed by the Charlson comorbidity index (CCI) and classified as high (CCI ≥3) or low (CCI <3) grade. Propensity score matching and random effects model were performed. RESULTS: Patients included 228 women and 284 men with a median age of 67 years. High and low comorbidity burdens were found in 193 and 319 patients, respectively. The postoperative mortality, pulmonary and cardiovascular complication rates and overall morbidity in patients with high comorbidity burden were comparable to those with low comorbidity burden (1.6% vs. 0.6%, 9.3% vs. 8.5%, 6.2% vs. 6.0%, 24.4% vs. 22.9%, respectively). Similar results were seen after propensity score matching, which balanced differences in demographics and preoperative characteristics between the comorbidity groups. On the analyses of propensity-matched data using generalized linear mixed model, a high comorbidity burden was not related to greater postoperative complication rates. CONCLUSIONS: Our results suggest that thoracoscopic lobectomy can be performed with low mortality and reasonable morbidity in lung cancer patients presenting with multiple comorbid diseases. The presence of a high comorbidity burden measured by CCI does not have a perceptible impact on adverse postoperative outcomes following thoracoscopic lobectomy.

American Society of Anesthesiologists physical status facilitates risk stratification of elderly patients undergoing thoracoscopic lobectomy.

OBJECTIVES: Accurate risk assessments are particularly important for elderly patients being considered for lobectomy. Considering the positive effects of the thoracoscopic approach on postoperative outcomes, we sought to review the reliability of the established risk factors for elderly patients undergoing thoracoscopic lobectomy. METHODS: From January 2009 to March 2016, 441 patients in our institution underwent thoracoscopic lobectomy for early-stage lung cancer. Clinical outcomes were compared between elderly (>70 years, n = 176) and younger patients (n = 265). RESULTS: There was no significant difference in postoperative mortality and morbidity between elderly and younger patients. In the regression analyses restricted to elderly patients, American Society of Anesthesiologists physical status (ASA-PS) was the single strong predictor of postoperative morbidity. The odds of pulmonary and cardiopulmonary complications increased nearly 6- and 3-fold, respectively, in those with ASA-PS Grade 3 compared with patients with ASA-PS Grade <3. Additionally, male gender was found to have a possible causal effect of pulmonary complication in elderly patients. After confounder adjustment using propensity score matching, the generalized linear mixed model revealed more than an 8-fold increase in the odds of pulmonary complications in elderly men compared with elderly women. To check the robustness of the above-mentioned finding, inverse probability of treatment weighting was used as an alternative analysis indicating a weaker but still substantively significant effect of male gender, with an odds ratio >3. CONCLUSIONS: Our results suggest that ASA-PS is a strong predictor of morbidity among elderly patients considered for thoracoscopic lobectomy. Compared with elderly women, elderly men are particularly prone to postoperative pulmonary complications.

Increased cFLIP expression in thymic epithelial tumors blocks autophagy via NF-κB signalling.

The anti-apoptotic cellular FLICE-like inhibitory protein cFLIP plays a pivotal role in normal tissues homoeostasis and the development of many tumors, but its role in normal thymus (NT), thymomas and thymic carcinomas (TC) is largely unknown. Expression, regulation and function of cFLIP were analyzed in biopsies of NT, thymomas, thymic squamous cell carcinomas (TSCC), thymic epithelial cells (TECs) derived thereof and in the TC line 1889c by qRT-PCR, western blot, shRNA techniques, and functional assays addressing survival, senescence and autophagy. More than 90% of thymomas and TSCCs showed increased cFLIP expression compared to NT. cFLIP expression declined with age in NTs but not in thymomas. During short term culture cFLIP expression levels declined significantly slower in neoplastic than non-neoplastic primary TECs. Down-regulation of cFLIP by shRNA or NF-κB inhibition accelerated senescence and induced autophagy and cell death in neoplastic TECs. The results suggest a role of cFLIP in the involution of normal thymus and the development of thymomas and TSCC. Since increased expression of cFLIP is a known tumor escape mechanism, it may serve as tissue-based biomarker in future clinical trials, including immune checkpoint inhibitor trials in the commonly PD-L1high thymomas and TCs.

Albumin-glutaraldehyde glue for repair of superficial lung defect: an in vitro experiment.

BACKGROUND: Albumin-glutaraldehyde glue gained a widespread acceptance in repair of superficial lung defects associated with alveolar air leaks (AAL). As its sealing efficacy has not yet been thoroughly corroborated by clinical studies, we sought to assess the properties of commercially available albumin-glutaraldehyde glue (BioGlue™) in an in vitro lung model. METHODS: The lower lobe of freshly excised swine lung (n = 10) was intubated and ventilated. A focal superficial parenchymal defect (40 × 25 mm) was created on the inflated lung. AAL was assessed with increasing inspired tidal volume (TVi). After glue application, AAL was assessed until burst failure occurred. To evaluate glue elasticity, the length of defect was recorded in the inflated lung. RESULTS: Superficial parenchymal defects resulted in AAL increasing with ascending TVi. Multiple linear regression analysis revealed strong correlation between AAL and maximal inspiratory pressure. There was one application error. At TVi = 400, 500, 600, 700, 800 and 900 ml, BioGlue™ achieved complete sealing in nine, six, five, four two and one specimens, respectively. Mean burst pressure was 38.0 ± 4.2 cmH2O. All sealant failures were cohesive. BioGlue™ allowed an expansion of covered lung defects of 1.5 ± 1.7 mm. CONCLUSIONS: Our in vitro tests demonstrated a high sealing efficacy of BioGlue™ for repair of superficial lung defects. Due to the rigid nature, caution should be taken to use this kind of sealant in trapped lungs.

Tobacco company efforts to influence the Food and Drug Administration-commissioned Institute of Medicine report clearing the smoke: an analysis of documents released through litigation.

BACKGROUND: Spurred by the creation of potential modified risk tobacco products, the US Food and Drug Administration (FDA) commissioned the Institute of Medicine (IOM) to assess the science base for tobacco "harm reduction," leading to the 2001 IOM report Clearing the Smoke. The objective of this study was to determine how the tobacco industry organized to try to influence the IOM committee that prepared the report. METHODS AND FINDINGS: We analyzed previously secret tobacco industry documents in the University of California, San Francisco Legacy Tobacco Documents Library, and IOM public access files. (A limitation of this method includes the fact that the tobacco companies have withheld some possibly relevant documents.) Tobacco companies considered the IOM report to have high-stakes regulatory implications. They developed and implemented strategies with consulting and legal firms to access the IOM proceedings. When the IOM study staff invited the companies to provide information on exposure and disease markers, clinical trial design for safety and efficacy, and implications for initiation and cessation, tobacco company lawyers, consultants, and in-house regulatory staff shaped presentations from company scientists. Although the available evidence does not permit drawing cause-and-effect conclusions, and the IOM may have come to the same conclusions without the influence of the tobacco industry, the companies were pleased with the final report, particularly the recommendations for a tiered claims system (with separate tiers for exposure and risk, which they believed would ease the process of qualifying for a claim) and license to sell products comparable to existing conventional cigarettes ("substantial equivalence") without prior regulatory approval. Some principles from the IOM report, including elements of the substantial equivalence recommendation, appear in the 2009 Family Smoking Prevention and Tobacco Control Act. CONCLUSIONS: Tobacco companies strategically interacted with the IOM to win several favored scientific and regulatory recommendations.

The development of scientific consultants: how the tobacco industry creates controversy on the carcinogenicity of tobacco-specific nitrosamines.

BACKGROUND: Tobacco-specific nitrosamines (TSNAs) are a group of carcinogens, which originate from nicotine and other tobacco alkaloids during fermentation and burning of tobacco. Between 1990 and 2010, the tobacco industry-funded extensive academic research on TSNAs in Germany. The objective was to gain better knowledge of how industry aims and strategies correlate with contents of publications by German toxicologists accepting tobacco industry funding by focusing on one prominent such toxicologist. METHODS AND FINDINGS: The authors analysed previously secret tobacco industry documents that were disclosed following a series of litigation cases in the USA and compared them with peer-reviewed published results of tobacco industry-funded toxicologists. The tobacco industry, in particular Philip Morris, developed sophisticated strategies to downplay TSNA's carcinogenic potential. Over 2 decades, German toxicologist Elmar Richter, faculty member of the renowned Ludwig-Maximilians-University, Munich, received substantial financial support from the tobacco industry. Numerous publications show that his research findings supported the aims of the tobacco industry. In his commissioned work, he suggested that TSNA burden can be explained by misclassification of smokers or assay background levels caused by TSNA-like molecules from food. Other publications cast doubt on the relevance of animal testing for TSNAs to humans claiming a detoxifying effect of nicotine on the metabolism of TSNAs or suggesting that adducts of TSNAs are unsuitable as biomarkers of exposure to tobacco smoke. CONCLUSIONS: Economic interests of the tobacco industry have strongly influenced the research activity of Richter and his group. The publications of his working group about carcinogenic effects of TSNAs published between 1992 and 2009 should therefore not be regarded as independent. Scientists and policy makers should consider the long-standing and intensive inter-relation between certain toxicologists and the tobacco industry when assessing the research results and consider ignoring them.

Surgery on unfavourable persistent N2/N3 non-small-cell lung cancer after trimodal therapy: do the results justify the risk?

OBJECTIVES: Persistent mediastinal lymph node metastasis after neoadjuvant therapy is a significant negative indicator for survival. Even though there is still no consensus on the matter, some authors advocate a thorough restaging prior to surgery and deny surgery in cases of persistent N2 because of the poor outcome. We analysed our results after trimodal therapy in pN2/N3 stage III non-small-cell lung cancer (NSCLC) and persistent mediastinal lymph node metastasis after neoadjuvant chemoradiotherapy. METHODS: We conducted a retrospective cohort analysis of 167 patients who received trimodal therapy for stage III NSCLC. Progression-free interval and survival were calculated. T-stage, N-stage, ypT-stage, ypN2/3-stage and surgical procedure were tested as risk factors. RESULTS: Eighty-three patients with potentially resectable initial pN2/3 underwent 44 pneumonectomies and 76% extended resections. Thirty-five patients showed persistent mediastinal lymph node metastasis after trimodal therapy. Treatment-related comorbidity after an operative therapy was 58%. Hospital mortality was 2.4%. The ypT- and ypN2/N3 stages were significant risk factors and, in the case of persistent mediastinal lymph node metastasis, median progression-free period was 17 months and median survival time was 21 months. CONCLUSIONS: Persistent but resectable N2/N3 after chemoradiotherapy in stage III NSCLC is the least favourable subgroup of patients in neoadjuvant approaches. If surgery can be carried out with curative intent and low morbidity, completing trimodal therapy is justified, with an acceptable outcome.

The toxic effects of cigarette additives. Philip Morris' project mix reconsidered: an analysis of documents released through litigation.

BACKGROUND: In 2009, the promulgation of US Food and Drug Administration (FDA) tobacco regulation focused attention on cigarette flavor additives. The tobacco industry had prepared for this eventuality by initiating a research program focusing on additive toxicity. The objective of this study was to analyze Philip Morris' Project MIX as a case study of tobacco industry scientific research being positioned strategically to prevent anticipated tobacco control regulations. METHODS AND FINDINGS: We analyzed previously secret tobacco industry documents to identify internal strategies for research on cigarette additives and reanalyzed tobacco industry peer-reviewed published results of this research. We focused on the key group of studies conducted by Phillip Morris in a coordinated effort known as "Project MIX." Documents showed that Project MIX subsumed the study of various combinations of 333 cigarette additives. In addition to multiple internal reports, this work also led to four peer-reviewed publications (published in 2001). These papers concluded that there was no evidence of substantial toxicity attributable to the cigarette additives studied. Internal documents revealed post hoc changes in analytical protocols after initial statistical findings indicated an additive-associated increase in cigarette toxicity as well as increased total particulate matter (TPM) concentrations in additive-modified cigarette smoke. By expressing the data adjusted by TPM concentration, the published papers obscured this underlying toxicity and particulate increase. The animal toxicology results were based on a small number of rats in each experiment, raising the possibility that the failure to detect statistically significant changes in the end points was due to underpowering the experiments rather than lack of a real effect. CONCLUSION: The case study of Project MIX shows tobacco industry scientific research on the use of cigarette additives cannot be taken at face value. The results demonstrate that toxins in cigarette smoke increase substantially when additives are put in cigarettes, including the level of TPM. In particular, regulatory authorities, including the FDA and similar agencies elsewhere, could use the Project MIX data to eliminate the use of these 333 additives (including menthol) from cigarettes.

Phase II trial of a trimodality regimen for stage III non-small-cell lung cancer using chemotherapy as induction treatment with concurrent hyperfractionated chemoradiation with carboplatin and paclitaxel followed by subsequent resection: a single-center study.

PURPOSE We started a phase II trial of induction chemotherapy and concurrent hyperfractionated chemoradiotherapy followed by either surgery or boost chemoradiotherapy in patients with advanced, stage III disease. The purpose is to achieve better survival in the surgery group with minimum morbidity and mortality. PATIENTS AND METHODS Patients treated from 1998 to 2002 with neoadjuvant chemoradiotherapy and surgical resection for stage III NSCLC were analyzed. The treatment consisted of four cycles of induction chemotherapy with carboplatin/paclitaxel followed by chemoradiotherapy with a reduced dose of carboplatin/paclitaxel and accelerated hyperfractionated radiotherapy with 1.5 Gy twice daily up to 45 Gy. After restaging, operable patients underwent thoracotomy. Inoperable patients received chemoradiotherapy up to 63 Gy. Study end points included resectability, pathologic response, and survival. Results One hundred twenty patients were enrolled; 25% patients had stage IIIA, 73% had stage IIIB, and 2% stage IV. After treatment, 47.5% had downstaging, 29.2% had stable disease, and 23.3% had progressive disease. Thirty patients (25%) were not eligible for operation because of progressive disease, stable disease, and/or functional deterioration with one treatment-related death. The 30-day mortality was 5% in patients who underwent operation. The 5-year survival rate for 120 patients was 21.7%, and it was 43.1% in patients with complete resection. In postoperative patients with stage N0 disease, 5-year survival was 53.3%; if stage N2 or N3 disease was still present, 5-year survival was 33.3%. CONCLUSION Staging and treatment with chemoradiotherapy and complete resection performed in experienced centers achieve acceptable morbidity and mortality.

Impact of neo-adjuvant radiochemotherapy on bronchial tissue viability.

OBJECTIVE: In the treatment of advanced stages of lung cancer, increasingly more multimodality approaches applying radiotherapy and/or chemotherapy in a neo-adjuvant setting are being introduced. The impact of induction therapy, especially radiotherapy, on bronchial tissue viability has not been investigated so far. METHODS: In 2008, we determined the tissue viability of bronchial segments obtained during surgery in 45 consecutive patients, including patients after neo-adjuvant radiochemotherapy (RCTX). Bronchial tissue viability was analysed by histology, life-dead assay and cell proliferation in tissue-specific culture media. Biomedical findings were compared with the clinical course of the patients. RESULTS: Tissue samples of 44 patients were included into this study. Fourteen patients (32%) had undergone neo-adjuvant RCTX. Histology and life-dead assay of the bronchial segments did not show significant differences. While patient age, sex, tumour entity and site of resection had no influence on cell proliferation in vitro, previous RCTX resulted in a 46% decrease of bronchial tissue viability (P=0.01). However, this effect was not reflected by the clinical course of the operated patients. CONCLUSIONS: Neo-adjuvant RCTX reduces bronchial tissue viability substantially. However, this impairment does not necessarily translate into an increased rate of postoperative bronchial insufficiencies. Standard histological work-up is not sensitive enough to characterise changes in bronchial tissue viability following RCTX.

Trimodal therapy for histologically proven N2/3 non-small cell lung cancer: mid-term results and indicators for survival.

BACKGROUND: Surgery alone for stage III non-small cell lung cancer provides a 5-year survival of 20% and competes with multimodal treatments. In 1999, a trimodal protocol was implemented at the Schillerhöhe Clinic. The aim of this study was to verify the feasibility and outcome of this trimodal protocol including survival, risk factors for survival, and comorbidity in a single institution. METHODS: Included were all patients with potentially resectable, previously untreated stage III non-small cell lung cancer operated on between February 1999 and May 2006 in the General Thoracic Surgery Unit of the Schillerhöhe Clinic following the same neoadjuvant protocol. Treatment-related morbidity, recurrence, survival after R0 resection, and risk factors for survival (pN0 after trimodal therapy, downstaging of International Union Against Cancer stage, T downstaging, N downstaging, regression rate, and histologic type of tumor) were analyzed. RESULTS: From 107 patients with stage III non-small cell lung cancer, 55 patients with mediastinoscopy-positive N2 or N3 were eligible for this study. Forty patients (72%) had the effect of International Union Against Cancer downstaging. Treatment-related comorbidity was 54% with hospital and 120-day mortality of 3.6% and 5.4%, respectively. Overall mean survival (Kaplan-Meier) was 43 months (95% confidence interval, 35 to 52) with an estimated 5-year survival rate of 49%. In multivariate testing, International Union Against Cancer downstaging after trimodal therapy achieved a level of significance (p = 0.031), and patients with UICC-downstaging after trimodal therapy had a mean survival of 53 months (95% confidence interval, 44 to 63) with an estimated 5-year survival rate of 60%. CONCLUSIONS: Neoadjuvant trimodal treatment for histologically proven N2 or N3 stage III non-small cell lung cancer is promising and can, like no other approach at present time, considerably improve 5-year survival rates up to 63% in selected patients.

Full-thickness resection with myocutaneous flap reconstruction for locally recurrent breast cancer.

BACKGROUND: Despite available recommendations, therapeutic procedures of locally recurrent breast cancer are very different. This retrospective study presents the possibilities and results of complete, full-thickness chest wall resection. METHODS: Between 1985 and 2006, 63 women (mean age, 58 years) with local recurrence of breast cancer invading the chest wall underwent chest wall resection with myocutaneous flap coverage and are included in this study. Adequate lung, cardiovascular, renal, and hepatic functions were additional eligibility requirements for inclusion. Preoperative known extrapulmonary metastases, pleural dissemination, and Eastern Cooperative Oncology Group (ECOG) status 3 or 4 were exclusion criteria. Survival rates were calculated by the Kaplan-Meier method. Univariable and multivariable Cox regression analysis was used for relative risk factors. RESULTS: The median interval between operation for the primary tumor and of the local recurrence was 89 months, with median follow-up at 28 months. In the total collective, cumulative 5-, 10- and 15-year survival rates were 46%, 29%, and 22%, respectively, with a median survival of 56 months. R0 resection was associated with a 5-year survival of 50.4%. Prognostic factors were patient age at the time of the primary operation and tumor invasion of bony structures. Mortality was 1.6% and morbidity was 25%. CONCLUSIONS: Full-thickness chest wall resection of locally recurrent breast cancer performed by a team of thoracic and plastic surgeons provides the best survival rates, with low mortality and morbidity. An earlier application of this method may lead to further improvement of these results.

Morbidity and mortality after pneumonectomy in smokers with NSCLC.

OBJECTIVE: Perioperative morbidity and mortality in patients receiving pneumonectomy because of non-small cell lung cancer (NSCLC) remains quite high. The aim of this study is to identify risk factors to minimize perioperative mortality and morbidity. PATIENTS AND METHOD: The results of 156 Patients who received pneumonectomy between 1995 and 2004 were reviewed retrospectively. All patients had stage I or II NSCLC. In 81 cases a right sided and in 75 a left sided pneumonectomy was performed. Cardiopulmonary function tests were sufficient for pneumonectomy. RESULTS: Overall perioperative 30-day mortality was 7.1% (n=11), in hospital mortality 8.3% (n=13). The cause was sepsis in 6 cases, cardiac failure in 4 cases, and respiratory insufficiency in 3 cases. In univariable and multivariable regression analysis considering mortality, none of the prognostic factors reached significance. The odds ratio for postoperative death was 1.6 fold for smokers in comparison to non smokers. Complications after pneumonectomy were seen in 34.6%, with arrhythmia in 16.0%, sepsis in 1.9% and bronchopleural fistula (BPF) occurring in 6.4%. Smoking and intraoperative blood loss >500 ml were highly significant perioperative risk factors. CONCLUSION: Smoking until operation and intraoperative blood loss were independent postoperative risk factors leading to complications after pneumonectomy for NSCLC. The risk for complications was 2.8-fold higher for smokers.

Who gains most? A 10-year experience with 611 thoracoscopic talc pleurodeses.

BACKGROUND: Thoracoscopic talc pleurodesis is a therapeutic option for recurrent pleural effusion. METHODS: This retrospective study included 611 patients who underwent thoracoscopic talc pleurodesis between 1994 and 2003. We analyzed the risk factors, efficiency, outcome, follow-up, and survival, while taking into consideration primary disease and general condition. RESULTS: The mean follow-up was 319 days (range, 31 to 1994). A total of 105 (17.2%) of 611 patients died within 30 days after treatment. Risk factors for death within 30 days included a Karnofsky index of less than 50%, a body mass index of less than 25 kg/m2, malignant disease, and male gender. Treatment was successful in 347 (68.6%) of 506 patients, and 451 (89.1%) reported an improvement in symptoms. Previous thoracic irradiation and a chest tube drainage time exceeding 10 days negatively influenced the outcome of pleurodesis. The survival rate was negatively influenced by a preoperative Karnofsky index of less than 60% and by malignant disease. CONCLUSIONS: Patients with pleural effusion due to malignant disease gain from early pleurodesis. The most favorable outcome after talc pleurodesis was seen in women whose lungs were fully expandable, in patients whose Karnofsky index exceeded 60%, in patients whose body mass index was greater than 25 kg/m2, and in patients with benign disease.

Carcinoid lung tumors: long-term results from 111 resections.

OBJECTIVE: Carcinoids are rare neuroendocrine tumors of the bronchial system. Only recently, the histological classification was standardized, and there are varying opinions about the extent of surgical resection. This research reports on the long-term results of 111 consecutive patients, who underwent surgery in a department for thoracic surgery. METHODS: Between 1/1988 and 2/2001, 111 consecutive pulmonary resections were conducted in patients with bronchial carcinoids. Retrospectively, researchers obtained clinical and surgical data and re-classified all histological specimen according to the WHO classification of 1999. Information regarding long-term results was obtained by using data obtained during follow-up visits and by talking to the patient on the phone. RESULTS: 97 patients with typical and 14 with atypical carcinoids were identified. The preoperative diagnosis of typical or atypical carcinoid had been correct in 56 patients (50.5%). Surgical procedures included 79 lobectomies, 16 bilobectomies, 8 pneumonectomies, 5 segmental resections, 2 sleeve resections of the main bronchus without parenchymal resection and one exploratory thoracotomy. Mediastinal lymphadenectomies were performed on 105 patients (94.6%). Postoperative staging revealed 91 patients (81.2%) in UICC stage I, 12 (10.8%) in stage II, 7 in stage III and one in stage IV. 97 (87.4%) typical and 14 (12.6%) atypical carcinoids were classified. 30-day mortality was 1.8% (n=2). Mean follow-up was 73.4 months. The total cohort showed a 5-year survival rate of 94% and a 10-year survival rate of 82%. In patients with typical and atypical carcinoids, the 5-year survival rates were 94% and 82%, respectively (n.s.), and the 10-year survival rates were 92% and 62%, respectively (p<0.01). The 5- (10-) year survival rate without lymph node involvement was 96% (85%), with N1 involvement 88% (65%), with N2 involvement 67% (no 10-year survival). CONCLUSIONS: Patients with bronchial carcinoids who underwent a radical oncological resection with mediastinal lymphadenectomy have very good survival chances. There are no prospective randomized studies evaluating the surgical procedures as they relate to the classification. Since a preoperative diagnosis cannot clearly determine if the lymph nodes are involved and what histology type the physician dealing with, a limited resections without lymphadenectomy is insufficient. It is absolutely necessary to conduct retrospective and multi-center studies on the prognostic importance of lymph node involvement and on the impact of adjuvant therapies.

Full-thickness chest wall resection for locally recurrent breast cancer.

AIM: In spite of available recommendations, therapeutic procedures of locally recurrent breast cancer are very different. In a retrospective study, the possibilities and results of complete, full-thickness chest wall resection are presented. METHODS: Between 1985 and 2004, 51 women underwent complete, full-thickness chest wall resection with primary coverage. Primary surgical therapy of breast cancer had been mastectomy in 88%. Median age of patients undergoing surgery for a local recurrence was 57 (29 - 81) years. The median interval between surgery of the primary tumour and of the local recurrence was 70.3 (10.7 - 327.2) months; median follow-up was 29.4 (1.8 - 230.9) months. 40 (78.4%) patients required rib resections, 15 (29.4%) of them in combination with partial sternal resection. In 4 (7.8%) patients complete and in 7 (13.7%) patients partial sternal resection without additional rib resection were performed.Coverage was mainly realized using latissimus dorsi myocutaneous flaps (n=44; 86.3%). Survival rates were calculated by means of the Kaplan-Meier method, the relative risk using univariate and multivariate Cox-regression analysis. RESULTS: In the total collective, cumulative 5-, 10- and 15-year survival (YS) rates were 39%, 31% and 23%, respectively, median survival 46.4 months. R0 resection was associated with a 5-YS of 42%. Prognostic factors were age at the time of primary surgery, disease-free interval and tumour invasion of bony structures. Mortality was 2%, morbidity 35%. CONCLUSION: Full-thickness chest wall resection of locally recurrent breast cancer is possible in almost any patient when performed by a team of thoracic and plastic surgeons. Only radical resection provides good long-term results with low mortality and morbidity.

Prognosis in N2 NSCLC.

The prognosis of bronchogenic carcinoma in stage III N2 is poor. Five-year survival ranges between 0 and 5%. Lymph-node involvement itself still is the main prognostic factor. Complete lymphadenectomy improves long-term survival in contrast to lymph-node sampling. Recent studies have indicated that the number of involved lymph nodes could be another prognostic factor. It has also been proved that complete lymphadenectomy is necessary for correct staging. This also applies to preoperative staging prior to neoadjuvant treatment. For this reason exact knowledge of lymph-node anatomy and drainage is required. To achieve assessment and comparison of mediastinal staging and of lymphadenectomy, the number of pathologically examined lymph nodes should be documented. Other prognostic factors within N2 stages are age and T stage. Molecular markers are subject to major investigation. A definite clinical relevance, however, could so far not be verified for any of them.