New experimental model of hind limb ischemia in pot-bellied pigs.

BACKGROUND: The simulation of limb ischemia in large laboratory animals is a complex and currently topical task in experimental medicine. Meanwhile, there is a demand for a reliable and effective model of limb ischemia for further testing of medicines to stimulate circulation and induce angiogenesis, gene medicines in particular. Aim of this study was to develop and experimentally test an effective method of simulation of hind limb ischemia. METHODS: Female Vietnamese pot-bellied pigs were chosen as biological models. The reproduction of the pathology was evaluated using the following methods: laser doppler flowmetry, laboratory test of venous blood, immunohistochemical reaction with antibodies against CD31, a specific marker of endothelial cells, Van Gieson's staining of muscles for presence of connective tissue and clinical observation to detect the presence of lameness in pigs. RESULTS: Laser doppler flowmetry recorded a significant decrease in the intensity of the blood circulation and a marked decrease in temperate in the operated limb. Increased lactate and creatine kinase were registered immediately after the surgery and were absent 3 or more days later. Clinical observation demonstrated presence of walking lameness. Histological and immunohistochemical methods revealed a credible increase in connective tissue area and a reduction in the number of blood vessels in the muscles, confirming the presence of ischemia. CONCLUSIONS: An effective approach to modeling limb ischemia has been developed and experimentally tested. The proposed model may be used in cardiovascular surgery and will allow further testing of new medications designed to treat ischemia of hind limbs.

Redefining the role of surgery in early small-cell lung cancer.

PURPOSE: Resection is guideline recommended in stage I small-cell lung cancer (SCLC) but not in stage II. In this stage, patients are treated with a non-surgical approach. The aim of this meta-analysis was to assess the role of surgery in both SCLC stages. Surgically treated patients were compared to non-surgical controls. Five-year survival rates were analysed. METHODS: A systematic literature search was performed on December 01, 2021 in Medline, Embase and Cochrane Library. Studies published since 2004 on the effect of surgery in SCLC were considered and assessed using ROBINS-I. We preformed I2-tests, Q-statistics, DerSimonian-Laird tests and Egger-regression. The meta-analysis was conducted according to PRISMA. RESULTS: Out of 6826 records, we identified seven original studies with a total of 15,170 patients that met our inclusion criteria. We found heterogeneity between these studies and ruled out any publication bias. Patient characteristics did not significantly differ between the two groups (p-value > 0.05). The 5-year survival rates in stage I were 47.4 ± 11.6% for the 'surgery group' and 21.7 ± 11.3% for the 'non-surgery group' (p-value = 0.0006). Our analysis of stage II SCLC revealed a significant survival benefit after surgery (40.2 ± 21.6% versus 21.2 ± 17.3%; p-value = 0.0474). CONCLUSION: Based on our data, the role of surgery in stage I and II SCLC is robust, since it improves the long-term survival in both stages significantly. Hence, feasibility of surgery as a priority treatment should always be evaluated not only in stage I SCLC but also in stage II, for which guideline recommendations might have to be reassessed.

Stage I and II Small-Cell Lung Cancer-New Challenge for Surgery.

PURPOSE: The recommended treatment for small-cell lung cancer (SCLC) currently is surgery in stage I disease. We wondered about stage II SCLC and present a meta-analysis on mean-survival of patients that underwent surgery for stage I and II compared to controls. METHODS: A systematic literature search was performed on December 01st 2021 in Medline, Embase and Cochrane Library. We considered studies published on the effect of surgery in SCLC since 2004 and assessed them using ROBINS-I. We preformed I2-tests, Q-statistics, DerSimonian-Laird tests and Egger-regression. The meta-analysis was conducted according to PRISMA. RESULTS: Out of 6826 records, seven studies with a total of 11,241 patients ('surgery group': 3911 patients; 'non-surgery group': 7330; treatment period: 1984-2015) were included. Heterogeneity between the studies was revealed in absence of any publication bias. Patient characteristics did not differ between the groups (p-value > 0.05). The mean-survival in an analysis of patients in stage I was 36.7 ± 10.8 months for the 'surgery group' and 20.3 ± 5.7 months for the 'non-surgery group' (p-value = 0.0084). A combined analysis of patients in stage I and II revealed a mean-survival of 32.0 ± 16.7 months for the 'surgery group' and 19.1 ± 6.1 months for the 'non-surgery group' (p-value = 0.0391). In a separate analysis of stage II, we were able to demonstrate a significant survival benefit after surgery (21.4 ± 3.6 versus 16.2 ± 3.9 months; p-value = 0.0493). CONCLUSION: Our meta-analysis shows a significant survival benefit after surgery not only in the recommended stage I but also in stage II SCLC. Our data suggests that both stages should be considered for surgery of early SCLC.

Closing the RCT Gap-A Large Meta-Analysis on the Role of Surgery in Stage I-III Small Cell Lung Cancer Patients.

INTRODUCTION: Despite clear guideline recommendations, surgery is not consistently carried out as part of multimodal therapy in stage I small cell lung cancer (SCLC) patients. The role of surgery in stages II and III is even more controversial. In the absence of current randomized control trials (RCT), we performed a meta-analysis comparing surgery versus non-surgical treatment in stage I to III SCLC patients. METHODS: A systematic review of the literature was conducted on 1 July 2023, focusing on studies pertaining to the impact of surgery on small cell lung cancer (SCLC). These studies were evaluated using the ROBINS-I tool. Statistical analyses, including I² tests, Q-statistics, DerSimonian-Laird tests, and Egger regression, were performed to assess the data. In addition, 5-year survival rates were analyzed. The meta-analysis was conducted according to PRISMA standards. RESULTS: Among the 6826 records identified, 10 original studies encompassing a collective cohort of 95,323 patients were incorporated into this meta-analysis. Heterogeneity was observed across the included studies, with no discernible indication of publication bias. Analysis of patient characteristics revealed no significant differences between the two groups (p-value > 0.05). The 5-year survival rates in a combined analysis of patients in stages I-III were 39.6 ± 15.3% for the 'surgery group' and 16.7 ± 12.7% for the 'non-surgery group' (p-value < 0.0001). SCLC patients in stages II and III treated outside the guideline with surgery had a significantly better 5-year survival compared to non-surgery controls (36.3 ± 20.2% vs. 20.2 ± 17.0%; p-value = 0.043). CONCLUSIONS: In the absence of current RCTs, this meta-analysis provides robust suggestions that surgery might significantly improve survival in all SCLC stages. Non-surgical therapy could lead to a shortening of life. The feasibility of surgery in non-metastatic SCLC should always be evaluated as part of a multimodal treatment.

Postoperative Tobacco Cessation Improves Quality of Life, Lung Function and Long-Term Survival in Non-Small-Cell Lung Cancer Patients.

OBJECTIVES: About 90% of all non-small cell lung cancer (NSCLC) cases are associated with inhalative tabacco smoking. Half of patients continue smoking during lung cancer therapy. We examined the effects of postoperative smoking cessation on lung function, quality of life (QOL) and long-term survival. MATERIALS AND METHODS: In total, 641 patients, who underwent lobectomy between 2012 and 2019, were identified from our single institutional data base. Postoperatively, patients that actively smoked at the time of operation were offered a structured 'smoking cessation' program. For this retrospective analysis, two patient groups (total n = 90) were selected by pair matching. Group A (n = 60) had no postoperative tobacco smoking. Group B (n = 30) involved postoperative continued smoking. Lung function (FEV1, DLCO) and QOL ('SF-36' questionnaire) were measured 12 months postoperatively. We compared long-term outcomes using Kaplan-Meier curves. RESULTS: The mean age in group A was 62.6 ± 12.5 years and that in group B was 64.3 ± 9.7 years (p = 0.82); 64% and 62%, respectively, were male (p = 0.46). Preoperative smoking habits were similar ('pack years': group A, 47 ± 31; group B, 49 ± 27; p = 0.87). All relevant baseline characteristics we collected were similar (p > 0.05). One year after lobectomy, FEV1 was reduced by 15% in both groups (p = 0.98). Smoking cessation was significantly associated with improved DLCO (group A: 11 ± 16%; group B: -5 ± 14%; p <0.001) and QOL (vitality (VT): +10 vs. -10, p = 0.017; physical role function (RP): +8 vs. -17, p = 0.012; general health perceptions (GH): +12 vs. -5, p = 0.024). Patients who stopped smoking postoperatively had a significantly superior overall survival (median survival: 89.8 ± 6.8 [95% CI: 76.6-103.1] months vs. 73.9 ± 3.6 [95% CI: 66.9-80.9] months, p = 0.034; 3-year OS rate: 96.2% vs. 81.0%, p = 0.02; 5-year OS rate: 80.0% vs. 64.0%, p = 0.016). The hazard ratio (HR) was 2.31 [95% CI: 1.04-5.13] for postoperative smoking versus tobacco cessation. CONCLUSION: Postoperative smoking cessation is associated with improved quality of life and lung function testing. Notably, a significant increase in long-term survival rates among non-smoking NSCLC patients was observed. These findings could serve as motivation for patients to successfully complete a non-smoking program.

A comparative study of four thoracic mortality scores.

BACKGROUND: The percentage of patients in resectable stages at initial diagnosis of non-small cell lung cancer (NSCLC) raises due to better screening programs. Therefore, risk prediction models are becoming more critical. Here, we validated and compared four established scoring models, the Thoracoscore, Epithor, Eurloung 2, and the simplified Eurolung 2 (2b), in their ability to predict 30-day mortality. METHODS: All consecutive patients undergoing anatomical pulmonary resection were included. The performance of the four scoring systems was assessed with Hosmer-Lemeshow goodness-of-fit test (calibration) and receiver operating characteristic (ROC) curves (discrimination). We compared the area under the curve (AUC) of the ROC curves by DeLong's method. RESULTS: A total of 624 patients underwent surgery for NSCLC at our institution between 2012 and 2018 30-day mortality was 2.2% (14 patients). The AUC for Eurolung 2 and the simplified Eurolung 2 (0.82) were greater than those of the other scoring systems, Epithor (0.71) and Thoracoscore (0.65). In addition, the DeLong analysis showed a significant superiority of Eurolung 2 and Eurolung 2b over the Thoracoscore (p = 0.04); there were no significant differences compared to Epithor. CONCLUSION: Eurolung 2 and the simplified Eurolung 2 were the favorable scoring systems for predicting 30-day mortality compared to Thoracoscore and Epithor. Therefore, we recommend using Eurolung 2 or the simplified Eurolung 2 for preoperative risk stratification.

Prognostic impact of lymph node spreading pattern in N2 NSCLC patients.

BACKGROUND: One-third of non-small cell lung cancer (NSCLC) patients are diagnosed with locally advanced disease. Long-term survival in stage IIIA/B-N2 remains poor; this may also be due to lymph node spreading pattern. Therefore, we compared the overall survival of stage IIIA/B-N2 patients with superior mediastinal lymph nodes (SML) with infracarinal- or inferior mediastinal lymph nodes (IML) and with multilevel disease (MLD). RESEARCH DESIGN AND METHODS: One-, three-and five-year survival rates were measured. Kaplan-Meier curves and Cox proportional hazards model assessed survival and were used to identify prognostic factors. RESULTS: We reviewed data of stage IIIA/B-N2 patients (n = 129) who underwent surgery for NSCLC between 2012 and 2020. Patients with SML (n = 62) were compared to ILM (n = 37) and MLD (n = 30). SML patients showed significantly better one- (SML: 95.2% vs. IML: 78.6% vs. MLD: 69.4%, p = 0.03), three- (78.8% vs. 27.7 vs. 13.3%; p = <0.001) and five-year (61.1% vs. 17.1 vs. 3%; p < 0.001) survival rates, than IML and MLD patients. Kaplan-Meier curves showed prolonged overall survival for SML patients (log-rank SML, ILM, MLD p < 0.0001). CONCLUSIONS: This study showed significantly better long-term survival of SML patients than IML and MLD patients. The long-term survival of ILM and MLD patients was equally poor.

Do skip-N2 metastases significantly impact overall survival and disease-free interval in N2 non-small-cell lung cancer patients? A multicentre analysis.

OBJECTIVES: Skip-N2 metastasis (N0N2), thus N2 metastasis in the absence of N1 metastasis, occurs in ∼20-30% of non-small-cell lung cancer patients. N0N2 patients have a better prognosis than continuous-N2 metastasis (N1N2) patients following surgery. However, this effect remains controversial. Therefore, we conducted a multicentre study to compare the long-term survival and disease-free interval (DFI) of N1N2- and N0N2 patients. METHODS: One- and 3-year survival rates were measured. Kaplan-Meier curves and a Cox proportional hazards model assessed survival and were used to identify prognostic factors for overall survival. In addition, we performed propensity score matching (PSM) to rule out confounding factors. All patients received adjuvant chemoradiation therapy according to European guidelines. RESULTS: Between January 2010 and December 2020, 218 stage IIIA/B N2 patients were included in our analysis. The Cox regression analysis revealed that N1N2 significantly influenced the overall survival rate. Before PSM, N1N2 patients showed significantly more metastatic lymph nodes (P < 0.001) and significantly larger tumours (P = 0.05). After PSM, baseline characteristics did not differ between groups. Before and after PSM, N0N2 patients showed significantly better 1- (P = 0.01; P = 0.009) and 3-year (P < 0.001) survival rates than N1N2 patients. Furthermore, N0N2 patients showed significantly longer DFI than N1N2 patients before and after PSM (P < 000.1). CONCLUSIONS: Prior and after PSM analysis, N0N2 patients were confirmed to have better survival and DFI than N1N2 patients. Our results demonstrate that stage IIIA/B N2 patients are heterogeneous and would benefit from a more precise subdivision and differential treatment.

Pulmonary metastasectomy for metastatic head and neck cancer prolongs survival significantly compared to non-surgical therapy.

OBJECTIVES: Pulmonary metastasectomy (PM) is an established procedure for selected patients with metastatic head and neck cancer (HNC). Non-surgical therapy in the form of chemo- and immunotherapy and checkpoint inhibitors and radiation therapy are also treatment options. There are no randomized controlled trials comparing PM with non-surgical therapy. Here, we retrospectively compare the long-term survival of patients, undergoing PM with patients receiving non-surgical therapy. METHODS: All HNC patients with pulmonary metastases were included, if the primary HNC was treated curatively and distant metastases, apart from the lungs were excluded. The pulmonary metastases were confirmed by biopsy as metastases of the HNC primary tumour in the non-surgical therapy group. To further clarify that PM prolonged survival, a propensity score-matched analysis was performed. RESULTS: Between January 2010 and December 2020, 62 HNC patients with isolated pulmonary metastases were included in our analysis. Thirty-three underwent PM and 29 received non-surgical therapy. Histology, tumour stage and localization of the primary HNC did not differ between groups. The number of metastases, age and ASA classification did also not differ between the groups. Patients undergoing PM showed significantly better 1- (n = 31; 93.5% vs n = 19; 65.5%; P = 0.006), 3- (n = 17; 72.2% vs n = 9; 30.4%; P = 0.004) and 5-year (n = 10; 53.4% vs n = 4; 20.0%; P = 0.001) survival rates, compared to patients receiving non-surgical therapy. CONCLUSIONS: Patients with pulmonary metastatic HNC undergoing PM had a significantly better overall survival compared to patients receiving non-surgical therapy. Therefore, selected patients should undergo PM to improve survival.

[The value of thymectomy in the treatment of non-thymomatous myasthenia gravis]. / Der Stellenwert der Thymektomie ohne Thymom in der Therapie der Myasthenia gravis.

The value of thymectomy in the treatment of non-thymomatous myasthenia gravis has been controversially discussed. The relatively low incidence and prevalence of this disease, the inconsistent documentation in various studies and the necessity of a long-term follow-up to assess the therapeutic effects has made the generation of valid data difficult. The publication in 2016 of the MGTX trial in the New England Journal of Medicine delivered the first randomized controlled data in which patients aged 18-65 years with generalized myasthenia gravis and positive for acetylcholine receptor antibodies showed a significant benefit after surgical resection of the thymus via median sternotomy. Despite a lack of validation of the advantages of thymectomy by minimally invasive surgery from randomized controlled studies, this technique seems to positively influence the outcome of certain patient groups in a similar way. Video-assisted thoracoscopic surgery (VATS) and robotic-assisted thoracic surgery (RATS) using subxyphoidal and transcervical access routes showed not only esthetic advantages but also showed no relevant inferiority in the influence on clinical outcomes of myasthenia gravis compared to median sternotomy; however, not only the benefits and the esthetic results show differences but also the advantages in the various subtypes of myasthenia gravis show divergent prospects of success with respect to remission. The clinical spectrum of myasthenia is heterogeneous with respect to the occurrence of antibodies, the body region affected and the age of the patient at first diagnosis. Ultimately, thymectomy is an effective causal treatment of myasthenia gravis.

Different pulmonary adenocarcinoma growth patterns significantly affect survival.

OBJECTIVE: Adenocarcinoma (AC) is the number one pathological entity of lung cancer with approximately 30-40% of cases. It is known to be heterogeneous and has 5 histopathological growth patterns. We evaluated the long-term survival rates of patients with predominant subtypes. METHODS: 290 patients with AC underwent pulmonary resection between 2012 and 2017 at our institution. We excluded all patients with lymph node involvement and distant metastases. Hence, 163 patients were included for further analysis. Predominant growth pattern was defined if more than 10% of cells showed a growth pattern. 1, 3, and 5-year survival rates were evaluated. Survival was assessed by Kaplan-Meier curves and the Cox proportional hazards model was used to identify prognostic factors for overall survival. RESULTS: Predominant growth patterns >10% were compared to <10% growth patterns of the same subtype. 1-year, 3-year, and 5-year overall survival rates of patients with predominant solid tumor growth >10% differed significantly from patients with <10% (88.4% vs. 97.6%, p = 0.04; 65.8% vs. 87.4% p = 0.001, 36.4% vs. 65.9% p = 0.01). Survival rates did not differ between >10% papillary and acinar growth compared to <10%. Kaplan-Meier curves showed reduced overall survival for patients with solid tumor growth >10% (log-rank 0.002). Solid tumor growth >10% was an independent prognostic factor for worse long-term survival (Hazard ratio: 3.05, p = 0.01). CONCLUSION: Our study demonstrates that the presence of a predominant solid pattern in pulmonary adenocarcinoma is a factor for an unfavorable prognosis. This should be kept in mind in daily clinical practice.

Sublobar resection without staging and lymphadenectomy for ≤2 cm Non-Small Cell Lung Cancer is no adequate therapy.

OBJECTIVE: Sublobar resection is frequently performed for Non-Small Cell Lung Cancer (NSCLC) patients with ≤2 cm nodules. Frequently, both proper staging and radical lymphadenectomy are omitted in these operations. Therefore, we decided to evaluate the number of lymph node metastases and the number of postoperative nodal upstaging in patients undergoing pulmonary resection due to NSCLC with tumors ≤2 cm at our institution. METHODS: Nodal upstaging, lymphangiosis- (L1), and hemangiosis carcinomatosa (V1) were analyzed. pN0 patients were compared to patients with postoperative nodal upstaging. One-, three, and five-year survival rates were measured. Survival was also assessed by the Kaplan-Meier method. RESULTS: 747 patients underwent surgery for NSCLC at our institution between 2012 and 2020. We retrospectively reviewed data of 236 NSCLC patients with ≤2 cm tumors. The mean tumor size was 1.4 cm ± 0.39 in our cohort. Of our patients, 14% showed a cT1a tumor, and 86% of patients cT1b. 24.0 ± 12.3 lymph nodes were dissected and analyzed per patient, and 0.7 ± 2.0 of those were affected. Of our patients, 16.1% showed L1 affection, and 7.6% a V1 affection. Lymph node involvement was diagnosed in 11(4.7%) patients preoperatively. 39(16.5%) patients were upstaged due to lymph node involvement postoperatively (p < 0.001). Upstaged patients showed significantly worse 3- (upstaged: 60.6% vs. pN0: 83.2%; p = 0.01) and 5-year (upstages: 38% vs. pN0 71.5%; p = 0.02) survival rates. CONCLUSION: 16.5% of patients with ≤2 cm NSCLC were nodal upstaged postoperatively. These results underline that lymphadenectomy and proper staging are crucial for NSCLC patients irrespective of the tumor size and the surgical approach.

Perigraft reaction and incorporation of porcine and bovine pericardial patches.

OBJECTIVES: Bovine and porcine pericardial patches are frequently used in cardiothoracic and vascular surgery. There are no guidelines recommending the usage of these patches for particular surgical approaches. However, these 2 materials supposedly possess different properties. The clinical advantage of porcine compared with bovine patches remains controversial. In this experimental study, we analysed the incorporation and vascularization of bovine and porcine pericardial patches during the initial phase after implantation. METHODS: Bovine and porcine pericardial patches were implanted into the dorsal skinfold chamber of C57BL/6 mice (n = 8 per group) to study vascularization and inflammation at the implantation site using repetitive intravital fluorescence microscopy over a 14-day period. At the end of the in vivo experiments, CD-31-positive cells were determined to evaluate the vascularization by immunohistochemistry. Furthermore, cell proliferation and apoptosis were analysed immunohistochemically. RESULTS: Implanted bovine patches exhibited an enhanced vascularization, as indicated by a significantly higher number of CD-31-positive cells and micro-vessels (23.2 ± 4.3 vs 16.5 ± 5.8 mm-2; P = 0.001). Furthermore, bovine patches showed a slightly but not significantly higher functional capillary density. Both patches induced a moderate leukocytic inflammatory host tissue response, and neither bovine nor porcine patches significantly affected apoptosis and cell proliferation at the implantation site. CONCLUSIONS: Bovine and porcine pericardial patches are similarly suitable for surgery. Bovine patches exhibited an improved vascularization during the first 14 days after implantation. This may result in a quicker and improved incorporation into the surrounding tissue compared with porcine pericardial patches.

Lymphangiosis carcinomatosa independently affects long-term survival of Non-Small Cell Lung Cancer patients.

OBJECTIVE: The significance of postoperatively diagnosed Lymphangiosis Carcinomatosa (L1) as an independent risk factor for long-term survival in Non-Small Cell Lung Cancer (NSCLC) remains controversial. We analyzed the effect of L1 on postoperative survival in stage I, II and III NSCLC-patients. METHODS: We investigated all consecutive patients with NSCLC between January 2012 and December 2019 who underwent an anatomical resection and radical lymphadenectomy at our institute. L1-were compared to L0-patients. All patients received adjuvant chemotherapy in accordance with European guidelines. 3- and 5- year survival rates and median-survival were assessed. To investigate whether L1 is an independent risk factor, we carried out a multivariate cox regression and a pair-match analysis looking at different properties such as TNM. RESULTS: A total of 641 patients (L0: 74%; L1: 26%) were analyzed. Baseline characteristics were comparable between groups. The mean age was 65.3 ± 10.2 years and 64.9 ± 9.4 years in the L0 and L1-groups respectively (p-value = 0.703). 58.5% of L0-patients were male (L1: 62.7%; p-value = 0.351). Overall survival in the L1-group was significantly shorter compared to the L0-group (L1: 42.3 ± 2.8; L0: 67.6 ± 2.1 months; p-value<0.0001). We confirmed this finding in a pair-matched analysis (L0: 73.9 ± 4.7 months; L1: 42.2 ± 4.2; p-value = 0.009). 3- and 5-year survival were significantly shorter for L1-patients (3-year: L0: 65.9%; L1: 35.9%; p-value<0.0001) (5-year: L0: 34.9%; L1: 7.5%; p-value<0.0001). CONCLUSION: L1 is an independent risk factor for long-term survival of patients with NSCLC. This cohort supports that the L0/L1 status should be included in pathological reports. We suggest to further include L0/L1-status in guideline recommendations for NSCLC patients.

Postoperative long-term survival of non-small cell lung cancer patients with skip-N2 metastases.

OBJECTIVE: Radical lymphadenectomy is crucial in operations for non-small cell lung cancer (NSCLC). Usually pN1 and pN2 lymph nodes are affected consecutively (N1N2). Nevertheless, pN2 metastases may also occur in the absence of pN1 as skip-N2 metastases (N0N2). Here we compare the long-term survival of N1N2- and N0N2 patients. MATERIALS AND METHODS: 464 patients underwent surgery for NSCLC at our institution between 2012 and 2017. We retrospectively reviewed data of pN2 stage patients (n = 68). Patients with N1N2 (n = 39) were compared to N0N2 (n = 29) patients. 1-, 3-and 5-year survival rates were measured. Survival was assessed by Kaplan-Meier curves and the cox proportional hazards model was used to identify prognostic factors for overall survival. All patients received adjuvant chemoradiation therapy according to European guidelines. RESULTS: The baseline characteristics did not differ between groups. We observed no differences in the histology, localization, or gender in our cohort. N0N2 patients showed significantly better 1- (N1N2: 82.4% vs. N0N2 100%; p = 0.001), 3- (14.7% vs. 63.6%; p=<0.001) and 5-year (9.4% vs. 43.8%; p = 0.001) survival rates. Tumor size (Hazard ratio (HR) 1.46, Confidence interval (CI 95%) 1.03-2.04; p = 0.03) and the occurrence of N1N2 (HR 4.26, CI 2.04-8.91; p < 0.0001) were independent prognostic factors for worse long-term survival. The Kaplan-Meier curves showed a reduced overall survival for N1N2 patients (log-rank N1N2, N0N2 p < 0.0001). CONCLUSION: N1N2 patients have a significantly worse prognosis compared to N0N2 patients. This will aid to classify the heterogeneous pN2-NSCLC patient population more precisely. Further, multimodal therapy should be considered for N1N2 patients.

Combination of European System for Cardiac Operative Risk Evaluation (EuroSCORE) and Cardiac Surgery Score (CASUS) to Improve Outcome Prediction in Cardiac Surgery.

BACKGROUND We hypothesized that the combination of a preoperative and a postoperative scoring system would improve the accuracy of mortality prediction and therefore combined the preoperative 'additive EuroSCORE' (European system for cardiac operative risk evaluation) with the postoperative 'additive CASUS' (Cardiac Surgery Score) to form the 'modified CASUS'. MATERIAL AND METHODS We included all consecutive adult patients after cardiac surgery during January 2007 and December 2010 in our prospective study. Our single-centre study was conducted in a German general referral university hospital. The original additive and the 'modified CASUS' were tested using calibration and discrimination statistics. We compared the area under the curve (AUC) of the receiver characteristic curves (ROC) by DeLong's method and calculated overall correct classification (OCC) values. RESULTS The mean age among the total of 5207 patients was 67.2 ± 10.9 years. Whilst the ICU mortality was 5.9% we observed a mean length of ICU stay of 4.6 ± 7.0 days. Both models demonstrated excellent discriminatory power (mean AUC of 'modified CASUS': ≥ 0.929; 'additive CASUS': ≥ 0.920), with no significant differences according to DeLong. Neither model showed a significant p-value (<0.05) in calibration. We detected the best OCC during the 2nd day (modified: 96.5%; original: 96.6%). CONCLUSIONS Our 'additive' and 'modified' CASUS are reasonable overall predictors. We could not detect any improvement in the accuracy of mortality prediction in cardiac surgery by combining a preoperative and a postoperative scoring system. A separate calculation of the two individual elements is therefore recommended.

Inclusion of 'ICU-Day' in a Logistic Scoring System Improves Mortality Prediction in Cardiac Surgery.

BACKGROUND Prolonged intensive care unit (ICU) stay is a predictor of mortality. The length of ICU stay has never been considered as a variable in an additive scoring system. How could this variable be integrated into a scoring system? Does this integration improve mortality prediction? MATERIAL AND METHODS The 'modified CArdiac SUrgery Score' (CASUS) was generated by implementing the length of stay as a new variable to the 'additive CASUS'. The 'logistic CASUS' already considers this variable. We defined outcome as ICU mortality and statistically compared the three CASUS models. Discrimination, comparison of receiver operating characteristic curves (DeLong's method), and calibration (observed/expected ratio) were analyzed on days 1-13. RESULTS Between 2007 and 2010, we included 5207 cardiac surgery patients in this prospective study. The mean age was 67.2 ± 10.9 years. The mean length of ICU stay was 4.6 ± 7.0 days and ICU mortality was 5.9%. All scores had good discrimination, with a mean area under the curve of 0.883 for the additive and modified, and 0.895 for the 'logistic CASUS'. DeLong analysis showed superiority in favor of the logistic model as from day 5. The calibration of the logistic model was good. We identified overestimation (days 1-5) and accurate (days 6-9) calibration for the additive and 'modified CASUS'. The 'modified CASUS' remained accurate but the 'additive CASUS' tended to underestimate the risk of mortality (days 10-13). CONCLUSIONS The integration of length of ICU stay as a variable improves mortality prediction significantly. An 'ICU-day' variable should be included into a logistic but not an additive model.

A comparative study of four intensive care outcome prediction models in cardiac surgery patients.

BACKGROUND: Outcome prediction scoring systems are increasingly used in intensive care medicine, but most were not developed for use in cardiac surgery patients. We compared the performance of four intensive care outcome prediction scoring systems (Acute Physiology and Chronic Health Evaluation II [APACHE II], Simplified Acute Physiology Score II [SAPS II], Sequential Organ Failure Assessment [SOFA], and Cardiac Surgery Score [CASUS]) in patients after open heart surgery. METHODS: We prospectively included all consecutive adult patients who underwent open heart surgery and were admitted to the intensive care unit (ICU) between January 1st 2007 and December 31st 2008. Scores were calculated daily from ICU admission until discharge. The outcome measure was ICU mortality. The performance of the four scores was assessed by calibration and discrimination statistics. Derived variables (Mean- and Max- scores) were also evaluated. RESULTS: During the study period, 2801 patients (29.6% female) were included. Mean age was 66.9 ± 10.7 years and the ICU mortality rate was 5.2%. Calibration tests for SOFA and CASUS were reliable throughout (p-value not < 0.05), but there were significant differences between predicted and observed outcome for SAPS II (days 1, 2, 3 and 5) and APACHE II (days 2 and 3). CASUS, and its mean- and maximum-derivatives, discriminated better between survivors and non-survivors than the other scores throughout the study (area under curve ≥ 0.90). In order of best discrimination, CASUS was followed by SOFA, then SAPS II, and finally APACHE II. SAPS II and APACHE II derivatives had discrimination results that were superior to those of the SOFA derivatives. CONCLUSIONS: CASUS and SOFA are reliable ICU mortality risk stratification models for cardiac surgery patients. SAPS II and APACHE II did not perform well in terms of calibration and discrimination statistics.