Search

Enthusiasm for minimally invasive thoracic surgery is increasing. Thoracoscopy plays a significant therapeutic role in the fibrinopurulent stage (stage II) of empyema, in which loculated fluid cannot often be adequately drained by chest tube alone. For some debilitated and septic patients, further procedures such as open-window thoracostomy (OWT) with daily wound care or vacuum-assisted closure (VAC) therapy are necessary. In the present article, we propose a new option of minimally invasive VAC therapy including a topical solution of the empyema without open-window thoracostomy (Mini-VAC-instill). Three patients who underwent surgery using this technique are also presented. The discussion is focused on the advantages and disadvantages of the approach.

Objective: Iatrogenic tracheobronchial ruptures are seldom but severe complications after intubation or bronchoscopy. Therefore, we evaluated the reasons, the subsequent therapy and the outcome of patients with tracheal rupture, who were admitted to our hospital. Methods: In a retrospective study we examined 19 patients (15 women, four men; 43–87 years) treated for acute tracheobronchial lesions. Eleven (58%) patients had a tracheobronchial rupture by single-lumen tube, four (21%) by double-lumen tube and two patients (10%) by tracheal cannula. A total of 47% of whom were carried out under emergency conditions. Two patients had a rupture due to a stiff bronchoscopy. Mean symptoms were mediastinal and subcutaneous emphysema. Two emergency collar incisions had been done. Results: The localization of ruptures was in all cases in the paries membranaceus, length: 1–7 cm (mean: 4.8 cm). The interval between the onset of symptoms and the diagnose differed widely (up to 72 h), nine (47%) diagnoses were made during intubation/bronchoscopy. One patient, with a small tear (1 cm) was treated conservatively with fibrin-glue. The other 18 patients had surgical repair through a thoracotomy. The postoperative mortality was determined with 42%, which was not dependent on the rupture but basically by the underlying diseases requiring intubation. Conclusions: Iatrogenic tracheal rupture is a dangerous complication with potentially high postoperative mortality, mostly influenced by the underlying disease. Early surgical repair must be the preferred treatment. q 2002 Elsevier Science B.V. All rights reserved.

Objectives: This retrospective study evaluates the probability of survival in patients who had undergone resection for non-small cell lung cancer (NSCLC) and in whom residual disease at the resection margins was found. Methods: During a period of 6 years, 596 patients with NSCLC were operated upon with curative intention. Residual disease at the resection margin was divided into microscopic (R1) and macroscopic (R2). Results: Twenty-six patients (4.4%) showed R1 and 12 (2%) R2 residual disease. An extrabronchial (thoracic wall, vessels) R1 situation was found in five patients and a bronchial R1 infiltration in 21 cases. The bronchial resection margin was subject to peribronchial infiltration in most cases (16/21). A total of 17/21 (65%) patients with bronchial infiltration had N2 disease. Thirty day lethality was 3.8% in the R1 group. Fifteen patients had postoperative irradiation. The 5-year survival rate for patients with R1 resection was 14%. The differences in survival between patients with extrabronchial vs. bronchial infiltration and N0/N1 vs. N2 were significant using univariate analysis. Adjuvant radiation did not result (especially in N2 disease) in a survival benefit. Among 12 patients with macroscopic residual disease (R2), 3/12 (25%) died within the first 30 days after the operation, and none of the R2 patients survived the first year after the operation. Conclusions: Patients with an R1 situation have a survival rate of 14% comparable to curative resected patients (RO) in stage III. Adjuvant radiation had no clear effect on survival. Patients with macroscopic tumor (R2) should receive palliative treatment after the operation depending on their condition. q 2002 Elsevier Science B.V. All rights reserved.

Background Despite significant advances in the treatment of thoracic infections, complex lung abscess remains a problem in modern thoracic surgery. We describe the novel application of vacuum-assisted closure for the treatment of a lung abscess. The technical details and preliminary results are reported. Methods After the initial failed conservative treatment of an abscess, minimally invasive surgical intervention was performed with vacuum-assisted closure. The vacuum sponges were inserted in the abscess cavity at the most proximal point to the pleural surface. The intercostal space of the chest wall above the entering place was secured by a soft tissue retractor. The level of suction was initially set to 100 mm Hg, with a maximum suction of 125 mm Hg. The sponge was changed once on the 3rd postoperative day. Results The abscess cavity was rapidly cleaned and decreased in size. The mini-thoracotomy could be closed on the 9th postoperative day. Closure of the cavity was simple, without any short- or long-term treatment failure. This technique reduced the trauma associated with the procedure. The patient was discharged on the 11th postoperative day. Conclusions Vacuum-assisted closure systems should be considered for widespread use as an alternative option for the treatment of complicated pulmonary abscess in elderly, debilitated, immunocompromised patients after failed conservative treatment. Electronic supplementary material The online version of this article (doi:10.1186/s13019-014-0157-x) contains supplementary material, which is available to authorized users.

Background In cases of intravenous placement failure of the left ventricular (LV) lead for cardiac resynchronisation therapy (CRT) and obliteration of the left pleural space, the alternative approach of transthoracic placement by video-assisted thoracoscopic surgery (VATS) is difficult and not commonly practiced. Methods Here, we present a simple technique for transthoracic introduction of an epicardial LV lead using a wound retractor (ALEXIS®) in a patient with heart failure. This wound retractor enables atraumatic tissue retraction without rib spreading, an optimal direct view in the pleural space for surgical pleurolysis and a high degree of safety for the patient. Results No perioperative complications occurred. The tube drainage was removed on the second postoperative day, and the patient was discharged on the third postoperative day. Conclusions The decided advantage of this new method is the lack of any need for rib spreading using a mechanical retractor. Especially in patients with a history of open-heart surgery (including internal mammary artery bypass grafting and/or revascularisation of the left lateral wall) or known pleural adhesions (e.g., pleuritis or lung operations), the described technique provides a rapid and save access with minimal surgical effort and greater safety.

The danger of thoracic aneurysm rupture increases with the size of the aneurysm. We report on a 59-year-old man who developed a secondary aneurysm of the descending thoracic aorta within the residual type A dissection that was approximately 9-cm long and in which a contained rupture occurred. The patient died as a result of a massive hemorrhage during the anesthesiological preparation for emergency operation a short time after double-lumen intubation and commencement of controlled artificial ventilation. Autopsy revealed an atelectatic lower pulmonary lobe that had partially fused with the aneurysm. The fusion may have been so substantial that it may have acutely eliminated the covering of the contained rupture during artificial ventilation.

SUMMARY Background: Pleural carcinosis is caused by tumors of the chest (e.g., lung and breast cancer) or elsewhere in the body (e.g., ovarian carcinoma) that metastasize to the visceral and/or parietal pleura. Recurrent malignant pleural effusion due to pleural carcinosis is one of the most common findings in oncology. It affects about 56 000 patients per year in Germany alone. Methods: This review is based on pertinent literature retrieved by a selective search of the Medline database (key words: malignant pleural effusion, pleural carcinosis) and on the authors’ clinical experience. Results: Although many retrospective studies have been published, there has been only one randomized controlled trial of treatment, in which permanent pleural catheters were compared with talcum pleurodesis. Patients with pleural carcinosis have a median survival of less than 12 months. Many are suffering from progression of their underlying disease, with generalized tumor involvement; thus, the symptomatic treatment of pain and dyspnea is often the main therapeutic issue. The underlying tumor, usually an adenocarcinoma, can be diagnosed either by histology or by cytology. The main complication is progressive respiratory failure. The treatment is palliative, rather than curative. The main approaches are drainage of the effusion (by thoracocentesis or with permanent pleural catheters) and pleurodesis (obliteration of the pleural space by causing the visceral and parietal pleura to adhere to each other). Conclusion: Pleural carcinosis with symptomatic malignant pleural effusion is treated palliatively. The appropriate treatment in each case should be determined through discussion with the patient, with the goal of improving the patient’s quality of life.

OBJECTIVES: The pool of potential candidates for pleural empyema is expanding. In a previous technical report, we tested the feasibility of the minimally invasive insertion of a vacuum-assisted closure (Mini-VAC) system without the insertion of an open-window thoracostomy (OWT). In this study, we describe a consecutive case series of complex pleural empyemas that were managed by this Mini-VAC therapy. METHODS: In this retrospective study, we investigated 6 patients with multimorbidity (Karnofsky index ≤50%) who were consecutively treated with Mini-VAC for a primary, postoperative or recurrent pleural empyema between January 2011 and February 2012. RESULTS: Local control of the infection and control of sepsis were satisfactory in all 6 of the patients treated by Mini-VAC therapy. The suction used did not create any air leaks or bleeding from the lung or mediastinal structures. Mini-VAC therapy allowed a reduction of the empyema cavity and improved the re-expansion of the residual lung. Mini-VAC therapy resulted in a rapid eradication of the empyema. The chest wall was closed in all patients during the first hospital stay. All patients left the hospital in good health (Karnofsky index >70%) and with a non-infected pleural cavity at a mean of 22 ± 11 days after Mini-VAC installation. Pleural empyema was not detected in any of the 6 patients at the 3-month follow-up appointment. CONCLUSIONS: The Mini-VAC procedure with the abdication of an OWT offers a rapid treatment for complex pleural empyema with minimal surgical effort and the opportunity for a primary closure of the empyema cavity.

OBJECTIVES: A combination of cytoreductive surgery and hyperthermic intrathoracic chemotherapy perfusion (HITHOC) was performed for the treatment of primary and secondary pleural malignancies. We describe the perioperative management and our clinical experience. METHODS: Between September 2008 and August 2011, eight patients with pleural manifestation of thymoma (Masaoka stage IVa) and eight patients with malignant pleural mesothelioma (MPM) were prospectively enrolled. Postoperative morbidity, recurrence and survival rates were analysed. RESULTS: All the patients received multimodality therapy, including chemotherapy, radiation and surgical resection (pleurectomy/ decortication) followed by the HITHOC procedure. Chemotherapy perfusion was performed with cisplatin (100–150 mg/m 2 ) at 42°C for 1 h. Severe chemotherapy-related complications were not observed. Reoperation was necessary in two patients. There was no 30-day mortality. The median stay on the intensive care unit was 1 day, and the median duration of hospitalization was 15 days. Pleural recurrence of thymoma was evident in one thymoma patient 6 months after HITHOC. At mean follow-up of 22 months, seven thymoma patients (7/8; 88%) are alive without recurrence. Tumour progression was present in six mesothelioma patients (6/8; 75%). Four patients (50%) with MPM are alive, including two with no evidence of mesothelioma, and the median survival is 18 months. CONCLUSIONS: Cytoreductive surgery in combination with HITHOC can be performed with acceptable morbidity and mortality rates in selected patients. Patients should be evaluated by an interdisciplinary team to determine their eligibility for this therapeutic alternative. Early clinical results may encourage the use of this surgical option to provide better local tumour control in a multimodality treatment setting.

Preoperative renal impairment predicts postoperative mortality in patients undergoing cardiac surgery. We examined the impact of three equations for glomerular filtration rate (GFR) estimation on mortality. This is a retrospective, observational study on patients undergoing valve (n = 594) and combined valve and coronary procedures (n = 412). Glomerular filtration rate was estimated with modification in diet and renal disease (MDRD), Cockcroft-Gault (CG) equation, and Mayo-Clinic (MC) equation. Mean age was 65 ± 11 years and mean logistic EuroSCORE was 9.0 [95% confidence interval (CI): 8.4-9.7]. Preoperative kidney dysfunction (eGFR

The omicron-acyltransferase porcupine contributes to secretion and function of Wnt signaling molecules, which stimulate the expression of various cancer-related genes. Porcupine is also involved in the Wnt-induced cell signaling via beta-catenin in non-small cell lung carcinoma (NSCLC) cells. Herein, we report that the expression level of porcupine in human NSCLC tissues (n=89) positively correlates with the expression of several genes coding for cancer-related molecules such as beta-catenin, hypoxia-inducible factor-1alpha and jun B. However, the mRNA expression of porcupine was not generally increased in NSCLC compared to normal lung tissues. In NSCLC tissues we also found a positive correlation between the expression level of porcupine and the calcium-binding protein S100P, which contributes to initiation and invasion of cancer cells. Subsequent studies showed that the DNA hypomethylation with 5-aza-2'deoxycytidine increased the mRNA expression of S100P in NSCLC cells but did not alter that of porcupine. Silencing the expression of porcupine with small interfering (si)RNA reduced the expression of S100P in NSCLC cells, whereas silencing the expression of S100P with siRNA did not effect the level of Porcupine expression. In conclusion, besides DNA methylation processes, porcupine might regulate the expression of some cancer-related molecules including S100P in human NSCLC.

Background Limited information exists on the influence of preoperative renal dysfunction on in-hospital mortality after valve and combined valve and coronary procedures. The impact of preoperative renal dysfunction on patient outcome was investigated. Methods This was a retrospective observational study of 916 patients who underwent solitary valve or combined procedures. Primary outcome was in-hospital mortality. Preoperative estimated glomerular filtration rate (eGFR) was calculated with the abbreviated Modification of Diet in Renal Disease formula. Results Independent predictors of death were prolonged stay in the intensive care unit (odds ratio [OR], 1.03; 95% confidence interval [CI], 1.01 to 1.05), preoperative atrial fibrillation (OR, 1.61; 95% CI, 1.02 to 2.54), chronic obstructive pulmonary disease (OR, 2.2; 95% CI, 1.06 to 4.55), and prolonged operation time (OR, 1.01; 95% CI, 1.00 to 1.01). Each unit of the eGFR (mL/min/1.73m 2 ) above average exerted a renoprotective effect (OR, 0.97; 95% CI, 0.96 to 0.98). The final regression model showed no lack of fit (Hosmer-Lemeshow test, p = 0.38) and a good discrimination performance in a receiver operating characteristic analysis (area under the curve, 0.84; 95% CI, 0.80 to 0.88). The lower the preoperative eGFR rate, the longer the postoperative stay at the intensive care unit. Conclusions Renal dysfunction is an important independent predictor of in-hospital mortality in adult patients after valve and combined valve and coronary procedures.

Lung adenocarcinoma is characterised by an upregulation of S100P, which mediates its function intracellularly but also extracellularly. Recent studies suggest that extracellular S100P contributes to tumour development following interaction with the receptor for advanced glycation end-products (RAGE). As RAGE is highly downregulated in lung cancer, one might speculate that S100P supports tumorigenesis via other pathways. Here, we showed that S100P primarily localises in the cytoplasmic and nuclear region as determined for lung adenocarcinoma specimens (immunohistochemistry) and H358 lung adenocarcinoma cells stably overexpressing S100P (GFP-S100P; fluorescence microscopy). S100P overexpression in H358 cells induced a more frequent formation of tumour colonies in vitro (soft agar assay). However, the S100P-overexpressing cell colonies showed a smaller colony size. This observation was supported by proliferation assays demonstrating a reduced proliferation per increasing cell density of the H358 cells overexpressing S100P. Migration of S100P-overexpressing H358 cells was diminished (transwell migration and in vitro wound scratch assays). Inhibiting DNA methylation with 5-aza-2'deoxycytidine enhanced the mRNA expression of S100P, whereas high S100P levels following overexpression suppressed the mRNA expression of endogenous S100P. In this regard, an upregulation of S100P in lung adenocarcinomas was only determined for early/T1 stage but not more advanced/T2 stage tumours compared with normal lung tissues. Thus, S100P induction may be considered an important step in the initial stage of lung adenocarcinomas, whereas its downregulation in advanced stages seems to be important for tumour progression in which DNA methylation and/or feedback transcription processes play a critical role.

The efficient treatment of lung carcinomas with chemotherapeutics still poses a challenge for anti-cancer therapy. Since stromal cells of the tumor may alter the responsiveness of tumor cells to chemotherapeutics, we studied the impact of lung fibroblasts (WI-38) on the chemotherapy-induced death of non-small cell lung carcinoma cells (H358). Conditioned medium from WI-38 fibroblasts impaired the H358 cell death induced by paclitaxel but not by cisplatin. Comparable results were observed when culturing H358 cells in conditioned medium from primary tumor fibroblasts or co-culturing H358 cells with fibroblasts. This anti-apoptotic effect induced by paracrine signaling from fibroblasts was associated with less necrosis (membrane leakage, mitochondrial dysfunction) and apoptosis (outer membrane phosphatidylserine exposure, pycnotic nuclei, nuclear translocation of the apoptosis-inducing factor from mitochondria, caspase-9 and -3/-7 activation) in response to paclitaxel but not cisplatin. Additionally, we demonstrated that WI-38 fibroblasts mediate activation of both extracellular signal-regulated kinases (Erk) 1/2 and Akt kinase in H358 cells. Subsequent application of specific inhibitors revealed that the paclitaxel-induced cell death is highly impaired by active Erk1/2 and Akt, whereas the cisplatin-induced cell death is independent of both kinases. Pro-apoptotic Bcl-2 family proteins such as Bim cannot explain the differential impact of fibroblasts on the H358 cell death induced by paclitaxel compared with cisplatin. Our data support the preferential use of the cisplatin-based lung carcinoma therapy, because the cell death-inducing efficiency of cisplatin is not impaired by stromal fibroblasts.

Intraaortic balloon pump replacement (IABP) is the most widely used circulatory assist device today and is utilized in a wide range of serious cardiovascular conditions. We examined the effects on mortality of pre-, intra-, or postoperative IABP support in patients undergoing cardiac surgery compared to high-risk patients without IABP support.Between June 2001 and April 2004, 267 patients either received preoperative IABP support (n=62), an intra- or postoperative IABP (n=113) or had no IABP (n=92). Perioperative mortality was calculated with the EuroSCORE.Patients with preoperative IABP and without IABP support had a lower ejection fraction [37 (29; 50) % and (39 (30; 53)) % vs. (50 (39; 65)) %, P = 0.0001], more frequent unstable angina (38/62 and 53/92 vs. 37/113, P = 0.0004) and recent myocardial infarctions (33/62 and 51/92 vs. 26/113, P = 0.0001). The number of emergency procedures was also significantly higher (36/62 and 65/92 vs. 27/113, Por = 0.01). Patients with intra-, or postoperative IABP support and patients without IABP support had a longer ICU-stay [7.5 (5; 17.75)) and (7 (5; 15.5)) days vs. (6 (3; 10) days, P = 0.023, P = 0.015]. The overall hospital stay of patients without IABP [18.5 (14; 29) days] and intra-/postoperative IABP support [19, (14; 28) days] were significantly longer (P = 0.007) compared to patients with preoperative support [14 (11.5; 20.5) days]. Whereas we found a trend towards reduced mortality in high-risk non-emergency patients with preoperative support, emergency patients and patients receiving intra- and postoperative support had significantly higher mortality rates than predicted by the EuroSCORE. Both emergency and non-emergency patients without IABP insertion had a significantly higher actual mortality than predicted (29.5% vs. 13.7%, P = 0.03 and 38.1% vs. 26.3%, P0.0001). The overall actual mortality between patients with preoperative IABP insertion and patients without preoperative IABP did not significantly differ (14/62 vs. 29/92, P = 0.27). The EuroSCORE proved to be a valid predictor for perioperative mortality among high-risk non-emergency and emergency patients with preoperative IABP support at lower score sums, but failed at higher score sums (8) and among patients with intra- and postoperative IABP insertion.Preoperative IABP support is indicated in high-risk non-emergency patients. The benefit of preoperative IABP insertion in emergency patients and intra- and postoperative IABP support still remains controversial and needs to be elucidated in further prospective, randomized studies.

We report on a 19-year-old male with a congenital Long-QT syndrome who was admitted to our hospital because of insulation defects of both atrial and ventricular ICD leads resulting in inappropriate delivered shocks and a non-responding pulse generator during telemetrical evaluation. The insulation defects led to multiple arc marks within the ICD pocket and there was a short circuit between denuded leads and the electrically active pulse generator. The high current flow generated sufficient heat to damage several circuits of the generator. A new ICD system was implanted successfully and the postoperative course has been remained uneventful for almost 6 years.

Objective: Statins were ascribed pleiotropic effects besides their lipid lowering features. Although statins reduce the risk of cardiovascular events there is a minor risk for adverse events during statin therapy. Therefore, we assessed the influence of preoperative statin treatment on early postoperative mortality and major morbidity in patients undergoing coronary artery bypass graft surgery. Methods: From 2001 to 2006, coronary artery bypass grafting was performed in 1517 patients (1034 of which had preoperative statin treatment) in two centres. We compared in-hospital outcomes in a propensity-matched sub-cohort of 842 (421 in each treatment group). In this sub-cohort, patients were similar with respect to age, sex, weight, height, LVEF, previous MI, previous stroke, diabetes, hypertension, priority, renal insufficiency, degree of CVD, instable angina, left main stenosis, other cardiac pre-medication, and PVD (all p-values >0.24) in the statin and the non-statin group. Results: No significant differences were seen in mortality, stroke, acute renal failure, atrial fibrillation, epinephrine treatment and norepinephrine treatment, ventilation time, re-intubation, stay on intensive care unit, and the onset of systemic inflammatory response syndrome. Conclusions: In our propensity-matched sample we did find neither a statistically nor a clinically relevant influence of preoperative statin treatment on postoperative mortality and morbidity in patients undergoing coronary artery bypass surgery. Therefore, we conclude that preoperative statin therapy does not alter perioperative outcome after coronary artery bypass graft surgery.

Purpose: Patient survival after resection of non-small cell lung cancer (NSCLC) strongly correlated with the occurrence of distant metastasis. Cathepsins are members of the lysosomal cysteine proteases family and can support the metastatic process by degrading the extracellular matrix. The purpose of this study was to identify members of the Cathepsin family that correlate with recurrence-free and overall survival of NSCLC patients. Patients and methods: The expression of 13 Cathepsins was examined using DNA-microarray technology in tumor tissues of 89 surgically treated NSCLC patients. All NSCLC samples were classified according to median Cathepsin expression value into either a high or a low expression group. All Cathepsin expression groups were subjected to clinical prognostic analyses regarding survival and local as well as distant recurrences. Results: Patients with high Cathepsin C tumor expression showed higher tumor recurrence rate compared to patients with low Cathepsin C expression (p = 0.02). The tumor expression of Cathepsins K and B significantly correlated with recurrence-free and overall survival as determined by multivariate analysis. A high expression of Cathepsin B or K was associated with a considerable reduction of recurrence-free as well as overall survival. NSCLC patients with a high expression of both Cathepsin B and K had a significantly (p = 0.001) poorer outcome (5-year survival rate: 13%) than patients with low expression of both genes (5-year survival rate: 75%). Conclusions: The combined expression level of Cathepsins B and K identifies high-risk NSCLC patients. A selection of gene expression panels is theoretically superior to established clinical and pathological criteria.

In the present paper we discuss the indication and follow-up of 42 patients with iatrogenic tracheobrochial ruptures. Thirty-five patients were treated by operation and 7 patients were treated conservatively. In the operated patients, four developed an insufficiency of the tracheal closure and the rupture related mortality was 2.8%. A significant effect on suture dehiscence was seen for mediastinitis (P

Early and correct diagnosis of non-small cell lung carcinoma (NSCLC) is essential for the choice of an appropriate anti-cancer therapy. Besides the histopathological diagnosis, molecular profiling by detection of the tumour-associated gene expression might play an upcoming role. As proteins of the S100 gene family show a distinct cell type-specific expression profile, our study focused on the relevance of the S100 family for identification and classification of NSCLCs. Among the S100 members, we identified the expression of S100A1, S100A2, S100A4, S100A6, S100A9 and S100P in human lung carcinoma cells (H358(p53-), A549(p53+)) or NSCLC tissues. Distinct S100 members are increased in NSCLCs compared with control lung specimens depending on the histopathological subtype. In particular, S100A2 was upregulated in squamous cell carcinomas, whereas S100P was mainly increased in adenocarcinomas. The upregulation of either S100A2 or S100P was detected in early but less in advanced tumour stages and not at all in NSCLC patients who had received neoadjuvant chemotherapy. In conclusion, our study indicates an important role of the S100A2-S100P expression profile for molecular diagnosis of NSCLCs at early and, therefore, prognostically more favourable tumour stage. As the S100A2-S100P profile also allows the histopathological classification, it might significantly support the conventional tumour diagnostics.

Objective: The incidence of second primary malignancies seems to be increasing. The aim of this study was to investigate the incidence, treatment and outcome for patients with second primary lung cancer (SPLC). Methods: Between January 1996 and December 2005, 163 patients with SPLC, occurring after an extrapulmonary malignancy, were recruited by the Tumor Center of Halle (Saale), which represents a region of nearly 1.0 million inhabitants in Germany. The SPLCs were treated under curative aim (n = 59), with palliative intend (n =7 6) or best supportive care (n = 28). Results: The incidence of SPLC was 1.6 per 100,000 inhabitants. The localization of the first tumor differed depending on the sex of the patients. The actuarial 5-year survival rate of all patients was 12.7% (median survival time 11.4 months). Univariate analysis revealed treatment strategy as a prognostic factor (p = 0.0001). Patients with SPLC having undergone curative treatment turned out to have the best prognosis (median survival: 31.0 months). The Cox proportional hazards model demonstrated that only TNMstaging system was a multivariate and significant independent prognostic predictor for overall survival. The method of surgery, standard lung resection (e.g. lobectomy) versus limited resection had no considerable influence on overall survival (p = 0.22), respectively recurrence-free survival (p = 0.55). Conclusions: In cases of operability, standard resection must be the method of choice, because of its best survival rates. The results support the demand of an exact and short-term oncological care system to detect early stages of SPLC for patients operated upon for tumors at different sites. # 2007 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Primary pulmonary sarcomas are extremely rare tumors. Since the first description by Mandelstamm 1 in 1923, only about 100 case reports have been published, and only a few have dealt with combined treatment of primary sarcoma. We report on a woman with a metastasizing pulmonary sarcoma of the pulmonary valve with infiltration of the pulmonary artery. After complete remission of the pulmonary metastases with polychemotherapy, the patient underwent curative resection of the tumor and insertion of a cryopreserved homograft. A 49-year-old woman was admitted because of increasing short of breath with exercise. She had pericarditis about 6 months previously. Since then, both chest and back pain occurred frequently, associated with tachycardia and dyspnea. Auscultation revealed a 3/6 systolic ejection murmur in the second left intercostal space and a markedly split second heart sound. There were signs of right ventricular overload on the electrocardiogram. The initial chest radiograph showed several bilateral pulmonary nodular lesions, confirmed by computed tomographic scan. Two-dimensional and transesophageal echocardiography revealed an enlarged right ventricle and an abnormal structure in the main and right pulmonary arteries. Right heart catheterization showed elevated right ventricular and pulmonary arterial pressures, with a ventricular-distal pulmonary artery gradient of 40 mmHg. The main and right pulmonary arteries were seen by cineangiography to be incompletely perfused. Needle biopsy was carried out for cytologic and histologic examination of the pulmonary nodular lesions, which we had suspected and later confirmed to be hemangiosarcoma. Elective resection of the right sided lung metastases was incomplete as a result of life-threatening hemodynamic instability. Histologic examination of one of these tumors revealed granulation and scar tissue without evidence of malignancy. Because of progression of right heart failure and growth of the pulmonary lesions seen on the computed tomographic scan, chemotherapy was initiated. In the subsequent 7 months, polychemotherapy (etoposide, vincristine, ifosfamide, adriamycin) was administered for six

Pulmonary metastasectomy as well as immunotherapy have reproducible, albeit limited efficacy in advanced renal cell carcinoma (RCC). We examined whether metastasectomy improved overall survival compared with results of immunotherapy.Between 1975 and 2003, 64 patients (41 men, 23 women) underwent pulmonary resection of metastatic RCC. Only patients who met the criteria for potentially curative operation, that means, control of primary tumor, ability to resect metastatic disease and no other extrapulmonary metastases, were included.The overall 5-year survival was 33.4% (median survival: 39.2 months). A significant longer survival was observed using multivariate analysis in patients with complete pulmonary resection (R0), with a 5-year survival of 39.9% and a median survival of 46.6 months in correlation to patients with incomplete resection (5-year survival 0%, median survival 13.3 months). In multivariate analysis patients with synchronous metastases had a significant worse prognosis in correlation to patients with metachronous metastases. The 5-year survival of curative resected patients with metachronous metastases was 43.7% versus 0% for synchronous metastases, respectively. In patients with solitary metastasis and R0 resection, we observed a 5-year survival of 49%, whereas the rate was 23% in patients with more than a single metastasis. When establishing prognostic groups as suggested by the International Registry based on the risk factors disease-free interval, number of metastasis and complete resection the group with the best prognosis showed a 5-year survival of 52% (median survival 75.2 months).Metastasectomy nowadays is the best treatment option in cases with technical resectable metastases with as much as possible good prognostic factors (metachronous metastases with long DFI, number up to 6 metastases).

Expression profiling by gene microarray techniques have been developed to predict malignant tissue but there are no experiences with the application of antibody arrays to identify malignancy-related proteins. Because altered protein patterns might also better interpret biological processes, we applied tumour samples from 12 patients with squamous cell lung carcinoma and individual lung tissue controls to antibody arrays spotted with 378 distinct monoclonal antibodies. Array analysis defined 20 proteins with higher and nine with lower abundance in lung tumours. Comparison with gene microarray data revealed that 31% of the differentially regulated proteins correlate with altered mRNA expression in squamous cell lung carcinomas, including PEX1, MKK7 and HDAC3 for up-regulated proteins. The histone deacetylase (HDAC) 3 was investigated in detail by immunoblot analysis showing that HDAC3 is indeed elevated in 92% of tumours (n=22/24; P

The receptor for advanced glycation end-products (RAGE) is a transmembrane receptor of the immunoglobulin superfamily. Several ligands binding to RAGE have been identified, including amphoterin. Experimental studies have given rise to the discussion that RAGE and its interaction with amphoterin contribute to tumour growth and metastasis. However, none of the studies considered a differential transcription profile in cancer that might change the interpretation of the study results when comparing RAGE in tumours with histologically normal tissues. Here we show that RAGE is strongly reduced at the mRNA and even more so at the protein level in non-small cell lung carcinomas compared with normal lung tissues. Down-regulation of RAGE correlates with higher tumour (TNM) stages but does not depend on the histological subtypes, squamous cell lung carcinoma and adenocarcinoma. Subsequent overexpression of full-length human RAGE in lung cancer cells (NCI-H358) showed diminished tumour growth under some conditions. While proliferation of RAGE-expressing cells was less than that of cells expressing the cytoplasmic domain deletion mutant DeltacytoRAGE or mock-transfected NCI-H358 in monolayer cultures, RAGE cells also formed smaller tumours in spheroid cultures and in vivo in athymic mice compared with DeltacytoRAGE cells. Moreover, we observed a more epithelial growth of RAGE-expressing, but also of DeltacytoRAGE-expressing, cells on collagen layers, whereas mock NCI-H358 cells kept their tumour morphology. This observation was supported by immunofluorescence analyses demonstrating that RAGE preferentially localizes at intercellular contact sites, independent of expression of the cytoplasmic domain. Thus, down-regulation of RAGE may be considered as a critical step in tissue reorganization and the formation of lung tumours.

Simple tools for discrimination of lung tissues can be useful in a fast machine-aided diagnosis, for example, by tumor-specific microarrays. We demonstrate that an easy ratio technique, based on the expression levels of only two genes differentially expressed in lung tumor and normal lung samples, allows discrimination of normal and neoplastic lung with a sensitivity of 100% and specificity of 90.5%. DNA microarray analysis of 99 lung tumor samples and 15 normal lung tissues revealed that receptor for advanced glycation end products (RAGE) mRNA is reduced fourfold (p = 7.8 x 10(-11)) and cyclin-B2 mRNA is upregulated twofold (p = 5.9 x 10(-18)) in lung carcinoma compared with normal lung. The microarray-calculated expression ratio of RAGE to cyclin-B2 was used in polymerase chain reaction analysis of 84 independent blinded samples to discriminate tumor and corresponding normal lung tissues. In 94.7% of the samples this quotient correctly distinguished non-small cell lung cancer from normal lung tissue, suggesting the RAGE/cyclin-B2 quotient as a potential means for diagnosis of lung cancer.

Sternumwundinfektionen (SWI) nach herzchirurgischen Eingriffen sind selten, stellen aber auf Grund hoher Morbiditat und Mortalitat eine schwere Komplikation dar. Das Ziel der Studie war die multivariate Evaluierung von Risikofaktoren, um somit geeignete Praventionsmasnahmen zu etablieren. 6 895 Patienten, die sich in der Zeit von 1988–1999 einer kardiochirurgischen Operation unter extrakorporaler Zirkulation (ECC) unterzogen haben, wurden hinsichtlich der Entwicklung einer SWI untersucht. Den Patienten mit SWI (Untersuchungsgruppe, n = 112) wurde zur Auswertung von Risikofaktoren eine reprasentative Kontrollgruppe (n = 241) gegenuber gestellt. Der Vergleich von potenziellen Risikofaktoren zwischen diesen Gruppen erfolgte uni- und multivariat (logistisches Regressionsmodell). Die Inzidenz von SWI betrug 1,6%. In der Untersuchungsgruppe sind 26 Patienten (23,2%) verstorben. Diese Mortalitatsrate lag signifikant (p < 0,001) uber der der Kontrollgruppe (6,7%). Als unabhangige Risikofaktoren konnten multivariat das Low-Cardiac-Output-Syndrom [odds ratio 13,0; 95% Konfidenzintervall, (1,84, 92,6)], die Adipositas [8,9; (4,0, 19,8)], das Rauchen [5,0; (1,84, 92,6)], das Alter [0,96; (0,93, 0,99)], die respiratorische Insuffizienz [5,0; (1,47, 17,3)] und die Art des Sternumverschlusses [0,22; (0,10, 0,52)] evaluiert werden. Die evaluierten Risikofaktoren beweisen, dass Sternuminstabilitaten (ineffektiver Sternumverschluss), mechanische Belastungen der Sternotomie (Adipositas) und systemische Faktoren wie die verminderte Gewebeperfusion (LCOS) SWI fordern. Gezielte Masnahmen zur Bekampfung dieser Risikofaktoren sind indiziert.

This study was designed to examine the effect of rutin and cinchonine on the uptake and metabolism of idarubicin (IDA) in the isolated perfused rat lung. IDA (2 mg) was infused for 2 min into the truncus pulmonalis in thepresence of P-glycoprotein (P-gp) modulators cinchonine (1 μM) or rutin (6 μM). (Rutin is also known as an aldo-keto reductase inhibitor.) Venous outflow samples were collected up to 60 min, and the concentration of IDA and its primary metabolite idarubicinol (IDOL) were measured by high-performance liquid chromatography) with fluorescence detection. Thereafter, the tissue concentrations of IDA and IDOL were determined in the lung (n = 5 in each group). The estimated mean transit times for IDA in the treatment groups (MTT c i n c h o n i n e = 21.8′3.5 min; MTT r u t i n = 20.1 ′ 5.0 min) were significantly higher than in the control group (11.6 ′ 2.1 min). Both cinchonine and rutin significantly enhanced the lung tissue concentrations of IDA (1.7- and 2.4-fold), as well as of IDOL (2.1- and 2.4-fold). Cinchonine and rutin also increased the outflow recovery of IDOL 2.6- and 2.7-fold, respectively. The results suggest that uptake kinetics of IDA into the rat lung is partly controlled by a P-gp efflux pump and its inhibition enhances the accumulation of IDA.

We report a 61-year-old male smoker who was admitted to our hospital for treatment of a moderately growing tumour on the right anterolateral chest wall causing chest pain during coughing. Chest computed tomography and magnetic resonance imaging showed a 55 x 50 mm inhomogeneous mass around the 4th rib but not penetrating the subcutis and lung. Neither a preoperative technetium scintigraphy nor a needle biopsy revealed the primary nature of the tumour. The patient was treated with en bloc resection and partial resection of the adjacent 3rd and 4th rib. The frozen section diagnosis confirmed a metastasis from a primary hepatocellular carcinoma.

A 64-year-old man was diagnosed with complex empyema after a second course of palliative chemotherapy for metastatic lung cancer. Because of the poor general condition of the patient, the decision was made to proceed with vacuum-assisted closure (VAC) therapy of the empyema without Eloesser or Clagett open-window thoracostomy (OWT). Installation and changing of the VAC sponge were performed using the ALEXIS Wound Protector/Retractor (Applied Medical, Rancho Santa Margarita, CA), a flexible polymer membrane tube. After 10 days of VAC treatment, the pleural cavity was sterile and was closed with single stitches. Chemotherapy was resumed 1 week later.

Purpose. Apoptotic cell death contributes to the regulation of tumour regression but can be prevented by proteins of the IAP family. Although survivin can be identified as tumour-specific gene product, the role of other members of the IAP family is mainly unclear in non-small cell lung cancer (NSCLC). Therefore, we hypothesise that hIAP-1, hIAP-2, and XIAP are associated with lung carcinogenesis, too. Methods. To define IAP expression levels, lung tumour samples from 34 NSCLC patients with adenocarcinoma (16) and squamous cell carcinoma (18) were included. Analyses were performed by standardised RT-PCR and immunoblotting. Paired non-tumour lung tissues served as controls. All tumour samples showed a strong survivin mRNA up-regulation compared with non-tumour controls. Results. Investigations of the XIAP mRNA expression revealed an overall increase in lung carcinoma (median: 1,083 vs 605 rel. U; P =0.02). In contrast, hIAP-2 mRNA was nearly identical in all tumour and control samples. Furthermore, we identified an elevated hIAP-1 mRNA expression especially in patients with adenocarcinoma (median: 8.58 vs 3.44 rel. U; P

Between 1975–1996, 39 patients underwent resection of pulmonary metastases from renal cell carcinoma. Multivariate analysis (COX model) for survival of preoperative risk factors showed that time of diagnosis (syn-/metachronous) of the metastases (p = 0.05) and the number of metastases (p = 0.01) were of prognostic significance. It is concluded that metastasectomy in patients with not more than six metachronous metastases after renal cell carcinoma has significant benefit and in cases of synchronous metastases or more than 6 pulmonary metastases indication for resection should be restricted.

A 67-year-old woman presented to the emergency department with acute back pain and progressive dyspnea during a 7-day period. In addition, the patient noticed reduced urine production and we documented elevated plasma D-Dimers (3.99 mg/L) that were nearly 40-fold higher than normal ( 0.19 mg/L). A spiral chest computerized contrast tomography scan was obtained to screen for thromboemboli within the pulmonary arteries. The scan revealed that several thrombi were embedded in the main and segmental pulmonary arteries (Figure 1). Subsequent venous ultrasonography was negative for deep venous thrombosis. Next, we performed transthoracic echocardiography that was partially obscured because the patient was obese. Nevertheless, the right ventricle was enlarged and we observed a free-floating structure within the right atrium. Therefore, we performed transesophageal echocardiography that detected an intracardial thrombus. The thrombus size was 50 25 mm in the right atrium and 20 20 mm in the left atrium. This free-floating thrombus crossed a persistent foramen ovale (Figure 2). The patient underwent open heart operation to remove the thrombus (140 11 mm) and the persistent foramen ovale was closed with an atrial septum Dacron patch (Figure 3). The cause of the thromboemboli was unclear because all of the coagulation factors were within the normal range. However, a subsequent abdominal computerized contrast tomography scan demonstrated that a suggestive tumor was lodged between the right uterine tube and ovary. A laparotomy performed by colleagues in the department of gynecology revealed that the tumor was an ovarian

7105 Background: The therapeutic outcome for unresectable, locally advanced, malignant thymoma is poor. Most important factor for long-term survival in thymoma patients is complete resection (R0) of the tumor. The study was performed to evaluate the efficacy of octreotide LAR plus prednisone in patients with primary inoperable or local recurrent thymoma to reduce tumor size. Methods: This was an open label, single-arm study in patients with inoperable or local recurrent thymoma. Patients were considered unlikely to achieve R0 resection at enrollment. Octreotide LAR was administered once every 2 weeks in combination with prednisone. Two stages were planned according to Fleming’s one sample multiple testing procedure for phase II clinical trials. The objective of the study was to show that octreotide LAR is effective in this patient population with respect to tumor shrinkage. Response was defined as decrease in tumor volume of at least 20% at month 3 as compared to baseline. Results: 17 thymoma patients at Masaoka stage III were recruited. Octreotide LAR showed a response in 15 of 17 patients (88.24%) at week 12. Two patients had discontinued the study before week 12 due to unsatisfactory therapeutic effect or adverse events. At Week 12, 5 patients (29.41%) operable for radical resection. 10 patients (58.82%) were not operable for radical resection. 16 of 17 patients (94.12%) experienced adverse events (AEs). The most frequent AEs were gastrointestinal disorders (70.59%), infections and infestations (64.71%), and blood/lymphatic system disorders (41.18%). Conclusions: Octreotide LAR was shown to be effective in patients with inoperable thymoma with respect to tumor shrinkage.Octreotide LAR was generally well tolerated. The reported AEs are in accordance with the known safety profile.

The relationship between DNA content and TNM stage, histology, histological differentiation, survival as well as recurrence was assessed in a study of 215 patients with non-small cell lung cancer (NSCLC) who had undergone complete resection (R0). Cellular DNA content was obtained by image cytometry on paraffinembedded- tumor tissue and by flow cytometry on tumor cell suspension. DNA aneuploidy was measured in 179 (83% out of the 215 NSCLC. The aneuploid/diploid ratio were identical in TNM stage, histology and grading. Only in adenosquamous careionomas the proportion of DNA aneuploid tumors was significantly higher. Aneuploid tumors showed higher recurrence rates (23.2%) during follow-up as diploid tumors (11%). Survival analysis showed that life expectancy of patients with diploid tumors was longer than those with aneuploid carcinomas (5-year survival rate of 69% vs. 49%). The most significant difference was found in patients with adenocarcinoma (5-year survival rate of 100% for diploid tumors vs. 45% for aneuploid tumors). These results suggest that DNA aneuploidy may provide an independent prognostic factor for patients with NSCLC. The study made possible by a grant of the German Ministry lor Research and Technology (BMFT nr. 0 1ZZ9105).

International audience; INTRODUCTION:Adjuvant platinum-based chemotherapy is standard treatment for surgically resected stage II to IIIA NSCLC, but the relapse rate is high. The preferentially expressed antigen of melanoma (PRAME) tumor antigen is expressed in two-thirds of NSCLC and offers an attractive target for antigen-specific immunization. A phase I dose escalation study assessed the safety and immunogenicity of a PRAME immunotherapeutic consisting of recombinant PRAME plus proprietary immunostimulant AS15 in patients with surgically resected NSCLC (NCT01159964).METHODS:Patients with PRAME-positive resected stage IB to IIIA NSCLC were enrolled in three consecutive cohorts to receive up to 13 injections of PRAME immunotherapeutic (recombinant PRAME protein dose of 20 μg, 100 μg, or 500 μg, with a fixed dose of AS15). Adverse events, predefined dose-limiting toxicity, and the anti-PRAME humoral response (measured by enzyme-linked immunosorbent assay) were coprimary end points. Anti-PRAME cellular responses were assessed.RESULTS:A total of 60 patients were treated (18 received 20 μg of PRAME, 18 received 100 μg of PRAME, and 24 received 500 μg of PRAME). No dose-limiting toxicity was reported. Adverse events considered by the investigator to be causally related to treatment were grade 1 or 2, and most were injection site reactions or fever. All patients had detectable anti-PRAME antibodies after four immunizations. The percentages of patients with PRAME-specific CD4-positive T cells were higher at the dose of 500 μg compared with lower doses. No predefined CD8-positive T-cell responses were detected.CONCLUSION:The PRAME immunotherapeutic had an acceptable safety profile. All patients had anti-PRAME humoral responses that were not dose related, and 80% of those treated at the highest dose showed a cellular immune response. The dose of 500 μg was selected. However, further development was stopped after negative results with a similar immunotherapeutic in patients with NSCLC.