Pulmonary actinomycosis is a rare and slowly progressing bacterial lung infection. Actinomyces are commensal bacteria of the oropharynx. Risk factors for pulmonary infection include aspiration and poor dental hygiene; it is not necessarily associated with an immunosuppressed state. Radiological and clinical appearances are nonspecific and mimic a variety of other lung diseases including cancer. Diagnosis requires microbiological isolation of the bacteria from an infected specimen or histopathological evidence of sulfur granules, usually obtained after bronchoscopic, transthoracic or surgical biopsy. Long-term and high-dose antibiotic treatment is essential to achieve high clinical cure rates and good prognosis. Penicillin remains the drug of choice; doxycycline, macrolides and clindamycin have been used successfully as alternatives. Duration of antibiotic treatment should be individualised according to the resolution of symptoms and radiological lesions. Surgical treatment is reserved for patients developing complications, such as massive haemoptysis or empyema, and for those in whom a medical diagnosis cannot be established.

Invasive pulmonary aspergillosis (IPA) is encountered in immunocompromised or neutropenic patients presenting with a high mortality rate. A high index of suspicion is necessary in patients with risk factors such as haematopoietic stem cell transplantation and solid organ transplantation. Radiological imaging is the cornerstone in diagnosing IPA. Modern antifungal therapy with voriconazole and liposomal amphotericin B plays a major role. In selected patients, surgery may be necessary to prevent massive haemoptysis or to prevent re-infection during subsequent chemotherapy. Parenchyma-sparing surgery with open wedge resections or thoracoscopic procedures is recommended, whereas pneumonectomy has a high mortality and is only indicated in emergency situations. In carefully selected patients and with excellent interdisciplinary management, surgery can be performed with low operative morbidity and with a beneficial effect on disease control and survival. Prognosis of IPA is strongly influenced by the underlying disease.

The term mediastinitis refers to inflammation of the tissues located in the mediastinal space. Many aetiological factors contribute to acute and chronic infection of the mediastinum. Although long recognised as a complication of certain infectious diseases, most cases of acute mediastinitis follow oesophageal perforation and open chest surgery. Less common causes include tracheal, bronchial perforation or direct infection from adjacent tissues. Acute mediastinitis is a life-threatening condition that is almost always a complication of other clinical problems. Chronic fibrosing mediastinitis is a slow deposition of thick fibrous tissue encasing any of the mediastinal structures, most commonly secondary to tuberculosis, histoplasmosis, other fungal infections, cancer or sarcoidosis. Descending necrotising mediastinitis is the most dreaded and lethal form of mediastinitis originating from oropharyngeal infection that extends through the deep neck planes to the mediastinum. The clinical spectrum ranges from the subacute to the fulminate critically ill patient, and therefore early diagnosis and prompt aggressive medical and surgical treatment are required to prevent death.

This study is aimed at evaluating the potential of a biochip assay to sensitively detect KRAS mutation in DNA from non-small cell lung cancer (NSCLC) tissue samples. The assay covers 10 mutations in codons 12 and 13 of the KRAS gene, and is based on mutant-enriched PCR followed by reverse-hybridization of biotinylated amplification products to an array of sequence-specific probes immobilized on the tip of a rectangular plastic stick (biochip). Biochip hybridization identified 17 (21%) samples to carry a KRAS mutation of which 16 (33%) were adenocarcinomas and 1 (3%) was a squamous cell carcinoma. All mutations were confirmed by DNA sequencing. Using 10 ng of starting DNA, the biochip assay demonstrated a detection limit of 1% mutant sequence in a background of wild-type DNA. Our results suggest that the biochip assay is a sensitive alternative to protocols currently in use for KRAS mutation testing on limited quantity samples.

In 2007, the International Association for the Study of Lung Cancer proposed changes to the sixth edition of the lung cancer stage classification system, which were adopted by the Union Internationale Contre le Cancer in 2009 (TNM-7). Using historic patient data, the effects of reclassification from the TNM-6 to the TNM-7 system were researched within a single institution. We retrospectively reclassified the pathological records of 145 patients who underwent bronchoplastic resection for non-small cell lung cancer between 1991 and 2004, by applying the new TNM-7 classification for lung cancer. A comparison between the previous and the new system was conducted. Out of 145 patients, 49 (33.8%) were reclassified into a new stage, 42 (85.7% of reclassified cases) being allocated to a lower and seven (14.3%) being assigned to a higher stage. Most of the patients switched from stage IIB to IIA (n=31, 63.3%). The application of the new TNM-7 staging system resulted in a more accurate stratification of five-year survival curves. The newly revised TNM classification for lung cancer appears to be superior in defining different prognostic groups for this cohort and should lead to an improvement in stage specific tumor therapy.

Incidence, aetiology, diagnosis and treatment of round lesions in the lungs were analysed in 64 patients after lung transplantation (33 men, 31 women; mean age 45 [21-68] years; postoperative survival > 2 weeks). These lesions were found in 8 patients 1-10 months (median of 5.8 months) after the transplantation, singly in two, multiple in six. In six patients it was an incidental finding, further elucidated by computed tomography or fine-needle biopsy. The aetiology varied from B-cell "lymphoma" (posttransplant lymphoproliferative disorder-PTLD) in three patients, aspergilloma in two, and bacterial abscess in one. Two patients died of septicaemia (Aspergillus; Pseudomonas aeruginosa/Staphylococcus aureus), while four had a full remission. The solitary lesions disappeared without specific treatment in 2-3 weeks. If round lesions are noted after lung transplantation, rapid histological and microbiological diagnosis and aggressive treatment are necessary to combat an otherwise high death-rate. PTLD and infection (bacterial or mycotic) are the most frequent causes.

The significance of cytomegalovirus (CMV) infection after lung transplantation was investigated in 20 patients (ten women and ten men; mean age 46 [21-67] years). Indications for transplantation were emphysema (n = 6), cystic fibrosis (n = 2), primary pulmonary hypertension (n = 2), pulmonary fibrosis (n = 5), obliterating bronchiolitis (n = 2), cystic lung (n = 2) and bronchiectasis (n = 1). Incidence, diagnostic parameters (serology, virus isolation and histology) and efficacy of prophylactic and therapeutic measures were recorded. 16 of the 20 patients developed a CMV infection, which in 12 was clinically significant. CMV pneumonia developed in two patients, proving fatal in one. The infection occurred a median of 47 (17-200) days after the transplantation. Administration of Ganciclovir (5 mg/kg twice daily intravenously) brought about remission of symptoms in all but one of the patients and improved the clinical parameters.--This experience demonstrates that regular monitoring of the patients for possible CMV infection and its early therapy can achieve a low death rate.

Objective: The objective of this study is to establish clinical evidence that the p53 genotype can serve as a predictive marker for response to cisplatin-based induction therapy.Methods: Patients with advanced non-small cell lung cancer who had received neoadjuvant chemotherapy in the context of a prospective phase II trial were analyzed for the p53 genotype of their tumors. Response to induction therapy was then correlated to the p53 genotype as assessed by complete direct DNA sequencing. Patients had received 3 cycles of cisplatin and etoposide, and 1 cycle of simultaneous radiochemotherapy. All 3 treatment components mediate their cytotoxic effect through induction of apoptosis, which is suggested to require an intact p53 gene. In addition, the results from a previously published hypothesis-finding study are updated to demonstrate the consistency of clinical results and summarize currently available clinical evidence.Results: In the phase II trial, 35 patients underwent resection after induction chemotherapy, allowing a pathohistologic response assessment. The presence of a mutant p53 genotype was highly indicative of resistance to induction chemotherapy (P < .002). The sensitivity of a mutant p53 genotype to identify nonresponders was 94% (71.3-99.9 confidence interval). A normal p53 gene was significantly associated with radical resection (P < .004) and survival advantage (P = .02).Conclusion: This is the second clinical evaluation demonstrating a significant relation between p53 genotype and response to induction therapy in non-small cell lung cancer. We conclude that the p53 genotype should be evaluated as a predictive marker for response to induction therapy in prospective randomized protocols.

Postoperative einseitige Rekurrensparesen („unilateral recurrent laryngeal nerve paralysis“, URLNP) mit insuffizientem Glottisschluss können durch Dysphonie, Dysphagie und Störung der Atemstromkontrolle das Allgemeinbefinden beeinträchtigen. Ziel der interdisziplinären prospektiven Studie war es, die Lebensqualität von thoraxchirurgischen Patienten mit URLNP im Vergleich zu Patienten ohne Rekurrensschädigung zu beurteilen.

BACKGROUND: The prognosis of lung tumors is determined by histology and staging (nodal status). The most common tumor is non-small cell lung carcinoma (NSCLC) with a 5-year survival rate of 67 % (stage IA) to <5 % (stage IV). METHODS: By reviewing the literature guidelines for diagnosis and treatment of non-small cell lung cancer and neurendocrine tumors are presented. RESULTS: Functional operability provided, (bi)lobectomy or pneumonectomy with mediastinal lymph node dissection are the standard procedures. In case of positive mediastinal lymph nodes (stage IIIA/IIIB) induction chemo(radio)therapy is indicated. Cervical mediastinoscopy is performed in patients with enlarged mediastinal nodes (CT >1 cm), especially in PET-positive cases. Adjuvant chemotherapy is used in clinical trials. Small-cell lung cancer (SCLC, neuroendocrine tumor grade III) has a poor prognosis, and is treated with chemotherapy; resection may be performed in early stages. Neuroendocrine tumors grade I (typical carcinoid) are resected by segmentectomy, lobectomy, or bronchoplastic resection. Neuroendocrine tumors grade II (atypical carcinoids) are treated like NSCLC. CONCLUSIONS: The incidence of lung cancer is decreased by tobacco control, and the chances of survival are improved by early detection and multimodality regimens.

BACKGROUND:Postoperative unilateral vocal cord paralysis (URLNP) may lead to a lower quality of life due to dysphonia, dysphagia, and reduced breathing control. The aim of this study was to evaluate quality of life in a group of patients with URLNP compared to a group without URLNP.PATIENTS AND METHODS:Laryngoscopically, 379 patients were examined before and after thoracic surgery. Of the group with permanent URLNP (n=14), nine patients were compared to ten without URLNP regarding voice function and quality of life using selected European Organization for Research and Treatment of Cancer questionnaires (QLQ-C30, H&N35, OES18, and LC13) and the voice dysfunction index by Nawka.RESULTS:Patients with URLNP reported more voice problems and less effective coughing. Further, they had a reduced of quality of life.CONCLUSION:We recommend early diagnosis of URLNP and therapy management by routine laryngoscopic examinations following thoracic surgery.

Few data on the influence of vessel invasion on the progression of neuroendocrine lung tumors are available. Because of the lack of specific markers, previous studies could not reliably discriminate lymphatic and blood vessels. By immunostaining for podoplanin, specific for lymphatic endothelium, and CD34 antigen, we assessed lymphatic and blood vessel invasion in 120 tissue specimens of patients with neuroendocrine lung tumors. Lymphovascular invasion was correlated with clinicopathologic parameters, and its prognostic relevance was evaluated. Lymphatic vessels were identified exclusively at the tumor invasion front, whereas blood capillaries were also seen within tumors. Lymphatic vessel as well as lymphatic and blood vessel invasion was prevalent in patients with high-grade neuroendocrine tumors and advanced tumor stages, closely associated with lymph node metastases (P<0.0001). In univariate analysis, these two invasion types correlated with decreased disease-free survival (both P<0.0001), whereas blood vessel invasion alone did not. In multivariate analysis, only tumor grade and lymph node status remained statistically significant factors for prognosis (P = 0.016 and P<0.0001). Our results suggest that evaluation of lymphatic vessel invasion is important in neuroendocrine lung tumors serving as a prognostic parameter for disease-free survival.

Objective: To compare survival of patients with isolated synchronous and metachronous brain metastases from non-small cell lung cancer (NSCLC) after combined surgical treatment. Methods: A total of 991 patients underwent surgical resection of primary NSCLC between January 1994 and November 1999. Out of these, 32 patients (21 males and 11 females) were further treated for isolated brain metastases. In a retrospective survey, the outcome of patients with either synchronous (group 1, n = 16) or metachronous (group 2, n = 16) brain metastases was evaluated. Five patients out of each group received either adjuvant or neo-adjuvant chemotherapy. Data analysis includes descriptive statistics, Wilcoxon test, Kaplan-Meier method and Cox's proportional hazards model. Results: There was no significant difference in local tumour stage and histology of the primary turnout between both groups. Median of the disease free interval (DFI) after primary lung surgery (group 2) was 10 months, range 3-60 months. Median survival after lung surgery was 8.5 months in group 1 and 16.4 months in group 2 (P = 0.094). Median survival after cerebral procedures was 9.3 and 6.2 months, respectively (P = 0.127). Estimated survival rates by Kaplan-Meier method after cerebral procedures operation in group 1 were 37.5% at 1 year, 25.0% at 2 years and 18.8% at 5 years; in group 2 estimated survival rates were 31.3% at 1 year, 15.6% at 2 years and 0% at 5 years (P = 0.148). Calculated survival rates after lung surgery were identical in group 1; in group 2 survival rates were 62.5, 43.8 and 18.8% at 1, 2 and 5 years, respectively (P = 0.101). In the univariate model, none of the following variables had effect on survival: sex, age, T stage of the turnout, nodal status, timing of metastatic lesions, number of cerebral metastases, complete resection of primary tumour and histological type. Multivariate analysis did not reveal any risk factor, which significantly predicted survival. DFI did not correlate with survival of patients in group 2. Conclusions: Once isolated synchronous or metachronous brain metastases from NSCLC have developed, there is no difference in prognosis after combined surgery between analysed groups. This questions the value of lung resection in patients with isolated synchronous brain metastases. (C) 2004 Elsevier B.V. All rights reserved.

HYPOTHESISIndividual, group, and organizational factors influence the professional satisfaction of women surgeons in Austria.DESIGNSurvey on professional and private issues sent out by mail in 2000 and 2001.SETTINGWomen surgeons working in hospitals and/or in private practices and those who were retired or on maternity leave.PARTICIPANTSAll 351 Austrian women surgeons of all core surgical specialties (general, trauma, pediatric, plastic, thoracic, and cardiovascular), certified or in training, were addressed.MAIN OUTCOME MEASURESProportional odds regression models were used to correlate professional satisfaction with objectively measurable prognostic factors such as age, surgical subspecialty, status of training, type of hospital, location of work (federal states vs the capital), status of activity (active vs on maternity leave), profession of private partner, number of children, and subjectively assessed prognostic factors such as operative volume and departmental organization.RESULTSThe response rate was 58.7% (206/351). One hundred eighty-seven surgeons-active or on maternity leave-were included in the analysis. Higher satisfaction was reported by active surgeons in subspecialties, certified surgeons, comparatively younger and older surgeons, surgeons working in hospitals outside the capital, and surgeons with a physician as a partner. When entering subjectively assessed variables into the model, the quality of departmental organization and operative volume (P<.001), as well as the status of activity (P<.001), had the strongest effect.CONCLUSIONSWomen surgeons' professional satisfaction highly depends on departmental organization and status of activity. Inadequate leadership, low operative volume, and being on maternity leave have a negative effect on job satisfaction. Private factors seem to be of little influence. Optimal departmental organization would help women to reconcile their professional and their private lives.

7297 Background: Adjuvant chemotherapy treatment for early stage NSCLC patients is not yet standard practice. The aim of the present trial is to compare the activity, safety, and quality of life effects of adjuvant docetaxel plus cisplatin versus observation only. Methods: Patients with completely resected stage I-II NSCLC, no prior chemotherapy and/or radiotherapy, and a WHO performance status of ≤2, were randomized to docetaxel plus cisplatin, 75 mg/m2 each, both on day 1, every 21 days for 6 cycles (arm A) versus observation only (arm B). Time-to-event endpoints were calculated using the Kaplan-Meier method and compared between arms using the log-rank test. The incidence of grade 3 and 4 toxicity was compared using Pearson's chi-squared test. The primary objective is disease-free survival; secondary objectives are overall survival, treatment-related toxicity, and quality of life. Planned recruitment is 80 patients. Results: From December 2001 to December 2003, 30 patients were randomized to each arm. There were 22 males and 8 females in each arm. Arm A: 17 patients had stage I and 13 patients stage II disease; arm B: 18 patients had stage I and 12 stage II disease. Mean age (range) arm A was 58.1 years (44 – 77) and arm B was 56.9 (46 – 72). An interim analysis of toxicities in the treatment arm after inclusion of 40 patients (20 arm A; 20 arm B) revealed that 64% (13 of 20) experienced leucopenia grade 3 or 4; 43% (9 of 20) peripheral neurotoxicity 2 or 3; and 50% (10 of 20) experienced fatigue grade 2 or 3. Furthermore a significant decrease in patients' quality of life was noted during the 5th and 6th chemotherapy cycles. Based on this analysis, a protocol amendment reduced the total number of cycles to 4, with a further 2 cycles administered at investigators' discretion. Current relapse rates and time to progression will be reported at the meeting. Conclusions: The administration of 4 cycles of docetaxel plus cisplatin is feasible in the adjuvant setting for patients with stage I/II NSCLC. No significant financial relationships to disclose.