Biochip-based detection of KRAS mutation in non-small cell lung cancer.

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.

Prognostic value of lymphatic and blood vessel invasion in neuroendocrine tumors of the lung.

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.

Professional satisfaction of women in surgery: results of a national study.

HYPOTHESIS: Individual, group, and organizational factors influence the professional satisfaction of women surgeons in Austria. DESIGN: Survey on professional and private issues sent out by mail in 2000 and 2001. SETTING: Women surgeons working in hospitals and/or in private practices and those who were retired or on maternity leave. PARTICIPANTS: All 351 Austrian women surgeons of all core surgical specialties (general, trauma, pediatric, plastic, thoracic, and cardiovascular), certified or in training, were addressed. MAIN OUTCOME MEASURES: Proportional 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. RESULTS: The 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. CONCLUSIONS: Women 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.

External vocal fold medialization in patients with recurrent nerve paralysis following cardiothoracic surgery.

OBJECTIVES: Recurrent laryngeal nerve injury is a possible complication following cardiothoracic surgery. Due to insufficient glottal closure, dysphonia and dysphagia with aspiration may occur. The purpose of the study was to outline the effect of vocal fold medialization thyroplasty on voice, swallowing and breathing impairments. METHODS: Between 1999 and 2001, medialization thyroplasty using the titanium implant (TVFMI) according to Friedrich was performed in 14 patients with postoperative left-sided recurrent nerve paralysis (five female and nine male patients, mean age 64 years) by an external approach. Previous surgical procedures comprised six lobectomies (combined with resection and replacement of the subclavian artery in one case), two pneumonectomies, one resection of a schwannoma in the aortopulmonary window, two replacements of the descending aorta, one aortocoronary bypass procedure (with LIMA), and two esophageal resections using Akiyama technique, respectively. Before and after thyroplasty, the patients underwent an otolaryngological/phoniatric examination including videostroboscopy, voice sound analysis, voice range profile measurement, pulmonary function testing, and in selected cases videofluoroscopy of swallowing. RESULTS: Following thyroplasty, all patients reported on subjective improvement of voice, swallowing and breathing functions. Videostroboscopy revealed an improved glottal closure (six complete, six with posterior gap). All voice related parameters (e.g. roughness, breathiness, hoarseness, maximum sound pressure levels of the singing and shouting voices) were significantly improved. CONCLUSIONS: Due to potential risk of recurrent nerve alteration in left-sided intrathoracic procedures, a preoperative and postoperative laryngoscopic examination is recommended. The external medialization of the vocal folds can be regarded as an excellent method for improvement of voice, swallowing and breathing, in particular, when the quality of life is impaired due to persistent recurrent nerve paralysis.

Prognosis of patients with non-small cell lung cancer with isolated brain metastases undergoing combined surgical treatment.

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 tumour 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 tumour, 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.

[National Health Care Plan for Austria: development and critical considerations]. / Perspektiven eines nationalen Gesundheitsplanes für Osterreich.

Compared to health services in other countries in the world, the Austrian health care system works relatively well. At the moment it is shaped and dominated by various structures, decision makers and financial backers, which means that it does not work as well as it could under ideal circumstances. The government now wants to develop a national health care plan which, in a concerted action by all those involved in the health service, shall guarantee superior medical care while at the same time taking into account economic aspects. This paper takes a critical look at the idea of an Austrian health care plan from a clinical point of view.

Effects of reclassification from the TNM-6 into the TNM-7 staging system in bronchoplastic resection for non-small cell lung cancer.

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.

Growing clinical evidence for the interaction of the p53 genotype and response to induction chemotherapy in advanced non-small cell lung cancer.

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.