Lymph Node Log-Odds Ratio Accurately Defines Prognosis in Resectable Non-Small Cell Lung Cancer.

OBJECTIVES: The ratio of positive and resected lymph nodes (LN ratio) has been shown to be prognostic in non-small cell lung cancer (NSCLC). Contrary to the LN ratio, calculating the LN log-odds ratio (LN-LOR) additionally considers the total number of resected lymph nodes. We aim to evaluate LN-LOR between positive and resected lymph nodes as a prognostic factor in operable NSCLC. METHODS: Patients with NSCLC who underwent curative intent lobectomy treated at two high-volume centers were retrospectively studied. LN-LOR was dichotomized according to impact on OS and further combined with N descriptors and correlated with clinical variables and survival. RESULTS: 944 patients were included. Cut-off analysis revealed that an LN-LOR of -0.34 significantly discriminated patients according to OS (p < 0.001, chi-squared test 41.26). When combined with N1 and N2 descriptors, LN-LOR low risk (median OS not reached and 83 months) and LN-LOR high-risk patients (median OS 50 and 59 months) had similar survival irrespective of the anatomical location of the positive lymph nodes. Multivariable Cox regression analysis revealed that age (HR 1.02, 95% CI 1.001-1.032), sex (male, HR 1.65, 95% CI 1.25-2.19), histological subtype (HR 2.11, 95% CI 1.35-3.29), pathological stage (HR 1.23, 95% CI 1.01-1.45) and LN-LOR risk groups (low risk, HR 0.48, 95% CI 0.32-0.72) were independent prognostic factors for OS. CONCLUSIONS: This retrospective two-center analysis shows that LN-LOR is significantly associated with OS in resectable NSCLC and might better reflect the biological behavior of the disease, regardless of anatomical lymph node locations. This finding may additionally support the value of extensive LN dissection.

Results of the Austrian National Lung Cancer Audit.

OBJECTIVES: The Austrian Lung Cancer Audit (ALCA) is a pilot study to evaluate clinical and organizational factors related to lung cancer care across Austria. MATERIALS AND METHODS: The ALCA is a prospective, observational, noninterventional cohort study conducted in 17 departments in Austria between September 2013 and March 2015. Participating departments were selected based on an annual case load of >50 patients with lung cancer. RESULTS: The ALCA included 745 patients, representing 50.5% of all newly diagnosed cancer cases during that time period. In 75.8% of patients, diagnosis was based on histology, and in 24.2% on cytology; 83.1% had non-small-cell lung cancer, 16.9% small-cell lung cancer; and only 4.6% had to be classified as not otherwise specified cancers. The median time elapsed between first presentation at hospital and diagnosis was 8 days (interquartile range [IQR]: 4-15; range: 0-132); between diagnosis and start of treatment it was 15 days for chemotherapy (IQR: 9-27; range: 0-83), 21 days (IQR: 10-35; range: 0-69) for radiotherapy, and 24 days (IQR: 11-36; range: 0-138) for surgery, respectively. In 150 patients undergoing surgical treatment, only 3 (2.0%; n = 147, 3 missings) were seen with postoperative restaging indicating unjustified surgery. One-year follow-up data were available for 723 patients, indicating excellent 49.8% survival; however, a wide range of survival between departments (range: 37.8-66.7) was seen. CONCLUSIONS: The ALCA conducted in high case load departments indicated management of lung cancer in accordance with international guidelines, and overall excellent 1-year survival.

Transcutaneous Stimulation of Auricular Branch of the Vagus Nerve Attenuates the Acute Inflammatory Response After Lung Lobectomy.

OBJECTIVES: Systemic inflammation is a potentially debilitating complication of thoracic surgeries with significant physical and economic morbidity. There is compelling evidence for the role of the central nervous system in regulating inflammatory processes through humoral mechanisms. Activation of the afferent vagus nerve by cytokines triggers anti-inflammatory responses. Peripheral electrical stimulation of the vagus nerve in vivo during lethal endotoxemia in rats inhibited tumor necrosis factor synthesis and prevented shock development. However, the vagal regulatory role of systemic inflammation after lung lobectomy is unknown. METHODS: One hundred patients who underwent lobectomy via thoracotomy were recruited and equally randomized to treated group or controls. Intermittent stimulation of the auricular branch of vagus nerve in the triangular fossa was applied in the treated group using neurostimulator V (Ducest®, Germany), starting 24 h preoperatively and continued till the 4th postoperative day (POD). Inflammatory interleukins (IL) were analyzed using ELISA preoperatively, on the 1st and 4th POD. RESULTS: On the 1st POD, patients who underwent neurostimulation had reduced serum concentrations of CRP (p = 0.01), IL6 (p = 0.02) but elevated IL10 (p = 0.03) versus controls. On the 4th POD, serum concentrations of CRP, IL6 and IL10 were similar in both groups. Moreover, the treated group was associated with lower incidence of pneumonia (p = 0.04) and shorter hospitalization time (p = 0.04) versus controls. CONCLUSIONS: Modulations in the brain stem caused by noninvasive transcutaneous stimulation of the vagus nerve after lung lobectomy attenuate the acute postsurgical inflammatory response by the regulation of IL6 and IL10, resulting in  reduced incidence of postoperative pneumonia and short hospitalization time. CLINICAL TRIAL REGISTRY NUMBER: NCT03204968.

Canine scent detection for the diagnosis of lung cancer in a screening-like situation.

The prognosis in lung cancer depends largely on early stage detection, and thus new screening methods are attracting increasing attention. Canine scent detection has shown promising results in lung cancer detection, but there has only been one previous study that reproduces a screening-like situation. Here breath samples were collected from 122 patients at risk for lung cancer (smokers and ex-smokers); 29 of the subjects had confirmed diagnosis of lung cancer but had not yet been treated and 93 subjects had no signs or symptoms of lung cancer at the time of inclusion. The breath samples were presented to a trained sniffer dog squadron in a double-blind manner. A rigid scientific protocol was used with respect to earlier canine scent detection studies, with one difference: instead of offering one in five positive samples to the dogs, we offered a random number of positive samples (zero to five). The final positive and negative predictive values of 30.9% and 84.0%, respectively, were rather low compared to other studies. The results differed from those of previous studies, indicating that canine scent detection might not be as powerful as is looked for in real screening situations. One main reason for the rather poor performance in our setting might be the higher stress from the lack of positive responses for dogs and handlers.

The anticipation and management of air leaks and residual spaces post lung resection.

The incidence of any kind of air leaks after lung resections is reportedly around 50% of patients. The majority of these leaks doesn't require any specific intervention and ceases within a few hours or days. The recent literature defines a prolonged air leak (PAL) as an air leak lasting beyond postoperative day 5. PAL is associated with a generally worse outcome with a more complicated postoperative course anxd prolonged hospital stay and increased costs. Some authors therefore consider any PAL as surgical complication. PAL is the most prevalent postoperative complication following lung resection and the most important determinant of postoperative length of hospital stay. A low predicted postoperative forced expiratory volume in 1 second (ppoFEV1) and upper lobe disease have been identified as significant risk factors involved in developing air leaks. Infectious conditions have also been reported to increase the risk of PAL. In contrast to the problem of PAL, there is only limited information from the literature regarding apical spaces after lung resection, probably because this common finding rarely leads to clinical consequences. This article addresses the pathogenesis of PAL and apical spaces, their prediction, prevention and treatment with a special focus on surgery for infectious conditions. Different predictive models to identify patients at higher risk for the development of PAL are provided. The discussion of surgical treatment options includes the use of pneumoperitoneum, blood patch, intrabronchial valves (IBV) and the flutter valve, and addresses the old question, whether or not to apply suction to chest tubes. The discussed prophylactic armentarium comprises of pleural tenting, prophylactic intraoperative pneumoperitoneum, sealing of the lung, buttressing of staple lines, capitonnage after resection of hydatid cysts, and plastic surgical options.

Fleece bound sealing prevents pleural adhesions.

This study assessed the value of haemostatic fleece (HF) in prevention of pleural adhesions in an experimental animal model. Forty rats were randomly assigned to four equal groups and underwent bilateral thoracotomy. In Group 1 standardized defects of 5 mm were generated in the visceral and the opposite parietal pleura without further coverage. In Group 2 a 5-mm piece of HF (TachoSil) was applied onto the intact pleura. In Group 3 a standardized pleural defect was completely covered by HF. The same kind of defect was only partially covered by HF in group 4 animals. Autopsy at 6 weeks (n=5, each group) revealed the fleece widely unchanged and covered by a smooth serous membrane. After 12 weeks (n=5, each group) the fleece had been completely resorbed. Histological studies revealed the area of the defect covered by regular mesothelium. In all animals pleural adhesions were detected only in the area without fleece coverage. In this experimental model HF prevented the development of pleural adhesions. This property may have clinical impact in patients with some probability of re-thoracotomy enabling to reduce the risk of pleural adhesions significantly.

Reconstitution of blood supply of the denuded bronchial stump.

BACKGROUND: Our aim was to study the process of microcirculatory reconstitution in the bronchial stump after pneumonectomy. METHODS: Eighteen juvenile pigs (median weight 40.6 kg) were randomly assigned to three groups. In all animals left pneumonectomy was performed and the stapled bronchial stump (median length 3.8 cm) carefully denuded. Group I animals received coverage of the stump by intercostal flap. In group II, the stump was covered with TachoComb, an impermeable hemostatic fleece; and group III served as a control without any coverage of the stump. Animals were sacrificed at day 14 after surgery. Vascular density was evaluated in serial histologic sections at multiple levels stained with CD-31 antibody. One-way analysis of variance and the Wilcoxon test were used for data analysis. RESULTS: At autopsy, stumps of group III animals were totally covered by adjacent mediastinal structures. In group I, intercostal flaps were viable and completely healed to the bronchial stumps. There were no signs of infection or stump insufficiency in these groups. In all group II animals, empyema developed, and stumps were found necrotic at macroscopic and histologic evaluation. Statistical analysis revealed significantly lower vascular density of mature vessels in the area of the bronchial stump in group II compared with both other groups. CONCLUSIONS: Reconstitution of microcirculation of the denuded bronchial stump after pneumonectomy takes place in a centripetal way from adjacent viable tissue. Hence, the purpose of covering the bronchial stump is the improvement of blood supply rather than mechanical reinforcement.

Successful treatment of an aortoesophageal fistula after emergency endovascular thoracic aortic stent-graft placement.

We report the case of a 57-year-old man who underwent emergency stent-graft placement in August 2003 due to a contained rupture of a distal descending aortic aneurysm. After 1 month the patient was readmitted with chest pain as well as swallowing disorders. A computed tomographic scan revealed a fistula between the distal esophagus and the excluded aneurysm sac. The patient was treated by an esophagectomy, a cervical esophagostomy, as well as a feeding gastrostomy. The infectious parietal thrombus was partially debrided and the aneurysm sac was filled with vancomycin. After 3 months continuity was reinstalled with a pedicled isoperistaltic transverse colonic conduit. The patient recovered uneventfully. At a 3 month follow-up, he showed no signs of infection. However, he is still being treated with antibiotic therapy of ciprofloxacin for a minimum of 1 year.

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.

Lung wedge resection improves outcome in stage I primary spontaneous pneumothorax.

BACKGROUND: To evaluate the role of apical lung wedge resection in patients with recurrent primary spontaneous pneumothorax with no endoscopic abnormalities at surgery as compared with simple apical pleurectomy. METHODS: We performed a retrospective analysis on 126 consecutive video-assisted thoracoscopic surgery (VATS) procedures in 113 patients treated for stage I recurrent PSP between January 1994 and December 2001. Two surgical strategies were applied: simple apical pleurectomy (57 procedures, 45.2%: group A) and apical pleurectomy together with an apical lung wedge resection (69 procedures, 54.8%: group B). RESULTS: Mean duration of chest tubes was 1.4 days (range, 1 to 7), mean hospital stay was 2.4 days. Three patients (2.4%) required redo VATS, 2 in group A (3.5%) for persistent air leak and 1 (1.4%) in group B for apical hematothorax. Mean follow-up was 38.7 months. Overall recurrence rate was 3.2%. Four patients in group A (7%) experienced recurrent ipsilateral pneumothoraces 4 to 73 weeks (mean, 30.2) after surgery. No recurrences were observed in group B (p = 0.009). CONCLUSIONS: In this selected group of patients without endoscopical abnormalities, VATS offers low recurrence rates. However, these data suggest that apical pleurectomy should be accompanied by apical lung wedge resection even for this favorable category of patients.

Sealing of the mediastinum with a local hemostyptic agent reduces chest tube duration after complete mediastinal lymph node dissection for stage I and II non-small cell lung carcinoma.

BACKGROUND: We assessed the impact of coverage of the mediastinum with a local hemostyptic agent as well as the impact of perioperative thromboembolic prophylaxis on cumulative chest drain volume and on the duration of chest tubes after surgical resection with complete mediastinal lymph node dissection for stage I or II non-small cell lung cancer. METHODS: In a prospective, randomized two-by-two factorial design, 80 patients with clinical stage I or II non-small cell lung cancer were allocated to one of two surgical therapy arms (TachoComb or conventional surgical hemostasis) and one of two anticoagulation arms (enoxaparin 4,000 IU or dalteparin 5,000 IU). Primary end point was cumulative chest drain volume; secondary end point was duration of chest tubes. Additionally clinical data were obtained. RESULTS: Comparison of the surgical arms revealed significantly lower cumulative chest drain volumes and thereby an earlier chest tube removal in the TachoComb group (p = 0.045). With regard to thromboembolic prophylaxis, a significantly earlier chest tube removal was found for patients treated with dalteparin (p = 0.039). Analysis of the interaction of surgical and anticoagulation treatment revealed the combined use of TachoComb and dalteparin was superior to other combinations (cumulative chest drain volumes 498 +/- 67 mL versus 1,000 +/- 88 mL, 924 +/- 87 mL, and 895 +/- 118 mL; p = 0.008; mean duration of chest tubes 1.78 +/- 0.15 days versus 2.96 +/- 0.21 days, 2.93 +/- 0.17 days, and 3.06 +/- 0.27 days; p = 0.019). CONCLUSIONS: The combined use of a local hemostyptic agent and dalteparin seems superior as compared with other regimens of hemostasis and thromboembolic prophylaxis in patients undergoing surgical resection and complete mediastinal lymph node dissection for stage I and II non-small cell lung cancer with regard to cumulative chest drain volume as well as duration of chest tubes.

Efficacy and safety of topical application of human fibrinogen/thrombin-coated collagen patch (TachoComb) for treatment of air leakage after standard lobectomy.

OBJECTIVES: Persisting air leakage after pulmonary resection remains a significant problem. The aim of the study was to evaluate the incidence of air leakage after standard lobectomy and test the efficacy and safety of TachoComb (TC). METHODS: A total of 189 patients undergoing lobectomy were enrolled in a multi-centre, open, randomised, and prospective study to test the efficacy and safety of TachoComb (TC) for air leakage treatment. Air leakage was assessed by water submersion test, and scored as grades 0 if no, 1 if countable, 2 if a stream of and 3 if coalescent bubbles have been observed. Any sites with grade 3 air leakage received further stapling or limited suturing until grade 0, 1 or 2 was obtained. Treatment of air leakage was done with TC or suturing according to randomisation. Air leakage was assessed by further submersion tests. Postoperative air leakage was assessed using the Pleur-Evac system. RESULTS: Overall incidence of air leakage 48+/-6 h after surgery was 34% for TC and 37% for standard treatment (P=0.76). The reduction of intra-operative air leak intensity in the subgroup with grades 1-2 was significantly higher for the TC group (P=0.015). Postoperative air leakage intensity in the subgroup with air leakage grades 1-2 was lower for TC than standard treatment (P=0.047). The mean duration of postoperative air leakage in the subgroup with grades 1-2 was shorter for the TC group than for standard treatment, i.e. 1.9+/-1.4 vs. 2.7+/-2.2 days (P=0.015). CONCLUSIONS: TC could be proven as well-tolerated and safe. In the subgroup of patients with established air leakage, TC showed superior potential in reduction of intra-operative air leakage as well as in reduction of intensity and duration of postoperative air leakage.