Repeated lung volume reduction surgery is successful in selected patients.

OBJECTIVES: Lung volume reduction surgery (LVRS) improves dyspnoea, quality of life and may even prolong survival in carefully selected patients with end-stage emphysema. The benefit may be sustained for several years and vanishes with the natural progression of the disease. Data on repeated surgical treatment of emphysema are scarce. The aim of this study was to evaluate the safety, effects and outcomes of repeated LVRS (Re-LVRS) in patients no longer benefiting from their initial LVRS. METHODS: Between June 2002 and December 2013, 22 patients (9 females) with advanced emphysema underwent Re-LVRS at a median of 60 months (25-196) after their initial LVRS. While initial LVRS was performed thoracoscopically as a bilateral procedure, Re-LVRS was performed unilaterally by a video-assisted thoracoscopic technique in 19 patients and, due to adhesions, by thoracotomy in 3 patients. Pulmonary function test (PFT) was performed at 3 and 12 months postoperatively. RESULTS: Lung function at Re-LVRS was similar to that prior to the first LVRS. The 90-day mortality rate was 0%. The first patient died 15 months postoperatively. The median hospitalization time after Re-LVRS was significantly longer compared with the initial LVRS [14 days, interquartile range (IQR): 11-19, vs 9 days, IQR: 8-14; P = 0.017]. The most frequent complication was prolonged air leak with a median drainage time of 11 days (IQR: 6-13); reoperations due to persistent air leak were necessary in 7 patients (32%). Five patients (23%) had no complications. Lung function and Medical Research Council (MRC) score improved significantly for up to 12 months after Re-LVRS, with results similar to those after initial bilateral LVRS. The average increase in the forced expiratory volume in 1 s (FEV1) was 25% (a 7% increase over the predicted value or 0.18 l) at 3 months, and the mean reduction in hyperinflation, assessed by relative decrease in RV/TLC (residual volume/total lung capacity), was 12% at 3 months (a decrease of 8% in absolute ratios). The mean MRC breathlessness score decreased significantly after 3 months (from 3.7 to 2.2). CONCLUSIONS: Re-LVRS can be performed successfully in carefully selected patients as a palliative treatment. It may be performed as a bridge to transplantation or in patients with newly diagnosed intrapulmonary nodules or during elective cardiac surgery. Morbidity is acceptable and outcomes may be satisfactory with significantly improved lung function and reduced dyspnoea for at least 12 months postoperatively.

First clinical results of (D)-18F-Fluoromethyltyrosine (BAY 86-9596) PET/CT in patients with non-small cell lung cancer and head and neck squamous cell carcinoma.

UNLABELLED: (D)-(18)F-fluoromethyltyrosine (d-(18)F-FMT), or BAY 86-9596, is a novel (18)F-labeled tyrosine derivative rapidly transported by the l-amino acid transporter (LAT-1), with a faster blood pool clearance than the corresponding l-isomer. The aim of this study was to demonstrate the feasibility of tumor detection in patients with non-small cell lung cancer (NSCLC) or head and neck squamous cell cancer (HNSCC) compared with inflammatory and physiologic tissues in direct comparison to (18)F-FDG. METHODS: 18 patients with biopsy-proven NSCLC (n = 10) or HNSCC (n = 8) were included in this Institutional Review Board-approved, prospective multicenter study. All patients underwent (18)F-FDG PET/CT scans within 21 d before d-(18)F-FMT PET/CT. For all patients, safety and outcome data were assessed. RESULTS: No adverse reactions were observed related to d-(18)F-FMT. Fifty-two lesions were (18)F-FDG-positive, and 42 of those were malignant (34 histologically proven and 8 with clinical reference). Thirty-two of the 42 malignant lesions were also d-(18)F-FMT-positive, and 10 lesions had no tracer uptake above the level of the blood pool. Overall there were 34 true-positive, 8 true-negative, 10 false-negative, and only 2 false-positive lesions for d-(18)F-FMT, whereas (18)F-FDG was true-positive in 42 lesions, with 10 false-positive and only 2 false-negative, resulting in a lesion-based detection rate for d-(18)F-FMT and (18)F-FDG of 77% and 95%, respectively, with an accuracy of 78% for both tracers. A high d-(18)F-FMT tumor-to-blood pool ratio had a negative correlation with overall survival (P = 0.050), whereas the (18)F-FDG tumor-to-blood pool ratio did not correlate with overall survival. CONCLUSION: d-(18)F-FMT imaging in patients with NSCLC and HNSCC is safe and feasible. The presented preliminary results suggest a lower sensitivity but higher specificity for d-(18)F-FMT over (18)F-FDG, since there is no d-(18)F-FMT uptake in inflammation. This increased specificity may be particularly beneficial in areas with endemic granulomatous disease and may improve clinical management. Further clinical investigations are needed to determine its clinical value and relevance for the prediction of survival prognosis.

Sleeve resections with unprotected bronchial anastomoses are safe even after neoadjuvant therapy.

OBJECTIVES: Sleeve resection is the operation of choice in patients with centrally located tumours, in order to avoid a pneumonectomy. Most surgeons protect the bronchial anastomoses with tissue to prevent insufficiencies. The purpose of this study is to report on outcome of unwrapped bronchial anastomoses, especially after neoadjuvant chemo- or chemoradiotherapy. METHODS: Between 2000 and 2010, 103 patients [59 years (range 16-80), 40 females] underwent bronchial sleeve resections without coverage of the anastomosis with a tissue flap. We retrospectively reviewed the data for morbidity, mortality and survival, especially with regard to the type of resection, neoadjuvant therapy and stage. RESULTS: Sleeve lobectomy was performed in 88, sleeve bilobectomy in 8, sleeve pneumonectomy in 4 and sleeve resection of the main bronchus in 3 patients. Twenty-seven patients had a combined vascular sleeve resection. Neoadjuvant chemotherapy was performed in 20 and radiochemotherapy in 5 patients. Non-small cell lung cancer (NSCLC) was present in 76 patients (squamous cell carcinoma in 44, adenocarcinoma in 24, large cell carcinoma in 6 and mixed cell in 2) and neuroendocrine tumour in 20 and other histological types in 7 patients. The pathologic tumour stage in NSCLC was stage I in 26, stage II in 26, stage IIIA in 16, stage IIIB in 7 and stage IV in 1 patient. There were no anastomotic complications, especially no fistulas. One patient developed narrowing of the intermediate bronchus without need for intervention. Twenty-four patients had early postoperative complications, including 11 surgery-related complications (air leakage, nerve injury, haemothorax or mediastinal emphysema). The 30-day mortality was 3% (one patient died due to heart failure and two with multiorgan failure). The 5-year survival rate was 63% in NSCLC patients and 86% in neuroendocrine tumour patients. CONCLUSIONS: Sleeve resection without wrapping the bronchial anastomoses with a tissue flap is safe even in patients who underwent neoadjuvant chemo- or chemoradiotherapy. Therefore, wrapping of the bronchial anastomoses is not routinely mandatory.

Induction of senescence markers after neo-adjuvant chemotherapy of malignant pleural mesothelioma and association with clinical outcome: an exploratory analysis.

The aim of this study was to assess the induction of senescence markers versus apoptosis pathways in malignant pleural mesothelioma (MPM) tumour samples before and after neo-adjuvant platinum-based chemotherapy and to investigate their relationship with clinical outcome. Specific senescence pathways were assessed by quantifying the expression of p21 and plasminogen activator inhibitor-1 (PAI-1) for the p21-p53 pathway, IGFBP7 for the IGF pathway and ALDH1A3 for the IFN pathway. p21 and PAI-1 expression were also assessed by immunohistochemistry. In addition, beta-galactosidase activity staining at pH 6.0 was performed. Apoptosis was determined by TUNEL assay. Clinical outcome was assessed by modified RECIST criteria, progression-free and overall survival. In a training set (n=9 patients) paired comparison demonstrated a significant increase in p21 (p<0.05), PAI-1 (p<0.01) and apoptosis (p<0.01) after neo-adjuvant chemotherapy. The patients with the highest increase in PAI-1 had stable disease, whilst patients with little change in senescence markers accompanied by a high increase in apoptosis had an objective response after chemotherapy. The hypothesis that stable disease might be associated with an increase in senescence markers was confirmed in a tissue microarray (n=26 patients) using p21 and PAI-1 immunohistochemistry as readouts. For patients where survival and time to progression data were available, increased PAI-1 levels were significantly associated with a worst outcome. Our results demonstrate induction of senescence markers by neo-adjuvant chemotherapy in a proportion of patients with MPM and its potential association with a poor outcome.

Pulmonary Kaposi's sarcoma after heart transplantation: a case report.

INTRODUCTION: Kaposi's sarcomas have been associated with different conditions of immunosuppression and are also known to be a typical complication of solid organ transplantations. CASE PRESENTATION: We report the case of a 65-year-old Turkish man with a history of heart transplantation 10 months ago who presented for clarification of his dyspnea. The patient had a known history of chronic obstructive pulmonary disease and a smoking history of 40 pack years. Radiologically, three progressively growing intra-pulmonary nodules were detected. The histology was diagnostic for a Kaposi's sarcoma. Visceral and especially primary intra-pulmonary Kaposi's sarcomas are very rare and have been described to have a rather unfavorable prognosis. CONCLUSIONS: Even with a history suggestive for conventional lung cancer, Kaposi's sarcomas should be considered in patients after transplantation of solid organs. It should be noted that in a minority of cases this tumor exists in the absence of the typical cutaneous lesions.

Lung volume reduction surgery in nonheterogeneous emphysema.

Patients with a homogeneous type of emphysema have been excluded a priori from LVRS in many centers because of the fear of removing parenchyma, which potentially contributes to gas exchange, and because the observation that heterogeneity of emphysema is a predictor of functional improvement. It is obvious that resection of functionless tissue, such as in heterogeneous emphysema with bullae, can be advised to the patient with a relative low risk. However, as the main positive effect of LVRS is its improvement on respiratory mechanics, it is not surprising that well-selected patients with homogeneous emphysema also benefit from surgery. Their selection has to be done cautiously. It is crucial to exclude patients with a very low functional reserve, such as with diffusing capacity below 20% predicted or with pulmonary hypertension, and with extreme parenchymal loss (vanished lungs) on CT from LVRS. Additionally, cofactors which may potentially interfere with a smooth postoperative course, such as previous recurrent infections, extensive scarring of the lungs, or previous surgery, have to be taken into consideration. When respecting these caveats, LVRS in patients with complete homogeneous emphysema provides a comparable symptomatic and almost the same functional improvement as in patients with heterogeneous emphysema. Although the perioperative mortality is low, patients with homogeneous emphysema have a slightly reduced long-term survival without lung transplantation compared with patients with heterogeneous emphysema. Based on our own experience, we conclude that LVRS can be recommended to selected symptomatic patients with advanced homogenous emphysema associated with severe hyperinflation, if diffusing capacity is not below 20% of predicted values and if the CT scan does not show aspects of vanished lungs.

Persistent benefit from lung volume reduction surgery in patients with homogeneous emphysema.

BACKGROUND: The purpose of this study was to evaluate whether favorable short-term results achieved by lung volume reduction surgery in selected patients with homogeneous emphysema would persist for longer periods. Their symptoms, lung function, and survival for several years were analyzed in comparison to patients with heterogeneous emphysema. METHODS: Two hundred fifty consecutive patients (105 women), mean (+/- standard deviation) age 64 +/- 8.4 years, with advanced emphysema underwent bilateral thoracoscopic lung volume reduction surgery. Forced expiratory volume in 1 second was 28% +/- 8% of predicted, 6-minute walking distance was 245 +/- 118 m, and Medical Research Council dyspnea score was 3.5 +/- 0.7. In 138 patients (55%) computed tomography revealed homogeneous emphysema (including 82 intermediate type) distribution and in 112 patients (45%) heterogeneous emphysema. Baseline characteristics were otherwise similar in the two groups that were prospectively observed for several years. RESULTS: Thirty-day mortality was 2.4%. Both groups revealed significant improvements 3 months after lung volume reduction surgery: in homogeneous emphysema, predicted forced expiratory volume in 1 second was 38% +/- 14% (35% improvement), 6-minute walk distance was 324 +/- 87 m, and dyspnea score was 1.8 +/- 0.9 (p < 0.05 all outcomes). Corresponding results in heterogeneous emphysema were 44% +/- 15% (61% improvement), 382 +/- 95 m, and 1.3 +/- 0.9 points (p < 0.05 versus baseline; not significant versus homogeneous). Median time until predicted forced expiratory volume in 1 second and 6-minute walk distance had returned to baseline was 36 months in both groups. One-year survival was similar in both groups. At 5 years, median survival without lung transplantation was 64% in the homogeneous and 73% in the heterogeneous group (Cox proportional hazard, 0.81; 95% confidence interval, 0.66 to 0.98; p = 0.03). CONCLUSIONS: In selected patients with homogeneous pulmonary emphysema, lung volume reduction surgery can be successfully performed with low perioperative mortality. Significant improvements in dyspnea, lung function, and exercise capacity are maintained for several years.

Imaging in early posttraumatic complex regional pain syndrome: a comparison of diagnostic methods.

OBJECTIVES: The complex regional pain syndrome type I (CRPS I) still is difficult to diagnose in posttraumatic patients. As CRPS I is a clinical diagnosis the characteristic symptoms have to be differentiated from normal posttraumatic states. Several diagnostic procedures are applied to facilitate an early diagnosis, although their value for diagnosing posttraumatic CRPS I is unclear. METHODS: One hundred fifty-eight consecutive patients with distal radial fracture were followed up for 16 weeks after trauma. To assess the diagnostic value of the commonly applied methods a detailed clinical examination was carried out 2, 8, and 16 weeks after trauma in conjunction with bilateral thermography, plain radiographs of the hand skeleton, three phase bone scans (TPBSs), and contrast-enhanced magnetic resonance imaging (MRI). All imaging procedures were assessed blinded. RESULTS: At the end of the observation period 18 patients (11%) were clinically identified as having CRPS I and 13 patients (8%) revealed an incomplete clinical picture which were defined as CRPS borderline cases. The sensitivity of all diagnostic procedures used was poor and decreased between the first and the last examinations (thermography: 45% to 29%; TPBS: 19% to 14%; MRI: 43% to 13%; bilateral radiographs: 36%). In contrast a high specificity was observed in the TPBS and MRI at the eighth and sixteenth-week examinations (TPBS: 96%, 100%; MRI: 78%, 98%) and for bilateral radiographs 8 weeks after trauma (94%). The thermography presented a fair specificity that improved from the second to the sixteenth week (50% to 89%). DISCUSSION: The poor sensitivity of all tested procedures combined with a reasonable specificity produced a low positive predictive value (17% to 60%) and a moderate negative predictive value (79% to 86%). These results suggest, that those procedures cannot be used as screening tests. Imaging methods are not able to reliably differentiate between normal posttraumatic changes and changes due to CRPS I. Clinical findings remain the gold standard for the diagnosis of CRPS I and the procedures described above may serve as additional tools to establish the diagnosis in doubtful cases.

Lung-volume reduction surgery as an alternative or bridging procedure to lung transplantation.

BACKGROUND: In this study, we prospectively analyzed the functional outcome and the survival after lung-volume reduction surgery (LVRS) in patients with end-stage emphysema who were initially potential candidates for lung transplantation (LTX), and investigated the impact of LVRS on posttransplant course in patients who underwent LTX after LVRS. METHODS: Of the 216 patients who underwent LVRS between 1994 and 2005, 58 were potential candidates for LTX at the time of LVRS (age 65 years or younger, forced expiratory volume in 1 second 25% of predicted or less; LVRS/LTX group). Lung-volume reduction surgery was performed by means of video-assisted, bilateral stapled resection of target areas. During the same period, 31 patients underwent primary LTX for end-stage emphysema (LTX group). Spirometry, plethysmography, carbon monoxide diffusing capacity, 6-minute walking distance, and dyspnea score were assessed preoperatively and at predetermined times after operation. Survival analysis was performed by use of the Kaplan-Meier method. RESULTS: All the functional variables significantly improved after LVRS and peaked within the first year. Subjective improvement was observed for up to 5 years after LVRS, and 53% (31 of 58) of the patients were still alive and had not undergone transplantation after a median follow-up of 44 months. Fourteen percent (8 of 58) of the patients underwent secondary LTX because of progressive worsening of the respiratory function after a median bridging time between LVRS and LTX of 33 months. Postoperative recovery after transplantation and median survival time were comparable between the 8 patients of the LVRS/LTX group and the 31 patients of the LTX group (96.5 months versus 118.5 months, p = 0.9). CONCLUSIONS: Lung-volume reduction surgery can significantly improve symptoms and lung function in selected patients who are initially potential candidates for LTX. Lung-volume reduction surgery can allow the postponement of LTX for up to 4 to 5 years and does not impair the chances for a subsequent successful LTX.

Etiology of solitary extrapulmonary positron emission tomography and computed tomography findings in patients with lung cancer.

PURPOSE: The aim of this prospective study was to assess the incidence and the nature of solitary extrapulmonary [18F] fluorodeoxyglucose (FDG) accumulations in patients with non-small-cell lung cancer (NSCLC) staged with integrated positron emission tomography and computed tomography (PET/CT) and to evaluate the impact on management. PATIENTS AND METHODS: A total of 350 patients with NSCLC underwent whole-body PET/CT imaging. All solitary extrapulmonary FDG accumulations were evaluated by histopathology, further imaging, or clinical follow-up. RESULTS: PET/CT imaging revealed extrapulmonary lesions in 110 patients. In 72 patients (21%), solitary lesions were present. A diagnosis was obtained in 69 of these patients, including 37 (54%) with solitary metastases and 32 (46%) with lesions unrelated to the lung primary. Histopathologic examinations of these 32 lesions revealed a second clinically unsuspected malignancy or a recurrence of a previous diagnosed carcinoma in six patients (19%) and a benign tumor or inflammatory lesion in 26 patients (81%). The six malignancies consisted of carcinoma of the breast in two patients, and carcinoma of the orbit, esophagus, prostate, and non-Hodgkin's lymphoma in one patient each. Benign tumors and inflammatory lesions included eight colon adenomas, four Warthin's tumors, one granuloma of the lower jaw, one adenoma of the thyroid gland, one compensatory muscle activity due to vocal chord palsy, two occurrences of arthritis, three occurrences of reflux esophagitis, two occurrences of pancreatitis, two occurrences of diverticulitis, one hemorrhoidal inflammation, and one rib fracture. CONCLUSION: Solitary extrapulmonary FDG accumulations in patients with newly diagnosed lung cancer should be analyzed critically for correct staging and optimal therapy, given that up to half of the lesions may represent unrelated malignancies or benign disease.

Long-term results after lung volume reduction surgery in patients with alpha1-antitrypsin deficiency.

BACKGROUND: The favorable effects of lung volume reduction surgery for selected patients with smoker's emphysema has been demonstrated. However, outcome data for patients with alpha(1)-antitrypsin deficiency emphysema are scarce. METHODS: We prospectively studied pulmonary function, dyspnea, and 6-minute walking distance in 21 patients with severe alpha(1)-antitrypsin deficiency emphysema (PiZZ 18, PiZO 1, PiSZ 2, 10 female patients, median age 56 years, range 38-74 years) for as long as 5 years after thoracoscopic lung volume reduction surgery. RESULTS: Lung volume reduction surgery improved the mean dyspnea score, from 3.7 +/- 0.1 preoperatively to 1.4 +/- 0.2 at 3 months; the score remained improved for as long as 3.5 years. Mean vital capacity (% predicted) improved from 79% +/- 4.4% to 98% +/- 4.8% at 3 months, and the ratio of residual volume to total lung capacity decreased from 0.67 to 0.51. These improvements lasted for as long as 2 years. The mean airflow obstruction (forced expiratory volume in 1 second % predicted) improved from 27% +/- 1.9% to 38% +/- 3.3% at 3 months and remained statistically improved for 1 year. Four patients showed long-term improvement in lung function for as long as 3.5 years. These patients had markedly heterogeneous emphysema and showed no radiologic signs of airway inflammation. CONCLUSIONS: Lung volume reduction surgery in patients with advanced emphysema from alpha(1)-antitrypsin deficiency results in a significant improvement in dyspnea and lung function for as long as 3.5 years in some cases. It appears that magnitude and duration of these effects are inferior and shorter than those in patients with pure smoker's emphysema. Patients with heterogeneous disease and no or minor inflammatory airway disease may benefit most.