George Ladas

Pulmonary fibrosis and lung cancer: risk and benefit analysis of pulmonary resection

OBJECTIVE Pulmonary fibrosis is associated with an increased risk of lung cancer and outcome of surgical resection in this setting is unknown. METHODS We studied 22 patients (24 operations) with pulmonary fibrosis and non-small cell lung cancer treated between 1991 and 2000 (study group) and compared outcome with 951 other patients (964 operations) treated for non-small cell lung cancer over the same period (control patients). RESULTS The two groups did not differ significantly in age (68 vs 65 years), smoking history (86% vs 95% smokers), forced expiratory volume in 1 second (2.5 L/min vs 2.3 L/min) or forced vital capacity (3.2 L vs 3.7 L), but patients with pulmonary fibrosis were more likely to be male (72% vs 58%, P <.05). The operative mortality was higher in patients with pulmonary fibrosis than in control patients (17% vs 3.1%, P <.01) and there was a higher procedure-specific mortality in pulmonary fibrosis for pneumonectomy (33% vs 5.1%, P <.01) and lobectomy (12% vs 2.6%, P <.01). Patients with pulmonary fibrosis had a higher incidence of postoperative lung injury, (21% vs 3.7%, P <.01) and a longer mean hospital stay (17 vs 9 days, P <.05). In patients with pulmonary fibrosis, the actuarial 3-year survival was 54%. There were 11 deaths in the study group, 4 postoperatively (all acute respiratory distress syndrome) and 7 late deaths (metastatic disease, n = 2; progressive pulmonary fibrosis, n = 5). Median follow-up (to death or last review) was 13 months (range, 0-120 months). Five patients developed postoperative acute respiratory distress syndrome and in 4 of these patients this proved to be fatal. Postoperative acute respiratory distress syndrome was associated with lower preoperative total lung carbon monoxide diffusion capacity (median, 58% vs 70%, P =.03) and lower preoperative carbon monoxide diffusion capacity corrected for alveolar volume (median, 48% vs 58%, P =.05) and a higher preoperative composite physiological index (median, 44 vs 33, P =.008). None of the preoperative lung function parameters or operative finding were predictors of late death. CONCLUSION Patients with pulmonary fibrosis undergoing pulmonary resection for non-small cell lung cancer have increased postoperative morbidity and mortality, but an important subgroup has a good long-term outcome. Postoperative acute respiratory distress syndrome is associated with low preoperative gas transfer and a high composite physiological index. Resection of non-small cell lung cancer is appropriate in pulmonary fibrosis, provided that the level of functional impairment is carefully factored into patient selection.

Large cell neuroendocrine carcinoma and large cell carcinomas with neuroendocrine morphology of the lung: prognosis after complete resection and systematic nodal dissection

BACKGROUND Large cell neuroendocrine carcinoma (LCNEC) and large cell carcinoma with neuroendocrine morphology of the lung are both currently classified as subtypes of large cell carcinomas according to the World Health Organization IASLC classification system for lung and pleural tumors. Prognosis is reported as similar to that of small cell carcinomas. There is no consensus on management of this subset and adjuvant chemotherapy is recommended by some for early stage LCNEC to impact long-term prognosis. We retrospectively reviewed a cohort of patients at our institution who had this type of tumor to determine factors that might influence survival. METHODS Twenty-one cases of LCNEC and large cell carcinoma with neuroendocrine morphology were identified in the files of the Royal Brompton Hospital between 1986 and 1999. All patient data were reviewed, and complete follow-up was achieved with 20 of these patients. RESULTS Of the 21 patients identified, 20 underwent resection with systematic nodal dissection in 18. There was no in-hospital mortality. Of those patients fully staged by systematic nodal dissection, 9 were stage I, 5 were stage II and 4 were stage III. Median follow-up was 25 months (range, 2 to 120 months). At the time of review, 11 patients were alive and free of disease. One patient was alive and free of disease when lost to follow-up. Nine patients had died, 7 related and 2 unrelated to disease. The 5-year actuarial survival for the entire group was 47%. The actuarial survival of accurately staged, stage I patients at 5 years was 88%. The actuarial survival of patients in stage II and III was 28% at 5 years. CONCLUSIONS LCNEC and large cell carcinoma with neuroendocrine morphology are aggressive tumors, but patients with completely resected disease after systematic nodal dissection have a better prognosis than previously described. Patients with more advanced disease have a poor prognosis.

Immunohistochemical markers in the differentiation of thymic and pulmonary neoplasms

Immunohistochemical markers in the differentiation of thymic and pulmonary neoplasms

The mortality from acute respiratory distress syndrome after pulmonary resection is reducing: a 10-year single institutional experience.

OBJECTIVE Acute respiratory distress syndrome (ARDS) is a major cause of death following lung resection. At this institution we reported an incidence of 3.2% and a mortality of 72.2% in a review of patients who underwent pulmonary resection from 1991 to 1997 [Kutlu C, Williams E, Evans E, Pastorino U, Goldstraw P. Acute lung injury and acute respiratory distress syndrome after pulmonary resection. Ann Thorac Surg 2000;69:376-80]. The current study compares our recent experience with this historical data to assess if improved recognition of ARDS and treatment strategies has had an impact on the incidence and mortality. METHODS We identified and studied all patients who developed ARDS following a lung resection of any magnitude between 2000 and 2005 using the 1994 consensus definition: characteristic chest X-ray or CT, PaO2/FiO2 < 200 mmHg, pulmonary capillary wedge pressure < 18 mmHg and clinical acute onset. Overall incidence and mortality were recorded. Univariate analyses (t-test or chi(2), as appropriate) were carried out to identify correlations between pre-, peri- and postoperative variables and outcomes. RESULTS We performed 1376 lung resections during the study period. Of these 705 (51.2%) were for lung cancer and 671 (48.8%) for other diseases. Twenty-two patients fulfilled the criteria for ARDS with 10 deaths in this group. The incidence and mortality from ARDS had fallen significantly over the two study periods (incidence from 3.2% to 1.6%, p=0.01; mortality from 72% to 45%, p=0.05). Although no significant correlations with incidence and mortality were identified, we found a number of significant trends. In keeping with the ARDS network study recommendations, postoperative tidal volumes were maintained at a lower level when a higher number of pulmonary segments were excised (p=0.001). Furthermore, consistent with findings in previous studies, the highest incidence and death from ARDS were in pneumonectomy patients (incidence 11.4%; mortality 50%). Although the incidence and mortality from ARDS following pneumonectomy were not significantly different between the two study periods (p=0.08, p=0.35), we found that fewer pneumonectomies were performed in the later period (pneumonectomy rate of 6.4% vs 17.4%). CONCLUSIONS The incidence and mortality of ARDS have decreased in our institution. We postulate that this is due to more aggressive strategies to avoid pneumonectomy, greater attention to protective ventilation strategies during surgery and to the improved ICU management of ARDS.

Prognostic Factors for Survival after Surgical Palliation of Malignant Pleural Effusion

Introduction: To investigate prognostic factors for patient survival after surgical palliation of malignant pleural effusion (MPE). Method: We reviewed 278 consecutive nonoverseas patients (108 men, median age: 60 years [range 26–89]) undergoing 310 surgical procedures for palliation of MPE over a 72-month period. There were 195 thoracoscopic talc pleurodesis, 39 pleuroperitoneal shunts, 38 pleurodesis by an intercostal drain, 29 pleural biopsies alone, and nine long-term drains. Referring physicians provided survival data. The significance of prognostic factors was examined with the log-rank test (Kaplan-Meier), those significant entered a Cox logistic multivariate regression analysis. Results: Follow-up was complete until death (following 264 procedures) and for a median 648 days (range 173–2135) for surviving patients. Overall median postoperative survival was 211 days (95% confidence interval: 169–253). Survival was not significantly different for tumor type or method of palliation. In univarate analysis, preoperative leucocytosis, hypoxemia, raised alanine transaminase, body mass index below 18 and hypoalbuminemia were associated with a significantly reduced postoperative survival. In multivariate analysis, leucocytosis (p < 0.0001), hypoxemia (p = 0.014), and hypoalbuminemia (p < 0.0001) maintained significance. Conclusions: The survival reported demonstrates the necessity of an active approach to palliation of MPE. The identification of prognostic factors will assist the choice of palliative technique. In addition, an appreciation of the influence of selection on survival after surgical palliation of malignant pleural mesothelioma, especially that of unforeseen prognostic factors, is useful when evaluating the results of aggressive treatment such as chemoradiotherapy and radical surgery for these diseases.

Inter-observer variability in systematic nodal dissection: comparison of European and Japanese nodal designation

BACKGROUND Systematic nodal dissection is accepted as an important component of the intrathoracic staging of patients undergoing thoracotomy for lung cancer. Several lymph node maps have been proposed in an attempt to ensure uniformity in designating lymph node stations. The Japan Lung Cancer Society has published detailed definitions for each nodal station adopting the Naruke map. However, since these definitions had not been interpreted into other languages, they have not been universally accepted. The objective of this study was to assess the inter-observer variability in the interpretation of lymph node stations. METHODS A total of 424 lymph node stations were removed from 41 patients undergoing thoracotomy for non-small cell lung cancer. All nodal stations were labeled using the Naruke map. As each station was excised, it was designated in a blind fashion by one of two surgeons trained in the UK and one surgeon trained in Japan. The designation accorded to each nodal station was analyzed. RESULTS The total concordance was 68.5% (right side 67.0%, left side 69.9%). The concordance rate for individual nodal stations varied from 0% to 100%. Considerable discordance existed between the Japanese and European surgeons in the designation of nodal stations 2, 4, 8 and N1 station 12. In 14 (34.1%) patients, discordance in the labeling of lymph nodes led to disease being categorized as N1 by one observer, whereas the other considered the same nodes to be N2. CONCLUSIONS Considerable discordance in the designation of nodal station has been demonstrated. We would expect similar inter-observer variability elsewhere between surgeons, institutions, or countries. More detailed nodal charts and precise, easily understood definitions of nodal stations are needed for intrathoracic staging. The first English version of the Japan Lung Cancer Society staging manual goes some way to address this.

Anterior cervical-transsternal approach for resection of benign tumors at the thoracic inlet.

BACKGROUND Neural tumors at the thoracic apex, even when benign, present technical problems for the surgeon because of their inaccessibility. The standard approach from below, using a posterolateral thoracotomy, offers suboptimal access to the vascular and neural structures of the thoracic inlet. METHODS We present a new technique for the resection of benign tumors of the thoracic inlet, combining an anterior cervical approach with a limited median sternotomy. We do not find it necessary to resect any part of the clavicle or to add a thoracotomy. We used this technique in 4 patients with apical tumors. In 3 patients the tumor arose from the sympathetic chain and in 1 patient from the T1 component of the brachial plexus. RESULTS The tumors ranged from 30 to 70 mm in diameter, and histologic findings were neurilemoma in 3 cases and ganglioneuroma in 1. There were no complications or deaths. All 4 patients were discharged 3 to 6 days postoperatively. CONCLUSIONS In our experience this new technique provides improved exposure, good control of the neurovascular bundle, and less morbidity than that associated with thoracotomy. For malignant Pancoasts tumors we would still advocate the approach of Dartevelle or Grunenwald, supplemented by lateral thoracotomy to facilitate systematic intrathoracic evaluation.

A prospective, randomized trial comparing BioGlue and Vivostat for the control of alveolar air leak

OBJECTIVE BioGlue (CryoLife, Europa Ltd, Surrey, UK) is effective in reducing alveolar air leak after pulmonary resection. However, concerns exist regarding the use of bovine-derived products. Vivostat (Vivostat A/S, Alleroed, Denmark) is an autologous fibrin sealant that confers certain advantages. It shows superior elastic properties, a faster absorption time, and the absence of risk of transmission of blood-borne diseases. METHODS We conducted a randomized, single blind controlled study to compare BioGlue and Vivostat in the control of postoperative air leak. Primary endpoints were duration of air leak, time to intercostal drain removal, and length of hospital stay. Secondary endpoints related to postoperative complications. RESULTS Between December 2005 and December 2007, 103 patients were randomized. The analysis included 102 patients; 67% were male. Median age was 56 +/- 19 years. Indications for surgery were primary lung cancer in 41 patients (40%), secondary malignancy in 48 patients (47%), carcinoid in 6 patients (6%), and 7 patients underwent surgery for benign disease (7%). Bilobectomy was performed in 2 patients (2%), lobectomy in 41 patients (40%), lobectomy with lesser resection in 3 patients (3%), segmentectomy in 16 patients (16%), precision excision in 34 patients (33%), and 6 patients underwent other resections (6%). Median duration of air leak was 3 (0-32) days versus 2 (0-33) days for patients who received BioGlue and Vivostat, respectively (P = .677). Time to intercostal drain removal was 5 (1-32) days in the BioGlue group compared with 5 (1-34) days for the Vivostat group (P = .473). Median hospital stay was 8 (3-22) days versus 7 (2-29) days for the BioGlue and Vivostat groups, respectively (P = .382). There was no significant difference in the incidence of complications between the 2 groups (20 patients receiving BioGlue versus 19 patients receiving Vivostat, P = .839). CONCLUSIONS There were no significant differences in the 3 clinical outcome measures of duration of air leak, time to intercostal drain removal, and length of hospital stay in those patients receiving BioGlue or Vivostat. Given the inherent advantages of our institutional preference is to use Vivostat in the control of postoperative air leaks after pulmonary resection.

Tracheobronchial obstruction in children: experience with endoscopic airway stenting

BACKGROUND We reviewed our experience to determine the role of endoscopic airway stents in children with tracheobronchial obstruction. METHODS Seventeen children (10 boys and 7 girls) aged 2 months to 16 years underwent tracheobronchial stenting. Etiology of the tracheobronchial obstruction included external vascular compression (n = 9); tracheobronchial anastomotic strictures after heart-lung/lung transplantation (n = 4); airway compression by malignant mediastinal mass (n = 2), and subglottic/high tracheal stenosis after prolonged intubation with a tracheostomy in situ (n = 2). Indications for airway stenting were failure to wean from ventilator after a mean of 82.5 days (range, 2 to 210) in 8 children; and dyspnea or stridor in the remaining 9 children. RESULTS Ten children had a total of 24 uncovered self-expanding metal stents (either Magic Wallstent or Ultraflex Microvasive) and 7 children had silicone stents (2 straight, 3 Y and 2 T tube stents). At follow-up at 1 week to 72 months (median 21), only 8 of 17 (47%) children were alive but all the deaths were secondary to the underlying pathology and not related to tracheobronchial stenting. Six of 8 ventilator-dependent children were extubated after a mean of 5.3 days (range, 2 to 11) after airway stenting. For the 9 children stented for dyspnea, mean Medical Research Council dyspnea score decreased from 3.0 to 1.6 after stenting. CONCLUSIONS Tracheobronchial stenting in children is only rarely needed and often undertaken in dire circumstances. The procedure has led to significant symptomatic benefit in dyspneic children and has enabled ventilator-dependent children to be extubated. Medium-term outlook after stenting with self-expanding metal stents for vascular compression of the airway is encouraging. The long-term outcome remains uncertain, however, and is ultimately influenced by the underlying disease.

Peri-operative chemotherapy in the management of resectable colorectal cancer pulmonary metastases

BackgroundSurgery is often advocated in patients with resectable pulmonary metastases from colorectal cancer (CRC). Our study aims to evaluate peri-operative chemotherapy in patients with metastastic CRC undergoing pulmonary metastasectomy.MethodsPatients treated for CRC who underwent pulmonary metastasectomy by a single surgeon were identified. Outcome measures included survival, peri-operative complications, radiological and histological evidence of chemotherapy-induced lung toxicities.ResultsBetween 1997 and 2009, 51 eligible patients were identified undergoing a total of 72 pulmonary resections. Thirty-eight patients received peri-operative chemotherapy, of whom 9 received an additional biological agent. Five-year overall survival rate was 72% in the whole cohort - 74% and 68% in those who received peri-operative chemotherapy (CS) and those who underwent surgery alone (S) respectively. Five-year relapse free survival rate was 31% in the whole cohort - 38% and ≤18% in CS and S groups respectively. Only 8% had disease progression during neoadjuvant chemotherapy. There were no post-operative deaths. Surgical complications occurred in only 4% of patients who received pre-operative chemotherapy. There was neither radiological nor histological evidence of lung toxicity in resected surgical specimens.ConclusionsPeri-operative chemotherapy can be safely delivered to CRC patients undergoing pulmonary metastasectomy. Survival in this selected group of patients was favourable.