Markus Furrer

Mediastinal Lymph Node Clearance After Docetaxel-Cisplatin Neoadjuvant Chemotherapy Is Prognostic of Survival in Patients With Stage IIIA pN2 Non–Small-Cell Lung Cancer: A Multicenter Phase II Trial

PURPOSE A multicenter, phase II trial investigated the efficacy and toxicity of neoadjuvant docetaxel-cisplatin in locally advanced non-small-cell lung cancer (NSCLC) and examined prognostic factors for patients not benefiting from surgery. PATIENTS AND METHODS Ninety patients with previously untreated, potentially operable stage IIIA (mediastinoscopically pN2) NSCLC received three cycles of docetaxel 85 mg/m2 day 1 plus cisplatin 40 mg/m2 days 1 and 2, with subsequent surgical resection. RESULTS Administered dose-intensities were docetaxel 85 mg/m2/3 weeks (range, 53 to 96) and cisplatin 95 mg/m2/3 weeks (range, 0 to 104). The 265 cycles were well tolerated, and the overall response rate was 66% (95% confidence interval [CI], 55% to 75%). Seventy-five patients underwent tumor resection with positive resection margin and involvement of the uppermost mediastinal lymph node in 16% and 35% of patients, respectively (perioperative mortality, 3%; morbidity, 17%). Pathologic complete response occurred in 19% of patients with tumor resection. In patients with tumor resection, downstaging to N0-1 at surgery was prognostic and significantly prolonged event-free survival (EFS) and overall survival (OS; P =.0001). At median follow-up of 32 months, the median EFS and OS were 14.8 months (range, 2.4 to 53.4) and 33 months (range, 2.4 to 53.4), respectively. Local relapse occurred in 27% of patients with tumor resection, with distant metastases in 37%. Multivariate analyses identified mediastinal clearance (hazard ratio, 0.22; P =.0003) and complete resection (hazard ratio, 0.26; P =.0006) as strongly prognostic for increased survival. CONCLUSION Neoadjuvant docetaxel-cisplatin is effective and tolerable in stage IIIA pN2 NSCLC. Resection is recommended only for patients with mediastinal downstaging after chemotherapy.

Three years' experience in video-assisted in thoracic surgery (VATS) for spontaneous pneumothorax

In a prospective study (June 1990 to June 1993), 79 patients were treated for spontaneous pneumothorax by video-assisted thoracoscopic methods with regular follow-up. The observation time was from 3 to 36 months (mean 19.6 months) and was more than 24 months in 27 patients. In 57 patients spontaneous pneumothorax was primary and in 22 secondary. The 53 male and 26 female patients were aged between 17 and 87 years (mean 37 years). Twenty-one patients were treated thoracoscopically for first episode, 22 for persistent pneumothorax (> 7 days), and 36 for a recurrence. Endoscopic examination failed to reveal any lung alteration in four patients (5.1%), and treatment then consisted of simple drainage. Leaks were sealed 26 times by means of a Roeder loop with local anesthesia and 14 times by wedge resection with endotracheal anesthesia and one-lung ventilation; 34 patients were treated by pleurectomy. No deaths occurred. Surgical morbidity was 3.8%, and the postoperative complication rate was 5.1%. One patient was excluded from the follow-up study after conversion to a thoracotomy for control of arterial bleeding. We noted six recurrences; four occurred in the first 21 days and three after ligation of the leak with a Roeder loop. We conclude that video-assisted thoracoscopic treatment of spontaneous pneumothorax by wedge resection and pleurectomy has a recurrence-free rate of 93.8% (45/48) and is therefore an effective treatment for all forms of spontaneous pneumothorax.

Thoracotomy and thoracoscopy: postoperative pulmonary function, pain and chest wall complaints.

OBJECTIVE Two different surgical accesses combined with standard pain management procedures are compared regarding early and intermediate pulmonary function and pain relief. METHODS In a prospective study, 15 consecutive patients undergoing video-thoracoscopy for pulmonary wedge resection (group 1) were matched to 15 patients undergoing standard postero-lateral thoracotomy for lobectomy (group 2) according to age, gender and preoperative pulmonary function. Postoperative pain control consisted of patient controlled analgesia in group 1 and epidural analgesia in group 2. Pain intensity was scored from 0-4. The predicted postoperative pulmonary function (FVC and FEV 1) after lobectomies was calculated from the preoperative value according to the extent of resection. A clinical measurement was obtained after a mean follow-up time of 4.2 months. RESULTS The ratios of postoperative measured to predicted values of FVC and FEV1 for group 1 compared with group 2 were 0.64 +/- 0.15 and 0.65 +/- 0.14 compared with 0.60 +/- 0.19 and 0.59 +/- 0.13, resp. (both n.s.) at the first day postoperative; 0.92 +/- 0.18 and 0.95 /- 0.17 compared with 0.76 +/- 0.20 (P < 0.05) and 0.83 +/- 0.23 (n.s.), resp. at hospital discharge; 0.98 +/- 0.10 and 0.94 +/- 0.14 compared with 1.01 +/- 0.17 (n.s.) and 1.10 +/- 0.17 (P < 0.05), resp. at follow-up. Pain intensity score one day after surgery ranged from 0.4 (resting position) to 1.6 (coughing) for group 1, and from 0.3 to 1.2 for group 2. Thirty-six percent of the thoracoscopy patients and 33% of the thoracotomy group complained of persistent pain or discomfort on the site of the operation after 3-18 months. CONCLUSION Post-thoracotomy pain can be effectively controlled with epidural analgesia and pain intensity is no higher than in patients after thoracoscopy who are managed with patient controlled analgesia. FVC is slightly more decreased after thoracotomy during the early postoperative period. FVC and FEV 1 approach the predicted values after four months in both groups. The rate of persistent pain is similar after thoracoscopy and thoracotomy.

Prognostic factors affecting long-term outcomes in patients with resected stage IIIA pN2 non-small-cell lung cancer: 5-Year follow-up of a phase II study

The aim was to investigate the efficacy of neoadjuvant docetaxel–cisplatin and identify prognostic factors for outcome in locally advanced stage IIIA (pN2 by mediastinoscopy) non-small-cell lung cancer (NSCLC) patients. In all, 75 patients (from 90 enrolled) underwent tumour resection after three 3-week cycles of docetaxel 85 mg m−2 (day 1) plus cisplatin 40 or 50 mg m−2 (days 1 and 2). Therapy was well tolerated (overall grade 3 toxicity occurred in 48% patients; no grade 4 nonhaematological toxicity was reported), with no observed late toxicities. Median overall survival (OS) and event-free survival (EFS) times were 35 and 15 months, respectively, in the 75 patients who underwent surgery; corresponding figures for all 90 patients enrolled were 28 and 12 months. At 3 years after initiating trial therapy, 27 out of 75 patients (36%) were alive and tumour free. At 5-year follow-up, 60 and 65% of patients had local relapse and distant metastases, respectively. The most common sites of distant metastases were the lung (24%) and brain (17%). Factors associated with OS, EFS and risk of local relapse and distant metastases were complete tumour resection and chemotherapy activity (clinical response, pathologic response, mediastinal downstaging). Neoadjuvant docetaxel–cisplatin was effective and tolerable in stage IIIA pN2 NSCLC, with chemotherapy contributing significantly to outcomes.

Video-Assisted Thoracoscopic Surgery for Fibrinopurulent Pleural Empyema in 67 Patients

BACKGROUND The roles of different drainage procedures in the management of empyema have to be redefined now that video-assisted thoracoscopic surgery (VATS) has been introduced. The debridement of fibrinopurulent stage II empyema with the use of VATS was assessed prospectively in regard to control of infection and restoration of pulmonary function. METHODS Between January 1992 and May 1996, all patients at our institution with fibrinopurulent empyema that did not respond to chest tube drainage and antibiotic therapy were treated by debridement with the use of VATS. The patients were followed up prospectively by clinical and radiologic assessments 3 and 6 months after the operation and by spirometry 6 months after the operation. RESULTS Video-assisted thoracoscopic surgery was initiated in 67 patients, but conversion to open decortication was required because of the finding of advanced disease in 19 patients (28%). Forty-eight patients underwent successful debridement with the use of VATS. The mean operative time was 82.1 minutes (range, 50 to 135 minutes), the mean duration of postoperative chest tube placement was 4.1 days (range, 2 to 8 days), and the mean duration of postoperative hospitalization was 12.3 days (range, 4 to 42 days). No wound infections were observed during the postoperative course. Both the 30-day mortality rate and the recurrence (ie, need for thoracotomy) rate were 4%. The mean predicted vital capacity was 84.8% +/- 14.9% and the mean predicted forced expiratory volume in 1 second was 88.6% +/- 19.2% 6 months after the operation. CONCLUSIONS Debridement with the use of VATS is safe and efficient for stage II empyema, but open decortication should be used for more advanced disease.

Functional assessment of chest wall integrity after methylmethacrylate reconstruction

BACKGROUND All patients with extensive resection of the anterolateral chest wall and the sternum followed by reconstruction with methylmethacrylate substitutes were assessed prospectively 6 months after the operation to delineate chest wall integrity with pulmonary function and cine-magnetic resonance imaging. METHODS Twenty-six patients underwent chest wall reconstruction by use of methylmethacrylate between 1994 and 1998 due to primary tumors in 35%, metastases in 27%, T3 lung cancer in 19%, and debridement for radionecrosis and osteomyelitis in 19% of patients. Three to eight ribs were resected and additional sternum resection was performed in 39% of patients. RESULTS There was no 30-day mortality. All patients were extubated after the operation without need for reintubation. Prosthesis dislocation occurred in 1 patient and infection in 2 patients during follow-up. Nineteen patients (73%) suffered no restrictions of daily activities. Clinical examination revealed normal shoulder girdle function in 77% of patients. There was no significant difference between preoperative and postoperative FEV1 (forced expiratory volume in 1 second) measurements in patients with lobectomy or wedge resections. Cinemagnetic resonance imaging revealed concordant chest wall movements during respiration in 92% of patients without paradoxical movements or implant dislocations being observed. CONCLUSIONS Large defects of the anterolateral chest wall and sternum can be reconstructed efficiently with methylmethacrylate substitutes with minimal morbidity and excellent cosmetic and functional outcome.

Descending necrotizing mediastinitis: surgical treatment via clamshell approach.

BACKGROUND Descending necrotizing mediastinitis requires an early and aggressive surgical approach to reduce the high morbidity and mortality associated with this disease. The clamshell incision has provided excellent exposure of the entire mediastinum and both pleural cavities and was assessed in patients suffering from descending necrotizing mediastinitis. METHODS Three patients with descending necrotizing mediastinitis and bilateral pleural empyema due to invasive streptococcal infections were operated on with this method. Radical debridement of the mediastinum and bilateral decortication was performed through a clamshell incision, including pericardiectomy in 2 patients. All patients received initially a high dose of antibiotic regimen, 2 had bilateral chest tube drainage, and 1 had mediastinal drainage and pleural debridement via cervical mediastinotomy and thoracoscopy, respectively. All these measures alone, however, failed to control the disease. RESULTS The clamshell incision offered an excellent exposure for bilateral decortication and debridement of the entire mediastinum including pericardiectomy. One patient, who was referred in critically ill condition, died of multiorgan failure in the postoperative period. The remaining 2 patients recovered without further interventions and without evidence of phrenic nerve palsy, sternum osteomyelitis, or sternal override. CONCLUSIONS The clamshell approach offers an excellent exposure for a complete one-stage surgical treatment with mediastinal debridement and bilateral decortication in patients suffering from descending necrotizing mediastinitis in the absence of profound septic shock.

Cytostatic Lung Perfusion by Use of an Endovascular Blood Flow Occlusion Technique

BACKGROUND Different modalities of cytostatic lung perfusion were compared regarding plasma and tissue drug concentrations to assess the efficacy of an endovascular blood flow occlusion technique. METHODS A cytostatic lung perfusion study with doxorubicin hydrochloride was performed on large white pigs (n = 12). Plasma and tissue concentrations of doxorubicin were compared for isolated lung perfusion with open cannulation (ILP), blood flow occlusion perfusion with open cannulation of the pulmonary artery alone (BFO), and intravenous drug administration (i.v.). In a fourth group, thoracotomy-free BFO perfusion was performed by endovascular balloon catheterization of the pulmonary artery (endovascular BFO). The 3 animals in this group were used to compare the doxorubicin-perfused pulmonary tissue with the contralateral nonperfused lobes after 1 month. RESULTS The mean lung tissue doxorubicin concentration at the end of perfusion was 19.8 +/- 1.6 microg/g after ILP, 27.6 +/- 2.2 microg/g after BFO (p = not significant), and 3.0 +/- 0.8 microg/g after i.v. perfusion (p < 0.01). Whereas doxorubicin was not detectable in the plasma in the ILP group, concentrations ranged from not detectable to 0.44 microg/mL in the BFO group and from 0.31 to 0.84 microg/mL in the i.v. group (p < 0.05). Mean myocardial tissue concentration was not significantly different after BFO than i.v. perfusion (1.1 +/- 0.5 microg/g and 1.8 +/- 0.1 microg/g, respectively). In the endovascular BFO group, balloon-blocked pulmonary artery perfusion was successfully performed in all animals, and after 1 month, lung tissue showed no cytostatic-induced histologic changes. CONCLUSIONS Compared with ILP, BFO cytostatic lung perfusion produced an insignificantly higher lung-tissue concentration, corresponding to a sixfold to ninefold higher level than after i.v. perfusion. Plasma drug levels during BFO perfusion were lower than during i.v. perfusion. Endovascular BFO may be a promising technique for repeated cytostatic lung perfusion.

Isolated Lung Perfusion: Single-Pass System Versus Recirculating Blood Perfusion in Pigs

BACKGROUND Cytostatic isolated lung perfusion has been advocated for treating pulmonary metastasis of soft tissue sarcoma. Different techniques of isolated lung perfusion have been developed. METHODS Isolated lung perfusion with and without doxorubicin was performed on white pigs during 15 minutes either by a single-pass system (n = 7) or by a recirculating-blood perfusion system (n = 7). Three animals with endovenous drug application served as controls. Leakage was assessed using isotopic tracers. Perfusion-induced lung tissue injury was determined by postperfusion chest radiographs, by angiotensin-converting enzyme-to-protein ratio in the plasma and in the bronchioalveolar lavage fluid, and by wet-to-dry weight ratio and histologic examination of lung biopsy specimens at 20 and 50 minutes. Doxorubicin concentration in lung tissue and plasma was compared between the three study groups. RESULTS All isolated lung perfusion studies were successfully performed without significant systemic leakage (< 0.6%). Wet-to-dry weight ratio was significantly lower after single-pass as compared with recirculating-blood perfusion and endovenous drug application at both time points (5.0 +/- 1.1 and 5.3 +/- 0.8 for single-pass versus 6.6 +/- 1.1 and 6.9 +/- 0.5 for recirculating-blood versus 6.6 +/- 0.2 and 5.9 +/- 0.7 for the control group, respectively; p < 0.05). Angiotensin-converting enzyme-to-protein plasma ratio in the single-pass group was significantly lower only at 20 minutes (6.3 +/- 2.4 versus 9.3 +/- 1.0 versus 9.7 +/- 1.9, respectively; p < 0.05) but not at 50 minutes. Angiotensin-converting enzyme-to-protein ratio in bronchoalveolar lavage fluid, histology of lung biopsy specimens, and chest radiographs did not differ significantly between the three groups. Doxorubicin lung tissue concentration was not significantly different after single-pass (17.5 micrograms/g) and recirculating-blood perfusion (21.9 micrograms/g), but was significantly higher than after endovenous drug application (3.0 micrograms/g; p < 0.01). CONCLUSIONS Both isolated lung perfusion techniques resulted in a sixfold to sevenfold higher doxorubicin lung tissue concentration than after endovenous application. Isolated lung perfusion-induced lung injury was similar for both techniques, but recirculating-blood perfusion appeared to result in more acute lung injury and was technically more demanding than single-pass perfusion.

Spontaneous pneumothorax from radiographically occult metastatic sarcoma

We present two cases of spontaneous pneumothorax secondary to metastatic synovial cell sarcoma. Radiographic techniques initially did not suggest lung nodules in either patients; thoracoscopy allowed sequential bilateral detection of small pulmonary metastases in one case and confirmed the diagnosis during treatment of recurrent pneumothorax in the second case. This report underlines that pneumothorax may be the first clinical manifestation of metastatic sarcoma and can occur even if current imaging techniques are not indicative of metastatic disease. In the latter instance, thoracoscopic exploration has to be envisaged in order to rule out the possibility of metastatic lung involvement.