Giorgio Furio Coloni

Long-Term Outcome after Multimodality Treatment for Stage III Thymic Tumors

BACKGROUND Surgery remains the cornerstone of therapy for thymic tumors, but the optimal treatment for advanced, infiltrative lesions is still controversial. The introduction of multimodality protocols has substantially modified survival and recurrence rate. We reviewed our 13-year prospective experience with multimodality treatment of stage III thymoma and thymic carcinoma. METHODS Since 1989 we have prospectively used a multimodality approach in 45 stage III thymic tumors. Sixteen patients (35%) had myasthenia gravis. Twenty-three patients (51%) had pure or predominantly cortical thymoma (group 1), 11 (24.5%) had well-differentiated thymic carcinoma (group 2), and 11 (24.5%) had thymic carcinoma (group 3). Tumors that were not considered radically resectable at preoperative workup underwent biopsy and induction chemotherapy (15 patients, 33%) followed by surgical resection; all patients were referred for adjuvant chemoradiotherapy. RESULTS No operative mortality was recorded; 1 treatment-related death during adjuvant chemotherapy was observed in group 1. Complete resection was feasible in 91% of patients in groups 1 and 2 and 82% in group 3. The overall 10-year survival was 78%. Ten-year survival for groups 1 and 2 was 90% and 85%, respectively; 8-year survival for group 3 was 56%. During follow-up, tumor recurrence was noted in 3 patients (13%) from group 1, 3 (27%) from group 2, and 3 (27%) from group 3. CONCLUSIONS Multimodality treatment with induction chemotherapy (when required) and adjuvant chemoradiotherapy offers encouraging results for stage III thymic tumors; the outcome is more favorable for cortical thymoma and well-differentiated thymic carcinoma.

Thymoma and thymic carcinoma

Thymoma and thymic carcinoma are an extremely heterogeneous group of neoplastic lesions with an exceedingly wide spectrum of morphologic appearances. They show different presentations with a variable and unpredictable evolution ranging from an indolent non-invasive attitude to a highly infiltrative and metastasising one. Prognosis can be predicted on the basis of a number of variables, mainly staging, the WHO histological pattern and diameter of the tumour. Complete surgical resection is certainly the gold standard to achieve cure. However, especially in patients with lesions at advanced stage, complete resection may be difficult and recurrence often occurs; at these stages, disease-free long-term survival may be difficult to be accomplished. Chemo- and radiotherapy protocols have been designed to complete surgical treatment and improve results in inoperable patients as well, based on the reported sensitivity of thymic tumours to these treatment modalities. The integration of clinical staging and histology, with the new histogenetic morphological classification, has contributed to design multimodality treatment protocols that help to improve prognosis. Induction therapy can now be applied before surgery in patients with tumours considered inoperable, improving resectability and outcome without adding morbidity and mortality to the surgical procedure. This newly developed approach helps to reduce the recurrence rate and to ameliorate disease-free survival. New therapies are now being evaluated as for many other tumours; however, they still need confirmation in prospective randomised studies. In the future, integrated treatment modality should be incorporated in a standardised approach that goes from a careful assessment of histology, staging and lymph node status, and a constructive and non-empirical co-operation between medical and radiation oncologists, pathologists and thoracic surgeons.

Sleeve resection and prosthetic reconstruction of the pulmonary artery for lung cancer

BACKGROUND Lobectomy associated with reconstruction of the pulmonary artery (PA) is a technically feasible alternative to pneumonectomy in patients with lung cancer. However, concern about postoperative complications and long-term survival limited its acceptance so far. METHODS Between 1989 and 1996, we performed a PA reconstruction in 52 patients (41 men, 11 women; age range 35 to 75 years, mean 60 years) with lung cancer. Eleven patients had induction chemotherapy. We performed 15 PA sleeve resections, 34 PA reconstructions by a pericardial patch, and three PA reconstructions by a pericardial conduit, associated with a bronchial sleeve lobectomy or bilobectomy (33), or with standard lobectomy (19). Immediate and long-term postoperative evaluation included spirometry, echocardiography, perfusion lung scans, computed tomography, and PA angiography. The follow-up ranged between 27 and 96 months and is complete for all patients. RESULTS We had one specific postoperative complication (PA thrombosis) and no mortality. Perfusion scans and PA angiography were normal in all but the 1 patient having thrombosis. Mean forced expiratory volume (FEV) in 1 s and forced vital capacity (FVC) were, respectively, 72% and 80% preoperatively, 65% and 76% 1 month after surgery, and then they plateaued at 70% and 78% after 6 months. Echocardiography showed patterns in the normal range and normal estimates of PA pressures in all but 2 patients. Five-year survival was 38.3% for the entire group, 18.6% for stages IIIA and B, and 64.4% for stages I and II. CONCLUSIONS Morbidity, mortality, and functional data do not differ from what is currently reported for standard lobectomy. Long-term survival is in line with that reported for standard resection. These data support PA reconstruction as a viable option in the treatment of lung cancer.

Thymectomy for myasthenia gravis: a 27-year experience

OBJECTIVE Thymectomy is considered an effective therapeutic option for patients with myasthenia gravis (MG). We reviewed our 27-year experience with surgical treatment of MG with respect to long-term results and factors affecting outcome. METHODS Between 1970 and 1997, we performed 232 thymectomies for MG. Fifteen patients were lost to follow-up; the remaining 217 form the object of our study. Sixty-two patients (28.4%) had thymoma. Myasthenia was graded according to a modified Osserman classification: 51 patients (23.5%) were in class I, 81(37.3%) in class IIA, 52 (24%) in class IIB, 26 (12%) in class III and seven (3.2%) in class IV. Mean duration of symptoms before the operation was 12+/-10 months. Fifty-eight thymectomies for thymoma were performed through a median sternotomy and four through a clamshell incision. Forty-six thymectomies for non-thymomatous MG were performed through a standard cervicotomy, 101 procedures through a partial upper sternal-splitting incision and eight through a complete median sternotomy. RESULTS Operative mortality was 0.92% (two patients). After a mean follow-up of 119 months, 71% of all patients improved their clinical status (25% without medications and asymptomatic; 46% with a reduction of medications and/or clinically improved); 39 (18%) have a stable disease with no clinical modifications; 12 (5%) presented a deterioration of their clinical status with worse symptoms, required more medications, or both. Thirteen patients (6%) died because of MG (mean survival 34.3+/-3.6 months). The presence of a thymoma negatively influenced the prognosis. Younger patients showed a more favorable outcome as well as patients with a shorter duration of symptoms before the operation; patients with lower classes of myasthenia showed a higher rate of remission. CONCLUSIONS Thymectomy is effective in the management of patients with MG at all stages with low morbidity. Patients with thymoma present a less favorable outcome.

Therapeutic video-assisted thoracoscopic surgical resection of colorectal pulmonary metastases

OBJECTIVE Careful patient selection is vital when video-assisted thoracoscopic surgical (VATS) therapeutic pulmonary metastasectomy of colorectal carcinoma is considered. Complete resection of all metastatic disease remains a vital concept. We reviewed our VATS experience for therapeutic metastasectomy of peripheral colorectal pulmonary metastases. METHODS Over 90 months, therapeutic VATS metastasectomy was accomplished upon 80 patients with colorectal metastases. Thin cut computed tomography (CT) was central in identifying lesions. The mean interval from primary carcinoma to VATS resection was 41 months (1-156 months; median, 33). A solitary lesion was resected in 60 patients and multiple (2-7) lesions resected in 20 patients. Statistics were obtained using the Students t-test. RESULTS No operative mortality or major postoperative complications occurred. The hospital stay was 4.5+/-2. 2 days (range, 1-13). All lesions were resected by VATS, with four conversions to thoracotomy to improve the margins. The mean survival of patients with one lesion was 34.8 months compared with 26.5 months for patients with multiple lesions (P=0.37). The mean survival was 20.5 months when metastases occurred <3 years vs. 28.1 months for >3 years from primary carcinoma resection (P=0.20). Twenty-five (31%) patients are disease free; with a mean interval of 38.7 (3-84; median, 35) months. Sixty-nine percent (55/80) of patients developed a recurrence: 6/80 (8%) local; 19/80 (24%) regional (same hemithorax away from resection); and 30/80 (38%) distant. The overall survival at 1 year was 81.2%, 48.4% at 3 years and 30.8% at 5 years. CONCLUSIONS Therapeutic VATS resection of colorectal metastases appears efficacious. Preoperative CT can identify peripheral colorectal metastases amenable to VATS. Conversion to thoracotomy is indicated when none of the lesions identified by CT are found or when clear surgical margins are jeopardized.

Preimplantation retrograde pneumoplegia in clinical lung transplantation

Abstract Objective: Retrograde pneumoplegia seems to improve early graft function in experimental and clinical lung transplantation. We evaluated the role of retrograde flushing in addition to antegrade pneumoplegia in clinical lung transplantation. Methods: Fourteen patients undergoing lung transplantation were randomized into 2 groups: in group I we performed antegrade pulmonary artery flushing with alprostadil (prostaglandin E 1 ) and modified Euro-Collins solution at the time of retrieval. In group II additional retrograde flushing through the pulmonary veins was performed at the back table, before reimplantation. Hemodynamic variables, mean airway pressure, and blood gas analysis were monitored at different time points. Postoperative volumetric monitoring was performed to assess extravascular lung water. The reimplantation response was assessed by a radiographic score; extubation time and intensive care unit stay were recorded. Results: During retrograde flushing, blood and clots coming out from the pulmonary artery were observed; 2 lungs harvested from a donor with multiple bone fractures had fat emboli in the retrograde perfusate. Hemodynamic monitoring did not demonstrate any difference between the 2 groups. The ratio of arterial oxygen tension to inspired oxygen fraction, extravascular lung water, duration of intubation, and length of stay in the intensive care unit were improved in group II, but the differences did not reach statistical significance. Intrapulmonary shunt fraction was significantly improved in group II at each time point ( P = .02), as well as indexed alveolar-arterial oxygen tension gradient ( P = .04), mean airway pressure ( P = .04), and chest x-ray score ( P = .03). Conclusions: Preimplantation retrograde flushing is not detrimental and helps to improve early graft function. (J Thorac Cardiovasc Surg 1999;118:107-14)

Nd:YAG laser resection of lung cancer invading the airway as a bridge to surgery and palliative treatment

BACKGROUND Thirty percent of patients with lung cancer have airway obstruction requiring palliation. In addition, endoscopic resection may be considered before surgery or induction therapy to improve quality of life and functional status, and to allow better staging. It may also help to prevent infectious complications during induction chemotherapy. METHODS Since 1993, 351 Nd:YAG laser resections were performed in 273 patients with lung cancer. The tumor involved the trachea in 36 patients, the carina in 28, the main bronchi in 154, the bronchus intermedius in 29, and the distal airway in 26. One hundred eight stents were placed. After the endoscopic treatment 36 patients were operated on (23 after induction chemotherapy) with 8 pneumonectomies (1 tracheal sleeve) and 28 lobectomies (15 bronchial sleeves). Spirometry, arterial blood gas analysis, and quality of life and performance status were recorded before and after laser treatment and after induction chemotherapy. Complications during chemotherapy, surgical morbidity and mortality, and survival were also recorded. RESULTS Major complications during laser resection were bleeding (7 patients) and hypoxia (5 patients). Three patients died within 24 hours after the procedure. No complications were observed in the group of patients who subsequently underwent induction chemotherapy or surgery. One patient developed pneumonia during induction chemotherapy. The airway caliber improved in 89% of patients undergoing palliation only. In the group of patients undergoing induction chemotherapy and/or surgery, the performance status, quality of life, and functional measurements significantly improved after endoscopic treatment (FEV1 from 1.4 +/- 0.5 L/s to 2.2 +/- 0.6 L/s). Three-year survival after induction chemotherapy and surgery, was 52%. Median survival after palliation alone was 12.1 months. CONCLUSIONS Nd:YAG laser resection is a safe and effective means of relieving airway obstruction. Before induction chemotherapy or surgery preliminary endoscopic palliation helps to improve evaluation and staging and contributes to reducing morbidity during chemotherapy without increasing surgical complications.

Long-term follow-up after bronchoscopic lung volume reduction in patients with emphysema

Bronchoscopic lung volume reduction (BLVR) is a novel emphysema therapy. We evaluated long-term outcome in patients with heterogeneous emphysema undergoing BLVR with one-way valves. 40 patients undergoing unilateral BLVR entered our study. Pre-operative mean forced expiratory volume in 1 s (FEV1) was 0.88 L·s−1 (23%), total lung capacity was 7.45 L (121%), intrathoracic gas volume was 6 L (174%), residual volume (RV) was 5.2 L (232%), and the 6-min walk test (6MWT) was 286 m. All patients required supplemental oxygen; the Medical Research Council (MRC) dyspnoea score was 3.9. High-resolution computed tomography (HRCT) results were reviewed to assess the presence of interlobar fissures. 33 patients had a follow-up of >12 months (median 32 months). 37.5% of the patients had visible interlobar fissures. 40% of the patients died during follow-up. Three patients were transplanted and one underwent lung volume reduction surgery. Supplemental oxygen, FEV1, RV, 6MWT and MRC score showed a statistically significant improvement (p≤0.0001, p=0.004, p=0.03, p=0.003 and p<0.0001, respectively). Patients with visible fissures had a functional advantage. BLVR is feasible and safe. Long-term sustained improvements can be achieved. HRCT-visible interlobar fissures are a favourable prognostic factor.

Pulmonary hemodynamics contribute to indicate priority for lung transplantation in patients with cystic fibrosis

OBJECTIVE Lung transplantation is a viable option for patients with cystic fibrosis. The current strategy of selection, based on spirometry and deterioration of quality of life, results in a high mortality on the waiting list. We reviewed the case histories of patients with cystic fibrosis accepted for lung transplantation to ascertain whether pulmonary hemodynamics could contribute to predict life expectancy. METHODS Forty-five patients with cystic fibrosis were accepted: 11 died on the waiting list (group I), 24 underwent transplantation (group II), and 10 are still waiting (group III). During evaluation we recorded spirometry, oxygen requirement, ratio of arterial oxygen tension to inspired oxygen fraction (PaO (2)/FIO (2)), arterial carbon dioxide tension (PaCO (2)), 6-minute walk test results, right ventricular ejection fraction, echocardiography, and pulmonary hemodynamics. We compared data from group I, II, and III patients. A comparison was also made within group II between the data collected at the time of evaluation and at the time of transplantation to quantify the deterioration during the waiting time. RESULTS The waiting time, spirometry, 6-minute walk test results, and right ventricular ejection fraction did not differ among the three groups. A statistically significant difference was found for PaO (2)/FIO (2), PaCO (2), mean pulmonary artery pressure, cardiac index, pulmonary arterial wedge pressure, and intrapulmonary shunt between groups I and II. Groups I and III showed statistically significant differences for mean pulmonary artery pressure, PaO (2)/FIO (2), and systemic vascular resistance indexed. No differences were observed between groups II and III. The comparison within group II showed a significant deterioration of pulmonary hemodynamics during the waiting time. CONCLUSIONS Pulmonary hemodynamics are worst in patients dying on the waiting list and deteriorate significantly during the waiting time. They may thus contribute to establish priority for lung transplantation in patients with cystic fibrosis.

Pneumoperitoneum for the management of pleural air space problems associated with major pulmonary resections.

BACKGROUND The use of pneumoperitoneum to treat prolonged air leaks or space problems, or both, after pulmonary resection has been recently resurrected and used successfully. METHODS During the last 3 years, 14 patients experienced short-term pleural space problems associated with prolonged air leaks after pulmonary resection for lung cancer. All patients, under sedation and local anesthesia, had a mean of 2,100 mL of air injected under the diaphragm, using a Veres needle after a mean time of 7 days (range, 5 to 10 days) from the operation. In 3 patients talc slurry was added to help control the air leak. RESULTS No patients experienced complications during the induction of the pneumoperitoneum. No patients complained of dyspnea, although blood gas analysis showed a slight increment of carbon dioxide partial pressure (p < 0.0004). Obliteration of the pleural space was observed in all cases after a mean time of 4 days (range, 1 to 7 days). Air leaks stopped in all patients after a mean time of 8 days (range, 4 to 12 days). The mean postoperative hospital stay after lung resection was 18 days (range, 14 to 22 days). No patients had significant complications or long-term sequelae. We found that patients who had undergone induction chemotherapy had longer air leak durations than observed in noninduction patients (p = 0.03). CONCLUSIONS Our experience supports the use of postoperative pneumoperitoneum whenever a space problem associated with prolonged air leaks is present. The procedure is effective, safe, and easy to perform.