Edoardo Mercadante

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.

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.

Thoracoscopic sympathectomy for symptomatic arterial obstruction of the upper extremities

BACKGROUND Severely symptomatic arterial insufficiency of the hand and upper extremities requires adequate treatment. Medical therapy and local care are usually unsuccessful, and thoracic sympathectomy can represent an effective procedure to control pain, to help ulcer healing, and to prevent or delay amputation. METHODS We performed 20 thoracoscopic sympathectomies in 15 patients (13 men and 2 women) with upper extremity ischemia. Mean age was 47 years (range 21 to 72 years). All patients were thought to have organic blockage of digital arteries. The condition was unilateral in 10 patients and bilateral in 5. Primary diagnosis was digital arteriosclerosis in 8 patients, Buergers disease in 4 patients and the remaining 3 were drug abusers with severe ischemia due to accidental intraarterial injection of drugs. Eleven patients (73%) presented with terminal digital necrosis, gangrene, or ulceration of the fingers associated with severe pain. Four patients complained of coldness, pain, and some degree of soft tissue infection without permanent loss of tissue. RESULTS We performed 10 unilateral and five bilateral staged (mean interval was 3 months) thoracoscopic sympathectomies. We had two minor complications and no mortality. Mean duration of postoperative chest drainage was 2.5 +/- 0.4 days and mean postoperative hospital stay was 5.3 +/- 0.5 days. Follow-up ranged from 3 to 71 months, with a mean of 33 months. All patients demonstrated clinical benefit after operation. CONCLUSIONS Thoracoscopic sympathectomy in patients with severe ischemia of upper limb extremities permits optimal symptomatic control and maximum tissue salvage. Because the procedure is minimally invasive, safe, and associated with a low rate of complications, it should be considered earlier the natural course of this disease.

Bullectomy is comparable to lung volume reduction in patients with end-stage emphysema

OBJECTIVES Emphysema is one of the most prevalent disabling diseases, not modified by current medical treatment and physical rehabilitation. Lung transplantation is an effective clinical option in end-stage emphysema but it is available only for a limited number of patients. Bullectomy and lung volume reduction represent other surgical options to improve symptoms and exercise tolerance in selected patients. Both procedures allow the removal of the area of emphysematous lung resulting in improvement in chest wall mechanics, ventilation/perfusion ratio and re-expansion and better function of the residual lung. There is some evidence that in patients with end-stage emphysema bullectomy and lung volume reduction work in the same manner and yield similar functional results. METHODS We compared and analyzed retrospectively two groups of patients with end-stage emphysema who underwent bullectomy or lung volume reduction. Over the last 5 years 20 patients with end-stage emphysema presenting with bullae underwent thoracoscopic bullectomy (Group I). During the same period of time 18 patients with end-stage non-bullous emphysema underwent thoracoscopic unilateral lung volume reduction. Pre-operative baseline respiratory function data, peri-operative data, and functional results recorded at 6 and 12 months were compared and analyzed. RESULTS Both groups were homogeneous in terms of age, degree of respiratory derangement and severity of emphysema. Complication rate and peri-operative data were similar in the two groups. Improvement in symptoms, respiratory function and exercise tolerance was comparable. CONCLUSIONS Our experience supports the hypothesis that the physiopathological basis of respiratory improvement after bullectomy and lung volume reduction surgery in patients with end-stage emphysema is the same, although the exact mechanism remains incompletely understood.

Endoscopic treatment of lung cancer invading the airway before induction chemotherapy and surgical resection

OBJECTIVE Many patients with advanced lung cancer invading the airway require only palliation; however, induction chemotherapy and surgery may sometimes be considered. Preliminary endoscopic palliation may improve quality of life and functional status, allows better evaluation of tumor extension and contributes to prevent infectious complications. We reviewed our experience with preliminary laser treatment, induction chemotherapy and surgical resection in patients with lung cancer invading the airway. METHODS Twenty-one patients with stage IIIA and IIIB lung cancer presenting with an 80% unilateral airway obstruction were treated with laser resection, induction chemotherapy and surgery. Spirometry, arterial blood gas analysis, quality of life (QLQ-C30 score) and performance status were recorded before and after laser treatment and after chemotherapy. Complications during chemotherapy, surgical morbidity and mortality, and survival were also recorded. RESULTS No complications were observed after endoscopic treatment. FEV(1) significantly improved from 1.4+/-0.4 l/s to 2.2+/-0.7 l/s, as well as FVC (from 2+/-0.5 to 3.1+/-0.8 l), and remained stable after chemotherapy. The QLQ-C30 score significantly improved after laser treatment (from 45+/-4.8 to 31+/-2.5) as well as the Karnofsky status (from 76+/-5 to 90). One patient developed pneumonia during induction chemotherapy. Three patients were not operated on. We performed five pneumonectomies (one right tracheal sleeve pneumonectomy) and 13 lobectomies (five associated to a bronchial sleeve resection). One patient (5.5%) died after the operation. Four patients experienced minor postoperative complications. Three-year survival after the operation was 52%. CONCLUSIONS Preliminary endoscopic palliation of lung cancer invading the airway is feasible, improves evaluation and staging, helps to reduce the incidence of complications during induction chemotherapy without increasing surgical morbidity and mortality.

Bilateral sequential lung transplantation without sternal division

Objectives: The ‘clamshell incision’ is considered the standard approach for bilateral sequential lung transplantation (BSLT); however, a considerable morbidity may be related to this incision. The bilateral anterolateral thoracotomy without sternal division is an alternative approach that may contribute to avoid chest wall complications. Methods: We have employed this approach in a prospective series of 34 patients undergoing bilateral transplantation (Group I). The results were retrospectively compared with an historical control group of 37 patients (Group II) undergoing transplantation through the clamshell incision. Results: The operative time in Groups I and II were 228 ^ 32 and 293 ^ 37 min, respectively; the difference between the ischemic time of the first and second lungs were 68 ^ 20 and 73 ^ 15 min. Intensive care unit stay was 5 ^ 6 vs. 13 ^ 10 days and length of hospitalization was 25 ^ 16 vs. 32 ^ 10 days. Vital capacity measured 3 weeks after the transplant was significantly higher in Group I (65 ^ 13 vs. 45 ^ 8% predicted) as well as FEV1 (71 ^ 8 vs. 58 ^ 7% predicted). No wound related complication was observed in Group I; in Group II, there were 17 chest wall complications: sternal osteomyelitis in three patients (surgical debridement and closure with a muscle flap), migration of the Kirshner wire in three (removal of the wire), sternal override in three (surgical correction) and prolonged pain in eight. Conclusions: The bilateral anterolateral thoracotomy without sternal splitting is a safe and effective approach for BSLT; it allows to avoid sternal complications and contributes to improve respiratory function in the early postoperative period. q 2003 Elsevier Science B.V. All rights reserved.

Improved Results With Lung Transplantation for Cystic Fibrosis

YSTIC fibrosis (CF) is the most frequently inheritedlethal disorder among caucasians. Improvements intherapy have resulted in an average life span extending intothe third decade of life; however, no cure is available at thepresent time and 95% of deaths are related to chronicobstructive lung disease, bronchiectasis, and consequentrespiratory failure.

Recovery of chronic renal impairment with sirolimus after lung transplantation

BACKGROUND Standard immunosuppression after lung transplantation includes calcineurin inhibitors, azathioprine, and steroids. Calcineurin inhibitor administration is associated with an increased renal impairment. Sirolimus shows no renal toxicity and could be used in selected patients. METHODS We have prospectively administered sirolimus as an alternative to calcineurin inhibitors in 15 lung transplantation recipients with persistent drug nephrotoxicity. Eight patients had also bronchiolitis obliterans syndrome. The mean serum creatinine and azotemia were 2.7 +/- 1.1 mg/dL and 111 +/- 39 mg/dL. After starting sirolimus, azathioprine was reduced to 50%-25% of baseline, calcineurin inhibitors were gradually reduced and eventually stopped, and steroids were maintained stable. Patients started sirolimus with 2 to 5 mg/d orally; adjustments were made according to trough levels (4 to 12 ng/mL for combined sirolimus + calcineurin inhibitors; 12 to 20 ng/mL as monotherapy), toxicity, and perceived efficacy. Patients were monitored for renal and graft function and clinical status. RESULTS A significant creatinine decrease was observed after 6 months of treatment (p < 0.02); azotemia decreased after 1 month and remained stable (p < 0.01). Pulmonary function tests did not show any significant modification from before sirolimus baseline in patients without bronchiolitis obliterans syndrome. There were eight infectious complications and 10 episodes of toxicity (4 dermatitis, 2 epistaxis, 1 headache, 1 diarrhea, 1 nausea, 1 laryngeal cancer). Moderate leukocytopenia (n = 3) and hypertriglyceridemia (n = 6) responded to dose reduction. One patient was lost to follow-up. Three patients died of complications related to bronchiolitis obliterans. One patient underwent transplantation again. CONCLUSIONS Sirolimus administration allows amelioration of renal function with a relatively low morbidity and is useful for chronic renal impairment rescue after lung transplantation.