Costante Ricci

Analysis of prognostic factors and clinicopathological staging of thymoma

The prognostic value of four clinical variables (age and sex of patients, association with myasthenia gravis, and clinical stage) and histological type was analyzed in 83 consecutive patients with thymoma, histologically classified as cortical, medullary, and mixed. Age, sex, and association with myasthenia gravis did not prove to represent significant prognostic factors; clinical stage and histological type, on the contrary, had a highly significant prognostic value (p less than 0.001). A model of clinicopathological staging, based on both clinical stage and histological type, in which three major prognostic groups are considered is proposed. The degree of significance of this model is higher (p less than 0.0001) than that of clinical stage and histological type considered individually; its validity is further supported by the results of multivariate analysis according to the Cox regression model (p = 0.0001). We think it represents a prognostically valuable approach to the problem of management of thymoma.

Multimodality Treatment of Thymoma: A Prospective Study

BACKGROUND Thymomas are a heterogeneous group of tumors. Treatment of invasive lesions is not well standardized. The aim of this study is to propose a clinicopathologically based protocol for multimodality therapy. METHODS Between 1965 and 1988, we operated on 83 patients with thymoma who did not receive standardized adjuvant therapy. In 1989, on the basis of the retrospective analysis of the data, we started a multimodality therapy protocol and used it for 65 patients. Twelve patients had medullary thymoma (11 stage I and 1 stage II), 13 had mixed type (6 stage I and 7 stage II), and 40 had cortical thymoma (4 stage I, 11 stage II, 12 stage III, and 13 stage IV). We considered three groups. Group I (n = 18 patients), benign thymoma, included stage I and II medullary and stage I mixed thymomas; radical resection with no adjuvant therapy was performed. Group II (n = 22), invasive thymoma, included stage I and II cortical and stage II mixed thymomas; postoperative chemotherapy plus radiotherapy was always administered. Group III (n = 25), malignant thymoma, comprised stage III and IV cortical thymomas and stage III mixed thymomas; resectable stage III lesions were removed, and highly invasive stage III and stage IV lesions underwent biopsy, neoadjuvant chemotherapy, and surgical resection; postoperative chemotherapy and radiotherapy was administered to all patients. RESULTS The 8-year survival rate for patients in stages I, II, III, and IV was 95%, 100%, 92%, and 68%, respectively. Patients with medullary thymoma had a 92% 8-year survival rate; those with mixed type, 100%; and those with cortical thymoma, 85%. Group I had an 8-year survival rate of 94%; group II, 100%; and group III, 76%. Survival was compared with that of patients operated on before 1989: differences were not significant for group I; survival improved in group II (100% versus 81%; p = not significant); and group III showed significant improvement (76% versus 43%; p < 0.049). CONCLUSIONS Multimodality treatment with neoadjuvant chemotherapy and adjuvant chemotherapy plus radiotherapy may improve the results of radical resection and the survival of patients with invasive and malignant thymoma.

Safety and efficacy of bronchovascular reconstruction after induction chemotherapy for lung cancer

OBJECTIVE The aim of this study was to ascertain the safety and efficacy of bronchial sleeve resection and reconstruction of the pulmonary artery in patients who had undergone induction chemotherapy for lung cancer. METHODS Between January 1991 and July 1996, we operated on 68 patients who had received three cycles of cisplatin-based induction chemotherapy. In 27 of these cases, we performed a lobectomy (n = 25) or bilobectomy (n = 2) associated with reconstruction of the bronchus, the pulmonary artery, or both. In only five additional patients, pneumonectomy had to be carried out. Before chemotherapy, 14 patients were in stage IIIA and 13 were in stage IIIB. All patients in stage IIIB had T4 disease; no N3 cases were included. At thoracotomy, one patient had no evidence of tumor, six were in stage I, 13 were in stage II, six were in stage IIIA, and one was in stage IIIB. Sixteen patients had epidermoid carcinoma and 11 had adenocarcinoma. RESULTS Sixteen patients underwent bronchial sleeve resection; 11 had various types of pulmonary artery reconstruction, associated with the bronchial sleeve in eight cases. In 26 patients, resection was radical with histologically negative margins. Neither bronchial complications nor deaths occurred. One patient had empyema and two had wound infections. Mean chest tube duration was 6 days. After a postoperative follow-up of 4 to 69 months (mean 25 months), 14 patients are alive and free of disease, one is alive with disease, and 12 have died. There were no local recurrences. The 1- and 4-year survival rates are 78% and 39%, respectively. CONCLUSIONS Although it is technically demanding, lobectomy associated with bronchovascular reconstruction is feasible, with good immediate and long-term results, after induction chemotherapy.

Comparative merits of thoracoscopy, mediastinoscopy, and mediastinotomy for mediastinal biopsy

Between April 1992 and April 1993, we performed fifty-four mediastinal biopsies in 51 patients with a mediastinal mass. Nine of these had lung cancer with mediastinal lymphadenopathy, and the remaining 42 had various primary mediastinal lesions. We have performed twenty video-assisted thoracic surgical procedure, twenty-six mediastinoscopies, and eight anterior mediastinotomies. In 3 patients the diagnosis was not obtained by mediastinoscopy, and video-assisted thoracoscopy was performed. We conclude that mediastinoscopy is indicated for the majority of lesions involving the peritracheal space. Restaging of lymphoma and highly infiltrative lesions are better managed by video-assisted thoracic surgery. Anterior mediastinotomy is indicated when feasible under local anesthesia for tumors infiltrating the anterior chest wall. In all other cases video-assisted thoracic surgery is preferable because it allows removal of large tissue biopsy specimens and even resection with wide surgical exposure and low operative trauma.

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.

Induction chemotherapy for T4 centrally located non–small cell lung cancer

OBJECTIVE We used induction chemotherapy in a prospective, single-institution clinical trial intended to achieve resectability in patients with centrally located, unresectable T4 non-small cell lung cancer. Other types of IIIB disease were excluded. METHODS Between January 1990 and April 1996, we enrolled 57 patients with histologically confirmed non-small cell lung cancer. Eligibility criteria for T4 were clinical (superior vena cava syndrome, 9 patients), vocal cord paralysis (6 patients), dysphagia from esophageal involvement (1 patient), radiologic (computed tomography and magnetic resonance evidence of infiltration, 10 patients), bronchoscopic (tracheal infiltration, 11 patients), and thoracoscopic (histologically proven mediastinal infiltration, 20 patients). After 3 cycles of cisplatin (120 mg/m2), vinblastine (4 mg/m2), and mitomycin (2 mg/m2), patients were reevaluated. RESULTS Forty-two patients (73%; 36 men, 6 women; age range, 42-75 years; mean, 58 years) responded to therapy and underwent thoracotomy; 11 patients did not respond, and 4 patients had major toxicity. Thirty-six patients (63% of the entire group) had complete resection. We performed 4 exploratory thoracotomies, 6 pneumonectomies, 32 lobectomies (20 procedures were associated with reconstruction of hilar-mediastinal structures). Overall, 4 patients had no histologic evidence of disease. We had 2 bronchopleural fistulas with 1 death and 5 other major complications. Overall survival at 1 and 4 years is 61.4% and 19.5%, respectively. Forty-two patients (73%) underwent exploratory operation, with a 4-year survival of 25.9%; 36 patients (63%) had complete resection, with a 4-year survival of 30.5%. CONCLUSIONS Induction chemotherapy is effective for downstaging and surgical reconversion of centrally located T4 non-small cell lung cancer. Survival is promising, especially in patients whose disease becomes resectable.

Protection and revascularization of bronchial anastomoses by the intercostal pedicle flap

We used an improved method for preparation of the intercostal pedicle flap for encircling bronchial anastomoses, and we studied its vascular supply after the operation. The flap was used in 56 patients undergoing various types of sleeve resection and in three patients undergoing single lung transplantation. The technique is simple, fast, and causes neither extra surgical trauma nor complications. It allows satisfactory isolation and sealing of the bronchial anastomosis. Even if complete anastomotic dehiscence occurs (one case), the flap preserves the continuity of the airway, thus avoiding bronchopleural fistulas or other complications. The postoperative arteriographic study of the intercostal artery supplying the flap (performed in 14 patients) demonstrated the full patency of the vessel in all cases. It also showed that a fine vascular network develops around the anastomosis early in the postoperative period.

Correlations between histological type, clinical behaviour, and prognosis in thymoma.

Seventy four cases of thymoma were reclassified into three histological categories--cortical (30), medullary (9), and mixed (34) (the remaining patient had an intrathymic thymoma)--for an investigation of the relation between histological type, clinical behaviour, and long term prognosis. There were significant differences between the histological types in the frequency of myasthenia gravis and of the different tumour stages, the mean age of the patients, and prognosis. Myasthenia gravis occurred more commonly in patients with cortical (33%) and mixed thymoma (35%) than in patients with medullary thymoma (11%). Five, 10, 15, and 20 year actuarial survival was 100% for medullary thymoma; 85%, 76%, 65% and 65% respectively for mixed thymoma; and 52%, 45%, 45%, and 45% for cortical thymoma. Medullary thymoma is a benign tumour arising late in life and there was no mortality in this series after surgery alone. Cortical thymoma usually presented in middle age and must be regarded as malignant; mortality was 50% at five years despite a multidisciplinary approach, with surgery and postoperative radiotherapy in all patients and chemotherapy in selected cases. Mixed thymoma had a better prognosis than cortical thymoma, but must be regarded as potentially malignant. One third of the total patients had died by 10 years despite radical tumour resection.

Thoracoscopic Staging of IIIB Non–Small Cell Lung Cancer Before Neoadjuvant Therapy

BACKGROUND Bronchoscopy and imaging techniques are the most valuable tools for noninvasive staging of patients with locally advanced non-small cell lung cancer but their overall accuracy is not satisfactory. Neoadjuvant therapy protocols require strict criteria for patient selection and invasive staging should be carried out to establish standardized inclusion criteria and to homogenize posttreatment results. The aim of this prospective study was to evaluate the role of thoracoscopy in the assessment of the real extent of lung cancer in patients with the clinical suspicion of stage IIIB disease. METHODS From January 1993 to March 1996, we observed 64 patients with suspected IIIB non-small cell lung cancer. Forty-three patients were considered eligible for this study and were divided into three groups: group I, cytologically negative pleural effusion (n = 10); group II, computed tomographic suspicion of mediastinal infiltration (n = 30); and group III, contralateral lymphadenopathy not accessible by mediastinoscopy (n = 3). RESULTS No complications related to thoracoscopy occurred. Of 10 patients in group I, thoracoscopy up-staged the disease to IIIB in 6 (60%). Of 30 patients with suspicion of T4 (group II), thoracoscopy confirmed T4 in 15 patients (50%). Nine (30%) were downstaged to stage IIIA and 2 (6.6%) to stage II. In 4 patients (13.4%) thoracoscopy failed to yield definitive staging. In all 3 patients of group III, thoracoscopy confirmed stage IIIB. CONCLUSIONS Thoracoscopy proved adequate for correct staging in 39 of 43 patients (91%); therefore, it should be considered in the staging work-up of suspected stage IIIB patients.

Recurrent thymoma: evidence for histological progression

The clinicopathological features of nine cases of recurrent thymomas have been studied. At presentation, all cases were histologically classified as thymomas with cortical differentiation, including predominantly cortical thymoma, cortical thymoma and well‐differentiated thymic carcinoma. In five cases the morphological features of the recurrence(s) were suggestive of a histological progression of the tumour from predominantly cortical thymoma to cortical thymoma and/or well‐differentiated thymic carcinoma, usually associated with a more advanced clinical stage, the latter indicating a clinical progression. These findings suggest that all types of thymoma with cortical differentiation are histologically and histogenetically related neoplasms, associated with a more aggressive clinical behaviour and a significant risk of recurrence. The overall outcome of patients with recurrent thymoma in this series was poor, since six patients (66.6%) died due to the disease, 2–14 years after the first diagnosis. The clinical implication of our findings is that thymomas with cortical differentiation always need careful follow‐up, even in those cases which are not obviously invasive at onset.