Elisa Meacci

Thirty-Five–Year Follow-Up Analysis of Clinical and Pathologic Outcomes of Thymoma Surgery

BACKGROUND The impact of myasthenia gravis on patients with thymoma is still controversial when perioperative and long-term outcomes are analyzed. With the unique opportunity of a 35-year follow-up in a single institution, thymomatous myasthenia gravis cohort, we investigated the influence of early and long-term clinical predictors. METHODS We reviewed a surgical series of 317 (1972 to 2007) patients with thymoma: clinical and pathologic features were analyzed as prognostic factors matched against the short- and long-term survival and recurrence rates. RESULTS Male to female ratio was 153:164; median age, 49 years. Myasthenia gravis coexisted in 276 patients (87.1%). Thymomas were classified according to the Masaoka (42.0% stage I, 32.2% stage II, 21.5% stage III, and 4.4% stage IV) and the World Health Organization (3.5% type A, 9.5% type AB, 19.2% type B1, 57.7% type B2, 8.2% type B3, and 1.9% thymic carcinoma) staging systems. The resection was complete in 295 patients (93.1%). Operative mortality and morbidity were respectively 1.6% and 7.6%. No differences were recorded in postoperative outcome stratifying for myasthenia gravis or comorbidities. Mean follow-up was 144.7 +/- 104.4 months. The overall 5-, 10-, 20-, and 30-year survival rates were 89.9%, 84.1%, 73%, and 58.6%, respectively. The completeness of resection (p < 0.001), the Masaoka staging (p = 0.010), and the World Health Organization classification (p < 0.001) all significantly influenced the long-term survival (univariate analysis). Only completeness of resection was significantly correlated with a better prognosis (p < 0.001) in multivariate analysis. Masaoka staging (p < 0.001) and World Health Organization classification (p < 0.001) significantly correlated with the disease-free survival in the univariate and multivariate analyses as significant prognostic factors (Masaoka, p < 0.001; World Health Organization, p = 0.011). Myasthenia gravis patients showed a better prognosis in terms of long-term survival (p = 0.046) and disease-free survival (p = 0.012) in the univariate analysis. CONCLUSIONS We confirm the evidence that the clinical staging and the histologic classification influence long-term survival. The presence of myasthenia gravis was not significantly related to operative outcome, but prolongs both long-term survival and disease-free survival.

Single-centre 40-year results of redo operation for recurrent thymomas

OBJECTIVE Modes of treatment for recurrent thymoma remain controversial. The aim of this study is to analyse the early and long-term results of surgical intervention for this condition. METHODS Between 1972 and 2008, 43 out of 315 patients, who underwent resection with radical intent for thymoma, subsequently relapsed. Of these, 30 cases were deemed suitable for resection and operation, and were surgically treated. The remaining 13 were treated with radio- and/or chemotherapy (RT/CT). Overall outcomes for long-term survival up to 5 years (LTS) and disease-free survival (DFS) were analysed using standard statistics. RESULTS The average age of the relapsed patients was 54.7±12.7 years. There were 21 males and 22 females. Forty out of the 43 had myasthenia gravis (MG). Fifteen cases concerned a single detected relapse lesion. Among the 43 patients, relapses were found in the following sites: pleura (25 cases), mediastinum (12), lung (five), liver and bone (one). The perioperative mortality was 0% and the morbidity was 27%. Twenty-two of the surgically treated patients had complete resection; their LTS was 77% and DFS was 71%. Those patients who underwent surgery had significantly better outcomes compared with patients treated with radio- and/or chemotherapy (LTS only 35%; hazard ratio (HR): 0.22; 95% confidence interval (CI): 0.08-0.59; p=0.001). Complete repeated resection yielded much better outcomes than partial resection (LTS 91% vs 31%, p<0.001), whereas incomplete resection was associated, as one might expect, with a poor prognosis (HR: 6.12; 95% CI: 1.18-31.55; p=0.031). No evidence for an association with other clinical, surgical and pathological characteristics was found with regard to LTS or DFS. CONCLUSIONS Surgical resection is recommended for the treatment of recurrent thymoma, provided that criteria for suitability for resection/operation are satisfactory at the time of diagnosis. Best survival outcomes are found to depend on the degree of completeness of the repeat resection.

Surgery for oligometastatic non-small cell lung cancer: long-term results from a single center experience.

OBJECTIVE The role of surgery in the multimodal therapy for selected stage IV oligometastatic non-small cell lung cancer (NSCLC) is still a forum of open discussion. METHODS We have retrospectively analyzed the records of 53 patients with oligometastatic NSCLC who had been treated with curative intent in the period January 1997 to May 2010. RESULTS The mean age and the male/female ratio were 61 years and 32:21, respectively. A single metastatic lesion was present in 45 (84.9%) subjects, in 2 patients there were 2 different anatomic sites involved, and in 8 patients there were 2 metastases in the same site. The most common involved sites were brain (39), followed by adrenal gland (7), bone (3), vertebrae (3), liver (1), and contralateral supraclavicular lymph node (1). Distant disease was completely resected in 42 patients; 10 patients were treated with exclusive chemotherapy and/or radiotherapy and 1 with local laser therapy. Twenty-nine patients had been administered concurrent chemoradiation in a neoadjuvant setting before the surgical treatment at the lung or both sites (primary/distant). The pulmonary resection was complete (R0) in 42 patients (79.2%). Overall, 1- and 5-year survivals were 73.1% and 24%, respectively (median follow-up, 28 months). Median overall survival, local disease-free survival, and distant disease-free survival, estimated using the Kaplan-Meier method, were respectively 19, 72, and 12 months. After stepwise multivariate analysis, the weight loss (P<.001), the completeness of pulmonary resection (P=.0019), and, interestingly, the performance of a positron emission tomography-computed tomography scan in preoperative staging (P=.05) maintained their independent prognostic value as overall survival determinants. CONCLUSIONS Surgical treatment for selected stage IV NSCLC is feasible and safe. Furthermore, good survival can be expected in those patients in whom a complete resection of the primary tumor and radical control of the distant diseases are accomplished.

Thymectomy in myasthenia gravis: proposal for a predictive score of postoperative myasthenic crisis

OBJECTIVES Thymectomy plays an important role in patients with myasthenia gravis (MG). This study aimed to explore predictors of postoperative myasthenic crisis (POMC) after thymectomy and to define a predictive score of respiratory failure. METHODS The clinical data of 177 patients with MG undergoing thymectomy from January 1995 to December 2011 were retrospectively reviewed. The following factors were analysed in relation to the occurrence of myasthenic crisis: gender, age, body mass index (BMI), anti-acetylcholine receptor-antibody level, bulbar symptoms, comorbidities, duration of symptoms, Osserman-stage, Myasthenia Gravis Foundation of America (MGFA) stage, history of myasthenic crisis, use of immoglobulins or plasmapheresis, kind of therapy, spirometric and blood gas parameters, histology, kind of surgery, non-myasthenic complications and duration of intubation. RESULTS Twenty-two patients experienced postoperative respiratory failure after thymectomy. Univariate analysis revealed a correlation with age >60 years (odds ratio (OR) = 1.79, 95% confidence interval (CI) = 1.04-6.78; P = 0.040); Osserman-stage (IIB- OR = 5.16, 95% CI = 1.10-24.18; P = 0.037, III-IV- OR = 8.75, 95% CI = 1.53-50.05; P = 0.015); bulbar symptoms (OR = 7.42, 95% CI = 1.67-32.84; P = 0.008); BMI >28 (OR = 3.99, 95% CI = 1.58-10.03; P = 0.003); preoperative plasmapheresis (OR = 2.97, 95% CI = 1.18-14.04; P = 0.021); duration of symptoms >2 years (OR = 4.00, 95% CI = 1.09-14.762; P = 0.036); extended surgery (OR = 2.52, 95% CI = 1.02-6.22; P = 0.045); lung (OR = 4.05, 95% CI = 1.44-11.42; P = 0.008), pericardial (OR = 3.78, 95% CI = 1.45-9.82; P = 0.006) or pleural resection (OR = 3.23, 95% CI = 1.30-8.03; P = 0.012); Vital Capacity % <80% (OR = 0.20, 95% CI = 0.05-0.82; P = 0.025) and PaCO2 >40 mmHg (OR = 3.76, 95% CI = 1.12-12.68; P = 0.032). Multivariate logistic regression analysis showed that Osserman-stage (IIB- OR = 5.69, 95% CI = 1.09-29.69; P = 0.039 (III-IV- OR = 11.33, 95% CI = 1.67-76.72; P = 0.013), BMI >28 (OR = 3.65, 95% CI = 1.10-12.15; P = 0.035), history of myasthenic crisis (OR = 24.10, 95% CI = 2.34-248.04; P = 0.007), duration of symptoms >2 years (OR = 5.94, 95% CI = 1.12-31.48; P = 0.036) and lung resection (OR = 8.48, 95% CI = 2.18-32.97; P = 0.002) independently predict POMC. Excluding history of preoperative myasthenic crisis (statistically associated with Osserman-stage), we built a scoring system according to the OR of Osserman-stage (I-IIA, IIB, III-IV), BMI (<28, ≥ 28), duration of symptoms (<1, 1-2, >2 years) and association with a pulmonary resection. This model helped in creating four classes with increasing risk of respiratory failure (Group I, 6%; Group II, 10%; Group III, 25%; Group IV, 50%). CONCLUSIONS Our model facilitates the stratification of patient risk and prediction of the occurrence of POMC. Moreover, it could help to guide the anaesthesiologists decision on the duration of intubation. Further studies based on larger series are needed to confirm these preliminary data.

Surgery for patients with persistent pathological N2 IIIA stage in non-small-cell lung cancer after induction radio-chemotherapy: the microscopic seed of doubt §

OBJECTIVE The surgical treatment of residual N2 disease following induction radio-chemotherapy (IT) for locally advanced cIIIA-N2 non-small-cell lung cancer (NSCLC) is still debated. The long-term results after resection in a pN2 series are at the focus of this study. METHODS From January 1992 to December 2008, 161 consecutive pathologically proven Stage IIIA-N2 NSCLC patients underwent IT. Among these, 40 pN2s were included in this retrospective analysis. The associations between the mortality and the disease-free status with potential risk factors were explored by means of the Kaplan-Meier and Cox regression analysis. RESULTS Mean age and male/female ratio were 58.7 ± 9.7 years and 36/4, respectively. Twelve patients (30%) showed a clinical partial response and 28 (70%) showed stable disease. There was one (3%) perioperative death and four (10%) major complications. In the total group, the 3- and 5-year survival rates were 24.2% and 19.3%, respectively. The Cox regression analysis suggested that the macroscopic pN2 status proved to be a negative prognostic factor (hazard ratio (HR)=2.8, confidence interval (CI) 95%: 1.1-7.3; p=0.04). The recurrence rate flattened at 30.8% at the 3rd year. Furthermore, the bilobectomy-pneumonectomy group had a risk of relapse 6.9 times higher than the lobectomy group (CI 95%: 2.5-18.8; p < 0.001). CONCLUSIONS The persistence of disease at the N2 level after IT and surgery for cIIIa-N2 NSCLC does not exclude favorable outcome after resection, in particular in those patients with minor residual disease.

Osteopontin is not a specific marker in malignant pleural mesothelioma

BACKGROUND AND AIMS Osteopontin (OPN) is an integrin-binding protein recently shown to be related to tumorigenesis, progression and metastasis in different experimental models of malignancy. Malignant pleural mesothelioma (MPM) is a fatal disease in which the prognosis remains very poor and the knowledge of predictive factors for outcome is insufficient. The identification of new molecules involved in cancer initiation and development is a fundamental step for improving the curability of this kind of tumor. The purpose of this study is to define the role of OPN in the diagnosis of MPM by determining its prognostic and diagnostic value. METHODS A group of 24 surgically staged MPM subjects was compared with a group of 31 subjects with nonmalignant pulmonary diseases, and with 37 healthy controls. Tumor tissue was analyzed for OPN by immunohistochemical tests, and plasma OPN levels were measured by an enzyme-linked immunosorbent assay. RESULTS Plasma OPN levels were not significantly higher in either of the patient groups compared with the control group. Immunohistochemical analysis revealed OPN staining of tumor cells in 21 of 24 MPMs. Receiver operating characteristic curve/area under the curve (ROC/AUC) analysis comparing the plasma OPN levels in the healthy group with those of MPM patients showed 40% sensitivity and 100% specificity at a cutoff value of 60.8 ng of OPN per milliliter (AUC 0.6). CONCLUSION Plasma OPN levels do not discriminate between chronic inflammatory and malignant lung diseases and staining intensity in MPM specimens does not correlate with OPN plasma levels.

Induction Therapy Followed by Surgery for T3-T4/N0 Non-Small Cell Lung Cancer: Long-Term Results

BACKGROUND The aim of this study was to analyze the impact of the induction chemoradiotherapy (IT) on the survival pattern in T3/T4-N0 non-small cell lung cancer (NSCLC) patients. METHODS The data of 71 patients treated from January 1992 to May 2007 were reviewed. Of these, 31 patients received IT prior to surgery (IT group: T3, 20 patients; and T4, 11 patients), and 40 directly underwent surgery (S group: T3, 34 patients; and T4, 6 patients). Survival rates were compared using the Kaplan-Meier analysis and the Cox proportional hazards models. RESULTS Mean ages were 62.5±9.9 years in the IT group and 67.7±7.1 in the S group. All patients but 1 completed the IT treatment and 27 patients (87%) were operated. A radical resection was possible in 21 patients (78%). In the IT group a complete pathologic response was obtained in 6 patients (22%), where 8 patients ended up in pI stage, 7 in pII stage, and 6 in pIII stage. The overall 5-year survival (long-term survival [LTS]) and disease-free 5-year survival (DFS) for the entire cohort were 40% and 34%, respectively. No significant differences were found when LTS in the IT group (44%) and in the S group (37%) were compared. At multivariate analysis, the completeness of resection was the only independent predictive factor (hazard ratio [HR]=5.18; 95% confidence interval [CI]=2.55 to 10.28) while Cox multivariate analysis (on the IT group only) confirmed the critical role of the pathologic downstaging (HR=4.62; 95% CI=1.54 to 13.89). CONCLUSIONS A multimodal strategy with IT treatment followed by surgery is a safe and reasonable treatment in T3/T4-N0 NSCLC patients, but no clear evidence of prognostic improvement may be assumed at the present time. Nevertheless, patients with radical resection and complete pathologic response have a very rewarding survival.

Is pulmonary function damaged by neoadjuvant lung cancer therapy? A comprehensive serial time-trend analysis of pulmonary function after induction radiochemotherapy plus surgery

OBJECTIVE We have analyzed short- and long-term variations of pulmonary function in locally advanced non-small cell lung cancer after induction chemoradiotherapy. METHODS Twenty-seven patients with stage IIIA (N2) non-small cell lung cancer underwent resection with radical intent after induction chemoradiotherapy in the period 2003 to 2006. Pulmonary function has been evaluated by spirometry, diffusing capacity of the lung for carbon monoxide, and blood gas analysis before induction chemoradiotherapy (T0), 4 weeks after induction chemoradiotherapy and before surgery (T1), and 1 (T2), 3 (T3), 6 (T4), and 12 months (T5) after surgery. RESULTS A 22.80% decrease of diffusing capacity of the lung for carbon monoxide (P < .001) was observed at T1. At T2 significant decreases in the following were present: vital capacity, -20.50% (P < .001); forced vital capacity, -22.50% (P < .001); forced expiratory volume in 1 second, -23.00% (P < .001); peak expiratory flow, -29.0 (P < .001); forced expiratory flow 25% to 75%, -13.7% (P = .005); and diffusing capacity of the lung for carbon monoxide, 43.6% (P < .001). However, in the interval between T2 and T5, a progressive improvement of lung function in most parameters was observed, but only diffusing capacity of the lung for carbon monoxide presented a significant increase (P < .001). Within the same time gap (T2 to T5), subjects 65 years of age or younger showed an increasing trend for vital capacity, forced expiratory volume in 1 second, total lung capacity, and residual volume significantly different from that of elderly patients, in whom a decrease in these parameters is reported. CONCLUSIONS An impairment of respiratory function is evident in the immediate postoperative setting in patients with non-small cell lung cancer receiving induction chemoradiotherapy. In the long-term period, a general recovery in diffusing capacity of the lung for carbon monoxide was found, whereas an improvement of forced expiratory volume in 1 second, vital capacity, total lung capacity, and residual volume was detected in the younger population only.

How Best to Assess the Quality of Life in Long-Term Survivors After Surgery for NSCLC? Comparison Between Clinical Predictors and Questionnaire Scores

BACKGROUND The determinants and predictors of QOL in lung cancer survivors who have received surgery remain defined vaguely and still debated. We evaluate clinical, surgical, and pulmonary function characteristics as predictors of QOL in long-term lung cancer survivors who received surgery. METHODS Quality of life was evaluated 5 years after surgery in 67 lung cancer patients using the European Organization for Research and Treatment of Cancer (EORTC) QOL Core Questionnaire, its lung cancer-specific module QLQ LC-13, and the Hospital Anxiety and Depression Scale questionnaire. Preoperative clinical, surgical, and pathologic data were matched with the questionnaire scores. RESULTS Sex was associated with role functioning and symptoms, with males more often reporting fatigue and pain, appetite loss, coughing, and hemoptysis (P < .05). Lower education was associated with better cognitive functioning (P < .05). Symptoms were worse for younger patients and for those with major comorbidity. Histology marginally influenced the global health status (P < .10) and the cognitive functioning (P < .05). Patients receiving complementary therapy more easily suffered from fatigue and insomnia (P < .05), and to a lesser extent from nausea and vomiting, constipation, and stress related to financial difficulties (P < .10). Higher values of forced expiratory volume at the first second (FEV(1)) and forced vital capacity (FVC) were significantly (P < .05) associated with a lower frequency of nausea and vomiting and appetite loss, while low percentage levels of FEV(1) and FVC were associated with lower global function and a greater severity of specific and nonspecific symptoms (P < .10 and P < .05). CONCLUSIONS Several preoperative features, particularly those reflecting pulmonary function, were moderately associated with QOL in long-term survivors and may be useful to address therapeutic strategies in lung cancer patients after surgery.

Staged axillary thoracotomy for bilateral lung metastases: an effective and minimally invasive approach.

OBJECTIVE We describe our experience with the staged axillary thoracotomy (SAT), for the treatment of bilateral lung metastases. MATERIALS AND METHODS Between January 1995 and June 1998, 75 lung metastasectomies were carried out in our institution, 49 (65%) monolateral, and 26 (35%) bilateral. In the latter group of patients we adopted a staged axillary thoracotomy. RESULTS All wedge resections and two lobectomies (1 LUL and 1 RLL) were performed through this approach. Resection has been complete in all patients. Histology was epithelial in 15 (57%), sarcoma in nine (35%) and germ cell in two (8%). Two to three metastases have been resected in 10 patients (38%); four to 10 in 12 patients (46%) and over 10 in four patients (15%). The radiological pre-operative assessment was accurate in 15 patients (57%), underestimated in nine (35%) and overestimated in two (8%). The average interval between the two procedures has been 24 +/- 6 days. The average operation duration time was 50 min (range 36-67). We do not report any post-operative death or major complication. The average hospitalization was 3.2 days (range 2-6) for each single procedure and 6.2 days (range 4-10) for both procedures. CONCLUSION This technique is adequate, fast and safe and did not affect the shoulder girdle motion at all providing an excellent cosmetic outcome. The operative trauma is limited and a minor post-operative pain is present. A shortening of the interval between the two operations is allowed.