Giacomo Cusumano

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.

Malignant solitary fibrous tumors of the pleura: retrospective review of a multicenter series.

Introduction: Available data on the malignant solitary fibrous tumor of the pleura (mSFTP), a very rare neoplasm with unpredictable prognosis, are scarce. The aim of this study is to collectively analyze the aggregated data from the largest series in the English literature to date, a multicenter, 10-year study of 50-cases. Methods: We retrospectively reviewed the clinical records of patients who underwent surgical resection for mSFTP in the period between January 2000 to July 2010. Long-term survival (LTS) and 5-year disease-free survival were analyzed in detail. Results: There were 24 men and 26 women (median age, 66 years; age range, 44–83 years). Thirty-two patients (64%) were symptomatic. A malignant pleural effusion was diagnosed in 12 cases. Surgical resection included isolated mass excision in 13 patients and extended resection in 35. In the remaining two cases only biopsies were undertaken. The resection was complete in 46 cases (92%). Adjuvant treatment was administered to 15 patients. Median follow-up was 116 months (range, 18–311 months). Overall LTS and disease-free survival were 81.1% and 72.1%, respectively. Fifteen patients (30%) experienced a relapse of the disease. Complete resection yielded much better LTS than partial resection (87.1% versus 0%; p < 0.001). At the Cox regression analysis, incomplete resection (hazards ratio [HR]: 39.02; 95% confidence interval [CI]:4.04–380.36; p = 0.002) and malignant pleural effusion (HR: 3.44; 95%CI: 0.98–12.05; p = 0.053) were demonstrated to be risk factors for earlier death. At multivariate analysis, chest-wall invasion and malignant pleural effusion increased the risk of recurrence (HR: 4.34; 95%CI: 1.5%–12.6%; p = 0.007 and HR: 3.48; 95%CI: 1.1%–11.0%; p = 0.038, respectively). Conclusions: Surgical resection remains the treatment of choice for mSFTP. Relapse is common (approximately 30%). Incomplete resection and malignant pleural effusion at diagnosis impact LTS negatively.

Risk factors for postoperative delirium after colorectal surgery for carcinoma

BACKGROUND AND AIM Data regarding the incidence and risk factors for postoperative delirium (PD) after gastrointestinal surgery are heterogeneous because they include both benign and malignant disease. The aim of this study was to investigate the incidence and risk factors for PD in 100 consecutive patients over 65 years who underwent colorectal surgery for carcinoma. METHODS Pre-operative cognitive function was assessed using the Mini Mental State Examination. The onset of PD was diagnosed by the Confusion Assessment Methods administered to the patients every 12 h starting from the first postoperative day to discharge. The severity of PD was also evaluated with the Delirium Rating Scale. Different parameters: pre-, intra- and postoperative, were analyzed. Univariate and multivariate analyses were performed. RESULTS PD developed in 18% of patients. Univariate analysis revealed that advanced age, a history of PD, alcohol abuse, lower blood albumin concentration, intra-operative hypotension, elevated infusion volume and excessive blood loss were significantly related to the development of PD. On multivariate analysis, only lower levels of albumin, alcohol abuse, and hypotension were independent risk factors for PD. CONCLUSIONS These findings suggest that PD is a frequent complication after colorectal surgery for carcinoma. A model based on pre, intra and postoperative risk factors allows prediction of the patients risk for developing PD in order to implement preventive measures for this complication.

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.

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.

Long-Term Results after Treatment for Recurrent Thymoma: A Multicenter Analysis

Objectives: The treatment for recurrent thymoma remains a very controversial issue. This study aims to investigate the long-term outcomes in patients with relapse according to treatment strategies and clinicopathological features. Methods: We retrospectively analyzed the database of three tertiary centers of thoracic surgery with the aim of reviewing the clinical records of 81 patients who experienced a recurrent thymoma after radical thymectomy, in the period between January 2001 and June 2013. The staging of both primitive and recurrent thymomas were based on the surgical and pathological criteria described by Masaoka. Experienced pathologists reassessed independently the histology of the initial thymoma and its relapse, according to the WHO classification. To the purposes of this study R+ resection or thymic carcinoma were considered as exclusion criteria. The overall outcome for long-term (5 years and 10 years) survival and disease-free survival after initial thymectomy and after treatment of recurrent thymoma were analyzed using standard statistics. Results: The population was gender balanced (41 M, 40 F), mean age: 46.4 ± 12.3 years. Fifty-four patients (66.7%) were affected by myasthenia gravis, while the other 14 by other paraneoplastic conditions. Surgery was performed in 61 patients (75.3%,), and radiotherapy and/or chemotherapy in 14 patients (17.3%). The mean follow-up duration after recurrence onset was 66.3 ± 56.4 months. Adjuvant therapy had no effect on prolonging the disease-free survival: no differences were found when investigating the administration of adjuvant chemotherapy (no CHT = 91.5 ± 76.4 months versus yes CHT=64.0 ± 41.3) and radiotherapy (no RT=86.2 ± 72.8 months versus yes RT= 93.0 ± 62.3; p = 0.8). Relapses were mostly local (mediastinum: 15 cases, pleura: 44 cases); hematogenous distant recurrences were observed in 15 cases (lung: 12; liver: 1; bone: 2 cases). An upgrade in the WHO class (defined as the “migration” of WHO class at initial thymectomy to more aggressive WHO class assigned at thymic recurrence resection) was found in 25/61 cases (40.9%), but this phenomenon apparently did not influence patient’s prognosis. Overall, the 5- and 10-year survival rates after the initial thymectomy were 94.8% and 71.7%, respectively, while the 5- and 10-year survival rates after the treatment of the recurrence at the thymic level were 73.6% and 48.3%, respectively (82.4% at 5 years and 65.4% at 10 years when a R0-re-resection was obtained). The analysis on the trends of disease-free survival indicated that the site of recurrence (hematogenous diffusion) seems to be associated to a higher risk of re-relapse (p = 0.01). Conclusions: Even following a thymectomy performed with radical intent, thymoma may recur several years later, usually as a locoregional relapse. A rewarding long-term survival may be expected after treatment, especially when a re-resection (radical) is performed (82.4% at 5 years). An histopathological “WHO upgrade” (from “low-risk” WHO classes at thymectomy to “high-risk classes” at relapse) may be observed in a remarkable percentage of patients (nearly 40% in this series), but this phenomenon seems to be not correlated with any worsening of the prognosis.

Surgical treatment of stage III thymic tumors: a multi-institutional review from four Italian centers §

OBJECTIVE Radical surgery is the cornerstone of treatment for thymic tumors, but a complete surgical resection in stage III is not always achievable; and recurrence of disease is not rare. We reviewed the results of four centers with large experience in multimodality treatment of stage III thymic tumors. METHODS Between 1980 and 2009, 249 patients (137 males: 112 females; median age 50 years) with stage III thymic tumors underwent surgery. Myasthenia gravis (MG) was present in 110 (44.2%) patients. A total of 94 (37.7%) patients received induction chemotherapy and 205 (82.7%) had adjuvant treatments. RESULTS Thirty-day mortality was 0.8%. A total of 203 (81.6%) had R0, 26 (10.4%) R1 and 20 (8%) R2 resection. World Health Organization (WHO) histotype was: A in 2.4%, AB in 15.3%, B1 in 16.5%, B2 in 31.3%, B3 in 22.1%, and thymic carcinoma in 12.4%. The R0 rate was lower in patients who received induction chemotherapy (p=0.04), in B1-B2-thymic carcinoma histotypes (p = 0.05), and in patients without MG (p = 0.04). Overall 10-year survival rate was 64%; tumor-related and disease-free survival were 76% and 74%, respectively. At univariate analysis, R2 resection (p < 0.0001), recurrence of disease (p < 0.0001), absence of MG (p = 0.0009), thymic carcinoma (p = 0.002), age more than 50 years (p = 0.01), and vascular invasion (p < 0.0001) were predictors of poor survival. At multivariate analysis, type of resection (p < 0.0001), vascular involvement (p = 0.007), and recurrent disease (p < 0.0001) were independent predictors of prognosis. During follow-up, 43 (21.2%) patients developed recurrence. Patients with recurrence, who underwent redo surgery (n = 24), showed a similar survival to patients without recurrence. CONCLUSIONS Multimodality treatment of stage III thymic tumors achieved good survival. Radical surgery, even at recurrence, seems to be the most important prognostic factor.

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.