Venanzio Porziella

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.

Enduring challenge in the treatment of nonsmall cell lung cancer with clinical stage IIIB: results of a trimodality approach

BACKGROUND Stage IIIb (T4/N3) non-small-cell lung cancer (NSCLC) is considered an inoperable disease and treatment is an enduring challenge. Surgery after induction therapy seems to improve locoregional control. We report the results of a phase II prospective trimodality trial (chemotherapy and concomitant radiotherapy plus surgery) in patients with stage IIIb NSCLC. METHODS From November 1992 to June 2000, 39 patients (37 men and 2 women, mean age 65 years) with clinical stage IIIb (34 T4N0 to 2, 4 T2 to 3N3, 1 T4N3, excluding T4 for malignant pleural effusion) entered the study. They received intravenous infusions of cisplatin 20 mg/m(2) and 5-fluorouracil 1,000 mg/m(2) (days 1 to 4 and 25 to 28) combined with a total dose of 50.4 Gy radiotherapy delivered over 4 weeks (1.8 Gy daily). Upon clinical restaging responders underwent surgery. RESULTS All patients were available for clinical restaging. No complete response was observed. Twenty-one patients had partial response (53.8%), 16 had stable disease (41%), and 2 had progressive disease (5.2%). Hematologic toxicity was moderate. Twenty-two patients (56.4%), 21 with partial response and 1 with stable disease, underwent surgery with no perioperative death. A radical resection was possible in 21 cases. Nine lobectomies, 3 bilobectomies, and 9 pneumonectomies were performed. Complications occurred in 5 patients (23.6%). Fourteen of the patients who underwent surgery (66.6%) showed a pathologic downstaging. A complete pathologic response was obtained in 9 cases (49%). Overall 5-year survival (Kaplan-Meier) was 23%. Resected versus non-resected patients showed a significant difference: 38% versus 5.6% (p = 0.028, log rank). CONCLUSIONS This trimodal approach for stage IIIb NSCLC appears safe and effective. It provides good therapeutic results with acceptable morbidity in surgical cases.

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.

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.

Pulmonary Neuroendocrine Tumor Incidentally Detected by 18F-CH PET/CT

We report the case of a pulmonary neuroendocrine tumor (NET) incidentally detected by F-CH PET/CT performed during restaging in a 68-year-old patient affected by prostate cancer. To clarify the nature of the pulmonary lesion, the patient underwent a CT-guided biopsy which revealed the presence of a pulmonary NET. A subsequent Ga-DOTANOC PET/CT demonstrated the somatostatin receptor expression in the pulmonary lesion. The patient underwent a right lung lobectomy; at pathology, a well-differentiated NET was confirmed. Our case highlights that pulmonary NETs should be considered in the differential diagnosis of pulmonary lesions showing uptake of radiolabeled choline.

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.

Paraneoplastic Acrokeratosis (Bazex Syndrome) in Lung Cancer

A 55-year-old white man, longstanding smoker (40 cigarettes a day for 30 years), with no past or family history of psoriasis, developed scaly erythematous hyperkeratotic lesions of the periungueal region of both hands, distributed symmetrically, first affecting thumb and second finger, then involving the other fingers, except the little finger (Fig 1). These lesions worsened during 1 year; a yellowish discoloration of nails with onychodystrophy involving both hands and feet was observed, together with hyperkeratosis and thickening of palms and soles, while sparing the other acral extremities. After 5 months, the patient underwent umbilical hernioplasty, and a chest x-ray performed at this stage did not show any abnormality. The skin lesions persisted for about 3 years showing resistance to a variety of topical treatments (ie, itraconazole, tioconazole, mometason). Shortly thereafter, about 3.5 years after the skin manifestations, the patient developed a whooping cough, and a chest-x-rays revealed a mass in the upper lobe of the right lung, subsequently confirmed with a computed tomography scan also showing omolateral nodes involvement. He was referred to the Division of Thoracic Surgery, Gemelli Hospital (Rome, Italy) presenting as paronichia-like lesions. All 20 nails showed dystrophic lesions and partial onicholysis resembling psoriasis or postinflammatory paronichia. No perilesional inflammation was seen, and the patient claimed he did not have any inflammation in past. Cultural and direct examination for fungi was negative. Familiar history for psoriasis was negative, and there was not any other sign of psoriasis on the skin and the nails. The patient underwent upper right lobectomy. The postoperative pathological diagnosis was G3 adenocarcinoma of the lung T2-N0-M0; immunohistochemistry showed that constituent cells were positive for cytokeratin 7 and thyroid transcription factor 1, while negative for cytokeratin 20 and synaptophysin. A 3-month course of treatment with cisplatin and navelbine was delivered. The skin lesions drastically improved in a few months, with complete healing in July 2008 (Fig 2). The diagnosis of Bazex syndrome (BS) associated with adenocarcinoma of the lung was given. Twenty-seven-months follow-up after successful surgical resection the patient has no evidence of disease. In 1922, Gougerot and Rupp first recognized paraneoplastic acrokeratosis (PA). The eponymous of BS is ascribed to André Bazex, who reported several cases since his first description of PA associated with a metastatic pyriform sinus cancer in 1965. At the same time, the term BS may also refer to a rare genodermatosis with cancer predisposition described by the same author. In this work, 143 cases of PA have been reviewed, mostly related to supradiaphragmatic squamous cell malignancies and affecting men older than age 40 years. The association with adenocarcinoma of the lung is rare. We observed a striking case of PA whose clinical outcome diverged from the standard three-stage course originally proposed by Bazex and Griffiths. As a rule, a cutaneous paraneoplastic disorder is mostly associated with squamous cell carcinoma of the upper aerodigestive tract and is characterized by a symmetric, psoriasiform, hyperkeratotic eruption of the extremities (ears, finger, toes, nose), which may also involve trunk and limbs. Itching and paining are uncommon, although the former may occur in up to 18% of cases. Hyperkeratotic eruption is typical of BS, some unusual features of the dermatosis have been described, such as hyperpigmented papules, plaques and bullous lesions. Diagnosis is clinical, based on the patient’s medical history and physical examination, paying attention to the characteristic distribution of the lesions. Other conditions such as acral psoriasis, palmoplantar keratoderma, onychomycosis, pityriasis rubra pilaris should be ruled out. To our knowledge, only 15 women (10.6%) with BS have been reported. Although pathogenesis is still unclear, several hypotheses have been proposed, pointing out to the cross reactivity between tumoral and cutaneous antigens as responsible for the skin damage. As observed by Bazex and Griffiths, PA generally present a well-defined three-stage course. In the first stage, acral regions are first involved including nails (77%), ears (76%), fingers (65%), and nose (62%) with no clinical evidence of the underlying tumor. In the

Farnesyltransferase Inhibitors and Human Malignant Pleural Mesothelioma: A First-Step Comparative Translational Study

It is known that the potential clinical use of farnesyltransferase inhibitors (FTI) could be expanded to include cancers harboring activated receptor tyrosine kinases. Approximately 70% of malignant pleural mesotheliomas (MPM) overexpress epidermal growth factor receptors (EGFR) and a subset express both EGFR and transforming growth factor α (TGF-α), suggesting an autocrine role for EGFR in MPM. We checked on MPM cells (10 human cell lines, 11 primary cultures obtained by human biopsies, and 7 short-term normal mesothelial cell cultures) concerning the following: (a) the relative overexpression of EGFR (Western blotting, flow cytometry, immunohistochemistry), (b) the relative expression of EGFR ligands (EGF, amphiregulin, TGF-α, ELISA), (c) the relative increase of the activated form of Ras (Ras-bound GTP) after EGF stimulation (Ras activation assay), (d) the efficacy of five different FTIs (HDJ2 prenylation, cell cytotoxicity, and apoptosis using ApopTag and gel ladder). EGFR was overexpressed in MPM cells compared with normal pleural mesothelial cells in equivalent levels as in non–small cell lung cancer cells A459. MPM cells constitutively expressed EGFR ligands; however, Ras activation was attenuated at high EGF concentrations (100 ng/mL). Growth of MPM cells was substantially not affected by treatment with different FTIs (SCH66336, BMS-214662, R115777, RPR-115135, and Manumycin). Among these, BMS-214662 was the only one moderately active. BMS-214662 triggered apoptosis in a small fraction of cells (not higher than 30%) that was paralleled by a slight decrease in the levels of TGF-α secreted by treated MPM cells. Our data highlighted the concept that the same signaling pathway can be regulated in different ways and these regulations can differ between different cells of different origin.

Idiopathic lipoid pneumonia successfully treated with prednisolone

Lipoid pneumonia (LP) is a rare type of pneumonia that is radiologically characterized by lung infiltrates, although imaging alone may not be diagnostic. We describe an unusual 61-year-old patient with idiopathic LP presenting as a solitary pulmonary nodule mimicking lung cancer because of its rapid growth. After treatment with oral prednisone, a control chest radiogram indicated complete normalization of the radiologic features. This case shows that LP should be considered in the diagnostic assessment of any undefined pulmonary mass, after malignancy has been pathologically excluded.

Huge primary pericardial liposarcoma.

Liposarcomas are the second most common soft tissue sarcoma in adults. They occur predominantly in the lower limbs and retroperitoneum, whereas primary mediastinal liposarcomas are extremely rare. Liposarcomas are often asymptomatic and may reach a considerable size before causing any symptoms related to direct invasion or compression of other thoracic organs. We report a case of a 69-year-old woman with a giant primary pericardial liposarcoma causing cardiac tamponade and discuss its clinical and imaging features and surgical treatment and review the literature.