Pier Luigi Filosso

Recurrence of thymoma: Analysis of clinicopathologic features, treatment, and outcome

OBJECTIVE AND METHODS This study reports clinicopathologic features, treatment, and outcome of 30 recurrent thymomas out of 266 totally resected thymomas. RESULTS The mean disease-free interval to recurrence was 86 months. Recurrence occurred less frequently and after a longer disease-free interval after resection of encapsulated versus invasive thymomas. The presence of associated myasthenia gravis did not affect recurrence proportion, disease-free interval, or survival after recurrence. A local recurrence occurred in 11 patients, 17 patients had a distant recurrence, and the extent of the recurrence could not be determined in 2 cases. Surgical treatment of the recurrent tumor was attempted in 16 cases, and a total resection was possible in 10 cases; exclusive radiotherapy was done in 11 cases. Overall 5- and 10-year survivals were 48% and 24%, respectively. In a univariate analysis, survival was significantly better in the presence of a local recurrence and in case of a total resection of the recurrent tumor. The use of adjuvant therapy after the resection of the initial thymoma had no effect on reducing the incidence of recurrence, in prolonging the disease-free interval, or in improving survival after the development of the recurrence. In a multivariate survival analysis, significant prognostic factors were the presence of a local recurrence and total resection of the recurrent tumor. CONCLUSIONS Surgical resection is recommended in patients with recurrent thymoma. Local recurrence and total resection of the recurrent tumor are associated with excellent prognosis. A poor prognosis may be anticipated in the presence of distant recurrence and when radical surgical treatment is not done.

Pulmonary resection for metastases from colorectal cancer: factors influencing prognosis. Twenty-year experience

OBJECTIVE We reviewed our experience in the surgical management of 80 patients with colorectal pulmonary metastases and investigated factors affecting survival. MATERIAL AND METHODS From January 1980 to December 2000, 80 patients, 43 women and 37 men with median age 63 years (range 38-79 years) underwent 98 open surgical procedure (96 muscle-sparing thoracotomy, one clamshell and one median sternotomy) for pulmonary metastases from colorectal cancer (three pneumonectomy, 17 lobectomy, seven lobectomy plus wedge resection, six segmentectomy, three segmentectomy plus wedge resection and 62 wedge resection). Pulmonary metastases were identified at a median interval of 37.5 months (range 0-167) from primary colorectal resection. Second and third resections for recurrent metastases were done in seven and in four patients, respectively. RESULTS Operative mortality rate was 2%. Overall, 5-year survival was 41.1%. Five-year survival was 43.6% for patients submitted to single metastasectomy and 34% for those submitted to multiple ones. Five-year survival was 55% for patients with disease-free interval (DFI) of 36 months or more, 38% for those with DFI of 0-11 months and 22.6% for those with DFI of 12-35 months (P=0.04). Five-year survival was 58.2% for patients with normal preoperative carcino-embryonic antigen (CEA) levels and 0% for those with pathologic ones (P=0.0001). Patients submitted to second-stage operation for recurrent local disease had 5-year survival rate of 50 vs. 41.1% of those submitted to single resection (P=0.326). CONCLUSIONS Pulmonary resection for metastases from colorectal cancer may help survival in selected patients. Single metastasis, DFI>36 months, normal preoperative CEA levels are important prognostic factors. When feasible, re-operation is a safe procedure with satisfactory long-term results.

Clinical significance of tumor-infiltrating lymphocytes in lung neoplasms.

BACKGROUND Tumor-infiltrating lymphocytes (TIL) are considered important in anticancer immunosurveillance, although their role has not been clearly established yet. We examined prevalence, correlations, and prognostic significance of TIL among our patient population of resected lung neoplasms. METHODS From 1993 to 2006, the presence of TIL was retrospectively evaluated in 1,290 patients operated on for primary lung neoplasms. Tumor-infiltrating lymphocytes were defined as those intraepithelial lymphocytes located within the cancer cell nests. RESULTS Tumor-infiltrating lymphocytes were detected in 294 patients (23%). A significant difference was found between prevalence in non-small cell lung carcinomas versus neuroendocrine tumors (290 of 1,208, 24% versus 4 of 82, 5%; p = 0.0001). Prevalence was similar in adenocarcinomas, squamous-cell carcinomas, and large-cell anaplastic carcinomas. Logistic regression analysis indicates that TIL correlate with grading (odds ratio, 1.27; 95% confidence interval, 1.04 to 1.55; p = 0.02), tumor dimension (odds ratio, 0.86; 95% confidence interval, 0.79 to 0.94; p = 0.0008), and vascular invasion (odds ratio, 1.62; 95% confidence interval, 1.21 to 2.16; p = 0.0009). A not significantly better survival in the presence of TIL was observed overall (p = 0.20), becoming significant in squamous-cell carcinomas (p = 0.03). In patients with stage I disease, TIL is associated with a significant survival advantage in squamous-cell carcinomas (p = 0.03). The survival advantage increases with the duration of follow-up and is more evident after 4 to 6 years. CONCLUSIONS Tumor-infiltrating lymphocytes are observed in about one fourth of resected lung neoplasms: they are rare in neuroendocrine tumors. Tumor-infiltrating lymphocytes are more frequent in poorly differentiated tumors and in tumors with microscopic vascular invasion. The presence of TIL correlates with an improved survival in squamous cell carcinomas, particularly at early stage. The survival advantage increases with the duration of follow-up.

Solitary fibrous tumour of the pleura: surgical treatment

OBJECTIVE Solitary fibrous tumours (SFT) of the pleura are rare tumours originated from the mesenchimal tissue underlying the mesothelial layer of the pleura. This tumours present unpredictable clinical course probably related to their histological and morphological characteristics. METHODS Twenty-one patients affected by SFT of the pleura were referred to us for surgical resection from September 1984 to April 2000. They were 15 males and six females with median age of 51 (range 15--73) years. Nine patients (43%) were symptomatic and predominant clinical symptoms or signs were dyspnoea (19%), coughing (14.3%), chest pain (28.5%), finger clubbing (14.3%) and hypoglycaemia (14.3%). Hypoglycaemia was related to a pathological incretion of insulin-like growth factor 2 by the tumour. Chest radiograph and computed tomography of the chest revealed intra-thoracic homogeneous sharply delineated round or lobulated mass sometimes associated with ipsilateral pleural effusion (19%) or causing pulmonary atelectasis with opacification of the complete hemithorax (19%). Surgical excision required 14 posterolateral thoracotomies, six anterior thoracotomies and one video-assisted thoracoscopy. Thirteen tumours arose from visceral pleura and wedge resection was performed, seven tumours arose from parietal pleura and extrapleural resection was carried out without any chest-wall resection, one tumour growth within the upper left lobe and required lobectomy. Tumours weighted from 22 to 1942 g and measured from 22x12x8 to 330x280x190 mm. At cut section seven cases (34%) revealed focal necrosis and hemorrhagic zones and on light microscopy six cases (28.5%) were characterized by high mitotic count: characteristics related with uncertain clinical behaviour. Immuno-histochemical reactions were in all cases positive for CD34. RESULTS In all our patients resections were complete. Paraneoplastic syndromes like hypoglycaemia and clubbing receded after surgery. No intraoperative or perioperative medical or surgical complications occurred. Median chest-drain duration timed 3 (range 2--5) days and median hospital stay was 5 (range 4--7) days. Perioperative mortality rate was 0%. Median follow-up was 68 (range 2--189) months: during this period patients were submitted to chest X-ray with 6-months interval to evaluate possible local recurrence. Only one patient experienced tumour recurrence after 124 months follow-up: the tumour was suspected after observation of finger clubbing. The tumour was detected and excised by redo-thoracotomy. CONCLUSIONS Surgical resection of benign solitary fibrous tumours is usually curative, but local recurrences can occur years after seemingly adequate surgical treatment. Malignant solitary fibrous tumours generally have a poor prognosis. Clinical follow-up and radiological follow-up are indicated for both benign and malignant solitary fibrous tumours.

Posttraumatic and iatrogenic foreign bodies in the heart: report of fourteen cases and review of the literature.

OBJECTIVE Our experience with posttraumatic and iatrogenic foreign bodies in the heart is presented and discussed along with a review of the literature on this subject. SUMMARY BACKGROUND DATA Posttraumatic or iatrogenic foreign bodies in the heart can be treated either conservatively or surgically. Controversy exists about optimal management. METHODS Fourteen cases of posttraumatic or iatrogenic foreign bodies in the heart observed between 1955 and 2000 were studied. Our series includes the following: bullets into the right or left ventricle (4 cases); needles in the left ventricle, atrium, and pulmonary artery (3 cases); retained catheter fragments in the right ventricle, right atrium, or in the pulmonary artery (4 cases); a grenade fragment into the right atrium (1 case); a circular saw fragment into the right ventricle (1 case); and a commissurotomy ring into the left atrium (1 case). RESULTS Foreign bodies were removed when in the cardiac cavities (1 case); when in the presence of associated risk factors like embolism, arrhythmia, or infection (3 cases); and when in the presence of associated signs or symptoms including cardiac tamponade (2 cases), arrhythmia (1 case), fever (2 cases), or anxiety (1 case). Removal was accomplished by a thoracotomy (7 cases) or sternotomy (2 cases), with (3 cases) or without cardiopulmonary bypass, or percutaneously (1 case). Four asymptomatic patients were conservatively treated and have no evidence of complications at a median follow-up of 20 years. CONCLUSIONS The management of foreign bodies in the heart should be individualized: (1) symptomatic foreign bodies should be removed irrespective of their location; (2) asymptomatic foreign bodies diagnosed immediately after the injury with associated risk factors should be removed; (3) asymptomatic foreign bodies without associated risks factors or diagnosed late after the injury may be treated conservatively, particularly if they are completely embedded in the myocardium or in the pericardium.

Frequency and mortality of acute lung injury and acute respiratory distress syndrome after pulmonary resection for bronchogenic carcinoma

OBJECTIVE We reviewed the frequency and mortality of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) in our population of patients submitted to pulmonary resection for primary bronchogenic carcinoma. METHODS From January 1993 to December 1999, a total of 1221 patients received pulmonary resection for primary bronchogenic carcinoma. Of these, 27 met the criteria of post-operative ALI/ARDS. There were 24 men and three women with a mean age of 64 years (range 45--79). Pre-operatively, predicted mean of PaO(2), PaCO(2) and %FEV1 were 72 mmHg (57--86), 37 mmHg (33--42) and 80% (37--114), respectively. Associated cardiac risk factors were present in eight patients. Three patients (11%) had pre-operative radiotherapy. Surgical-pathologic staging included 14 patients at Stage I, 8 patients at Stage II, four patients at Stage IIIa and one patient at Stage IIIb. RESULTS ALI/ARDS occurred in 2.2% of our operated lung cancer patients. ALI was diagnosed in 10 patients and ARDS in 17 patients. The mean time of presentation following surgery was 4 days (range 1--10) and 6 days (1--13) for ALI and ARDS, respectively. According to the type of operation, the frequency was highest following right pneumonectomy (4.5%), followed by sublobar resection (3.2%), left pneumonectomy (3%), bilobectomy (2.4%), and lobectomy (2%). The frequency following extended operations was 4%. No differences were found between the ALI/ARDS group and the total population of resected lung cancer patients (control group) with respect to sex, mean age, pre-operative blood gases, %FEV1, surgical--pathologic staging and the use of pre-operative radiotherapy. Four patients with ALI (40%) and 10 patients with ARDS (59%) died. Mortality was highest following right pneumonectomy, extended operations and sublobar resections. Hospital mortality of the total population of operated lung cancer patients in the same period was 2.8% (34 patients). ALI/ARDS accounted for 41% of our hospital mortality. CONCLUSIONS (1) ALI/ARDS is a severe complication following resection for primary bronchogenic carcinoma. (2) We did not detect any significant difference between the ALI/ARDS group and the control group regarding age, pre-operative lung function, staging and pre-operative radiotherapy. (3) ALI/ARDS is associated with high mortality, the highest mortality rates having been observed following right pneumonectomy and extended operation; it currently represents our leading cause of death following pulmonary resection for lung carcinoma. (4) ALI/ARDS may also occur after sublobar resections with an associated high mortality rate.

Long-term survival of atypical bronchial carcinoids with liver metastases, treated with octreotide

OBJECTIVE To demonstrate that liver metastases by radically resected atypical carcinoids of the lung can be effectively treated by new somatostatin analogs. METHODS Between January 1977 and December 1999, 126 patients affected by bronchial carcinoids were submitted to a radical resection of the lung. Seven of them (5.5%) presented liver metastases 27, 22, 14, 18, 16, 12 and 9 months after surgery: carcinoid syndrome (CS) was ever present. 111In-DTPA-pentetreotide scintigraphy (Octreoscan) and ultrasound guided biopsy were performed in all cases, and the presence of somatostatin receptors sst2 was demonstrated by polymerase chain reaction (PCR) method. RESULTS Five patients refused the proposed chemotherapy, and liver alcoholization was not feasible. Octreotide was administered at the dose of 1500 microg/daily subcutaneously. CS was controlled and also high urinary 5-hydroxyindoleacetic acid values returned to normal after a median of 7 days (range 4-10 days) of medical treatment. No important side effects were registered, and a good quality of life was observed. The patients are alive and well at 51, 36, 24, 24, 23, 19, and 16 months after the diagnosis of the metastases, respectively. In two cases ultrasounds revealed the reduction and in one case the complete resolution of the liver lesion. CONCLUSIONS Octreotide is effective in controlling symptoms of CS of patients with liver metastases of resected atypical bronchial carcinoid. The efficacy of the drug is due to the presence of sst2 somatostatin receptors in the pathologic tissue, as demonstrated by PCR method. The positivity to Octreoscan depends on the presence of the same receptors. Octreoscan may be used in the follow-up of these neuroendocrine neoplasms of the lung. A positivity to Octreoscan is predictive for an effective therapy with octreotide.

Postoperative Pain and Superficial Abdominal Reflexes After Posterolateral Thoracotomy

BACKGROUND Posterolateral thoracotomy can produce stretching of/or damage to the intercostal nerves and their branches. To assess intercostal nerve impairment after operation, we measured the superficial abdominal reflexes, which are mediated, at least in part, by the most inferior intercostal nerves. METHODS Using electrophysiologic techniques, we made recordings from the left and right abdominal walls to study the responses evoked by mechanical stimulation of the skin after operation. In addition, we assessed postoperative pain intensity according to a numeric rating scale and recorded postoperative opioid dose. RESULTS We found that the patients with complete disappearance of the superficial abdominal reflexes experienced more severe postoperative pain than those in whom the reflexes were maintained. Moreover, opioid treatment was less effective in the patients with no reflexes postoperatively. CONCLUSIONS Our findings show a strict correlation between pain intensity after posterolateral thoracotomy and absence of abdominal reflexes. We suggest that the higher pain intensity together with the absence of reflexes may be due to intercostal nerve impairment, be it anatomic or functional, and thus to a larger neuropathic component of postoperative pain. This finding may be used as a predictor of patients with high analgesic requirements.

The IASLC Lung Cancer Staging Project: Proposals for Coding T Categories for Subsolid Nodules and Assessment of Tumor Size in Part-Solid Tumors in the Forthcoming Eighth Edition of the TNM Classification of Lung Cancer

ABSTRACT This article proposes codes for the primary tumor categories of adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) and a uniform way to measure tumor size in part‐solid tumors for the eighth edition of the tumor, node, and metastasis classification of lung cancer. In 2011, new entities of AIS, MIA, and lepidic predominant adenocarcinoma were defined, and they were later incorporated into the 2015 World Health Organization classification of lung cancer. To fit these entities into the T component of the staging system, the Tis category is proposed for AIS, with Tis (AIS) specified if it is to be distinguished from squamous cell carcinoma in situ (SCIS), which is to be designated Tis (SCIS). We also propose that MIA be classified as T1mi. Furthermore, the use of the invasive size for T descriptor size follows a recommendation made in three editions of the Union for International Cancer Control tumor, node, and metastasis supplement since 2003. For tumor size, the greatest dimension should be reported both clinically and pathologically. In nonmucinous lung adenocarcinomas, the computed tomography (CT) findings of ground glass versus solid opacities tend to correspond respectively to lepidic versus invasive patterns seen pathologically. However, this correlation is not absolute; so when CT features suggest nonmucinous AIS, MIA, and lepidic predominant adenocarcinoma, the suspected diagnosis and clinical staging should be regarded as a preliminary assessment that is subject to revision after pathologic evaluation of resected specimens. The ability to predict invasive versus noninvasive size on the basis of solid versus ground glass components is not applicable to mucinous AIS, MIA, or invasive mucinous adenocarcinomas because they generally show solid nodules or consolidation on CT.

The IASLC/ITMIG Thymic Epithelial Tumors Staging Project: Proposal for an Evidence-Based Stage Classification System for the Forthcoming (8th) Edition of the TNM Classification of Malignant Tumors

A universal and consistent stage classification system, which describes the anatomic extent of a cancer, provides a foundation for communication and collaboration. Thymic epithelial malignancies have seen little progress, in part because of the lack of an official system. The International Association for the Study of Lung Cancer and the International Thymic Malignancies Interest Group assembled a large retrospective database, a multispecialty international committee and carried out extensive analysis to develop proposals for the 8th edition of the stage classification manuals. This tumor, node, metastasis (TNM)-based system is applicable to all types of thymic epithelial malignancies. This article summarizes the proposed definitions of the T, N, and M components and describes how these are combined into stage groups. This represents a major step forward for thymic malignancies.