Ottavio Rena

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.

Descending necrotizing mediastinitis: surgical management

OBJECTIVE Descending necrotizing mediastinitis (DNM) is a primary complication of cervical or odontogenical infections that can spread to the mediastinum through the anatomic cervical spaces. METHODS Between April 1994 and April 2000, 13 patients, mean age 39.23+/-18.47 (median 38, range 16-67) years, with DNM were submitted to surgical treatment. Primary odontogenic abscess occurred in six, peritonsillar abscess in five and post-traumatic cervical abscess in two patients. Diagnosis was confirmed by computed tomography (CT) of the neck and chest. All patients underwent surgical drainage of the cervico-mediastinal regions by a bilateral collar incision associated with right thoracotomy in ten cases. RESULTS Six patients out of 13 required reoperation. Two patients previously submitted only to cervical drainage required thoracotomy; four patients, which have been submitted to cervico-thoracic drainage, underwent contralateral thoracotomy in two cases and ipsilateral reoperation in two cases. Ten patients evolved well and were discharged without major sequelae; three patients died of multiorgan failure related to septic shock. Mortality rate was 23%. CONCLUSION Early diagnosis by CT of the neck and chest suggest a rapid indication of surgical approach to DNM. Ample cervicotomy associated with mediastinal drainage via large thoracotomic incision is essential in managing these critically ill patients and can significantly reduce the mortality rate for this condition, often affecting young people, to acceptable values.

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.

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.

Trimodality management of malignant pleural mesothelioma

OBJECTIVE We reviewed our experience with trimodality management of malignant pleural mesothelioma (MPM). METHODS From September 1998 to August 2000, 32 consecutive patients with histological diagnosis of MPM underwent trimodality therapy, including surgery followed by adjuvant chemotherapy and radiation therapy. Surgery consisted of pleurectomy/decortication (P/D) or pleural-pericardial-pneumonectomy and diaphragm (PPPD). Pre-operative staging according to the Brigham Staging System was accomplished using computed tomography (CT) and magnetic resonance imaging (MRI); patients with evident extrapleural spread were excluded. RESULTS Our series included 21 men and 11 women with a median age of 53.5 years (range 40-69). Histologically, there were 26 epithelial, four mixed and two sarcomatous MPM. Post-surgical staging was as follows: six patients were at Stage I; of these, two received a P/D and four a PPPD. Ten patients were at Stage II and all received a PPPD; 16 patients were at Stage III (under-staged pre-operatively): of these, nine patients presented extrapleural lymph node metastases (N2) and all received a PPPD, seven patients presented with chest wall or mediastinal invasion (T4) with macroscopic residual tumour, and all received a de-bulking P/D. We observed major complications in ten patients: six bleeding, two respiratory insufficiency and two nerve paralysis. There were two perioperative deaths (6.25% mortality). Twenty-seven patients out of 30 surviving surgery had a follow-up greater than 6 months; 21 patients out of 27 are alive with a median follow-up of 12.5 months. CONCLUSIONS (1) Trimodality therapy is feasible in selected patients with MPM and has an acceptable operative mortality rate. (2) Our current pre-operative staging based on CT/MRI looks rather inaccurate and needs to be improved. (3) The high rate of post-surgical N2 patients or with diffusion to the inferior surface of the diaphragm may suggest the use of routine mediastinoscopy and laparoscopy for a more appropriate patient selection.

Supraventricular arrhythmias after resection surgery of the lung

OBJECTIVE Two hundred consecutive patients undergoing resection surgery of the lung during 1999 were retrospectively reviewed to define prevalence, type, clinical course and risk factors for postoperative supraventricular arrhythmias (SVA) with particular reference to atrial fibrillation or flutter (AF). METHODS Records of 200 lung patients were collected and analysed with particular attention to preoperative physiologic values and associated pathologies, lung functional status, electrocardiogram registration, extent of surgical resection of the lung and were also analysed to confirm or exclude correlation between them and postoperative AF; three patients were excluded as they were affected preoperatively by SVA. RESULTS Forty-five episodes of SVA, 41 of AF were identified in 197 patients (22%) and were more prevalent in several groups of patients such as those with increased age, pneumonectomy and superior lobectomy. Rhythm disturbances were most likely to develop on the second day after surgery. Ninety-eight percent of AF disappeared within a day of discharge and sinus rhythm was restored with digitalis or other antiarrhythmic drugs in all patients except one who was discharged with persistent atrial fibrillation. Arrhythmias were not direct causes of any in-hospital deaths. There is a tendency in the difference of the AF rate between pneumonectomy and upper lobectomy patients versus inferior lobectomy ones, probably related to the different anatomic structure of the proximal trunks of the upper and inferior veins of the lung, respectively. CONCLUSIONS Statistical analysis revealed that increased age, extent and type of pulmonary resection, such as pneumonectomy and superior lobectomy were significant risk factors. Despite these factors, arrhythmias after lung surgery could be managed easily and were not closely related to higher mortality. Direct cause of AF after lung resection surgery remains unclear; anatomical substrate such as surgical damage to the cardiac plexus or to the proximal trunks of the pulmonary veins covered by myocardial sleeves with electrical properties are to be considered.

Extrapleural pneumonectomy for early stage malignant pleural mesothelioma: A harmful procedure

The effects on long-term post-operative quality of life (QoL) and disease-control in malignant pleural mesothelioma (MPM) of extrapleural pneumonectomy (EPP) and pleurectomy/decortication (P/D) are compared. Seventy-seven patients affected by early-stage MPM received EPP (40) or P/D (37) associated with multimodal treatment between 1998 and 2009 at our institution. The last consecutive 39 (19 EPP and 20 P/D) were asked to answer the EORTC-QLQ-C30 questionnaire at baseline and at 6- and 12-months after treatment completion to evaluate the impact on QoL of both procedures. QoL evaluation was stopped at recurrence demonstration. Twenty-five (62%) EPP vs 9 (24%) P/D patients (p = 0.002) had in-hospital major complications, and 2/40 (5%) EPP vs no one P/D patients died after surgery. Both procedures caused a significant impairment of all the considered variables of the EORTC-QLQ-C30 questionnaire after treatment completion; only P/D patients returned at baseline levels after 12 months. EPP patients had a worse long-term post-operative QoL when compared with P/D. Median post-operative disease-free period was longer for EPP patients (14 vs 11 months) whereas the residual life to death period after recurrence detection was significantly longer for P/D patients (13 vs 9 months) (p = 0.01). Median long-term survival was longer, even not significant, for P/D patients (25 vs 20 months). MPM patients submitted to EPP had a higher post-operative complication rate, a worse long-term QoL, a shorter residual life time after recurrent disease, despite a similar long-term survival when compared to P/D.

Videothoracoscopic lung biopsy in the diagnosis of interstitial lung disease

OBJECTIVE Interstitial lung diseases (ILD) require lung biopsy for the diagnosis in more than 30% of patients. Open lung biopsy (OLB) was generally considered the most reliable method of biopsy and tissue diagnosis. This study tests the diagnostic accuracy and safety of the videothoracoscopic lung biopsy (VTLB) in the diagnosis of ILD. METHODS During the last 5 years, 58 patients were submitted to VTLB under general anesthesia. The mean age was 49.6 +/- 12.0 years (range 21-69). All the biopsies were performed by an endostapler EndoPath 30 or 45. Conversion to minithoracotomy was necessary in only one patient because of extensive pleural sinfisis. All the specimens were sent to the microbiology and pathology department for microbiological and histopathological diagnosis. One chest-tube (28F) was positioned and connected to a drainage-system and placed on suction. RESULTS The histopathological diagnosis was obtained for all patients and therefore the diagnostic accuracy of the procedure was 100%. No postoperative haemothorax occurred and only two patients experienced a prolonged air-leakage (3.4%). The median duration of the chest-drain was 3 days (range 1-7) and the median hospital stay was 4 days (range 2-7). CONCLUSION VTLB provides adequate specimen volume for histopathologic diagnosis and achieves a very high diagnostic accuracy (100% in our series). The postoperative morbidity and mortality rates are lower than those related to OLB. We conclude that VTLB is an effective and safe procedure in the diagnosis of ILD.

Lung tumors with mixed histologic pattern. Clinico-pathologic characteristics and prognostic significance

OBJECTIVE To analyze and compare clinico-pathologic characteristics and survival between lung tumors with mixed histologic pattern and our population of resected lung tumors with single histology in the same period. METHODS From January 1993 to December 1999, 1158 patients received resection for lung tumors. Of these, 59 (5.1%) presented a mixed histologic pattern on the surgical specimen. There were 48 men and 11 women (mean age 64 years, range 43-79). Three groups of tumors were identified: adenosquamous carcinoma, combined neuroendocrine + non-neuroendocrine carcinoma (NNEC) and biphasic tumors (epithelial + mesenchymal malignant components) represented by carcinosarcoma and blastoma. The combined neuroendocrine tumors were further divided in small cell lung carcinoma (SCLC) + large cell neuroendocrine carcinoma (LCNEC)/NNEC and other neuroendocrine tumors/NNEC. Clinico-pathologic characteristics, pTNM and survival were analyzed and compared to our population of resected lung tumors with single histology. RESULTS There were 33 adenosquamous carcinomas, 19 combined SCLC+LCNEC/NNEC, two other neuroendocrine tumors/NNEC and five biphasic tumors (three carcinosarcomas and two blastomas). Among adenosquamous carcinomas, high cell grading (G2 or G3), advanced stage (IIIa or higher) and intratumoral perineural invasion were significantly more evident than in the single histology population. Among combined neuroendocrine/NNEC, high cell grading (G3) and intratumoral vascular invasion were significantly more evident than in the single histology population. Among biphasic tumors, all were at early stages and showed high cell grading (G3). Three-year survival rates were 46% in the single histology group, 28% in the adenosquamous group and 21% in the combined SCLC + LCNEC/NNEC. The difference among the three groups was significant (P = 0.013). Median survival of biphasic tumors was 19 months (range 8-37). CONCLUSIONS Lung tumors with mixed histologic pattern are rare tumors. Adenosquamous carcinoma and combined SCLC + LCNEC/NNEC present a more aggressive clinico-pathologic behaviour and reduced survival as compared to the single histology population of resected lung tumors.

Stage I non-small cell lung carcinoma: really an early stage?

OBJECTIVE We review our results on surgical treatment of patients with stage I non-small cell lung carcinoma and we attempted to clarify the prognostic significance of some surgical--pathologic variables. METHODS From 1993 to 1999, 667 patients received curative lung resection and complete hilar and mediastinal lymphadenectomy for non-small cell lung cancer. Of these, there were 436 Stage I disease (65%), of whom 144 T1N0 and 292 T2N0. No patients had pre- or postoperative radio- or chemotherapy. Prognostic significance of the following independent variables was tested using univariate (log-rank) and multivariate (Cox proportional-hazards) analysis: type of resection (sublobar vs lobectomy vs pneumonectomy), histology (squamous cell vs adenocarcinoma), tumour size (<or=3cm vs >3cm), histologic vascular invasion, visceral pleura involvement, positive bronchial resection margin, general T status. RESULTS Overall 5-year survival was 63%. In both univariate and multivariate survival analysis, significant prognostic factors were histology (adenocarcinoma 65% vs squamous cell carcinoma 51%), tumour size (<or=3cm 67% vs >3cm 46%), and the presence of negative resection margin. Five-year survival by general T status was 66% in T1N0 vs 55% in T2N0 disease (P=0.19). CONCLUSIONS Despite advances in early diagnosis and surgical technique, 5-year survival of stage I non-small cell lung carcinoma remains low as compared to survival of other solid organ neoplasm. Tumour size <or=3cm, adenocarcinoma histologic type and negative bronchial resection margins were associated with a more favourable outcome in our patient population. More effective multimodality treatments are needed to increase survival rates.