Maurizio Mancuso

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.

Thymomas: A review of 169 cases, with particular reference to results of surgical treatment

One hundred sixty‐five patients with surgically treated thymoma were followed over 28 years; 73% had myasthenia gravis at presentation. Invasiveness was based on macroscopic findings at operation. Post‐surgical radiotherapy or chemotherapy were not routinely used. Overall survival was 84%, 79%, and 65% at 3, 5, and 10 years, respectively. Patients with invasive thymoma survived for a shorter period than patients with noninvasive tumors (67% versus 85% at 5 years); when radical excision was possible, no difference was detectable between the two groups. Patients with subtotally resected or only biopsied invasive thymomas survived 59% and 42% at 5 years, respectively. Lymphoepithelial cases had the worst prognosis of the histologic types considered. Myasthenia gravis did not adversely affect survival. Surgery is the basic treatment of thymomas. Macroscopic invasiveness and degree of excision judged by the surgeon have prognostic value and are reliable criteria of malignancy. Radiotherapy and chemotherapy may be effective, but their use should be limited to controlled trials. Cancer 58:765‐776, 1986.

Control of postoperative pain by transcutaneous electrical nerve stimulation after thoracic operations

BACKGROUND Transcutaneous electrical nerve stimulation (TENS) has been used extensively to control postoperative pain, but its effects are controversial. This is probably due to the different types of operations performed and, therefore, to the varying intensity of postoperative pain. Here we present an extensive study with TENS in 324 patients who underwent different types of thoracic surgical procedures: posterolateral thoracotomy, muscle-sparing thoracotomy, costotomy, sternotomy, and video-assisted thoracoscopy. METHODS Each patient cohort was randomly subdivided into three treatment groups: TENS, placebo TENS and control. The effectiveness of TENS was assessed by two factors: the time from the beginning of treatment to the request for further analgesia and the total medication intake during the first 12 hours after operation. RESULTS Whereas posterolateral thoracotomy produced severe pain, muscle-sparing thoracotomy, costotomy, and sternotomy caused moderate pain, and video-assisted thoracoscopy caused only mild pain. The TENS treatment was not effective in the posterolateral thoracotomy group, but it was useful as an adjunct to other medications in the muscle-sparing thoracotomy, costotomy, and sternotomy groups. In contrast, representing the only pain control treatment with no adjunct drugs, it was very effective in patients having video-assisted thoracoscopy. CONCLUSIONS These findings show that TENS is useful after thoracic surgical procedures only when postoperative pain is mild to moderate; it is uneffective for severe pain.

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.

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.

Combined radiosurgical treatment of pancoast tumor

Operative technique and long-term results of 60 consecutive patients with Pancoast tumor treated with combined radiosurgical treatment were evaluated. External radiation therapy was administered preoperatively in a dose of 30 Gy in 50 patients. Operation was considered radical (R0) in 36 patients (60%). A microscopic invasion of the margin of resection (R1) was observed in 5 patients (8.3%). In 19 patients (31.6%) the operation was considered presumably not radical (R2). Three patients died in the postoperative period (5%). Fourteen major postoperative complications occurred in 13 patients (21%). Seven patients had recurrence of pain postoperatively. Overall 3- and 5-year actuarial survival rates were 34% and 17.4%, respectively. The corresponding figures for the R0 and combined R1-R2 groups were 45.8% and 23.5% (R0), and 11.4% (R1-R2; no 5-year survivors were observed in this group) (p < 0.025). Median survivals in the R0 and combined R1-R2 patients were 19 and 7 months, respectively. Different median survivals for the patients with residual tumor were as follows: intervertebral foramina, 5 months; subclavian artery (isolated), 9 months; subclavian artery (in association), 7 months; brachial plexus, 4 months; and vertebral body, 7 months. We conclude that combined radiosurgical treatment represents a valuable therapeutic option in the treatment of Pancoast tumor. In case of residual tumor a poor outcome may usually be anticipated, but in the majority of these patients the operation permits good control of the pain.

Tumours of the thymus: a cohort study of prognostic factors from the European Society of Thoracic Surgeons database

OBJECTIVES A retrospective database was developed by the European Society of Thoracic Surgeons, collecting patients submitted to surgery for thymic tumours to analyse clinico-pathological prognostic predictors. METHODS A total of 2151 incident cases from 35 institutions were collected from 1990 to 2010. Clinical-pathological characteristics were analysed, including age, gender, associated myasthenia gravis stage (Masaoka), World Health Organization histology, type of thymic tumour [thymoma, thymic carcinoma (TC), neuroendocrine thymic tumour (NETT)], type of resection (complete/incomplete), tumour size, adjuvant therapy and recurrence. Primary outcome was overall survival (OS); secondary outcomes were the proportion of incomplete resections, disease-free survival and the cumulative incidence of recurrence (CIR). RESULTS A total of 2030 patients were analysed for OS (1798 thymomas, 191 TCs and 41 NETTs). Ten-year OS was 0.73 (95% confidence interval 0.69-0.75). Complete resection (R0) was achieved in 88% of the patients. Ten-year CIR was 0.12 (0.10-0.15). Predictors of shorter OS were increased age (P < 0-001), stage [III vs I HR 2.66, 1.80-3.92; IV vs I hazard ratio (HR) 4.41, 2.67-7.26], TC (HR 2.39, 1.68-3.40) and NETT (HR 2.59, 1.35-4.99) vs thymomas and incomplete resection (HR 1.74, 1.18-2.57). Risk of recurrence increased with tumour size (P = 0.003), stage (III vs I HR 5.67, 2.80-11.45; IV vs I HR 13.08, 5.70-30.03) and NETT (HR 7.18, 3.48-14.82). Analysis using a propensity score indicates that the administration of adjuvant therapy was beneficial in increasing OS (HR 0.69, 0.49-0.97) in R0 resections. CONCLUSIONS Masaoka stages III-IV, incomplete resection and non-thymoma histology showed a significant impact in increasing recurrence and in worsening survival. The administration of adjuvant therapy after complete resection is associated with improved survival.

The specific effects of prior opioid exposure on placebo analgesia and placebo respiratory depression

&NA; Although in most of the cases the placebo response appears to be unpredictable, several factors have been considered in order to explain the placebo analgesic effect. For example, it is widely recognized, albeit with little empirical evidence, that placebo analgesia is more likely to occur after a successful analgesic therapy. On the basis of this assumption, we tested the placebo response in a population of patients who were treated with buprenorphine the day before for relieving postoperative pain. However, due to the high variability of opioid responsiveness, buprenorphine was effective in some patients and poorly effective in some others. Similarly, buprenorphine produced respiratory depression with a large variability, ranging from mild depression to no effect. We found that the placebo analgesic response depended on the buprenorphine analgesic effectiveness of the previous day. Analogously, we found that a placebo respiratory depressant response was more pronounced in those patients with a respiratory depressant response to buprenorphine on the day before, irrespective of the analgesic effectiveness. These specific effects suggest that (1) the placebo effect is experience‐dependent; (2) the mechanisms underlying placebo analgesia and placebo respiratory depression are independent from each other and, by considering the role of endogenous opioids in placebo analgesia, might involve different subpopulations of opioid receptors.

The significance of intraoperative pleural effusion during surgery for bronchogenic carcinoma

OBJECTIVES To analyze patients submitted to thoracotomy for lung carcinoma presenting with an intraoperative pleural effusion (PE). METHODS From 1993 to 1999, 1279 patients received thoracotomy with curative intent for primary lung carcinoma. Intraoperatively, 52 patients (4%) presented a PE >100ml which was not diagnosed preoperatively. Of these, seven patients had received preoperative transthoracic fine-needle biopsy FNB and were excluded from the analysis. In the remaining 45 patients pleural fluid cytology was undertaken. In patients with cytology-negative PE, clinico-pathologic characteristics including intratumoral vascular invasion, intratumoral perineural invasion, peritumoral lymphocytic infiltrate, visceral, parietal and mediastinal pleural involvement, pTNM and survival were analyzed and compared with our total population of lung cancer patients operated on during the same period. RESULTS The mean amount of collected fluid was 210ml (100-450ml). Of the 45 patients with intraoperative PE, 16 (35%) received exploratory thoracotomy because of pleural carcinosis or major involvement of mediastinal structures; eight (18%) received resection of the tumor, although the cytologic examination of the pleural fluid eventually resulted positive for neoplastic cells. Median survival for the two groups was 6 and 9 months, respectively. Twenty-one patients (47%) received resection of the tumor with a cytology-negative pleural fluid. In this group, analysis of clinico-pathologic characteristics revealed that squamous cell type and mediastinal pleural involvement were significantly associated with the presence of intraoperative PE (P=0.01 and P=0.05, respectively); 3- and 5-year survivals of this group were similar to those observed in our total population of resected lung cancer patients (68 and 56% vs. 54 and 42%, P=0.27). CONCLUSIONS The presence of a PE at thoracotomy during surgery for lung carcinoma is an infrequent occurrence. In more than 50% of the cases cytology is positive and prognosis is poor. In the remaining cases, however, cytology is negative and the PE should be considered as reactive; in these patients a curative resection can be accomplished with an anticipated chance of long-term survival.

Primary malignant melanoma of the bronchus intermedius

Melanoma is widely known as the most lethal of all skin cancers, and pulmonary metastases are the most common presentation of advanced disease. Melanoma of the eye, oral mucosa, genital and perineal areas, subungual and plantar surfaces, scalp, and palms are described, and although rare, they together make up about 10% of melanomas. Primary pulmonary melanoma is the rarest type of visceral melanoma: only 20 cases have been previously reported in the English literature. We describe the case of a patient in whom a primary melanoma of the bronchus was diagnosed and radically resected, and we discuss the cause and outcome of this rare pathology.