Alberto Oliaro

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.

Neurophysiologic assessment of nerve impairment in posterolateral and muscle-sparing thoracotomy

OBJECTIVE This study was aimed at analyzing the degree of intercostal nerve impairment in posterolateral and muscle-sparing thoracotomy and at correlating the nerve damage to the severity of long-lasting postthoracotomy pain. METHODS Neurophysiologic recordings were performed 1 month after either posterolateral or muscle-sparing thoracotomy to assess the presence of the superficial abdominal reflexes (mediated in part by the intercostal nerves), the somatosensory-evoked responses after electrical stimulation of the surgical scar, and the electrical thresholds for tactile and pain sensations of the surgical incision. RESULTS The patients who underwent a posterolateral thoracotomy showed a higher degree of intercostal nerve impairment than the muscle-sparing thoracotomy patients as revealed by the disappearance of the abdominal reflexes, a larger reduction in amplitude of the somatosensory-evoked potentials, and a larger increase of the sensory thresholds to electrical stimulation for both tactile perception and pain. In addition, these neurophysiologic parameters were highly correlated to the postthoracotomy pain experienced by the patients 1 month after surgery, indicating a causal role for nerve impairment in the long-lasting postoperative pain. CONCLUSIONS This study shows for the first time the pathophysiologic differences between posterolateral and muscle-sparing thoracotomy and suggests that the minor long-lasting postthoracotomy pain in muscle-sparing thoracotomy patients is partly due to a minor nerve damage. In addition, because nerve impairment is responsible for the long-lasting neuropathic component of postoperative pain, it is necessary to match specific treatments to the neuropathic pain-generating mechanisms.

Blockade of nocebo hyperalgesia by the cholecystokinin antagonist proglumide

Abstract In patients who reported mild postoperative pain, we evoked a nocebo response, a phenomenon equal but opposite to placebo. Patients who gave informed consent to increase their pain for 30 min received a substance known to be non–hyperalgesic (saline solution) and were told that it produced a pain increase. A nocebo effect was observed when saline was administered. However, if a dose of 0.5 or 5 mg of the cholecystokinin antagonist proglumide was added to the saline solution, the nocebo effect was abolished. A dose of 0.05 mg of proglumide was ineffective. The blockade of the nocebo hyperalgesic response was not reversed by 10 mg of naloxone. These results suggest that cholecystokinin mediates pain increase in the nocebo response and that proglumide blocks nocebo through mechanisms not involving opioids. Since the nocebo procedure represents an anxiogenic stimulus and previous studies showed a role for cholecystokinin in anxiety, we suggest that nocebo hyperalgesia may be due to a cholecystokinin‐dependent increase of anxiety.

Dose-response relationship of opioids in nociceptive and neuropathic postoperative pain

&NA; The treatment of neuropathic pain with opioid analgesics is a matter of controversy among clinicians and clinician scientists. Although neuropathic pain is usually believed to be only slightly responsive to opioids, several studies show that satisfactory analgesia can be obtained if adequate doses are administered. In the present study, we tested the effectiveness of buprenorphine in 21 patients soon after thoracic surgery (nociceptive postoperative pain) and 1 month after surgery in the same 21 patients who developed postthoracotomy neuropathic pain with a burning, electrical and shooting quality. According to a double‐blind randomized study, the analgesic dose (AD) of buprenorphine needed to reduce the long‐term neuropathic pain by 50% (AD50) was calculated and compared to the AD50 in the immediate postoperative period. We found that long‐term neuropathic pain could be adequately reduced by buprenorphine. However, the AD50 in neuropathic pain was significantly higher relative to the AD50 in the short‐term postoperative pain, indicating a lower responsiveness of neuropathic pain to opioids. We also found a strict relationship between the short‐term and long‐term AD50, characterized by a saturating effect. In fact, if the AD50 soon after surgery was low, the AD50 increase in the long‐term neuropathic pain was threefold. By contrast, if the AD50 soon after surgery was high, the AD50 in neuropathic pain was only slightly increased. This suggests that, though neuropathic pain is indeed less sensitive to opioids, in some neuropathic patients a large amount of opioid resistance is already present in other painful conditions.

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.

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.

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.