Membrane type matrix metalloproteinases (MMPs) show differential expression in non-small cell lung cancer (NSCLC) compared to normal lung: correlation of MMP-14 mRNA expression and proteolytic activity.

Improved understanding of the involvement of matrix metalloproteinases (MMPs), including membrane-type MMPs (MT-MMPs), in human tumours has potential diagnostic, prognostic and therapeutic implications. We assessed the relationship between MT-MMP expression and clinicopathological parameters in human non-small cell lung cancer (NSCLC) and histologically normal lung tissue by quantitative Real Time PCR (qRT-PCR). All MT-MMPs (MMPs 14-17, 24 and 25) were detected by qRT-PCR with significantly higher MMP-14, -15 and -17 expression observed in tumour relative to normal lung specimens. MMP-16 was undetectable in normal lung but expressed in 8% tumours. MMP-15 demonstrated significant overexpression in adenocarcinomas relative to squamous cell carcinomas and normal lung tissue. MMP-14 mRNA expression strongly correlated to MMP-14 proteolytic activity in preclinical tumour models, indicating that qRT-PCR may predict MMP-14 activity levels in NSCLC. These data suggest that MMP-14, -15 and -17 may be good markers of disease, or therapeutic targets for treatment of human NSCLC.

A prospective, randomized comparison of preoperative and continuous balanced epidural or paravertebral bupivacaine on post-thoracotomy pain, pulmonary function and stress responses.

Both epidural and paravertebral blocks are effective in controlling post-thoracotomy pain, but comparison of preoperative and balanced techniques, measuring pulmonary function and stress responses, has not been undertaken previously. We studied 100 adult patients, premedicated with morphine and diclofenac, allocated randomly to receive thoracic epidural bupivacaine or thoracic paravertebral bupivacaine as preoperative bolus doses followed by continuous infusions. All patients also received diclofenac and patient-controlled morphine. Significantly lower visual analogue pain scores at rest and on coughing were found in the paravertebral group and patient-controlled morphine requirements were less. Pulmonary function was significantly better preserved in the paravertebral group who had higher oxygen saturations and less postoperative respiratory morbidity. There was a significant increase in plasma concentrations of cortisol from baseline in both the epidural and paravertebral groups and in plasma glucose concentrations in the epidural group, but no significant change from baseline in plasma glucose in the paravertebral group. Areas under the plasma concentration vs time curves for cortisol and glucose were significantly lower in the paravertebral groups. Side effects, especially nausea, vomiting and hypotension, were troublesome only in the epidural group. We conclude that with these regimens, paravertebral block was superior to epidural bupivacaine.

Pleural bupivacaine placement for optimal postthoracotomy pulmonary function: a prospective, randomized study.

OBJECTIVE: To determine dependent chest tube losses of bupivacaine with paravertebral versus interpleural administration, thereby helping to explain the significant differences in pulmonary function that exist between these two techniques. DESIGN: A prospective, randomized study. SETTING: A single hospital. PARTICIPANTS: Twelve adult patients undergoing posterolateral thoracotomies. INTERVENTIONS: Paravertebral or interpleural administration of bupivacaine. MEASUREMENTS AND MAIN RESULTS: Analgesia, as assessed by visual analog pain scores and patient-controlled morphine requirements, was similar in both groups. Postoperative spirometric values were significantly better at most times with the paravertebral route of administration. Dependent chest tube bupivacaine losses were approximately four times higher in the interpleural group. CONCLUSION: Local anesthetic on the diaphragm might actively impair respiratory function through diaphragmatic and abdominal muscle weakness, while failing to contribute to pain relief.

Surgical treatment of primary malignant chest wall tumours.

OBJECTIVE: Primary malignant tumours of the bony chest wall are uncommon and data concerning treatment and results are sparse. METHODS: To assess the results of surgical resection and chest wall reconstruction we reviewed our experience with primary malignant chest wall tumours treated since 1958. RESULTS: Of the 49 lesions, 42 were found in the ribs and the remaining 7 in the sternum. These included chondrosarcomas [22], solitary plasmacytoma [18], Ewing's tumours [7], Askin's tumour [1] and Desmoid tumour [1]. Skeletal reconstruction was performed in 36 of the 49 patients. Marlex mesh alone was used in 17 patients. Since 1972, a sandwich of two layers of Marlex mesh with a filler of methyl methacrylate was utilised [19] successfully, producing better functional and cosmetic results. Primary soft tissue closure was possible in all but 8 cases in whom latissimus dorsi myocutaneous flaps were used. Bilaterally, partially transposed pectoralis major muscle was used to cover upper sternal defects in 4 cases. All but 1 patient had an uneventful post-operative recovery none requiring ventilatory support. SURVIVAL: Overall survival at 5 and 10 years was 68%. The differential figures for 10-year survival were for chondrosarcoma 67%, Ewing's sarcoma 43%, and solitary plasmacytoma 59%. These were the results of radical en-bloc excisions. The patient with Desmoid tumour is alive at 5 years, following incomplete initial resection and the patient with Askin's tumour survived for 3 years. CONCLUSION: Radical en-bloc excision remains the treatment of choice in all primary malignant chest wall neoplasms except large solitary plasmacytomas where incisional biopsy followed by irradiation appears to be the method of preference. In Ewing's and Askin's tumours, additional chemotherapy and radiotherapy have to be used. The extent of surgical excision should only be limited by the amount of tissue necessary to remove for adequate malignant tissue clearance, since even large defects can be reconstructed with little functional disturbance.

Chest wall resection and reconstruction.

Chest wall reconstruction may be required after resection of malignant tumours, radiation injuries, massive trauma or infection. The ideal reconstruction should provide enough stability in the chest wall to allow adequate, spontaneous ventilation, while protecting intrathoracic organs, and be cosmetically acceptable. Recent developments have enabled the reconstruction of defects of almost any size with minimal functional disturbance.

Results of surgical treatment of oesophageal cancer.

Oesophagogastrectomy is the best available treatment for patients with carcinoma of the oesophagus or cardia. A retrospective analysis of our experience with 485 patients who were treated surgically forms the basis of this report. Of the 317 patients who underwent resection (resectability rate of 65%) only 210 were considered to be potentially curative. Overall, the 5-year survival rate for oesophageal cancer was 3%, whilst curative resection had a 5-year survival rate of 22% and varied according to stages. Five-year survival rate was 67.7% for patients with Stage I disease compared with 27.6, 9.4 and 6.4% for Stages IIa, IIb and III disease respectively. There were no 5-year survivors with Stage IV disease or with those patients who underwent an incomplete resection. Curative resection carried a mortality rate of 3.8%, whereas incomplete resection or palliative procedure carried higher mortality rates of 14 and 20.7% respectively. Adequate post-operative analgesia was provided by continuous extrapleural intercostal nerve block. Morbidity, mainly caused by respiratory complications, occurred in 30 patients (6.2%), with three patients requiring ventilatory support. Outcome was influenced mostly by the extent of the disease and the completeness of surgical resection rather than by histological type. We conclude that surgical treatment provides better longevity than any other type of therapy and remains the standard against which combined modality treatment should be compared. Our experience suggests that surgical treatment can be achieved with minimal morbidity and mortality.

Stenting in malignant obstruction of superior vena cava.

The treatment of patients with malignant superior vena caval obstruction with minimal morbidity has been made possible by the recent introduction of expandable metal stents as the sole palliative treatment or as an adjunct to other treatment modalities. To alleviate the distressing symptoms of superior vena caval obstruction, self-expanding metal stents were used successfully in 12 (Wallstent device in 6 and Gianturco device in 6 patients) of 13 patients. The diagnoses were small cell carcinoma (n = 4), squamous cell carcinoma (n = 4), non-Hodgkin's lymphoma (n = 1), and mesothelioma (n = 1), and a diagnosis of malignancy was not confirmed (although strongly suspected) in the remaining three cases. Eleven patients had immediate relief of obstruction and there was no change in one patient. Mean follow-up was 3.7 months (range 1 to 10 months). Excellent palliation was obtained in all but one patient in whom recurrent superior vena caval obstruction developed 3 months after stenting. Mean survival was 4.8 months (range 1 to 10 months). The ease of insertion with the use of local anesthesia with radiologic control, the self-expanding nature of the stent, and the lack of major complications on follow-up of up to 10 months are particular advantages. The self-expanding superior vena caval stents are a useful addition to our armamentarium in the management of malignant superior vena caval obstruction.

Tumor embolism to LAD during pneumonectomy. A case report.

Arterial embolization from bronchogenic carcinoma is a rare complication and more commonly occurs intraoperatively during pneumonectomy. We report an unusual case of intraoperative tumour embolism to LAD (left anterior descending artery) and aorta during left pneumonectomy due to tumour involvement of the inferior pulmonary vein. High risk cases should be evaluated by preoperative transesophageal echocardiography. If tumour involvement of the inferior pulmonary vein is demonstrated, a modification of the surgical technique or alternative modality of treatment should be used.

Results of surgical treatment of stage I and II lung cancer.

Pulmonary resection remains the most appropriate treatment for localised bronchogenic carcinoma, since prognosis and outcome are currently dependent on surgical resectability. A retrospective analysis of our experience with three hundred and thirteen stage I (n=250) and stage II (n=63) patients treated surgically form the basis of this report. The initial pulmonary resection was lobectomy in 173 patients, bilobectomy in 38, sleeve lobectomy in 12, pneumonectomy in 59, wedge excision or segmentectomy in 31. The overall operative mortality was 3.2%; 4.03% for lobectomy and 1.6% for pneumonectomy. Morbidity was observed in 21 (6.7%) patients. Four out of sixteen small cell carcinoma patients had postoperative adjuvant chemotherapy. Survival in patients with stage I tumours was 71% at 5 years and 61% at 10 years compared with 41% at 5 years and 35% at 10 years for patients with stage II disease. The five year survival after pneumonectomy was significantly (p<0.05) better for both stage I and stage II lung cancer than after lobectomy. Five year survival in stage I carcinoma was not influenced by histological type, while there was statistically significant difference (p<0.05) in survival between adenocarcinoma (0%) and squamous cell carcinoma (46%) in stage II disease. We conclude that an aggressive surgical approach can provide an excellent prognosis for recovery and long term cure in most patients with early stage lung cancer.

Traumatic rupture of diaphragm.

Traumatic diaphragmatic rupture remains a diagnostic challenge, and associated injuries determine the outcome in those diagnosed early, whereas that of latent cases is dependent on the consequence of the diaphragmatic rupture: namely, the diaphragmatic hernia. To analyze the clinical and radiologic features and the therapeutic implications, we reviewed 980 patients reported in the English-language literature. This injury affects predominantly males (male:female = 4:1) in the third decade of life, and is often caused by blunt trauma (75%). There were 1,000 injuries, of which 685 (68.5%) were left-sided, 242 (24.2%) right-sided, 15 (1.5%) bilateral, and 9 (0.9%) pericardial ruptures; 49 cases were unclassified. Chest (43.9%) and splenic (37.6%) trauma were the most common associated injuries. The diagnosis was made preoperatively in 43.5% of cases, whereas in 41.3% it was made at exploration or at autopsy and on the remaining 14.6% of the cases the diagnosis was delayed. The mortality was 17% in those in whom acute diagnosis was made, and the majority of the morbidity in the group that underwent operation was due to pulmonary complications. Uniform diagnosis depends on a high index of suspicion, careful scrutiny of the chest roentgenogram in patients with thoracoabdominal or polytrauma, and meticulous inspection of the diaphragm when operating for concurrent injuries. Repeated evaluation for days after injury is necessary to discern injury in patients not requiring laparotomy. Acute diaphragmatic injuries are best approached through the abdomen, as more than 89% of patients with this injury have an associated intraabdominal injury. Patients with diaphragmatic rupture presenting in the latent phase have adhesion between the herniated abdominal and intrathoracic organs, and thus the rupture is best approached via a thoracotomy.

A prospective, randomized comparison of interpleural and paravertebral analgesia in thoracic surgery.

We have undertaken a prospective, randomized comparison of the superficially similar techniques of interpleural and paravertebral (extrapleural) analgesia in 53 patients undergoing posterolateral thoracotomy. Local anaesthetic placed anterior to the superior costotransverse ligament and posterior to the parietal pleura produces a paravertebral block and instilled between the parietal and visceral pleurae produces an interpleural block. Patients received preoperative and postoperative continuous bupivacaine paravertebral blocks in group 1 and interpleural blocks in group 2. Premedication comprised diclofenac and morphine, and after operation all patients had regular diclofenac and patient-controlled morphine (PCM). Analgesia was assessed by visual analogue pain scores (VAS), PCM requirements, ratio of preoperative to postoperative spirometric values (PFT), rates of postoperative respiratory morbidity (PORM) and hospital stay, all recorded by blinded observers. Eight patients were withdrawn and data from 45 patients were analysed. Patient characteristics, surgery, VAS scores and PCM use were similar in both groups. PFT were significantly better (P = 0.03-0.0001) in group 1, and PORM was lower and hospital stay approximately 1 day less in this group. Five patients in group 2 became temporarily confused, probably because of bupivacaine toxicity (P = 0.02). We conclude that bupivacaine deposited paravertebrally produced greater preservation of lung function and fewer side effects than bupivacaine administered interpleurally.

Self-expanding tracheobronchial stents in the management of major airway problems.

The management of patients with critical major airways obstruction has been made possible by the recent introduction of expandable metal stents as the sole treatment or as an adjunct to other treatment modalities, to alleviate the distressing symptoms from tracheobronchial obstructions Gianturco self-expanding stents were used successfully in the management of 27 patients. The indications were: stenosis from postoperative strictures and recurrent tumours (n = 6), extrinsic compression from metastatic disease (n = 9), inoperable primary tumours of central airways (n = 9), airway collapse from relapsing polychondritis (n = 1), excessive mediastinal shift following right pneumonectomy (n = 1) and endobronchial non-Hodgkin's lymphoma (n = 1). Twenty three patients had immediate relief of stridor and the remaining two patients were successfully weaned from ventilatory support. There were two postoperative deaths. The stents were inserted under general anaesthesia through a rigid bronchoscope under direct vision. The ease of insertion under radiological control, self-expanding nature of the stents and the lack of major complications on follow-up of up to 47 months are particular advantages. The self-expanding tracheobronchial stents are a useful addition to our armamentarium in maintenance of the airways in patients with major airway stenosis and collapse.

Gastric outlet obstruction of intrathoracic stomach.

Two rare cases of organic outlet obstruction of intrathoracic stomach following Ivor Lewis oesophagectomy are presented. Aetiology and the management of the same is discussed.

Efficacy of pre-emptive analgesia and continuous extrapleural intercostal nerve block on post-thoracotomy pain and pulmonary mechanics.

OBJECTIVE: Thoracotomy results in severe pain and deleterious changes in pulmonary physiology. The literature suggests that these alterations in pulmonary mechanics are inevitable and can only be minimised but not prevented by effective analgesia. We have re-evaluated this concept and assessed the efficacy of pre-emptive analgesia [preincisional afferent block, premedication with opiate and/or non-steroidal anti-inflammatory drug (NSAID)] in conjunction with postoperative extrapleural continuous intercostal nerve block on postoperative pain and pulmonary function. MATERIALS AND METHODS: A prospective randomized study was conducted on 56 patients undergoing elective thoracotomy. Subjective pain relief was assessed on a linear visual analogue scale. Pulmonary function was measured on the day before operation and 12 hourly for 48 hours after operation. There were seven patients in each of the eight groups. RESULTS: The balanced analgesia group comprising preincisional block and premedication with opiate and NSAID (Group 1) had significantly better analgesia, needed less postoperative supplementary analgesics and maintained their preoperative pulmonary function postoperatively irrespective of the nature of the operation. The ranking of importance of the three components of the pre-emptive analgesia as assessed in this study are preincisional block, opiate premedication and premedication with NSAID's. No significant change in plasma levels of cortisol or glucose occurred in Group 1 patients from prior to induction of anaesthesia to 24 hours postoperatively, suggesting effective somatic and sympathetic afferent blockade had been achieved in these patients. There were no complications related to the infusion or the use of NSAID's. CONCLUSIONS: We conclude that a balanced analgesic regime comprising preoperative pain prophylaxis and postoperative maintenance analgesia by NSAID and continuous extrapleural intercostal nerve block will minimise and even reverse the expected decline in lung function after thoracotomy. The postoperative decline in lung function is not obligatory but primarily due to incisional pain and thus is preventable by effective analgesia. An ideal balanced pre-emptive analgesic regime should include preincisional local anaesthetic afferent block and premedication with opiates and a NSAID:

Self-expanding tracheobronchial stents in the management of major airway problems.

The management of patients with critical major airway obstruction has been made possible by the recent introduction of expandable metal stents as the sole treatment or as an adjunct to other treatment modalities. To alleviate the distressing symptoms from tracheobronchial obstructions Gianturco self-expanding stents were used successfully in the management of 16 patients. The indications were; stenosis from postoperative strictures and recurrent tumours (n = 6), extrinsic compression from metastatic disease (n = 4), inoperable primary tumours of central airways (n = 4), airway collapse from relapsing polychondritis (n = 1), and endobronchial non-Hodgkin's lymphoma (n = 1). Fourteen patients have immediate relief of stridor and the remaining two patients were successfully weaned from ventilatory support. The stents were inserted under general anaesthesia through a rigid bronchoscope under direct vision. The ease of insertion under radiological control, self-expanding nature of the stents and the lack of major complications on follow-up of up to 22 months are particular advantages. The self-expanding tracheobronchial stents are a useful addition to our armamentarium in maintenance of the airways in patients with major airway stenosis and collapse.

Late esophageal fistula after pneumonectomy.

Esophageal fistula formation after pulmonary resection is rare. We present a case of esophagocutaneous fistula 9 years after left pneumonectomy for squamous cell carcinoma of the bronchus. This was confirmed on barium swallow and endoscopy. The fistula was sealed successfully with monomeric n-butyl-2-cyanoacrylate tissue adhesive. The simplicity and effectiveness of this method of management is discussed and the multitude of surgical options considered.

Results of surgical treatment of stage III lung cancer.

The role of surgery in the management of Stage III lung cancer is controversial. A retrospective analysis of our experience with 220 Stage III patients treated surgically (Stage IIIa n = 174, Stage IIIb n = 46) form the basis of this report. Of the 140 patients who underwent resection only 88 were considered to be potentially curative, all but two being operated in Stage IIIa. The overall 5-year survival rate for Stage III lung cancer was 12.1% whilst curative resection had a 5-year survival rate of 31.8%. The 5-year survival rate increased to 42% with curative resection for T3N0M0 patients. There were no 5-year survivors with incomplete resection. There were no 5-year survivors in Stage IIIb disease. Five-year survival rates for N0 (n = 62), N1 (n = 78), and N2 (n = 80) irrespective of T status were 37.2%, 3.4% and 5.6%, respectively. The operative mortality rate was only 3.4% for curative resection while palliative or non-resection patients had a mortality rate of 10.6%. Eighty-eight patients, 55 of Stage IIIa and 23 of Stage IIIb had postoperative radiotherapy with a median survival of 12 and 9 months, respectively. Fifteen small cell carcinoma patients had postoperative adjuvant chemotherapy with a median survival of 6.5 months. The only 5-year survivor in this group also had a curative resection. We conclude that metastasis to lymph nodes usually implies systemic disease and a poor prognosis. Surgical therapy continues to be the treatment of choice in a small subset of patients with Stage III resectable lung cancer discovered at thoracotomy.(ABSTRACT TRUNCATED AT 250 WORDS)