Tom Routledge

Is video-assisted thoracoscopic surgical decortication superior to open surgery in the management of adults with primary empyema?

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was whether video-assisted thoracoscopic surgical decortication (VATSD) might be superior to open decortication (OD) (or chest tube drainage) for the management of adults with primary empyema? Altogether 68 papers were found using the reported search, of which 14 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. We conclude that VATSD has superior outcomes for the treatment of persistent pleural collections in terms of postoperative morbidity, complications and length of hospital stay, and gives equivalent resolution when compared with OD. One study comparing VATSD and chest tube drainage of fibrinopurulent empyema found video-assisted thoracoscopic surgery (VATS) had higher treatment success (91% vs. 44%; P<0.05), lower chest tube duration (5.8+/-1.1 vs. 9.8+/-1.3 days; P=0.03), and lower number of total hospital days (8.7+/-0.9 vs. 12.8+/-1.1 days; P=0.009). Eight studies comparing early and late empyema report conversion rates to OD of 0-3.5% in early, 7.1-46% in late stage and significant reductions in length of stay with VATSD compared with OD both postoperatively (5 vs. 8 days; P=0.001) and in total stay (15 vs. 21; P=0.03). Additionally VATS resulted in reduced postoperative pain (P<0.0001) and complications including atelectasis (P=0.006), prolonged air-leak (P=0.0003), sepsis (P=0.03) and 30-day mortality (P=0.02). Five studies considered only chronic persistent empyema of which two directly compared VATSD to tube thoracostomy (TT). VATS resolved 88% of cases and had mortality rates of 1.3% compared with 62% and 11%, respectively, for TT. Moreover, conversion to OD was 10.5-17.1% with VATS and 18-37% with TT (P<0.05). In agreement with mixed stage empyema, hospital stay was reduced both postoperatively (8.3 vs. 12.8 days; P<0.05) and in total (14+/-1 vs. 17+/-1 days; P<0.05), and when compared with OD (one study), pain (P<0.0001), postoperative air-leak (P=0.004), hospital stay (P=0.020) and time to return to work (P<0.0001) were all reduced with VATS. Additionally, re-operation (4.8% vs. 1%; P=0.09) and mortality (4/123% vs. 0%) were lower in VATS vs. OD.

In elderly patients with lung cancer is resection justified in terms of morbidity, mortality and residual quality of life?

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was: In [patients over 70 years of age with lung cancer] is [lung resection] when compared with [non-surgical treatment] justified in terms of [postoperative morbidity, mortality and quality of life]? Altogether more than 297 papers were found using the reported search, of which 12 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. We conclude that patients over 70 years of age undergoing anatomical lung resection respond as well as younger patients in terms of morbidity, mortality and residual quality of life (QoL). Collective analysis of the papers reveals no significant difference in five-year survival rates following surgery for early stage disease (stage I non-small cell lung cancer: <70 years; 69-77%, >70 years; 59-78%), although, elderly patients currently receive far higher rates of palliative care (30-47% in patients 65-70 years vs. 8% in patients under 65 years). Additionally, 30-day mortality rates (5.7% <70 years vs. 1.3-3.3% >70 years), length of hospital stay [1.3 days vs. 1 day (video-assisted mini-thoracotomy) and 4.6 vs. 4.9-5.2 days (thoracotomy) for <70 years vs. >70 years, respectively] and postoperative lung function tests (FEV(1) decrease; 13% <70 years vs. 18% >70 years P=0.34, functional vital capacity decrease; 9% <70 years vs. 14% >70 years P=0.31) are equivalent between the two age groups. Residual QoL following lobectomy (evaluated by patient self-assessment) showed decreased social (P<0.001) and role (P<0.001) functioning but less pain at discharge (P<0.001) in those over 70 years. Global QoL, however, was not influenced by age (global QoL; <70 years 22.2+/-25.3 vs. >70 years 17.6+/-22.9). Pneumonectomy showed statistically significant decreases in physical functioning [six months postoperatively (MPO) P=0.045], role functioning (3 MPO P=0.035), social functioning (6 MPO P=0.006, 12 MPO P=0.001) and general pain (6 MPO P=0.037), but showed no age related differences (<70 years; 81.9+/-19.1, >70 years; 78.0+/-22.8).

Video-assisted thoracoscopic surgery or transsternal thymectomy in the treatment of myasthenia gravis?

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was how video-assisted thoracoscopic surgery (VATS) compares to median sternotomy in the surgical management of patients with myasthenia gravis (MG)? Overall 74 papers were found using the reported search, of which 15 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results are tabulated. We conclude that VATS produces equivalent postoperative mortality and complete stable remission (CSR) rates, with superior results in terms of hospital stay, operative blood loss and patient satisfaction at the expense of a doubling of operative time. Six studies comparing VATS and transsternal sternotomy in non-thymomatous myasthenia gravis (NTMG) patients found VATS to have lower operative blood loss (73.8±70.7 vs. 155.3±91.7 ml; P<0.05), reduced total hospital stay (5.6±2.2 vs. 8.1±3.0 days; P=0.008), whilst maintaining equivalent remission rates (33 vs. 44.7%; P=0.16) and mass of thymic tissue resection (37 vs. 34 g; P>0.05). One study comparing video-assisted thoracoscopic extended thymectomy to transsternal thymectomy in only thymoma-associated myasthenia gravis (T-MG) patients found equivalent CSR (11.3 vs. 8.7%, P=0.1090) at six-year follow-up. Thymoma recurrence rate (9.64%) was not significantly different (P=0.1523) between the two groups. Eight studies comparing VATS and transsternal approach in mixed T-MG and NTMG patients found a lower hospital stay (1.9±2.6 vs. 4.6±4.2 days, P<0.001), reduced need for postoperative medication (76.5 vs. 35.7%, P=0.022), lower intensive care unit stay (1.5 vs. 3.2 days, P=0.018), greater symptom improvement (100 vs. 77.9%, P=0.019) and better cosmetic satisfaction (100 vs. 83, P=0.042) with VATS. In concordance with NTMG and T-MG alone patient groups, VATS and transsternal methods had equivalent complication rates (23 vs. 19%, P=0.765) with no mortalities in either group. Even though VATS has a longer operative time (268±51 vs. 177±92 min, P<0.05), its improved cosmesis, reduced need for postoperative medication and equivalent disease resolution outcomes make it a preferable surgical option to the transsternal approach.

Does positron emission tomography offer prognostic information in malignant pleural mesothelioma

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was whether positron emission tomography is useful in the diagnosis and prognosis of malignant pleural mesothelioma (MPM). Altogether 136 papers were found using the reported search, of which 15 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. We conclude that fluorodeoxyglucose-positron emission tomography (FDG-PET) accurately differentiates benign from malignant pleural disease, helps detect recurrence and provides prognostic information in terms of staging, survival and mortality. Eleven studies evaluated the role of FDG-PET in the diagnosis and prognosis of MPM. Malignant disease had a higher standardised uptake value (SUV) (6.5 ± 3.4 vs. 0.8 ± 0.6; P < 0.001) than benign pleural disease. Shorter median survival (9.7 vs. 21 months; P = 0.02) was associated with high SUV (>10) than low SUV (<10). PET accurately upstaged 13% and downstaged 27% of cases initially staged with computed tomography (CT). In patients undergoing chemotherapy, higher total glycolytic volume led to a lower median survival (4.9 vs. 11.5 months; P = 0.09), while a decline in FDG uptake was associated with a longer time to tumour progression (14 vs. 7 months; P = 0.02). Four studies observed the role of FDG-PET-CT in the diagnosis and prognosis of MPM. SUV was found to be higher in MPM compared to benign pleural disease (6.5 vs. 0.8; P < 0.001). A higher SUV(max) was observed in primary pleural lesions of metastatic (7.1 vs. 4.7; P = 0.003) compared to non-metastatic disease. Patients who underwent surgery had equivalent survival to those excluded based on scan results (20 vs. 12 months; P = 0.3813). One study compared the utility of PET and PET-CT in the diagnosis and prognosis of mesothelioma. PET-CT was found to be more accurate than PET in terms of staging (P < 0.05) disease. Overall, PET accurately diagnoses MPM, predicts survival and disease recurrence. It can guide further management by predicting the response to chemotherapy and excluding surgery in patients with extrathoracic disease. Combined PET-CT has additional benefits in accurately staging disease.

Is limited pulmonary resection equivalent to lobectomy for surgical management of stage I non-small-cell lung cancer?

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was: is limited pulmonary resection equivalent to lobectomy in terms of morbidity, long-term survival and locoregional recurrence in patients with stage I non-small-cell lung cancer (NSCLC)? A total of 166 papers were found using the reported search; of which, 16 papers, including one meta-analysis and one randomized control trial (RCT), represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. With regards to 5-year survival rates, the evidence is conflicting: a 2005 meta-analysis and six other retrospective or prospective nonrandomized analyses did not find any statistically significant difference when comparing lobectomy with limited resection. However, three studies found evidence of a decreased overall survival with limited resection, including the only randomized control trial, which showed a 50% increase in the cancer-related death rate (P = 0.09), and a 30% increase in the overall death rate in patients undergoing limited resection (P = 0.08). Age, tumour size and specific type of limited resection were also factors influencing the survival rates. Four studies, including the RCT, found increased locoregional recurrence rates with limited resection. There is also evidence that wedge resections, compared with segmentectomies, lead to lower survival and higher recurrence rates. In conclusion, lobectomy is still recommended for younger patients with adequate cardiopulmonary function. Although limited resection carries a decreased rate of complications and shorter hospital stays, it may also carry a higher rate of loco-regional recurrences. However, limited resection may be comparable for patients >71 years of age, and those with small peripheral tumours.

What is the best treatment for malignant pleural effusions

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was whether chemical pleurodesis is superior to catheter drainage or pleuroperitoneal shunts (PPS) in the management of patients with pleural effusions. Overall 161 papers were found using the reported search, of which 14 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results are tabulated. We conclude that chemical pleurodesis is superior to chronic catheter drainage and PPS in terms survival length and mortality rates but in patients with trapped lung syndrome chronic intrapleural catheter placement is indicated. Six studies reported patient outcomes after treatment with chemical pleurodesis. They report high success rates (89.4%) and low mortality rates (2%) without any need to convert to open thoracotomy. Mean hospital stay of 2.33 days, complication rates of 16.5% and mean survival length of 23.8 ± 16.3 months were observed. Five studies managed malignant pleural effusions (MPEs) using chronic indwelling catheters. They reported mean survival length of 126 days. Symptomatic relief was achieved in 94.2% of patients. There was a significant reduction in the Medical Research Council dyspnoea score (3.0-1.9, P < 0.001) and despite complication rates of 22%, comparable mortality rates (7.5%) were observed. Even in patients with trapped lung syndrome, mean survival length was 125 days with symptomatic improvement being achieved in 90.9% of patients. Three studies treated MPEs using PPSs. Mean hospital stay was 6.2 days (range 2-26) with a mean survival length of 11 months. Pleurodesis success rates varied from 57.1% to 95% with a complication rate of 14.8%. PPSs were shown to produce lower success rates (57.1% vs. 92.3%), shorter survival lengths (4.3 ± 1.9 vs. 6.7 ± 2.1 months) and higher complication rates (14.3% vs. 2.8%) than talc pleurodesis. Overall, chemical pleurodesis is the optimal treatment option for MPE with use of chronic intrapleural catheters reserved in cases where talc pleurodesis is not possible.

Is pleurectomy and decortication superior to palliative care in the treatment of malignant pleural mesothelioma

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was whether pleurectomy/decortication (P/D) is superior to palliative care in the treatment of patients with malignant pleural mesothelioma (MPM). Overall 80 papers were found using the reported search, of which 11 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results are tabulated. We conclude that P/D may lead to superior survival rates but at the expense of higher morbidity rates to palliative treatment. Six studies reported patient outcomes after use of radical P/D to treat patients with MPM. Radical P/D leads to a higher median survival than supportive care (14.5 vs. 4.5 months) and non-radical decortication (15.3 vs. 7.1 months, P < 0.000). However, radical P/D had a complication rate of 30%, hospital stay of 12 days with an operative mortality rate of 9.1%. One-year survival rate was 65% but this fell to 0-24% at three years. Three studies highlighted the use of palliative chemotherapy to manage patients with MPM. Median survival (14 vs. 10 months) was higher in patients who received chemotherapy early compared to those on a delayed protocol. Early chemotherapy had a longer time to disease progression (25 vs. 11 weeks, P = 0.1) and greater one-year survival (66% vs. 36%) than the delayed group. Active symptom control (ASC) alone had lower symptom control rates than the combination of ASC plus MVP (mitomycin+vinblastine+cisplatin) (7% vs. 11%, P = 0.0017) and ASC plus vinorelbine (4% vs. 7%, P = 0.047). Three studies reported results of palliative surgery in patients with known MPM. Median survival period was 213 days with a 30-day mortality rate of 7.8%. Survival rates reduced from 70.6% at three months to 25.5% at one-year post-surgery. Prolonged air-leak and postoperative empyema complicated 9.8% and 4% of patients, respectively. P/D is a morbid operation that is associated with significant perioperative mortality and complication rates. Although a number of retrospective studies have shown a small benefit in survival with P/D, the heavily documented similarity in patient outcomes between P/D and extrapleural pneumonectomy along with the results of the Mesothelioma and Radical Surgery trial, should induce the surgical community to consider the use of P/D only in patients with malignant mesothelioma enrolled in prospective trials.

Does surgery have a role in T4N0 and T4N1 lung cancer

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed whether [surgery] has a role in [treatment of T4N0 and T4N1 lung cancer]. Altogether more than 151 papers were found using the reported search, of which 15 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. We conclude that upfront surgery for locally invasive T4 tumours without mediastinal lymph node involvement (T4N0 and T4N1 non-small cell lung cancer) is of benefit in terms of survival rates in carefully selected patients. Overall five-year survival rates following resection of T4N0-N2 tumours vary from 19.1% to 57% (from six studies), within which, involvement of certain structures were found to greatly affect prognosis. Pulmonary artery invasion has a good prognosis (five-year survival; 52.8%) relative to other mediastinal structures [five-year survival: left atrium; N0; 28.94%, N1; 27.92%, N2; 17.95% (three-year survival), aorta; N0; 100%, N1; 37.1%, N2; 0%, superior vena cava (SVC); 11%, -29.4% (from four studies), carina; 28-42.5% (two studies), veterbral bodies; 16%, oesophagus; 12%, pleural dissemination; 0%]. When considering isolated invasion of the pulmonary great vessels there are mixed outcomes, one study reporting reduced mortality (reduced risk -0.483, P=0.004) in contrast to another that found five-year survival of 35.7% with great vessel invasion vs. 58.3% for invasion of all other structures excluding the pulmonary great vessels. The prognostic variables found to be of greatest determinacy were; first, the completeness of resection, wherein five-year survival rates ranged from 37.5 to 46.2% (from three studies) with complete tumour removal, and 15.9-22.4% (from three studies) with incomplete resection, and second, nodal status of the patients, N0/N1 having five-year survival of 43-74% and N2 of 15.1-17.5% (P=0.022 and P=0.007, for two studies). Multiple intralobar lesions represent either multilobar metastasis or NSCLC with multifocal origin and have been found to behave differently to invasive T4 tumours. Reported five-year survival in NSCLC with satellite nodules is 48.2-57% compared with 18-30% from T4 invasive tumours (three studies), respectively (P=0.011) corroborating the change in TNM ipsilobar multifocal T4 disease to be recoded as T3.

Is surgery indicated in patients with stage IIIa lung cancer and mediastinal nodal involvement

The role of surgery in the treatment of patients with stage IIIa non-small cell lung cancer (NSCLC) and mediastinal node involvement is examined in this best evidence topic according to a structured protocol. A total of 579 papers were identified using the outlined search, 12 of which were deemed to represent the best available evidence. From the data summarized, we conclude that surgery, as part of a multimodality therapeutic approach, offers a survival benefit for patients with resectable N2 NSCLC. Overall five-year survival rates following primary resection ranged from 17% to 20% (four studies). Improved five-year survival was demonstrated with multimodality therapy (19-45%; 13 studies). Subgroup analysis demonstrates a five-year survival of 30.5% with postoperative chemo-radiotherapy, 22.2% with chemotherapy alone, and 27% with radiotherapy alone. In our review, we address three major issues regarding the management of stage IIIa NSCLC, the first of which is primary vs. postinduction surgery. The largest cohort series to date is the International Association for the Study of Lung Cancer Staging Committee paper on nodal disease, which reports that patients with single-zone N2 disease had the same survival outcome as patients with multizone N1 disease. The second issue is that of randomized vs. cohort studies: there have been five randomized trials reporting similar outcomes and hence equipoise. The third issue is postinduction staging. All studies evaluated reported a better outcome in patients with ypN0 (i.e. postinduction N0 disease). However, surgery should not be denied to patients with ypN1-N2, as there is evidence to demonstrate a significant improvement in survival time in all patients able to undergo surgery after induction chemo-radiotherapy. In conclusion, although some of the evidence available is equivocal regarding the survival benefit of resection for stage IIIa N2 disease, the authors believe surgery should be considered as part of a multimodality therapeutic strategy for patients with advanced nodal disease.

Extrapleural pneumonectomy or supportive care: treatment of malignant pleural mesothelioma?

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was whether extrapleural pneumonectomy (EPP) is superior to supportive care in the treatment of patients with malignant pleural mesothelioma (MPM). Overall, 110 papers were found using the reported search, of which 14 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results are tabulated. We conclude that EPP confers no advantage to chemotherapy and palliative treatment in terms of survival and symptom improvement. Ten studies evaluated the role of EPP in the management of MPM. The median survival was 13 months and perioperative and 30-day mortality rates were 5.7% and 9.1%, respectively. There was a high morbidity rate of 37% including atrial fibrillation, empyema and supraventricular arrhythmias. Disease recurred in 73% of patients at a median time of 10 months. Median hospital stay was 13 days and intensive care unit stay was 1.5 days. At three months postsurgery, improvement in symptoms was achieved in 68% of patients. Significant advantages were observed in patients with epithelial MPM (19 vs. 8 months, P<0.01) compared to non-epithelial MPM and with N2 disease (19 vs. 10 months) compared to N1 or N0 disease, respectively. Two studies reported outcomes after chemotherapy in patients with MPM. The median survival was 13 months and symptoms improved in 50% of patients. Response rate of 21% was achieved and the median time to disease progression was 7.2 months. Postoperative haematological toxicity was common and included neutropenia (25%), anaemia (5%) and thrombocytopenia (7.4%). Two studies analysed palliative treatment in mesothelioma and reported a median survival of seven months and improvement in symptoms in 25% of patients at one-year post-treatment. The 30-day mortality rate was 7.8% and complications included prolonged air leak (9.8%) and empyema (4%). Median hospital stay was seven days. Overall, EPP shows no benefit in terms of survival or symptom improvement which is compounded by its high operative mortality and recurrence rate.