Stereotactic Ablative Radiotherapy for Oligometastatic Disease: Great Enthusiasm but Scant Evidence.

The prospective study Pulmonary Metastasectomy in Colorectal Cancer (N = 391) showed that expert selection was made on known prognostic features - number of metastases, tumour markers, liver involvement, interval - and patient performance and outcomes replicated follow-up studies. In the nested controlled trial all factors were well balanced and no survival difference remained.

Pulmonary Metastasectomy in Colorectal Cancer: updated analysis of 93 randomized patients - control survival is much better than previously assumed.

AIM: Lung metastases from colorectal cancer are resected in selected patients in the belief that this confers a significant survival advantage. It is generally assumed that the 5-year survival of these patients would be near zero without metastasectomy. We tested the clinical effectiveness of this practice in Pulmonary Metastasectomy in Colorectal Cancer (PulMiCC), a randomized, controlled noninferiority trial. METHOD: Multidisciplinary teams in 14 hospitals recruited patients with resectable lung metastases into a two-arm trial. Randomization was remote and stratified according to site, with minimization for age, sex, primary cancer stage, interval since primary resection, prior liver involvement, number of metastases and carcinoembryonic antigen level. The trial management group was blind to patient allocation until after intention-to-treat analysis. RESULTS: From 2010 to 2016, 93 participants were randomized. These patients were 35-86 years of age and had between one and six lung metastases at a median of 2.7 years after colorectal cancer resection; 29% had prior liver metastasectomy. The patient groups were well matched and the characteristics of these groups were similar to those of observational studies. The median survival after metastasectomy was 3.5 (95% CI: 3.1-6.6) years compared with 3.8 (95% CI: 3.1-4.6) years for controls. The estimated unadjusted hazard ratio for death within 5 years, comparing the metastasectomy group with the control group, was 0.93 (95% CI: 0.56-1.56). Use of chemotherapy or local ablation was infrequent and similar in each group. CONCLUSION: Patients in the control group (who did not undergo lung metastasectomy) have better survival than is assumed. Survival in the metastasectomy group is comparable with the many single-arm follow-up studies. The groups were well matched with features similar to those reported in case series.

Meta-analysis of colorectal cancer follow-up after potentially curative resection.

BACKGROUND: After potentially curative resection of primary colorectal cancer, patients may be monitored by measurement of carcinoembryonic antigen and/or CT to detect asymptomatic metastatic disease earlier. METHODS: A systematic review and meta-analysis was conducted to find evidence for the clinical effectiveness of monitoring in advancing the diagnosis of recurrence and its effect on survival. MEDLINE (Ovid), Embase, the Cochrane Library, Web of Science and other databases were searched for randomized comparisons of increased intensity monitoring compared with a contemporary standard policy after resection of primary colorectal cancer. RESULTS: There were 16 randomized comparisons, 11 with published survival data. More intensive monitoring advanced the diagnosis of recurrence by a median of 10 (i.q.r. 5-24) months. In ten of 11 studies the authors reported no demonstrable difference in overall survival. Seven RCTs, published from 1995 to 2016, randomly assigned 3325 patients to a monitoring protocol made more intensive by introducing new methods or increasing the frequency of existing follow-up protocols versus less invasive monitoring. No detectable difference in overall survival was associated with more intensive monitoring protocols (hazard ratio 0·98, 95 per cent c.i. 0·87 to 1·11). CONCLUSION: Based on pooled data from randomized trials published from 1995 to 2016, the anticipated survival benefit from surgical treatment resulting from earlier detection of metastases has not been achieved.

Effects of aortic root motion on wall stress in the Marfan aorta before and after personalised aortic root support (PEARS) surgery.

Aortic root motion was previously identified as a risk factor for aortic dissection due to increased longitudinal stresses in the ascending aorta. The aim of this study was to investigate the effects of aortic root motion on wall stress and strain in the ascending aorta and evaluate changes before and after implantation of personalised external aortic root support (PEARS). Finite element (FE) models of the aortic root and thoracic aorta were developed using patient-specific geometries reconstructed from pre- and post-PEARS cardiovascular magnetic resonance (CMR) images in three Marfan patients. The wall and PEARS materials were assumed to be isotropic, incompressible and linearly elastic. A static load on the inner wall corresponding to the patients' pulse pressure was applied. Cardiovascular MR cine images were used to quantify aortic root motion, which was imposed at the aortic root boundary of the FE model, with zero-displacement constraints at the distal ends of the aortic branches and descending aorta. Measurements of the systolic downward motion of the aortic root revealed a significant reduction in the axial displacement in all three patients post-PEARS compared with its pre-PEARS counterparts. Higher longitudinal stresses were observed in the ascending aorta when compared with models without the root motion. Implantation of PEARS reduced the longitudinal stresses in the ascending aorta by up to 52%. In contrast, the circumferential stresses at the interface between the supported and unsupported aorta were increase by up to 82%. However, all peak stresses were less than half the known yield stress for the dilated thoracic aorta.

Aortic flow patterns before and after personalised external aortic root support implantation in Marfan patients.

Implantation of a personalised external aortic root support (PEARS) in the Marfan aorta is a new procedure that has emerged recently, but its haemodynamic implication has not been investigated. The objective of this study was to compare the flow characteristics and hemodynamic indices in the aorta before and after insertion of PEARS, using combined cardiovascular magnetic resonance imaging (CMR) and computational fluid dynamics (CFD). Pre- and post-PEARS MR images were acquired from 3 patients and used to build patient-specific models and upstream flow conditions, which were incorporated into the CFD simulations. The results revealed that while the qualitative patterns of the haemodynamics were similar before and after PEARS implantation, the post-PEARS aortas had slightly less disturbed flow at the sinuses, as a result of reduced diameters in the post-PEARS aortic roots. Quantitative differences were observed between the pre- and post-PEARS aortas, in that the mean values of helicity flow index (HFI) varied by -10%, 35% and 20% in post-PEARS aortas of Patients 1, 2 and 3, respectively, but all values were within the range reported for normal aortas. Comparisons with MR measured velocities in the descending aorta of Patient 2 demonstrated that the computational models were able to reproduce the important flow features observed in vivo.

Biomechanical properties of the Marfan's aortic root and ascending aorta before and after personalised external aortic root support surgery.

Marfan syndrome is an inherited systemic connective tissue disease which may lead to aortic root disease causing dilatation, dissection and rupture of the aorta. The standard treatment is a major operation involving either an artificial valve and aorta or a complex valve repair. More recently, a personalised external aortic root support (PEARS) has been used to strengthen the aorta at an earlier stage of the disease avoiding risk of both rupture and major surgery. The aim of this study was to compare the stress and strain fields of the Marfan aortic root and ascending aorta before and after insertion of PEARS in order to understand its biomechanical implications. Finite element (FE) models were developed using patient-specific aortic geometries reconstructed from pre and post-PEARS magnetic resonance images in three Marfan patients. For the post-PEARS model, two scenarios were investigated-a bilayer model where PEARS and the aortic wall were treated as separate layers, and a single-layer model where PEARS was incorporated into the aortic wall. The wall and PEARS materials were assumed to be isotropic, incompressible and linearly elastic. A static load on the inner wall corresponding to the patients' pulse pressure was applied. Results from our FE models with patient-specific geometries show that peak aortic stresses and displacements before PEARS were located at the sinuses of Valsalva but following PEARS surgery, these peak values were shifted to the aortic arch, particularly at the interface between the supported and unsupported aorta. Further studies are required to assess the statistical significance of these findings and how PEARS compares with the standard treatment.

Pulmonary metastasectomy in colorectal cancer: a prospective study of demography and clinical characteristics of 543 patients in the Spanish colorectal metastasectomy registry (GECMP-CCR).

OBJECTIVES: To capture an accurate contemporary description of the practice of pulmonary metastasectomy for colorectal carcinoma in one national healthcare system. DESIGN: A national registry set up in Spain by Grupo Español de Cirugía Metástasis Pulmonares de Carcinoma Colo-Rectal (GECMP-CCR). SETTING: 32 Spanish thoracic units. PARTICIPANTS: All patients with one or more histologically proven lung metastasis removed by surgery between March 2008 and February 2010. INTERVENTIONS: Pulmonary metastasectomy for one or more pulmonary nodules proven to be metastatic colorectal carcinoma. PRIMARY AND SECONDARY OUTCOME MEASURES: The age and sex of the patients having this surgery were recorded with the number of metastases removed, the interval between the primary colorectal cancer operation and the pulmonary metastasectomy, and the carcinoembryonic antigen level. Also recorded were the practices with respect to mediastinal lymphadenopathy and coexisting liver metastases. RESULTS: Data were available on 543 patients from 32 units (6-43/unit). They were aged 32-88 (mean 65) years, and 65% were men. In 55% of patients, there was a solitary metastasis. The median interval between the primary cancer resection and metastasectomy was 28 months and the serum carcinoembryonic antigen was low/normal in the majority. Liver metastatic disease was present in 29% of patients at some point prior to pulmonary metastasectomy. Mediastinal lymphadenectomy varied from 9% to 100% of patients. CONCLUSIONS: The data represent a prospective comprehensive national data collection on pulmonary metastasectomy. The practice is more conservative than the impression gained when members of the European Society of Thoracic Surgeons were surveyed in 2006/2007 but is more inclusive than would be recommended on the basis of recent outcome analyses. Further analyses on the morbidity associated with this surgery and the correlation between imaging studies and pathological findings are being published separately by GECMP-CCR.

Thoracic surgical management of colorectal lung metastases: a questionnaire survey of members of the Society for Cardiothoracic Surgery in Great Britain and Ireland.

INTRODUCTION: Distant metastases to liver and lung are not uncommon in colorectal cancer. Resection of metastases is accepted widely as the standard of care. However, there is no firm evidence base for this. This questionnaire survey was carried out to assess the current practice preferences of cardiothoracic surgeons in Great Britain and Ireland. METHODS: An online questionnaire survey was emailed to cardiothoracic surgeons in Great Britain and Ireland. The survey was live for 12 weeks. Responses were collated with SurveyMonkey(®). RESULTS: Overall, there were 75 respondents. The majority (83%) indicated thoracic surgery as a specialist interest. Almost all (99%) used thoracic computed tomography (CT) for staging; 70% added liver CT and 51% added pelvic CT. Fluorodeoxy-glucose positron emission tomography was used by 86%. The most frequent indication for pulmonary resection (97%) was solitary lung metastasis without extrathoracic disease. Video assisted thoracoscopic surgery (VATS) was used by 85%. In addition, thoracotomy was used by 96%. A third (33%) used radiofrequency ablation. Synchronous liver and lung resection was contraindicated for 83% of respondents. Over three-quarters (77%) thought that scientific equipoise exists presently for lung resection for colorectal lung metastases but only 21% supported a moratorium on this type of surgery until further evidence becomes available. CONCLUSIONS: The results confirm that the majority of respondents use conventional cross-sectional imaging and either VATS or formal thoracotomy for resection. The results emphasise the continuing need for formal randomised trials to provide evidence of any survival benefit from pulmonary metastasectomy for colorectal lung metastases.

The history of adoption of hepatic resection for metastatic colorectal cancer: 1984-95.

BACKGROUND: Liver resection for metastatic colorectal cancer became established without randomized trials. Proponents of surgical resection point out 5-year survival approaching 50% whilst critics question how much of the apparent effect is due to patient selection. METHOD: A 2006 systematic review of reported outcomes provided the starting point for citation analysis followed by thematic analysis of the texts of the most cited papers. RESULTS: 54 reports from 1988 to 2002 cited 709 unique publications a total of 1714 times. The 15 most cited papers were explored in detail, and showed clear examples of duplicate reporting and overlapping data sets. Textual analysis revealed proposals for a randomized controlled trial, but this was argued to be unethical by others, and no trial was undertaken. CONCLUSIONS: This critical review reveals how the case for this surgery was made, and examines the arguments that influenced acceptance and adoption of this surgery.