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.

Effectiveness of a gentamicin impregnated collagen sponge on reducing sternal wound infections following cardiac surgery: a meta-analysis of randomised controlled trials.

INTRODUCTION: Gentamicin impregnated collagen sponges are licensed for use after cardiac surgery in over 50 countries but their effectiveness at preventing sternal wound infections (SWIs) remains uncertain. The aim of this meta-analysis was to assess the current evidence for effectiveness of such sponges at preventing SWIs in patients after cardiac surgery. METHODS: A systematic search of the literature was undertaken and meta-analyses were performed on the results of the identified, eligible studies. Using random effects models, odds ratios (OR) and corresponding 95% confidence intervals (CI) were calculated for all SWIs and deep SWIs for: a) all participants, and b) participants deemed as high risk. RESULTS: Three unique randomised controlled trials (published between 2005 and 2010) involving 3,994 participants met the inclusion criteria. There was insufficient evidence of a significant difference between intervention and control groups for all SWIs (all participants: OR: 0.66, 95% CI: 0.39-1.14; high risk participants: OR: 0.60, 95% CI: 0.24-1.52). There was insufficient evidence of a significant benefit of the sponge in deep SWIs across all participants (OR: 0.72, 95% CI: 0.47-1.10) but some evidence of benefit in terms of reducing the incidence of deep SWIs in high risk participants (OR: 0.62, 95% CI: 0.39-0.98). CONCLUSIONS: There is insufficient evidence of the effectiveness (or otherwise) of gentamicin impregnated sponges in preventing SWIs following cardiac surgery. However, some evidence does exist that such sponges can reduce the incidence of deep infections in high risk patients.

Diagnostic and therapeutic performance of video-assisted thoracoscopic surgery (VATS) in investigation and management of pleural exudates.

INTRODUCTION: Video-assisted thoracoscopic surgery (VATS) is the gold standard investigation for diagnosis of pleural exudates. It is invasive and it is important to ensure that it is performed to acceptable national standards. We assumed that VATS empyema fluid culture would not contribute further to microbiological diagnosis in referred culture-negative empyemas. PATIENTS AND METHODS: Eighty-six consecutive external referrals for VATS for diagnosis of a cytology-negative pleural exudate (or for further management of the exudate) were studied retrospectively. Diagnostic yield, pleurodesis efficacy and complications were compared to national standards and good practice recommendations. VATS empyema fluid microbiological culture results were compared to pre-VATS empyema fluid culture results. RESULTS: VATS was performed well within national standards with a diagnostic yield of 82.3% for cytology-negative exudates, 100% pleurodesis efficacy, 5.8% postoperative fever, with only one significant complication (1.2% rate) and no deaths. Compliance with good practice pleural fluid documentation points was greater than 70%. VATS empyema fluid culture positivity (84.6%) was significantly higher than pre-VATS fluid culture (35%). CONCLUSIONS: VATS was performed to acceptable standards. These data confirm the utility and safety of VATS in the right context but also suggest the potential diagnostic utility of VATS empyema fluid culture. Further studies are required to investigate this latter possibility further.

Impact of preoperative screening for meticillin-resistant Staphylococcus aureus by real-time polymerase chain reaction in patients undergoing cardiac surgery.

We report a significant reduction in the number of surgical site infections (SSIs) due to meticillin-resistant Staphylococcus aureus (MRSA) in patients undergoing cardiac surgery after the introduction of preoperative screening using a same-day polymerase chain reaction (PCR) test. This was an observational cohort study set in a cardiac surgery unit based in southwest England. We studied 1462 patients admitted for cardiac surgery between October 2004 and September 2006. The IDI MRSA PCR test was used preoperatively to screen 765 patients between October 2005 and September 2006. Patients identified as carriers were treated with nasal mupirocin ointment and topical triclosan for five days, with single-dose teicoplanin instead of flucloxacillin as perioperative antibiotic prophylaxis. The rate of SSI following cardiac surgery in this group was compared to 697 patients who underwent surgery without screening between October 2004 and September 2005. After introduction of PCR screening, the overall rate of SSI fell from 3.30% to 2.22% with a significant reduction in the rate of MRSA infections (relative risk reduction: 0.77; 95% confidence interval: 0.056-0.95). PCR screening combined with suppression of MRSA at the time of cardiac surgery is feasible in routine clinical practice and is associated with a significant reduction in subsequent MRSA SSIs.

Implementation of the British Thoracic Society recommendations for organising the care of patients with lung cancer: the surgeon's perspective.

BACKGROUND: The British Thoracic Society (BTS) recognises that it is of paramount importance to ensure that all patients with a working diagnosis of lung cancer have access to first class care [The Lung Cancer Working Party of the British Thoracic Society Standards of Care Committee. BTS recommendations to respiratory physicians for organising the care of patients with lung cancer. Thorax 1998; 53 (Suppl 1): S1-81. METHODS: A retrospective audit of the time involved in the management of patients with lung cancer referred for consideration of surgery at the Royal Brompton Hospital was carried out. Our performance was compared with the BTS recommendations. RESULTS: The notes from 194 patients were analysed, accounting for 93.7% of patients referred with lung cancer in a 1-year period. A total of 90 patients fulfilled the criteria for analysis as they had potentially resectable disease at referral; 59 (65.5%) underwent thoracotomy, and 31 (34.5%) were considered inoperable. The median interval between the onset of symptoms and their first chest radiograph was 39 days, and between the onset of symptoms and referral to a surgeon by a chest physician was 112 days. The median interval between referral by a respiratory physician and surgical out-patient attendance was 14 days, and between referral by a respiratory physician and the surgical procedure was 32.5 days. The median length of time from surgical out-patient attendance to the surgical procedure was 17 days. There was no association between the interval between the onset of symptoms and the surgical procedure with advanced tumour stage at surgery. CONCLUSIONS: There are a number of sources of delay in the referral process for a patient with potentially resectable lung cancer. Most patients referred to our unit were treated within the time scale recommended by the BTS. Our survey has shown that there are cumulative delays in the overall investigation and management of lung cancer patients, which are not covered by the BTS guidelines, and which result in unacceptable delays for most patients.

CUSP/p63 expression in rat and human tissues.

The human homolog of KET, p63, bears strong homology to the tumor suppressor p53 and plays an essential role in epithelial development. CUSP, the most abundant cutaneous product of p63, has been identified as an autoantigen in chronic ulcerative stomatitis (CUS). The original report of KET expression at least partially contradicts p63 expression subsequently reported by many different groups. We have examined p63 expression by Northern analysis of RNA from multiple human tissues and by indirect immunofluorescence of rat tissue with CUS patient sera. Northern analysis reveals p63 RNA in skin, thymus, placenta, skeletal muscle, kidney, and lung, with non-transactivating p63 RNA in skin, thymus, and placenta. Reverse transcriptase polymerase chain reaction (rtPCR) assays show abundant non-transactivating p63 RNA, and little to no transactivating p63 RNA, in human basal cell carcinoma as well as in normal skin adjacent to the tumors. p63 RNA expression was not detected in brain, heart, colon, spleen, liver, or small intestine. Immunofluorescence reveals p63 expression in skin, oral epithelium, tongue, kidney, and trachea, but not in liver, large intestine, testis, skeletal muscle, or heart. Focal p63 expression within tissues, the complex array of isoforms encoded by the gene, and the specificity of the probes and antibodies utilized, may all contribute to contradictory accounts of CUSP/p63 expression.

Extramedullary plasmacytoma presenting with myasthenia gravis and mediastinal mass.

A 68-year-old woman presented with myasthenia gravis and an anterior mediastinal mass, which proved to be an extramedullary plasmacytoma in the thymus with associated extracellular light chain deposition. Further specimens revealed plasma cell proliferation in an internal thoracic lymph node and in a subsequent colectomy specimen, indicating systemic disease. This case demonstrates the rare association between a plasmacytoma in the thymus and myasthenia gravis.

Characterization of an autoantigen associated with chronic ulcerative stomatitis: the CUSP autoantigen is a member of the p53 family.

A unique clinical syndrome has been described in which patients have chronic oral ulceration and autoantibodies to nuclei of stratified squamous epithelium. We have characterized the autoantibodies from patients sera and found that the major autoantigen is a 70 kDa epithelial nuclear protein. Sequencing of the cDNA for this protein, chronic ulcerative stomatitis protein, revealed it to be homologous to the p53 tumor suppressor and to the p73 putative tumor suppressor, and to be a splicing variant of the KET gene. The p53-like genes, p73 and the several KET splicing variants, are recently described genes of uncertain biologic and pathologic significance. This study provides the first clear association of a p53-like protein with a disease process.

Coronary vasoconstriction to endothelin-1 increases with age before and after ischaemia and reperfusion.

OBJECTIVE: Ageing is known to be associated with changes within the heart. We investigated whether the coronary response to endothelin-1 (ET) and sarafotoxin S6c (S6c) is altered with increasing age, before and after cardioplegic arrest. METHODS: Using an isolated rat heart model, increasing concentrations of ET and S6c were administered to rats of different ages (group I = one month; group II = five months; group III = 21 months). An identical series of experiments was performed following the addition of indomethacin and NG-nitro-L-arginine methyl ester (L-NAME) to the Krebs perfusion fluid. In a third series of experiments, increasing doses of ET-1 were added to hearts following 4 h of cardioplegic arrest at 4 degrees C. RESULTS: Coronary flows are expressed as a percentage of initial coronary flow +/- SEM. There was a greater decrease in coronary flow in the older rats for all doses of ET-1. ET-1 (10(-9) M) reduced coronary flows to 72.8 +/- 3.7, 53.2 +/- 6.7 and 56.5 +/- 10.7% for groups I-III respectively (P = 0.01 I vs. II; P = 0.1 I vs. III). A similar response to ET-1 was seen in hearts perfused with indomethacin and L-NAME when compared to those perfused without (P = NS). Perfusion with ET-1 (10(-9) M) following 4 h of cardioplegic arrest reduced coronary flows to 40.5 +/- 4.9, 26.8 +/- 4.8 and 24.1 +/- 3.9%, respectively (P = 0.08 I vs. II; P = 0.03 I vs. III). Perfusion with S6c (10(-10) M) produced coronary flows of 93.3 +/- 5.5, 77.0 +/- 3.5 and 73.9 +/- 3.9% for groups I-III, respectively (P = 0.03 I vs. II; P = 0.01 I vs. III). Perfusion with S6c (10(-9) M) in the presence of L-NAME and indomethacin reduced coronary flows to 85.7 +/- 3.0, 81.6 +/- 2.2 and 74.6 +/- 3.6% (P = NS I vs. II; P = 0.03 I vs. III). CONCLUSIONS: The coronary vasoconstrictor response to ET-1 and S6c increases with age. The increased vasoconstriction in response to ET-1 is independent of the decrease in NO release seen with ageing.

Tricuspid valve repair in a mountaineer.

Lord Hunt of Everest presented with aortic stenosis but predominant right ventricular failure. He was found to have signs of pulmonary hypertension with a dilated right ventricle, severe tricuspid regurgitation, and right atrial hypertrophy in the absence of elevated pulmonary artery pressures. He is a lifelong mountaineer and we attribute these findings to intermittent prolonged exposure to high altitude.

Comparison of the morphologic and vascular reactivity of the proximal and distal radial artery.

BACKGROUND: Variations in the morphology and vascular reactivity of the proximal and distal radial artery might influence its performance as a bypass conduit. METHODS: The morphologic and functional characteristics of the proximal and distal RAs were compared with those of the left and right internal mammary arteries by using histologic and in vitro organ bath techniques. RESULTS: Proximal RA had a significantly greater medial cross-sectional area compared with that of the distal RA (2.48+/-0.27 mm2 compared with 1.86+/-0.21 mm2, p< 0.05), which were both significantly greater than the left internal mammary artery (0.54+/-0.09 mm2) or the right internal mammary artery (0.67+/-0.03 mm2). Proximal RA had a significantly greater response to 90 mmol/L potassium chloride than that of distal RA (88.4+/-7.3 compared with 60.2+/-10.3 mN, p<0.05), and both contracted more than the left internal mammary artery (30.3+/-2.9 mN) and the right internal mammary artery (32.6+/-4.1 mN). There was no difference in the response to noradrenaline and adrenaline between proximal and distal RA, both of which contracted more than the left and right internal mammary arteries. CONCLUSIONS: When choosing a segment of RA for use as a bypass conduit, regional variations in biologic properties should be considered.

Fluorocarbon emulsions.

Perfluorocarbon emulsions have been the topic of intense investigation for many years and presently there are still no absolute indications for their use in clinical practice. The relatively disappointing results of the early clinical studies, as a consequence of using low concentrations of a relatively underdeveloped emulsion, have been responsible for a largely negative impression and it is now essential that the newer second generation emulsions should be judged individually with regard to their efficacy and toxicity under different circumstances. Technological advancement in the fields of chemistry and detergent/emulsifier research will continue and new formulations are being developed which which will require to be tested in models in the laboratory. In the future, this class of drugs will continue to be the topic of intense investigation and their mechanisms of action, which are undoubtedly more complex than the simple carriage of dissolved gases in solution, will be clarified. However, whether fluorocarbon emulsions will ever be used as a 'blood substitute' as was originally anticipated is doubtful.