Piers R. Boshier

Transthoracic versus transhiatal esophagectomy for the treatment of esophagogastric cancer: a meta-analysis.

Objective:To study the differences in short and long-term outcomes of transthoracic and transhiatal esophagectomy for cancer. Background:Studies have compared transthoracic with transhiatal esophagectomy with varying results. Previous systematic reviews (1999, 2001) do not include the latest randomized controlled trials. Methods:Systematic review of English-language studies comparing transthoracic with transhiatal esophagectomy up to January 31, 2010. Meta-analysis was used to summate the study outcomes. Methodological and surgical quality of included studies was assessed. Results:Fifty-two studies, comprising 5905 patients (3389 transthoracic and 2516 transhiatal) were included in the analysis. No study met all minimum surgical quality standards. Transthoracic operations took longer and were associated with a significantly longer length of stay. There was no difference in blood loss. The transthoracic group had significantly more respiratory complications, wound infections, and early postoperative mortality, whereas anastomotic leak, anastomotic stricture, and recurrent laryngeal nerve palsy rate was significantly higher in the transhiatal group. Lymph node retrieval was reported in 4 studies and was significantly greater in the transthoracic group by on average 8 lymph nodes. Analysis of 5-year survival showed no significant difference between the groups and was subject to significant heterogeneity. Conclusions:This meta-analysis of studies comparing transthoracic with transhiatal esophagectomy for cancer demonstrates no difference in 5-year survival, however lymphadenectomy and reported surgical quality was suboptimal in both groups and the transthoracic group had significantly more advanced cancer. The finding of equivalent survival should therefore be viewed with caution.

Repeatability of the measurement of exhaled volatile metabolites using selected ion flow tube mass spectrometry.

Selected ion flow tube mass spectrometry, SIFT-MS, has been used to determine the repeatability of the analysis of volatile metabolites within the breath of healthy volunteers, with emphasis on the influence of sampling methodology. Baseline instrument specific coefficients of variability for examined metabolites were as follows: acetone (1%), ammonia (1%), isoprene (2%), propanol (6%), ethanol (7%), acetic acid (7%), and hydrogen cyanide (19%). Metabolite concentration and related product ion count rate were identified as strong determinants of measurement variation. With the exception of ammonia, an orally released metabolite, variability in repeated on-line breath analysis tended to be lower for metabolites of systemic origin. Standardization of sampling technique improved the repeatability of the analysis of selected metabolites. Off-line (bag) alveolar breath sampling, as opposed to mixed (whole) breath sampling, likewise improved the repeatability of the analysis of all metabolites investigated, with the exception of acetic acid. We conclude that SIFT-MS analysis of common volatile metabolites within the breath of healthy volunteers is both reliable and repeatable. For selected metabolites, the finding that repeatability is improved through modification of sampling methodology may have implications in terms of future recommended practices.

Improving Outcomes After Gastroesophageal Cancer Resection: Can Japanese Results Be Reproduced in Western Centers?

HYPOTHESIS Extended lymphadenectomy in gastroesphageal cancer leads to improved long-term survival without compromising postoperative outcomes in Western patients to attain the standard achieved in Japanese centers. DESIGN Cohort study comparing postoperative outcomes and long-term survival with data from the National Cancer Center (NCC) of Tokyo, Japan. Outcomes were also compared with data from the UK National Oesophago-Gastric Cancer Audit (NOGCA) and a representative cohort from southeast England. Prospectively collected data were independently audited. SETTING University medical center. PATIENTS From 2003 to 2010, 100 patients underwent gastrectomy and 109 underwent esophagectomy. MAIN OUTCOME MEASURES Postoperative mortality and morbidity and long-term overall survival. Lymph node count was used as a measure for the extent of lymphadenectomy. RESULTS One death occurred after esophagectomy and none after gastrectomy. Anastomotic leak rate was approximately 2% in both cohorts. Kaplan-Meier estimates of 5-year overall survival after gastrectomy and esophagectomy were 58.4% and 47.8%, respectively. Postoperative mortality and technical complications for gastric and esophageal cancer resections were similar to NCC rates (P = .20). Stage for stage 5-year survival rates in patients with esophageal cancer and stages II and III gastric cancer were similar to outcomes in the NCC. The 5-year survival for patients with gastric cancer was worse for those with stage I (P < .001) and better for those with stage IV (P < .001) disease compared with NCC rates. Postoperative outcomes and long-term survival were significantly better than those reported by the NOGCA and the data from the southeast of England (P < .05). CONCLUSIONS This study demonstrates that postoperative outcomes and long-term survival after gastroesophageal cancer resection can be improved in Western patients to the highest standard achieved in Japan.

Variation in the levels of volatile trace gases within three hospital environments: implications for clinical breath testing.

Selected ion flow tube mass spectrometry, SIFT-MS, has been used to determine the levels of volatile trace gases in the room air of three clinical environments within a busy teaching hospital. The main aims of this study were to establish background levels of trace gases and to compare them to levels typically found within exhaled breath. Over a period of one month, room air samples were collected daily from an outpatient clinic, a hospital ward and an operating theatre, in either the morning or the evening. The concentrations of seven volatile compounds were compared between different locations and different times of the day. Having established the baseline levels for these compounds, breath was collected from healthy volunteers working within each of the three clinical locations. The concentrations of isoprene, acetone, hydrogen cyanide and ammonia within room air samples collected from at least one of the three clinical environments were less than 25% of levels typically found in human breath. Based on the recommendation of previous authors these compounds may therefore be suitable for use as exhaled markers of disease. In comparison high levels of ethanol, propanol and acetic acid within room air samples collected from each location may diminish confidence in their use as breath biomarkers.

Techniques to increase lymph node harvest from gastrointestinal cancer specimens: a systematic review and meta-analysis.

Abbassi‐Ghadi N, Boshier P R, Goldin R & Hanna G B (2012) Histopathology61, 531–542 
Techniques to increase lymph node harvest from gastrointestinal cancer specimens: a systematic review and meta‐analysis

Exhaled nitric oxide as biomarker of acute lung injury: an unfulfilled promise?

The discovery of nitric oxide (NO) as a signalling and regulatory molecule and its subsequent detection in the exhaled breath has not only yielded new mechanistic insights but also diagnostic opportunities and therapeutic targets in several important medical conditions. In diseases involving chronic pulmonary inflammation such as asthma that affects millions worldwide, exhaled NO has achieved spectacular successes with patients currently owning handheld devices and monitoring inflammatory aspects of their conditions in their own homes. This has been facilitated by recognition by regulatory bodies, scientific and clinical societies and insurance companies. While characteristic changes in exhaled NO have also been observed in acute lung injury (ALI), the promise of exhaled NO as a surrogate biomarker of this life-threatening disease has not been achieved. In this work, we have analysed factors contributing to successes of exhaled NO in the asthma field and contrasted these on the ALI field. We provide a snapshot of current status of exhaled NO field in ALI and propose a framework for definite evaluation of exhaled NO as a clinically useful biomarker.

Improving the standard of lymph node retrieval after gastric cancer surgery

To examine factors that influence lymph node count and to study the relationship between nodal size and metastatic involvement in gastric cancer.

Influence of respiratory variables on the on-line detection of exhaled trace gases by PTR-MS

Background Modern gas analysis techniques permit real time and on-line quantification of multiple volatile trace gases within a single exhalation. However, the influence of various respiratory manoeuvres affecting exhalation flow and the kinetics of metabolite release to the gas-phase remain largely unknown. Methods We examined variation in the concentrations of selected trace gases over a range of expiratory flows (50; 100; 250 ml/s) and after 30 second periods of breathold and paced hyperventilation. On-line measurement of breath samples from healthy volunteers (n=10) was performed by proton transfer mass spectrometry. Results Exhaled acetone increased with higher expiratory flow rate (805, 838, 898 ppb, p=0.02). Levels of methanol (206 vs 179 ppb, p<0.01), acetaldehyde (26 vs 22 ppb, p<0.01), ethanol (410 vs 208 ppb, p=0.01) and dimethyl sulphide (113 vs 103 ncps, p<0.01) fell significantly following 30s hyperventilation. After 30 second breathold levels of methanol (206 vs 217 ppb, p=0.02), acetone (805 vs 869 ppb, p<0.01), isoprene (348 vs 390 ppb, p=0.02) and dimethyl sulphide (113 vs 136 ncps, p=0.02) increased significantly. Variation in respiratory parameters did not significantly alters the level of acetonitrile, propanol and butyric acid within the breath of healthy subjects. Conclusions These findings demonstrate that respiratory manoeuvres significantly influence the measured concentration of a number of exhaled VOCs that are of potential importance within the clinical setting. Our results support the adoption of standardised practices for breath gas analysis by on-line and real time mass spectrometry methods.

Influence of glutathione- S -transferase (GST) inhibition on lung epithelial cell injury: role of oxidative stress and metabolism

Oxidant-mediated tissue injury is key to the pathogenesis of acute lung injury. Glutathione-S-transferases (GSTs) are important detoxifying enzymes that catalyze the conjugation of glutathione with toxic oxidant compounds and are associated with acute and chronic inflammatory lung diseases. We hypothesized that attenuation of cellular GST enzymes would augment intracellular oxidative and metabolic stress and induce lung cell injury. Treatment of murine lung epithelial cells with GST inhibitors, ethacrynic acid (EA), and caffeic acid compromised lung epithelial cell viability in a concentration-dependent manner. These inhibitors also potentiated cell injury induced by hydrogen peroxide (H2O2), tert-butyl-hydroperoxide, and hypoxia and reoxygenation (HR). SiRNA-mediated attenuation of GST-π but not GST-μ expression reduced cell viability and significantly enhanced stress (H2O2/HR)-induced injury. GST inhibitors also induced intracellular oxidative stress (measured by dihydrorhodamine 123 and dichlorofluorescein fluorescence), caused alterations in overall intracellular redox status (as evidenced by NAD(+)/NADH ratios), and increased protein carbonyl formation. Furthermore, the antioxidant N-acetylcysteine completely prevented EA-induced oxidative stress and cytotoxicity. Whereas EA had no effect on mitochondrial energetics, it significantly altered cellular metabolic profile. To explore the physiological impact of these cellular events, we used an ex vivo mouse-isolated perfused lung model. Supplementation of perfusate with EA markedly affected lung mechanics and significantly increased lung permeability. The results of our combined genetic, pharmacological, and metabolic studies on multiple platforms suggest the importance of GST enzymes, specifically GST-π, in the cellular and whole lung response to acute oxidative and metabolic stress. These may have important clinical implications.

Redefining the stress cortisol response to surgery

Cortisol levels rise with the physiological stress of surgery. Previous studies have used older, less‐specific assays, have not differentiated by severity or only studied procedures of a defined type. The aim of this study was to examine this phenomenon in surgeries of varying severity using a widely used cortisol immunoassay.