Breath metabolite response to major upper gastrointestinal surgery.

BACKGROUND: Esophagectomy and gastrectomy are associated with profound metabolic changes and significant postoperative morbidity. The aim of this prospective clinical study was to determine whether breath analysis can offer novel insight into the surgical metabolic response and identify biomarkers of postoperative complications, including lung injury. METHODS: Breath samples were collected preoperatively and at 24, 48, 72, 96 and 168 h after esophagectomy (n = 25) and gastrectomy (n = 15). Targeted analysis of four prominent breath metabolites was performed by selected ion flow-tube mass spectrometry. Patients with nonsurgical lung injury (community-acquired pneumonia) were recruited as positive controls. RESULTS: Perioperative starvation and subsequent reintroduction of nutritional input were associated with significant changes in breath acetone levels. Breath acetone levels fell after esophagectomy (P = 0.008) and were significantly lower than in gastrectomy patients at postoperative time points 48 (P < 0.001) and 72 h (P < 0.001). In contrast, concentrations of isoprene increased significantly after esophagectomy (P = 0.014). Pneumonia was the most frequently observed postoperative complication (esophagectomy 36% and gastrectomy 7%). The concentration of hydrogen cyanide was significantly lower in the breath of patients who developed pneumonia, 72 h after surgery (P = 0.008). Exhaled hydrogen cyanide (P = 0.001) and isoprene (P = 0.014) were also reduced in patients with community-acquired pneumonia compared with healthy controls. CONCLUSIONS: Selected ion flow-tube mass spectrometry can be used as a totally noninvasive resource to monitor multiple aspects of metabolic alterations in the postoperative period. Exhaled concentrations of several prominent metabolites are significantly altered after major upper gastrointestinal surgery and in response to pneumonia.

Selected ion flow tube-MS analysis of headspace vapor from gastric content for the diagnosis of gastro-esophageal cancer.

Gastric content is a complex biofluid within the human stomach which has an important role in digestive processes. It is believed that gastric content may be a contributory factor in the development of upper gastro-intestinal diseases. In this work, selected ion flow tube mass spectrometry (SIFT-MS) has been applied to the quantification of volatile organic compounds (VOCs) in the headspace vapor of gastric content samples, which were retrieved from three groups of patients, including those with gastro-esophageal cancer, noncancer diseases of the upper gastro-intestinal tract, and a healthy cohort. Twelve VOCs have been investigated in this study; the following 7 VOCs, acetone, formaldehyde, acetaldehyde, hexanoic acid, hydrogen sulphide, hydrogen cyanide, and methyl phenol, were found to be significantly different between cancer and healthy groups by the Mann-Whitney U test. Receiver operating characteristics (ROC) analysis was applied for the combined VOCs of acetaldehyde, formaldehyde, hydrogen sulphide, and methyl phenol to discriminate cancer patients from healthy controls. The area under the curve (AUC) was 0.9. This result raises the prospect that a VOC profile rather than a single biomarker may be preferable in the molecular-orientated diagnosis of gastro-oseophageal cancer, and this warrants further investigation to assess its potential application as a new diagnostic test.

On-line, real time monitoring of exhaled trace gases by SIFT-MS in the perioperative setting: a feasibility study.

A study is described of the first on line, real time analyses of the exhaled breath of five anaesthetized patients during the complete perioperative periods of laparoscopic surgery. These breath analyses were achieved using a selected ion flow tube, SIFT-MS, instrument, located in the operating theatre at an acceptable distance from the operating table, and coupled to the endotracheal tube in the ventilation circuit via a 5 metre long capillary tube. Thus, inhalation/exhalation breathing cycles, set to be at a frequency of 10 per minute, were sampled continuously for water vapour, the metabolites acetone and isoprene and the propofol used to induce anaesthesia for each operating period that ranged from 20 min (shortest) to 80 min (longest). Whilst there was some loss of water vapour along the long sampling line, the concentrations of the other trace compounds were not diminished. The breath acetone was essentially at a constant level for each patient, but increased somewhat over the longest operating period due to the onset of lipolysis. Most interesting is the clear increase of breath isoprene following abdomen inflation with carbon dioxide. The vapour of the intravenously injected propofol was detected in the exhaled breath and remained essentially constant during the perioperative period. These analyses were performed totally non-invasively and the data were immediately and constantly available to the anaesthetist and surgeon. Exploitation of this development could influence decision making and potentially improve patient safety within the perioperative setting.

Scaffold hopping with molecular field points: identification of a cholecystokinin-2 (CCK2) receptor pharmacophore and its use in the design of a prototypical series of pyrrole- and imidazole-based CCK2 antagonists.

A new molecular modeling approach has been used to derive a pharmacophore of the potent and selective cholecystokinin-2 (CCK(2)) receptor antagonist 5 (JB93182), based on features shared with two related series. The technique uses "field points" as simple and effective descriptions of the electrostatic and van der Waals maxima and minima surrounding a molecule equipped with XED (extended electron distribution) charges. Problems associated with the high levels of biliary elimination of 5 in vivo required us to design a compound with significantly lower molecular weight without sacrificing its nanomolar levels of in vitro activity. Two new series of compounds were designed to mimic the arrangement of field points present in the pharmacophore rather than its structural elements. In a formal sense, two of the three amides in 5 were replaced with either a simple pyrrole or imidazole, while some features thought to be essential for the high levels of in vitro activity of the parent compounds were retained and others deleted. These compounds maintained activity and selectivity for this receptor over CCK(1). In addition, the reduction in molecular weight coupled with lower polarities greatly reduced levels of biliary elimination associated with 5. This makes them good lead compounds for development of drug candidates whose structures are not obviously related to those of the parents and represents the first example of scaffold hopping using molecular field points.