Breath Testing in the Surgical Setting: Applications, Challenges, and Future Perspectives.

BACKGROUND: The potential for exhaled breath to be a valuable diagnostic tool is often overlooked as it can be difficult to imagine how a barely visible sample of breath could hold such a rich source of information about the state of our health. However, technological advances over the last 50 years have enabled us to detect volatile organic compounds (VOCs) present in exhaled breath, and this provides the key to understanding the wealth of information contained within these readily available samples. SUMMARY: VOCs are produced as a by-product of metabolism; hence, changes in the underlying physiological processes will be reflected in the exact composition of VOCs in exhaled breath. It has been shown that characteristic changes occur in the breath VOC profile associated with certain diseases including cancer, which may enable the non-invasive detection of cancer at primary care level for patients with vague symptoms. The use of breath testing as a diagnostic tool has many advantages. It is non-invasive and quick, and the test is widely accepted by patients and clinicians. However, breath samples provide a snapshot of the VOCs present in a particular patient at a given point in time, so this can be heavily influenced by external factors such as diet, smoking, and the environment. These must all be accounted for when attempting to draw conclusions about disease status. This review focuses on the current applications for breath testing in the field of surgery, as well as discussing the challenges encountered with developing a breath test in a clinical environment. The future of breath testing in the surgical setting is also discussed, including the translation of breath research into clinical practice. KEY MESSAGES: Analysis of VOCs in exhaled breath can identify the presence of underlying disease including cancer as well as other infectious or inflammatory conditions. Despite the patient factors, environmental factors, storage, and transport considerations that must be accounted for, breath testing demonstrates ideal characteristics for a triage test, being non-invasive, simple, and universally acceptable to patients and clinicians. Many novel biomarkers and diagnostic tests fail to translate into clinical practice because their potential clinical application does not align with the requirements and unmet needs of the healthcare sector. Non-invasive breath testing, however, has the great potential to revolutionise the early detection of diseases, such as cancer, in the surgical setting for patients with vague symptoms.

Prognostic relevance of lymph node regression on survival in esophageal cancer: a systematic review and meta-analysis.

INTRODUCTION: The prognostic value of histomorphologic regression in primary esophageal cancer has been previously established, however the impact of lymph node (LN) response on survival still remains unclear. The aim of this review was to assess the prognostic significance of LN regression or downstaging following neoadjuvant therapy for esophageal cancer. METHODS: An electronic search was performed to identify articles evaluating LN regression or downstaging after neoadjuvant therapy. Random effects meta-analyses were performed to assess the influence of regression in the LNs and nodal downstaging on overall survival. Histomorphologic tumor regression in LNs was defined by the absence of viable cells or degree of fibrosis on histopathologic examination. Downstaged LNs were defined as pN0 nodes by the tumor, node, and metastasis classification, which were positive prior to treatment neoadjuvant. RESULTS: Eight articles were included, three of which assessed tumor regression (number of patients = 292) and five assessed downstaging (number of patients = 1368). Complete tumor regression (average rate of 29.1%) in the LNs was associated with improved survival, although not statistically significant (hazard ratio [HR] = 0.52, 95% confidence interval [CI] = 0.26-1.06; P = 0.17). LNs downstaging (average rate of 32.2%) was associated with improved survival compared to node positivity after neoadjuvant treatment (HR = 0.41, 95%CI = 0.22-0.77; P = 0.005). DISCUSSION: The findings of this meta-analysis have shown a survival benefit in patients with LN downstaging and are suggestive for considering LN downstaging to ypN0 as an additional prognostic marker in staging and in the comparative evaluation of differing neoadjuvant regimens in clinical trials. No statistically significant effect of histopathologic regression in the LNs on long-term survival was seen.

Assurance of surgical quality within multicenter randomized controlled trials for bariatric and metabolic surgery: a systematic review.

BACKGROUND: Surgical quality assurance methods aim to ensure standardization and high quality of surgical techniques within multicenter randomized controlled trials (RCTs), thereby diminishing the heterogeneity of surgery and reducing biases due to surgical variation. This study aimed to establish the measures undertaken to ensure surgical quality within multicenter RCTs investigating bariatric and metabolic surgery, and their influence upon clinical outcomes. METHODS: An electronic literature search was performed from the Embase, Medline, and Web of Science databases to identify multicenter RCTs investigating bariatric and metabolic surgery. Each RCT was evaluated against a checklist of surgical quality measures within 3 domain: (1) standardization of surgical techniques; (2) credentialing of surgical experience; and (3) monitoring of performance. Outcome measures were postoperative weight change and complications. RESULTS: Nineteen multicenter RCTs were included in the analysis. Three studies undertook pretrial education of surgical standard. Fourteen studies described complete standardization of surgical techniques. Four studies credentialed surgeons by case volume prior to enrollment. Two studies used intraoperative or video evaluation of surgical technique prior to enrollment. Only two studies monitored performance during the study. Although there were limited quality assurance methods undertaken, utilization of these techniques was associated with reduced overall complications. Standardization of surgery was associated with reduced re-operation rates but did not influence postoperative weight loss. CONCLUSION: The utilization of methods for surgical quality assurance are very limited within multicenter RCTs of bariatric and metabolic surgery. Future studies must implement surgical quality assurance methods to reduce variability of surgical performance and potential bias within RCTs.

Impact of gastrointestinal surgery upon the gut microbiome: A systematic review.

BACKGROUND: There is evidence from preclinical models that the gut microbiome may impact outcomes from gastrointestinal surgery, and that surgery may alter the gut microbiome. However, the extent to which gastrointestinal surgery modulates the gut microbiome in clinical practice is currently poorly defined. This systematic review aims to evaluate the changes observed in the gut microbiome after gastrointestinal surgery. METHODS: A systematic review and meta-analysis were conducted according to the PRISMA guidelines by screening EMBASE, MEDLINE/PubMed, Web of Science, and CENTRAL for comparative studies meeting the predetermined inclusion criteria. The primary outcome was the difference between pre and postoperative bacterial taxonomic composition and diversity metrics among patients receiving gastrointestinal surgery. RESULTS: In total, 33 studies were identified including 6 randomized controlled trials and 27 prospective cohort studies reporting a total of 968 patients. Gastrointestinal surgery was associated with an increase in α diversity and a shift in ß diversity postoperatively. Multiple bacterial taxa were identified to consistently trend toward an increase or decrease postoperatively. A difference in microbiota across geographic provenance was also observed. There was a distinct lack of studies showing correlation with clinical outcomes or performing microbiome functional analysis. Furthermore, there was a lack of standardization in sampling, analytical methodology, and reporting. CONCLUSION: This review highlights changes in bacterial taxa associated with gastrointestinal surgery. There is a need for standardization of microbial analysis methods and reporting of results to allow interstudy comparison. Further adequately powered multicenter studies are required to better assess variation in microbial changes and its potential associations with clinical outcomes.

Assessment of chest wall movement following thoracotomy: a systematic review.

Thoracotomy is a major cause of respiratory impairment, increasing the risk of postoperative pulmonary complications (PPC). Systems assessing ribcage kinematics may detect changes in chest expansion following thoracotomy and may thus aid in the development of patient-tailored chest physiotherapy. Hence, we aimed to identify studies assessing changes in chest wall movement following thoracotomy using objective measures. The Cochrane library, MEDLINE, EMBASE, Scopus and Web of Science databases were searched to find relevant articles providing an objective assessment of chest wall movement following thoracotomy. Methodological quality of included studies concerning chest wall movement following thoracotomy was assessed by use of QUADAS-2 tool. A total of 12 articles were included for the assessment of chest wall changes following thoracotomy using objective measures. Four studies measured changes in the cross-sectional area of the ribcage and abdomen using the respiratory inductive plethysmography (RIP), 1 study computed the chest wall compliance by monitoring the intra-pleural pressure, 3 studies measured changes in chest circumference with a simple tape measure and 4 articles performed a compartmental analysis of the chest wall volume by means of an optoelectronic plethysmography (OEP). There was no delay in the collection of data of the index test and reference standard, resulting in a low risk of bias for the flow and timing domain. Across all studies, participants underwent the same reference standard, resulting in a low risk of verification bias. Several objective measures were able to detect changes in chest wall displacement following thoracotomy and differed in the practical use and invasive nature. OEP allows a compartmental analysis of the chest wall volume. Hence, this system allows to assess chest wall movement changes following thoracotomy and the impact of different types of surgical approach. Furthermore, it could aid in the development of tailored physiotherapy.

An international comparison of the utilisation of and outcomes from minimal access surgery for the treatment of common abdominal surgical emergencies.

BACKGROUND: Minimal access surgery (MAS) has suggested improvements in clinical outcomes compared to open surgery in several abdominal elective and emergency surgeries. The aims of this study were to compare England with the United States in the utilisation of MAS and mortality from four common abdominal surgical emergencies. METHODS: Between 2006 and 2012, the rate of MAS and in-hospital mortality for appendicitis, incarcerated or strangulated abdominal hernia, small or large bowel and peptic ulcer perforation were compared between England and the United States. Univariate and multivariate analyses were performed to adjust for differences in baseline patient demographics. RESULTS: 132,364 admissions in England were compared to an estimated 1,811,136 admissions in the United States. Minimal access surgery was used less commonly in England for appendicitis (odds ratio (OR) 0.27, 95% CI 0.267-0.278), abdominal hernia (OR 0.16, 95% CI 0.15-0.17), small or large bowel perforation (OR 0.33, 95% CI 0.32-0.35) and peptic ulcer perforation (OR 0.93, 95% CI 0.87-0.99). In-hospital mortality was increased in England compared to the United States for all four conditions: appendicitis (OR 2.11, 95% CI 1.66-2.68), abdominal hernia (OR 3.25, 95% CI 3.10-3.40), small or large bowel perforation (OR 3.88, 95% CI 3.76-3.99) and peptic ulcer perforation (OR 3.09, 95% CI 2.94-3.25). In England, after adjustment for patient demographics, open surgery was associated with increased in-hospital mortality for abdominal hernia (OR 1.80, 95% CI 1.26-2.71), small or large bowel perforation (OR 1.59, 95% CI 1.37-1.87) and peptic ulcer perforation (OR 2.31, 95% CI 1.91-2.82). CONCLUSIONS: Minimal access surgery was performed less commonly and in-hospital mortality was increased in England compared to the United States for common abdominal surgical conditions. Therefore, strategies to enhance adoption of MAS in emergency conditions in England need to be optimised and include appropriate patient selection and improved surgeon MAS training.

Detection and management of oligometastatic disease in oesophageal cancer and identification of prognostic factors: A systematic review.

BACKGROUND: Oesophageal cancer is the eighth most common cancer worldwide. The prognosis of oesophageal cancer patients still remains poor. The 5-year survival rate rarely exceeds 5% in case of metastatic disease. Some patients may however present with oligometastasis which can be treated with loco-regional therapy. AIM: To assess the current practice regarding the management of patients with oligometastatic oesophageal cancer and identify prognostic factors affecting survival following treatment for oligometastasis. METHODS: A systematic search of the literature was performed in Cochrance Library, MEDLINE and EMBASE databases from September 1950 to January 2019. Relevant electronic databases were searched for studies assessing the clinical outcome of oligometastasis. RESULTS: A total of 14 publications were included, of which 12 studies assessing metachronous oligometastasis and 2 on synchronous oligometastasis. All included articles evaluated the specific outcomes of metastasis, management modality and survival outcomes. The majority of the patients presented with oesophageal squamous cell carcinoma. The median disease free interval (time to recurrence) in patients was 19.6 mo and the overall survival reached 30.8 months. Unfavourable prognostic factors were assessed in eight studies and included time to recurrence < 12 mo, large diameter pulmonary lesions (> 20 mm), disease free interval (DFI) < 12 mo, extra-pulmonary metastasis, primary tumour pathological stage III/IV. CONCLUSION: Oligometastatic oesophageal cancer in selected patients is amenable to loco-regional treatment, and the overall survival of this patient cohort may be improved with patient and tumour-specific treatments.

The evolution of fast track protocols after oesophagectomy.

Fast track is a standardised goal directed patient's care pathway that aims to facilitate recovery following surgery. Currently, there are large variations in the fast track protocols used in oesophagectomy due to the complexity of the procedure. The objective of this systematic review is to assess the evolution of fast track protocols following oesophagectomy since its implementation and the resulting effect on postoperative outcomes. Relevant electronic databases were searched for studies assessing the clinical outcome from fast track in oesophagectomy and also those assessing the effects of the individual key components in fast track protocols. The search yielded twenty-three publications regarding fast track implementation in oesophagectomy. A pattern of consistent evolution in fast-track protocols was clearly demonstrated and these have shown variations in the core-identified components across the studies. However, evolution in fast track protocols over time showed, an overall improvement in length of stay, anastomotic leak, pulmonary complications and mortality over time. Thirty publications were included that evaluated specific components of fast track protocols, with an increasing trend towards addressing the nutritional aspect in oesophagectomy care in more recent years. The variations in the key components of fast track protocol of care identify the need for continued assessment and identification for areas of improvement. In the future incremental gains through focused improvements in key components will lend itself to even better postoperative outcomes and patient experience during oesophageal cancer treatment.

Evolution in the management of acute cholecystitis in the elderly: population-based cohort study.

BACKGROUND: Acute cholecystitis is a life-threatening emergency in elderly patients. This population-based cohort study aimed to evaluate the commonly used management strategies for elderly patients with acute cholecystitis as well as resulting mortality and re-admission rates. METHODS: Data from all consecutive elderly patients (≥ 80 years) admitted with acute cholecystitis in England from 1997 to 2012 were captured from the Hospital Episode Statistics database. Influence of management strategies upon mortality was analyzed with adjustment for patient demographics and treatment year. RESULTS: 47,500 elderly patients were admitted as an emergency with acute cholecystitis. On the index emergency admission the majority of patients (n = 42,620, 89.7%) received conservative treatment, 3539 (7.5%) had cholecystectomy, and 1341 (2.8%) underwent cholecystostomy. In the short term, 30-day mortality was increased in the emergency cholecystectomy group (11.6%) compared to those managed conservatively (9.9%) (p < 0.001). This was offset by the long-term benefits of cholecystectomy with a reduced 1-year mortality [20.8 vs. 27.1% for those managed conservatively (p < 0.001)]. Management with percutaneous cholecystostomy had increased 30-day and 1-year mortality (13.4 and 35.0%, respectively). The annual proportion of cholecystectomies performed laparoscopically increased from 27% in 2006 to 59% in 2012. Within the cholecystectomy group, laparoscopic approach was an independent predictor of reduced 30-day mortality (OR 0.16, 95% CI 0.10-0.25). Following conservative management, there were 16,088 admissions with further cholecystitis. Only 11% of patients initially managed conservatively or with cholecystostomy received subsequent cholecystectomy. CONCLUSION: Acute cholecystitis is associated with significant mortality in elderly patients. Potential benefits of emergency cholecystectomy in selected elderly patients include reduced rate of readmissions and 1-year mortality. Laparoscopic approach for emergency cholecystectomy was associated with an 84% relative risk reduction in 30-day mortality compared to open surgery.

Prognostic significance of peritoneal lavage cytology in staging gastric cancer: systematic review and meta-analysis.

BACKGROUND: Peritoneal cytology has been used as a part of the cancer staging of gastric cancer patients. The primary aim of this systematic review was to evaluate the value of peritoneal cytology as part of the staging of gastric cancer and survival prediction. The second aim was to establish if positive cytology may be modified by neoadjuvant therapy, to improve prognosis. METHODS: An electronic literature search was performed using Embase, Medline, Web of Science, and Cochrane library databases up to January 2016. The logarithm of the hazard ratio (HR) with 95% confidence intervals (CI) was used as the primary summary statistic. Comparative studies were used, and the outcome measure was survival in three groups: (1) positive versus negative cytology at staging laparoscopy immediately preceding surgery; (2) effect of neoadjuvant therapy on cytology and survival; and (3) positive cytology in the absence of macroscopic peritoneal disease was compared with obvious macroscopic peritoneal disease. RESULTS: Pooled analysis demonstrated that positive cytology was associated with significantly reduced overall survival (HR, 3.46; 95% CI, 2.77-4.31; P < 0.0001). Interestingly, negative cytology following neoadjuvant chemotherapy was associated with significantly improved overall survival (HR, 0.42; 95% CI, 0.31-0.57; P < 0.0001). The absence of macroscopic peritoneal disease with positive cytology was associated with significantly improved overall survival (HR, 0.64; 95% CI, 0.56-0.73; P < 0.0001). CONCLUSION: This study suggests that patients with initial positive cytology may have a good prognosis following neoadjuvant treatment if the cytology results change to negative after treatment.

Salvage esophagectomy: safe therapeutic strategy?

The objectives of this review were to assess both the short- and long-term clinical outcomes in patients managed with definitive chemoradiotherapy, and salvage esophagectomy subsequently in comparison to those neoadjuvant chemoradiotherapy followed by planned esophagectomy (NCRS) for esophageal cancer from published literature. Eleven studies comprising 1,906 patients were included, 563 in the salvage group and 1,343 in the NCRS group. Pooled analysis showed no significant difference between salvage and NCRS groups in overall survival [hazard ratio (HR) =1.17; 95% confidence interval (95% CI), 0.94-1.46, P=0.148], postoperative mortality [pooled odds ratios (POR) =1.12; 95% CI, 0.52-2.41, P=0.775], pulmonary complications (POR =1.24; 95% CI, 0.83-1.86, P=0.292) and positive resection margin incidence (POR =1.29; 95% CI, 0.94-1.76, P=0.114). However, within the salvage group there were increases in postoperative morbidity (POR =1.30; 95% CI, 1.00-1.67, P=0.046) and anastomotic leak (POR =1.88; 95% CI, 1.41-2.51, P<0.001). Herein we found that salvage esophagectomy has similar short- and long-term mortality in comparison to planned esophagectomy following neoadjuvant chemoradiotherapy. However, anastomotic leak is increased following salvage esophagectomy suggesting the need for this practice to be reserved for high volume surgeons within high volume centers.

Practice Patterns and Outcomes After Hospital Admission With Acute Para-esophageal Hernia in England.

OBJECTIVE: (i) To establish at a national level clinical outcomes from patients presenting with acute para-esophageal hernia (PEH); and (ii) to determine if a hospital volume-outcome relationship exists for the management of acute PEH. BACKGROUND: Currently, no clear guidelines exist regarding the management of acute PEH, and practice patterns are based upon relatively small case series. METHODS: Patients admitted as an emergency for the treatment of acute PEH between 1997 and 2012 were included from the Hospital Episode Statistics database. The influence of hospital volume upon clinical outcomes was analyzed in unmatched and matched comparisons to control for patient age, medical comorbidities, and incidence of PEH hernia gangrene. RESULTS: Over the 16-year study period, 12,441 patients were admitted as an emergency with a PEH causing obstruction or gangrene. Of these, 90.8% patients were admitted with PEH with obstruction in the absence of gangrene and 9.2% with PEH with gangrene. The incidences of 30 and 90-day mortality were 7% and 11.5%, respectively, which did not decrease during the study period. Unmatched and matched comparisons showed, in high-volume centers, there were significant reductions in utilization of emergency surgery (8.8% vs 14.9%; P < 0.0001), 30-day (5.3% vs 7.8%; P < 0.0001), and 90-day mortality (9.3% vs 12.7%; P < 0.0001). Multivariate analysis also confirmed high hospital volume was independently associated with reduced 30 and 90-day mortality from acute PEH. CONCLUSIONS: Acute PEH represents a highly morbid condition, and treatment in high-volume centers provides the appropriate multidisciplinary infrastructure to manage these complex patients reducing associated mortality.

Transaortic transcatheter aortic valve implantation for failed surgical aortic valve replacement due to 'porcelain aorta'.

Transcatheter aortic valve implantation (TAVI) is an emerging surgical approach in patients with severe aortic stenosis unsuitable for conventional aortic valve replacement (AVR). TAVI has been performed through both transfemoral and transapical approaches, each with a specific suitability criterion. A transaortic (TAo-TAVI) approach has been recently established at the authors' institution for high-risk patients who are unsuited to the above techniques. Herein, the case is described of a successful aortic valve implantation using TAo-TAVI in a patient with porcelain ascending aorta that was identified as an incidental finding during conventional AVR. The patient recovered well and was discharged home without any complications.

Management of an infected aortic graft with endovascular stent grafting.

Aortic graft infection, one of the most common fatal complications of aortovascular surgery, is managed mainly by the removal of infected graft material and re-establishment of vascular continuity using an extra-anatomical bypass or in situ graft replacement. Despite significant progress in perioperative, surgical, and medical treatments, the mortality and morbidity for this condition remain high. Here, we report the use of endograft implantation and prolonged intravenous antibiotics to successfully treat a life-threatening Dacron aortic tube graft infection and anastomotic leak. Although the gold standard is surgical removal of infected material and repair with a homograft, in certain extremely high-risk patients such as ours, an alternate strategy may be warranted when the risks associated with surgery are prohibitive. Endovascular repair of a surgical Dacron graft leak may provide a novel temporizing measure in the acute setting, allowing for delayed semi-urgent surgical intervention, or it may provide a definitive treatment, as in our case. At the four-year follow-up, our patient was well with a good quality of life and with no clinical, radiological, or biochemical evidence of infection.

Intramural collection caused by contrast extravasation into the ascending aortic wall.

Cardiac catheterization is a procedure routinely performed worldwide, with an estimated amount of 61,000 coronary angioplasties performed in the UK annually. Associated mortality--in the region of 0.1-0.2%--is minimal and complication rate approximately 1.5%. The most serious complications described are embolic stroke, cardiac chamber perforation, aortic dissection, coronary occlusions or dissection, and major peripheral vascular complications, including retroperitoneal haematoma and life-threatening haemorrhage. We report the case of a 75-year old patient who had inadvertent contrast agent injection into the aortic wall, leading to a localized contrast collection within the tunica media. This complication has been described before but only in association with coronary artery dissection. It is important to diagnose and manage such a situation, as most iodinated intravascular contrast agents exert a high osmotic load and thereby lead to tissue oedema and necrosis on extravasation. We describe the management of the case and discuss relevant therapeutic strategies.

Central nervous system (CNS) delivery of glucocorticoids is fine-tuned by saturable transporters at the blood-CNS barriers and nonbarrier regions.

Proper functioning of the hypothalamic-pituitary-adrenal axis depends on the ability of glucocorticoids (GCs), mainly cortisol in humans and corticosterone in rodents, to access brain targets and regulate their own secretion. Being highly lipophilic, GCs have been assumed to passively diffuse through the cell membrane. However, the access of these GCs to the brain may be a more complicated process, because the free movement of molecules into the central nervous system (CNS) is restricted by the presence of the blood-brain and blood-cerebrospinal fluid barriers. GCs do interact with some transporter systems, including the efflux transporter, P-glycoprotein, and members of the organic anion transporter polypeptide (oatp) family, both of which have been found at the blood-CNS barriers. Using an in situ brain/choroid plexus perfusion, P-glycoprotein was shown to not majorly regulate the access of [(3)H]cortisol and [(3)H]corticosterone to the choroid plexus or pituitary gland. Interactions of [(3)H]cortisol and [(3)H]corticosterone with saturable influx transporters were detected at the hypothalamus, cerebellum, choroid plexus, and pituitary gland. Oatp2 seems to have some role in the influx of [(3)H]cortisol and [(3)H]corticosterone to the choroid plexus and the pituitary gland and other transporters, unlikely to be oatp2, may play a very minor role in the access of [(3)H]cortisol and [(3)H]corticosterone to the brain, as well as having a significant effect on [(3)H]glucocorticoid receptor accumulation in the pituitary gland. Overall, these data suggest that the majority of cortisol and corticosterone present in the plasma diffuse into the CNS and that transporters do not play a major role in the accumulation of these GCs in the brain.