Biomarkers of acute appendicitis: systematic review and cost–benefit trade-off analysis

BACKGROUND: Acute appendicitis is the most common surgical emergency and can represent a challenging diagnosis, with a negative appendectomy rate as high as 20 %. This review aimed to evaluate the clinical utility of individual biomarkers in the diagnosis of appendicitis and appraise the quality of these studies. METHODS: A systematic review of the literature between January 2000 and September 2015 using of PubMed, OvidMedline, EMBASE and Google Scholar was conducted. Studies in which the diagnostic accuracy, statistical heterogeneity and predictive ability for severity of several biomarkers could be elicited were included. Information regarding costs and process times was retrieved from the regional laboratory. European surgeons blinded to these reviews were independently asked to rank which characteristics of biomarkers were most important in acute appendicitis to inform a cost-benefit trade-off. Sensitivity testing and the QUADAS-2 tool were used to assess the robustness of the analysis and study quality, respectively. RESULTS: Sixty-two studies met the inclusion criteria and were assessed. Traditional biomarkers (such as white cell count) were found to have a moderate diagnostic accuracy (0.75) but lower costs in the diagnosis of acute appendicitis. Conversely, novel markers (pro-calcitonin, IL 6 and urinary 5-HIAA) were found to have high process-related costs including analytical times, but improved diagnostic accuracy. QUADAS-2 analysis revealed significant potential biases in the literature. CONCLUSION: When assessing biomarkers, an appreciation of the trade-offs between the costs and benefits of individual biomarkers is needed. Further studies should seek to investigate new biomarkers and address concerns over bias, in order to improve the diagnosis of acute appendicitis

Applied investigation of person-specific and context-specific factors on postoperative recovery and clinical outcomes of patients undergoing gastrointestinal cancer surgery: multicentre European study

INTRODUCTION: Cancer treatments have greatly advanced over the past two decades causing survival improvements and reduced complications from cancer surgery. However, the cancer diagnosis and the effects of treatment modalities pose a major risk to patients' psychological well-being. Given current interest and emerging evidence about the importance of psychological and social factors on cancer survival and coping with cancer treatments, this study will build and expand research in order to identify key modifiable psychosocial variables that contribute to better physical and mental health following gastrointestinal cancer (GIC) surgery. OBJECTIVES: To elucidate the incidence of postoperative psychiatric morbidity within 6 months following GIC surgery. To identify key measurable modifiable preoperative psychological factors that can significantly affect postoperative psychiatric morbidity in patients undergoing surgery for GIC. To clarify the changes seen in a patient's psychological well-being during their treatment pathway for GIC. METHODS AND ANALYSIS: This multicentre study has an observational longitudinal study design. In total, 1000 patients will be screened with a multicomponent psychological questionnaire at four different time points: at diagnosis, preoperatively, 1 and 6 months after surgery. Data from this questionnaire will be linked to postoperative complications including psychiatric morbidity, length of hospital stay and recovery to normal activity. ETHICS AND DISSEMINATION: NHS Health Research Authority approval was gained on (REC reference 15.LO/1847) for the completion of this study. Multiple platforms will be used for the dissemination of the research data, including international clinical and patient group presentations and publication of research outputs in a high impact clinical journal

Comparisons of model simulations with observations of mean flow and turbulence within simple obstacle arrays

A three-dimensional numerical code with unstructured tetrahedral grids, the finite element flow solver (FEFLO), was used to simulate the mean flow and the turbulence within obstacle array configurations consisting of simple cubical elements. Model simulations were compared with observations from a hydraulic water flume at the University of Waterloo. FEFLO was run in large eddy simulation mode, using the Smagorinsky closure model, to resolve the larger scales of the flow field. There were four experiment test cases consisting of square and staggered arrays of cubical obstacles with separations of 1.5 and 0.5 obstacle heights. The mean velocity profile for the incoming neutral boundary layer was approximated by a power law, and the turbulent fluctuations in the approach flow were generated using a Monte Carlo model. The numerical simulations were able to capture, within 40% on average, the general characteristics of the mean flow and the turbulence, such as the strong mean wind shears and the maximum turbulence at the elevation of the obstacles and the nearly constant mean wind and the 50% reduction in the turbulent velocity within the obstacle canopy. As expected, the mean wind speeds were significantly decreased (by about a factor of two or three) in the array with closer obstacle packing. It was found that, a “street canyon” effect was more obvious for the square arrays, with higher flow speeds in between the obstacles, than for the staggered arrays

Surgical proficiency gain and survival after esophagectomy for cancer

Purpose We aimed to identify the presence and length of esophagectomy proficiency gain curves in terms of short- and long-term mortality for esophageal cancer. Patients and Methods Patients who underwent esophagectomy for esophageal cancer between 1987 and 2010 with follow-up until 2014 were identified from a well-established, population-based, nationwide Swedish cohort study. Proficiency gain curves were created by using risk-adjusted cumulative sum analysis for 30-day, 90-day, 1-year, 3-year, and 5-year all-cause and disease-specific mortality measures. Similarly, the proficiency gain curves for lymph node harvest, resection margin status, and reoperation incidence were assessed as performance-contributing factors to the observed changes in long-term survival. Results Esophagectomies in 1,821 patients with esophageal cancer were conducted by 139 surgeons. The change-point in proficiency gain curve for all-cause 30-day mortality was early, at 15 cases, when mortality decreased from 7.9% to 3.1% (P , .001). Later change-points, which ranged from 35 to 59 cases, were observed for 1-, 3- and 5-year mortality rates, for which all-cause mortality decreased from 34.9% to 27.7% (P = .011), from 47.4% to 41.5% (P = .049), and from 31.4% to 19.1% (P = .009), respectively. Similar change-points were observed in disease-specific mortality at 1 and 3 years. There was a continuous increase in lymph node harvest, which did not plateau. Also, change-points were observed for resection margin with tumor involvement at 17 cases, with a reduction from 20.9% to 15.2% (P = .004), and for reoperation rate at 55 cases, with a reduction from 12.6% to 5.0% (P , .001). Conclusion The gain of proficiency in esophagectomy for cancer is associated with measurable changes in short- and long-term mortality results. These findings indicate a need for structured national training and mentorship programs for esophageal cancer surgery

A complete pipeline for untargeted urinary volatolomic profiling with sorptive extraction and dual polar and nonpolar column methodologies coupled with gas chromatography time-of-flight mass spectrometry.

Volatolomics offers an opportunity for noninvasive detection and monitoring of human disease. While gas chromatography-mass spectrometry (GC-MS) remains the technique of choice for analyzing volatile organic compounds (VOCs), barriers to wider adoption in clinical practice still exist, including: sample preparation and introduction techniques, VOC extraction, throughput, volatolome coverage, biological interpretation, and quality control (QC). Therefore, we developed a complete pipeline for untargeted urinary volatolomic profiling. We optimized a novel extraction technique using HiSorb sorptive extraction, which exhibited high analytical performance and throughput. We achieved a broader VOC coverage by using HiSorb coupled with a set of complementary chromatographic methods and time-of-flight mass spectrometry. Furthermore, we developed a data preprocessing strategy by evaluating internal standard normalization, batch correction, and we adopted strict QC measures including removal of nonlinearly responding, irreproducible, or contaminated metabolic features, ensuring the acquisition of high-quality data. The applicability of this pipeline was evaluated in a clinical cohort consisting of pancreatic ductal adenocarcinoma (PDAC) patients (n = 28) and controls (n = 33), identifying four urinary candidate biomarkers (2-pentanone, hexanal, 3-hexanone, and p-cymene), which can successfully discriminate the cancer and noncancer subjects. This study presents an optimized, high-throughput, and quality-controlled pipeline for untargeted urinary volatolomic profiling. Use of the pipeline to discriminate PDAC from control subjects provides proof of principal of its clinical utility and potential for application in future biomarker discovery studies

In-street wind direction variability in the vicinity of a busy intersection in central London

We present results from fast-response wind measurements within and above a busy intersection between two street canyons (Marylebone Road and Gloucester Place) in Westminster, London taken as part of the DAPPLE (Dispersion of Air Pollution and Penetration into the Local Environment; www.dapple.org.uk) 2007 field campaign. The data reported here were collected using ultrasonic anemometers on the roof-top of a building adjacent to the intersection and at two heights on a pair of lamp-posts on opposite sides of the intersection. Site characteristics, data analysis and the variation of intersection flow with the above-roof wind direction (θref) are discussed. Evidence of both flow channelling and recirculation was identified within the canyon, only a few metres from the intersection for along-street and across-street roof-top winds respectively. Results also indicate that for oblique rooftop flows, the intersection flow is a complex combination of bifurcated channelled flows, recirculation and corner vortices. Asymmetries in local building geometry around the intersection and small changes in the background wind direction (changes in 15-min mean θref of 5–10 degrees) were also observed to have profound influences on the behaviour of intersection flow patterns. Consequently, short time-scale variability in the background flow direction can lead to highly scattered in-street mean flow angles masking the true multi-modal features of the flow and thus further complicating modelling challenges

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

ASO author reflections: the role of physiotherapy regimens in esophagectomy and gastrectomy for cancer

PAST Despite advancements in surgical management, esophageal and gastric cancer surgery is still associated with a significant morbidity. Traditionally, esophagectomy and gastrectomy via an open surgical approach has been the treatment of choice for esophageal and gastric cancer, respectively.1,2 Enhanced recovery after surgery (ERAS) protocols commonly include physiotherapy regimens or early mobilization intervention. These programs are well-established in colorectal cancer surgery and have shown to reduce postoperative complication rates and shortened the length of hospital stay (LOS).3 Only a small number of studies have assessed the role of respiratory physiotherapy in gastrointestinal cancer surgery, while this patient group commonly present with pre-existing respiratory disease and is particularly at risk for malnutrition and loss of muscle mass.4 Although there is growing evidence of the benefits of physiotherapy implementation in decreasing the risk for postoperative morbidity, there is currently insufficient strong evidence for routine implementation of standardized respiratory physiotherapy in esophageal and gastric cancer surgery. PRESENT This is the first meta-analysis assessing the effect of prehabilitation and peri- or postoperative physiotherapy regimens on postoperative mortality and morbidity in esophageal and gastric cancer surgery.5 A lower incidence of pneumonia was observed following both prehabilitation and peri- or postoperative rehabilitation. Furthermore, a lower incidence of postoperative morbidity was seen in patients undergoing prehabilitation, while peri- or postoperative rehabilitation resulted in a shorter LOS and better health-related quality-of-life scores for dyspnea and physical functioning. These results suggest that implementation of a physiotherapy regimen in both the pre- and peri- or postoperative setting may be beneficial. This meta-analysis is however limited by the lack of a standardized physiotherapy protocol for patients undergoing esophagectomy or gastrectomy, and by the lack of functional data in long-term survivors. FUTURE Further research is required focusing on the mechanism in which surgery might contribute to the development of postoperative complications and what outcomes are most likely to be affected. This information may aid in identifying which components of physiotherapy regimens have the greatest impact on clinical outcomes. In the future, tailored physiotherapy regimens may be developed aimed at decreasing the risk for complications in the preoperative setting (prehabilitation) and improve clinical outcomes postoperatively (rehabilitation) in major gastrointestinal cancer surgery. Discloure Karina Tukanova, Swathikan Chidambaram, Nadia Guidozzi, George B. Hanna, Alison H. McGregor, and Sheraz R. Markar declared no conflicts of interest

Cardiorespiratory comorbidity and postoperative complications following esophagectomy: a European multicenter cohort study

BACKGROUND: The impact of cardiorespiratory comorbidity on operative outcomes after esophagectomy remains controversial. This study investigated the effect of cardiorespiratory comorbidity on postoperative complications for patients treated for esophageal or gastroesophageal junction cancer. PATIENTS AND METHODS: A European multicenter cohort study from five high-volume esophageal cancer centers including patients treated between 2010 and 2017 was conducted. The effect of cardiorespiratory comorbidity and respiratory function upon postoperative outcomes was assessed. RESULTS: In total 1590 patients from five centers were included; 274 (17.2%) had respiratory comorbidity, and 468 (29.4%) had cardiac comorbidity. Respiratory comorbidity was associated with increased risk of overall postoperative complications, anastomotic leak, pulmonary complications, pneumonia, increased Clavien-Dindo score, and critical care and hospital length of stay. After neoadjuvant chemoradiotherapy, respiratory comorbidity was associated with increased risk of anastomotic leak [odds ratio (OR) 1.83, 95% confidence interval (CI) 1.11-3.04], pneumonia (OR 1.65, 95% CI 1.10-2.47), and any pulmonary complication (OR 1.52, 95% CI 1.04-2.22), an effect which was not observed following neoadjuvant chemotherapy or surgery alone. Cardiac comorbidity was associated with increased risk of cardiovascular and pulmonary complications, respiratory failure, and Clavien-Dindo score ≥ IIIa. Among all patients, forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio > 70% was associated with reduced risk of overall postoperative complications, cardiovascular complications, atrial fibrillation, pulmonary complications, and pneumonia. CONCLUSIONS: The results of this study suggest that cardiorespiratory comorbidity and impaired pulmonary function are associated with increased risk of postoperative complications after esophagectomy performed in high-volume European centers. Given the observed interaction with neoadjuvant approach, these data indicate a potentially modifiable index of perioperative risk