A systematic review and meta-analysis of the utility of EUS for preoperative staging for gastric cancer

Background Accurate preoperative staging is important in determining the appropriate treatment of gastric cancer. Recently, endoscopic ultrasound (EUS) has been introduced as a staging modality. However, reported test characteristics for EUS in gastric cancer vary. Our purpose in this study was to identify, synthesize, and evaluate findings from all articles on the performance of EUS in the preoperative staging of gastric cancer.Methods Electronic literature searches were conducted using Medline, Embase, and the Cochrane Central Register of Controlled Trials from 1 January 1998 to 1 December 2009. All search titles and abstracts were independently rated for relevance by a minimum of two reviewers. Meta-analysis for the performance of EUS was analyzed by calculating agreement (Kappa statistic), and pooled estimates of accuracy, sensitivity, and specificity for all EUS examinations, using histopathology as the reference standard. Subgroup analyses were also performed.Results Twenty-two articles met our inclusion criteria and were included in the review. EUS pooled accuracy for T staging was 75% with a moderate Kappa (0.52). EUS was most accurate for T3 disease, followed by T4, T1, and T2. EUS pooled accuracy for N staging was 64%, sensitivity was 74%, and specificity was 80%. There was significant heterogeneity between the included studies. Subgroup analyses found that annual EUS volume was not associated with EUS T and N staging accuracy (P = 0.836, 0.99, respectively).Conclusion EUS is a moderately accurate technique that seems to describe advanced T stage (T3 and T4) better than N or less advanced T stage. Stratifying by EUS annual volume did not affect EUS performance in staging gastric cancer.Canadian Cancer SocietyMinistry of Health and Long Term CareCIHRHanna Family Chair in Surgical OncologySunnybrook Hlth Sci Ctr, Sunnybrook Res Inst, Toronto, ON M4N 3M5, CanadaSunnybrook Hlth Sci Ctr, Div Surg Oncol, Toronto, ON M4N 3M5, CanadaOdette Canc Ctr, Toronto, ON M4N 3M5, CanadaInst Clin Evaluat Sci, Toronto, ON, CanadaUniversidade Federal de São Paulo, Dept Surg, São Paulo, BrazilSunnybrook Hlth Sci Ctr, Div Gastroenterol, Dept Med, Toronto, ON M4N 3M5, CanadaUniversidade Federal de São Paulo, Dept Surg, São Paulo, BrazilCanadian Cancer Society: 019325Web of Scienc

How useful is preoperative imaging for tumor, node, metastasis (TNM) staging of gastric cancer? A meta-analysis

Background Surgery is the fundamental curative option for gastric cancer patients. Imaging scans are routinely prescribed in an attempt to stage the disease prior to surgery. Consequently, the correlation between radiology exams and pathology is crucial for appropriate treatment planning.Methods Systematic searches were conducted using Medline, Embase, and the Cochrane Central Register of Controlled Trials from January 1, 1998 to December 1, 2009. We calculated the accuracy, overstaging rate, understaging rate, Kappa statistic, sensitivity, and specificity for abdominal ultrasound (AUS), computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET) with respect to the gold standard (pathology). We also compared the performance of CT by detector number and image type. A meta-analysis was performed.Results for pre-operative T staging MRI scans had better performance accuracy than CT and AUS; CT scanners using >= 4 detectors and multi-planar reformatted (MPR) images had higher staging performances than scanners with <4 detectors and axial images only. for pre-operative N staging PET had the lowest sensitivity, but the highest specificity among modalities; CT performance did not significantly differ by detector number or addition of MPR images. for pre-operative M staging performance did not significantly differ by modality, detector number, or MPR images.Conclusions the agreement between pre-operative TNM staging by imaging scans and post-operative staging by pathology is not perfect and may affect treatment decisions. Operator dependence and heterogeneity of data may account for the variations in staging performance. Physicians should consider this discrepancy when creating their treatment plans.Canadian Cancer SocietyOntario Ministry of Health and Long-Term CareHanna Family Chair in Surgical OncologySunnybrook Hlth Sci Ctr, Sunnybrook Res Inst, Toronto, ON M4N 3M5, CanadaSunnybrook Hlth Sci Ctr, Dept Med Imaging, Toronto, ON M4N 3M5, CanadaUniversidade Federal de São Paulo, Dept Surg, São Paulo, BrazilQueens Univ, Dept Community Hlth & Epidemiol, Kingston, ON, CanadaUniv Toronto, Div Biostat, Dalla Lana Sch Publ Hlth, Toronto, ON, CanadaInst Clin Evaluat Sci, Toronto, ON, CanadaSunnybrook Hlth Sci Ctr, Div Surg Oncol, Odette Canc Ctr, Toronto, ON M4N 3M5, CanadaUniv Toronto, Dept Hlth Policy Management & Evaluat, Toronto, ON, CanadaUniversidade Federal de São Paulo, Dept Surg, São Paulo, BrazilCanadian Cancer Society: 019325Web of Scienc

A systematic review of the accuracy and utility of peritoneal cytology in patients with gastric cancer

Background There is lack of uniformity in the utilization of peritoneal cytology in gastric cancer management. the identification of intraperitoneal free cancer cells (IFCCs) is believed to confer poor prognosis. However, while some of these patients are palliated, others may undergo more aggressive therapies. in this review, we aimed to identify and synthesize findings on the use of peritoneal cytology in predicting peritoneal recurrence and overall survival in curative gastric cancer patients.Methods Electronic literature searches were conducted using Medline, EMBASE, and the Cochrane Central Register of Controlled Trials from January 1, 1998 to December 31, 2009. We determined the accuracy, sensitivity, and specificity of peritoneal cytology in predicting peritoneal recurrence based on four techniques-conventional cytology, immunoassay, immunohistochemistry, and reverse transcriptase-polymerase chain reaction. Recurrence rates and overall survival rates for curative patients were determined, based on positivity or negativity for IFCCs.Results Twenty-eight articles were included. All four techniques showed wide variations in accuracy, sensitivity, and specificity in predicting peritoneal recurrence. Recurrence rates for patients positive for IFCCs ranged from 11.1 to 100%, while those negative for IFCCs had recurrence rates of 0-51%. Overall survival was significantly reduced for patients with positive IFCCs. Short follow-up periods and possible duplication of results may limit result interpretation.Conclusion the presence of IFCCs appears to increase the risk of peritoneal recurrence and is associated with worse overall survival in gastric cancer patients. Further incorporation of peritoneal cytology in clinical decision-making in gastric cancer depends on the development of a consistently accurate and rapid IFCC detection method.Canadian Cancer SocietyOntario Ministry of Health and Long-Term CareUniv Toronto, Dept Surg, Toronto, ON, CanadaSunnybrook Hlth Sci Ctr, Sunnybrook Res Inst, Toronto, ON M4N 3M5, CanadaUniversidade Federal de São Paulo, Dept Surg, São Paulo, BrazilDalhousie Univ, Dept Surg, Halifax, NS B3H 4H2, CanadaQueens Univ, Dept Community Hlth & Epidemiol, Kingston, ON, CanadaSunnybrook Hlth Sci Ctr, Dept Anat Pathol, Toronto, ON M4N 3M5, CanadaUniv Toronto, Div Surg Oncol, Sunnybrook Hlth Sci Ctr, Odette Canc Ctr, Toronto, ON, CanadaUniversidade Federal de São Paulo, Dept Surg, São Paulo, BrazilCanadian Cancer Society: 019325Web of Scienc

A systematic review of the accuracy and indications for diagnostic laparoscopy prior to curative-intent resection of gastric cancer

Background Despite improved preoperative imaging techniques, patients with incurable or unresectable gastric cancer are still subjected to non-therapeutic laparotomy. Diagnostic laparoscopy (DL) has been advocated by some to be essential in decision-making in gastric cancer. We aimed to identify and synthesize findings on the value of DL for patients with gastric cancer, in this era of improved preoperative imaging.Methods Electronic literature searches were conducted using Medline, EMBASE, and the Cochrane Central Register of Controlled Trials from January 1, 1998 to December 31, 2009. We calculated the change in management and avoidance of laparotomy based on the addition of DL and laparoscopic ultrasound (LUS). the accuracy, agreement (kappa), sensitivity, and specificity of DL in assessing tumor extent, nodal involvement, and the presence of metastases with respect to the gold standard (pathology) were also calculated.Results Twenty-one articles were included. DL showed moderate to substantial agreement with final pathology for T stage, but only fair agreement for N stage. for M staging, DL had an overall accuracy, sensitivity, and specificity ranging from 85-98.9%, 64.3-94%, and 80-100%, respectively. the use of DL altered treatment in 8.5-59.6% of cases, avoiding laparotomy in 8.5-43.8% of cases. LUS provided additional benefit in 5.8-7.2% of cases.Conclusions Despite evolving preoperative imaging techniques, diagnostic laparoscopy continues to be of substantial value in staging patients with gastric cancer and in avoiding unnecessary laparotomy. the current data support DL for all patients with advanced gastric cancer.Canadian Cancer SocietyOntario Ministry of Health and Long-Term CareHanna Family Chair in Surgical OncologyUniv Toronto, Dept Surg, Toronto, ON, CanadaSunnybrook Hlth Sci Ctr, Sunnybrook Res Inst, Toronto, ON M4N 3M5, CanadaUniversidade Federal de São Paulo, Dept Surg, São Paulo, BrazilDalhousie Univ, Dept Surg, Halifax, NS B3H 4H2, CanadaQueens Univ, Dept Community Hlth & Epidemiol, Kingston, ON, CanadaUniv Toronto, Sunnybrook Hlth Sci Ctr, Div Surg Oncol, Odette Canc Ctr, Toronto, ON, CanadaUniversidade Federal de São Paulo, Dept Surg, São Paulo, BrazilCanadian Cancer Society: 019325Web of Scienc

Lessons learned: Linking patient-reported outcomes data with administrative databases

Introduction Since 2007, Cancer Care Ontario (CCO) has systematically collected patient-reported outcomes (PROs) in the form of symptom data, for cancer outpatients visiting regional cancer centres or affiliate institutions. Data are used in real-time to facilitate conversation between clinicians and patients and have recently been combined with provincial administrative databases. Objectives and Approach CCO collects PROs using the Edmonton Symptom Assessment System (ESAS), which scores 9 symptoms on a scale of 0 (no symptoms) to 10 (worst symptom severity). Data were imported from CCO in 2015 and linked to a cancer cohort at ICES. We investigated differences between patients who completed $\geq$1 ESAS record and patients who did not, as well as the number of records, timing of data collection and missingness. We describe our experience linking and using the PRO data to administrative data, including presenting trajectories of symptoms over time and combining scores into composite indices. Results 120,745 cancer patients had 729,861 symptom records between 2007 and 2014. Not all patients with a cancer diagnosis had $\geq$1 ESAS record and this varied by patient, disease and system level factors. Because implementation occurred from a clinical perspective, data collection was irregular within and across patients and depended on treatment and other factors; the number of records per patient varied, as well the number of contributing patients in each time period following diagnosis. Attempts were made to create meaningful composite indices by combining all symptom scores as well as combining multiple high scores for each individual symptom. As a result, selecting the best statistical analysis to use these PRO data as an exposure or outcome is still uncertain. Conclusion/Implications PRO data linked to provincial, administrative data holdings represent a new frontier for population-based cancer research, both in their challenging structure as well as their implications for clinical practice and health system. These lessons learned will hopefully support other researchers rigorous use of these data in the future

Medial open transversus abdominis plane (MOTAP) catheters for analgesia following open liver resection: study protocol for a randomized controlled trial

Background: The current standard for pain control following liver surgery is intravenous, patient-controlled analgesia (IV PCA) or epidural analgesia. We have developed a modification of a regional technique called medial open transversus abdominis plane (MOTAP) catheter analgesia. The MOTAP technique involves surgically placed catheters through the open surgical site into a plane between the internal oblique muscle and the transverse abdominis muscle superiorly. The objective of this trial is to assess the efficacy of this technique. Methods/design: This protocol describes a multicentre, prospective, blinded, randomized controlled trial. One hundred and twenty patients scheduled for open liver resection through a subcostal incision will be enrolled. All patients will have two MOTAP catheters placed at the conclusion of surgery. Patients will be randomized to one of two parallel groups: experimental (local anaesthetic through MOTAP catheters) or placebo (normal saline through MOTAP catheters). Both groups will also receive IV PCA. The primary endpoint is mean cumulative postoperative opioid consumption over the first 2 postoperative days (48 hours). Secondary outcomes include pain intensity, patient functional outcomes, and the incidence of complications. Discussion: This trial has been approved by the ethics boards at participating centres and is currently enrolling patients. Data collection will be completed by the end of 2014 with analysis mid-2015 and publication by the end of 2015. Trial registration: The study is registered with http://clinicaltrials.gov (NCT01960049; 23 September 2013)This research is supported by the Innovation Fund of the Alternative Funding Plan from the Academic Health Sciences Centres of Ontario

Major liver resection, systemic fibrinolytic activity, and the impact of tranexamic acid

The final publication is available at Elsevier via http://dx.doi.org/10.1016/j.hpb.2016.09.005 © 2016. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/Background: Hyperfibrinolysis may occur due to systemic inflammation or hepatic injury that occurs during liver resection. Tranexamic acid (TXA) is an antifibrinolytic agent that decreases bleeding in various settings, but has not been well studied in patients undergoing liver resection. Methods: In this prospective, phase II trial, 18 patients undergoing major liver resection were sequentially assigned to one of three cohorts: (i) Control (no TXA); (ii) TXA Dose I - 1 g bolus followed by 1 g infusion over 8 h; (iii) TXA Dose II - 1 g bolus followed by 10 mg/kg/hr until the end of surgery. Serial blood samples were collected for thromboelastography (TEG), coagulation components and TXA concentration. Results: No abnormalities in hemostatic function were identified on TEG. PAP complex levels increased to peak at 1106 mu g/L (normal 0-512 mu g/L) following parenchymal transection, then decreased to baseline by the morning following surgery. TXA reached stable, therapeutic concentrations early in both dosing regimens. There were no differences between patients based on TXA. Conclusions: There is no thromboelastographic evidence of hyperfibrinolysis in patients undergoing major liver resection. TXA does not influence the change in systemic fibrinolysis; it may reduce bleeding through a different mechanism of action

Prospective, observational, multicenter study on minimally invasive gastrectomy for gastric cancer: robotic, laparoscopic and open surgery compared on operative and follow-up outcomes - IMIGASTRIC II study protocol: IMIGASTRIC II

Background:Several meta-analyses have tried to defi ne the role of minimally invasive approaches.&nbsp;However, further evidence to get a wider spread of these methods is necessary. Current&nbsp;studies describe minimally invasive surgery as a possible alternative to open surgery&nbsp;but deserving further clarifi cation. However, despite the increasing interest, the&nbsp;difficulty of planning prospective studies of adequate size accounts for the low level of&nbsp;evidence, which is mostly based on retrospective experiences.A multi-institutional prospective study allows the collection of an impressive amount&nbsp;of data to investigate various aspects of minimally invasive procedures with the&nbsp;opportunity of developing several subgroup analyses.A prospective data collection with high methodological quality on minimally invasive&nbsp;and open gastrectomies can clarify the role of diff erent procedures with the aim to&nbsp;develop specifi c guidelines.Methods and analysis:a multi-institutional prospective database will be established including information on&nbsp;surgical, clinical and oncological features of patients treated for gastric cancer with&nbsp;robotic, laparoscopic or open approaches and subsequent follow-up.The study has been shared by the members of the International study group on&nbsp;Minimally Invasive surgery for GASTRIc Cancer (IMIGASTRIC)The database is designed to be an international electronic submission system and a&nbsp;HIPPA protected real time data repository from high volume gastric cancer centers.Ethics:This study is conducted in compliance with ethical principles originating from the&nbsp;Helsinki Declaration, within the guidelines of Good Clinical Practice and relevantlaws/regulations.Trial registration number:NCT0275108

Study protocol for a group randomized controlled trial of a classroom-based intervention aimed at preventing early risk factors for drug abuse: integrating effectiveness and implementation research

<p>Abstract</p> <p>Background</p> <p>While a number of preventive interventions delivered within schools have shown both short-term and long-term impact in epidemiologically based randomized field trials, programs are not often sustained with high-quality implementation over time. This study was designed to support two purposes. The first purpose was to test the effectiveness of a universal classroom-based intervention, the Whole Day First Grade Program (WD), aimed at two early antecedents to drug abuse and other problem behaviors, namely, aggressive, disruptive behavior and poor academic achievement. The second purpose--the focus of this paper--was to examine the utility of a multilevel structure to support high levels of implementation during the effectiveness trial, to sustain WD practices across additional years, and to train additional teachers in WD practices.</p> <p>Methods</p> <p>The WD intervention integrated three components, each previously tested separately: classroom behavior management; instruction, specifically reading; and family-classroom partnerships around behavior and learning. Teachers and students in 12 schools were randomly assigned to receive either the WD intervention or the standard first-grade program of the school system (SC). Three consecutive cohorts of first graders were randomized within schools to WD or SC classrooms and followed through the end of third grade to test the effectiveness of the WD intervention. Teacher practices were assessed over three years to examine the utility of the multilevel structure to support sustainability and scaling-up.</p> <p>Discussion</p> <p>The design employed in this trial appears to have considerable utility to provide data on WD effectiveness and to inform the field with regard to structures required to move evidence-based programs into practice.</p> <p>Trial Registration</p> <p><b>Clinical Trials Registration Number</b>: NCT00257088</p

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707