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

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

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

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p&lt;0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p&lt;0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p&lt;0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP &gt;5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

A novel approach to T classification in tumor-node-metastasis staging of breast cancer

Background The aim of this study was to examine the effect of measurement bias in breast cancer and to create a more rational T-size categorization in tumor-node-metastasis staging in response to smaller, screen-detected cancers and measurement bias. Methods From 1987 to 2003, 10,853 invasive nonmetastatic breast cancers enlisted in the Rhode Island Cancer Registry with a known dimension were reviewed. Data analyzed by proposed classifications included the rate of lymph node metastases and the mortality rate from breast cancer. Results The median diameter was 16 mm. Cancer measurements reflected the bias in pathologists\u92 dimension recording, which is centered strongly about whole- and half-centimeter sizes. A new T classification is proposed with the following sizes and frequencies in the Rhode Island Cancer Registry: 1 to 2 mm =3D T1 mic (3% of registered cases); 3 to 7 mm =3D T1a (11%); 8 to 12 mm =3D T1b (23%); 13 to 17 mm =3D T1c (18%); 18 to 22 mm =3D T2a (17%); 23 to 27 mm =3D T2b (8%); 28 to 32 mm =3D T2c (8%); 33 to 42 mm =3D T3a (6%); 43 to 52 mm =3D T3b (3%), and greater than 52 mm =3D T3c (4%). The unadjusted odds ratio for the probability of node metastases was 1.43 (confidence interval, 1.40\u961.46; P < .001) with each increase in proposed grouping. The range in the lymph node metastatic rate was 5.5% for tumors 1 to 2 mm to 64% for cancers greater than 52 mm. By Cox proportional hazard, the unadjusted hazard ratio for death from breast cancer for each increase in proposed grouping was 1.33 (confidence interval, 1.29\u961.37; P < .001). The 10-year survival rate ranged from 98.3% for tumors 1 to 2 mm to 70.3% for cancers greater than 52 mm. Conclusions A more rational T category for use in tumor-node-metastasis staging is presented to reflect the much smaller invasive breast cancers encountered by screening and to account for the dimension recording bias of pathologists. This new T category shows a clinically and statistically significant linear relationship for both incidence of lymph node metastases and hazard ratio of death

Validating an algorithm to identify metastatic gastric cancer in the absence of routinely collected TNM staging data

Abstract Background Accurate TNM stage information is essential for cancer health services research, but is often impractical and expensive to collect at the population-level. We evaluated algorithms using administrative healthcare data to identify patients with metastatic gastric cancer. Methods A population-based cohort of gastric cancer patients diagnosed between 2005 and 2007 identified from the Ontario Cancer Registry were linked to routinely collected healthcare data. Reference standard data identifying metastatic disease were obtained from a province-wide chart review, according to the Collaborative Staging method. Algorithms to identify metastatic gastric cancer were created using administrative healthcare data from hospitalization, emergency department, and physician billing records. Time frames of data collection in the peri-diagnosis period, and the diagnosis codes used to identify metastatic disease were varied. Algorithm sensitivity, specificity, and accuracy were evaluated. Results Of 2366 gastric cancer patients, included within the chart review, 54.3% had metastatic disease. Algorithm sensitivity ranged from 50.0- 90%, specificity ranged from 27.6 - 92.5%, and accuracy from 61.5 - 73.4%. Sensitivity and specificity were maximized when the most conservative list of diagnosis codes from hospitalization and outpatient records in the six months prior to and the six months following diagnosis were included. Conclusion Algorithms identifying metastatic gastric cancer can be used for research purposes using administrative healthcare data, although they are imperfect measures. The properties of these algorithms may be generalizable to other high fatality cancers and other healthcare systems. This study provides further support for the collection of population-based, TNM stage data