Publications by authors named "Sergio A Acuna"

65 Publications

Long-term Outcomes of Laparoscopic Lavage for Perforated Diverticulitis Remain Unfavorable.

JAMA Surg 2021 Jul 28. Epub 2021 Jul 28.

Division of General Surgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.

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http://dx.doi.org/10.1001/jamasurg.2021.3305DOI Listing
July 2021

Improving the reporting of non-inferiority trials by incorporating non-efficacy benefits: not all on-inferiority trials are created equal.

Eur J Epidemiol 2021 Jul 19. Epub 2021 Jul 19.

Division of General Surgery, Department of Surgery, University of Toronto, 2075 Bayview Avenue, Room H3-17, Toronto, ON, M4N 3M5, Canada.

Non-inferiority trials are used to test if a novel intervention is not worse than a standard treatment by more than a prespecified amount, the non-inferiority margin (ΔNI). The ΔNI indicates the amount of efficacy loss in the primary outcome that is acceptable in exchange for non-efficacy benefits in other outcomes. However, non-inferiority designs are sometimes used when non-efficacy benefits are absent. Without non-efficacy benefits, loss in efficacy cannot be easily justified. Further, non-efficacy benefits are scarcely defined or considered by trialists when determining the magnitude of and providing justification for the non-inferiority margin. This is problematic as the importance of a treatment's non-efficacy benefits are critical to understanding the results of a non-inferiority study. Here we propose the routine reporting in non-inferiority trial protocols and publications of non-efficacy benefits of the novel intervention along with the reporting of non-inferiority margins and their justification. The justification should include the specific trade-off between the accepted loss in efficacy (ΔNI) and the non-efficacy benefits of the novel treatment and should describe whether patients and other relevant stakeholders were involved in the definition of the ΔNI.
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http://dx.doi.org/10.1007/s10654-021-00791-zDOI Listing
July 2021

Comments and Concerns on the LASER Trial.

JAMA Surg 2021 Jun 9. Epub 2021 Jun 9.

Division of General Surgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.

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http://dx.doi.org/10.1001/jamasurg.2021.2250DOI Listing
June 2021

Long-term outcomes of resection for locoregional recurrence of colon cancer: A retrospective descriptive cohort study.

Eur J Surg Oncol 2021 Sep 19;47(9):2390-2397. Epub 2021 May 19.

Department of Surgery, University of Toronto, Toronto, Canada; Division of General Surgery, Mount Sinai Hospital, Toronto, Canada; Institute of Medical Science, University of Toronto, Canada. Electronic address:

Introduction: Resection for isolated distant recurrence of colon cancer is well accepted. Resection for locoregionally recurrent colon cancer (LRCC) is not well studied. We evaluated the long-term outcomes of curative-intent resection for LRCC.

Methods: All patients undergoing curative-intent resection for LRCC at three specialized cancer centers affiliated with the University of Toronto were identified (1993-2017). Follow-up included serial clinical assessment, colonoscopy, CEA, and cross-sectional imaging. Overall survival (OS), cancer-specific survival (CSS) and time to re-recurrence were estimated using Kaplan-Meier method and cumulative incidence function. The association between resection margins and outcome was assessed with Cox models.

Results: 117 patients were included in the study cohort. Median follow-up was 53 months (IQR: 34-101). OS was 75% (95% CI: 68-84) at 5 years, and 69% (95% CI: 59-79) at 10 years. CSS was 78% (95% CI: 70-86) at 5 years and 72% (95% CI: 63-83) at 10 years. The rate of re-recurrence was 22% (95% CI: 14-31) at 5 years, and 27% (95% CI: 16-39) at 10 years. Negative resection margin (R0) was associated with improved OS (HR 3.33, 95% CI: 1.85-6.00, p < 0.01). There were no postoperative deaths; complications with Clavien-Dindo grade > II occurred in 12% of patients. Perioperative chemotherapy was used in 63% of patients and radiotherapy in 37%.

Conclusion: In selected patients with LRCC, excellent OS, CSS and low re-recurrence rates were observed, and R0 resection predicted better outcomes. These findings support consideration of resection for LRCC in fit patients after review at a multidisciplinary cancer conference.
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http://dx.doi.org/10.1016/j.ejso.2021.05.003DOI Listing
September 2021

Association of perioperative red blood cell transfusions with all-cause and cancer-specific death in patients undergoing surgery for gastrointestinal cancer: Long-term outcomes from a population-based cohort.

Surgery 2021 Sep 6;170(3):870-879. Epub 2021 Mar 6.

Division of General Surgery, Department of Surgery, University of Toronto, Canada; Institute of Health Policy, Management, and Evaluation, University of Toronto, Canada; Division of General Surgery, Sunnybrook Health Sciences Centre, Toronto, Canada; Evaluative Clinical Sciences, Sunnybrook Research Institute, Toronto, Canada. Electronic address:

Background: Red blood cell transfusions are common in patients undergoing gastrointestinal cancer surgery. Yet, to adequately balance their risks and benefits, clinicians must understand how transfusions may affect long-term outcomes. We aimed to determine if perioperative red blood cell transfusions are associated with a higher risk of all-cause and cancer-specific death among patients who underwent gastrointestinal cancer resection.

Method: We identified a population-based cohort of patients who underwent gastrointestinal cancer resection in Ontario, Canada (2007-2019). All-cause death was compared between transfused and nontransfused patients using Cox proportional hazards regression, while cancer-specific death was compared with competing risk regression.

Result: A total of 74,962 patients (mean age, 67.7 years; 55.4% male; 79.7% colorectal cancer) had gastrointestinal cancer surgery during the study period; 20.8% received perioperative red blood cell transfusions. Patients who received red blood cell transfusions had increased hazards of all-cause and cancer-specific death relative to patients who did not (hazard ratio: 1.39, 95% confidence interval 1.34-1.44; cause-specific hazard ratio: 1.36, 1.30-1.43). The adjusted risk of all-cause death was higher in early follow-up intervals (3-6 months postoperatively) but remained elevated in each interval over 5 years. The association persisted after restricting to patients without postoperative complications or bleeding and was robust to unmeasured confounding.

Conclusion: Red blood cell transfusion among patients with gastrointestinal cancer is associated with increased all-cause death. This was observed long beyond the immediate postoperative period and independent of short-term postoperative morbidity and mortality. These findings should help clinicians balance the risks and benefits of transfusion before well-designed trials are conducted in this patient population.
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http://dx.doi.org/10.1016/j.surg.2021.02.003DOI Listing
September 2021

Optimizing opioid prescriptions after laparoscopic appendectomy and cholecystectomy

Can J Surg 2021 02 9;64(1):E69-E75. Epub 2021 Feb 9.

From the Department of Colorectal Surgery, Cleveland Clinic Foundation, Cleveland, Ohio, USA (Feinberg); the Department of Surgery, University of Toronto, Toronto, Ont. (Acuna); the Department of Surgery, North York General Hospital, Toronto, Ont. (Smith); the Department of Anesthesia, North York General Hospital, Toronto, Ont. (Kashin, Mocon, Yau, Srikandarajah) and the Department of Pharmacy, North York General Hospital, Toronto, Ont. (Chiu).

Background: There has been an increase in opioid usage and opioid-related deaths. Opioids prescribed to surgical patients have similarly increased. The aim of this study was to assess opioid consumption in patients undergoing laparoscopic appendectomy (LA) and laparoscopic cholecystectomy (LC) and to determine whether a standardized prescription could affect opioid consumption without affecting patient satisfaction.

Methods: Patients undergoing LA or LC were recruited prospectively during 2 time periods (April to June 2017 and November 2017 to January 2018). In the first phase, surgeons continued their usual postoperative analgesia prescribing patterns. In the second phase, a standardized prescription was implemented. Patients were contacted by telephone and a questionnaire was completed for both phases of the study. The primary outcome was the quantity of opioids prescribed and consumed.

Results: In the first phase, 166 patients who underwent LC or LA were recruited. The median number of prescribed opioid tablets was 20 and the median number consumed was 2. Ninety-five percent of patients reported satisfaction with their analgesia. Based on these results, a standardized prescription for multimodal analgesia was implemented for the second phase, consisting of 10 opioid tablets. In the second phase, 129 patients who underwent LA or LC were recruited. There was a significant decrease in the median number of opioid pills filled (10) and consumed (0), with no difference in reported satisfaction with analgesia.

Conclusion: Patients are prescribed an excess of opioids after LA or LC. Implementation of a standardized prescription based on a quality improvement intervention was effective at decreasing the number of opioids prescribed and consumed.
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http://dx.doi.org/10.1503/cjs.001319DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955819PMC
February 2021

Outcomes of Highly Selected Live Donors With a Future Liver Remnant Less Than or Equal to 30%: A Matched-Cohort Study.

Transplantation 2020 Nov 24. Epub 2020 Nov 24.

Multi-Organ Transplant Unit, Toronto General Hospital, University of Toronto, Toronto, Canada.

Background: The main concern with live donor liver transplantation (LDLT) is the risk to the donor. Given the potential risk of liver insufficiency, most centres will only accept candidates with future liver remnants (FLR) >30%. We aimed to compare postoperative outcomes of donors who underwent LDLT with FLR ≤30% and >30%.

Methods: Adults who underwent right hepatectomy for LDLT between 2000 and 2018 were analyzed. Remnant liver volumes were estimated using hepatic volumetry. To adjust for between-group differences, donors with FLR ≤30% and >30% were matched 1:2 based on baseline characteristics. Postoperative complications including liver dysfunction were compared between the groups.

Results: 604 live donors were identified, 28 (4.6%) of which had a FLR ≤30%. Twenty-eight cases were successfully matched with 56 controls; the matched cohorts were mostly similar in terms of donor and graft characteristics. The calculated median FLR was 29.8 (range 28.0-30.0) and 35.2 (range 30.1-68.1) in each respective group. Median follow-up was 36.5 months (IQR 11.8-66.1). Postoperative outcomes were similar between groups. No difference was observed in overall complication rates (FLR ≤30%: 32.1% vs FLR >30%: 28.6%; odds ratio (OR) 1.22, 95% CI 0.46-3.27) or major complication rates (FLR ≤30%: 14.3% vs FLR >30%: 14.3%; OR 1.17, 95% CI 0.33-4.10). Posthepatectomy liver failure was rare, and no difference was observed (FLR ≤30%: 3.6% vs FLR >30%: 3.6% OR 1.09, 95% CI 0.11-11.1).

Conclusion: A calculated FLR between 28% and 30% on its own should not represent a formal contraindication for live donation.
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http://dx.doi.org/10.1097/TP.0000000000003559DOI Listing
November 2020

Meta-analysis of noninferiority and equivalence trials: ignoring trial design leads to differing and possibly misleading conclusions.

J Clin Epidemiol 2020 11 12;127:134-141. Epub 2020 Jun 12.

Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada; Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada; Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Victoria, Australia; Division of General Surgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada. Electronic address:

Objective: The objective of the study is to examine the analytic approach of meta-analyses that include noninferiority or equivalence (NI/EQ) trials.

Study Design And Setting: We used Scopus to identify meta-analyses including NI/EQ trials. We extracted data from the meta-analyses and their included randomized clinical trials (RCTs). We used the RCT's NI/EQ margins to reinterpret the results of the meta-analyses, assessed for risk of biases unique to NI/EQ trials, and evaluated the consistency of the meta-analysis interpretation when using NI/EQ margins.

Results: We identified 38 unique meta-analyses including 515 RCTs, of which 125 (24.3%) were NI/EQ trials. Fourteen meta-analyses (36.8%) reported the study design of their included trials, but only one (2.6%) interpreted their pooled estimates using NI/EQ margins and none assessed for risks of bias unique to NI/EQ trials. Nearly all NI/EQ trials (n = 116, 92.8%) included in the meta-analyses reported NI/EQ margins. The meta-analyses of 30 outcomes were reinterpreted using the NI/EQ margins; reinterpretations conflicted with the conclusion of the meta-analyses in most cases (n = 20, 66.7%).

Conclusion: Most meta-analyses including NI/EQ trials ignore trial design and do not assess risks of bias unique to NI/EQ studies. Meta-analyses addressing questions previously explored as NI/EQ should conduct an NI/EQ meta-analysis or use clear language when performing standard (i.e., superiority) meta-analyses.
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http://dx.doi.org/10.1016/j.jclinepi.2020.05.034DOI Listing
November 2020

Does oncoplastic surgery increase immediate (30-day) postoperative complications? An analysis of the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database.

Breast Cancer Res Treat 2020 Jul 25;182(2):429-438. Epub 2020 May 25.

Division of General Surgery, Department of Surgery, University of Toronto, Toronto, ON, Canada.

Purpose: Although there has been a significant increase in the use of oncoplastic surgery (OPS), data on the postoperative safety of this approach are limited compared to traditional lumpectomy. This study aimed to compare the immediate (30-day) postoperative complications associated with OPS and traditional lumpectomy.

Methods: An analysis of the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database was performed on women with breast cancer who underwent OPS or traditional lumpectomy. Logistic regression was used to explore the effect of type of surgery on the outcome of interest.

Results: A total of 109,487 women were analyzed of whom 8.3% underwent OPS. OPS had a longer median operative time than traditional lumpectomy. The unadjusted immediate (30-day) overall complication rate was significantly higher with OPS than traditional lumpectomy (3.8% versus 2.6%, p < 0.001). After adjusting for baseline differences, overall 30-day postoperative complications were significantly higher amongst women undergoing OPS compared with traditional lumpectomy (OR 1.41, 95%CI 1.24-1.59). Factors that were independent predictors of overall 30-day complications included higher age, higher BMI, race, smoking status, lymph node surgery, neoadjuvant chemotherapy, ASA class ≥ 3, in situ disease, and year of operation. The interaction term between type of surgery and operative time was not statistically significant, indicating that operative time did not modify the effect of type of surgery on immediate postoperative complications.

Conclusions: Although there were slightly higher overall complication rates with OPS, the absolute rates remained quite low for both groups. Therefore, OPS may be performed in women with breast cancer who are suitable candidates.
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http://dx.doi.org/10.1007/s10549-020-05665-8DOI Listing
July 2020

Optimal Operative Strategy for Hinchey III Sigmoid Diverticulitis: A Decision Analysis.

Dis Colon Rectum 2020 08;63(8):1108-1117

Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, Ontario, Canada.

Background: Operative approaches for Hinchey III diverticulitis include the Hartmann procedure, primary resection and anastomosis, and laparoscopic lavage. Several randomized controlled trials and meta-analyses have compared these approaches; however, results are conflicting and previous studies have not captured the complexity of balancing surgical risks and quality of life.

Objective: This study aimed to determine the optimal operative strategy for patients with Hinchey III sigmoid diverticulitis.

Design: We developed a Markov cohort model, incorporating perioperative morbidity/mortality, emergency and elective reoperations, and quality-of-life weights. We derived model parameters from systematic reviews and meta-analyses, where possible. We performed a second-order Monte Carlo probabilistic sensitivity analysis to account for joint uncertainty in model parameters.

Setting: This study measured outcomes over patients' lifetime horizon.

Patients: The base case was a simulated cohort of 65-year-old patients with Hinchey III diverticulitis. A scenario simulating a cohort of highly comorbid 80-year-old patients was also planned.

Interventions: Hartmann procedure, primary resection and anastomosis (with or without diverting ileostomy), and laparoscopic lavage were performed.

Main Outcome Measures: Quality-adjusted life years were the primary outcome measured.

Results: Following surgery for Hinchey III diverticulitis, 39.5% of patients who underwent the Hartmann procedure, 14.3% of patients who underwent laparoscopic lavage, and 16.7% of patients who underwent primary resection and anastomosis had a stoma at 12 months. After applying quality-of-life weights, primary resection and anastomosis was the optimal operative strategy, yielding 18.0 quality-adjusted life years; laparoscopic lavage and the Hartmann procedure yielded 9.6 and 13.7 fewer quality-adjusted life months. A scenario analysis for elderly, highly comorbid patients could not be performed because of a lack of high-quality evidence to inform model parameters.

Limitations: This model required assumptions about the long-term postoperative course of patients who underwent laparoscopic lavage because few long-term data for this group have been published.

Conclusions: Although the Hartmann procedure is widely used for Hinchey III diverticulitis, when considering both surgical risks and quality of life, both laparoscopic lavage and primary resection and anastomosis provide greater quality-adjusted life years for patients with Hinchey III diverticulitis, and primary resection and anastomosis appears to be the optimal approach. See Video Abstract at http://links.lww.com/DCR/B223. ESTRATEGIA OPERATIVA ÓPTIMA EN DIVERTICULITIS HINCHEY III DE SIGMOIDES: UN ANÁLISIS DE DECISION: Los enfoques quirúrgicos para la diverticulitis Hinchey III incluyen el procedimiento de Hartmann, la resección primaria y anastomosis, y el lavado laparoscópico. Varios ensayos controlados aleatorios y metanálisis han comparado estos enfoques; sin embargo, los resultados son contradictorios y los estudios previos no han captado la complejidad de equilibrar los riesgos quirúrgicos y la calidad de vida.Determinar la estrategia operativa óptima para pacientes con diverticulitis Hinchey III de sigmoides.Desarrollamos un modelo de cohorte de Markov, incorporando morbilidad / mortalidad perioperatoria, reoperaciones electivas y de emergencia, y pesos de calidad de vida. Derivamos los parámetros del modelo de revisiones sistemáticas y metaanálisis, cuando fue posible. Realizamos un análisis de sensibilidad probabilístico Monte Carlo de segundo orden para tener en cuenta la incertidumbre conjunta en los parámetros del modelo.Seguimiento de por vida.El caso base fue una cohorte simulada de pacientes de 65 años con diverticulitis de Hinchey III. También se planeó un escenario que simulaba una cohorte de pacientes de 80 años altamente comórbidos.Procedimiento de Hartmann, resección primaria y anastomosis (con o sin desviación de ileostomía) y lavado laparoscópico.Años de vida ajustados por calidad.Después de la cirugía para la diverticulitis de Hinchey III, el 39.5% de los pacientes que se sometieron al procedimiento de Hartmann, el 14.3% de los pacientes que se sometieron a un lavado laparoscópico, y el 16.7% de los pacientes que se sometieron a resección primaria y anastomosis tuvieron un estoma a los 12 meses. Después de aplicar el peso de la calidad de vida, la resección primaria y la anastomosis fueron la estrategia operativa óptima, que dio como resultado 18.0 años de vida ajustados en función de la calidad; el lavado laparoscópico y el procedimiento de Hartmann arrojaron 9.6 y 13.7 meses de vida ajustados en función de la calidad, respectivamente. No se pudo realizar un análisis de escenarios para pacientes de edad avanzada altamente comórbidos debido a la falta de evidencia de alta calidad para informar los parámetros del modelo.Este modelo requirió suposiciones sobre el curso postoperatorio a largo plazo de pacientes que se sometieron a lavado laparoscópico, ya que se han publicado pocos datos a largo plazo para este grupo.Aunque el procedimiento de Hartmann se usa ampliamente para la diverticulitis de Hinchey III, cuando se consideran tanto los riesgos quirúrgicos como la calidad de vida, tanto el lavado laparoscópico como la resección primaria y la anastomosis proporcionan una mayor calidad de años de vida ajustada para los pacientes con diverticulitis de Hinchey III y la resección primaria y anastomosis parece ser el enfoque óptimo. Consulte Video Resumen en http://links.lww.com/DCR/B223.
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http://dx.doi.org/10.1097/DCR.0000000000001648DOI Listing
August 2020

Local excision after preoperative chemoradiation for T2 and T3 rectal cancers: is the wait over?

Lancet Gastroenterol Hepatol 2020 05 7;5(5):422-424. Epub 2020 Feb 7.

Department of Surgery, University of Toronto, St. Michael's Hospital, Toronto, ON, M5B 1W8, Canada. Electronic address:

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http://dx.doi.org/10.1016/S2468-1253(20)30001-7DOI Listing
May 2020

Comparing Observation, Axillary Radiotherapy, and Completion Axillary Lymph Node Dissection for Management of Axilla in Breast Cancer in Patients with Positive Sentinel Nodes: A Systematic Review.

Ann Surg Oncol 2020 Aug 4;27(8):2664-2676. Epub 2020 Feb 4.

Division of General Surgery, Department of Surgery, St. Michael's Hospital, University of Toronto, Toronto, ON, Canada.

Purpose: Several randomized controlled trials (RCTs) have investigated observation or axillary radiotherapy (ART) in place of completion axillary lymph node dissection (cALND) for management of positive sentinel nodes (SNs) in clinically node-negative women with breast cancer. The optimal treatment strategy for this population is not known.

Methods: MEDLINE, Embase, and EBM Reviews-NHS Economic Evaluation Database were searched from inception until July 2019. A systematic review and narrative summary was performed of RCTs comparing observation or ART versus cALND in clinically node-negative female breast cancer patients with positive SNs. The Cochrane risk of bias tool for RCTs was used to assess risk of bias. Outcomes of interest included overall survival (OS), disease-free survival (DFS), axillary recurrence, and axillary surgery-related morbidity.

Results: Three trials compared observation with cALND, and two trials compared ART with cALND. No studies blinded participants or personnel, and there was heterogeneity in inclusion criteria, study design, and follow-up. Neither observation nor ART resulted in statistically inferior 5- or 8-year OS or DFS compared with cALND. There was also no statistically significant increase in axillary recurrences associated with either approach. Four trials reported morbidity outcomes, and all showed cALND was associated with significantly more lymphedema, paresthesia, and shoulder dysfunction compared with observation or ART.

Conclusions: Women with clinically node-negative breast cancer and positive SNs can safely be managed without cALND.
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http://dx.doi.org/10.1245/s10434-020-08225-yDOI Listing
August 2020

Propofol versus midazolam with or without short-acting opioids for sedation in colonoscopy: a systematic review and meta-analysis of safety, satisfaction, and efficiency outcomes.

Gastrointest Endosc 2020 05 10;91(5):1015-1026.e7. Epub 2020 Jan 10.

Division of General Surgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada; Institute of Health Policy, Management, and Evaluation, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada; Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, Ontario, Canada; Department of Surgery, St Michael's Hospital, Toronto, Ontario, Canada.

Background And Aims: Propofol is increasingly being used for sedation in colonoscopy; however, its benefits over midazolam (± short-acting opioids) are not well quantified. The objective of this study was to compare safety, satisfaction, and efficiency outcomes of propofol versus midazolam (± short-acting opioids) in patients undergoing colonoscopy.

Methods: We systematically searched Medline, Embase, and the Cochrane library (to July 30, 2018) for randomized controlled trials of colonoscopies performed with propofol versus midazolam (± short-acting opioids). We pooled odds ratios for cardiorespiratory outcomes using mixed-effects conditional logistic models. We pooled standardized mean differences (SMDs) for patient and endoscopist satisfaction and efficiency outcomes using random-effects models.

Results: Nine studies of 1427 patients met the inclusion criteria. There were no significant differences in cardiorespiratory outcomes (hypotension, hypoxia, bradycardia) between sedative groups. Patient satisfaction was high in both groups, with most patients reporting willingness to undergo a future colonoscopy with the same sedative regimen. In the meta-analysis, patients sedated with propofol had greater satisfaction than those sedated with midazolam (± short-acting opioids) (SMD, .54; 95% confidence interval [CI], .30-.79); however, there was considerable heterogeneity. Procedure time was similar between groups (SMD, .15; 95% CI, .04-.27), but recovery time was shorter in the propofol group (SMD, .41; 95% CI, .08-.74). The median difference in recovery time was 3 minutes, 6 seconds shorter in patients sedated with propofol.

Conclusions: Both propofol and midazolam (± short-acting opioids) result in high patient satisfaction and appear to be safe for use in colonoscopy. The marginal benefits to propofol are small improvements in satisfaction and recovery time.
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http://dx.doi.org/10.1016/j.gie.2019.12.047DOI Listing
May 2020

Using Patient Preferences to Determine Noninferiority Margins in Trials-Reply.

JAMA 2019 12;322(21):2138

Department of Surgery, St Michael's Hospital, Toronto, Ontario, Canada.

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http://dx.doi.org/10.1001/jama.2019.16345DOI Listing
December 2019

Response to Comment on "Routine Use of Laparoscopic Surgery for Rectal Cancer".

Ann Surg 2019 12;270(6):e146-e147

Division of General Surgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada Division of General Surgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada Division of General Surgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada Department of Surgery, St. Michael's Hospital, Toronto, Ontario, Canada.

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http://dx.doi.org/10.1097/SLA.0000000000003650DOI Listing
December 2019

Incorporating Patient Preferences in Noninferiority Trials.

JAMA 2019 Jul;322(4):305-306

Division of General Surgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.

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http://dx.doi.org/10.1001/jama.2019.7059DOI Listing
July 2019

A note on competing risks in analyses of cancer-specific mortality.

Int J Cancer 2019 09 28;145(6):1704-1705. Epub 2019 Jun 28.

Division of General Surgery, Department of Surgery, University of Toronto, Toronto, ON, Canada.

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http://dx.doi.org/10.1002/ijc.32518DOI Listing
September 2019

The end of the Hartmann's era for perforated diverticulitis.

Lancet Gastroenterol Hepatol 2019 08 6;4(8):573-575. Epub 2019 Jun 6.

Department of Surgery, University of Toronto, St. Michael's Hospital, Toronto, ON M5B 1W8. Electronic address:

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http://dx.doi.org/10.1016/S2468-1253(19)30182-7DOI Listing
August 2019

Laparoscopic and robotic hysterectomy in endometrial cancer patients with obesity: a systematic review and meta-analysis of conversions and complications.

Am J Obstet Gynecol 2019 11 10;221(5):410-428.e19. Epub 2019 May 10.

Department of Surgery, Toronto, Ontario, Canada; Division of General Surgery, St. Michael's Hospital, Toronto, Ontario, Canada. Electronic address:

Objective Data: Robotic assistance may facilitate completion of minimally invasive hysterectomy, which is the standard of care for the treatment of early-stage endometrial cancer, in patients for whom conventional laparoscopy is challenging. The aim of this systematic review was to assess conversion to laparotomy and perioperative complications after laparoscopic and robotic hysterectomy in patients with endometrial cancer and obesity (body mass index, ≥30 kg/m).

Study: We systematically searched MEDLINE, EMBASE, and Evidence-Based Medicine Reviews (January 1, 2000, to July 18, 2018) for studies of patients with endometrial cancer and obesity (body mass index, ≥30 kg/m) who underwent primary hysterectomy.

Study Appraisal And Synthesis Methods: We determined the pooled proportions of conversion, organ/vessel injury, venous thromboembolism, and blood transfusion. We assessed risk of bias with the Institute of Health Economics Quality Appraisal Checklist for single-arm studies, and Newcastle-Ottawa Quality Scale for double-arm studies.

Results: We identified 51 observational studies that reported on 10,800 patients with endometrial cancer and obesity (study-level body mass index, 31.0-56.3 kg/m). The pooled proportions of conversion from laparoscopic and robotic hysterectomy were 6.5% (95% confidence interval, 4.3-9.9) and 5.5% (95% confidence interval, 3.3-9.1), respectively, among patients with a body mass index of ≥30 kg/m, and 7.0% (95% confidence interval, 3.2-14.5) and 3.8% (95% confidence interval, 1.4-9.9) among patients with body mass index of ≥40 kg/m. Inadequate exposure because of adhesions/visceral adiposity was the most common reason for conversion for both laparoscopic (32%) and robotic hysterectomy (61%); however, intolerance of the Trendelenburg position caused 31% of laparoscopic conversions and 6% of robotic hysterectomy conversions. The pooled proportions of organ/vessel injury (laparoscopic, 3.5% [95% confidence interval, 2.2-5.5]; robotic hysterectomy, 1.2% [95% confidence interval, 0.4-3.4]), venous thromboembolism (laparoscopic, 0.5% [95% confidence interval, 0.2-1.2]; robotic hysterectomy, 0.5% [95% confidence interval, 0.1-2.0]), and blood transfusion (laparoscopic, 2.8% [95% confidence interval, 1.5-5.1]; robotic hysterectomy, 2.1% [95% confidence interval, 1.6-3.8]) were low and not appreciably different between arms.

Conclusion: Robotic and laparoscopic hysterectomy have similar rates perioperative complications in patients with endometrial cancer and obesity, but robotic hysterectomy may reduce conversions because of positional intolerance in patients with morbid obesity. Existing literature is limited by selection and confounding bias, and randomized trials are needed to inform practice standards in this population.
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http://dx.doi.org/10.1016/j.ajog.2019.05.004DOI Listing
November 2019

The Fragility Index-P Values Reimagined, Flaws and All.

JAMA Surg 2019 07;154(7):674

Division of General Surgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.

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http://dx.doi.org/10.1001/jamasurg.2019.0567DOI Listing
July 2019

Unifying Design and Analysis for Superiority and Noninferiority Trials With Appropriate End Point-Reply.

JAMA Surg 2019 05;154(5):467-468

Division of General Surgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.

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http://dx.doi.org/10.1001/jamasurg.2018.5858DOI Listing
May 2019

Comparison of Radioactive Seed Localized Excision and Wire Localized Excision of Breast Lesions: A Community Hospital's Experience.

Clin Breast Cancer 2019 04 6;19(2):e364-e369. Epub 2019 Jan 6.

Department of Surgery, North York Hospital, Toronto, Ontario, Canada. Electronic address:

Background: Most data comparing wire localized excision (WLE) and radioactive seed localized excision (RSLE) derive from academic institutions with limited data from community hospitals. This study aimed to compare positive margin rates between WLE and RSLE and to determine if there were any differences in specimen volume and operation time.

Patients And Methods: A retrospective cohort study was conducted on patients who underwent WLE or RSLE at a Canadian community hospital. Group characteristics were compared as appropriate. Multivariable logistic regression was used determine if the localization techniques were independently associated with having a positive margin. Statistical significance was set as P < .05.

Results: The cohort consisted of 747 (WLE) and 577 (RSLE) patients. Both groups had similar mean age, mean tumor (invasive and ductal carcinoma-in-situ) size, histologic grade distribution, presence of lymphovascular invasion, and extensive intraductal component, nodal status, and hormone receptor and HER2 status. Compared to WLE, patients who underwent RSLE had significantly lower invasive positive margin rates (8.1% vs. 12.3%, P = .03), shorter operation time (39.5 minutes vs. 68.7 minutes, P = .0001), and smaller surgical specimens (21.4 cm³ vs. 30.2 cm³, P = .008). Ductal carcinoma-in-situ positive margin rates were not different between the groups. However, the localization technique was not independently associated with having a positive margin (odds ratio = 1.55; 95% confidence interval, 0.99-2.44).

Conclusion: RSLE led to a shorter operation time and smaller surgical specimens compared to WLE, but there was no difference in positive margin rates. RSLE is an effective technique to excise nonpalpable breast lesions in the community setting.
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http://dx.doi.org/10.1016/j.clbc.2019.01.001DOI Listing
April 2019

ASO Author Reflections: Clarifying the Controversy Generated by Non-inferiority Trials of Laparoscopic Surgery for Rectal Cancer.

Ann Surg Oncol 2019 Dec 17;26(Suppl 3):545-546. Epub 2018 Dec 17.

Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada.

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http://dx.doi.org/10.1245/s10434-018-7050-0DOI Listing
December 2019

Preclinical evaluation of a MAGE-A3 vaccination utilizing the oncolytic Maraba virus currently in first-in-human trials.

Oncoimmunology 2019;8(1):e1512329. Epub 2018 Sep 19.

Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.

Multiple immunotherapeutics have been approved for cancer patients, however advanced solid tumors are frequently refractory to treatment. We evaluated the safety and immunogenicity of a vaccination approach with multimodal oncolytic potential in non-human primates (NHP) (). Primates received a replication-deficient adenoviral prime, boosted by the oncolytic Maraba MG1 rhabdovirus. Both vectors expressed the human MAGE-A3. No severe adverse events were observed. Boosting with MG1-MAGEA3 induced an expansion of hMAGE-A3-specific CD4 and CD8 T-cells with the latter peaking at remarkable levels and persisting for several months. T-cells reacting against epitopes fully conserved between simian and human MAGE-A3 were identified. Humoral immunity was demonstrated by the detection of circulating MAGE-A3 antibodies. These preclinical data establish the capacity for the Ad:MG1 vaccination to engage multiple effector immune cell populations without causing significant toxicity in outbred NHPs. Clinical investigations utilizing this program for the treatment of MAGE-A3-positive solid malignancies are underway (NCT02285816, NCT02879760).
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http://dx.doi.org/10.1080/2162402X.2018.1512329DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6287790PMC
September 2018

Operative Strategies for Perforated Diverticulitis: A Systematic Review and Meta-analysis.

Dis Colon Rectum 2018 12;61(12):1442-1453

Division of General Surgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.

Background: The traditional approach for perforated diverticulitis, the Hartmann procedure, has considerable morbidity and the challenge of stoma reversal. Alternative procedures, including primary resection and anastomosis and laparoscopic lavage, have been proposed but remain controversial.

Objective: The purpose of this study was to compare operative strategies for perforated diverticulitis.

Data Sources: MEDLINE, Embase, Cochrane Library, and the grey literature were searched from inception to October 2017.

Study Selection: We included randomized clinical trials evaluating operative strategies for perforated diverticulitis.

Interventions: Hartmann procedure, primary resection and anastomosis, and laparoscopic lavage were included.

Main Outcome Measures: Data were independently extracted by 2 investigators. Risk of bias was evaluated using the Cochrane risk-of-bias tool. Pooled risk ratios for major complications, reoperation, and mortality were determined using random-effects models.

Results: Six trials including 626 patients with perforated diverticulitis were identified. Laparoscopic lavage and sigmoidectomy had comparable rates of early reoperation and postoperative mortality; major complications (Clavien-Dindo >IIIa) were more frequent after laparoscopic lavage (RR = 1.68 (95% CI, 1.10-2.56); 3 trials, 305 patients). Comparing approaches for sigmoidectomy, primary resection and anastomosis had similar rates of major complications (RR = 0.88 (95% CI, 0.49-1.55); 3 trials, 255 patients) and postoperative mortality (RR = 0.58 (95% CI, 0.20-1.70); 3 trials, 254 patients) compared with the Hartmann procedure. However, patients who underwent primary resection and anastomosis were more likely to be stoma free at 12 months compared with the Hartmann procedure (RR = 1.40 (95% CI, 1.18-1.67); 4 trials, 283 patients) and to experience fewer major complications related to the stoma reversal procedure (RR = 0.26 (95% CI, 0.07-0.89); 4 trials, 186 patients).

Limitations: There were no limitations to this study.

Conclusions: Laparoscopic lavage is associated with increased risk of major complications versus primary resection for Hinchey III diverticulitis. The lower rate of stoma reversal and higher rate of complications after the Hartmann procedure suggest primary resection and anastomosis as the optimal management of perforated diverticulitis.
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http://dx.doi.org/10.1097/DCR.0000000000001149DOI Listing
December 2018

Laparoscopic Versus Open Resection for Rectal Cancer: A Noninferiority Meta-analysis of Quality of Surgical Resection Outcomes.

Ann Surg 2019 05;269(5):849-855

Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada.

Objective: To determine whether laparoscopic surgery is noninferior to open surgery for rectal cancer in terms of quality of surgical resection outcomes.

Background: Randomized clinical trials (RCTs) have evaluated the oncologic safety of laparoscopic versus open surgery for rectal cancer with conflicting results. Prior meta-analyses comparing these operative approaches in terms of quality of surgical resection aimed to demonstrate if one approach was superior. However, this method is not appropriate and potentially misleading when noninferiority RCTs are included.

Methods: MEDLINE, EMBASE, and Cochrane were searched to identify RCTs comparing these operative approaches. Risk differences (RDs) were pooled using random-effects meta-analyses. One-sided Z tests were used to determine noninferiority. Noninferiority margins (ΔNI) for circumferential resection margin (CRM), plane of mesorectal excision (PME), distal resection margin (DRM), and a composite outcome ("successful resection") were based on the consensus of 58 worldwide experts.

Results: Fourteen RCTs were included. Laparoscopic resection was noninferior compared with open resection for the rate of positive CRM [RD 0.79%, 90% confidence interval (CI) -0.46 to 2.04, ΔNI = 2.33%, PNI = 0.026], incomplete PME (RD 1.16%, 90% CI -0.27 to 2.59, ΔNI = 2.85%, PNI = 0.025), and positive DRM (RD 0.15%, 90% CI -0.58 to 0.87, ΔNI = 1.28%, PNI = 0.005). For the rate of "successful resection" (RD 6.16%, 90% CI 2.30-10.02), the comparison was inconclusive when using the ΔNI generated by experts (ΔNI = 2.71%, PNI = 0.07), although no consensus was achieved for this ΔNI.

Conclusions: Laparoscopy was noninferior to open surgery for rectal cancer in terms of individual quality of surgical resection outcomes. These findings are concordant with RCTs demonstrating noninferiority for long-term oncologic outcomes between the 2 approaches.
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http://dx.doi.org/10.1097/SLA.0000000000003072DOI Listing
May 2019

Defining Non-inferiority Margins for Quality of Surgical Resection for Rectal Cancer: A Delphi Consensus Study.

Ann Surg Oncol 2018 Oct 26;25(11):3171-3178. Epub 2018 Jul 26.

Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada.

Introduction: Quality of surgical resection metrics (QSRMs) have been used as surrogates for long-term oncologic outcomes in non-inferiority randomized clinical trials (RCTs) comparing laparoscopic and open surgery for rectal cancer. However, non-inferiority margins (Δ) for QSRMs have not been previously defined.

Methods: A two-round, web-based Delphi was used to define Δ for four QSRMs: positive circumferential resection margin (CRM), incomplete plane of mesorectal excision (PME), positive distal resection margin (DRM), and a composite of these outcomes. Overall, 130 international experts in rectal cancer (68 surgeons, 20 medical oncologists, 16 radiation oncologists, and 26 pathologists) were invited to participate. Experts were presented with evidence syntheses summarizing the association between QSRMs and long-term outcomes, and pooled quality of surgical resection outcomes for open surgery, and were asked to provide Δ for all outcomes balancing the risks and benefits of minimally invasive surgery.

Results: Seventy-two experts participated: 57 completed the initial questionnaire and 58 completed the revised questionnaire, with 43 participating in both rounds. Consensus was reached for all individual QSRM Δ but not for the composite. The mean (standard deviation) Δ was an absolute difference of 2.33% (1.59%) for the proportion of positive CRMs when comparing surgical interventions for the treatment of rectal cancer: 2.85% (1.83%) for incomplete PME; 1.28% (1.13%) for positive DRMs; and 2.71% (2.28%) for the composite. However, opinions varied widely for the composite outcome.

Conclusions: Web-based Delphi processes are a feasible approach to generate Δ to evaluate novel surgical interventions. The generated Δ for QSRMs for rectal cancer can be used for future RCTs and non-inferiority meta-analyses.
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http://dx.doi.org/10.1245/s10434-018-6639-7DOI Listing
October 2018

Etiology of increased cancer incidence after solid organ transplantation.

Authors:
Sergio A Acuna

Transplant Rev (Orlando) 2018 10 9;32(4):218-224. Epub 2018 Jul 9.

Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada; Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Canada; Department of Surgery, St. Michael's Hospital, Toronto, Canada; Division of General Surgery, Department of Surgery, University of Toronto, Toronto, Canada. Electronic address:

Over the past decades, there has been an encouraging increase in survival after solid organ transplantation. However, with longer life spans, more transplant recipients are at risk of dying with functioning grafts from illnesses such as cancer and cardiovascular conditions. Malignancy has emerged as an important cause of death in transplant recipients and is expected to become the leading cause of death in transplanted patients within the next decade. While it is known that solid organ transplant recipients have a three to five-fold increased risk of developing cancer compared with the general population, the mechanisms that lead to the observed excess risk in transplant recipients are less clear. This review explores the etiology of the increased cancer incidence in solid organ transplant including the effect of immunosuppressants on immunosurveillance and activation of oncogenic viruses, and carcinogenic effects of these medications; the role of chronic stimulation of the immune system on the development of cancer; and the impact of pre-existing cancer risk factors and factors related to end-stage organ disease on the cancer excess incidence in solid organ transplant recipients.
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http://dx.doi.org/10.1016/j.trre.2018.07.001DOI Listing
October 2018
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