Debulking Hepatectomy for Colorectal Liver Metastasis Conveys Survival Benefit.

(1) Background: Despite advances in surgical technique and systemic chemotherapy, some patients with multifocal, bilobar colorectal liver metastases (CRLM) remain unresectable. These patients may benefit from surgical debulking of liver tumors in combination with chemotherapy compared to chemotherapy alone. (2) Methods: A retrospective study including patients evaluated for curative intent resection of CRLM was performed. Patients were divided into three groups: those who underwent liver resection with recurrence within 6 months (subtotal debulked, SD), those who had the first stage only of a two-stage hepatectomy (partially debulked, PD), and those never debulked (ND). Kaplan-Meier survival curves and log-rank test were performed to assess the median survival of each group. (3) Results: 174 patients underwent liver resection, and 34 patients recurred within 6 months. Of the patients planned for two-stage hepatectomy, 35 underwent the first stage only. Thirty-two patients were never resected. Median survival of the SD, PD, and ND groups was 31 months, 31 months, and 19.5 months, respectively (p = 0.012); (4) Conclusions: Patients who underwent a debulking of CRLM demonstrated a survival benefit compared to patients who did not undergo any surgical resection. This study provides support for the evaluation of intentional debulking versus palliative chemotherapy alone in a randomized trial.

Organ donation after medical assistance in dying: a descriptive study from 2018 to 2022 in Quebec.

BACKGROUND: Since the implementation of medical assistance in dying (MAiD), deceased organ donation after MAiD has been possible in Quebec. We sought to describe organ donations after MAiD in the first 5 years after this practice was implemented in Quebec. METHODS: We reviewed all cases referred for donation after MAiD from January 2018 to December 2022. We presented all data descriptively with no comparison statistics. RESULTS: Transplant Québec received 245 referrals for donation after MAiD, of which 82 were retained (33.5%). Of the 163 nonretained referrals, 152 (93.2%) had a recorded reason, including 91 (55.8%) for medical unsuitability on initial screen (e.g., organ dysfunction, medical history), 34 (20.8%) for patient refusal and 21 (12.9%) instances where patients withdrew from the MAiD process entirely. Six patients died before MAiD. Eighteen of the 82 retained cases were cancelled later in the process, almost all (n = 17, 94.4%) because of medical contraindication discovered during detailed donor evaluation. Sixty-four patients became actual donors after MAiD, increasing from 8 in 2018 to 24 in 2022. The total conversion rate from referral to an actual donor was 26.1% (64/245). A total of 182 organs (116 kidneys, 20 livers and 46 lungs) were transplanted after MAiD. During the study period, MAiD donors represented 8.0% (64/803) of total deceased donors, increasing from 4.9% (8/164) in 2018 to 14.0% (24/171) in 2022. INTERPRETATION: These data describe a substantial increase in deceased donation after MAiD in the first 5 years of implementation in Quebec. Future studies should focus on how to optimize systems to ensure these requests are treated in the most ethical and medically effective way.

A Practical Guide for the Systemic Treatment of Biliary Tract Cancer in Canada.

Biliary tract cancers (BTC) are rare and aggressive tumors with poor prognosis. Radical surgery offers the best chance for cure; however, most patients present with unresectable disease, and among those receiving curative-intent surgery, recurrence rates remain high. While other locoregional therapies for unresectable disease may be considered, only select patients may be eligible. Consequently, systemic therapy plays a significant role in the treatment of BTC. In the adjuvant setting, capecitabine is recommended following curative-intent resection. In the neoadjuvant setting, systemic therapy has mostly been explored for downstaging in borderline resectable tumours, although evidence for its routine use is lacking. For advanced unresectable or metastatic disease, gemcitabine-cisplatin plus durvalumab has become the standard of care, while the addition of pembrolizumab to gemcitabine-cisplatin has also recently demonstrated improved survival compared to chemotherapy alone. Following progression on gemcitabine-cisplatin, several chemotherapy combinations and biomarker-driven targeted agents have been explored. However, the optimum regimen remains unclear, and access to targeted agents remains challenging in Canada. Overall, this article serves as a practical guide for the systemic treatment of BTC in Canada, providing valuable insights into the current and future treatment landscape for this challenging disease.

Endoscopic Ultrasound-Guided Biliary Drainage of First Intent With a Lumen-Apposing Metal Stent vs Endoscopic Retrograde Cholangiopancreatography in Malignant Distal Biliary Obstruction: A Multicenter Randomized Controlled Study (ELEMENT Trial).

BACKGROUND & AIMS: Endoscopic ultrasound-guided choledochoduodenostomy with a lumen-apposing metal stent (EUS-CDS) is a promising modality for management of malignant distal biliary obstruction (MDBO) with potential for better stent patency. We compared its outcomes with endoscopic retrograde cholangiopancreatography with metal stenting (ERCP-M). METHODS: In this multicenter randomized controlled trial, we recruited patients with MDBO secondary to borderline resectable, locally advanced, or unresectable peri-ampullary cancers across 10 Canadian institutions and 1 French institution. This was a superiority trial with a noninferiority assessment of technical success. Patients were randomized to EUS-CDS or ERCP-M. The primary end point was the rate of stent dysfunction at 1 year, considering competing risks of death, clinical failure, and surgical resection. Analyses were performed according to intention-to-treat principles. RESULTS: From February 2019 to February 2022, 144 patients were recruited; 73 were randomized to EUS-CDS and 71 were randomized to ERCP-M. The mean (SD) procedure time was 14.0 (11.4) minutes for EUS-CDS and 23.1 (15.6) minutes for ERCP-M (P < .01); 40% of the former was performed without fluoroscopy. Technical success was achieved in 90.4% (95% CI, 81.5% to 95.3%) of EUS-CDS and 83.1% (95% CI, 72.7% to 90.1%) of ERCP-M with a risk difference of 7.3% (95% CI, -4.0% to 18.8%) indicating noninferiority. Stent dysfunction occurred in 9.6% vs 9.9% of EUS-CDS and ERCP-M cases, respectively (P = .96). No differences in adverse events, pancreaticoduodenectomy and oncologic outcomes, or quality of life were noted. CONCLUSIONS: Although not superior in stent function, EUS-CDS is an efficient and safe alternative to ERCP-M in patients with MDBO. These findings provide evidence for greater adoption of EUS-CDS in clinical practice as a complementary and exchangeable first-line modality to ERCP in patients with MDBO. CLINICALTRIALS: gov, Number: NCT03870386.

Calcineurin Inhibition in Deceased Organ Donors: A Systematic Review and Meta-analysis of Preclinical Studies.

Background: Preconditioning deceased organ donors with calcineurin inhibitors (CNIs) may reduce ischemia-reperfusion injury to improve transplant outcomes. Methods: We searched MEDLINE, EMBASE, Cochrane Library, and conference proceedings for animal models of organ donation and transplantation, comparing donor treatment with CNIs with either placebo or no intervention, and evaluating outcomes for organ transplantation. Reviewers independently screened and selected studies, abstracted data, and assessed the risk of bias and clinical relevance of included studies. Where possible, we pooled results using meta-analysis; otherwise, we summarized findings descriptively. Results: Eighteen studies used various animals and a range of CNI agents and doses and evaluated their effects on a variety of transplant outcomes. The risk of bias and clinical applicability were poorly reported. Pooled analyses suggested benefit of CNI treatment on early graft function in renal transplants (3 studies; serum creatinine: ratio of means [RoM] 0.54; 95% confidence interval [CI], 0.34-0.86) but not for liver transplants (2 studies; serum alanine transaminase: RoM 0.61; 95% CI, 0.30-1.26; and serum aspartate aminotransferase: RoM 0.58; 95% CI, 0.26-1.31). We found no reduction in graft loss at 7 d (2 studies; risk ratio 0.54; 95% CI, 0.08-3.42). CNI treatment was associated with reduced transplant recipient levels of interleukin-6 (4 studies; RoM 0.36; 95% CI, 0.19-0.70), tumor necrosis factor-alpha (5 studies; RoM 0.36; 95% CI, 0.12-1.03), and cellular apoptosis (4 studies; RoM 0.30; 95% CI, 0.19-0.47). Conclusions: Although this compendium of animal experiments suggests that donor preconditioning with CNIs may improve early kidney graft function, the limited ability to reproduce a true clinical environment in animal experiments and to assess for risk of bias in these experiments is a serious weakness that precludes current clinical application.

Perioperative clinical practice in liver transplantation: a cross-sectional survey.

PURPOSE: The objective of this study was to describe some components of the perioperative practice in liver transplantation as reported by clinicians. METHODS: We conducted a cross-sectional clinical practice survey using an online instrument containing questions on selected themes related to the perioperative care of liver transplant recipients. We sent email invitations to Canadian anesthesiologists, Canadian surgeons, and French anesthesiologists specialized in liver transplantation. We used five-point Likert-type scales (from "never" to "always") and numerical or categorical answers. Results are presented as medians or proportions. RESULTS: We obtained answers from 130 participants (estimated response rate of 71% in Canada and 26% in France). Respondents reported rarely using transesophageal echocardiography routinely but often using it for hemodynamic instability, often using an intraoperative goal-directed hemodynamic management strategy, and never using a phlebotomy (medians from ordinal scales). Fifty-nine percent of respondents reported using a restrictive fluid management strategy to manage hemodynamic instability during the dissection phase. Forty-two percent and 15% of respondents reported using viscoelastic tests to guide intraoperative and postoperative transfusions, respectively. Fifty-four percent of respondents reported not pre-emptively treating preoperative coagulations disturbances, and 91% reported treating them intraoperatively only when bleeding was significant. Most respondents (48-64%) did not have an opinion on the maximal graft ischemic times. Forty-seven percent of respondents reported that a piggyback technique was the preferred vena cava anastomosis approach. CONCLUSION: Different interventions were reported to be used regarding most components of perioperative care in liver transplantation. Our results suggest that significant equipoise exists on the optimal perioperative management of this population.

RéSUMé: OBJECTIF: L'objectif de cette étude était de décrire certaines composantes de la pratique périopératoire en transplantation hépatique telles que rapportées par les cliniciens. MéTHODE: Nous avons mené un sondage transversal sur la pratique clinique à l'aide d'un instrument en ligne comportant des questions sur des thèmes sélectionnés liés aux soins périopératoires des receveurs de greffe du foie. Nous avons envoyé des invitations par courriel à des anesthésiologistes canadiens, des chirurgiens canadiens et des anesthésiologistes français spécialisés en transplantation hépatique. Nous avons utilisé des échelles de type Likert à cinq points (de « jamais ¼ à « toujours ¼) et des réponses numériques ou catégorielles. Les résultats sont présentés sous forme de médianes ou de proportions. RéSULTATS: Nous avons obtenu des réponses de 130 participants (taux de réponse estimé à 71 % au Canada et à 26 % en France). Les répondants ont déclaré utiliser rarement l'échocardiographie transœsophagienne de routine, mais l'utiliser fréquemment pour l'instabilité hémodynamique, souvent en utilisant une stratégie de prise en charge hémodynamique peropératoire axée sur les objectifs, et jamais en utilisant une phlébotomie (médianes des échelles ordinales). Cinquante-neuf pour cent des répondants ont déclaré utiliser une stratégie restrictive de gestion liquidienne pour prendre en charge l'instabilité hémodynamique pendant la phase de dissection. Quarante-deux pour cent et 15 % des répondants ont déclaré utiliser des tests viscoélastiques pour guider les transfusions peropératoires et postopératoires, respectivement. Cinquante-quatre pour cent des répondants ont déclaré ne pas traiter préventivement les troubles préopératoires de la coagulation, et 91 % ont déclaré les traiter en peropératoire uniquement lorsque les saignements étaient importants. La plupart des répondants (48-64 %) n'avaient pas d'opinion sur les temps ischémiques maximaux du greffon. Quarante-sept pour cent des répondants ont déclaré qu'une technique de 'piggyback' (anastomose latéroterminale) était l'approche préférée pour l'anastomose de la veine cave. CONCLUSION: Différentes interventions ont été signalées pour la plupart des composantes des soins périopératoires dans la transplantation hépatique. Nos résultats suggèrent qu'il existe une incertitude significative concernant la prise en charge périopératoire optimale de cette population.

International Donation and Transplantation Legislative and Policy Forum: Methods and Purpose.

Organ and tissue donation and transplantation (OTDT) legislation and policies vary around the world, and this variability contributes to discrepancies in system performance. This article describes the purpose and methodology of an international forum that was organized to create consensus recommendations related to key legal and policy attributes of an ideal OTDT system. The intent is to create guidance for legislators, regulators, and other system stakeholders who aim to create or reform OTDT legislation and policy. Methods: This Forum was initiated by Transplant Québec and cohosted by the Canadian Donation and Transplantation Program partnered with multiple national and international donation and transplantation organizations. Seven domains were identified by the scientific committee' and domain working groups identified specific topics for recommendations: Baseline Ethical Principles, Legal Foundations, Consent Model and Emerging Legal Issues, Donation System Architecture, Living Donation, Tissue Donation, and Research and Innovation Systems and Emerging Issues. Patient, family, and donor partners were integrated into every stage of the planning and execution of the Forum. Sixty-one participants from 13 countries contributed to recommendation generation. Topic identification and recommendation consensus was completed over a series of virtual meetings from March to September 2021. Consensus was achieved by applying the nominal group technique informed by literature reviews performed by participants. Recommendations were presented at a hybrid in-person and virtual forum in Montreal, Canada, in October 2021. Output: Ninety-four recommendations (9-33 per domain) and an ethical framework for evaluating new policies were developed during the Forum proceedings. The accompanying articles include the recommendations from each domain and justifications that link the consensus to existing literature and ethical or legal concepts. Conclusions: Although the recommendations could not account for the vast global diversity of populations, healthcare infrastructure, and resources available to OTDT systems, they were written to be as widely applicable as possible.

Research and Innovation in Organ Donation: Recommendations From an International Consensus Forum.

This report provides recommendations from the Research and Innovation domain as part of the International Donation and Transplantation Legislative and Policy Forum (hereafter the Forum) to provide expert guidance on the structure of an ideal organ and tissue donation and transplantation system. The recommendations focus on deceased donation research and are intended for clinicians, investigators, decision-makers, and patient, family, and donor (PFD) partners involved in the field. Methods: We identified topics impacting donation research through consensus using nominal group technique. Members performed narrative reviews and synthesized current knowledge on each topic, which included academic articles, policy documents, and gray literature. Using the nominal group technique, committee members discussed significant findings, which provided evidence for our recommendations. The Forum's scientific committee then vetted recommendations. Results: We developed 16 recommendations in 3 key areas to provide stakeholders guidance in developing a robust deceased donor research framework. These include PFD and public involvement in research; donor, surrogate, and recipient consent within a research ethics framework; and data management. We highlight the importance of PFD and public partner involvement in research, we define the minimum ethical requirements for the protection of donors and recipients of both target and nontarget organ recipients, and we recommend the creation of a centrally administered donor research oversight committee, a single specialist institutional review board, and a research oversight body to facilitate coordination and ethical oversight of organ donor intervention research. Conclusions: Our recommendations provide a roadmap for developing and implementing an ethical deceased donation research framework that continually builds public trust. Although these recommendations can be applied to jurisdictions developing or reforming their organ and tissue donation and transplantation system, stakeholders are encouraged to collaborate and respond to their specific jurisdictional needs related to organ and tissue shortages.

Health System-Level Barriers to Living Donor Kidney Transplantation: Protocol for a Comparative Case Study Analysis.

BACKGROUND: Living donor kidney transplantation (LDKT) is the best treatment option for patients with kidney failure and offers significant medical and economic advantages for both patients and health systems. Despite this, rates of LDKT in Canada have stagnated and vary significantly across Canadian provinces, the reasons for which are not well understood. Our prior work has suggested that system-level factors may be contributing to these differences. Identifying these factors can help inform system-level interventions to increase LDKT. OBJECTIVE: Our objective is to generate a systemic interpretation of LDKT delivery across provincial health systems with variable performance. We aim to identify the attributes and processes that facilitate the delivery of LDKT to patients, and those that create barriers and compare these across systems with variable performance. These objectives are contextualized within our broader goal of increasing rates of LDKT in Canada, particularly in lower-performing provinces. METHODS: This research takes the form of a qualitative comparative case study analysis of 3 provincial health systems in Canada that have high, moderate, and low rates of LDKT performance (the percentage of LDKT to all kidney transplantations performed). Our approach is underpinned by an understanding of health systems as complex adaptive systems that are multilevel and interconnected, and involve nonlinear interactions between people and organizations, operating within a loosely bounded network. Data collection will comprise semistructured interviews, document reviews, and focus groups. Individual case studies will be conducted and analyzed using inductive thematic analysis. Following this, our comparative analysis will operationalize resource-based theory to compare case study data and generate explanations for our research question. RESULTS: This project was funded from 2020 to 2023. Individual case studies were carried out between November 2020 and August 2022. The comparative case analysis will begin in December 2022 and is expected to conclude in April 2023. Submission of the publication is projected for June 2023. CONCLUSIONS: By investigating health systems as complex adaptive systems and making comparisons across provinces, this study will identify how health systems can improve the delivery of LDKT to patients with kidney failure. Our resource-based theory framework will provide a granular analysis of the attributes and processes that facilitate or create barriers to LDKT delivery across multiple organizations and levels of practice. Our findings will have practice and policy implications and help inform transferrable competencies and system-level interventions conducive to increasing LDKT. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/44172.

Clinical consensus statement: Establishing the roles of locoregional and systemic therapies for the treatment of intermediate-stage hepatocellular carcinoma in Canada.

BACKGROUND: Hepatocellular carcinoma (HCC) a leading cause of cancer mortality worldwide and approximately one-third of patients present with intermediate-stage disease. The treatment landscape of intermediate-stage HCC is rapidly evolving due to developments in local, locoregional and systemic therapies. Treatment recommendations focused on this heterogenous disease stage and that take into account the Canadian reality are lacking. To address this gap, a pan-Canadian group of experts in hepatology, transplant, surgery, radiation therapy, nuclear medicine, interventional radiology, and medical oncology came together to develop consensus recommendations on management of intermediate-stage HCC relevant to the Canadian context. METHODS: A modified Delphi framework was used to develop consensus statements with strengths of recommendation and supporting levels of evidence graded using the AHA/ACC classification system. Tentative consensus statements were drafted based on a systematic search and expert input in a series of iterative feedback cycles and were then circulated via online survey to assess the level of agreement. RESULTS & CONCLUSION: The pre-defined ratification threshold of 80 % agreement was reached for all statements in the areas of multidisciplinary treatment (n = 4), intra-arterial therapy (n = 14), biologics (n = 5), radiation therapy (n = 3), surgical resection and transplantation (n = 7), and percutaneous ablative therapy (n = 4). These generally reflected an expansion in treatment options due to developments in previously established or emergent techniques, introduction of new and more active therapies and increased therapeutic flexibility. These developments have allowed for greater treatment tailoring and personalization as well as a paradigm shift toward strategies with curative intent in a wider range of disease settings.

Living Donor Kidney Transplantation in Quebec: A Qualitative Case Study of Health System Barriers and Facilitators.

Background: Patients with kidney failure represent a major public health burden, and living donor kidney transplantation (LDKT) is the best treatment option for these patients. Current work to optimize LDKT delivery to patients has focused on microlevel interventions and has not addressed interdependencies with meso and macro levels of practice. Objective: We aimed to learn from a health system with historically low LDKT performance to identify facilitators and barriers to LDKT. Our specific aims were to understand how LDKT delivery is organized through interacting macro, meso, and micro levels of practice and identify what attributes and processes of this health system facilitate the delivery of LDKT to patients with kidney failure and what creates barriers. Design: We conducted a qualitative case study, applying a complex adaptive systems approach to LDKT delivery, that recognizes health systems as being made up of dynamic, nested, and interconnected levels, with the patient at its core. Setting: The setting for this case study was the province of Quebec, Canada. Participants: Thirty-two key stakeholders from all levels of the health system. This included health care professionals, leaders in LDKT governance, living kidney donors, and kidney recipients. Methods: Semi-structured interviews with 32 key stakeholders and a document review were undertaken between February 2021 and December 2021. Inductive thematic analysis was used to generate themes. Results: Overall, we identified strong links between system attributes and processes and LDKT delivery, and more barriers than facilitators were discerned. Barriers that undermined access to LDKT included fragmented LDKT governance and expertise, disconnected care practices, limited resources, and regional inequities. Some were mitigated to an extent by the intervention of a program launched in 2018 to increase LDKT. Facilitators driven by the program included advocacy for LDKT from individual member(s) of the care team, dedicated resources, increased collaboration, and training opportunities that targeted LDKT delivery at multiple levels of practice. Limitations: Delineating the borders of a "case" is a challenge in case study research, and it is possible that some perspectives may have been missed. Participants may have produced socially desirable answers. Conclusions: Our study systematically investigated real-world practices as they operate throughout a health system. This novel approach has cross-disciplinary methodological relevance, and our findings have policy implications that can help inform multilevel interventions to improve LDKT.

Contexte: Les patients atteints d'insuffisance rénale représentent un lourd fardeau pour la santé publique, et la transplantation rénale provenant d'un donneur vivant (TRDV) est la meilleure option de traitement pour ces patients. Les travaux actuels visant à optimiser la TRDV chez les patients ont été limités à des interventions de niveau micro et n'ont pas abordé les interdépendances avec les niveaux méso et macro de la pratique. Objectifs: Notre objectif était d'apprendre d'un système de santé présentant un taux historiquement bas de TRDV pour arriver à déterminer les facteurs qui constituent un facilitateur ou un frein à la TRDV. Plus précisément, nous souhaitions, par le biais d'interactions entre les niveaux macro, méso et micro de la pratique, comprendre la façon dont la TRDV est organisée. Nous souhaitions également déterminer quels attributs et processus du système de santé constituent des facilitateurs ou des freins à la TRDV pour les patients atteints d'insuffisance rénale. Conception: Nous avons appliqué une approche de systèmes adaptatifs complexes à la TRDV pour mener une étude de cas qualitative qui reconnaît que les systèmes de santé sont constitués de niveaux dynamiques, imbriqués et interconnectés, où le patient est au cœur des interventions. Cadre: Cette étude de cas avait pour cadre la province de Québec (Canada). Participants: 32 intervenants clés de tous les niveaux du système de santé, notamment des professionnels de la santé, des leaders impliqués dans la gestion de la TRDV, des donneurs vivants d'un rein et des receveurs de rein. Méthodologie: Des entrevues semi-structurées avec 32 intervenants clés et un examen des documents ont été entrepris entre février 2021 et décembre 2021. L'analyse thématique inductive a servi à générer les thèmes. Résultats: De façon générale, nous avons constaté qu'il existait des liens solides entre la TRDV et les attributs et processus du système, et que les obstacles étaient plus nombreux que les facilitateurs. Les obstacles freinant l'accès à la TRDV comprenaient la gouvernance et l'expertise fragmentées en lien avec la TRDV, les pratiques de soins déconnectées, les ressources limitées et les inégalités régionales. Certains de ces obstacles ont été atténués dans une certaine mesure par l'intervention d'un programme lancé en 2018 pour accroître la TRDV. Les facilitateurs soutenus par le programme comprenaient la promotion de la TRDV par des membres individuels de l'équipe de soins, la disponibilité de ressources dédiées, une collaboration accrue et les possibilités de formation ciblant la TRDV à plusieurs niveaux de pratique. Limites: La délimitation des frontières de ce que constitue un « cas ¼ est un défi dans la recherche d'études de cas; il est ainsi possible que certaines perspectives aient été manquées. Les participants pourraient avoir donné des réponses socialement souhaitables. Conclusion: Notre étude a examiné systématiquement les pratiques en contexte réel, tel qu'elles fonctionnent dans l'ensemble d'un système de santé. Cette nouvelle approche présente une pertinence méthodologique interdisciplinaire et nos conclusions ont des implications politiques qui pourraient aider à orienter des interventions à plusieurs niveaux pour améliorer la TRDV.

Feasibility of Prospectively Comparing Opioid Analgesia With Opioid-Free Analgesia After Outpatient General Surgery: A Pilot Randomized Clinical Trial.

Importance: The overprescription of opioids to surgical patients is recognized as an important factor contributing to the opioid crisis. However, the value of prescribing opioid analgesia (OA) vs opioid-free analgesia (OFA) after postoperative discharge remains uncertain. Objective: To investigate the feasibility of conducting a full-scale randomized clinical trial (RCT) to assess the comparative effectiveness of OA vs OFA after outpatient general surgery. Design, Setting, and Participants: This parallel, 2-group, assessor-blind, pragmatic pilot RCT was conducted from January 29 to September 3, 2020 (last follow-up on October 2, 2020). at 2 university-affiliated hospitals in Montreal, Quebec, Canada. Participants were adult patients (aged ≥18 years) undergoing outpatient abdominal (ie, cholecystectomy, appendectomy, or hernia repair) or breast (ie, partial or total mastectomy) general surgical procedures. Exclusion criteria were contraindications to drugs used in the trial, preoperative opioid use, conditions that could affect assessment of outcomes, and intraoperative or early complications requiring hospitalization. Interventions: Patients were randomized 1:1 to receive OA (around-the-clock nonopioids and opioids for breakthrough pain) or OFA (around-the-clock nonopioids with increasing doses and/or addition of nonopioid medications for breakthrough pain) after postoperative discharge. Main Outcomes and Measures: Main outcomes were a priori RCT feasibility criteria (ie, rates of surgeon agreement, patient eligibility, patient consent, treatment adherence, loss to follow-up, and missing follow-up data). Secondary outcomes included pain intensity and interference, analgesic intake, 30-day unplanned health care use, and adverse events. Between-group comparison of outcomes followed the intention-to-treat principle. Results: A total of 15 surgeons were approached; all (100%; 95% CI, 78%-100%) agreed to have patients recruited and adhered to the study procedures. Rates of patient eligibility and consent were 73% (95% CI, 66%-78%) and 57% (95% CI, 49%-65%), respectively. Seventy-six patients were randomized (39 [51%] to OA and 37 [49%] to OFA) and included in the intention-to-treat analysis (mean [SD] age, 55.5 [14.5] years; 50 [66%] female); 40 (53%) underwent abdominal surgery, and 36 (47%) underwent breast surgery. Seventy-five patients (99%; 95% CI, 93%-100%) adhered to the allocated treatment; 1 patient randomly assigned to OFA received an opioid prescription. Seventeen patients (44%) randomly assigned to OA consumed opioids after discharge. Seventy-three patients (96%; 95% CI, 89%-99%) completed the 30-day follow-up. The rate of missing questionnaires was 37 of 3724 (1%; 95% CI, 0.7%-1.4%). All the a priori RCT feasibility criteria were fulfilled. Conclusions and Relevance: The findings of this pilot RCT support the feasibility of conducting a robust, full-scale RCT to inform evidence-based prescribing of analgesia after outpatient general surgery. Trial Registration: ClinicalTrials.gov Identifier: NCT04254679.

Preoperative Endoscopic Ultrasound Fine Needle Aspiration Versus Upfront Surgery in Resectable Pancreatic Cancer: A Systematic Review and Meta-analysis of Clinical Outcomes Including Survival and Risk of Tumor Recurrence.

Background and Aim: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is the standard of care in advanced pancreatic cancer. Its role in resectable disease, however, is controversial. This meta-analysis aims to ascertain the clinical outcomes of patients with resectable pancreatic cancer undergoing preoperative EUS-FNA compared to those going directly to surgery. Methods: A literature search was performed from 1996 to April 2019 using MEDLINE, EMBASE, and ISI Web of Knowledge for studies comparing preoperative EUS-FNA to EUS without FNA in resectable pancreatic cancer for clinical outcomes. The primary outcome is overall survival (OS). Secondary outcomes include cancer-free survival, tumor recurrence and peritoneal carcinomatosis, and post-FNA-pancreatitis rate. Results: Six retrospective studies were included. Preoperative EUS-FNA had better OS than the non-FNA group (WMD, 4.40 months [0.02 to 8.78]). Cancer-free survival did not differ significantly between the two groups (WMD, 2.08 months [-2.22 to 6.38]). EUS with FNA was not associated with increased rates of tumor recurrence or peritoneal carcinomatosis. Conclusion: Preoperative EUS-FNA in resectable pancreatic cancer may be associated with significantly greater OS when compared to the non-FNA group, with no significant difference in the rates of tumor recurrence or peritoneal seeding. Important limitations of our meta-analysis include the lack of prospective controlled data, which are unlikely to emerge given feasible constraints.

Tranexamic acid versus placebo to reduce perioperative blood transfusion in patients undergoing liver resection: protocol for the haemorrhage during liver resection tranexamic acid (HeLiX) randomised controlled trial.

INTRODUCTION: Despite use of operative and non-operative interventions to reduce blood loss during liver resection, 20%-40% of patients receive a perioperative blood transfusion. Extensive intraoperative blood loss is a major risk factor for postoperative morbidity and mortality and receipt of blood transfusion is associated with serious risks including an association with long-term cancer recurrence and overall survival. In addition, blood products are scarce and associated with appreciable expense; decreasing blood transfusion requirements would therefore have health system benefits. Tranexamic acid (TXA), an antifibrinolytic, has been shown to reduce the probability of receiving a blood transfusion by one-third for patients undergoing cardiac or orthopaedic surgery. However, its applicability in liver resection has not been widely researched. METHODS AND ANALYSIS: This protocol describes a prospective, blinded, randomised controlled trial being conducted at 10 sites in Canada and 1 in the USA. 1230 eligible and consenting participants will be randomised to one of two parallel groups: experimental (2 g of intravenous TXA) or placebo (saline) administered intraoperatively. The primary endpoint is receipt of blood transfusion within 7 days of surgery. Secondary outcomes include blood loss, postoperative complications, quality of life and 5-year disease-free and overall survival. ETHICS AND DISSEMINATION: This trial has been approved by the research ethics boards at participating centres and Health Canada (parent control number 177992) and is currently enrolling participants. All participants will provide written informed consent. Results will be distributed widely through local and international meetings, presentation, publication and ClinicalTrials.gov. TRIAL REGISTRATION NUMBER: NCT02261415.

Oncology clinic-based germline genetic testing for exocrine pancreatic cancer enables timely return of results and unveils low uptake of cascade testing.

BACKGROUND: Traditional medical genetics models are unable to meet the growing demand for germline genetic testing (GT) in patients with exocrine pancreatic cancer (PC). This study investigates the impact of an ambulatory oncology clinic-based GT model. METHODS: From 2012 to 2021, patients with PC were prospectively enrolled and considered for GT. Two chronological cohorts were compared: (1) the preuniversal genetic testing (pre-UGT) cohort, which received GT based on clinical criteria or family history; and (2) the post-UGT cohort, where an 86-gene panel was offered to all patients with PC. RESULTS: Of 847 eligible patients, 735 (86.8%) were enrolled (pre-UGT, n=579; post-UGT, n=156). A higher proportion of the post-UGT cohort received prospective GT (97.4% vs 58.5%, p<0.001). The rate of pathogenic germline alterations (PGA) across both cohorts was 9.9%, with 8.0% of PGAs in PC susceptibility genes. The post-UGT cohort had a higher prevalence of overall PGAs (17.2% vs 6.6%, p<0.001) and PGAs in PC susceptibility genes (11.9% vs 6.3%, p<0.001). The median turnaround time from enrolment to GT report was shorter in the post-UGT cohort (13 days vs 42 days, p<0.001). Probands with a PGA disclosed their GT results to 84% of their first-degree relatives (FDRs). However, only 31% of informed FDRs underwent GT, and the number of new cases per index case was 0.52. CONCLUSION: A point-of-care GT model is feasible and expedites access to GT for patients with PC. Strategies to increase the uptake of cascade testing are needed to maximise the clinical impact of an oncology clinic-based GT model.

Modified endoscopic ultrasound-guided double-balloon-occluded gastroenterostomy bypass (M-EPASS): a pilot study.

INTRODUCTION: We recently developed a double-balloon device, using widely available existing technology, to facilitate endoscopic ultrasound-guided gastroenterostomy (EUS-GE). Our aim is to assess the feasibility of this modified approach to EUS-guided double-balloon-occluded gastroenterostomy bypass (M-EPASS). METHODS: This was a single-center retrospective study of consecutive patients undergoing M-EPASS from January 2019 to August 2020. The double-balloon device consists of two vascular balloons that optimize the distension of a targeted small-bowel segment for EUS-guided stent insertion. The primary end point was the rate of technical success. RESULTS: 11 patients (45 % women; mean [standard deviation (SD)] age 64.9 [8.6]) with malignant gastric outlet obstruction were included. Technical and clinical success (ability to tolerate an oral diet) were achieved in 91 % (10/11) and 80 % (8/10) of patients, respectively. There was one adverse event (9 %) due to stent migration. Two patients (18 %) required re-intervention for stent obstruction secondary to food impaction. The mean (SD) time to a low residue diet was 3.5 (2.4) days. CONCLUSION: M-EPASS appears to facilitate the technique of EUS-GE, potentially enhancing its safety and clinical adoption. Larger studies are needed to validate this innovative approach to gastric outlet obstruction.

Endoscopic ultrasound (EUS)-guided fine needle biopsy alone vs. EUS-guided fine needle aspiration with rapid onsite evaluation in pancreatic lesions: a multicenter randomized trial.

BACKGROUND: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is the standard in the diagnosis of solid pancreatic lesions, in particular when combined with rapid onsite evaluation of cytopathology (ROSE). More recently, a fork-tip needle for core biopsy (FNB) has been shown to be associated with excellent diagnostic yield. EUS-FNB alone has however not been compared with EUS-FNA + ROSE in a large clinical trial. Our aim was to compare EUS-FNB alone to EUS-FNA + ROSE in solid pancreatic lesions. METHODS: A multicenter, non-inferiority, randomized controlled trial involving seven centers was performed. Solid pancreatic lesions referred for EUS were considered for inclusion. The primary end point was diagnostic accuracy. Secondary end points included sensitivity/specificity, mean number of needle passes, and cost. RESULTS: 235 patients were randomized: 115 EUS-FNB alone and 120 EUS-FNA + ROSE. Overall, 217 patients had malignant histology. The diagnostic accuracy for malignancy of EUS-FNB alone was non-inferior to EUS-FNA + ROSE at 92.2 % (95 %CI 86.6 %-96.9 %) and 93.3 % (95 %CI 88.8 %-97.9 %), respectively (P = 0.72). Diagnostic sensitivity for malignancy was 92.5 % (95 %CI 85.7 %-96.7 %) for EUS-FNB alone vs. 96.5 % (93.0 %-98.6 %) for EUS-FNA + ROSE (P = 0.46), while specificity was 100 % in both. Adequate histological yield was obtained in 87.5 % of the EUS-FNB samples. The mean (SD) number of needle passes and procedure time favored EUS-FNB alone (2.3 [0.6] passes vs. 3.0 [1.1] passes [P < 0.001]; and 19.3 [8.0] vs. 22.7 [10.8] minutes [P = 0.008]). EUS-FNB alone cost on average 45 US dollars more than EUS-FNA + ROSE. CONCLUSION: EUS-FNB alone is non-inferior to EUS-FNA + ROSE and is associated with fewer needle passes, shorter procedure time, and excellent histological yield at comparable cost.

Relative decrease in hemoglobin and outcomes in patients undergoing kidney transplantation surgery: A retrospective cohort study.

BACKGROUND: Recent surgical literature suggests that a relative decrease in hemoglobin (ΔHb) is predictive of adverse outcomes regardless of the absolute level. We aimed to examine the association between perioperative ΔHb and kidney transplantation (KT) outcomes. METHODS: This was a retrospective cohort study of transplant recipients, where ΔHb = [Hb0- Hb1Hb0]x 100 (Hb0 = hemoglobin pre-KT and Hb1 = lowest hemoglobin 24-h post-KT). The main outcome of interest was immediate graft function (IGF). RESULTS: Of the 899 eligible patients, 38% experienced IGF, and ΔHb was associated with 36% lower odds of IGF. Also, ΔHb was associated with higher all-cause graft failure and longer length of stay but not death-censored graft failure or mortality. ΔHb ≥30% was the threshold beyond which the odds of IGF were significantly lower even if Hb1 was ≥7 g/dL. CONCLUSION: ΔHb is associated with inferior outcomes independent of Hb1; whether it can be used to guide transfusion practices should be explored.

Association Between Patient Activation and Health Care Utilization After Thoracic and Abdominal Surgery.

Importance: Increased patient activation (PA) (ie, knowledge, skills, motivation, confidence to participate in care) may result in improved outcomes, especially in surgical settings. Objective: To estimate the extent to which PA is associated with 30-day postdischarge unplanned health care utilization after major thoracic or abdominal surgery. Design, Setting, and Participants: This cohort study was performed at 2 centers of a tertiary care hospital network between October 2017 and January 2019. Adult patients undergoing thoracic or abdominal surgery were included. Of 880 patients assessed for eligibility, 692 were deemed eligible, of whom 34 declined to participate, 1 withdrew consent, and 4 were excluded after consent. Exposures: Patient activation was measured immediately after surgery during the initial admission using the Patient Activation Measure (score range, 0-100). Patients were dichotomized into low and high PA groups using previously described thresholds (Patient Activation Measure score, ≤55.1). Main Outcomes and Measures: The primary outcome was unplanned 30-day postdischarge health care utilization (composite including emergency department and outpatient clinic visits and/or hospital readmission). Secondary outcomes were length of stay, 30-day emergency department visits, 30-day readmissions, and postoperative complications. Results: A total of 653 patients admitted for thoracic, general, colorectal, and gynecologic surgery were included in the study (mean [SD] age, 58 [15] years; 369 women [56%]; 366 [56%] had minimally invasive surgery; 52 [8%] had emergency surgery), of which 152 (23%) had a low level of PA. Baseline characteristics were similar between patients with low- and high-level PA. Low PA was associated with unplanned health care utilization (odds ratio [OR], 3.15; 95% CI, 2.05-4.86; P < .001), emergency department visits (OR, 1.64; 95% CI, 1.02-2.64; P = .04), complications (OR, 1.63; 95% CI, 1.11-2.41; P = .01), and length of stay (adjusted mean difference, 1.19 days; 95% CI, 0.06-2.33; P = .04). Low PA was not associated with a higher risk of readmission (adjusted OR, 1.04; 95% CI, 0.56-1.93; P = .90). Conclusions and Relevance: In this study, low level of PA was associated with postdischarge unplanned health care use, hospital stay, and complications after major surgery. Identification of patients with low activation may allow the implementation of interventions to improve health care knowledge and support self-management postdischarge.