Publications by authors named "Matthew Weiss"

351 Publications

Evidence of SARS-CoV-2 Infection in Cells, Tissues and Organs and the Risk of Transmission Through Transplantation.

Transplantation 2021 Mar 10. Epub 2021 Mar 10.

Medical Affairs and Innovation, Héma-Québec, Québec, QC, Canada Children's Hospital of Eastern Ontario Research Institute, Ottawa, ON, Canada Canadian Blood Services, Ottawa, ON, Canada Medical Affairs and Innovation, Héma-Québec, Saint-Laurent, QC, Canada Centre for Outcomes Research and Evaluation (CORE), Research Institute of McGill University Health Centre, Montréal, QC, Canada Division of Nephrology and the Multi Organ Transplant Program, Royal Victoria Hospital, McGill University Health Centre, Montréal, QC, Canada Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montréal, QC, Canada Canadian Blood Services, Edmonton, AB, Canada Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB, Canada Population Health and Optimal Health Practices Research Unit, Trauma-Emergency-Critical Care Medicine, CHU de Québec, Université Laval Research Center, Québec, QC, Canada. Pediatrics Department, Intensive Care Division, Faculté de Médecine, Université Laval, Québec, QC, Canada. Transplant Québec, Montréal, QC, Canada. Faculty of Medicine and Health Sciences, University of Sherbrooke, Sherbrooke, QC, Canada.

The emergence of the SARS-CoV-2 virus responsible for the COVID-19 pandemic has raised concerns for programs overseeing donation and transplantation of cells, tissues and organs (CTO) that this virus might be transmissible by transfusion or transplantation. Transplant recipients are considered particularly vulnerable to pathogens due to immunosuppression, and SARS-CoV-2 is likely to generate complications if contracted. Several signs and symptoms observed in COVID-19 positive patients reflect damage to multiple organs and tissues, raising the possibility of extra-pulmonary SARS-CoV-2 infections and risk of transmission. At the beginning of the pandemic, a consensus has emerged not to consider COVID-19 positive patients as potential living or deceased donors, resulting in a global decrease in transplantation procedures. Medical decision making at the time of organ allocation must consider safely alongside the survival advantages offered by transplantation. To address the risk of transmission by transplantation, this review summarizes the published cases of transplantation of cells or organs from donors infected with SARS-CoV-2 and assesses the current state of knowledge for the detection of this virus in different biological specimens, cells, tissues and organs. Evidence collected to date raises the possibility of SARS-CoV-2 infection and replication in some CTO, which makes it impossible to exclude transmission through transplantation. However, most studies focused on evaluating transmission under laboratory conditions with inconsistent findings, rendering the comparison of results difficult. Improved standardization of donors and CTO screening practices, along with a systematic follow-up of transplant recipients could facilitate the assessment of SARS-CoV-2 transmission risk by transplantation. The supplemental file associated with this article will be found at http://links.lww.com/TP/C182.
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http://dx.doi.org/10.1097/TP.0000000000003744DOI Listing
March 2021

Defining the Risk of Early Recurrence Following Curative-Intent Resection for Distal Cholangiocarcinoma.

Ann Surg Oncol 2021 Mar 11. Epub 2021 Mar 11.

Division of Surgical Oncology, Health Services Management and Policy, Department of Surgery, The Urban Meyer III and Shelley Meyer Chair for Cancer Research, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA.

Background: Although multidisciplinary treatments including the use of adjuvant therapy (AT) have been adopted for biliary tract cancers, patients with distal cholangiocarcinoma (DCC) can still experience recurrence. We sought to characterize the incidence and predictors of early recurrence (ER) that occurred within 12 months following surgery for DCC.

Patients And Methods: Patients who underwent resection for DCC between 2000 and 2015 were identified from the US multi-institutional database. Cox regression analysis was used to identify clinicopathological factors to develop an ER risk score, and the predictive model was validated in an external dataset.

Results: Among 245 patients included in the analysis, 67 patients (27.3%) developed ER. No difference was noted in ER rates between patients who did and did not receive AT (28.7% vs. 25.0%, p = 0.55). Multivariable analysis revealed that neutrophil-to-lymphocyte ratio (NLR), peak total bilirubin (T-Bil), major vascular resection (MVR), lymphovascular invasion, and R1 surgical margin status were associated with a higher ER risk. A DIstal Cholangiocarcinoma Early Recurrence Score was developed according to each factor available prior to surgery [NLR > 9.0 (2 points); peak T-bil > 1.5 mg/dL (1 points); MVR (2 points)]. Cumulative ER rates incrementally increased among patients who were low (0 points; 10.6%), intermediate (1-2 points; 26.8%), or high (3-5 points; 57.6%) risk (p < 0.001) in the training dataset, as well as in the validation dataset [low (0 points); 3.4%, intermediate (1-2 points); 32.7%, or high risk (3-5 points); 55.6% (p < 0.001)].

Conclusions: Among patients undergoing resection for DCC, 1 in 4 patients experienced an ER. Alternative treatment strategies such as neoadjuvant chemotherapy may be considered especially among individuals deemed to be at high risk for ER.
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http://dx.doi.org/10.1245/s10434-021-09811-4DOI Listing
March 2021

Comment on "Arterial Resection in Pancreatic Cancer Surgery: Effective After a Learning Curve".

Ann Surg 2021 Feb 10. Epub 2021 Feb 10.

Division of Surgical Oncology, University of Nebraska Medical Center, Omaha, NE, USA Division of Surgical Oncology, The Ohio State University, Columbus, OH, USA Division of Surgical Oncology, Northwell Health Cancer Institute, Donald and Barbara Zucker School of Medicine at Hofstra, New Hyde Park, NY, USA.

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http://dx.doi.org/10.1097/SLA.0000000000004789DOI Listing
February 2021

The variable impact of the overdose crisis on organ donation among five Canadian provinces: a retrospective study.

Can J Anaesth 2021 Feb 9. Epub 2021 Feb 9.

Division of Critical Care Medicine, Montreal Children's Hospital, MUHC Research Institute, McGill University, Deceased Organ Donation, Canadian Blood Services, Montreal, QC, Canada.

Background: While most overdose deaths in Canada occur in the community, some patients are resuscitated, admitted to intensive care units having sustained severe anoxic brain injury, and have the potential to be organ donors. The purpose of this study was to determine the impact of the overdose crisis on organ donation in selected Canadian provinces.

Methods: We obtained data on the total number of organ donors and those dying because of overdose in five Canadian provinces from 2014 to 2018. We also obtained data for January-June 2019 for four of five provinces (Quebec excepted). We accessed federal and provincial data on the number of overdose deaths and compared the proportion of organ donors who died of an overdose both over time and between provinces. The number of organ transplants resulting from donors dying of an overdose from three provinces was also determined.

Results: From 2014 to 2017, there was a 35% increase (554 to 747) in total deceased organ donors but a 294% increase (31 to 122) in organ donors dying of an overdose. While the proportion of organ donors dying from an overdose increased overall, this varied from 35% (42 of 121) in British Columbia to < 5% in both Quebec (9 of 182) and Nova Scotia (< 2 of 16). There were 1,043 organ transplants resulting from organ donors dying of overdose in BC, Ontario and Alberta although only 2.5-3.5% (297 of 10,858) of those dying of an overdose became organ donors.

Conclusions: There has been an increase in organ donors dying from drug overdose in Canada. Regional variation mirrors differences in total opiate-related death.
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http://dx.doi.org/10.1007/s12630-021-01945-zDOI Listing
February 2021

Resumption of Cardiac Activity after Withdrawal of Life-Sustaining Measures.

N Engl J Med 2021 01;384(4):345-352

From the Children's Hospital of Eastern Ontario (S.D.), Children's Hospital of Eastern Ontario Research Institute (S.D., L.H., A. van Beinum, M.H., H.T.), Faculty of Medicine (S.D.) and Centre for Health Law, Policy, and Ethics (J.A.C.), University of Ottawa, Canadian Blood Services (L.H., S.D.S.), Carleton University (A. van Beinum), the Dynamical Analysis Lab (N.B.S., C.H., A.S.), Clinical Epidemiology Program (N.B.S., C.H., A.S.), and Clinical Epidemiology Program Methods Centre (T.R.), Ottawa Hospital Research Institute, the Departments of Critical Care and General Surgery (G.P.) and Surgery (A.S.) and Division of Thoracic Surgery (A.S.), Ottawa Hospital, and Interventional Cardiology Program, University of Ottawa Heart Institute (D. So), Ottawa, the Department of Critical Care, Trauma and Neurosurgery Program, St. Michael's Hospital (A. Baker), Li Ka Shing Knowledge Institute, Unity Health-St. Michael's Hospital (J.O.F., D. Scales), University of Toronto (J.O.F.), Mount Sinai Hospital (S.M., L.M.) and Interdepartmental Division of Critical Care Medicine (S.M., L.M., D. Scales), University of Toronto, Department of Critical Care Medicine, Sunnybrook Health Sciences Centre (D. Scales), and the Canadian Donation and Transplantation Research Program (H.T.), Toronto, the Departments of Critical Care and Anesthesia, Dalhousie University, Halifax, NS (S.B.), the Departments of Medicine and Critical Care Medicine, Queen's University, Kingston, ON (J.G.B., D.M.M.), the Department of Medicine (Critical Care), Research Centre of the University of Montreal Hospital (M.C.), the Department of Critical Care, Division of Pulmonary Medicine, McGill University (J.S.), McGill University Health Centre and Research Institute (J.S., S.D.S.), Transplant Québec (M.W.), and the Division of Critical Care, Montreal Children's Hospital (S.D.S.), Montreal, the Department of Anesthesiology, Université de Sherbrooke and Centre de Recherche du Centre Hospitalier Universitaire (CHU) de Sherbrooke, Sherbrooke, QC (F. D'Aragon), the Departments of Critical Care Medicine, Community Health Sciences, and Medicine, Cumming School of Medicine (C.J.D.), and the Departments of Critical Care Medicine and Clinical Neurosciences (A.H.K.), University of Calgary, and Calgary Zone, Alberta Health Services (C.J.D.), Calgary, the Department of Clinical Neurological Sciences, London Health Sciences Centre (T.G.), Schulich School of Medicine and Dentistry (T.G.), the Department of Psychology, King's University College (L.N.), and the Department of Medicine and the Brain and Mind Institute (M. Slessarev), Western University, London, ON, the Division of Critical Care, Departments of Medicine and Anesthesia, University of British Columbia, Vancouver (G.I.), the Department of Critical Care Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton (D.J.K.), the Department of Medicine, McMaster University, and Hamilton Health Sciences Centre, Hamilton, ON (M.M.), and the Division of Pediatric Intensive Care, CHU de Québec, Centre Mère-Enfant Soleil, and the Department of Pediatrics, Faculté de Médecine, Université Laval, Quebec City, QC (M.W.) - all in Canada; Safar Center for Resuscitation Research, Critical Care Medicine Department, University of Pittsburgh School of Medicine, Pittsburgh (C.D.); Charles University, Third Faculty of Medicine and FNKV University Hospital (F. Duska, M. Schmidt, P.W.), and the Department of Palliative Medicine, First Faculty of Medicine, Charles University and General University Hospital (K.R.), Prague, Czech Republic; NHS Blood and Transplant, Bristol (D.G., D.H.), and Adult Critical Care, Nottingham University Hospitals NHS Trust, Nottingham (D.G., D.H.) - both in the United Kingdom; and the Department of Intensive Care Medicine, Maastricht University Medical Center, and the School of Health Professions Education, Maastricht University (W.N.K.A.M.), and the Heart and Vascular Center, Maastricht University Medical Center (J.T.W.), Maastricht, the Netherlands.

Background: The minimum duration of pulselessness required before organ donation after circulatory determination of death has not been well studied.

Methods: We conducted a prospective observational study of the incidence and timing of resumption of cardiac electrical and pulsatile activity in adults who died after planned withdrawal of life-sustaining measures in 20 intensive care units in three countries. Patients were intended to be monitored for 30 minutes after determination of death. Clinicians at the bedside reported resumption of cardiac activity prospectively. Continuous blood-pressure and electrocardiographic (ECG) waveforms were recorded and reviewed retrospectively to confirm bedside observations and to determine whether there were additional instances of resumption of cardiac activity.

Results: A total of 1999 patients were screened, and 631 were included in the study. Clinically reported resumption of cardiac activity, respiratory movement, or both that was confirmed by waveform analysis occurred in 5 patients (1%). Retrospective analysis of ECG and blood-pressure waveforms from 480 patients identified 67 instances (14%) with resumption of cardiac activity after a period of pulselessness, including the 5 reported by bedside clinicians. The longest duration after pulselessness before resumption of cardiac activity was 4 minutes 20 seconds. The last QRS complex coincided with the last arterial pulse in 19% of the patients.

Conclusions: After withdrawal of life-sustaining measures, transient resumption of at least one cycle of cardiac activity after pulselessness occurred in 14% of patients according to retrospective analysis of waveforms; only 1% of such resumptions were identified at the bedside. These events occurred within 4 minutes 20 seconds after a period of pulselessness. (Funded by the Canadian Institutes for Health Research and others.).
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http://dx.doi.org/10.1056/NEJMoa2022713DOI Listing
January 2021

Identification of patients who may benefit the most from adjuvant chemotherapy following resection of incidental gallbladder carcinoma.

J Surg Oncol 2021 Mar 26;123(4):978-985. Epub 2021 Jan 26.

Department of Surgery, Wexner Medical Center, The Ohio State University, Columbus, Ohio, USA.

Background: To develop a scoring system to identify the subset of patients who may benefit the most from adjuvant chemotherapy following curative-intent resection for incidental gallbladder cancer (IGBC).

Methods: A novel scoring system was utilized to stratify patients relative to overall survival (OS), as well as potential benefit from adjuvant chemotherapy following curative resection for IGBC.

Results: Among 266 patients with IGBC, a total of 99 (37.2%) patients received adjuvant chemotherapy. Five risk factors were used to develop an integer-based score to predict OS. Risk of death at 5-years incrementally increased among patients in the low (n = 42, 69.0%), medium (n = 64, 56.3%) and high-risk groups (n = 40, 30.0%) (median OS, 99.4 vs. 33.5 vs. 15.6 months, all p < .001). Use of adjuvant chemotherapy did not provide a survival benefit among patients in the low-risk group (median survival, 99.4 vs. 60.7 months, p = .56). In contrast, utilization of adjuvant chemotherapy was associated with an improvement in survival among medium- (median survival, 21.7 vs. 59.5 months, p = .04) and high-risk patients (median survival, 11.6 vs. 20.1 months, p = .01).

Conclusions: While low-risk patients did not benefit from adjuvant chemotherapy, individuals with medium or high-risk scores had an improved survival with the utilization of adjuvant chemotherapy.
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http://dx.doi.org/10.1002/jso.26389DOI Listing
March 2021

The optimal cut-off values for tumor size, number of lesions, and CEA levels in patients with surgically treated colorectal cancer liver metastases: An international, multi-institutional study.

J Surg Oncol 2021 Mar 5;123(4):939-948. Epub 2021 Jan 5.

Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA.

Background And Objectives: Despite the long-standing consensus on the importance of tumor size, tumor number and carcinoembryonic antigen (CEA) levels as predictors of long-term outcomes among patients with colorectal liver metastases (CRLM), optimal prognostic cut-offs for these variables have not been established.

Methods: Patients who underwent curative-intent resection of CRLM and had available data on at least one of the three variables of interest above were selected from a multi-institutional dataset of patients with known KRAS mutational status. The resulting cohort was randomly split into training and testing datasets and recursive partitioning analysis was employed to determine optimal cut-offs. The concordance probability estimates (CPEs) for these optimal cut offs were calculated and compared to CPEs for the most widely used cut-offs in the surgical literature.

Results: A total of 1643 patients who met eligibility criteria were identified. Following recursive partitioning analysis in the training dataset, the following cut-offs were identified: 2.95 cm for tumor size, 1.5 for tumor number and 6.15 ng/ml for CEA levels. In the entire dataset, the calculated CPEs for the new tumor size (0.52), tumor number (0.56) and CEA (0.53) cut offs exceeded CPEs for other commonly employed cut-offs.

Conclusion: The current study was able to identify optimal cut-offs for the three most commonly employed prognostic factors in CRLM. While the per variable gains in discriminatory power are modest, these novel cut-offs may help produce appreciable increases in prognostic performance when combined in the context of future risk scores.
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http://dx.doi.org/10.1002/jso.26361DOI Listing
March 2021

A Program of Research to Evaluate the Impact of Deceased Organ Donation Legislative Reform in Nova Scotia: The LEADDR Program.

Transplant Direct 2021 Jan 15;7(1):e641. Epub 2020 Dec 15.

Legacy of Life and Critical Care Organ Donation, Nova Scotia Health Authority, Halifax, NS, Canada.

Background: This is the first time deemed consent, where the entire population of a jurisdiction is considered to have consented for donation unless they have registered otherwise, will be implemented in North America. While relatively common in other regions of the world-notably Western Europe-it is uncertain how this practice will influence deceased donation practices and attitudes in Canada.

Methods: We describe a Health Canada funded program of research that will evaluate the implementation process and full impact of the deceased organ donation legislation and the health system transformation in Nova Scotia that includes opt-out consent.

Results: There is a need to evaluate the impact of these changes to inform not only Nova Scotia and Atlantic Canada, but also other provincial, national, and international stakeholders.

Conclusions: We establish a rigorous academic framework that we will use to evaluate this significant health system transformation.
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http://dx.doi.org/10.1097/TXD.0000000000001093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738157PMC
January 2021

Impact and clinical usefulness of genetic data in the surgical management of colorectal cancer liver metastasis: a narrative review.

Hepatobiliary Surg Nutr 2020 Dec;9(6):705-716

Department of Surgery, Northwell Health Cancer Institute and Zucker School of Medicine, Lake Success, NY, USA.

Importance: In patients who undergo surgery for colorectal cancer liver metastases (CRLM), a number of somatic mutations have been associated with worse overall (OS) and recurrence-free survival (RFS). Although useful, an association with prognosis does not necessarily equate to an impact on surgical management.

Objective: The aim of this review was to investigate whether the best-studied somatic mutations impact surgical management of CRLM by informing: (I) post-hepatectomy surveillance; (II) selection of surgical technique; (III) selection of optimal margin width; and (IV) selection of patients for surgery. Lastly, we discuss the refinement of genetic data from overall mutation status to specific variants, as well as lesser studied somatic mutations.

Evidence Review: We conducted a computerized search using PubMed and Google Scholar for reports published so far, using mesh headings and keywords related to genetic data and CRLM.

Findings: Genetic data may impact surgical management of CRLM in three ways. Firstly, KRAS mutations can predict lung recurrences. Secondly, KRAS mutations may help tailor margin width. Thirdly, KRAS mutations may help tailor surgical technique.

Conclusions: Although genetic data may impact post-hepatectomy surveillance, selection of surgical technique and optimal margin width, their use to guide surgical selection remains elusive, as the data cannot support denying surgery to patients according to their somatic mutation profile.
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http://dx.doi.org/10.21037/hbsn.2019.10.05DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7720057PMC
December 2020

Vaccine-Induced Intratumoral Lymphoid Aggregates Correlate with Survival Following Treatment with a Neoadjuvant and Adjuvant Vaccine in Patients with Resectable Pancreatic Adenocarcinoma.

Clin Cancer Res 2021 Mar 4;27(5):1278-1286. Epub 2020 Dec 4.

Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.

Purpose: Immunotherapy is currently ineffective for nearly all pancreatic ductal adenocarcinomas (PDAC), largely due to its tumor microenvironment (TME) that lacks antigen-experienced T effector cells (Teff). Vaccine-based immunotherapies are known to activate antigen-specific Teffs in the peripheral blood. To evaluate the effect of vaccine therapy on the PDAC TME, we designed a neoadjuvant and adjuvant clinical trial of an irradiated, GM-CSF-secreting, allogeneic PDAC vaccine (GVAX).

Patients And Methods: Eighty-seven eligible patients with resectable PDAC were randomly assigned (1:1:1) to receive GVAX alone or in combination with two forms of low-dose cyclophosphamide. Resected tumors following neoadjuvant immunotherapy were assessed for the formation of tertiary lymphoid aggregates (TLA) in response to treatment. The clinical endpoints are disease-free survival (DFS) and overall survival (OS).

Results: The neoadjuvant treatment with GVAX either alone or with two forms of low-dose cyclophosphamide is safe and feasible without adversely increasing the surgical complication rate. Patients in Arm A who received neoadjuvant and adjuvant GVAX alone had a trend toward longer median OS (35.0 months) than that (24.8 months) in the historical controls who received adjuvant GVAX alone. However, Arm C, who received low-dose oral cyclophosphamide in addition to GVAX, had a significantly shorter DFS than Arm A. When comparing patients with OS > 24 months to those with OS < 15 months, longer OS was found to be associated with higher density of intratumoral TLA.

Conclusions: It is safe and feasible to use a neoadjuvant immunotherapy approach for PDACs to evaluate early biologic responses. In-depth analysis of TLAs is warranted in future neoadjuvant immunotherapy clinical trials.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-2974DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925374PMC
March 2021

Tumor Burden Dictates Prognosis Among Patients Undergoing Resection of Intrahepatic Cholangiocarcinoma: A Tool to Guide Post-Resection Adjuvant Chemotherapy?

Ann Surg Oncol 2021 Apr 1;28(4):1970-1978. Epub 2020 Dec 1.

Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA.

Introduction: While tumor burden (TB) has been associated with outcomes among patients with hepatocellular carcinoma, the role of overall TB in intrahepatic cholangiocarcinoma (ICC) remains poorly defined.

Methods: Patients undergoing curative-intent resection of ICC between 2000 and 2017 were identified from a multi-institutional database. The impact of TB on overall (OS) and disease-free survival (DFS) was evaluated in the multi-institutional database and validated externally.

Results: Among 1101 patients who underwent curative-intent resection of ICC, 624 (56.7%) had low TB, 346 (31.4%) medium TB, and 131 (11.9%) high TB. OS incrementally worsened with higher TB (5-year OS; low TB: 48.3% vs medium TB: 29.8% vs high TB: 17.3%, p < 0.001). Similarly, patients with low TB had better DFS compared with medium and high TB patients (5-year DFS: 38.3% vs 18.7% vs 6.9%, p < 0.001). On multivariable analysis, TB was independently associated with OS (medium TB: HR = 1.40, 95% CI 1.14-1.71; high TB: HR = 1.89, 95% CI 1.46-2.45) and DFS (medium TB, HR = 1.61, 95% CI 1.33-1.96; high TB: HR = 2.03, 95% CI 1.56-2.64). Survival analysis revealed an excellent prognostic discrimination using the TB among the external validation cohort (3-year OS; low TB: 44.8%, medium TB: 29.3%; high TB: 23.3%, p = 0.03; 3-year DFS: low TB: 32.7%, medium TB: 10.7%; high TB: 0%, p < 0.001). While neoadjuvant chemotherapy was not associated with survival across the TB groups, receipt of adjuvant chemotherapy was associated with increased survival among patients with high TB (5-year OS: 24.4% vs 13.4%, p = 0.02).

Conclusion: Overall TB dictated prognosis among patients with resectable ICC. TB may be used as a tool to help guide post-resection treatment strategies.
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http://dx.doi.org/10.1245/s10434-020-09393-7DOI Listing
April 2021

Integrated immunological analysis of a successful conversion of locally advanced hepatocellular carcinoma to resectability with neoadjuvant therapy.

J Immunother Cancer 2020 11;8(2)

Department of Oncology, Johns Hopkins Medicine Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland, USA

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer death worldwide with a minority of patients being diagnosed early enough for curative-intent interventions. We report the first use of preoperative cabozantinib plus nivolumab to successfully downstage what presented as unresectable HCC as part of an ongoing phase 1b study. Preoperative treatment with cabozantinib and nivolumab led to >99% reduction in alpha-fetoprotein, -37.3% radiographic reduction by RECIST 1.1 and a near complete pathologic response (80% to 100% necrosis). An integrated immunological analysis was performed on the post-treatment surgical tumor sample and matched pre-treatment and post-treatment peripheral blood samples with high-dimensional imaging and cytometry techniques. Bayesian non-negative matrix factorization (CoGAPS, Coordinated Gene Activity in Pattern Sets) and self-organizing map (FlowSOM) algorithms were used to distinguish changes in functional markers across cellular neighborhoods in the single cell data sets. Brisk immunological infiltration into the tumor microenvironment was observed in non-random, organized cellular neighborhoods. Systemically, combination therapy led to marked promotion of effector cytotoxic T cells and effector memory helper T cells. Natural killer cells also increased with therapy. The patient remains without disease recurrence and with a normal alpha-fetoprotein approximately 2 years from presentation. Our study provides proof-of-concept that borderline resectable or locally advanced HCC warrants consideration of downstaging with effective neoadjuvant systemic therapy for subsequent curative resection.
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http://dx.doi.org/10.1136/jitc-2020-000932DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7682468PMC
November 2020

Invasive and Non-Invasive Progression after Resection of Non-Invasive Intraductal Papillary Mucinous Neoplasms.

Ann Surg 2020 Nov 12. Epub 2020 Nov 12.

Departments of Surgery.

Objective: To define frequencies, pattern of progression (invasive versus non-invasive), and risk factors of progression of resected non-invasive IPMNs BACKGROUND:: There is a risk of progression in the remnant pancreas after resection of intraductal papillary mucinous neoplasms (IPMNs).

Methods: 449 consecutive patients with resected IPMNs from 1995-2018 were included to the study. Patients with invasive carcinoma or with follow-up < 6 months were excluded. Non-invasive progression was defined as a new IPMN, increased main pancreatic duct (MPD) size, and increased size of an existing lesion (5 mm compared to preoperative imaging). Invasive progression was defined as development of invasive cancer in the remnant pancreas or metastatic disease.

Results: With a median follow-up of 48.9 months, progression was identified in 124 patients (27.6%); 108(24.1%) with non-invasive and 16(3.6%) with invasive progression. Median progression follow-up was longer for invasive progression (85.4 vs. 55.9 months; P = 0.001). Five- and 10-year estimates for a cumulative incidence of invasive progression were 6.4% and 12.9% versus 26.9% and 41.5% for non-invasive progression. After risk-adjustment, multifocality (HR 4.53, 95%CI 1.34-15.26; P = 0.02) and high-grade dysplasia (HGD) in the original resection (HR 3.60, 95%CI 1.13-11.48; P = 0.03) were associated with invasive progression.

Conclusions: Progression to invasive carcinoma can occur years after the surgical resection of a non-invasive IPMN. HGD in the original resection is a risk factor for invasive progression but some cases of low-grade dysplasia also progressed to cancer. Patients with high-risk features such as HGD and multifocal cysts should be considered for more intensive surveillance and represent an important cohort for future trials such as anti-inflammatory or prophylactic immunotherapy.
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http://dx.doi.org/10.1097/SLA.0000000000004488DOI Listing
November 2020

Summary of International Recommendations for Donation and Transplantation Programs During the Coronavirus Disease Pandemic.

Transplantation 2021 01;105(1):14-17

Division of Infectious Diseases, Department of Medicine, University of British Columbia, Vancouver, BC, Canada.

Background: The COVID-19 pandemic has disrupted all aspects of the international organ donation and transplantation (ODT) system. Multiple organizations have developed guidance, but to date, no comparative summary has emerged to understand differences in existing recommendations.

Methods: We developed and applied a comparative methodology to a convenience sample of recommendations available on The Transplantation Society website. Document types were classified according to characteristics such as type of organization (eg, governing body or professional society) and geographic region. Recommendations were grouped according to content, and summaries were posted on a public website. This process is ongoing and will be updated as new recommendations become available.

Results: Eighteen documents were extracted in the initial review. All documents were based on expert opinion, and none described a formal literature review or adherence with clinical guideline development processes. Recommendation categories included screening of potential donors, risk assessment of potential recipients, posttransplant risk, living/paired donation, protection of ODT professionals, and ethics/logistics. While many documents included similar recommendations, such as the need to screen and test patients who are potential donors, there was variation on some topics. Type of recommended laboratory testing varied with 64% recommending nasopharyngeal swabs, 43% oropharyngeal, and 24% bronchial aspirates. Updated results are available at https://cdtrp.ca/en/covid-19-international-recommendations-for-odt/.

Conclusions: The current state of COVID-19 ODT recommendations is limited to expert opinion. Substantial variation exists regarding recommendations, which are based on emerging but currently low-quality evidence. This summary of existing recommendations will serve to inform priorities for evidence-based recommendations.
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http://dx.doi.org/10.1097/TP.0000000000003520DOI Listing
January 2021

Challenges of the current precision medicine approach for pancreatic cancer: A single institution experience between 2013 and 2017.

Cancer Lett 2021 Jan 28;497:221-228. Epub 2020 Oct 28.

The Pancreatic Cancer "Precision Medicine" Program, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA. Electronic address:

Recent research on genomic profiling of pancreatic ductal adenocarcinoma (PDAC) has identified many potentially actionable alterations. However, the feasibility of using genomic profiling to guide routine clinical decision making for PDAC patients remains unclear. We retrospectively reviewed PDAC patients between October 2013 and December 2017, who underwent treatment at the Johns Hopkins Hospital and had clinical tumor next-generation sequencing (NGS) through commercial resources. Ninety-two patients with 93 tumors tested were included. Forty-eight (52%) patients had potentially curative surgeries. The median time from the tissue available to the NGS testing ordered was 229 days (interquartile range 62-415). A total of three (3%) patients had matched targeted therapies based on genomic profiling results. Genomic profiling guided personalized treatment for PDAC patients is feasible, but the percentage of patients who receive targeted therapy is low. The main challenges are ordering NGS testing early in the clinical course of the disease and the limited evidence of using a targeted approach in these patients. A real-time department level genomic testing ordering system in combination with an evidence-based flagging system for potentially actionable alterations could help address these shortcomings.
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http://dx.doi.org/10.1016/j.canlet.2020.10.039DOI Listing
January 2021

Prevalence of Acute Rehabilitation for Kids in the PICU: A Canadian Multicenter Point Prevalence Study.

Pediatr Crit Care Med 2021 Feb;22(2):181-193

Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD.

Objectives: To evaluate mobilization practices, barriers, and mobility-related adverse events in Canadian PICUs.

Design: National 2-day point prevalence study.

Setting: Thirteen PICUs across Canada.

Patients: Children with a minimum 72-hour PICU length of stay on the allocated study day.

Interventions: None.

Measurements And Main Results: Outcomes of interest were the prevalence and nature of mobilization activities, rehabilitation resources, adverse events, and factors associated with out-of-bed mobility and therapist-provided mobility. Two PICUs (15%) had early mobilization practice guidelines, and one PICU (8%) reported a formal process for engaging families in the mobilization of patients. The prevalence of mobilization was 110 of 137 patient-days (80%). The commonest activity was out-of-bed mobility (87/137; 64% patient-days); there was no active mobilization on 46 patient-days (34%). Therapists provided mobility on 33% of patient-days. Mobility was most commonly facilitated by nurses (74% events) and family (49% events). Family participation was strongly associated with out-of-bed mobility (odds ratio 6.4; p = 0.001). Intubated, mechanically ventilated patients were mobilized out-of-bed on 18 of 50 patient-days (36%). However, the presence of an endotracheal tube, vasoactive infusions, and age greater than or equal to 3 years were independently associated with not being mobilized out-of-bed. Barriers were reported on 58 of 137 patient-days (42%), and adverse events occurred in 22 of 387 mobility events (6%).

Conclusions: Mobilization is common and safe, and the majority of children in Canadian PICUs are being mobilized out-of-bed, even when mechanically ventilated. Family engagement in PICU-based rehabilitation is increasing. This study provides encouraging evidence that common barriers can be overcome in order to safely mobilize children in PICUs.
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http://dx.doi.org/10.1097/PCC.0000000000002601DOI Listing
February 2021

Implications of Perineural Invasion on Disease Recurrence and Survival After Pancreatectomy for Pancreatic Head Ductal Adenocarcinoma.

Ann Surg 2020 Oct 19. Epub 2020 Oct 19.

School of Medicine, Vita-Salute San Raffaele University, Division of Pancreatic Surgery, Pancreas Translational & Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy.

Objective: To describe PNI and to evaluate its impact on disease-free (DFS) and overall survival (OS) in patients with resected pancreatic ductal adenocarcinoma (PDAC).

Summary Of Background Data: Although PNI is a prognostic factor for survival in many GI cancers, there is limited knowledge regarding its impact on tumor recurrence, especially in "early stage disease" (PDAC ≤20 mm, R0/N0 PDAC).

Methods: This multicenter retrospective study included patients undergoing PDAC resection between 2009 and 2014. The association of PNI with DFS and OS was analyzed using Cox proportional-hazards models.

Results: PNI was found in 87% of 778 patients included in the study, with lower rates in PDAC ≤20 mm (78.7%) and in R0/N0 tumors (70.6%). PNI rate did not differ between patients who underwent neoadjuvant therapy and upfront surgery (88% vs 84%, P = 0.08). Although not significant at multivariate analysis (P = 0.07), patients with PNI had worse DFS at univariate analysis (median DFS: 20 vs 15 months, P < 0.01). PNI was the only independent predictor of DFS in R0/N0 tumors (hazard ratio [HR]: 2.2) and in PDAC ≤20 mm (HR: 1.8). PNI was an independent predictor of OS in the entire cohort (27 vs 50 months, P = 0.01), together with G3 tumors, pN1 status, carbohydrate antigen (CA) 19.9 >37 and pain.

Conclusions: PNI represents a major determinant of tumor recurrence and patients' survival in pancreatic cancer. The role of PNI is particularly relevant in early stages, supporting the hypothesis that invasion of nerves by cancer cells has a driving role in pancreatic cancer progression.
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http://dx.doi.org/10.1097/SLA.0000000000004464DOI Listing
October 2020

An Aggressive Approach to Locally Confined Pancreatic Cancer: Defining Surgical and Oncologic Outcomes Unique to Pancreatectomy with Celiac Axis Resection (DP-CAR).

Ann Surg Oncol 2020 Oct 13. Epub 2020 Oct 13.

The Division of Hepatobiliary and Pancreatic Surgery, Johns Hopkins Hospital, Baltimore, MD, USA.

Background: Modern chemotherapeutics have led to improved systemic disease control for patients with locally advanced pancreatic cancer (LAPC). Surgical strategies such as distal pancreatectomy with celiac axis resection (DP-CAR) are increasingly entertained. Herein we review procedure-specific outcomes and assess biologic rationale for DP-CAR.

Methods: A prospectively maintained single-institution database of all pancreatectomies was queried for patients undergoing DP-CAR. We excluded all patients for whom complete data were not available and those who were not treated with contemporary multi-agent therapy. Data were supplemented with dedicated chart review and outreach for long-term oncologic outcomes.

Results: Fifty-four patients underwent DP-CAR between 2008 and 2018. The median age was 62.7 years. Ninety-eight percent received induction chemotherapy. Arterial reconstruction was performed in 17% and concomitant visceral resection in 30%. The R0 resection rate was 87%. Postoperative complications were common (43%) with chyle leak being the most frequent (17%). Length of stay was 8 days, readmission occurred in one-third, and 90-day mortality was 2%. Disease recurrence occurred in 74% during a median follow up of 17.4 months. Median recurrence-free (RFS) and overall survival (OS) were 9 and 25 months, respectively.

Conclusions: Following modern induction paradigms, DP-CAR can be performed with low mortality, manageable morbidity, and excellent rates of margin-negative resection in high-volume settings. The profile of complications of DP-CAR is distinct from pancreaticoduodenectomy and simple distal pancreatectomy. OS and RFS are similar to those undergoing resection of borderline resectable and resectable disease. Improved systemic disease control will likely lead to increasing utilization of aggressive surgical approaches to LAPC.
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http://dx.doi.org/10.1245/s10434-020-09201-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041923PMC
October 2020

Gastric cancer following pancreaticoduodenectomy: Experience from a high-volume center and review of existing literature.

Surg Open Sci 2020 Oct 16;2(4):32-40. Epub 2020 Aug 16.

Johns Hopkins Hospital, Department of Surgery, Hepatobiliary and Pancreatic Surgery Section of the Division of Surgical Oncology, Baltimore, MD, USA.

Background: Prolonged survival of patients after pancreaticoduodenectomy can be associated with late complications due to altered gastrointestinal anatomy. The incidence of gastric cancer is increasingly reported. We set out to examine our experience with gastric cancer as a late complication after pancreaticoduodenectomy with a focus on incidence, risk factors, and outcomes.

Methods: We queried our prospectively collected institutional database for patients that developed gastric cancer after pancreaticoduodenectomy and conducted a systematic review of the literature.

Results: Our database revealed 6 patients who developed gastric cancer following pancreaticoduodenectomy, presenting with a mean age of 62.2 years and an even sex distribution. All of those patients underwent pancreaticoduodenectomy for malignant indications with an average time to development of metachronous gastric cancer of 8.3 years. Four patients complained of gastrointestinal discomfort prior to diagnosis of secondary malignancy. All of these cancers were poorly differentiated and were discovered at an advanced T stage (≥ 3). Only half developed at the gastrointestinal anastomosis. Four underwent surgery with a curative intent, and 2 patients are currently alive (mean postgastrectomy survival = 25.5 months). In accordance with previous literature, biliopancreatic reflux from pancreaticoduodenectomy reconstruction, underlying genetic susceptibility, and adjuvant therapy may play a causative role in later development of gastric cancer.

Conclusion: Long-term survivors after pancreaticoduodenectomy who develop nonspecific gastrointestinal complaints should be evaluated carefully for complications including gastric malignancy. This may serve as an opportunity to intervene on tumors that typically present at an advanced stage and with aggressive histology.
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http://dx.doi.org/10.1016/j.sopen.2020.06.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7486455PMC
October 2020

Utilization of hepatitis C viremic donors for liver transplant recipients without hepatitis C. A veterans transplant center report.

Transpl Infect Dis 2020 Sep 15:e13466. Epub 2020 Sep 15.

University of Wisconsin School of Medicine and Public Health and William S Middleton, VA Medical Center, Madison, WI, USA.

Background: We report our experience utilizing liver donors with HCV Viremia (RNA+) for HCV-negative recipients (HCV D+R-) at a Veterans Affairs (VA) transplant center.

Methods: In 2018, we introduced an informed consent process for HCV D+R- liver transplants.

Results: Eight HCV D+R- liver transplants (LT) were performed. Median time from listing to LT was 189 days (range 41-511). Median MELD at LT was 23.5 (median MELD at LT of 31 for center). All recipients developed HCV viremia after transplant. Median time to DAA initiation was 10 days after viremia (range 3-25). After transplant, the DAAs used were Mavyret in five recipients and Epclusa in three, all for 12 weeks. All eight patients completed DAA therapy and achieved negative HCV RNA by end of therapy (ETR) and seven reached sustained virologic response (SVR) by 12 weeks after end of therapy. One patient died from chronic ischemic encephalopathy after ETR, before SVR.

Conclusions: HCV D+R- is a practical strategy to expand the pool of donor organs. It shortened waiting time, allowing patients to receive transplants at lower MELD scores. VA liver transplant programs have provided universal and timely access to post-transplant HCV DAA therapy after donor-derived infection.
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http://dx.doi.org/10.1111/tid.13466DOI Listing
September 2020

Perioperative CT angiography assessment of locally advanced distal pancreatic carcinoma to evaluate feasibility of the modified Appleby procedure.

Eur J Radiol 2020 Oct 31;131:109248. Epub 2020 Aug 31.

Department of Radiology and Radiological Science, Johns Hopkins Hospital, Johns Hopkins University, 601 N. Caroline Street, Baltimore, MD 21287, United States. Electronic address:

Purpose: To study the perioperative CT angiography (CTA) findings of modified Appleby procedure candidates for the surgical feasibility in patients with locally advanced distal pancreatic cancer (LAPC) and to assess CTA performance.

Materials And Methods: This retrospective study evaluated CTA of patients with distal LAPC who underwent modified Appleby procedure between March 2004 and October 2017. Preoperative CT scans performed within up to three months prior to the surgery and postoperative scans, at least one of which was within one month of surgery, were reviewed. Data was collected reporting tumor size, relation to vessels, changes from neoadjuvant chemoradiation, modifications to the surgery and complications. The CTA findings were correlated with operative notes and surgical pathology. Statistical analysis was performed using binary classification method to evaluate CTA performance.

Results: Consecutive 20 patients underwent modified Appleby procedure in the study period. In 18/20 patients who received neoadjuvant chemoradiation, mean pancreatic mass size significantly reduced from 4.58 + 1.17 cm to 3.55 + 0.84 cm (p = 0.002). The celiac axis (CA) was encased in all, whereas none of the patients had encasement of the superior mesenteric artery (SMA) or involvement of gastroduodenal artery (GDA). The CTA had 88.89% sensitivity, 100% specificity, and 90% accuracy for evaluating the arterial involvement.

Conclusion: Distal LAPC patients, in particular those who have significant size reduction after neoadjuvant chemoradiation, with encasement of CA and without encasement of SMA and GDA can undergo a technically successful modified Appleby procedure. CTA offers accurate and valuable perioperative assessment of the surgical candidates.
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http://dx.doi.org/10.1016/j.ejrad.2020.109248DOI Listing
October 2020

Minimal main pancreatic duct dilatation in small branch duct intraductal papillary mucinous neoplasms associated with high-grade dysplasia or invasive carcinoma.

HPB (Oxford) 2021 Mar 8;23(3):468-474. Epub 2020 Sep 8.

Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address:

Background: The aim of this study was to determine the incidence of high-grade dysplasia (HGD) or invasive carcinoma in patients with small branch duct intraductal papillary mucinous neoplasms (BD-IPMNs).

Methods: 923 patients who underwent surgical resection for an IPMN were identified. Sendai-negative patients were identified as those without history of pancreatitis or jaundice, main pancreatic duct size (MPD) <5 mm, cyst size <3 cm, no mural nodules, negative cyst fluid cytology for adenocarcinoma, or serum carbohydrate antigen 19-9 (CA 19-9) <37 U/L.

Results: BD-IPMN was identified in 388 (46.4%) patients and 89 (22.9%) were categorized as Sendai-negative. Overall, 68 (17.5%) of BD-IPMN had HGD and 62 (16.0%) had an associated invasive-carcinoma. Among the 89 Sendai-negative patients, 12 (13.5%) had IPMNs with HGD and only one patient (1.1%) had invasive-carcinoma. Of note, older age (OR 1.13, 95% CI 1.03-1.23; P = 0.008) and minimal dilation of MPD (OR 11.3, 95% CI 2.40-53.65; P = 0.002) were associated with high-risk disease in Sendai-negative patients after multivariable risk adjustment.

Conclusion: The risk of harboring a high-risk disease remains low in small BD-IPMNs. However, Sendai-negative patients who are older than 65 years old and those with minimal dilation of MPD (3-5 mm) are at greater risk of high-risk lesions and should be given consideration to be included as a "worrisome feature" in a future guidelines update.
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http://dx.doi.org/10.1016/j.hpb.2020.08.004DOI Listing
March 2021

Pancreatic circulating tumor cell detection by targeted single-cell next-generation sequencing.

Cancer Lett 2020 11 5;493:245-253. Epub 2020 Sep 5.

Departments of Surgery, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; Departments of Oncology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; Departments of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address:

Background And Aims: Single-cell next-generation sequencing (scNGS) technology has been widely used in genomic profiling, which relies on whole-genome amplification (WGA). However, WGA introduces errors and is especially less accurate when applied to single nucleotide variant (SNV) analysis. Targeted scNGS for SNV without WGA has not been described. We aimed to develop a method to detect circulating tumor cells (CTCs) with DNA SNVs.

Methods: We tested this targeted scNGS method with three driver mutant genes (KRAS/TP53/SMAD4) on one pancreatic cancer cell line AsPC-1 and then applied it to patients with metastatic PDAC for the validation.

Results: All single-cell of AsPC-1 and spiked-in AsPC-1 cells in healthy donor blood, which were isolated by the filtration with size or by flow cytometry, were detected by targeted scNGS method. All blood samples from six patients with metastatic PDAC, for the validation of target scNGS method, showed CTCs with SNVs of KRAS/TP53/SMAD4 and the positive confirmation of immunofluorescent stainings with Pan-CK/Vimentin/CD45. Four patients with early stage disease, one patient with benign pancreatic cyst and a healthy control sample all showed concordant results between targeted scNGS and CTC enumeration.

Conclusions: The novel technique of targeted scNGS for SNV analysis, without pre-amplification, is a promising method for identifying and characterizing circulating tumor cells.
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http://dx.doi.org/10.1016/j.canlet.2020.08.043DOI Listing
November 2020

Defining and Predicting Early Recurrence after Resection for Gallbladder Cancer.

Ann Surg Oncol 2021 Jan 5;28(1):417-425. Epub 2020 Sep 5.

Division of Surgical Oncology, Department of Surgery, The Urban Meyer III and Shelley Meyer Chair for Cancer Research, James Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, Columbus, OH, USA.

Background: The optimal time interval to define early recurrence (ER) among patients who underwent resection of gallbladder cancer (GBC) is not well defined. We sought to develop and validate a novel GBC recurrence risk (GBRR) score to predict ER among patients undergoing resection for GBC.

Patients And Methods: Patients who underwent curative-intent resection for GBC between 2000 and 2018 were identified from the US Extrahepatic Biliary Malignancy Consortium database. A minimum p value approach in the log-rank test was used to define the optimal cutoff for ER. A risk stratification model was developed to predict ER based on relevant clinicopathological factors and was externally validated.

Results: Among 309 patients, 103 patients (33.3%) had a recurrence at a median follow-up period of 15.1 months. The optimal cutoff for ER was defined at 12 months (p = 3.04 × 10). On multivariable analysis, T3/T4 disease (HR: 2.80; 95% CI 1.58-5.11) and poor tumor differentiation (HR: 1.91; 95% CI 1.11-3.25) were associated with greater hazards of ER. The GBRR score was developed using β-coefficients of variables in the final model, and patients were classified into three distinct groups relative to the risk for ER (12-month RFS; low risk: 88.4%, intermediate risk: 77.9%, high risk: 37.0%, p < 0.001). The external validation demonstrated good model generalizability with good calibration (n = 102: 12-month RFS; low risk: 94.2%, intermediate risk: 59.8%, high risk: 42.0%, p < 0.001). The GBRR score is available online at https://ktsahara.shinyapps.io/GBC_earlyrec/ .

Conclusions: A novel online calculator was developed to help clinicians predict the probability of ER after curative-intent resection for GBC. The proposed web-based tool may help in the optimization of surveillance intervals and the counselling of patients about their prognosis.
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http://dx.doi.org/10.1245/s10434-020-09108-yDOI Listing
January 2021

Predicting Lymph Node Metastasis in Intrahepatic Cholangiocarcinoma.

J Gastrointest Surg 2020 Jul 14. Epub 2020 Jul 14.

Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA.

Background: The objective of the current study was to develop a model to predict the likelihood of occult lymph node metastasis (LNM) prior to resection of intrahepatic cholangiocarcinoma (ICC).

Methods: Patients who underwent hepatectomy for ICC between 2000 and 2017 were identified using a multi-institutional database. A novel model incorporating clinical and preoperative imaging data was developed to predict LNM.

Results: Among 980 patients who underwent resection of ICC, 190 (19.4%) individuals had at least one LNM identified on final pathology. An enhanced imaging model incorporating clinical and imaging data was developed to predict LNM ( https://k-sahara.shinyapps.io/ICC_imaging/ ). The performance of the enhanced imaging model was very good in the training data set (c-index 0.702), as well as the validation data set with bootstrapping resamples (c-index 0.701) and outperformed the preoperative imaging alone (c-index 0.660). The novel model predicted both 5-year overall survival (OS) (low risk 48.4% vs. high risk 18.4%) and 5-year disease-specific survival (DSS) (low risk 51.9% vs. high risk 25.2%, both p < 0.001). When applied among Nx patients, 5-year OS and DSS of low-risk Nx patients was comparable with that of N0 patients, while high-risk Nx patients had similar outcomes to N1 patients (p > 0.05).

Conclusion: This tool may represent an opportunity to stratify prognosis of Nx patients and can help inform clinical decision-making prior to resection of ICC.
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http://dx.doi.org/10.1007/s11605-020-04720-5DOI Listing
July 2020

Survey of Canadian critical care physicians' knowledge and attitudes towards legislative aspects of the deceased organ donation system.

Can J Anaesth 2020 Oct 21;67(10):1349-1358. Epub 2020 Jul 21.

Canadian Donation and Transplant Research Program, Ottawa, ON, Canada.

Purpose: We surveyed Canadian critical care physicians who may care for patients who are potential organ donors to understand their attitudes and knowledge of legislation governing the deceased organ donation system.

Methods: We used a web-based, self-administered survey that included questions related to opt-out consent and mandatory referral legislation. Potential participants were identified through membership lists of professional societies and manual searches. We designed our survey using standardized methods and administered it in February and March 2018.

Results: Fifty percent (263/529) of potential participants completed the questionnaire. A majority (61%; 144/235) supported a change towards an opt-out consent model, and 77% (181/235) stated they believe it would increase donation rates. Asked if opt-out consent would change their practices, 71% (166/235) stated an opt-out model would not change how or if they approach families to discuss donation. Fifty-six percent (139/249) supported mandatory referral laws, while only 42% (93/219) of those working in provinces with mandatory referral correctly stated that such laws exist in their province. Respondents gave variable responses on who should be accountable when patients are not referred, and 16% (40/249) believed no one should be held accountable.

Conclusions: While a majority of critical care physicians supported opt-out consent and mandatory referral, many were neutral or against it. Many were unaware of existing laws and had variable opinions on how to ensure accountability. Efforts to increase understanding of how legislative models influence practice are required for any law to achieve its desired effect.
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http://dx.doi.org/10.1007/s12630-020-01756-8DOI Listing
October 2020

Increasing access to multidisciplinary care in pancreatic cancer.

Psychooncology 2020 12 5;29(12):2105-2108. Epub 2020 Aug 5.

Northwell Health Cancer Institute, Northwell Health, New York, New York, USA.

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http://dx.doi.org/10.1002/pon.5493DOI Listing
December 2020

Cardiac donation after circulatory determination of death: protocol for a mixed-methods study of healthcare provider and public perceptions in Canada.

BMJ Open 2020 07 20;10(7):e033932. Epub 2020 Jul 20.

School of Health Administration, Faculty of Health, Dalhousie University, Halifax, New Brunswick, Canada.

Introduction: Cardiac transplantation remains the best treatment for patients with end-stage heart disease that is refractory to medical or device therapies, however, a major challenge for heart transplantation is the persistent discrepancy between the number of patients on waiting lists and the number of available hearts. While other countries (eg, UK, Australia and Belgium) have explored and implemented alternative models of transplantation, such as cardiac donation after circulatory determination of death (DCDD) to alleviate transplantation wait times, ethical concerns have hindered implementation in some countries. This study aims to explore the attitudes and opinions of healthcare providers and the public about cardiac DCDD in order to identify and describe opportunities and challenges in ensuring that proposed cardiac DCDD procedures in Canada are consistent with Canadian values and ethical norms.

Methods And Analysis: This study will include two parts that will be conducted concurrently. Part 1 is a qualitative study consisting of semi-structured interviews with Canadian healthcare providers who routinely care for organ donors and/or transplant recipients to describe their perceptions about cardiac DCDD. Part 2 is a convergent parallel mixed-methods design consisting of a series of focus groups and follow-up surveys with members of the Canadian general public to describe their perceptions about cardiac DCDD.

Ethics And Dissemination: This study has been approved by the Research Ethics Board at Western University. The findings will be presented at regional and national conferences and reported in peer-reviewed publications.
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http://dx.doi.org/10.1136/bmjopen-2019-033932DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7375636PMC
July 2020

Genomic basis of white pine blister rust quantitative disease resistance and its relationship with qualitative resistance.

Plant J 2020 10 28;104(2):365-376. Epub 2020 Jul 28.

School of Forestry, Northern Arizona University, 200 E. Pine Knoll, Flagstaff, AZ, 86011, USA.

The genomic architecture and molecular mechanisms controlling variation in quantitative disease resistance loci are not well understood in plant species and have been barely studied in long-generation trees. Quantitative trait loci mapping and genome-wide association studies were combined to test a large single nucleotide polymorphism (SNP) set for association with quantitative and qualitative white pine blister rust resistance in sugar pine. In the absence of a chromosome-scale reference genome, a high-density consensus linkage map was generated to obtain locations for associated SNPs. Newly discovered associations for white pine blister rust quantitative disease resistance included 453 SNPs involved in wide biological functions, including genes associated with disease resistance and others involved in morphological and developmental processes. In addition, NBS-LRR pathogen recognition genes were found to be involved in quantitative disease resistance, suggesting these newly reported genes are qualitative genes with partial resistance, they are the result of defeated qualitative resistance due to avirulent races, or they have epistatic effects on qualitative disease resistance genes. This study is a step forward in our understanding of the complex genomic architecture of quantitative disease resistance in long-generation trees, and constitutes the first step towards marker-assisted disease resistance breeding in white pine species.
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http://dx.doi.org/10.1111/tpj.14928DOI Listing
October 2020

Very Early Recurrence After Liver Resection for Intrahepatic Cholangiocarcinoma: Considering Alternative Treatment Approaches.

JAMA Surg 2020 09;155(9):823-831

James Comprehensive Cancer Center, Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center, Columbus.

Importance: Although surgery offers the best chance of a potential cure for patients with localized, resectable intrahepatic cholangiocarcinoma (ICC), prognosis of patients remains dismal largely because of a high incidence of recurrence.

Objective: To predict very early recurrence (VER) (ie, recurrence within 6 months after surgery) following resection for ICC in the pre- and postoperative setting.

Design, Setting, And Participants: Patients who underwent curative-intent resection for ICC between May 1990 and July 2016 were identified from an international multi-institutional database. The study was conducted at The Ohio State University in collaboration with all other participating institutions. The data were analyzed in December 2019.

Main Outcomes And Measures: Two logistic regression models were constructed to predict VER based on pre- and postoperative variables. The final models were used to develop an online calculator to predict VER and the tool was internally and externally validated.

Results: Among 880 patients (median age, 59 years [interquartile range, 51-68 years]; 388 women [44.1%]; 428 [50.2%] white; 377 [44.3%] Asian; 27 [3.2%] black]), 196 (22.3%) developed VER. The 5-year overall survival among patients with and without VER was 8.9% vs 49.8%, respectively (P < .001). A preoperative model was able to stratify patients relative to the risk for VER: low risk (6-month recurrence-free survival [RFS], 87.7%), intermediate risk (6-month RFS, 72.3%), and high risk (6-month RFS, 49.5%) (log-rank P < .001). The postoperative model similarly identified discrete cohorts of patients based on probability for VER: low risk (6-month RFS, 90.0%), intermediate risk (6-month RFS, 73.1%), and high risk (6-month RFS, 48.5%) (log-rank, P < .001). The calibration and predictive accuracy of the pre- and postoperative models were good in the training (C index: preoperative, 0.710; postoperative, 0.722) as well as the internal (C index: preoperative, 0.715; postoperative, 0.728; bootstrapping resamples, n = 5000) and external (C index: postoperative, 0.672) validation data sets.

Conclusion And Relevance: An easy-to-use online calculator was developed to help clinicians predict the chance of VER after curative-intent resection for ICC. The tool performed well on internal and external validation. This tool may help clinicians in the preoperative selection of patients for neoadjuvant therapy as well as during the postoperative period to inform surveillance strategies.
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http://dx.doi.org/10.1001/jamasurg.2020.1973DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7344787PMC
September 2020