Publications by authors named "Matthew J Weiss"

210 Publications

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

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

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
October 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) 2020 Sep 7. Epub 2020 Sep 7.

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
September 2020

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

Cancer Lett 2020 Nov 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

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

Radical antegrade modular pancreatosplenectomy versus standard distal pancreatosplenectomy for pancreatic cancer, a dual-institutional analysis.

Chin Clin Oncol 2020 Aug 16;9(4):54. Epub 2020 Jun 16.

Department of Surgery, Johns Hopkins Hospital, Baltimore, Maryland, USA.

Background: Radical antegrade modular pancreatosplenectomy (RAMPS) has been adopted by some surgeons in the treatment of left-sided pancreatic cancer (PDAC). Low disease incidence and heterogenous disease biology make robust prospective comparison of RAMPS and standard distal pancreatosplenectomy (DPS) difficult.

Methods: Consecutive cases of chemo-naïve patients undergoing open RAMPS and DPS for PDAC between 2010-2017 at two international high-volume pancreatectomy centers were compared. Cox proportional hazard modeling was utilized for multivariate analysis.

Results: We identified 193 DPS and 253 RAMPS during the study period. DPS was associated with higher rates of median estimated blood loss (500 vs. 300 cc, P<0.001), median total harvested lymph nodes (18 vs. 12, P<0.001) and R0 resection (94.3% vs. 88.9%, P=0.013). There were no differences in rates of postoperative pancreatic fistula (16.5% vs. 17.8%, P=1) or postoperative hemorrhage (5.9% vs. 3.6%, P=0.385) (DPS vs. RAMPS). After controlling for significant clinical pathological parameters, RAMPS was associated with non-superior recurrence-free survival (RFS) (HR 0.29; 95% CI, 0.07-1.27, P=0.101) and overall-survival (HR 1.03; 95% CI, 0.71-1.49, P=0.895) compared with DPS. Similar results were observed in node-positive patients.

Conclusions: RAMPS is safe and effective in the treatment of PDAC, but is not associated with an improvement in either RFS or overall-survival over DPS.
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http://dx.doi.org/10.21037/cco-20-6DOI Listing
August 2020

Response to Bernat and Delmonico.

Transplantation 2020 07;104(7):e217

Medical Director of Transplantation, Transplant Québec, Montreal, QC, Canada.

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http://dx.doi.org/10.1097/TP.0000000000003184DOI Listing
July 2020

Yttrium-90 Radioembolization in Intrahepatic Cholangiocarcinoma: A Multicenter Retrospective Analysis.

J Vasc Interv Radiol 2020 Jul 28;31(7):1035-1043.e2. Epub 2020 May 28.

Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Room E.01.1.29, Internal Mail E01.132, P.O. 85500, 3508 GA Utrecht, The Netherlands. Electronic address:

Purpose: To report outcomes of yttrium-90 (Y) radioembolization in patients with unresectable intrahepatic cholangiocarcinoma (ICC).

Materials And Methods: Retrospective review was performed of 115 patients at 6 tertiary care centers; 92 were treated with resin microspheres (80%), 22 were treated with glass microspheres (19%), and 1 was treated with both. Postintervention outcomes were compared between groups with χ tests. Survival after diagnosis and after treatment was assessed by Kaplan-Meier method.

Results: Grade 3 laboratory toxicity was observed in 4 patients (4%); no difference in toxicity profile between resin and glass microspheres was observed (P = .350). Clinical toxicity per Society of Interventional Radiology criteria was noted in 29 patients (25%). Partial response per Response Evaluation Criteria In Solid Tumors 1.1 was noted in 25% of patients who underwent embolization with glass microspheres and 3% of patients who were treated with resin microspheres (P = .008). Median overall survival (OS) from first diagnosis was 29 months (95% confidence interval [CI], 21-37 mo) for all patients, and 1-, 3-, and 5-year OS rates were 85%, 31%, and 8%, respectively. Median OS after treatment was 11 months (95% CI, 8-13 mo), and 1- and 3-year OS rates were 44% and 4%, respectively. These estimates were not significantly different between resin and glass microspheres (P = .730 and P = .475, respectively). Five patients were able to undergo curative-intent resection after Y radioembolization (4%).

Conclusions: This study provides observational data of treatment outcomes after Y radioembolization in patients with unresectable ICC.
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http://dx.doi.org/10.1016/j.jvir.2020.02.008DOI Listing
July 2020

Risk Factors for Complications Requiring Interventional Radiological Treatment After Hepatectomy.

J Gastrointest Surg 2020 May 27. Epub 2020 May 27.

Department of Radiology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Purpose: To identify perioperative factors that are significantly associated with complications requiring interventional radiology (IR) treatment after hepatectomy.

Methods: We retrospectively reviewed data from 11,243 patients in the USA who underwent hepatectomy from 2014 to 2016 using the National Surgical Quality Improvement Program database. Data on the following IR procedures were extracted: abscess drain placement, endovascular treatment for bleeding, and postoperative percutaneous biliary drain (PBD) placement up to 30 days postoperatively. Patients' clinical and intraoperative factors were examined. Population, univariate, and multivariable analyses were performed. P < 0.05 was considered significant.

Results: A total of 704 patients (6%) required IR treatment postoperatively, and 10,539 patients (94%) did not. On multivariable analysis, biliary reconstruction was a significant predictor of postoperative abscess drain placement (hazard ratio (HR), 3.5; 95% confidence interval (CI) 1.8, 6.5; P < .001), endovascular treatment for bleeding (HR, 3.3; 95% CI 1.4, 7.8 P = .006), and postoperative PBD placement (HR, 2.9; 95% CI 1.9, 4.2; P < .001). Compared with hepatectomy without biliary reconstruction, hepatectomy with biliary reconstruction was associated with significantly higher rates of complications treated with IR procedures (26% vs. 4.9%) and death within 30 days (6.0% vs. 1.2%) (both, P < .001).

Conclusion: Biliary reconstruction is a strong predictor of the need for postoperative IR treatment after hepatectomy. One in four patients who underwent biliary reconstruction required IR treatment of a complication during the first 30 days after hepatectomy.
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http://dx.doi.org/10.1007/s11605-020-04609-3DOI Listing
May 2020

Management of the neurologically deceased organ donor: A Canadian clinical practice guideline.

CMAJ 2020 04;192(14):E361-E369

Departments of Medicine (Ball), Internal Medicine (Basmaji) and Surgery (Luke), Western University, London, Ont.; Children's Hospital of Eastern Ontario Research Institute (Hornby); Deceased Donation (Hornby, Shemie, Wilson), Canadian Blood Services, Ottawa, Ont.; Department of Medicine (Division of Critical Care) and Department of Health Research Methods, Evidence and Impact (Rochwerg, Meade), McMaster University, Hamilton, Ont.; Faculté de médecine (Weiss), Université Laval; Transplant Quebec (Weiss), Québec, Que.; Canadian Blood Services (Gillrie), Ottawa, Ont.; Department of Medicine and School of Public Health (Chassé), University of Montreal, Montréal, Que.; Department of Anesthesiology, Faculty of Medicine and Health Sciences (D'Aragon), University of Sherbrooke, Sherbrooke, Que.; Critical Care (Soliman), Queen's University, Kingston, Ont.; Latner Thoracic Surgery Research Laboratories, Institute of Medical Sciences (Ali), University of Toronto, Toronto, Ont.; Northern Ontario School of Medicine (Arora), Thunder Bay, Ont.; Department of Medicine (Neurology) and Critical Care, Centre for Neuroscience Studies (Boyd), Queen's University, Kingston, Ont.; Department of Medicine (Cantin), Université Laval, Québec, Que.; Gerald Bronfman Department of Oncology (Cantin), McGill University, Montréal, Que.; Departments of Surgery (Cypel) and Medicine (Singh), University of Toronto, Toronto, Ont.; Division of Cardiac Surgery (Freed), University of Alberta, Edmonton, Alta.; Faculty of Pharmacy (Frenette), University of Montreal, Montréal, Que.; Alberta Health Services (Hruska), Calgary, Alta.; Department of Critical Care Medicine (Karvellas), University of Alberta, Edmonton, Alta.; BC Transplant (Keenan), Vancouver, BC; Division of Critical Care (Keenan), University of British Columbia, Vancouver, BC; Departments of Critical Care Medicine and Clinical Neurosciences, Hotchkiss Brain Institute (Kramer), University of Calgary, Calgary, Alta.; Faculty of Medicine and Dentistry (Kutsogiannis), University of Alberta, Edmonton, Alta.; Department of Medicine (Lien), University of Alberta, Edmonton, Alta.; London Health Sciences Centre (Luke), London, Ont.; Department of Pediatrics (Mahoney), University of Calgary, Calgary, Alta.; Division of Infectious Diseases (Wright), University of British Columbia, Vancouver, BC; Division of Nephrology (Zaltzman), University of Toronto, Toronto, Ont.; Department of Pediatrics (Shemie), McGill University, Montréal, Que.

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http://dx.doi.org/10.1503/cmaj.190631DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7145376PMC
April 2020

Ensuring nondiscrimination in pandemic prioritization decisions.

CMAJ 2020 04;192(15):E421

Pediatric intensive care unit chief, Children's Hospital of Eastern Ontario, Ottawa, Ont.

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http://dx.doi.org/10.1503/cmaj.75254DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7162440PMC
April 2020

Reaching out to understand.

Authors:
Matthew J Weiss

Pediatr Transplant 2020 05;24(3):e13681

Pediatric Intensivist, Centre Mère-Enfant Soleil du CHU de Québec, Transplant Québec, Quebec, QC, Canada.

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http://dx.doi.org/10.1111/petr.13681DOI Listing
May 2020

Recurrence in Patients Achieving Pathological Complete Response After Neoadjuvant Treatment for Advanced Pancreatic Cancer.

Ann Surg 2019 Nov 25. Epub 2019 Nov 25.

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

Objective: The aim of this study was to characterize the patterns and treatment of disease recurrence in patients achieving a pathological complete response (pCR) following neoadjuvant chemoradiation for advanced pancreatic ductal adenocarcinoma (PDAC).

Summary Of Background Data: A pCR is an independent predictor for improved survival in PDAC. However, disease recurrence is still observed in these patients.

Methods: Patients with advanced PDAC who were treated with neoadjuvant therapy and had a pCR were identified between 2009 and 2017. Overall survival (OS) was determined from the initiation of neoadjuvant, disease-free survival (DFS) from the date of surgery, and post-recurrence survival (PRS) from the date of recurrence. Factors associated with recurrence were analyzed using a Cox-regression model.

Results: Of 331 patients with borderline resectable or locally advanced PDAC, 30 achieved a pCR following neoadjuvant treatment and pancreatectomy. The median DFS for pCR patients was 29 months and OS 76 months. Recurrence was observed in 14 patients. No clinicopathologic or treatment characteristics were associated with survival. The median PRS following recurrence was 25 months. Treatment following recurrence included chemotherapy, radiation or ablation, and surgical resection. Hepatectomy or completion pancreatectomy was accomplished in 2 patients that remain alive 13 and 62 months, respectively, following metastasectomy.

Conclusions: A pCR following neoadjuvant therapy in patients with advanced PDAC is associated with remarkable survival, although recurrence occurs in about half of patients. Nevertheless, patients with pCR and recurrence respond well to treatment and survival remains encouraging. Advanced molecular characterization and longitudinal liquid biopsy may offer additional assistance with understanding tumor biologic behavior after achieving a pCR.
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http://dx.doi.org/10.1097/SLA.0000000000003570DOI Listing
November 2019

Role of Lymph Node Resection and Histopathological Evaluation in Accurate Staging of Nonfunctional Pancreatic Neuroendocrine Tumors: How Many Are Enough?

J Gastrointest Surg 2021 Feb 5;25(2):428-435. Epub 2020 Feb 5.

Department of Surgery, The Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Halsted 614, Baltimore, MD, 21287, USA.

Background: Nodal involvement has been identified as one of the strongest prognostic factors in patients with nonfunctional pancreatic neuroendocrine tumors (NF-PanNETs). Sufficient lymphadenectomy and evaluation is vital for accurate staging. The purpose of this study was to identify the optimal number of examined lymph nodes (ELN) required for accurate staging.

Methods: The SEER database was used to identify patients with resected NF-PanNETs between 2004 and 2014. The distributions of positive lymph nodes (PLN) ratio and total lymph nodes were used to develop a mathematical model. The sensitivity of detecting nodal disease at each cutoff of ELN was estimated and used to identify the optimal cutoff for ELN.

Results: A total of 1098 patients were included in the study of which 391 patients (35.6%) had nodal disease. The median ELN was 12 (interquartile range [IQR]: 7-19.5), and the median PLN was 2 (IQR: 1-4) for patients with nodal disease. With an increase in ELN, the sensitivity of detecting nodal disease increased from 12.0% (ELN: 1) to 92.2% (ELN: 20), plateauing at 20 ELN (< 1% increase in sensitivity with an additional ELN). This sensitivity increase pattern was similar in subgroup analyses with different T stages.

Conclusions: The sensitivity of detecting nodal disease in patients with NF-PanNETs increases with an increase in the number of ELN. Cutoffs for adequate nodal assessment were defined for all T stages. Utilization of these cutoffs in clinical settings will help with patient prognostication and management.
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http://dx.doi.org/10.1007/s11605-020-04521-wDOI Listing
February 2021

A systematic review of surgical resection of liver-only synchronous metastases from pancreatic cancer in the era of multiagent chemotherapy.

Updates Surg 2020 Mar 29;72(1):39-45. Epub 2020 Jan 29.

Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute, Milan, Italy.

Recent studies considered surgery as a treatment option for patients with pancreatic ductal adenocarcinoma (PDAC) and synchronous liver metastases. The aim of this study was to evaluate systematically the literature on the role of surgical resection in this setting as an upfront procedure or following primary chemotherapy. A systematic search was performed of PubMed, Embase and the Cochrane Library in accordance with PRISMA guidelines. Only studies that included patients with synchronous liver metastases published in the era of multiagent chemotherapy (after 2011) were considered, excluding those with lung/peritoneal metastases or metachronous liver metastases. Median overall survival (OS) was the primary outcome. Six studies with 204 patients were analyzed. 63% of patients underwent upfront pancreatic and liver resection, 35% had surgery after primary chemotherapy with strict selection criteria and 2% had an inverse approach (liver surgery first). 38 patients (18.5%) did not undergo any liver resection since metastases disappeared after chemotherapy. Postoperative mortality was low (< 2%). Median OS ranged from 7.6 to 14.5 months after upfront pancreatic/liver resection and from 34 to 56 months in those undergoing preoperative treatment. This systematic review suggests that surgical resection of pancreatic cancer with synchronous liver oligometastases is safe, and it can be associated with improved survival, providing a careful selection of patients after primary chemotherapy.
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http://dx.doi.org/10.1007/s13304-020-00710-zDOI Listing
March 2020

Attitudes of healthcare providers towards cardiac donation after circulatory determination of death: a Canadian nation-wide survey.

Can J Anaesth 2020 03 2;67(3):301-312. Epub 2020 Jan 2.

Department of Medicine, Western University, London Health Sciences Centre, London, ON, Canada.

Purpose: The number of patients on cardiac transplant waitlists exceeds the number of available donor organs. Cardiac donation is currently limited to those declared dead by neurologic criteria in all but three countries. Cardiac donation after circulatory determination of death (cardiac DCDD) can be conducted using direct procurement and perfusion (DPP) or normothermic regional perfusion (NRP). Implementation of cardiac DCDD in many countries has been slowed by ethical debates within the donation and transplantation community. We conducted a national survey to determine the perceptions of healthcare providers regarding cardiac DCDD.

Methods: We conducted an electronic survey of 398 healthcare providers who are involved in the management of heart donors and/or heart transplant recipients in Canada (226 nurses, 82 critical care physicians, 31 donation specialists, and 59 transplant specialists). Our primary outcomes were their attitudes towards and concerns regarding cardiac DCDD protocols and their implementation in Canada. We distributed the survey electronically through several Canadian donation and transplantation organizations.

Results: We identified that 361 of 391 respondents (92.3%; 95% confidence interval [CI], 89.6 to 95.1) believed that DPP is acceptable, and 329 of 377 respondents (87.3%; 95% CI, 83.9 to 90.7) supported its implementation in Canada. We found that 301 of 384 respondents (78.4%; 95% CI, 74.2 to 82.6) believed that NRP is acceptable and 266 of 377 respondents (70.6%; 95% CI, 66.0 to 75.2) supported its implementation in Canada.

Conclusion: This is the first survey describing the attitudes of healthcare providers towards cardiac DCDD. We identified widespread support for cardiac DCDD and its implementation in Canada among Canadian healthcare providers within the organ donation and transplantation community in Canada.
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http://dx.doi.org/10.1007/s12630-019-01559-6DOI Listing
March 2020

Acceptability of cardiac donation after circulatory determination of death: a survey of the Canadian public.

Can J Anaesth 2020 03 2;67(3):292-300. Epub 2020 Jan 2.

Department of Medicine, London Health Sciences Centre, Western University, London, ON, Canada.

Purpose: Cardiac transplantation is a definitive therapy for end-stage heart failure, but demand exceeds supply. Cardiac donation after circulatory determination of death (cardiac DCDD) can be performed using direct procurement and perfusion (DPP), where cardiac activity is restored after heart recovery, or (NRP), where brain blood supply is surgically interrupted, circulation to the thoraco-abdominal organs is restored within the donor's body, followed by heart recovery. While cardiac DCDD would increase the number of heart donors, uptake of programs has been slowed in part because of ethical concerns within the medical community. These debates have been largely devoid of discussion regarding public perceptions. We conducted a national survey of public perceptions regarding cardiac DCDD.

Methods: We surveyed 1,001 Canadians about their attitudes towards cardiac DCDD using a rigorously designed and pre-tested survey.

Results: We found that 843 of 1,001 respondents (84.2%; 95% confidence interval [CI], 81.8 to 86.3) accepted the DPP approach, 642 (64.1%; 95% CI, 61.1 to 67.0) would agree to donate their heart using DPP, and 696 (69.5%; 95% CI, 66.6 to 72.3) would consent to the same for a family member. We found that 779 respondents of 1,001 respondents (77.8%; 95% CI, 75.1 to 80.3) accepted the NRP approach, 587 (58.6%; 95% CI, 55.5 to 61.6) would agree to donate their heart using NRP, and 636 (63.5%; 95% CI, 60.5 to 66.4) would consent to the same for a family member. Most respondents supported the implementation of DPP (738 respondents or 73.7%; 95% CI, 70.9 to 76.3) and NRP (655 respondents or 65.4%; 95% CI, 62.4 to 68.3) in Canada.

Conclusion: The results of this national survey of public attitudes towards cardiac DCDD will inform the implementation of cardiac DCDD programs in a manner that is consistent with public values.
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http://dx.doi.org/10.1007/s12630-019-01560-zDOI Listing
March 2020

The impact of high body mass index on patients undergoing robotic pancreatectomy: A propensity matched analysis.

Surgery 2020 03 11;167(3):556-559. Epub 2019 Dec 11.

Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD; The Pancreatic Cancer Precision Medicine Center of Excellence Program, The Johns Hopkins University School of Medicine, Baltimore, MD. Electronic address:

Background: Patients with high body mass index are associated with a higher risk of complications after open pancreatectomy. We aimed to investigate the perioperative outcome for patients with high body mass index after robotic pancreatectomy.

Methods: This is a retrospective, propensity-score matched cohort analysis. From our prospectively maintained database, we identified consecutive patients with body mass index >25 who underwent robotic pancreatectomy between January 2016 and December 2018. Propensity score matching with open pancreatectomy was applied in 1:2 fashion based on age, gender, American Society of Anesthesiologists classification, surgery type, histology, neoadjuvant therapy, and body mass index during the same study period.

Results: A total of 127 patients were included. The mean age for all patients was 61.7 ± 12.8 years and 65 (51.2%) were male. Median body mass index was 29.9 (interquartile range, 27.0-31.8) for both groups. Propensity score matching provided equally distributed general demographic and clinicopathological factors. Robotic pancreatectomy was associated with decreased blood loss (100 mL vs 300 mL, P < .001) and shorter hospital stay (7 vs 9 days, P = .019).

Conclusion: Robotic pancreatectomy is associated with decreased blood loss and shorter length of hospital stay in overweight patients. Robotic approach may help alleviate morbidity in overweight patients undergoing pancreatectomy.
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http://dx.doi.org/10.1016/j.surg.2019.11.002DOI Listing
March 2020