Citations

Objective: To define benchmark values for liver transplantation (LT) in patients with perihilar cholangiocarcinoma (PHC) enabling unbiased comparisons. Background: Transplantation for PHC is used with reluctance in many centers and even contraindicated in several countries. Although benchmark values for LT are available, there is a lack of specific data on LT performed for PHC. Methods: PHC patients considered for LT after Mayo-like protocol were analyzed in 17 reference centers in 2 continents over the recent 5-year period (2014–2018). The minimum follow-up was 1 year. Benchmark patients were defined as operated at high-volume centers (≥50 overall LT/year) after neoadjuvant chemoradiotherapy, with a tumor diameter <3 cm, negative lymph nodes, and with the absence of relevant comorbidities. Benchmark cutoff values were derived from the 75th to 25th percentiles of the median values of all benchmark centers. Results: One hundred thirty-four consecutive patients underwent LT after completion of the neoadjuvant treatment. Of those, 89.6% qualified as benchmark cases. Benchmark cutoffs were 90-day mortality ≤5.2%; comprehensive complication index at 1 year of ≤33.7; grade ≥3 complication rates ≤66.7%. These values were better than benchmark values for other indications of LT. Five-year disease-free survival was largely superior compared with a matched group of nodal negative patients undergoing curative liver resection (n=106) (62% vs 32%, P<0.001). Conclusion: This multicenter benchmark study demonstrates that LT offers excellent outcomes with superior oncological results in early stage PHC patients, even in candidates for surgery. This provocative observation should lead to a change in available therapeutic algorithms for PHC.

Abstract The classification of myeloid neoplasms and acute leukemias was last updated in 2016 within a collaboration between the World Health Organization (WHO), the Society for Hematopathology, and the European Association for Haematopathology. This collaboration was primarily based on input from a clinical advisory committees (CACs) composed of pathologists, hematologists, oncologists, geneticists, and bioinformaticians from around the world. The recent advances in our understanding of the biology of hematologic malignancies, the experience with the use of the 2016 WHO classification in clinical practice, and the results of clinical trials have indicated the need for further revising and updating the classification. As a continuation of this CAC-based process, the authors, a group with expertise in the clinical, pathologic, and genetic aspects of these disorders, developed the International Consensus Classification (ICC) of myeloid neoplasms and acute leukemias. Using a multiparameter approach, the main objective of the consensus process was the definition of real disease entities, including the introduction of new entities and refined criteria for existing diagnostic categories, based on accumulated data. The ICC is aimed at facilitating diagnosis and prognostication of these neoplasms, improving treatment of affected patients, and allowing the design of innovative clinical trials.

Abstract Background: Genome-wide association studies (GWAS) of multiple myeloma in populations of European ancestry (EA) identified and confirmed 24 susceptibility loci. For other cancers (e.g., colorectum and melanoma), risk loci have also been associated with patient survival. Methods: We explored the possible association of all the known risk variants and their polygenic risk score (PRS) with multiple myeloma overall survival (OS) in multiple populations of EA [the International Multiple Myeloma rESEarch (IMMEnSE) consortium, the International Lymphoma Epidemiology consortium, CoMMpass, and the German GWAS] for a total of 3,748 multiple myeloma cases. Cox proportional hazards regression was used to assess the association between each risk SNP with OS under the allelic and codominant models of inheritance. All analyses were adjusted for age, sex, country of origin (for IMMEnSE) or principal components (for the others) and disease stage (ISS). SNP associations were meta-analyzed. Results: SNP associations were meta-analyzed. From the meta-analysis, two multiple myeloma risk SNPs were associated with OS (P &lt; 0.05), specifically POT1-AS1-rs2170352 [HR = 1.37; 95% confidence interval (CI) = 1.09–1.73; P = 0.007] and TNFRSF13B-rs4273077 (HR = 1.19; 95% CI = 1.01–1.41; P = 0.04). The association between the combined 24 SNP MM-PRS and OS, however, was not significant. Conclusions: Overall, our results did not support an association between the majority of multiple myeloma risk SNPs and OS. Impact: This is the first study to investigate the association between multiple myeloma PRS and OS in multiple myeloma.

9569 Background: Guidelines addressing melanoma in-transit metastasis (ITM) recommend immune checkpoint inhibitors (ICI) as a first-line treatment option, despite the fact that there are no efficacy data available from prospective trials for exclusively ITM disease. The aim of this study was to analyze the outcome of patients with ITM treated with ICI based on data from a large cohort of patients treated at international high‐volume melanoma centers. Methods: A multicenter retrospective cohort study of patients treated between January 2015 and December 2020 from Australia, Europe, and USA, evaluating treatment with ICI for ITM with or without nodal involvement (AJCC8 N1c, N2c and N3c) and without distant disease (M0). Patients were treated with PD-1 inhibitor (nivolumab or pembrolizumab) and/or CTLA-4 inhibitor (ipilimumab). We assessed response rates, progression-free survival (PFS), melanoma-specific survival (MSS) and overall survival (OS). Results: A total of 287 patients from 21 institutions in 8 countries were included. Immunotherapy was first-line treatment in 64 (22%) patients. Monotherapy with a PD-1 or CTLA-4 inhibitor was given in 233 (81%) and 23 (8%) patients respectively, while 31 (11%) received both in combination. Overall response rate was 56%, complete response (CR) rate 36% and progressive disease (PD) rate 32%. Median PFS was 10 months (95% CI 7.4-12.6 months) with a 1-, 2- and 5-year PFS rate of 48%, 33% and 18% respectively. Median MSS was not reached, and the 1-, 2- and 5-year MSS rates were 95%, 83% and 71% respectively. Conclusions: Systemic immunotherapy is an effective treatment for melanoma ITM. Future studies should evaluate the optimal role for systemic immunotherapy in the context of multimodality therapy including locoregional treatments such as surgery, intralesional therapy, and regional therapies.

Purpose: To perform a semiquantitative and quantitative analysis of interstitial lung disease (ILD), through computed tomography (CT), in different serological subgroups of idiopathic inflammatory myopathies (IIM) patients, to find radiologic and clinical differences of disease related to serology. Materials and Methods: This was a prospective study, which included 98 IIM patients, divided into serological subgroups: anti-aminoacyl-transfer-RNA-synthetases (anti-ARS) positive and myositis-specific autoantibodies (MSA) negative. For each baseline CT the total semiquantitative score of Warrick (WS) and the automated software (Computer-Aided Lung Informatics for Pathology Evaluation and Rating) quantitative scores interstitial lung disease % (ILD%) and vascular-related structure % (VRS%) were calculated. Pulmonary function tests included total lung capacity % (TLC%), forced vital capacity % (FVC%), and diffusing capacity of the lung for carbon monoxide % (DLCO%). Results: Inverse correlations (P<0.001) between the radiologic scores and the functional scores DLCO% and TLC% were found, the most relevant being between ILD% and DLCO% (ρ=−0.590), VRS% and DLCO% (ρ=−0.549), and WS and DLCO% (ρ=−0.471). Positive correlations between ILD% and VRS% (ρ=0.916; P<0.001), WS and ILD% (ρ=0.663; ρ<0.001), and WS and VRS% (ρ=0.637; P<0.001) were obtained. Statistically significant higher values of WS, ILD%, and VRS% were found in the anti-ARS group (WS=15; ILD%=11; VRS%=3.5) compared with the MSA negative one (WS=2.5; ILD%=0.84; VRS%=2.2). The nonspecific interstitial pneumonia pattern was dominant. No statistically significant differences emerged at pulmonary function tests. Conclusions: In this study, ILD in anti-ARS-positive and MSA-negative groups was defined through semiquantitative and quantitative analysis of lung CT. The inverse correlations between the radiologic scores and TLC% and DLCO% (P<0.001) confirm the role of lung CT in the evaluation of ILD in IIM.

Abstract Rationale Cardiovascular instability/collapse is a common peri-intubation event in patients who are critically ill. Objectives To identify potentially modifiable variables associated with peri-intubation cardiovascular instability/collapse (i.e., systolic arterial pressure &lt;65 mm Hg [once] or &lt;90 mm Hg for &gt;30 minutes; new/increased vasopressor requirement; fluid bolus &gt;15 ml/kg, or cardiac arrest). Methods INTUBE (International Observational Study to Understand the Impact and Best Practices of Airway Management In Critically Ill Patients) was a multicenter prospective cohort study of patients who were critically ill and undergoing tracheal intubation in a convenience sample of 197 sites from 29 countries across five continents from October 1, 2018, to July 31, 2019. Measurements and Main Results A total of 2,760 patients were included in this analysis. Peri-intubation cardiovascular instability/collapse occurred in 1,199 out of 2,760 patients (43.4%). Variables associated with this event were older age (odds ratio [OR], 1.02; 95% confidence interval [CI], 1.02–1.03), higher heart rate (OR, 1.008; 95% CI, 1.004–1.012), lower systolic blood pressure (OR, 0.98; 95% CI, 0.98–0.99), lower oxygen saturation as measured by pulse oximetry/Fi O2 before induction (OR, 0.998; 95% CI, 0.997–0.999), and the use of propofol as an induction agent (OR, 1.28; 95% CI, 1.05–1.57). Patients with peri-intubation cardiovascular instability/collapse were at a higher risk of ICU mortality with an adjusted OR of 2.47 (95% CI, 1.72–3.55), P &lt; 0.001. The inverse probability of treatment weighting method identified the use of propofol as the only factor independently associated with cardiovascular instability/collapse (OR, 1.23; 95% CI, 1.02–1.49). When administered before induction, vasopressors (OR, 1.33; 95% CI, 0.84–2.11) or fluid boluses (OR, 1.17; 95% CI, 0.96–1.44) did not reduce the incidence of cardiovascular instability/collapse. Conclusions Peri-intubation cardiovascular instability/collapse was associated with an increased risk of both ICU and 28-day mortality. The use of propofol for induction was identified as a modifiable intervention significantly associated with cardiovascular instability/collapse. Clinical trial registered with clinicaltrials.gov (NCT03616054).

Background: Measuring quality of care indicators is important for clinicians and decision making in health care to improve patient outcomes. Objective: The primary objective was to identify quality of care indicators for patients with upper tract urothelial carcinoma (UTUC) and to validate these in an international cohort treated with radical nephroureterectomy (RNU). The secondary objective was to assess the factors associated with failure to validate the pentafecta. Design: We performed a retrospective multicenter study of patients treated with RNU for EAU high-risk (HR) UTUC. Outcome measurements and statistical analysis: Five quality indicators were consensually approved, including a negative surgical margin, a complete bladder-cuff resection, the absence of hematological complications, the absence of major complications, and the absence of a 12-month postoperative recurrence. After multiple imputations and propensity-score matching, log-rank tests and a Cox regression were used to assess the survival outcomes. Logistic regression analyses assessed predictors for pentafecta failure. Results: Among the 1718 included patients, 844 (49%) achieved the pentafecta. The median follow-up was 31 months. Patients who achieved the pentafecta had superior 5-year overall- (OS) and cancer-specific survival (CSS) compared to those who did not (68.7 vs. 50.1% and 79.8 vs. 62.7%, respectively, all p < 0.001). On multivariable analyses, achieving the pentafecta was associated with improved recurrence-free survival (RFS), CSS, and OS. No preoperative clinical factors predicted a failure to validate the pentafecta. Conclusions: Establishing quality indicators for UTUC may help define prognosis and improve patient care. We propose a pentafecta quality criteria in RNU patients. Approximately half of the patients evaluated herein reached this endpoint, which in turn was independently associated with survival outcomes. Extended validation is needed.

Abstract Objectives To systematically review the psychometric properties of outcome measurement instruments used in ANCA-associated vasculitis (AAV). Methods Medline, EMBASE, Cochrane, Scopus and Web of Science were searched from inception to 14 July 2020 for validation studies of instruments used in AAV. Following the COnsensus-based Standards for the selection of health status Measurement INstruments (COSMIN) and OMERACT frameworks, different psychometric properties (validity, reliability, responsiveness and feasibility) were summarized. Risk of bias was assessed according to the COSMIN checklist. Results From 2505 articles identified, 32 met the predefined selection criteria, providing information on 22 instruments assessing disease activity (n = 7), damage (n = 2), activity and damage (n = 1), health-related quality of life (HRQoL; n = 9) and function (n = 3). Most of the instruments were tested in AAV as a group or in granulomatosis with polyangiitis only. The BVAS, any version, the Vasculitis Damage Index (VDI) and the AAV-Patient-Reported Outcome (AAV-PRO) have been more extensively validated than the other instruments. BVAS for Wegener Granulomatosis (BVAS/WG) has been shown to be valid for measuring disease activity [correlation with Physician global assessment (r = 0.90)], reliability (inter-observer intraclass correlation coefficient = 0.97), responsiveness and feasibility. For damage, VDI was shown to be moderately valid (correlations with BVAS version 3 at 6 months r = 0.14, BVAS/WG at 1 year r = 0.40 and 5 years r = 0.20), and feasible. For HRQoL, AAV-PRO demonstrated validity (correlations of the six AAV-PRO domains with EQ-5D-5L: −0.78 to −0.55; discrimination between active disease and remission, P &lt; 0.0001 for all comparisons). The overall performance of instruments assessing function was low-to-moderate. Conclusion Among the 22 outcome measurement instruments used for AAV, BVAS (any version), VDI and AAV-PRO had the strongest psychometric properties.