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Context.— Resident physicians face a higher rate of burnout and depression than the general population. Few studies have examined burnout and depression in Canadian laboratory medicine residents, and none during the COVID-19 pandemic. Objective.— To identify the prevalence of burnout and depression, contributing factors, and the impact of COVID-19 in this population. Design.— An electronic survey was distributed to Canadian laboratory medicine residents. Burnout was assessed using the Oldenburg Burnout Inventory. Depression was assessed using the Patient Health Questionnaire 9. Results.— Seventy-nine responses were collected. The prevalence of burnout was 63% (50 of 79). The prevalence of depression was 47% (37 of 79). Modifiable factors significantly associated with burnout included career dissatisfaction, below average academic performance, lack of time off for illness, stress related to finances, lack of a peer or staff physician mentor, and a high level of fatigue. Modifiable factors significantly associated with depression further included a lack of access to wellness resources, lack of time off for leisure, and fewer hours of sleep. Fifty-five percent (41 of 74) of participants reported direct impacts to their personal circumstances by the COVID-19 pandemic. Conclusions.— Burnout and depression are significant issues affecting Canadian laboratory medicine residents. As the COVID-19 pandemic continues, we recommend the institution of flexible work arrangements, protected time off for illness and leisure, ongoing evaluation of career satisfaction, formal and informal wellness programming with trainee input, formal mentorship programming, and a financial literacy curriculum as measures to improve trainee wellness.

Tumor budding (TB) and poorly differentiated clusters (PDCs) are powerful prognostic factors in colorectal cancer (CRC). Despite their morphologic and biological overlap, TB and PDC are assessed separately and are distinguished by an arbitrary cutoff for cell cluster size. This cutoff can be challenging to apply in practice and its biological significance remains unclear. We developed a novel scoring system that incorporates TB and PDC into a single parameter ("Combined Score"; CS), eliminating the need for such cutoffs and allowing the prognostic value of PDC to be captured alongside TB. In a cohort of 481 stage I-III CRC resections, CS was significantly associated with American Joint Committee on Cancer (AJCC) stage, T-stage, N-stage, histologic grade, tumor deposits, lymphovascular invasion, and perineural invasion ( Plt;0.0001). In addition, CS was significantly associated with decreased 5-year recurrence-free survival, overall survival, and disease-specific survival ( Plt;0.0001). TB and PDC showed similar associations with oncologic outcomes, with hazard ratios consistently lower than for CS. The association between CS and oncologic outcomes remained significant in subgroup analyses stratified by AJCC stage, anatomic location (rectum/colon) and neoadjuvant therapy status. On multivariable analysis, CS retained its significant association with oncologic outcomes ( P =0.0002, 0.005, and 0.009) for recurrence-free survival, disease-specific survival, and overall survival, respectively. In conclusion, CS provides powerful risk stratification in CRC which is at least equivalent to that of TB and PDC assessed individually. If validated elsewhere, CS has practical advantages and a biological rationale that may make it an attractive alternative to assessing these features separately.

Venous invasion (VI) is a powerful prognostic factor in colorectal cancer (CRC) that is widely underreported. The ability of elastin stains to improve VI detection is now recognized in several international CRC pathology protocols. However, concerns related to the cost and time required to perform and evaluate these stains in addition to routine hematoxylin and eosin (HE) stains remains a barrier to their wider use. We therefore sought to determine whether an elastin trichrome (ET) stain could be used as a "stand-alone" stain in CRC resections, by comparing the sensitivity, accuracy, and reproducibility of detection of CAP-mandated prognostic factors using ET and HE stains. Representative HE- and ET-stained slides from 50 CRC resections, including a representative mix of stages and prognostic factors, were used to generate 2 study sets. Each case was represented by HE slides in 1 study set and by corresponding ET slides from the same blocks in the other study set. Ten observers (3 academic gastrointestinal [GI] pathologists, 4 community pathologists, 3 fellows) evaluated each study set for CAP-mandated prognostic factors. ET outperformed HE in the assessment of VI with respect to detection rates (50% vs. 28.6%; P0.0001), accuracy (82% vs. 59%, P0.0001), and reproducibility (k=0.554 vs. 0.394). No significant differences between ET and HE were observed for other features evaluated. In a poststudy survey, most observers considered the ease and speed of assessment at least equivalent for ET and HE for most prognostic factors, and felt that ET would be feasible as a stand-alone stain in practice. If validated by others, our findings support the use of ET, rather than HE, as the primary stain for the evaluation of CRC resections.

Resident physicians face a higher rate of burnout and depression than the general population. Few studies have examined burnout and depression in Canadian laboratory medicine residents, and none during the COVID-19 pandemic.To identify the prevalence of burnout and depression, contributing factors, and the impact of COVID-19 in this population.An electronic survey was distributed to Canadian laboratory medicine residents. Burnout was assessed using the Oldenburg Burnout Inventory. Depression was assessed using the Patient Health Questionnaire 9.Seventy-nine responses were collected. The prevalence of burnout was 67% (50 of 79). The prevalence of depression was 47% (37 of 79). Modifiable factors significantly associated with burnout included career dissatisfaction, below average academic performance, lack of time off for illness, stress related to finances, lack of a peer or staff physician mentor, and a high level of fatigue. Modifiable factors significantly associated with depression further included a lack of access to wellness resources, lack of time off for leisure, and fewer hours of sleep. Fifty-five percent (41 of 74) of participants reported direct impacts to their personal circumstances by the COVID-19 pandemic.Burnout and depression are significant issues affecting Canadian laboratory medicine residents. As the COVID-19 pandemic continues, we recommend the institution of flexible work arrangements, protected time for illness and leisure, ongoing evaluation of career satisfaction, formal and informal wellness programming with trainee input, formal mentorship programming, and a financial literacy curriculum as measures to improve trainee wellness.

To examine whether quantitative pathologic analysis of digitized hematoxylin and eosin slides of colorectal carcinoma (CRC) correlates with clinicopathologic features, molecular alterations, and prognosis.A quantitative segmentation algorithm (QuantCRC) was applied to 6468 digitized hematoxylin and eosin slides of CRCs. Fifteen parameters were recorded from each image and tested for associations with clinicopathologic features and molecular alterations. A prognostic model was developed to predict recurrence-free survival using data from the internal cohort (n = 1928) and validated on an internal test (n = 483) and external cohort (n = 938).There were significant differences in QuantCRC according to stage, histologic subtype, grade, venous/lymphatic/perineural invasion, tumor budding, CD8 immunohistochemistry, mismatch repair status, KRAS mutation, BRAF mutation, and CpG methylation. A prognostic model incorporating stage, mismatch repair, and QuantCRC resulted in a Harrell's concordance (c)-index of 0.714 (95% confidence interval [CI], 0.702-0.724) in the internal test and 0.744 (95% CI, 0.741-0.754) in the external cohort. Removing QuantCRC from the model reduced the c-index to 0.679 (95% CI, 0.673-0.694) in the external cohort. Prognostic risk groups were identified, which provided a hazard ratio of 2.24 (95% CI, 1.33-3.87, P = .004) for low vs high-risk stage III CRCs and 2.36 (95% CI, 1.07-5.20, P = .03) for low vs high-risk stage II CRCs, in the external cohort after adjusting for established risk factors. The predicted median 36-month recurrence rate for high-risk stage III CRCs was 32.7% vs 13.4% for low-risk stage III and 15.8% for high-risk stage II vs 5.4% for low-risk stage II CRCs.QuantCRC provides a powerful adjunct to routine pathologic reporting of CRC. A prognostic model using QuantCRC improves prediction of recurrence-free survival.

Venous invasion (VI) is a powerful yet underreported prognostic factor in colorectal cancer (CRC). Its detection can be improved with an elastin stain. We evaluated the impact of routine elastin staining on VI detection in resected CRC and its relationship with oncologic outcomes. Pathology reports from the year before (n=145) and the year following (n=128) the implementation of routine elastin staining at our institution were reviewed for established prognostic factors, including VI. A second review, using elastin stains, documented the presence/absence, location, number, and size of VI foci. The relationship between VI and oncologic outcomes was evaluated for original and review assessments. VI detection rates increased from 21% to 45% following implementation of routine elastin staining (odds ratio [OR]=3.1; 95% confidence interval [CI]: 1.8-5.3; P

AIMS To develop and validate a deep learning algorithm to quantify a broad spectrum of histological features in colorectal carcinoma. METHODS AND RESULTS A deep learning algorithm was trained on haematoxylin and eosin-stained slides from tissue microarrays of colorectal carcinomas (N = 230) to segment colorectal carcinoma digitised images into 13 regions and one object. The segmentation algorithm demonstrated moderate to almost perfect agreement with interpretations by gastrointestinal pathologists, and was applied to an independent test cohort of digitised whole slides of colorectal carcinoma (N = 136). The algorithm correctly classified mucinous and high-grade tumours, and identified significant differences between mismatch repair-proficient and mismatch repair-deficient (MMRD) tumours with regard to mucin, inflammatory stroma, and tumour-infiltrating lymphocytes (TILs). A cutoff of >44.4 TILs per mm2 carcinoma gave a sensitivity of 88% and a specificity of 73% in classifying MMRD carcinomas. Algorithm measures of tumour budding (TB) and poorly differentiated clusters (PDCs) outperformed TB grade derived from routine sign-out, and compared favourably with manual counts of TB/PDCs with regard to lymphatic, venous and perineural invasion. Comparable associations were seen between algorithm measures of TB/PDCs and manual counts of TB/PDCs for lymph node metastasis (all P

Poorly differentiated clusters (PDC), defined as small groups of ≥5 tumour cells without glandular differentiation, have gained recent attention as a promising prognostic factor in colorectal cancer (CRC). Numerous studies have shown PDC to be significantly associated with other adverse histopathological features and worse clinical outcomes. PDC may hold particular promise in stage II colon cancer, where risk stratification plays a critical role in patient selection for adjuvant chemotherapy. In addition, emerging evidence suggests that PDC can predict lymph node metastasis in endoscopically resected pT1 CRC, potentially helping the selection of patients for oncological resection. In 'head-to-head' comparisons, PDC grade has consistently outperformed conventional histological grading systems both in terms of risk stratification and reproducibility. With a number of large-scale studies now available, this review evaluates the evidence regarding the prognostic significance of PDC, considers its relationship with other emerging invasive front prognostic markers (such as tumour budding and stroma type), assesses its 'practice readiness', addressing issues such as interobserver reproducibility, scoring methodologies and special histological subtypes (e.g. micropapillary and mucinous carcinoma), and draws attention to ongoing challenges and areas in need of further study. Finally, emerging data on the role of PDC in non-colorectal cancers are briefly considered.

Selection was initially site-dependent, which then evolved into a partially voluntary basis, made in collaboration with the Post-Graduate Medical Education Office (PGME), AP Residency Program Committee, and the AP resident body. Resident representatives noted that these were due to technical reasons such as lack of appropriate hardware, spotty connectivity, and the inconsistent use of different devices ranging from smartphones to desktop computers. [...]in-person teaching with glass slides became challenging as sign-outs using multiheaded microscopes were discontinued across most training sites. A recent review on the psychological impacts of COVID-19 on health care workers found that depression, anxiety, and other psychological distresses affect a quarter to a third of health care workers.4 Our program widely promoted and supported formal and informal wellness initiatives, including online wellness resources, a virtual trivia night, distribution of jackets with the U of T AP logo to all trainees, physically distanced outdoor and virtual parties for incoming and graduating residents, and a wellness photo social media competition. Carlo Hojilla, MD, PhD1,2;Susan Armstrong, MD, PhD1;Cherry Pun, MD1;Tyler Bruce Malcolm Hickey, MD, PhD1,3;Ozgur Mete, MD14;Rachel Han, MD1;Elan Hahn, MD1;Sameer Shivji, MD2;Susan Done, MA, MB, BChir MBA, PhD1,4;Fang-I Lu, MD1,5 1Department of Laboratory Medicine and Pathobiology, University of Toronto, Ontario, Canada;2Department of Pathology & Laboratory Medicine, Sinai Health System, Toronto, Ontario, Canada;3Ontario Forensic Pathology Service, Toronto, Ontario, Canada;4Laboratory Medicine Program, Department of Anatomical Pathology, University Health Network, Toronto, Ontario, Canada;5Department of Laboratory Medicine and Molecular Diagnostics, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada Accepted for publication April 8, 2021.

114 Background: ExtraMural Venous Invasion (EMVI) is considered an indicator of poor prognosis in patients who have undergone resection of primary CRC, but its use has not been widely adopted in staging systems or nomograms. Staining for elastin may facilitate the accurate detection of EMVI and minimize interobserver variability, as well as enable the assessment of specific features of EMVI including focality and size. We examined the prognostic potential of EMVI detected by elastin staining at a tertiary center that performs a high volume of CRC resections. Methods: This is a single-institution, observational study of consecutive patients who underwent resection of primary CRC between 01/2011 and 12/2016 (n=556). All pathology specimens were re-assessed by expert reviewers who were blinded to patient outcomes. Venous invasion was detected using an elastin trichrome stain and classified as IntraMural or ExtraMural. The number of VI foci, as well as the maximum foci width and length, were also determined. Disease-specific and recurrence-free survival (DSS, RFS) were estimated using the Kaplan-Meier method and group differences were assessed using the log-rank test. Cox proportional-hazard models were used to calculate hazard ratios (HR) and 95% CI. For the present analysis, patients with stage IV (n=86) CRC were excluded. Results: The cohort for analysis included 470 patients (264M, 206F; TNM 8th edition Stage I/II n=291; Stage III n=179) with a median follow-up time of 63 months (0.1-114). EMVI was detected in 33% of all cases (20% in Stage I/II vs. 55% in Stage III; p4 foci: HR 7.9; p