Feasibility and Performance of Elastin Trichrome as a Primary Stain in Colorectal Cancer Resection Specimens: Results of an Interobserver Variability Study.

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 (H&E) 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 H&E stains. Representative H&E- 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 H&E 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 H&E in the assessment of VI with respect to detection rates (50% vs. 28.6%; P<0.0001), accuracy (82% vs. 59%, P<0.0001), and reproducibility (k=0.554 vs. 0.394). No significant differences between ET and H&E 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 H&E 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 H&E, as the primary stain for the evaluation of CRC resections.

The impact of knowledge transfer on the detection of venous invasion in colorectal cancer.

Venous invasion (VI) is an independent predictor of hematogenous metastasis and mortality in colorectal cancer (CRC) yet remains widely underreported. Its detection may require recognition of subtle morphologic clues, which at times are only unmasked with an elastin stain. This study evaluates the impact of a knowledge transfer initiative (KTI) on VI detection in a "real-world" pathology practice setting. Following participation in an interobserver variability study of VI detection (Kirsch et al, 2013), 12 participants received educational materials highlighting key issues in VI detection. Eighteen months later, participants were invited to submit pathology reports from all CRC resections signed out 18 months prior to and 18 months following the KTI (n = 266 and n = 244, respectively). Nine pathologists participated. Reports were reviewed for VI and other established prognostic factors. Numbers of elastin stains and tumor-containing blocks were also recorded. Comparative analyses were adjusted for baseline differences in tumor, lymph node, and metastasis stage; tumor location; use of neoadjuvant therapy; and number of tumor-containing blocks. VI detection increased significantly post-KTI versus pre-KTI (39.3% versus 18.4%, adjusted odds ratio [OR] 2.86 [1.91-4.28], P < .001). Increased VI detection post-KTI was observed in both stage II (31.8% versus 12.5%, adjusted OR 3.27 [1.45-7.42], P = .004) and stage III CRC (62.4% versus 28.2%, adjusted OR 4.23 [2.37-7.55], P < .001). All pathologists demonstrated increased VI detection post-KTI. Use of elastin stains was significantly higher post-KTI versus pre-KTI (61.5% versus 5.3% of cases respectively, P < .001). This study demonstrates the effectiveness of knowledge transfer in increasing VI detection in routine pathology practice.

Interobserver variability in assessing dysplasia and architecture in colorectal adenomas: a multicentre Canadian study.

AIMS: Following the introduction of colorectal cancer screening programmes throughout Canada, it became necessary to standardise the diagnosis of colorectal adenomas. Canadian guidelines for standardised reporting of adenomas were developed in 2011. The aims of the present study were (a) to assess interobserver variability in the classification of dysplasia and architecture in adenomas and (b) to determine if interobserver variability could be improved by the adoption of criteria specified in the national guidelines. METHODS: An a priori power analysis was used to determine an adequate number of cases and participants. Twelve pathologists independently classified 40 whole-slide images of adenomas according to architecture and dysplasia grade. Following a wash-out period, participants were provided with the national guidelines and asked to reclassify the study set. RESULTS: At baseline, there was moderate interobserver agreement for architecture (K=0.4700; 95% CI 0.4427 to 0.4972) and dysplasia grade (K=0.5680; 95% CI 0.5299 to 0.6062). Following distribution of the guidelines, there was improved interobserver agreement in assessing architecture (K=0.5403; 95% CI 0.5133 to 0.5674)). For dysplasia grade, overall interobserver agreement remained moderate but decreased significantly (K=0.4833; 95% CI 0.4452 to 0.5215). Half of the cases contained high-grade dysplasia (HGD). Two pathologists diagnosed HGD in ≥75% of cases. CONCLUSIONS: The improvement in interobserver agreement in classifying adenoma architecture suggests that national guidelines can be useful in disseminating knowledge, however, the variability in the diagnosis of HGD, even following guideline review suggests the need for ongoing knowledge-transfer exercises.

Venous invasion in colorectal cancer: impact of an elastin stain on detection and interobserver agreement among gastrointestinal and nongastrointestinal pathologists.

Venous invasion (VI) is an independent prognostic indicator in colorectal cancer and may prompt consideration for adjuvant chemotherapy in patients with stage II tumors. Recent evidence suggests that VI is underreported in colorectal cancer and that detection may be enhanced by an elastin stain. This study aimed (1) to determine the impact of an elastin stain on VI detection and on interobserver agreement between gastrointestinal (GI) and non-GI pathologists, and (2) to identify factors associated with increased VI detection. Forty hematoxylin and eosin (H&E)-stained slides were circulated to 6 GI and 6 non-GI pathologists who independently assessed the VI status as positive, negative, or equivocal. Six weeks later, 40 corresponding Movat-stained slides were recirculated together with the original H&E slides and reassessed for VI status. Detection of VI was >2-fold higher with a Movat stain compared with an H&E stain alone (46.4% vs. 19.6%, P=0.001). GI pathologists detected VI more frequently than non-GI pathologists on both H&E (30.0% vs. 9.2%, P=0.029) and Movat (58.3% vs. 34.6%, P=0.018) stains. There was higher interobserver agreement in the case of a Movat stain, particularly for extramural VI (H&E: κ=0.23 vs. Movat: κ=0.41). A poststudy survey indicated that GI pathologists and non-GI pathologists applied similar diagnostic criteria but that GI pathologists more frequently applied "orphan arteriole" and "protruding tongue" signs as diagnostic clues to VI. This study confirms that VI is underdetected on H&E and highlights the role of elastin staining in improving VI detection and interobserver agreement. Strategies to improve VI detection are warranted.

Cancer Care Ontario Guidelines for radical prostatectomy: striving for continuous quality improvement in community practice.

OBJECTIVE: : Cancer Care Ontario has published an evidence-based guideline on their website "Guideline for Optimization of Surgical and Pathological Quality Performance for Radical Prostatectomy in Prostate Cancer Management: Surgical and Pathological Guidelines." The evidentiary base for this guideline was recently published in CUAJ. The CCO guideline proposes the following: a positive surgical margin (PSM) rate of <25% for organ-confined disease (pT2), a perioperative mortality of <1%, a rate of rectal injury <1%, and a blood transfusion rate <10% in non-anemic patients. The objective of this study was to review the radical prostatectomy practice at the Grey Bruce Health Services, an Ontario community hospital, and to compare our performance in relation to the Cancer Care Ontario guideline and the literature. METHODS: : We conducted a retrospective review of all radical prostatectomies performed at the Grey Bruce Health Services from January 1, 2006 to December 31, 2007. The following data were obtained from clinical records and pathology reports: patient age, pre-biopsy prostate-specific antigen, biopsy Gleason score, resected prostate gland weight, radical prostatectomy Gleason score, surgical margin status, pathological tumour stage (pT), lymph node dissection status, perioperative incidence of transfusion of blood products and if the patient was anemic (hemoglobin <140 g/L) preoperatively, incidence of rectal injury, and perioperative mortality within 30 days following surgery. RESULTS: : Using the method proposed by D'Amico, most patients undergoing radical prostatectomy were intermediate risk (62%), with a minority of low-risk (24%) and high-risk (14%) patients. The overall PSM rate was 37%. The rate of PSMs in organ-confined disease (pT2) was 26%. There was a statistically significant trend between increasing D'Amico risk category and increasing rate of PSM (Cochran-Armitage trend test, p = 0.023). There was a strong correlation between the pathological tumour stage and the rate of PSM (Cochran-Armitage trend test, p = 0.0003). The rate of blood transfusion in non-anemic patients was 6%. There was 1 patient (0.8%) who experienced a rectal injury. There were no perioperative deaths in our study group. CONCLUSION: : Our results show that a community hospital group can appropriately select patients to undergo radical prostatectomy, as well as achieve an acceptable rate of PSMs. We believe that ongoing critical appraisal and reflective practice are essential to improving surgical outcomes and providing quality care.

Prostate gland biopsies and prostatectomies: an Ontario community hospital experience.

OBJECTIVE: Transrectal ultrasound-guided core biopsies of the prostate gland and prostatectomies have become common procedures at many community hospitals in Canada, especially in the era of serum prostate-specific antigen (PSA) screening for prostate cancer. The Gleason grading of prostate cancer in biopsies and prostatectomies is a major determinant used for treatment planning. There is evidence in the literature that suggests important discordance between community hospital pathologists and urological pathologists with respect to the Gleason grading of prostate cancer. Our objective was to determine the diagnostic rates and Gleason scoring patterns for prostate gland biopsies and prostatectomies at our institution compared with the literature. METHODS: We conducted a retrospective review of all prostate gland biopsies and prostatectomies performed at the Grey Bruce Health Services from January 2005 to September 2005. We collected data from 194 biopsies and 44 prostatectomies. We obtained prebiopsy serum PSA levels and digital rectal exam results for all patients from urologists' office records. RESULTS: The average age for men having biopsies was 65.8 (standard deviation [SD] 8.6) years, and the average prebiopsy serum PSA level was 8.7 (median 7.1, SD 6.2) mug/L. The rates of diagnosis from prostate gland biopsies of benign (17.6%), high-grade prostatic intraepithelial neoplasia (11.0%), atypical small acinar proliferation suspicious for invasive malignancy (13.2%) and invasive prostatic adenocarcinoma (58.2%) at our institution were significantly different than those reported in the literature (p < 0.001). We observed a significant variation in the rates of these diagnoses among the community hospital pathologists in our study (p = 0.004). There was a strong correlation between the increasing number of positive core biopsy sites and increasing Gleason scores in biopsies (p < 0.001). There was also a strong correlation between increasing pre-biopsy serum PSA levels and increasing Gleason scores in biopsies (p < 0.001). A substantial proportion (21.9%) of the biopsies given the Gleason score of 6 had a Gleason score of 7 in the prostatectomy specimen. CONCLUSION: Our results showed a significant difference in prostate gland biopsy categorical diagnoses compared with the literature. There were also significant differences in categorical diagnoses of prostate gland biopsies among the community hospital pathologists in our study. The data identify a strong positive correlation between the increasing number of positive core biopsy sites and increasing Gleason scores in biopsies, as well as a strong positive correlation between increasing prebiopsy serum PSA levels and increasing Gleason scores in biopsies that revealed cancer. We would encourage other community hospital pathologists, in collaboration with their urologists, to review periodically their prostate gland pathology practices in an attempt to improve the uniformity of diagnoses.

Matrilysin (matrix metalloproteinase-7) expression in ulcerative colitis-related tumorigenesis.

Matrilysin (matrix metalloproteinase-7) plays a part in the initiation and growth of colorectal tumors; expression of this protein has been implicated in tumor invasion and metastasis. To date, matrilysin expression in ulcerative colitis (UC)-associated tumorigenesis has not been studied. The aim of this study was to assess the immunohistochemical expression of matrilysin at different stages of UC-associated neoplasia. Paraffin-embedded specimens from 25 patients with UC without dysplasia, UC-related low-grade dysplasia (LGD) and high-grade dysplasia (HGD), and UC-associated carcinoma as well as four colon biopsy samples with no abnormality were examined using an anti-human matrilysin monoclonal antibody and standard immunoperoxidase techniques. Matrilysin expression was recorded as the number of positive cases and the percentage of positive crypts as follows: normal: none of four; negative results for dysplasia: seven of 12 (< 10%); LGD: nine of 15 (< 10%); HGD: nine of 13 (11-50%); and invasive carcinoma: six of seven (> 50%). The results indicated an apparent switch from focal expression of matrilysin in UC-related low-grade dysplasia to widespread expression in high-grade dysplasia and invasive cancer, mimicking the pattern of expression in sporadic colorectal cancer. Although the sample size is small and further investigation therefore is required, the results suggest the possible role of anti-matrix metalloproteinase therapy in reducing the risk of progression from LGD to cancer in patients with ulcerative colitis. Published 2002 Wiley-Liss, Inc.