Publications by authors named "Richard Kirsch"

79 Publications

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

Am J Surg Pathol 2021 Mar 24. Epub 2021 Mar 24.

Mount Sinai Hospital Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto Lakeridge Health, Oshawa Royal Victoria Regional Health Centre, Barrie Grey Bruce Health Services, Owen Sound Department of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/PAS.0000000000001707DOI Listing
March 2021

Evaluation of a multiparametric MRI scoring system for histopathologic treatment response following preoperative chemoradiotherapy for rectal cancer.

Eur J Radiol 2021 May 6;138:109628. Epub 2021 Mar 6.

Joint Department of Medical Imaging, University Health Network, Mount Sinai Hospital, University of Toronto, Ontario, Canada. Electronic address:

Purpose: To evaluate the performance of a multiparametric (mp) MRI scoring system for assessment of tumour response in patients with locally advanced rectal cancer (LARC) after neoadjuvant chemoradiotherapy (CRT).

Method: Fifty-nine consecutive patients with LARC who had rectal MRI before and after CRT followed by surgery were included. Two radiologists retrospectively assessed tumour response using a proposed mpMRI scoring system. Treatment response was classified as complete, near complete, partial or poor. Accuracy, sensitivity, specificity, positive predictive value and negative predictive values were calculated and inter-reader agreements were assessed. Pathologic tumour regression grade (pTRG) was the reference standard.

Results: Treatment response was correctly predicted by both readers in 32.2%-40.7% of patients. Overestimation was more common than underestimation. Sensitivity, specificity, PPV and NPV for pathologic complete response (pCR) among both readers was 16.7-33.0 %, 88.7-94.2 %, 14.3-40.0 % and 92.5-94.2 % respectively. Sensitivity and PPV for both readers improved to 56.0-60.0 % and 53.6-66.7 % respectively when complete response and near complete response categories (good responders) were combined. Inter-reader agreement using the scoring system was fair (κ = 0.383). Agreement between mpMRI score and pathological tumour response was poor to fair for both readers (κ = 0.050 to 0.258) but improved when complete and near complete response categories (good responders) were combined (κ = 0.214 to 0.362).

Conclusions: Despite low agreement between radiological tumour response and pTRG, the proposed mpMRI-based scoring system appears useful in identifying good responders who may benefit from nonoperative management strategies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejrad.2021.109628DOI Listing
May 2021

The gastric disease of Napoleon Bonaparte: brief report for the bicentenary of Napoleon's death on St. Helena in 1821.

Virchows Arch 2021 Mar 4. Epub 2021 Mar 4.

Sorbonne Université, AP-HP, Hôpital Saint-Antoine, Service d'Anatomie et cytologie pathologiques, Paris, France.

After the defeat at the battle of Waterloo on June 18, 1815, Napoleon Bonaparte was sent into exile to the Island of St. Helena where he died 6 years later on May 5, 1821. One day after his death, Napoleon's personal physician, Dr. Francesco Antommarchi, performed the autopsy in the presence of Napoleon's exile companions and the British medical doctors. Two hundred years later, mysteries still surround the cause of his death and different hypotheses have been postulated in the medical and historical literature. The main reasons seem to be the presence of several autopsy reports, their interpretation and perhaps the greed for thrill and mystery. Therefore, for the bicentenary of Napoleon's death, an international consortium of gastrointestinal pathologists assembled to analyse Napoleon's autopsy reports based on the level of medical evidence and to investigate if the autopsy reports really do not allow a final statement.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00428-021-03061-1DOI Listing
March 2021

Improving tumor budding reporting in colorectal cancer: a Delphi consensus study.

Virchows Arch 2021 Mar 1. Epub 2021 Mar 1.

Department of Pathology, Radboud University Medical Center, P.O. Box 9101, 6525 GA, Nijmegen, Netherlands.

Tumor budding is a long-established independent adverse prognostic marker in colorectal cancer, yet methods for its assessment have varied widely. In an effort to standardize its reporting, a group of experts met in Bern, Switzerland, in 2016 to reach consensus on a single, international, evidence-based method for tumor budding assessment and reporting (International Tumor Budding Consensus Conference [ITBCC]). Tumor budding assessment using the ITBCC criteria has been validated in large cohorts of cancer patients and incorporated into several international colorectal cancer pathology and clinical guidelines. With the wider reporting of tumor budding, new issues have emerged that require further clarification. To better inform researchers and health-care professionals on these issues, an international group of experts in gastrointestinal pathology participated in a modified Delphi process to generate consensus and highlight areas requiring further research. This effort serves to re-affirm the importance of tumor budding in colorectal cancer and support its continued use in routine clinical practice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00428-021-03059-9DOI Listing
March 2021

Quality indicator selection for the Canadian Partnership against Cancer rectal cancer project: A modified Delphi study.

Colorectal Dis 2021 Feb 24. Epub 2021 Feb 24.

Department of Surgery, Mount Sinai Hospital, Toronto, ON, Canada.

Aim: It is well established that (i) magnetic resonance imaging, (ii) multidisciplinary cancer conference (MCCs), (iii) preoperative radiotherapy, (iv) total mesorectal excision surgery and (v) pathological assessment as described by Quirke are key processes necessary for high quality, rectal cancer care. The objective was to select a set of multidisciplinary quality indicators to measure the uptake of these clinical processes in clinical practice.

Method: A multidisciplinary panel was convened and a modified two-phase Delphi method was used to select a set of quality indicators. Phase 1 included a literature review with written feedback from the panel. Phase 2 included an in-person workshop with anonymous voting. The selection criteria for the indicators were strength of evidence, ease of capture and usability. Indicators for which ≥90% of the panel members voted 'to keep' were selected as the final set of indicators.

Results: During phase 1, 68 potential indicators were generated from the literature and an additional four indicators were recommended by the panel. During phase 2, these 72 indicators were discussed; 48 indicators met the 90% inclusion threshold and included eight pathology, five radiology, 11 surgical, six radiation oncology and 18 MCC indicators.

Conclusion: A modified Delphi method was used to select 48 multidisciplinary quality indicators to specifically measure the uptake of key processes necessary for high quality care of patients with rectal cancer. These quality indicators will be used in future work to identify and address gaps in care in the uptake of these clinical processes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/codi.15599DOI Listing
February 2021

An International Consensus to Standardize Integration of Histopathology in Ulcerative Colitis Clinical Trials.

Gastroenterology 2021 Feb 19. Epub 2021 Feb 19.

Alimentiv Inc (formerly Robarts Clinical Trials, Inc), London, Ontario, Canada; Department of Medicine, Division of Gastroenterology, Western University, London, Ontario, Canada; Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada.

Background & Aims: Histopathology is an emerging treatment target in ulcerative colitis (UC) clinical trials. Our aim was to provide guidance on standardizing biopsy collection protocols, identifying optimal evaluative indices, and defining thresholds for histologic response and remission after treatment.

Methods: An international, interdisciplinary expert panel of 19 gastroenterologists and gastrointestinal pathologists was assembled. A modified RAND/University of California, Los Angeles appropriateness methodology was used to address relevant issues. A total of 138 statements were derived from a systematic review of the literature and expert opinion. Each statement was anonymously rated as appropriate, uncertain, or inappropriate using a 9-point scale. Survey results were reviewed and discussed before a second round of voting.

Results: Histologic measurements collected using a uniform biopsy strategy are important for assessing disease activity and determining therapeutic efficacy in UC clinical trials. Multiple biopsy strategies were deemed acceptable, including segmental biopsies collected according to the endoscopic appearance. Biopsies should be scored for architectural change, lamina propria chronic inflammation, basal plasmacytosis, lamina propria and epithelial neutrophils, epithelial damage, and erosions/ulcerations. The Geboes score, Robarts Histopathology Index, and Nancy Index were considered appropriate for assessing histologic activity; use of the modified Riley score and Harpaz Index were uncertain. Histologic activity at baseline should be required for enrollment, recognizing this carries operational implications. Achievement of histologic improvement or remission was considered an appropriate and realistic therapeutic target. Current histologic indices require validation for pediatric populations.

Conclusions: These recommendations provide a framework for standardized implementation of histopathology in UC trials. Additional work is required to address operational considerations and areas of uncertainty.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1053/j.gastro.2021.02.035DOI Listing
February 2021

Development and initial validation of a deep learning algorithm to quantify histological features in colorectal carcinoma including tumour budding/poorly differentiated clusters.

Histopathology 2021 Feb 15. Epub 2021 Feb 15.

Department of Pathology and Laboratory Medicine, Mayo Clinic Arizona, Scottsdale, AZ, USA.

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 mm 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 < 0.001); however, stronger correlations were seen between the proportion of positive lymph nodes and algorithm measures of TB/PDCs. Stronger associations were also seen between distant metastasis and algorithm measures of TB/PDCs (P = 0.004) than between distant metastasis and TB (P = 0.04) and TB/PDC counts (P = 0.06).

Conclusions: Our results highlight the potential of deep learning to identify and quantify a broad spectrum of histological features in colorectal carcinoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/his.14353DOI Listing
February 2021

Histopathological Diagnosis of Tumour Deposits in Colorectal Cancer: A Delphi Consensus Study.

Histopathology 2021 Jan 28. Epub 2021 Jan 28.

Radbound University Medical Centre, Nijmegen, Netherlands.

Introduction: Tumour deposits (TDs) are an important prognostic marker in colorectal cancer. However, the classification, and inclusion in staging, of TDs has changed significantly in each TNM Edition since their initial description in TNM 5, and terminology remains controversial. Expert consensus is needed to guide the future direction of precision staging.

Methods: A modified Delphi consensus process was used. Statements were formulated and sent to participants as an online survey. Participants were asked to rate their agreement with each statement on a 5-point Likert scale and also to suggest additional statements for discussion. These responses were circulated, together with anonymised comments, and statements were modified prior to carrying out a second online round. Consensus was set at 70%.

Results: Overall, 32 statements reached consensus. There were concerns that TDs were currently incorrectly placed in the TNM system and that their prognostic importance was being underestimated. There were concerns about interobserver variation and it was felt that a clearer, more reproducible definition of TDs was needed.

Conclusions: Our main recommendations are that the number of TDs should be recorded even if LNMs are also present and that nodules with evidence of origin (EMVI, PNI, LI) should still be categorised as TDs and not excluded as TNM 8 specifies. Whether TDs should continue to be included in the N category at all is controversial and did not achieve consensus, however participants agreed that TDs are prognostically worse than LNMs and the N1c category is suboptimal as it does not reflect this.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/his.14344DOI Listing
January 2021

Tumour budding in solid cancers.

Nat Rev Clin Oncol 2021 02 8;18(2):101-115. Epub 2020 Sep 8.

Department of Pathology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Centre, Nijmegen, The Netherlands.

Tumour budding is an emerging prognostic biomarker in colorectal cancer (CRC) and other solid cancers. Tumour buds are usually defined as isolated single cancer cells or clusters of up to four cancer cells located at the invasive tumour front. The prognostic value of tumour budding is now supported by a large body of evidence, whereas the utility of this phenotype as a predictive biomarker remains under investigation. The application of tumour budding indices in clinical practice requires a standardized scoring system that can be tailored to specific tumour types and clinical scenarios. In the context of CRC, tumour budding can be assessed according to the method agreed at the International Tumour Budding Consensus Conference (ITBCC) in 2016. Using the ITBCC scoring system, tumour budding is an independent predictor of lymph node metastasis in patients with pT1 CRC and of unfavourable survival in patients with stage II colon cancer. Regardless of the clinical scenario or tumour type, the assertion that 'the more tumour buds, the worse the clinical outcome' applies. In this Review, we provide an overview of tumour budding in solid cancers, highlighting the molecular and biological aspects of this phenomenon, including its associations with epithelial-mesenchymal transition and features of the tumour microenvironment. We also describe the available evidence demonstrating the value of tumour budding as a biomarker across various solid cancers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41571-020-0422-yDOI Listing
February 2021

Poorly differentiated clusters in colorectal cancer: a current review and implications for future practice.

Histopathology 2020 Sep 23;77(3):351-368. Epub 2020 Jul 23.

Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, ON, Canada.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/his.14128DOI Listing
September 2020

The Canadian Partnership Against Cancer Rectal Cancer Project: Protocol for a Pan-Canadian, Multidisciplinary Quality Improvement Initiative to Optimize the Quality of Rectal Cancer Care.

JMIR Res Protoc 2020 Jan 29;9(1):e15535. Epub 2020 Jan 29.

Department of Surgery, Mount Sinai Hospital, Toronto, ON, Canada.

Background: Over the last 2 decades, the use of multimodal strategies, including total mesorectal excision (TME) surgery, preoperative chemotherapy, multidisciplinary case conference, pelvic magnetic resonance imaging, and pathologic assessment using Quirke method, has led to significant improvements in oncologic outcomes for patients with rectal cancer. Although the literature supports claims on the effectiveness of these multimodal strategies, the uptake of these multimodal strategies varies considerably among centers, suggesting that the best evidence is not always implemented into clinical practice.

Objective: This study aims to perform a quality improvement initiative to (1) identify existing gaps in care for these multimodal strategies and (2) implement knowledge translation (KT) interventions to close these gaps to optimize quality of care for patients with rectal cancer across high-volume centers in Canada.

Methods: Process indicators for the selected multimodal strategies to optimize rectal cancer care will be selected and prospectively collected for all patients with stages 1 to 3 rectal cancer undergoing TME surgery. KT interventions, including audit and feedback, opinion leaders, and community of practice, will be implemented to increase the uptake of these clinical strategies.

Results: The uptake of the process indicators over time and the effect of the uptake of the process indicators on short- and long-term oncologic outcomes will be evaluated for each multimodal strategy.

Conclusions: This quality improvement initiative will identify existing gaps in care for the selected multimodal strategies and implement KT interventions to close these gaps. The results of this study will inform further efforts to optimize rectal cancer care.

International Registered Report Identifier (irrid): DERR1-10.2196/15535.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2196/15535DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7016615PMC
January 2020

Histological Markers of Clinical Relapse in Endoscopically Quiescent Ulcerative Colitis.

Inflamm Bowel Dis 2020 Oct;26(11):1722-1729

Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, Ontario, Canada.

Background: In ulcerative colitis (UC) patients who have achieved mucosal healing, active microscopic colonic mucosal inflammation is commonly observed. We aimed to assess the association between histological activity and disease relapse in endoscopically quiescent UC.

Methods: Ulcerative colitis patients with endoscopically quiescent disease and ≥12 months of follow-up were included. Biopsies were reviewed for the presence of basal plasmacytosis (BPC) and active histological inflammation, defined as a Geboes score (GS) ≥3.2. Primary outcome measures were disease relapse at 18 months and time to first relapse after index colonoscopy.

Results: Seventy-six UC patients (51% male; mean age, 38.6 years; median follow-up [range], 75.2 [2-118] months) were included. Sixty-two percent had an endoscopic Mayo score of 0 at index colonoscopy. Basal plasmacytosis was present in 46% and active histological inflammation in 30% of subjects. Presence of BPC was associated with a significantly shorter time to disease relapse (P = 0.01). Active histological inflammation was significantly associated with clinical relapse at 18 months (P = 0.0005) and shorter time to clinical relapse (P = 0.0006). Multivariate analysis demonstrated active histological inflammation to be independently associated with clinical relapse at 18 months and time to clinical relapse.

Conclusions: In endoscopically quiescent UC, active histological inflammation and the presence of BPC are adjunctive histological markers associated with increased likelihood of disease relapse. Although prospective studies are required, the presence of these histological markers should be a factor considered when making therapeutic decisions in UC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ibd/izz308DOI Listing
October 2020

Impact of Referral Center Pathology Review on Diagnosis and Management of Patients With Appendiceal Neoplasms.

Arch Pathol Lab Med 2020 06 12;144(6):764-768. Epub 2019 Nov 12.

From the Department of Pathology, University of Utah, Salt Lake City (Dr Jedrzkiewicz); the Department of Pathology, Yokohama City University, Yokohama, Japan (Dr Tateishi); and the Departments of Pathology (Drs Kirsch, Conner, Riddell, and Pollett) and Surgery (Drs Bischof, McCart, and Govindarajan, and Ms Taylor), Sinai Health System, University of Toronto, Toronto, Ontario, Canada.

Context.—: Data regarding the clinical impact of subspecialist pathology review of appendiceal neoplasms are limited.

Objective.—: To determine whether pathology review by gastrointestinal pathologists at a tertiary-care referral center resulted in significant changes in the diagnosis and clinical management of appendiceal neoplastic lesions.

Design.—: We conducted a retrospective review of all patients with an initial diagnosis of appendiceal neoplasm referred to a tertiary-care referral center in Ontario, Canada, from 2010-2016. The discordance rate between original and review pathology reports, the nature of discordances, and the impact of any discordance on patient management were recorded.

Results.—: A total of 145 patients with appendiceal lesions were identified (low-grade mucinous appendiceal neoplasm [n = 79], invasive mucinous adenocarcinoma [n = 12], "colorectal type" adenocarcinoma [n = 12], goblet cell carcinoid and adenocarcinomas ex goblet cell carcinoid [n = 24], and other lesions/neoplasms [n = 20]). One or more changes in diagnoses were found in 36 of 145 cases (24.8%), with changes within the same category of interpretation (n = 10), stage (n = 7), grade (n = 6), and categoric interpretation (n = 5) being the most common. In 10 of 36 patients (28%), the diagnostic change led to a significant change in management, including recommendation for additional surveillance, systemic chemotherapy, additional surgery, or discontinuation of surveillance.

Conclusions.—: Subspecialist pathology review of appendiceal neoplastic lesions led to a change in diagnosis in 36 of 145 cases (24.8%), of which nearly 30% (10 of 36 cases) led to a change in clinical management. The overall rate of clinically significant discordances was 7% (10 of 145). Our findings suggest that subspecialist pathology review of appendiceal neoplasms referred to specialized centers is justified.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5858/arpa.2019-0214-OADOI Listing
June 2020

An American Path to Universal Coverage.

Authors:
Richard Kirsch

J Ambul Care Manage 2019 Jul/Sep;42(3):211-217

Proteus Fund, Amherst, Massachusetts.

The politics of health care policy create opportunities driven by public demands for lowering costs and providing health security, constrained by fear of loss of what people have now, fears that will be inflamed by opponents. The best course toward reform will provide people a choice of improved public coverage and the ability to keep improved employer coverage. There are a variety of ways to design these proposals, some of which can be characterized as Medicare for All. Inclusion of a Medicare/public plan in the Affordable Care Act marketplaces is a policy option but one of relatively low significance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/JAC.0000000000000291DOI Listing
July 2020

Safety and Feasibility of Using Magnetic Resonance Imaging Criteria to Identify Patients With "Good Prognosis" Rectal Cancer Eligible for Primary Surgery: The Phase 2 Nonrandomized QuickSilver Clinical Trial.

JAMA Oncol 2019 Jul;5(7):961-966

Department of Diagnostic Radiology, Queen Elizabeth II Health Sciences Centre, Halifax, Nova Scotia, Canada.

Importance: Chemoradiotherapy (CRT), followed by surgery, is the recommended approach for stage II and III rectal cancer. While CRT decreases the risk of local recurrence, it does not improve survival and leads to poorer functional outcomes than surgery alone. Therefore, new approaches to better select patients for CRT are important.

Objective: To conduct a phase 2 study to evaluate the safety and feasibility of using magnetic resonance imaging (MRI) criteria to select patients with "good prognosis" rectal tumors for primary surgery.

Design, Setting, And Participants: Prospective nonrandomized phase 2 study at 12 high-volume colorectal surgery centers across Canada. From September 30, 2014, to October 21, 2016, a total of 82 patients were recruited for the study. Participants were patients newly diagnosed as having rectal cancer with MRI-predicted good prognosis rectal cancer. The MRI criteria for good prognosis tumors included distance to the mesorectal fascia greater than 1 mm; definite T2, T2/early T3, or definite T3 with less than 5 mm of extramural depth of invasion; and absent or equivocal extramural venous invasion.

Interventions: Patients with rectal cancer with MRI-predicted good prognosis tumors underwent primary surgery.

Main Outcomes And Measures: The primary outcome was the proportion of patients with a positive circumferential resection margin (CRM) rate. Assuming a 10% baseline probability of a positive CRM, a sample size of 75 was estimated to yield a 95% CI of ±6.7%.

Results: Eighty-two patients (74% male) participated in the study. The median age at the time of surgery was 66 years (range, 37-89 years). Based on MRI, most tumors were midrectal (65% [n = 53]), T2/early T3 (60% [n = 49]), with no suspicious lymph nodes (63% [n = 52]). On final pathology, 91% (n = 75) of tumors were T2 or greater, 29% (n = 24) were node positive, and 59% (n = 48) were stage II or III. The positive CRM rate was 4 of 82 (4.9%; 95% CI, 0.2%-9.6%).

Conclusions And Relevance: The use of MRI criteria to select patients with good prognosis rectal cancer for primary surgery results in a low rate of positive CRM and suggests that CRT may not be necessary for all patients with stage II and III rectal cancer.

Trial Registration: ISRCTN.com identifier: ISRCTN05107772.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamaoncol.2019.0186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6583831PMC
July 2019

A rare presentation of hypovolemic shock secondary to Whipple's disease.

Eur J Gastroenterol Hepatol 2019 05;31(5):642-645

Department of Medicine, Division of Gastroenterology, Mount Sinai Hospital, University of Toronto.

Whipple's disease is a rare, multisystem infection caused by the Gram-positive Tropheryma whippelii organism. In addition to neurological and rheumatological manifestations, this disease can result in significant gastrointestinal symptoms such as malabsorption, diarrhea, and weight loss. Given the diagnostic challenge and rare occurrence, a high index of suspicion is critical to prevent morbidity and mortality from this otherwise highly infectious disease transmitted via the fecal-oral route. We present a very rare but near-fatal case of hypovolemic shock secondary to protein-losing enteropathy and gastrointestinal bleeding from small bowel T. whippelii infection. Furthermore, the epidemiology, clinical presentation, diagnosis, and management of Whipple's disease is reviewed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MEG.0000000000001363DOI Listing
May 2019

A Review of Current Challenges in Colorectal Cancer Reporting.

Arch Pathol Lab Med 2019 07 23;143(7):869-882. Epub 2019 Jan 23.

From the Institute of Pathology, University of Bern, Bern, Switzerland (Dr Dawson); Pathology and Laboratory Medicine, Mount Sinai Hospital and University of Toronto, Toronto, Ontario, Canada (Drs Dawson and Kirsch); the Department of Colorectal Surgery, University Hospitals Bristol NHS Foundation Trust, Bristol, United Kingdom (Dr Messenger); and Pathology and Laboratory Medicine, Western University and London Health Sciences Centre, London, Ontario, Canada (Dr Driman).

Context.—: Pathologic assessment of colorectal cancer resection specimens plays an important role in postsurgical management and prognostication in patients with colorectal cancer. Challenges exist in the evaluation and reporting of these specimens, either because of difficulties in applying existing guidelines or related to newer concepts.

Objective.—: To address challenging areas in colorectal cancer pathology and to provide an overview of the literature, current guidelines, and expert recommendations for the handling of colorectal cancer resection specimens in everyday practice.

Data Sources.—: PubMed (US National Library of Medicine, Bethesda, Maryland) literature review; reporting protocols of the College of American Pathologists, the Royal College of Pathologists of the United Kingdom, and the Japanese Society for Cancer of the Colon and Rectum; and classification manuals of the American Joint Committee on Cancer and the Union for International Cancer Control.

Conclusions.—: This review has addressed issues and challenges affecting quality of colorectal cancer pathology reporting. High-quality pathology reporting is essential for prognostication and management of patients with colorectal cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5858/arpa.2017-0475-RADOI Listing
July 2019

Reply to: Interobserver variability in colorectal cancer and the 2016 ITBCC consensus.

Mod Pathol 2019 01 19;32(1):161-162. Epub 2018 Dec 19.

Institute of Pathology, University of Bern, Bern, Switzerland.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41379-018-0104-9DOI Listing
January 2019

Telocytes as possible precursors of PDGFRA-mutant gastrointestinal mesenchymal tumors-reply to rejoinder.

Hum Pathol 2019 02 17;84:337-338. Epub 2018 Oct 17.

Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada M5G 1X5.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.humpath.2018.08.036DOI Listing
February 2019

Telocytes as possible precursors of PDGFRA-mutant gastrointestinal mesenchymal tumors-reply.

Hum Pathol 2018 12 5;82:299-300. Epub 2018 Jul 5.

Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario M5G 1X5.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.humpath.2018.04.035DOI Listing
December 2018

Extramural venous invasion in rectal cancer: overview of imaging, histopathology, and clinical implications.

Abdom Radiol (NY) 2019 01;44(1):1-10

Joint Department of Medical Imaging, University Health Network, Mount Sinai Hospital, and Women's College Hospital, University of Toronto, Toronto, ON, Canada.

Objective: Extramural venous invasion (EMVI) is an independent prognostic factor for prediction of overall unfavorable outcomes in rectal cancer. While EMVI has traditionally been detected in postoperative pathologic specimens, MRI can provide this important piece of information preoperatively. This article reviews the methods of EMVI detection and their clinical implications for treatment and outcomes of rectal cancer.

Conclusion: EMVI has fundamental implications for rectal cancer prognosis and long-term outcomes. Since MRI has the advantage of preoperative detection of EMVI, it has been suggested that MRI-detected EMVI be incorporated for preoperative chemoradiotherapy (CRT) treatment stratification of rectal cancer for better patient triage and outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00261-018-1673-2DOI Listing
January 2019

Utility of shear-wave elastography to differentiate low from advanced degrees of liver fibrosis in patients with hepatitis C virus infection of native and transplant livers.

J Clin Ultrasound 2018 Jun 6;46(5):311-318. Epub 2018 Mar 6.

Department of Medical Imaging, University of Toronto, Toronto, Ontario, Canada.

Objective: To determine the accuracy of shear-wave elastography (SWE) to differentiate low from advanced degrees of liver fibrosis in hepatitis C patients.

Material & Method: Consented native/transplant hepatitis C patients underwent SWE using a C1-6 MHz transducer before ultrasound (US)-guided liver biopsy. Five interpretable SWE samples were obtained from the right lobe of the liver immediately before US-guided random biopsy of the right lobe. Average kilopascal (kPa) values were compared to the meta-analysis of histological data in viral hepatitis (METAVIR) fibrosis grading. SWE values were correlated with the degree of inflammation and fatty infiltration.

Results: Study population consisted of 115 patients (63 with transplant, and 52 with native liver) including 29 women and 86 men, with a mean ± SD age of 56 ± 8.7 years. Mean ± SD SWE values were 7.9 ± 3 kPa in 83 patients with METAVIR scores of 0-2 and 13.2 ± 5.9 kPa in 32 patients with METAVIR scores of 3 or 4 (P < .001). Area under curve (AUC) of a Receiver Operating Characteristics curve for advanced degrees of fibrosis was 0.81 (95% CI: 0.71, 0.90) (P < .001). AUCs of transplant versus native livers (0.78 [CI:0.62, 0.94] versus 0.85 [CI: 0.73, 0.96]), degree of inflammation (0.81 [CI: 0.65, 0.97] versus 0.72 [0.56, 0.88]), or degree of fat deposition (0.81 [CI:0.70, 0.92] versus 0.80 [CI:0.61, 1]) were not statistically different (P > .05). for kPa threshold of SWE value of 10.67 kPa to differentiate advanced from low degree of fibrosis had a sensitivity of 59% (CI: 41%-76%) and specificity of 90% (CI: 82%-96%).

Conclusion: Liver stiffness evaluated by SWE can differentiate low from advanced liver fibrosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jcu.22583DOI Listing
June 2018

Familial PDGFRA-mutation syndrome: somatic and gastrointestinal phenotype.

Hum Pathol 2018 06 25;76:52-57. Epub 2018 Feb 25.

Department of Pathology and Molecular Medicine, Queens University and Kingston General Hospital, Kingston, Ontario, K7L3N6, Canada; Division of Medical Genetics in the Department of Pediatrics, Kingston General Hospital, Kingston, Ontario K7L 2V7, Canada. Electronic address:

Germline activating platelet-derived growth factor receptor alpha (PDGFRA) mutations have been described in four families. All the index patients have presented with multiple mesenchymal tumors of the gastrointestinal tract. We identified a fifth family with four first-degree relatives that harbor a PDGFRA exon 18 (D846V) germline mutation. The affected kindred have a unique phenotype including coarse facies and skin, broad hands and feet, and previously undescribed premature tooth loss. While the index patient presented with multiple small bowel inflammatory fibroid polyps (IFPs) and has a gastric gastrointestinal stromal tumor (GIST), no tumors have yet been identified in other family members. We describe the pathology, genetics, the incomplete penetrance and variable expressivity of the familial PDGFRA-mutation syndrome referencing the mouse knock-in Pdgfra model. We speculate on the role of the telocyte, a recently described CD34, PDGFRA+ stromal cell, in the development of inflammatory fibroid polyps and the somatic phenotype.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.humpath.2018.02.014DOI Listing
June 2018

Venous invasion detection in colorectal cancer specimens: risk assessment of modifying the dissection method using a tangential approach.

J Clin Pathol 2018 02 6;71(2):186-188. Epub 2017 Dec 6.

Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, University of Toronto, Toronto, Canada.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/jclinpath-2017-204822DOI Listing
February 2018

Cytokeratin-based assessment of tumour budding in colorectal cancer: analysis in stage II patients and prospective diagnostic experience.

J Pathol Clin Res 2017 Jul 26;3(3):171-178. Epub 2017 Jul 26.

Institute of PathologyUniversity of BernBernSwitzerland.

Tumour budding in colorectal cancer is an important prognostic factor. A recent consensus conference elaborated recommendations and key issues for future studies, among those the use of pan-cytokeratin stains, especially in stage II patients. We report the first prospective diagnostic experience using pan-cytokeratin for tumour budding assessment. Moreover, we evaluate tumour budding using pan-cytokeratin stains and disease-free survival (DFS) in stage II patients. To this end, tumour budding on pan-cytokeratin-stained sections was evaluated by counting the number of tumour buds in 10 high-power fields (0.238 mm), then categorizing counts as low/high-grade at a cut-off of 10 buds, in two cohorts. Cohort 1: prospective setting with 236 unselected primary resected colorectal cancers analysed by 17 pathologists during diagnostic routine. Cohort 2: retrospective cohort of 150 stage II patients with information on DFS. In prospective analysis of cohort 1, tumour budding counts correlated with advanced pT, lymph node metastasis, lymphovascular invasion, perineural invasion (all  < 0.0001), and distant metastasis ( = 0.0128). In cohort 2, tumour budding was an independent predictor of worse DFS using counts [ = 0.037, HR (95% CI): 1.007 (1.0-1.014)] and the low-grade/high-grade scoring approach [ = 0.02; HR (95% CI): 3.04 (1.2-7.77), 90.7 versus 73%, respectively]. In conclusion, tumour budding assessed on pan-cytokeratin slides is feasible in a large pathology institute and leads to expected associations with clinicopathological features. Additionally, it is an independent predictor of poor prognosis in stage II patients and should be considered for risk stratification in future clinical studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cjp2.73DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5527316PMC
July 2017

HtrA3 stromal expression is correlated with tumor budding in stage II colorectal cancer.

Exp Mol Pathol 2017 08 15;103(1):94-100. Epub 2017 Jul 15.

Albert Einstein College of Medicine, Department of Anatomy & Structural Biology, Bronx, NY, United States. Electronic address:

Tumor budding is a well-established adverse prognostic factor in colorectal carcinoma (CRC). It may represent a form of epithelial-to-mesenchymal transition (EMT), although the underlying mechanisms remain unclear. High-temperature requirement A3 (HtrA3) is an inhibitor of the bone morphogenetic protein pathway, the suppression of which has been linked to EMT. Since HtrA3 is highly expressed in the desmoplastic stroma at the CRC invasive front, we sought to evaluate the relationship between tumor budding and HtrA3 expression in 172 stage II CRC resection specimens. All tumors were evaluated for tumor budding, with the highest budding slide selected for pan-keratin (CK) and HtrA3 immunohistochemistry. Representative areas of tumor core and invasive front, including budding and non-budding areas, were marked on CK stained slides, and then evaluated on HtrA3 stained slides. HtrA3 expression in tumor cells (tHtrA3) and peritumoral stroma (sHtrA3) was assessed for staining percentage and intensity (the product yielding a final score). Tumors with high-grade tumor budding (HGTB) showed increased expression of sHtrA3 in budding areas compared to non-budding areas at the invasive front (P<0.001). In addition, sHtrA3 expression at the invasive front was significantly higher in HGTB tumors compared to minimally budding tumors (P<0.05). tHtrA3 expression at the invasive front was significantly associated with high histological grade (P<0.05). Higher sHtrA3 expression in the tumor core (but not invasive front) was significantly associated with decreased 5-year overall survival on univariate analysis (P<0.05), but not multivariate analysis. HtrA3 expression in the peritumoral stroma of patients with stage II CRC is associated with HGTB and may be a novel marker of poor outcome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.yexmp.2017.07.002DOI Listing
August 2017

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

Hum Pathol 2017 09 15;67:45-53. Epub 2017 Jul 15.

London Health Sciences Centre, London, Ontario, Canada, N6A 5A5.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.humpath.2017.07.004DOI Listing
September 2017

Recommendations for reporting tumor budding in colorectal cancer based on the International Tumor Budding Consensus Conference (ITBCC) 2016.

Mod Pathol 2017 09 26;30(9):1299-1311. Epub 2017 May 26.

Pathology and Tumour Biology, University of Leeds, St James's University Hospital, Leeds, UK.

Tumor budding is a well-established independent prognostic factor in colorectal cancer but a standardized method for its assessment has been lacking. The primary aim of the International Tumor Budding Consensus Conference (ITBCC) was to reach agreement on an international, evidence-based standardized scoring system for tumor budding in colorectal cancer. The ITBCC included nine sessions with presentations, a pre-meeting survey and an e-book covering the key publications on tumor budding in colorectal cancer. The 'Grading of Recommendation Assessment, Development and Evaluation' method was used to determine the strength of recommendations and quality of evidence. The following 10 statements achieved consensus: tumor budding is defined as a single tumor cell or a cell cluster consisting of four tumor cells or less (22/22, 100%). Tumor budding is an independent predictor of lymph node metastases in pT1 colorectal cancer (23/23, 100%). Tumor budding is an independent predictor of survival in stage II colorectal cancer (23/23, 100%). Tumor budding should be taken into account along with other clinicopathological features in a multidisciplinary setting (23/23, 100%). Tumor budding is counted on H&E (19/22, 86%). Intratumoral budding exists in colorectal cancer and has been shown to be related to lymph node metastasis (22/22, 100%). Tumor budding is assessed in one hotspot (in a field measuring 0.785 mm) at the invasive front (22/22, 100%). A three-tier system should be used along with the budding count in order to facilitate risk stratification in colorectal cancer (23/23, 100%). Tumor budding and tumor grade are not the same (23/23, 100%). Tumor budding should be included in guidelines/protocols for colorectal cancer reporting (23/23, 100%). Members of the ITBCC were able to reach strong consensus on a single international, evidence-based method for tumor budding assessment and reporting. It is proposed that this method be incorporated into colorectal cancer guidelines/protocols and staging systems.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/modpathol.2017.46DOI Listing
September 2017

The pathology and causes of tissue eosinophilia in the gastrointestinal tract.

Histopathology 2017 Aug 26;71(2):177-199. Epub 2017 May 26.

Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, ON, Canada.

Eosinophilic inflammation in the gastrointestinal tract may occur as a primary eosinophilic disorder or as a secondary response with other causes. Primary eosinophilic gastrointestinal disorders (EGIDs) are Th2-mediated allergic diseases that overlap pathogenetically with atopic conditions involving other organs. The pathological diagnosis of primary EGIDs can be challenging, as the quantity of eosinophils considered to be 'abnormal' is difficult to define, and the diagnosis, by definition, requires exclusion of the far more common secondary causes. Our understanding of the basic biology and natural history of eosinophilic oesophagitis has advanced considerably over the last decade, whereas other EGIDs have proven more difficult to characterize; nonetheless, some recent advances have been made. This review summarizes current knowledge regarding the clinical presentation, diagnosis, natural history and treatment of EGIDs, including eosinophilic oesophagitis. We also draw attention to the numerous secondary causes of tissue eosinophilia in the gastrointestinal tract, and suggest a practical approach to the histological assessment, diagnosis and reporting of EGIDs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/his.13228DOI Listing
August 2017

Investigation of volumetric apparent diffusion coefficient histogram analysis for assessing complete response and clinical outcomes following pre-operative chemoradiation treatment for rectal carcinoma.

Abdom Radiol (NY) 2017 05;42(5):1310-1318

Joint Department of Medical Imaging, University Health Network, Mount Sinai Hospital and Women's College Hospital, University of Toronto, 610 University Ave, 3-957, Toronto, ON, M5G 2M9, Canada.

Purpose: To investigate the relationship of pre-treatment volumetric apparent diffusion coefficient (ADC) histogram parameters with post-operative histopathologic treatment response and clinical outcomes following pre-operative chemoradiation treatment (CRT) in rectal cancer.

Materials And Methods: In a Health Insurance Portability and Accountability Act compliant retrospective study, 78 rectal cancer patients treated with pre-operative CRT and rectal MRI were included. MR imaging analysis was performed using OncoTREAT (software tool). Multiple volumetric ADC histogram parameters (voxel distribution across ADC ranges, kurtosis, and skewness) were assessed. Correlation was made to post-operative pathological complete response, clinical, or radiological evidence of disease progression using the Mann-Whitney test.

Results: Post CRT, 8 patients showed pathologic complete response and 13 patients showed distant disease progression. Pre-treatment mean ADC was 1.2 × 10 mm/s (range 0.3-1.99 × 10 mm/s). Mean kurtosis measured was 0.56 (range -1 to 6; SD 1.36). Mean skewness was 0.3 (range -1 to 2; SD 0.69). Skewness had significant correlation (p value = 0.006) with disease progression. The mean rectal tumor volume was 24cc (range 1cc-134cc). Pre-treatment MRI tumor volume showed significant correlation (p value = 0.013) with pathologic complete response. Mean ADC and percentage voxels distribution against ADC ranges had no significant correlation with treatment response or disease outcomes.

Conclusion: Volumetric ADC histogram analysis of pre-CRT rectal cancer MRI appears promising for prediction of post-CRT complete response and disease progression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00261-016-1010-6DOI Listing
May 2017