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Duan K, Chow B, Tsui W, Elliot C, Sari A, Shivji S, Kirsch R, Conner JR. Impact of tissue sampling on detection of venous invasion in colorectal cancer: a prospective analysis. Histopathology 2023; 83:891-902. [PMID: 37580911 DOI: 10.1111/his.15030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2023] [Revised: 07/04/2023] [Accepted: 08/01/2023] [Indexed: 08/16/2023]
Abstract
AIMS Venous invasion (VI) is a powerful yet under-reported prognostic factor in colorectal cancer (CRC). Efforts to improve its detection have largely focused upon histological assessment, with less attention paid to tissue-sampling strategies. This study aimed to prospectively determine the number of tumour blocks required to optimise VI detection in CRC resections. In addition, the relationship between linear spiculation (LS) and extramural venous invasion (EMVI) was investigated. METHODS AND RESULTS A standardised tissue sampling protocol was developed and applied prospectively to 217 CRC resections [AJCC 8th edition, stage 1 (n = 32); stage 2 (n = 84); stage 3 (n = 87); stage 4 (n = 14); and post-neoadjuvant therapy (n = 46)]. Elastin stains were performed on all tumour blocks. VI was identified in 55% of cases (EMVI = 37%; IMVI alone = 18%). The sensitivity of VI detection increased with increasing numbers of tumour blocks submitted [one block (35%), three blocks (66%), five blocks (84%), six blocks (95%) and seven blocks (97%)]. Similar findings were observed for EMVI [one block (35%), three blocks (73%), five blocks (89%), six blocks (96%) and seven blocks (96%)]. LS was identified macroscopically in 22% of specimens. In cases where no neoadjuvant therapy had been given, EMVI was significantly associated with LS (71% in LS+ cases versus 29% in LS- cases; P < 0.001). In addition, tumour blocks targeting LS were associated with a fivefold higher rate of EMVI compared with blocks that did not (P < 0.001). CONCLUSIONS Our findings demonstrate the impact of tissue sampling and quality of gross examination on VI detection and may inform practices in future CRC protocols.
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Affiliation(s)
- Kai Duan
- Department of Pathology and Laboratory Medicine, Sinai Health System, Toronto, ON, Canada
- Department of Pathology, University Health Network, Toronto, ON, Canada
- Department of Pathobiology and Laboratory Medicine, University of Toronto, Toronto, ON, Canada
| | - Brian Chow
- Department of Pathology and Laboratory Medicine, Sinai Health System, Toronto, ON, Canada
- Department of Pathobiology and Laboratory Medicine, University of Toronto, Toronto, ON, Canada
| | - William Tsui
- Department of Pathology and Laboratory Medicine, Sinai Health System, Toronto, ON, Canada
- Department of Pathobiology and Laboratory Medicine, University of Toronto, Toronto, ON, Canada
| | - Colin Elliot
- Department of Pathology and Laboratory Medicine, Sinai Health System, Toronto, ON, Canada
| | - Aysegul Sari
- Department of Pathology and Laboratory Medicine, Sinai Health System, Toronto, ON, Canada
- Department of Pathology, Izmir Katip Celebi University Ataturk Training and Research Hospital, Izmir, Turkey
| | - Sameer Shivji
- Department of Pathology and Laboratory Medicine, Sinai Health System, Toronto, ON, Canada
| | - Richard Kirsch
- Department of Pathology and Laboratory Medicine, Sinai Health System, Toronto, ON, Canada
- Department of Pathobiology and Laboratory Medicine, University of Toronto, Toronto, ON, Canada
- Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, Canada
| | - James R Conner
- Department of Pathology and Laboratory Medicine, Sinai Health System, Toronto, ON, Canada
- Department of Pathobiology and Laboratory Medicine, University of Toronto, Toronto, ON, Canada
- Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, Canada
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Bahmad HF, Alloush F, Salami A, Sawah R, Lusnia C, Kilinc E, Sutherland T, Alghamdi S, Poppiti RJ. Routine elastin staining improves venous invasion detection in colorectal carcinoma. Ann Diagn Pathol 2023; 66:152170. [PMID: 37295037 DOI: 10.1016/j.anndiagpath.2023.152170] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Revised: 05/29/2023] [Accepted: 05/30/2023] [Indexed: 06/12/2023]
Abstract
BACKGROUND Colorectal carcinoma is the second most common cause of cancer-related deaths in North America. Invasion of tumor cells into lymphatic and blood vessels is an imperative step in the metastatic progression of colorectal carcinoma. OBJECTIVES This is a before-and-after study conducted by the Department of Pathology and Laboratory Medicine of Mount Sinai Medical Center of Florida to assess the impact on venous invasion (VI) detection by implementing routine elastin staining on all tumor-containing blocks per case, where feasible, in colorectal carcinoma (CRC) resection specimens. METHODS Clinicopathological parameters of CRC specimens were collected from January until December 2021 (n = 93) for the pre-implementation cohort and from January until December 2022 (n = 61) for the post-implementation cohort. RESULTS VI detection was significantly increased in the post-implementation cohort at a rate of 50.8 % compared to only 18.6 % in the pre-implementation cohort. The majority of VI identified in the pre-implementation cohort was extramural (61.5 %), whereas in the post-implementation cohort it was intramural (41.9 %). On univariate analysis, implementation of routine elastin stain was associated with strikingly increased VI detection rates (OR = 4.5, p-value < 0.001). On multivariate analysis, after adjusting for other clinicopathologic variables, elastin staining retained its independent statistically significant impact on VI detection (OR = 2.6, p-value = 0.034). Of note, there were no significant differences in the pre- and post-implementation cohorts in the frequency of nodal metastases, tumor extent, histologic grade, perineural invasion, T stage or M stage. CONCLUSION Based on our results and what has been published recently, we confirm an increase in the VI detection rate after implementing routine elastin staining on all tumor-containing blocks in CRC resection specimens.
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Affiliation(s)
- Hisham F Bahmad
- Arkadi M. Rywlin M.D. Department of Pathology and Laboratory Medicine, Mount Sinai Medical Center, Miami Beach, FL 33140, USA.
| | - Ferial Alloush
- Arkadi M. Rywlin M.D. Department of Pathology and Laboratory Medicine, Mount Sinai Medical Center, Miami Beach, FL 33140, USA
| | - Ali Salami
- Department of Mathematics, Faculty of Sciences, Lebanese University, Nabatieh, Lebanon
| | - Rachel Sawah
- Herbert Wertheim College of Medicine, Florida International University, Miami, FL 33199, USA
| | - Ciara Lusnia
- Herbert Wertheim College of Medicine, Florida International University, Miami, FL 33199, USA
| | - Ekim Kilinc
- Arkadi M. Rywlin M.D. Department of Pathology and Laboratory Medicine, Mount Sinai Medical Center, Miami Beach, FL 33140, USA
| | - Tyson Sutherland
- Arkadi M. Rywlin M.D. Department of Pathology and Laboratory Medicine, Mount Sinai Medical Center, Miami Beach, FL 33140, USA
| | - Sarah Alghamdi
- Arkadi M. Rywlin M.D. Department of Pathology and Laboratory Medicine, Mount Sinai Medical Center, Miami Beach, FL 33140, USA; Department of Pathology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL 33199, USA
| | - Robert J Poppiti
- Arkadi M. Rywlin M.D. Department of Pathology and Laboratory Medicine, Mount Sinai Medical Center, Miami Beach, FL 33140, USA; Department of Pathology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL 33199, USA
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Wang Z, Fan Z, Yang L, Liu L, Sheng C, Song F, Huang Y, Chen K. Higher risk of cardiovascular mortality than cancer mortality among long-term cancer survivors. Front Cardiovasc Med 2023; 10:1014400. [PMID: 36760569 PMCID: PMC9905625 DOI: 10.3389/fcvm.2023.1014400] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2022] [Accepted: 01/02/2023] [Indexed: 01/26/2023] Open
Abstract
Background Previous studies focused more on the short-term risk of cardiovascular (CV) death due to traumatic psychological stress after a cancer diagnosis and the acute cardiotoxicity of anticancer treatments than on the long-term risk of CV death. Methods Time trends in the proportions of CV death (PCV), cancer death (PCA), and other causes in deaths from all causes were used to show preliminary relationships among the three causes of death in 4,806,064 patients with cancer from the Surveillance, Epidemiology, and End Results (SEER) program. Competing mortality risk curves were used to investigate when the cumulative CV mortality rate (CMRCV) began to outweigh the cumulative cancer mortality rate (CMRCA) for patients with cancer who survived for more than 10 years. Multivariable competing risk models were further used to investigate the potential factors associated with CV death. Results For patients with cancer at all sites, the PCV increased from 22.8% in the 5th year after diagnosis to 31.0% in the 10th year and 35.7% in the 20th year, while the PCA decreased from 57.7% in the 5th year after diagnosis to 41.2 and 29.9% in the 10th year and 20th year, respectively. The PCV outweighed the PCA (34.6% vs. 34.1%) since the 15th year for patients with cancer at all sites, as early as the 9th year for patients with colorectal cancer (37.5% vs. 33.2%) and as late as the 22nd year for patients with breast cancer (33.5% vs. 30.6%). The CMRCV outweighed the CMRCA since the 25th year from diagnosis. Multivariate competing risk models showed that an increased risk of CV death was independently associated with older age at diagnosis [hazard ratio and 95% confidence intervals [HR (95%CI)] of 43.39 (21.33, 88.28) for ≥ 80 vs. ≤ 30 years] and local metastasis [1.07 (1.04, 1.10)] and a decreased risk among women [0.82 (0.76, 0.88)], surgery [0.90 (0.87, 0.94)], and chemotherapy [0.85 (0.81, 0.90)] among patients with cancer who survived for more than 10 years. Further analyses of patients with cancer who survived for more than 20 years and sensitivity analyses by cancer at all sites showed similar results. Conclusion CV death gradually outweighs cancer death as survival time increases for most patients with cancer. Both the cardio-oncologist and cardio-oncology care should be involved to reduce CV deaths in long-term cancer survivors.
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Affiliation(s)
- Zhipeng Wang
- Department of Epidemiology and Biostatistics, Key Laboratory of Molecular Cancer Epidemiology, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, China
| | - Zeyu Fan
- Department of Epidemiology and Biostatistics, Key Laboratory of Molecular Cancer Epidemiology, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, China
| | - Lei Yang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Beijing Office for Cancer Prevention and Control, Peking University Cancer Hospital and Institute, Beijing, China
| | - Lifang Liu
- Department of Statistics, European Organization for Research and Treatment of Cancer, Brussels, Belgium
| | - Chao Sheng
- Department of Epidemiology and Biostatistics, Key Laboratory of Molecular Cancer Epidemiology, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, China
| | - Fengju Song
- Department of Epidemiology and Biostatistics, Key Laboratory of Molecular Cancer Epidemiology, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, China,Fengju Song,
| | - Yubei Huang
- Department of Epidemiology and Biostatistics, Key Laboratory of Molecular Cancer Epidemiology, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, China,*Correspondence: Yubei Huang,
| | - Kexin Chen
- Department of Epidemiology and Biostatistics, Key Laboratory of Molecular Cancer Epidemiology, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, China,Kexin Chen,
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Sari A, Cyr DP, Brar A, Messenger DE, Driman DK, Shivji S, Assarzadegan N, Juda A, Swallow CJ, Kennedy ED, Brar MS, Conner J, Kirsch R. Routine Elastin Staining in Surgically Resected Colorectal Cancer: Impact on Venous Invasion Detection and its Association With Oncologic Outcomes. Am J Surg Pathol 2022; 46:200-212. [PMID: 34411028 DOI: 10.1097/pas.0000000000001790] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
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<0.0001). The second review revealed a lower VI miss rate postimplementation than preimplementation (22% vs. 48%, respectively; P=0.007); this difference was even greater for extramural VI-positive cases (9% vs. 38%, respectively; P=0.0003). Missed VI cases postimplementation had fewer VI foci per missed case (P=0.02) and a trend towards less extramural VI than those missed preimplementation. VI assessed with an elastin stain was significantly associated with recurrence-free survival (P=0.003), and cancer-specific survival (P=0.01) in contrast to VI assessed on hematoxylin and eosin alone (P=0.053 and 0.1, respectively). The association between VI and hematogenous metastasis was far stronger for elastin-detected VI (OR=11.5; 95% CI: 3.4-37.1; P<0.0001) than for hematoxylin and eosin-detected VI (OR=3.7; 95% CI: 1.4-9.9; P=0.01). Routine elastin staining enhances VI detection and its ability to stratify risk in CRC and should be considered for evaluation of CRC resection specimens.
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Affiliation(s)
- Aysegul Sari
- Department of Pathology and Laboratory Medicine
- Department of Pathology, Izmir Katip Celebi University Ataturk Training and Research Hospital, Izmir, Turkey
| | - David P Cyr
- Lunenfeld-Tanenbaum Research Institute, Sinai Health System
- Department of Surgical Oncology, Princess Margaret Cancer Centre and Mount Sinai Hospital
- Department of Surgery, Division of General Surgery
- Institute of Medical Science
| | | | - David E Messenger
- Division of General Surgery, Royal United Hospital NHS Trust, Bath, UK
| | - David K Driman
- Department of Pathology, London Health Sciences Centre and Western University, London, ON, Canada
| | | | - Naziheh Assarzadegan
- Department of Pathology and Laboratory Medicine, The Johns Hopkins Hospital, Baltimore, MD
| | - Ari Juda
- Department of Pathology and Laboratory Medicine
| | - Carol J Swallow
- Lunenfeld-Tanenbaum Research Institute, Sinai Health System
- Department of Surgical Oncology, Princess Margaret Cancer Centre and Mount Sinai Hospital
- Department of Surgery, Division of General Surgery
- Institute of Medical Science
| | - Erin D Kennedy
- Department of Surgical Oncology, Princess Margaret Cancer Centre and Mount Sinai Hospital
- Department of Surgery, Division of General Surgery
| | | | - James Conner
- Department of Pathology and Laboratory Medicine
- Lunenfeld-Tanenbaum Research Institute, Sinai Health System
- Department of Pathobiology and Laboratory Medicine, University of Toronto, Toronto
| | - Richard Kirsch
- Department of Pathology and Laboratory Medicine
- Lunenfeld-Tanenbaum Research Institute, Sinai Health System
- Department of Pathobiology and Laboratory Medicine, University of Toronto, Toronto
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Shivji S, Kak I, Reid SL, Muir J, Hafezi-Bakhtiari S, Li-Chang H, Deliallisi A, Newell KJ, Grin A, Conner J, Kirsch R. 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; 45:1419-1427. [PMID: 33756495 DOI: 10.1097/pas.0000000000001707] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
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.
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Affiliation(s)
- Sameer Shivji
- Mount Sinai Hospital
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto
| | - Ipshita Kak
- Mount Sinai Hospital
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto
| | - Stephanie L Reid
- Mount Sinai Hospital
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto
| | - Jennifer Muir
- Mount Sinai Hospital
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto
| | - Sara Hafezi-Bakhtiari
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto
- Lakeridge Health, Oshawa
| | | | | | | | - Andrea Grin
- Department of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada
| | - James Conner
- Mount Sinai Hospital
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto
| | - Richard Kirsch
- Mount Sinai Hospital
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto
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Sofic A, Husic-Selimovic A, Efendic A, Sehic A, Julardzija F, Cizmic M, Beslagic E, Aladjuz-Granov L. MRI Evaluation of Extramural Venous Invasion (EMVI) with Rectal Carcinoma Using High Resolution T2 and Combination of High Resolution T2 and Contrast Enhanced T1 Weighted Imaging. Acta Inform Med 2021; 29:113-117. [PMID: 34584334 PMCID: PMC8443141 DOI: 10.5455/aim.2021.29.113-117] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2021] [Accepted: 06/17/2021] [Indexed: 01/12/2023] Open
Abstract
Background: EMVI is a direct invasion of a vein by a tumor. As a predictor of hematogenous metastasis, it is a poor prognostic factor in rectal cancer and can be accurately identified on MRI prior to surgical procedure. Objective: To evaluate the role of contrast-enhanced T1-weighted magnetic resonance imaging (CET1WI) in addition to high-resolution T2-weighted imaging (HRT2WI) in assessing extramural venous invasion (EMVI) of rectal cancer. Methods: In all 195 patients with rectal cancer, HRT2WI and CET1WI sequences were produced within pre-operative MRI for the purpose of assessing for the presence of EMVI (mrEMVI). CET1WI sequences were produced following administration of Gadolinium contrast medium. mrEMVI assessment results were classified into two groups. Group A consisted of mrEMVI assessment results obtained using HRT2WI sequences only. Group B consisted of mrEMVI assessment results obtained using a combination of HRT2WI + CET1WI sequences. Results obtained for each group (A and B) were correlated with a histopathological finding (pEMVI) as a reference standard. Results: Out of a total of 195 rectal cancer patients, mrEMVI was positive in 41 (21%) patients in group A, and in 45 (23%) patients in group B. Histopathological finding demonstrated pEMVI in 54 (27.7%) patients. A statistical analysis of group A (HRT2WI sequences) resulted in 75.9% sensitivity to mrEMVI and 96.4% specificity, Positive Predictive Value of 89.1% and Negative Predictive Value of 91.2% (95% confidence interval (CI), p< 0.05). Statistical analysis of group B (HRT2WI + CET1WI sequences) resulted in 83.3% sensitivity to mrEMVI and 98.5% specificity, Positive Predictive Value of 89.1% and Negative Predictive Value of 91.2% (CI 95%, p< 0.05). Conclusion: T1-weighted magnetic resonance imaging (CET1WI) in addition to high-resolution T2-weighted imaging (HRT2WI) increased evaluation of extramural venous invasion (EMVI) of rectal cancer.
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Affiliation(s)
- Amela Sofic
- Department of Radiology, General Hospital "Prim.dr.Abdulah Nakaš" Sarajevo, Bosnia and Herzegovin
| | - Azra Husic-Selimovic
- Department of Internal medicine, General Hospital "Prim.dr.Abdulah Nakaš", Sarajevo, Bosnia and Herzegovina
| | - Alma Efendic
- Department of Radiology, Cantonal Hospital Zenica, Zenica, Bosnia and Herzegovina
| | - Adnan Sehic
- Department of Radiological Technology, Faculty of Health Studies, University of Sarajevo, Bosnia and Herzegovina
| | - Fuad Julardzija
- Department of Radiological Technology, Faculty of Health Studies, University of Sarajevo, Bosnia and Herzegovina
| | - Midhat Cizmic
- Department of Radiology, General Hospital "Prim.dr.Abdulah Nakaš" Sarajevo, Bosnia and Herzegovin
| | - Eldina Beslagic
- Department of Radiology, General Hospital "Prim.dr.Abdulah Nakaš" Sarajevo, Bosnia and Herzegovin
| | - Lejla Aladjuz-Granov
- Department of Radiology, General Hospital "Prim.dr.Abdulah Nakaš" Sarajevo, Bosnia and Herzegovin
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Naso JR, Yang HM, Schaeffer DF. Variability in Synoptic Reporting of Colorectal Cancer pT4a Category and Lymphovascular Invasion. Arch Pathol Lab Med 2021; 145:343-351. [PMID: 32886771 DOI: 10.5858/arpa.2020-0124-oa] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/04/2020] [Indexed: 11/06/2022]
Abstract
CONTEXT.— Serosal involvement (pT4a category) and lymphovascular invasion have prognostic significance in colorectal carcinoma, but are subject to interobserver variation in assessment. OBJECTIVES.— To provide the first large-scale assessment of interobserver variability in pT4a category and lymphovascular invasion reporting in real-world practice and to explore the impact of information from guidelines on variability in reporting these features. DESIGN.— Analysis of 1555 consecutive synoptic reports of colorectal carcinoma was performed using multivariate logistic regression. Interobserver variability before and after the presentation of guideline information was assessed using an image-based survey. RESULTS.— Significant differences in the odds of reporting pT4a versus pT3 category, detecting lymphovascular invasion of any type, and detecting large vessel invasion were identified among hospital sites and for individual pathologists compared with the median pathologist at the same site. Consistent with these results, interobserver agreement was only moderate in the image-based survey regarding T4a staging and lymphovascular invasion (all κ ≤ 0.57). The provision of information from guidelines did not tend to increase interobserver agreement in the survey, though responses in favor of using an elastic stain increased following recommendations for their use. However, when observers were provided with elastic-stained images, interobserver agreement remained only moderate (κ = 0.55). CONCLUSIONS.— Real-world reporting of pT4a category and lymphovascular invasion shows substantial variability at both local and regional levels. Our study underscores the need to address these features in quality initiatives, and provides a novel method through which existing synoptic data can be harnessed to monitor reporting patterns and provide individualized feedback.
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Affiliation(s)
- Julia R Naso
- From the Division of Anatomic Pathology, Vancouver General Hospital, Vancouver, British Columbia, Canada.,The Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada
| | - Hui-Min Yang
- From the Division of Anatomic Pathology, Vancouver General Hospital, Vancouver, British Columbia, Canada.,The Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada
| | - David F Schaeffer
- From the Division of Anatomic Pathology, Vancouver General Hospital, Vancouver, British Columbia, Canada.,The Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada
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Comparison of safety between self-expanding metal stents as a bridge to surgery and emergency surgery based on pathology: a meta-analysis. BMC Surg 2020; 20:255. [PMID: 33109142 PMCID: PMC7592574 DOI: 10.1186/s12893-020-00908-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2020] [Accepted: 10/12/2020] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND To explore the long-term oncological safety of using self-expanding metal stents (SEMS) as a bridge to surgery for acute obstructive colorectal cancer by comparing the pathological results of emergency surgery (ES) with elective surgery after the placement of SEMS. METHODS Studies comparing SEMS as a bridge to surgery with emergency surgery for acute obstructive colorectal cancer were retrieved through the databases of Pubmed, Embase, and Cochrane libraries, and a meta-analysis was conducted based on the pathological results of the two treatments. Risk ratios (OR) or mean differences (MD) with 95% confidence intervals (CI) were calculated for the outcomes under random effects model. RESULTS A total of 27 studies were included, including 3 randomized controlled studies, 2 prospective studies, and 22 retrospective studies, with a total of 3737 patients. The presence of perineural invasion (RR = 0.58, 95% CI 0.48, 0.71, P < 0.00001), lymphovascular invasion (RR = 0.68, 95% CI 0.47, 0.99, P = 0.004) and vascular invasion (RR = 0.66, 95% CI 0.45, 0.99, P = 0.04) in SEMS group were significantly higher than those in ES group, and there was no significant difference in lymphatic invasion (RR = 0.92, 95% CI 0.77, 1.09, P = 0.33). The number of lymph nodes harvested in SEMS group was significantly higher than that in ES group (MD = - 3.18, 95% CI - 4.47, - 1.90, P < 0.00001). While no significant difference was found in the number of positive lymph nodes (MD = - 0.11, 95% CI - 0.63, 0.42, P = 0.69) and N stage [N0 (RR = 1.03, 95% CI 0.92, 1.15, P = 0.60), N1 (RR = 0.99, 95% CI 0.87, 1.14, P = 0.91), N2 (RR = 0.94, 95% CI 0.77, 1.15, P = 0.53)]. CONCLUSIONS SEMS implantation in patients with acute malignant obstructive colorectal cancer may lead to an increase in adverse tumor pathological characteristics, and these characteristics are mostly related to the poor prognosis of colorectal cancer. Although the adverse effect of SEMS on long-term survival has not been demonstrated, their adverse effects cannot be ignored. The use of SEMS as the preferred treatment for patients with resectable obstructive colorectal cancer remains to be carefully weighed, especially when patients are young or the surgical risk is not very high.
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Fukada M, Matsuhashi N, Takahashi T, Sugito N, Heishima K, Akao Y, Yoshida K. Tumor Tissue MIR92a and Plasma MIRs21 and 29a as Predictive Biomarkers Associated with Clinicopathological Features and Surgical Resection in a Prospective Study on Colorectal Cancer Patients. J Clin Med 2020; 9:jcm9082509. [PMID: 32759718 PMCID: PMC7465950 DOI: 10.3390/jcm9082509] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2020] [Revised: 07/15/2020] [Accepted: 07/29/2020] [Indexed: 12/21/2022] Open
Abstract
Cancer-related microRNAs (miRNAs) are emerging as non-invasive biomarkers for colorectal cancer (CRC). This study aimed to analyze the correlation between the levels of tissue and plasma miRNAs and clinicopathological characteristics and surgical resection. This study was a prospective study of CRC patients who underwent surgery. Forty-four sample pairs of tissue and plasma were analyzed. The miRNA levels were evaluated by RT-qPCR. The level of tumor tissue MIR92a showed a significant difference in CRC with lymph node metastasis, stage ≥ III, and high lymphatic invasion. In preoperative plasma, there were significant differences in CRC with stage ≥ III (MIR29a) and perineural invasion (MIR21). In multivariate analysis of lymphatic invasion, the levels of both preoperative plasma MIR29a and tumor tissue MIR92a showed significant differences. Furthermore, in cases with higher plasma miRNA level, the levels of plasma MIRs21 and 29a were significantly decreased after the operation. In this study, there were significant differences in miRNAs levels with respect to the sample type, clinicopathological features, and surgical resection. The levels of tumor tissue MIR92a and preoperative plasma MIR29a may have the potential as a biomarker for prognosis. The plasma MIRs21 and 29a level has the potential to be a predictive biomarker for treatment efficacy.
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Affiliation(s)
- Masahiro Fukada
- Department of Surgical Oncology, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu City 501-1194, Japan; (M.F.); (N.M.); (T.T.)
| | - Nobuhisa Matsuhashi
- Department of Surgical Oncology, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu City 501-1194, Japan; (M.F.); (N.M.); (T.T.)
| | - Takao Takahashi
- Department of Surgical Oncology, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu City 501-1194, Japan; (M.F.); (N.M.); (T.T.)
| | - Nobuhiko Sugito
- United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, 1-1 Yanagido, Gifu City 501-1194, Japan; (N.S.); (K.H.); (Y.A.)
| | - Kazuki Heishima
- United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, 1-1 Yanagido, Gifu City 501-1194, Japan; (N.S.); (K.H.); (Y.A.)
| | - Yukihiro Akao
- United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, 1-1 Yanagido, Gifu City 501-1194, Japan; (N.S.); (K.H.); (Y.A.)
| | - Kazuhiro Yoshida
- Department of Surgical Oncology, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu City 501-1194, Japan; (M.F.); (N.M.); (T.T.)
- Correspondence: ; Tel.: +81-058-230-6235
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Dawson H, Kirsch R, Messenger D, Driman D. A Review of Current Challenges in Colorectal Cancer Reporting. Arch Pathol Lab Med 2019; 143:869-882. [DOI: 10.5858/arpa.2017-0475-ra] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
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.
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Affiliation(s)
- Heather Dawson
- 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 Univer
| | - Richard Kirsch
- 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 Univer
| | - David Messenger
- 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 Univer
| | - David Driman
- 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 Univer
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11
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[Venous invasions in colonic adenocarcinoma: Value of elastic stain]. Ann Pathol 2018; 38:352-362. [PMID: 29843970 DOI: 10.1016/j.annpat.2018.02.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2017] [Revised: 01/23/2018] [Accepted: 02/26/2018] [Indexed: 11/23/2022]
Abstract
The aim of our study was to assess the value of Elastic stain in the diagnosis of venous invasion (VI) in colonic adenocarcinoma. MATERIAL AND METHODS All patients who undergone surgery for colonic adenocarcinoma at the University Hospital of Amiens, between 2004 and 2007, were included. Hematein-phloxin-saffron (HPS) stained slides of colectomy specimens were reviewed by two pathologists. Tumor blocks were stained with Elastic Stain (Roche - Ventana®). The presence or absence of VI, their number and localization were correlated with overall survival. RESULTS Two hundred and thirty-one cases were investigated and 3274 slides were examined. VI were more often diagnosed by Elastic Stain than HPS stain (66% vs. 40%). Ninety percent of VI were revealed within the first 6 HPS slides, and from the first 5 in Elastic Stain. The presence of VI revealed by Elastic Stain and/or HPS was significantly associated with decreased overall survival in multivariate analysis (P=0.029), especially for stage IIA tumors (P=0.016). Tumor differentiation (P=0.006) and pTNM stage (P=0.001) were also independent prognostic factors. The localization and the number of VI were not prognostic factors. CONCLUSION Our study confirms the prognostic value of VI, revealed by an elastic stain, in colonic adenocarcinoma. A systematic elastic stain of all tumor blocks (number at least 5) could be considered in the future, during pathological examination of colectomy for adenocarcinoma.
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12
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Role of Lymphovascular Invasion in Pattern C Invasive Endocervical Adenocarcinoma. Am J Surg Pathol 2017; 41:1205-1211. [DOI: 10.1097/pas.0000000000000822] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
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Kirsch R, Assarzadegan N, Messenger DE, Juda A, Riddell RH, Pollett A, Streutker CJ, Divaris DX, Newell KJ, Price RG, Smith S, Al-Haddad S, Parfitt JR, Driman DK. The impact of knowledge transfer on the detection of venous invasion in colorectal cancer. Hum Pathol 2017; 67:45-53. [DOI: 10.1016/j.humpath.2017.07.004] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2017] [Revised: 06/21/2017] [Accepted: 07/05/2017] [Indexed: 12/27/2022]
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MRI Detection of Extramural Venous Invasion in Rectal Cancer: Correlation With Histopathology Using Elastin Stain. AJR Am J Roentgenol 2016; 206:747-55. [PMID: 26933769 DOI: 10.2214/ajr.15.15568] [Citation(s) in RCA: 65] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
OBJECTIVE The purpose of this article is to evaluate the diagnostic performance of MRI for detection of extramural venous invasion (EMVI) compared with histopathologic analysis using elastin stain. MATERIALS AND METHODS Forty-nine patients with rectal cancer who had undergone surgical resection with preoperative MRI were identified. Thirty-seven patients had received preoperative chemoradiation therapy (CRT). Sixty-nine MRI studies were independently reviewed by two blinded radiologists for EMVI using a score of 0-4. Comparison was made with histopathologic results obtained by two pathologists reviewing the elastin-stained slides in consensus. EMVI status was also correlated with other tumoral and prognostic features on imaging and pathologic analysis. Statistical analysis was performed using Fisher exact and McNemar tests. RESULTS EMVI was present in 31% of the pathology specimens. An MRI EMVI score of 3-4 was 54% sensitive and 96% specific in detecting EMVI in veins 3 mm in diameter or larger. Inclusion of a score of 2 as positive for EMVI increased the sensitivity to 79% but decreased the specificity to 74%, with poor positive predictive value. Preoperative CRT had no significant effect on the diagnostic performance of MRI. Contrast-enhanced MRI increased reader confidence for diagnosis or exclusion of EMVI compared with T2-weighted imaging. EMVI status correlated with depth of extramural invasion and proximity to mesorectal fascia. CONCLUSION Despite an anticipated increase in sensitivity for EMVI detection by histopathologic analysis using elastin compared with H and E staining, MRI maintains a high specificity and moderate sensitivity for the detection of EMVI.
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15
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Cserni G, Bori R, Sejben I, Ágoston EI, Ács B, Szász AM. The Petersen prognostic index revisited in Dukes B colon cancer--Inter-institutional differences. Pathol Res Pract 2016; 212:73-6. [PMID: 26724146 DOI: 10.1016/j.prp.2015.08.006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2015] [Revised: 06/12/2015] [Accepted: 08/14/2015] [Indexed: 10/23/2022]
Abstract
A prognostic index (Petersen index, PI) was created for patients with pT3-4 pN0 M0 (Stage II, Dukes' B) colon cancers to distinguish between patients with better and worse outcome, and to help in recommending adjuvant chemotherapy for high risk patients in this stage. The prognostic value of the PI was evaluated in two independent retrospective series of stage II (Dukes' B) colon cancer patients. The parameters defining the PI (venous invasion, peritoneal involvement, circumferential margin involvement, perforation through the tumour) and performance of the PI were compared in two institutions. The two series of patients consisted of 127 and 87 patients. Venous invasion was more frequently detected at one of the centres (p<0.01) and tumour perforation was more frequent at the other (p<0.01). There were no significant differences in the 5-year survival estimates of all patients (p=0.19), and of either the low PI value groups (p=0.52) or that of the high PI value groups (p=0.99) between the two sites. In contrast, there were significant differences in the survival estimates between patients of the low PI category and those of the high PI category altogether (p<0.01) and in either centre. Although, it was expected that differences in the frequency of the parameters involved in the PI would influence its performance, this was not confirmed by the data. Our results suggest that using the PI may be of value in prognostic factor based therapy selection of colon carcinoma patients.
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Affiliation(s)
- Gábor Cserni
- Department of Pathology, Bács-Kiskun County Teaching Hospital, Nyíri út 38., Kecskemét 6000, Hungary; Department of Pathology, University of Szeged, Állomás u. 2., Szeged 6725, Hungary.
| | - Rita Bori
- Department of Pathology, Bács-Kiskun County Teaching Hospital, Nyíri út 38., Kecskemét 6000, Hungary
| | - István Sejben
- Department of Pathology, Bács-Kiskun County Teaching Hospital, Nyíri út 38., Kecskemét 6000, Hungary
| | - Emese I Ágoston
- 1(st) Department of Surgery, Semmelweis University, Üllői út 78., Budapest 1082, Hungary
| | - Balázs Ács
- 2(nd) Department of Pathology, Semmelweis University, Üllői út 93., Budapest 1091, Hungary
| | - A Marcell Szász
- Department of Pathology, Bács-Kiskun County Teaching Hospital, Nyíri út 38., Kecskemét 6000, Hungary; 2(nd) Department of Pathology, Semmelweis University, Üllői út 93., Budapest 1091, Hungary
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16
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Sejben I, Kocsis L, Török L, Cserni G. Elastic staining does not assist detection of venous invasion in cutaneous melanoma. Pathol Res Pract 2015; 212:51-3. [PMID: 26639870 DOI: 10.1016/j.prp.2015.11.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2015] [Revised: 07/03/2015] [Accepted: 11/11/2015] [Indexed: 12/01/2022]
Abstract
The aim of the present study was to determine the benefit of orcein elastic staining of primary cutaneous melanoma specimens in detecting venous invasion. Primary cutaneous melanomas in vertical growth phase were assessed for vascular invasion. All tumour blocks were stained with haematoxylin and eosin (H&E) and orcein. The cases were reviewed by two pathologists. Vascular invasion was not identified more frequently on orcein stained slides than on H&E stained ones. Elastosis and periappendiceal elastic fibres interfered with vascular invasion detection with elastic staining. Based on our study, we conclude that elastic stains such as orcein do not improve the detection rate of venous invasion in primary cutaneous melanomas.
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Affiliation(s)
- István Sejben
- Department of Pathology, Bács-Kiskun County Teaching Hospital, Nyíri út 38, H-6000 Kecskemét, Hungary.
| | - Lajos Kocsis
- Department of Pathology, Bács-Kiskun County Teaching Hospital, Nyíri út 38, H-6000 Kecskemét, Hungary; Department of Dermatology, Bács-Kiskun County Teaching Hospital, Nyíri út 38, H-6000 Kecskemét, Hungary
| | - László Török
- Department of Dermatology, Bács-Kiskun County Teaching Hospital, Nyíri út 38, H-6000 Kecskemét, Hungary
| | - Gábor Cserni
- Department of Pathology, Bács-Kiskun County Teaching Hospital, Nyíri út 38, H-6000 Kecskemét, Hungary; Department of Pathology, University of Szeged, Állomás u. 2, H-6720 Szeged, Hungary
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17
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Dawson H, Kirsch R, Driman DK, Messenger DE, Assarzadegan N, Riddell RH. Optimizing the detection of venous invasion in colorectal cancer: the ontario, Canada, experience and beyond. Front Oncol 2015; 4:354. [PMID: 25601902 PMCID: PMC4283716 DOI: 10.3389/fonc.2014.00354] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2014] [Accepted: 11/26/2014] [Indexed: 12/16/2022] Open
Abstract
Venous invasion (VI) is a well-established independent prognostic indicator in colorectal cancer (CRC). Its accurate detection is particularly important in stage II CRC as it may influence the decision to administer adjuvant therapy. The Royal College of Pathologists (RCPath) of the United Kingdom state that VI should be detected in at least 30% of CRC resection specimens. However, our experience in Ontario, Canada suggests that this (conservative) benchmark is rarely met. This article highlights the “Ontario experience” with respect to VI reporting and the key role that careful morphologic assessment, elastin staining and knowledge transfer has played in improving VI detection provincially and beyond.
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Affiliation(s)
- Heather Dawson
- Department of Pathology and Laboratory Medicine, Mount Sinai Hospital and University of Toronto , Toronto, ON , Canada ; Clinical Pathology Division, Institute of Pathology, University of Bern , Bern , Switzerland
| | - Richard Kirsch
- Department of Pathology and Laboratory Medicine, Mount Sinai Hospital and University of Toronto , Toronto, ON , Canada
| | - David K Driman
- Department of Pathology, London Health Sciences Centre, Western University , London, ON , Canada
| | - David E Messenger
- Division of General Surgery, Taunton and Somerset NHS Foundation Trust , Taunton , UK
| | - Naziheh Assarzadegan
- Department of Pathology and Laboratory Medicine, Mount Sinai Hospital and University of Toronto , Toronto, ON , Canada
| | - Robert H Riddell
- Department of Pathology and Laboratory Medicine, Mount Sinai Hospital and University of Toronto , Toronto, ON , Canada
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Maguire A, Sheahan K. Controversies in the pathological assessment of colorectal cancer. World J Gastroenterol 2014; 20:9850-9861. [PMID: 25110416 PMCID: PMC4123367 DOI: 10.3748/wjg.v20.i29.9850] [Citation(s) in RCA: 70] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2013] [Revised: 01/10/2014] [Accepted: 04/03/2014] [Indexed: 02/06/2023] Open
Abstract
Pathologic assessment of colorectal cancer specimens plays an essential role in patient management, informing prognosis and contributing to therapeutic decision making. The tumor-node-metastasis (TNM) staging system is a key component of the colorectal cancer pathology report and provides important prognostic information. However there is significant variation in outcome of patients within the same tumor stage. Many other histological features such as tumor budding, vascular invasion, perineural invasion, tumor grade and rectal tumor regression grade that may be of prognostic value are not part of TNM staging. Assessment of extramural tumor deposits and peritoneal involvement contributes to TNM staging but there are some difficulties with the definition of both of these features. Controversies in colorectal cancer pathology reporting include the subjective nature of some of the elements assessed, poor reporting rates and reproducibility and the need for standardized examination protocols and reporting. Molecular pathology is becoming increasingly important in prognostication and prediction of response to targeted therapies but accurate morphology still has a key role to play in colorectal cancer pathology reporting.
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The clinical utility of the combination of T stage and venous invasion to predict survival in patients undergoing surgery for colorectal cancer. Ann Surg 2014; 259:1156-65. [PMID: 24100338 DOI: 10.1097/sla.0000000000000229] [Citation(s) in RCA: 50] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
OBJECTIVE To examine the clinical utility of improved detection of venous invasion (VI) in patients undergoing potentially curative resection of colorectal cancer. BACKGROUND VI is a feature of colorectal cancer (CRC) progression. Elastica staining can be used to improve detection of VI and correspondingly its prediction of patient survival. METHODS A single-center, observational study of pathology variables, including detection of VI by staining for elastica, using 631 stage I to III CRC specimens, collected from 1997 to 2009 (176 analyzed retrospectively and 455 analyzed prospectively), was performed. RESULTS VI was detected in 56% of patients with CRC. Over a median follow-up period of 73 months, 238 patients died (134 from cancer). On multivariate analysis, VI by elastica staining was associated with a shorter survival duration, independent of other pathology features, in all cases [hazard ratio (HR) = 3.94, 95% confidence interval (CI): 2.33-6.65, P < 0.001] and in node-negative cases (HR = 3.55, 95% CI: 1.81-6.97; P < 0.001). In the absence of elastica-detected VI, with the exception of T stage, no other pathology features were associated with survival time. Therefore, the combination of T stage and VI (TVI) on survival was examined. Five-year cancer mortality could be stratified between 100% and 54% for patients with node-negative tumors and between 100% and 33% for patients with node-positive tumors. In all cases, the TVI had similar predictive value as that of T stage and node status (TNM). In node-negative disease, TVI had superior predictive value. CONCLUSIONS The results of the present study have prompted the development of a novel tumor staging system based on TVI. The TVI has clinical utility, especially in node-negative disease, in predicting outcome following curative resection for CRC.
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Castonguay MC, Li-Chang HH, Driman DK. Venous invasion in oesophageal adenocarcinoma: enhanced detection using elastic stain and association with adverse histological features and clinical outcomes. Histopathology 2013; 64:693-700. [PMID: 24117900 DOI: 10.1111/his.12308] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2013] [Accepted: 10/07/2013] [Indexed: 12/16/2022]
Abstract
AIMS In oesophageal adenocarcinoma, detection rates of venous invasion using haematoxylin and eosin (H&E) and elastic stains have not been compared. The aims of this study were to investigate whether or not elastic stains facilitate the detection of venous invasion, and to determine the prognostic significance of venous invasion following review with elastic stains. METHODS AND RESULTS One hundred and three resection specimens containing oesophageal adenocarcinoma, all reported originally as negative for venous invasion, were examined for the presence of venous invasion using H&E and subsequently Movat pentachrome stains. Venous invasion was detected in eight cases with H&E and an additional 66 cases using Movat pentachrome; overall, 72% of cases contained venous invasion. Venous invasion was associated with advanced stage, tumour size, lymphatic and perineural invasion and subsequent distant metastases. Venous invasion, stage, size, grade, lymphatic invasion and perineural invasion were prognostically significant on univariate analysis. Only tumour stage was independently prognostic. Two of eight patients with venous invasion but no other indication for adjuvant treatment died of recurrent disease. CONCLUSIONS Elastic stains improve detection of venous invasion significantly in oesophageal adenocarcinoma. Venous invasion is associated with multiple adverse clinicopathological features. Its identification may facilitate the stratification of patients at risk for visceral metastases and disease-related death.
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van Wyk HC, Roxburgh CS, Horgan PG, Foulis AF, McMillan DC. The detection and role of lymphatic and blood vessel invasion in predicting survival in patients with node negative operable primary colorectal cancer. Crit Rev Oncol Hematol 2013; 90:77-90. [PMID: 24332522 DOI: 10.1016/j.critrevonc.2013.11.004] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2013] [Revised: 10/09/2013] [Accepted: 11/14/2013] [Indexed: 12/15/2022] Open
Abstract
Although vascular invasion in colorectal cancer has been recognised since 1938, detection methods and results remain inconsistent. Vascular invasion is currently an independent prognostic factor in colorectal cancer influencing disease progression and survival. The vascular system consists of three components, arterial, venous and lymphatic vessels, all of which can be invaded but accurate distinction between the components remains difficult with routine staining techniques. Even though higher detection rates with elastica staining, for large vessel invasion, and recent techniques for immunohistochemistry for small vessel invasion, have been reported, a standardised method of detection has not been agreed upon which is reflected in the variability of published results. As a result of the Bowel Cancer Screening Programme in the UK it will be necessary to attempt to identify and stratify patients better, to be able to handle the stage migration to early node negative colorectal cancer. At present up to a third of patients, with node-negative colorectal cancer on conventional histopathological analysis, ultimately die of recurrent disease. It is therefore important to develop and standardised methods to identify lymphatic and blood vessel invasion which will influence ultimate survival. The present review summarises the current status of detection methods for these components of vascular invasion.
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Affiliation(s)
- Hester C van Wyk
- Academic Unit of Surgery, College of Medical, Veterinary and Life of Sciences, University of Glasgow, Glasgow, UK.
| | - Campbell S Roxburgh
- Academic Unit of Surgery, College of Medical, Veterinary and Life of Sciences, University of Glasgow, Glasgow, UK
| | - Paul G Horgan
- Academic Unit of Surgery, College of Medical, Veterinary and Life of Sciences, University of Glasgow, Glasgow, UK
| | - Alan F Foulis
- University Department of Pathology, College of Medical, Veterinary and Life of Sciences, University of Glasgow, Southern General Hospital, Glasgow, UK
| | - Donald C McMillan
- Academic Unit of Surgery, College of Medical, Veterinary and Life of Sciences, University of Glasgow, Glasgow, UK
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Preoperative evaluation of lymphovascular invasion using high-resolution pelvic magnetic resonance in patients with rectal cancer: a 2-year follow-up study. J Comput Assist Tomogr 2013; 37:583-8. [PMID: 23863536 DOI: 10.1097/rct.0b013e31828d616a] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
OBJECTIVES The objectives of this study were to preoperatively evaluate lymphovascular invasion (LVI) using pelvic magnetic resonance (MR) in patients with rectal cancer and to determine the correlation with distant metastasis rate. METHODS If the mesorectal perivascular infiltrative signal was visible on pelvic MR imaging, the possibility of LVI was recorded. Distant metastatic lesions were also recorded at the time of the initial diagnostic workup and over a 2-year follow-up period. RESULTS Fifteen (68.2%) of the 22 LVI patients showed mesorectal perivascular infiltrative signals on pelvic MRI. For the prediction of LVI in rectal cancer, MR had a sensitivity of 68.2% and a specificity of 93.2. The initial distant metastasis rate was significantly higher in patients with MR LVI (52%) than in patients without MR LVI (5.7%) (P < 0.0001). CONCLUSIONS On pelvic MR, the presence of mesorectal perivascular infiltration by nodes is a specific sign of LVI in rectal cancer, and the presence of LVI is a predictor of distant metastasis.
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Kojima M, Shimazaki H, Iwaya K, Kage M, Akiba J, Ohkura Y, Horiguchi S, Shomori K, Kushima R, Ajioka Y, Nomura S, Ochiai A. Pathological diagnostic criterion of blood and lymphatic vessel invasion in colorectal cancer: a framework for developing an objective pathological diagnostic system using the Delphi method, from the Pathology Working Group of the Japanese Society for Cancer of the Colon and Rectum. J Clin Pathol 2013; 66:551-8. [PMID: 23592799 PMCID: PMC3711366 DOI: 10.1136/jclinpath-2012-201076] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Aims The goal of this study is to create an objective pathological diagnostic system for blood and lymphatic vessel invasion (BLI). Methods 1450 surgically resected colorectal cancer specimens from eight hospitals were reviewed. Our first step was to compare the current practice of pathology assessment among eight hospitals. Then, H&E stained slides with or without histochemical/immunohistochemical staining were assessed by eight pathologists and concordance of BLI diagnosis was checked. In addition, histological findings associated with BLI having good concordance were reviewed. Based on these results, framework for developing diagnostic criterion was developed, using the Delphi method. The new criterion was evaluated using 40 colorectal cancer specimens. Results Frequency of BLI diagnoses, number of blocks obtained and stained for assessment of BLI varied among eight hospitals. Concordance was low for BLI diagnosis and was not any better when histochemical/immunohistochemical staining was provided. All histological findings associated with BLI from H&E staining were poor in agreement. However, observation of elastica-stained internal elastic membrane covering more than half of the circumference surrounding the tumour cluster as well as the presence of D2-40-stained endothelial cells covering more than half of the circumference surrounding the tumour cluster showed high concordance. Based on this observation, we developed a framework for pathological diagnostic criterion, using the Delphi method. This criterion was found to be useful in improving concordance of BLI diagnosis. Conclusions A framework for pathological diagnostic criterion was developed by reviewing concordance and using the Delphi method. The criterion developed may serve as the basis for creating a standardised procedure for pathological diagnosis.
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Affiliation(s)
- Motohiro Kojima
- Pathology Division, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan
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Cserni G, Sejben I, Bori R. Diagnosing vascular invasion in colorectal carcinomas: improving reproducibility and potential pitfalls. J Clin Pathol 2013; 66:543-7. [PMID: 23592798 DOI: 10.1136/jclinpath-2013-201587] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
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Venous invasion in colorectal cancer: impact of an elastin stain on detection and interobserver agreement among gastrointestinal and nongastrointestinal pathologists. Am J Surg Pathol 2013; 37:200-10. [PMID: 23108018 DOI: 10.1097/pas.0b013e31826a92cd] [Citation(s) in RCA: 83] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
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.
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Francis NJ, Rowlands M, Workman P, Jones K, Aherne W. Small-molecule inhibitors of the protein methyltransferase SET7/9 identified in a high-throughput screen. JOURNAL OF BIOMOLECULAR SCREENING 2012; 17:1102-9. [PMID: 22772057 DOI: 10.1177/1087057112452137] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/08/2023]
Abstract
Aberrant expression of chromatin-modifying enzymes (CMEs) is associated with a range of human diseases, including cancer. CMEs are now an important target area in drug discovery. Although the role that histone and protein (lysine) methyltransferases (PMTs) play in the regulation of transcription and cell growth is increasingly recognized, few small-molecule inhibitors of this class of enzyme have been reported. Here we describe an assay suitable for primary compound screening for the identification of PMT inhibitors. The assay followed the methylation of histones in the presence of the PMT SET7/9 and the radioactive cofactor S-adenosyl-methionine using scintillating microplates (FlashPlate) and was used to screen approximately 65 000 compounds (% coefficient of variation = 10%; Z' = 0.6). The hits identified from a library of more than 63 000 diverse small molecules included a series of rhodanine compounds with micromolar activity. A screen of the National Cancer Institute Diversity Set (2000 compounds) identified an orsein derivative that inhibited SET7/9 (~20 µM) and showed modest growth inhibition associated with the expected cellular phenotype of reduced histone methylation in a human tumor cell line. The assay represents a useful tool for the identification of inhibitors of PMT activity.
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Affiliation(s)
- Nicola-Jane Francis
- Cancer Research UK Cancer Therapeutics Unit, Division of Cancer Therapeutics, The Institute of Cancer Research, Haddow Laboratories, Sutton, UK
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Dirschmid K, Sterlacci W, Oellig F, Edlinger M, Jasarevic Z, Rhomberg M, Dirschmid H, Offner F. Absence of extramural venous invasion is an excellent predictor of metastasis-free survival in colorectal carcinoma stage II--a study using tangential tissue sectioning. J Clin Pathol 2012; 65:619-23. [PMID: 22554966 DOI: 10.1136/jclinpath-2011-200552] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
AIMS Extramural venous invasion (EVI) is an important predictor of haematogenous metastasis in colorectal cancer (CRC). However, remarkable discrepancies in incidence rates indicate major problems regarding EVI assessment. The present prospective study applies tangential vessel preparation to CRC resection specimens and correlates results of EVI with metachronous haematogenous metastatic (MHM) spread. METHODS Stage II CRC diagnosed at the Institute of Pathology, University Teaching Hospital Feldkirch, Austria over a period of 30 months were analysed and tangential sectioning of the pericolonic tissue was performed. Confirmation, or exclusion of MHM, as assessed by computerised tomography, sonography or biopsy, was recorded. RESULTS In 50/79 (63%) cases EVI was detected. In 13/50 (26%), MHM developed. Of the 29/79 (37%) patients without EVI, only one (3.5%) developed MHM. Statistically, the rate of MHM for patients with EVI was independent of adjuvant chemotherapy. CONCLUSIONS Tangential sectioning of the tumour periphery in CRC stage II yields a high rate of histologically evaluable extramural veins and permits proper assessment of EVI. Absence of EVI is significantly associated with metastasis-free survival, a finding of potential therapeutic value. On the other hand, one-third of the patients with EVI and circumferential tumour growth develop MHM, a setting in which the option for adjuvant chemotherapy should be considered. This study emphasises the importance of tangential sectioning of the invasive tumour front in CRC compared with the recommended perpendicular technique. The sensitivity and specificity of this method regarding MHM are characterised.
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Affiliation(s)
- Klaus Dirschmid
- Institute for Pathology, Academic Teaching Hospital Feldkirch, Feldkirch, Austria
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Messenger DE, Driman DK, Kirsch R. Developments in the assessment of venous invasion in colorectal cancer: implications for future practice and patient outcome. Hum Pathol 2012; 43:965-73. [PMID: 22406362 DOI: 10.1016/j.humpath.2011.11.015] [Citation(s) in RCA: 84] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2011] [Revised: 11/15/2011] [Accepted: 11/18/2011] [Indexed: 12/17/2022]
Abstract
Venous invasion, or "large vessel" invasion, is a known independent prognostic indicator of distant recurrence and survival in colorectal cancer. Accurate assessment of venous invasion is of particular importance in stage II disease because it may influence the decision to administer adjuvant therapy. Venous invasion is widely believed to be an underreported finding with significant variability in its reported incidence. In the most recent College of American Pathologists' cancer reporting protocol, venous invasion is not recorded separately from lymphovascular, or "small vessel" invasion, which may not be appropriate because these features confer differing prognostic information. The presence of extramural venous invasion is strongly predictive of adverse outcome, although the prognostic significance of intramural venous invasion remains unknown. There are no formal guidelines regarding the pathologic assessment of venous invasion or the application of specific reporting criteria. The routine use of an elastic stain results in an almost 3-fold increase in the venous invasion detection rate when compared with a standard hematoxylin and eosin stain and may be a cost-effective means of increasing the diagnostic yield of venous invasion. The development of high-resolution magnetic resonance imaging, where extramural venous invasion can be detected preoperatively, may also influence the manner in which pathologists process specimens. This review focuses on recent developments in the assessment of venous invasion and highlights their potential impact on future practice.
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Affiliation(s)
- David E Messenger
- Division of General Surgery, Royal United Hospital NHS Trust, Bath, BA1 3NG, UK
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Caldesmon is useful in demonstrating extramural venous invasion in colorectal carcinomas showing mucinous differentiation. Pathology 2012; 44:48-51. [DOI: 10.1097/pat.0b013e32834e426d] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
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TNM staging system of colorectal carcinoma: surgical pathology of the seventh edition. ACTA ACUST UNITED AC 2011. [DOI: 10.1016/j.mpdhp.2011.03.006] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
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