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1
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Ulkucu A, Erkaya M, Inal E, Gorgun E. The critical role of tumor size in predicting lymph node metastasis in early-stage colorectal cancer. Am J Surg 2025; 241:116152. [PMID: 39729965 DOI: 10.1016/j.amjsurg.2024.116152] [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: 07/30/2024] [Revised: 11/27/2024] [Accepted: 12/16/2024] [Indexed: 12/29/2024]
Abstract
BACKGROUND Main purpose of this study is to investigate impact of tumor size on risk of lymph node metastasis (LNM) in pT1-stage colorectal cancer (CRC), focusing on colon, rectosigmoid junction, and rectum. METHOD Patients diagnosed with primary pT1 CRC between 2015 and 2019 were selected from National Cancer Database, utilizing International Classification of Diseases for Oncology, Third Edition (ICD-O-3) codes. We analyzed factors influencing LNM using uni- and multivariate analysis, then isolated tumor size to study its impact on LNM. RESULTS In this study of 27,649 pT1-stage tumor patients, we found that 10 % of colon, 16 % of rectosigmoid junction, and 13 % of rectum were LNM+. The study had 14,339 males (51.97 %). Mean age was 64.9 (±11.7). In multivariate analysis, sample was adjusted by excluding confounding factors, isolating impact of tumor size on LNM. Analysis for only tumor size, patients with colon tumors >45 mm had 53 % increased odds of LNM (95 % CI [1.06, 2.23], p = 0.03), whereas tumor size did not significantly affect LNM in rectosigmoid and rectum cases, with odds ratios of 2.05 (95 % CI [0.82, 5.09], p = 0.12) and 1.62 (95 % CI [0.97, 2.71], p = 0.065) respectively, for tumors ≥45 mm compared to those <15 mm. CONCLUSION This investigation refines predictors of LNM, crucial for tailoring organ-sparing strategies in early-stage CRC management. While tumor size is significant determinant of LNM in colon cancer, early rectal and rectosigmoid cancers may be associated with lower risk of LNM.
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Affiliation(s)
- Attila Ulkucu
- Department of Colorectal Surgery, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Metincan Erkaya
- Department of Colorectal Surgery, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Ekin Inal
- Department of Colorectal Surgery, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Emre Gorgun
- Department of Colorectal Surgery, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA.
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2
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Öztürk SK, Bokhorst JM, Baumann E, Sheahan K, van de Velde CJH, Marijnen CAM, Hospers GAP, Doukas M, Vieth M, Lugli A, Nagtegaal ID. Exploring Intratumoral Budding in Colorectal Cancer Using Computational Pathology: A Biopsy-Based Evaluation. Mod Pathol 2025; 38:100655. [PMID: 39522647 DOI: 10.1016/j.modpat.2024.100655] [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: 07/26/2024] [Revised: 10/08/2024] [Accepted: 11/04/2024] [Indexed: 11/16/2024]
Abstract
Owing to insufficient evidence, tumor budding (TB) is not currently evaluated in colorectal cancer (CRC) biopsies. This study investigates TB in CRC by establishing the value of intratumoral budding (ITB) in resection specimens and assessing the feasibility and clinical value of TB in biopsies. TB was assessed using an algorithm in all cases. In a test cohort of 555 primarily surgically treated CRC patients, we assessed the prognostic impact of ITB compared with peritumoral budding (PTB). The distribution of ITB in the uppermost 5 mm of resection specimens was analyzed to validate TB counting in biopsies. We further validated the prognostic and predictive impact of TB in biopsies of 285 rectal cancer patients, focusing on overall survival and response to neoadjuvant therapy. High-grade TB, whether intratumoral or peritumoral and in biopsies or resections, was associated with advanced pathological stage, lymphatic invasion, infiltrative tumor border, and poor overall survival in the test cohort. Superficial ITBs (0-3 mm from the lumen) accurately predicted the final TB grade based on PTB in 87% of tumors, with 87% of tumors having at least 1 superficial ITB hotspot. ITB (hazard ratio, 3.5; 95% CI, 1.1-10.8) was an independent predictor of overall survival, unlike PTB. In the validation cohort, TB presence in biopsies significantly reduced the likelihood of achieving a pathological complete response (odds ratio, 0.3; 95% CI, 0.1-0.7; P = .007). ITB is as prognostic as PTB, and evaluating both can improve risk stratification in CRC. TB assessment in biopsies can identify poor prognosis and predict response to neoadjuvant therapy.
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Affiliation(s)
- Sonay Kuş Öztürk
- Department of Pathology, Radboud University Medical Centre, Nijmegen, the Netherlands.
| | - John-Melle Bokhorst
- Department of Pathology, Radboud University Medical Centre, Nijmegen, the Netherlands
| | - Elias Baumann
- Institute of Tissue Medicine and Pathology, University of Bern, Bern, Switzerland
| | - Kieran Sheahan
- Department of Pathology, St. Vincent's University Hospital, Dublin, Ireland; School of Medicine and Medical Sciences, University College Dublin, Dublin, Ireland
| | | | - Corrie A M Marijnen
- Department of Radiotherapy, Leiden University Medical Centre, Leiden, the Netherlands; Department of Radiotherapy, Antoni van Leeuwenhoek, Amsterdam, the Netherlands
| | - Geke A P Hospers
- Department of Medical Oncology, University of Groningen, University Medical Centre Groningen, Groningen, the Netherlands
| | - Michail Doukas
- Department of Pathology, Erasmus Medical Centre, Rotterdam, the Netherlands
| | - Michael Vieth
- Institute of Pathology, Friedrich-Alexander-University Erlangen-Nuremberg, Klinikum Bayreuth, Bayreuth, Germany
| | - Alessandro Lugli
- Institute of Tissue Medicine and Pathology, University of Bern, Bern, Switzerland
| | - Iris D Nagtegaal
- Department of Pathology, Radboud University Medical Centre, Nijmegen, the Netherlands
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3
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Sasaki B, Yamada M, Mishima Y, Ohmine T, Tani M, Sato A, Toda K, Yazawa T, Ohe H, Yamanaka K. Risk Factors Associated With Lymph Node Metastasis and Recurrence in Surgical Cases of pT1 Colorectal Cancer. Cureus 2024; 16:e76333. [PMID: 39734562 PMCID: PMC11682683 DOI: 10.7759/cureus.76333] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/23/2024] [Indexed: 12/31/2024] Open
Abstract
Objective This study aims to investigate the risk factors for lymph node metastasis (LNM) and postoperative recurrence in patients undergoing surgery for pT1 colorectal cancer (pT1-CRC). Materials and methods We retrospectively analyzed 150 patients who underwent bowel resection with lymph node dissection for pT1-CRC at our department between September 2011 and December 2021. Univariate and multivariate analyses were performed to examine the effects of sex, depth of tumor invasion, venous invasion, lymphatic invasion, tumor budding (BD), and histological type on LNM and recurrence. We analyzed recurrence-free survival (RFS) curves. Results LNM was observed in 21 (14.0%) patients. Univariate analysis identified female sex, undifferentiated histological type, positive lymphatic invasion, and tumor budding grade 2/3 (BD2/3) as significant risk factors for LNM, whereas multivariate analysis identified female sex, undifferentiated histological type, and BD2/3 as independent risk factors. No cancer-related deaths were observed during the median observation period of 60.7 months. The five-year RFS rate differed significantly between LNM- and LNM+ patients, at 97.3% and 66.4%, respectively (p=0.0005). BD2/3 was also the significant risk factor for recurrence in the univariate analysis (p<0.0001). In LNM- patients, the five-year RFS was 98.7% for BD1 and 88.2% for BD2/3 (p=0.0014), while in LNM+ patients, it was 100% for BD1 and 37.0% for BD2/3 (p=0.036), with significant differences observed. Conclusion In pT1-CRC patients, female sex, undifferentiated histological type, and BD2/3 were the risk factors for LNM. The recurrence rate was higher in patients with LNM than in those without LNM. Regardless of LNM, BD2/3 was the risk factor for the postoperative recurrence of pT1-CRC.
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Affiliation(s)
- Ben Sasaki
- Surgery, Shiga General Hospital, Moriyama, JPN
| | | | | | | | - Masaki Tani
- Surgery, Shiga General Hospital, Moriyama, JPN
| | - Asahi Sato
- Surgery, Shiga General Hospital, Moriyama, JPN
| | - Kosuke Toda
- Surgery, Shiga General Hospital, Moriyama, JPN
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4
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Mateos Sanchez C, Quintanilla Lazaro E, Rabago LR. How secure can we expect the surveillance policies to be after the implementation in T1 polyps with carcinoma? World J Gastrointest Endosc 2024; 16:502-508. [PMID: 39351175 PMCID: PMC11438583 DOI: 10.4253/wjge.v16.i9.502] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2024] [Revised: 08/08/2024] [Accepted: 08/20/2024] [Indexed: 09/12/2024] Open
Abstract
Approximately 7% of the polyps resected endoscopically have an adenocarcinoma focus, with no previous endoscopic evidence of malignancy. This raises the question of whether endoscopic resection has been curative. Furthermore, there is no consensus on what the endoscopic and histological criteria for good prognosis are, the appropriate follow-up strategy and what are the long-term results. The aim of the retrospective study by Fábián et al was to evaluate the occurrence of local relapse or distant metastasis in those tumors that were resected endoscopically compared to those that underwent oncologic surgery. They concluded that, regardless of the treatment strategy chosen, there was a higher recurrence rate than described in the literature and that adherence to follow-up was poor. The management approach for an endoscopically benign polyp histologically confirmed as adenocarcinoma depends on the presence of any of the previously described poor prognostic histological factors. If none of these factors are present and the polyp has been completely resected en bloc (R0), active surveillance is considered appropriate as endoscopic resection is deemed curative. These results highlight, once again, the need for further multicentric clinical practice studies to obtain more evidence for the purpose of establishing appropriate treatment and follow-up strategies.
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Affiliation(s)
| | | | - Luis Ramon Rabago
- Department of Gastroenterology, San Rafael Hospital, Madrid 28016, Spain
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5
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Watanabe J, Ichimasa K, Kataoka Y, Miyahara S, Miki A, Yeoh KG, Kawai S, Martínez de Juan F, Machado I, Kotani K, Sata N. Diagnostic Accuracy of Highest-Grade or Predominant Histological Differentiation of T1 Colorectal Cancer in Predicting Lymph Node Metastasis: A Systematic Review and Meta-Analysis. Clin Transl Gastroenterol 2024; 15:e00673. [PMID: 38165075 PMCID: PMC10962900 DOI: 10.14309/ctg.0000000000000673] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2023] [Accepted: 12/15/2023] [Indexed: 01/03/2024] Open
Abstract
INTRODUCTION Treatment guidelines for colorectal cancer (CRC) suggest 2 classifications for histological differentiation-highest grade and predominant. However, the optimal predictor of lymph node metastasis (LNM) in T1 CRC remains unknown. This systematic review aimed to evaluate the impact of the use of highest-grade or predominant differentiation on LNM determination in T1 CRC. METHODS The study protocol is registered in the International Prospective Register of Systematic Reviews (PROSPERO, registration number: CRD42023416971) and was published in OSF ( https://osf.io/TMAUN/ ) on April 13, 2023. We searched 5 electronic databases for studies assessing the diagnostic accuracy of highest-grade or predominant differentiation to determine LNM in T1 CRC. The outcomes were sensitivity and specificity. We simulated 100 cases with T1 CRC, with an LNM incidence of 11.2%, to calculate the differences in false positives and negatives between the highest-grade and predominant differentiations using a bootstrap method. RESULTS In 42 studies involving 41,290 patients, the differentiation classification had a pooled sensitivity of 0.18 (95% confidence interval [CI] 0.13-0.24) and 0.06 (95% CI 0.04-0.09) ( P < 0.0001) and specificity of 0.95 (95% CI 0.93-0.96) and 0.98 (95% CI 0.97-0.99) ( P < 0.0001) for the highest-grade and predominant differentiations, respectively. In the simulation, the differences in false positives and negatives between the highest-grade and predominant differentiations were 3.0% (range 1.6-4.4) and -1.3% (range -2.0 to -0.7), respectively. DISCUSSION Highest-grade differentiation may reduce the risk of misclassifying cases with LNM as negative, whereas predominant differentiation may prevent unnecessary surgeries. Further studies should examine differentiation classification using other predictive factors.
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Affiliation(s)
- Jun Watanabe
- Department of Surgery, Division of Gastroenterological, General and Transplant Surgery, Jichi Medical University, Shimotsuke, Tochigi, Japan
- Division of Community and Family Medicine, Jichi Medical University, Shimotsuke-City, Tochigi, Japan
| | - Katsuro Ichimasa
- Digestive Disease Center, Showa University, Northern Yokohama Hospital, Tsuzuki-ku, Yokohama, Japan
- Department of Medicine, National University of Singapore, Singapore
| | - Yuki Kataoka
- Department of Internal Medicine, Kyoto Min-iren Asukai Hospital, Sakyo-ku, Kyoto, Japan
- Scientific Research WorkS Peer Support Group (SRWS-PSG), Osaka, Japan
- Section of Clinical Epidemiology, Department of Community Medicine, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto, Japan
- Department of Healthcare Epidemiology, Kyoto University Graduate School of Medicine/Public Health, Sakyo-ku, Kyoto, Japan
| | - Shoko Miyahara
- Department of Medicine, Division of Gastroenterology, Jichi Medical University, Shimotsuke, Tochigi, Japan
| | - Atsushi Miki
- Department of Surgery, Division of Gastroenterological, General and Transplant Surgery, Jichi Medical University, Shimotsuke, Tochigi, Japan
| | - Khay Guan Yeoh
- Department of Medicine, National University of Singapore, Singapore
- Department of Gastroenterology and Hepatology, National University Hospital, Singapore
| | - Shigeo Kawai
- Department of Diagnostic Pathology, Tochigi Medical Center Shimotsuga, Tochigi-City, Tochigi, Japan
| | - Fernando Martínez de Juan
- Department of Gastroenterology and Endoscopy Unit, Instituto Valenciano de Oncología, Valencia, Spain
- Endoscopy Unit, Hospital Quiron Salud, Valencia, Spain
- Medicine, Universidad Cardenal Herrrera-CEU, CEU Universities, Valencia, Spain
| | - Isidro Machado
- Pathology Department, Instituto Valenciano de Oncología, Patologika Laboratory Hospital Quiron Salud and Pathology Department University of Valencia, Valencia, Spain
- CIBERONC, Madrid, Spain
| | - Kazuhiko Kotani
- Division of Community and Family Medicine, Jichi Medical University, Shimotsuke-City, Tochigi, Japan
| | - Naohiro Sata
- Department of Surgery, Division of Gastroenterological, General and Transplant Surgery, Jichi Medical University, Shimotsuke, Tochigi, Japan
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Shah AH, Gami AJ, Desai NH, Gandhi JS, Trivedi PP. Tumor budding as a prognostic indicator in colorectal carcinoma: a retrospective study of primary colorectal carcinoma cases in a tertiary care center. Indian J Surg Oncol 2022; 13:459-467. [PMID: 36187533 PMCID: PMC9515303 DOI: 10.1007/s13193-022-01498-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2021] [Accepted: 01/11/2022] [Indexed: 10/19/2022] Open
Abstract
Colorectal carcinoma (CRC) is the third most common cancer worldwide. Along with many established prognostic factors, tumor budding is emerging as a valuable marker of prognosis. Tumor budding is not yet universally reported but it has recently been suggested in guidelines by ITBCC (International Tumor Budding Consensus Conference). Our aim is to study prognostic implications of tumor budding in CRC. Hundred cases of primary CRC specimens were retrospectively studied from January, 2016, to February, 2017. Tumor bud count and other histopathological parameters were evaluated from hematoxyline and eosin (H & E) stained slides. Survival analysis was done using Cox proportional hazards model. Association of tumor budding and cancer-specific survival was found to be statistically significant (P = 0.018 for average tumor budding and P = 0.035 for highest tumor budding) Tumor budding was found to be significantly associated with other clinicopathological parameters such as T stage, N stage, TNM stage, and lymphovascular invasion with p value < 0.05. Tumor budding is a valuable prognostic indictor for primary CRC and also significantly associated with other prognostic parameters. It should be reported routinely as a guide to prognosis and further management of patients.
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Affiliation(s)
- Ashini H. Shah
- Department of Oncopathology, Gujarat Cancer and Research Institute, Ahmedabad, 380016 Gujarat India
| | - Amisha J. Gami
- Department of Oncopathology, Gujarat Cancer and Research Institute, Ahmedabad, 380016 Gujarat India
| | - Neetal H. Desai
- Department of Oncopathology, Gujarat Cancer and Research Institute, Ahmedabad, 380016 Gujarat India
| | - Jahnavi S. Gandhi
- Department of Oncopathology, Gujarat Cancer and Research Institute, Ahmedabad, 380016 Gujarat India
| | - Priti P. Trivedi
- Department of Oncopathology, Gujarat Cancer and Research Institute, Ahmedabad, 380016 Gujarat India
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7
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Ichimasa K, Kudo SE, Miyachi H, Kouyama Y, Mochizuki K, Takashina Y, Maeda Y, Mori Y, Kudo T, Miyata Y, Akimoto Y, Kataoka Y, Kubota T, Nemoto T, Ishida F, Misawa M. Current problems and perspectives of pathological risk factors for lymph node metastasis in T1 colorectal cancer: Systematic review. Dig Endosc 2022; 34:901-912. [PMID: 34942683 DOI: 10.1111/den.14220] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2021] [Revised: 12/18/2021] [Accepted: 12/20/2021] [Indexed: 02/08/2023]
Abstract
With the prevalence of endoscopic submucosal dissection and endoscopic full thickness resection, which enable complete resection of T1 colorectal cancer with a negative margin, the treatment strategy following endoscopic resection has become more important. The necessity of secondary surgical resection is determined on the basis of the risk of lymph node metastasis according to the histopathological findings of resected specimens because ~10% of T1 colorectal cancer cases have lymph node metastasis. The current Japanese treatment guidelines state four risk factors for lymph node metastasis: lymphovascular invasion, histological differentiation, depth of submucosal invasion, and tumor budding. These guidelines have succeeded in stratifying the low-risk group for lymph node metastasis, in which endoscopic resection alone is acceptable for cure. On the other hand, there are some problems: there is variation in diagnosis methods and low interobserver agreement for each pathological factor and 90% of surgical resections are unnecessary, with lymph node metastasis negativity. To ensure patients with T1 colorectal cancer receive more appropriate treatment, these problems should be addressed. In this systematic review, we gave some suggestions to these practical issues of four pathological factors as predictors.
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Affiliation(s)
- Katsuro Ichimasa
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Kanagawa, Japan
| | - Shin-Ei Kudo
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Kanagawa, Japan
| | - Hideyuki Miyachi
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Kanagawa, Japan
| | - Yuta Kouyama
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Kanagawa, Japan
| | - Kenichi Mochizuki
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Kanagawa, Japan
| | - Yuki Takashina
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Kanagawa, Japan
| | - Yasuharu Maeda
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Kanagawa, Japan
| | - Yuichi Mori
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Kanagawa, Japan
- Clinical Effectiveness Research Group, Institute of Health and Society, University of Oslo, Oslo, Norway
| | - Toyoki Kudo
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Kanagawa, Japan
| | - Yuki Miyata
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Kanagawa, Japan
| | - Yoshika Akimoto
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Kanagawa, Japan
| | - Yuki Kataoka
- Department of Internal Medicine, Kyoto Min-Iren Asukai Hospital, Kyoto, Japan
- Section of Clinical Epidemiology, Department of Community Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
- Department of Healthcare Epidemiology, Kyoto University Graduate School of Medicine/School of Public Health, Kyoto, Japan
- Systematic Review Workshop Peer Support Group (SRWS-PSG), Osaka, Japan
| | - Takafumi Kubota
- Systematic Review Workshop Peer Support Group (SRWS-PSG), Osaka, Japan
- Department of Neurology, Tohoku University Graduate School of Medicine, Miyagi, Japan
| | - Tetsuo Nemoto
- Pathology Department, Showa University Northern Yokohama Hospital, Kanagawa, Japan
| | - Fumio Ishida
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Kanagawa, Japan
| | - Masashi Misawa
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Kanagawa, Japan
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8
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Zwager LW, Bastiaansen BAJ, Montazeri NSM, Hompes R, Barresi V, Ichimasa K, Kawachi H, Machado I, Masaki T, Sheng W, Tanaka S, Togashi K, Yasue C, Fockens P, Moons LMG, Dekker E. Deep Submucosal Invasion Is Not an Independent Risk Factor for Lymph Node Metastasis in T1 Colorectal Cancer: A Meta-Analysis. Gastroenterology 2022; 163:174-189. [PMID: 35436498 DOI: 10.1053/j.gastro.2022.04.010] [Citation(s) in RCA: 97] [Impact Index Per Article: 32.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2021] [Revised: 03/17/2022] [Accepted: 04/02/2022] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Deep submucosal invasion (DSI) is considered a key risk factor for lymph node metastasis (LNM) and important criterion to recommend surgery in T1 colorectal cancer. However, metastatic risk for DSI is shown to be low in the absence of other histologic risk factors. This meta-analysis determines the independent risk of DSI for LNM. METHODS Suitable studies were included to establish LNM risk for DSI in univariable analysis. To assess DSI as independent risk factor, studies were eligible if risk factors (eg, DSI, poor differentiation, lymphovascular invasion, and high-grade tumor budding) were simultaneously included in multivariable analysis or LNM rate of DSI was described in absence of poor differentiation, lymphovascular invasion, and high-grade tumor budding. Odds ratios (OR) and 95% CIs were calculated. RESULTS Sixty-seven studies (21,238 patients) were included. Overall LNM rate was 11.2% and significantly higher for DSI-positive cancers (OR, 2.58; 95% CI, 2.10-3.18). Eight studies (3621 patients) were included in multivariable meta-analysis and did not weigh DSI as a significant predictor for LNM (OR, 1.73; 95% CI, 0.96-3.12). As opposed to a significant association between LNM and poor differentiation (OR, 2.14; 95% CI, 1.39-3.28), high-grade tumor budding (OR, 2.83; 95% CI, 2.06-3.88), and lymphovascular invasion (OR, 3.16; 95% CI, 1.88-5.33). Eight studies (1146 patients) analyzed DSI as solitary risk factor; absolute risk of LNM was 2.6% and pooled incidence rate was 2.83 (95% CI, 1.66-4.78). CONCLUSIONS DSI is not a strong independent predictor for LNM and should be reconsidered as a sole indicator for oncologic surgery. The expanding armamentarium for local excision as first-line treatment prompts serious consideration in amenable cases to tailor T1 colorectal cancer management.
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Affiliation(s)
- Liselotte W Zwager
- Amsterdam University Medical Centers location University of Amsterdam, Department of Gastroenterology and Hepatology, Amsterdam, the Netherlands; Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, the Netherlands; Cancer Center Amsterdam, Amsterdam, the Netherlands
| | - Barbara A J Bastiaansen
- Amsterdam University Medical Centers location University of Amsterdam, Department of Gastroenterology and Hepatology, Amsterdam, the Netherlands; Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, the Netherlands; Cancer Center Amsterdam, Amsterdam, the Netherlands.
| | - Nahid S M Montazeri
- Biostatistics Unit, Department of Gastroenterology and Hepatology, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands
| | - Roel Hompes
- Department of Surgery, Amsterdam University Medical Center, Amsterdam Cancer Center, University of Amsterdam, Amsterdam, The Netherlands
| | - Valeria Barresi
- Department of Diagnostics and Public Health, University of Verona, Verona, Italy
| | - Katsuro Ichimasa
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Tsuzuki, Yokohama, Japan
| | - Hiroshi Kawachi
- Department of Pathology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Isidro Machado
- Pathology Department, Instituto Valenciano de Oncología and Patologika Laboratory Hospital Quiron Salud, Valencia, Spain
| | - Tadahiko Masaki
- Department of Surgery, Kyorin University, Shinkawa, Mitaka City, Tokyo, Japan
| | - Weiqi Sheng
- Department of Pathology, Fudan University, Shanghai Cancer Center, Shanghai, China
| | - Shinji Tanaka
- Department of Endoscopy, Hiroshima University Hospital, Hiroshima, Japan
| | - Kazutomo Togashi
- Coloproctology, Aizu Medical Center, Fukushima Medical University, Aizuwakamatsu, Fukushima, Japan
| | - Chihiro Yasue
- Department of Gastroenterology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Koto-ku, Tokyo, Japan
| | - Paul Fockens
- Amsterdam University Medical Centers location University of Amsterdam, Department of Gastroenterology and Hepatology, Amsterdam, the Netherlands; Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, the Netherlands; Cancer Center Amsterdam, Amsterdam, the Netherlands
| | - Leon M G Moons
- Department of Gastroenterology and Hepatology, Utrecht University Medical Center, Utrecht, The Netherlands
| | - Evelien Dekker
- Amsterdam University Medical Centers location University of Amsterdam, Department of Gastroenterology and Hepatology, Amsterdam, the Netherlands; Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, the Netherlands; Cancer Center Amsterdam, Amsterdam, the Netherlands
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9
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Komut N, Bektaş S, EmineYıldırım. The relationship of tumor budding with GOLPH3 expression and histopathological prognostic parameters in colorectal adenocarcinoma. Ann Diagn Pathol 2022; 58:151933. [DOI: 10.1016/j.anndiagpath.2022.151933] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2021] [Revised: 01/16/2022] [Accepted: 02/21/2022] [Indexed: 11/26/2022]
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10
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Takashina Y, Kudo SE, Ichimasa K, Kouyama Y, Mochizuki K, Akimoto Y, Maeda Y, Mori Y, Misawa M, Ogata N, Kudo T, Hisayuki T, Hayashi T, Wakamura K, Sawada N, Baba T, Ishida F, Yokoyama K, Daita M, Nemoto T, Miyachi H. Clinicopathological features of small T1 colorectal cancers. World J Clin Cases 2021; 9:10088-10097. [PMID: 34904078 PMCID: PMC8638043 DOI: 10.12998/wjcc.v9.i33.10088] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2021] [Revised: 06/14/2021] [Accepted: 10/11/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Although small colorectal neoplasms (< 10 mm) are often easily resected endoscopically and are considered to have less malignant potential compared with large neoplasms (≥ 10 mm), some are invasive to the submucosa. AIM To clarify the clinicopathological features of small T1 colorectal cancers. METHODS Of 32025 colorectal lesions between April 2001 and March 2018, a total of 1152 T1 colorectal cancers resected endoscopically or surgically were included in this study and were divided into two groups by tumor size: a small group (< 10 mm) and a large group (≥ 10 mm). We compared clinicopathological factors including lymph node metastasis (LNM) between the two groups. RESULTS The incidence of small T1 cancers was 10.1% (116/1152). The percentage of initial endoscopic treatment in small group was significantly higher than in large group (< 10 mm 74.1% vs ≥ 10 mm 60.2%, P < 0.01). In the surgical resection cohort (n = 798), the rate of LNM did not significantly differ between the two groups (small 12.3% vs large 10.9%, P = 0.70). In addition, there were also no significant differences between the two groups in pathological factors such as histological grade, vascular invasion, or lymphatic invasion. CONCLUSION Because there was no significant difference in the rate of LNM between small and large T1 colorectal cancers, the requirement for additional surgical resection should be determined according to pathological findings, regardless of tumor size.
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Affiliation(s)
- Yuki Takashina
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama 224-8503, Japan
- Department of Gastroenterology, Nikko Kinen Hospital, Muroran 051-8501, Japan
| | - Shin-Ei Kudo
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama 224-8503, Japan
| | - Katsuro Ichimasa
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama 224-8503, Japan
| | - Yuta Kouyama
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama 224-8503, Japan
| | - Kenichi Mochizuki
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama 224-8503, Japan
| | - Yoshika Akimoto
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama 224-8503, Japan
| | - Yasuharu Maeda
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama 224-8503, Japan
| | - Yuichi Mori
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama 224-8503, Japan
- Clinical Effectiveness Research Group, Institute of Health and Society, University of Oslo, Oslo 0001, Norway
| | - Masashi Misawa
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama 224-8503, Japan
| | - Noriyuki Ogata
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama 224-8503, Japan
| | - Toyoki Kudo
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama 224-8503, Japan
| | - Tomokazu Hisayuki
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama 224-8503, Japan
| | - Takemasa Hayashi
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama 224-8503, Japan
| | - Kunihiko Wakamura
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama 224-8503, Japan
| | - Naruhiko Sawada
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama 224-8503, Japan
| | - Toshiyuki Baba
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama 224-8503, Japan
| | - Fumio Ishida
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama 224-8503, Japan
| | - Kazunori Yokoyama
- Department of Gastroenterology, Nikko Kinen Hospital, Muroran 051-8501, Japan
| | - Mitsuru Daita
- Department of Gastroenterology, Nikko Kinen Hospital, Muroran 051-8501, Japan
| | - Tetsuo Nemoto
- Department of Pathology, Showa University Nothern Yokohama Hospital, Yokohama 224-8503, Japan
| | - Hideyuki Miyachi
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama 224-8503, Japan
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11
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Dykstra MA, Gimon TI, Ronksley PE, Buie WD, MacLean AR. Classic and Novel Histopathologic Risk Factors for Lymph Node Metastasis in T1 Colorectal Cancer: A Systematic Review and Meta-analysis. Dis Colon Rectum 2021; 64:1139-1150. [PMID: 34397562 DOI: 10.1097/dcr.0000000000002164] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Treatment of endoscopically resected T1 colorectal cancers is based on the risk of lymph node metastasis. Risk is based on histopathologic features, although there is lack of consensus as to what constitutes high-risk features. OBJECTIVE The purpose of this study was to conduct a systematic review and meta-analysis of histopathologic risk factors for lymph node metastasis. DATA SOURCES A search of MEDLINE, Embase, Scopus, and Cochrane controlled register of trials for risk factors for lymph node metastasis was performed from inception until August 2018. STUDY SELECTION Included patients must have had an oncologic resection to confirm lymph node status and reported at least 1 histopathologic risk factor. INTERVENTION Rates of lymph node positivity were compared between patients with and without risk factors. MAIN OUTCOME MEASURES We report the results of the meta-analysis as ORs. RESULTS Of 8592 citations, 60 met inclusion criteria. Pooled analyses found that lymphovascular invasion, vascular invasion, neural invasion, and poorly differentiated histology were significantly associated with lymph node metastasis, as were depths of 1000 µm (OR = 2.76), 1500 µm (OR = 4.37), 2000 µm (OR = 2.37), submucosal level 3 depth (OR = 3.08), and submucosal level 2/3 (OR = 3.08) depth. Depth of 3000 µm, Haggitt level 4, and widths of 3000 µm and 4000 µm were not significantly associated with lymph node metastasis. Tumor budding (OR = 4.99) and poorly differentiated clusters (OR = 14.61) were also significantly associated with lymph node metastasis. LIMITATIONS Included studies reported risk factors independently, making it impossible to examine the additive metastasis risk in patients with numerous risk factors. CONCLUSIONS We identified 1500 μm as the depth most significantly associated with lymph node metastasis. Novel factors tumor budding and poorly differentiated clusters were also significantly associated with lymph node metastasis. These findings should help inform guidelines regarding risk stratification of T1 tumors and prompt additional investigation into the exact contribution of poorly differentiated clusters to lymph node metastasis.
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Affiliation(s)
- Mark A Dykstra
- Department of Surgery, University of Alberta, Edmonton, Alberta, Canada
| | - Tamara I Gimon
- Department of Surgery, University of Calgary, Calgary, Alberta, Canada
| | - Paul E Ronksley
- Department of Community Health Sciences, O'Brien Institute for Public Health, University of Calgary, Calgary, Alberta, Canada
| | - W Donald Buie
- Department of Surgery, University of Calgary, Calgary, Alberta, Canada
| | - Anthony R MacLean
- Department of Surgery, University of Calgary, Calgary, Alberta, Canada
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Garfinkle R, Lee L, Boutros M, Cardin MJ, Spatz A, Morin N. Tumour budding predicts increased recurrence after curative resection for T2N0 colorectal cancer. Can J Surg 2019; 62:334-339. [PMID: 31550095 DOI: 10.1503/cjs.019017] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
Background Tumour budding is defined as the presence of a cluster of fewer than 5 cells along the invasive margin. It may confer a worse prognosis in colorectal cancer, but its importance in pT2N0 colorectal cancer is unknown. This study aimed to determine the prognostic value of tumour budding in pT2N0 colorectal cancer. Methods This was a retrospective cohort study with prospective assessment of tumour budding by 2 pathologists. We included all patients who underwent elective curative resection for pT2N0 colorectal cancer except those with hereditary colorectal cancer syndromes, inflammatory bowel disease or positive resection margins, those who received neoadjuvant or adjuvant therapy and those who died within 90 days of operation. Patients were classified as having high-grade tumour budding (≥ 10 budding foci per high-power field) or low-grade tumour budding (< 9 budding foci per high-power field). The main outcome measure was locoregional or distant recurrence. Results Of 85 patients, 36 had high-grade tumour budding and 49 had low-grade tumour budding. The overall recurrence rate was 11% (9/85) and median follow-up was 41.0 months (interquartile range 22.0–68.0). Interrater reliability for tumour budding assessment was excellent (κ = 0.86, 95% confidence interval [CI] 0.76–0.96). There were more recurrences in patients with high-grade tumour budding (7/36, 19.4% v. 2/49, 4.1%; p = 0.020). On multivariate analysis, after we adjusted for confounders, the presence of high-grade tumour budding was independently associated with recurrence (hazard ratio 5.11, 95% CI 1.01–25.9). Conclusion Tumour budding was independently associated with increased recurrence after pT2N0 colorectal cancer resection. It offers additional prognostic information that may affect treatment strategy.
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Affiliation(s)
- Richard Garfinkle
- From the Division of Colon and Rectal Surgery (Garfinkle, Lee, Boutros, Morin) and the Department of Pathology (Spatz, Cardin), Sir Mortimer B. Davis Jewish General Hospital, Montreal, Que
| | - Lawrence Lee
- From the Division of Colon and Rectal Surgery (Garfinkle, Lee, Boutros, Morin) and the Department of Pathology (Spatz, Cardin), Sir Mortimer B. Davis Jewish General Hospital, Montreal, Que
| | - Marylise Boutros
- From the Division of Colon and Rectal Surgery (Garfinkle, Lee, Boutros, Morin) and the Department of Pathology (Spatz, Cardin), Sir Mortimer B. Davis Jewish General Hospital, Montreal, Que
| | - Marie-Josee Cardin
- From the Division of Colon and Rectal Surgery (Garfinkle, Lee, Boutros, Morin) and the Department of Pathology (Spatz, Cardin), Sir Mortimer B. Davis Jewish General Hospital, Montreal, Que
| | - Alan Spatz
- From the Division of Colon and Rectal Surgery (Garfinkle, Lee, Boutros, Morin) and the Department of Pathology (Spatz, Cardin), Sir Mortimer B. Davis Jewish General Hospital, Montreal, Que
| | - Nancy Morin
- From the Division of Colon and Rectal Surgery (Garfinkle, Lee, Boutros, Morin) and the Department of Pathology (Spatz, Cardin), Sir Mortimer B. Davis Jewish General Hospital, Montreal, Que
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13
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Tumor Budding in Colorectal Carcinoma Showing a Paradoxical Mitotic Index (Via PHH3) With Possible Association to the Tumor Stromal Microenvironment. Appl Immunohistochem Mol Morphol 2019; 28:627-634. [PMID: 31567276 DOI: 10.1097/pai.0000000000000805] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND Colorectal carcinomas (CC) are one of the most commonly diagnosed malignancies. Tumor budding (the histologic process of dissociation that occurs at the invasive margin of colorectal cancer), has significant prognostic implications, in that higher tumor budding is associated with adverse histopathologic and clinical outcomes. Because of this prognostic significance, more research is needed to further understand the pathologic and immunohistochemical (IHC) associations pertaining to this important prognostic variable. In this study, we will further evaluate selective clinopathologic and IHC variables with possible association to tumor budding. DESIGN A total of 234 cases of CC diagnosed in our health system were retrospectively reviewed and routine hematoxylin and eosin-stained slides of these cases were collected. A representative slide for tumor budding was selected per case and selective IHC staining was performed. Clinicopathologic data were collected for each case and analyzed in relation to tumor budding scores. In exploratory analyses, tumor budding scores per individual investigator and consensus tumor budding scores were compared with selected IHC stains (MLH1, PMS2, and PHH3) as well as numerous clinicopathologic variables. RESULTS We found a paradoxical association between tumor budding and mitosis score using PHH3 immunostaining in univariate and multivariable analysis. Furthermore, patients with intact nuclear expression for MLH1 and/or PMS2 are more likely to have higher tumor budding compared with patients with lost expression. For multivariable analysis, the following covariates were significantly associated with higher tumor budding: the presence of lymphovascular invasion, higher pathologic tumor stage, and finally infiltrating border was more likely to be associated with higher tumor budding compared with cases with a pushing border. Regarding nonmucinous versus mucinous CC, nonmucinous adenocarcinoma (MCA) was more likely to be associated with higher tumor budding compared with MCA. CONCLUSION Numerous clinicopathologic variables were found to be associated with tumor budding including lymphovascular invasion, tumor stage, infiltrating tumor border, non-MCA was more likely to be associated with higher tumor budding compared with MCA, possibly related to MUC-2 and MSI. Furthermore, regarding the paradoxical association between tumor budding and mitosis score using a PHH3 immunostaining (high tumor budding having lower mitosis), this is possibly related to the tumoral stomal microenvironment and cancer associated fibroblasts. An idea for a future study would be to look at the maturity of cancer-associated fibroblasts (immature vs. mature) and the tumoral stroma microenvironment, with regards to markers of tumor aggressiveness such as mitosis. In addition, we found that patients with intact nuclear expression for MLH1 and/or PMS2 were more likely to have higher tumor budding compared with patients with lost expression, possibly related to mismatch repair CC's not being as reliant on tumor budding. Future research will hopefully concede further insight into the variables that affect tumor budding, especially regarding the tumoral microenvironment and variations between different patient populations, inclusive of patients lacking activity of the mismatch repair. Ultimately, this will allow for better prognostic information, and more precise treatment modalities.
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14
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Cho SJ, Kakar S. Tumor Budding in Colorectal Carcinoma: Translating a Morphologic Score Into Clinically Meaningful Results. Arch Pathol Lab Med 2019; 142:952-957. [PMID: 30040461 DOI: 10.5858/arpa.2018-0082-ra] [Citation(s) in RCA: 41] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
CONTEXT - Tumor budding has received increasing recognition as an important independent prognostic factor in colorectal carcinoma. Prominent tumor budding in adenocarcinoma arising in a polyp has been shown to be a risk factor for lymph node involvement. The variability in methods used for evaluating tumor budding in different studies and lack of standardized guidelines have impeded routine inclusion of tumor budding in pathology reports. This changed last year with consensus guidelines based on the International Tumor Budding Consensus Conference (ITBCC). These guidelines have been included in the recent College of American Pathologists (CAPs) Colorectal Cancer Protocol. The consensus methodology will allow uniform reporting of this finding, but challenges in interpretation in the setting of intense inflammation, fibrosis, or gland fragmentation need to be addressed in future guidelines. OBJECTIVE - To provide a brief overview of the known clinical significance of tumor budding in colorectal carcinoma and discuss the practical aspects of its implementation on a routine basis. DATA SOURCES - English-language pathology literature. CONCLUSIONS - Tumor budding has been shown to be an independent prognostic marker in colorectal carcinomas and the routine reporting of tumor buds is now advocated by using the approach outlined by the ITBCC guidelines. Tumor budding is included in the CAP protocol as a recommended element. Presence of prominent tumor budding in an adenocarcinoma in a polyp may have implications for management, such as additional resection, while it serves as a prognostic factor in other settings.
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Affiliation(s)
| | - Sanjay Kakar
- From the Department of Pathology, University of California, San Francisco
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15
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Bagmet NN, Shatveryan GA, Sekacheva MI, Chardarov NK, Bedzhanyan AL, Galyan TN, Kamalov YR, Fedorov DN. [The role of lymphadenectomy for treatment of colorectal liver metastases with regional lymph nodes involvement]. Khirurgiia (Mosk) 2018:45-49. [PMID: 30560844 DOI: 10.17116/hirurgia201812145] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Liver resection remains the method of choice for treatment of colorectal liver metastases with good long-term results. Regional lymph nodes involvement is significant negative prognostic factor. Moreover, it has been considered as a contraindication for liver resection for a long time. The role of lymphadenectomy remains controversial. Current state of this problem is reviewed in the article. Liver regional lymph nodes involvement takes place in 10-20% of cases. PET/CT is the most sensitive method of preoperative diagnosis. Involvement of liver regional lymph nodes is currently not absolute contraindication for liver resection. Routine lymphadenectomy does not make sense, and, perhaps, is justified only within scientific trials for more accurate disease staging. Indications for lymphadenectomy are suspicious changes of lymph nodes revealed by preoperative visualization methods or by intraoperative exploration. Modern chemotherapy regimens allow to reconsider the prognostic importance of liver regional lymph node metastases and to extend indications for liver resections.
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Affiliation(s)
- N N Bagmet
- Petrovsky Russian Research Center for Surgery, Moscow, Russia
| | - G A Shatveryan
- Petrovsky Russian Research Center for Surgery, Moscow, Russia
| | - M I Sekacheva
- Sechenov First Moscow State Medical University, Moscow, Russia
| | - N K Chardarov
- Petrovsky Russian Research Center for Surgery, Moscow, Russia
| | - A L Bedzhanyan
- Petrovsky Russian Research Center for Surgery, Moscow, Russia; Sechenov First Moscow State Medical University, Moscow, Russia
| | - T N Galyan
- Petrovsky Russian Research Center for Surgery, Moscow, Russia
| | - Yu R Kamalov
- Petrovsky Russian Research Center for Surgery, Moscow, Russia
| | - D N Fedorov
- Petrovsky Russian Research Center for Surgery, Moscow, Russia
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16
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Ni S, Ren F, Xu M, Tan C, Weng W, Huang Z, Sheng W, Huang D. CTHRC1 overexpression predicts poor survival and enhances epithelial-mesenchymal transition in colorectal cancer. Cancer Med 2018; 7:5643-5654. [PMID: 30302922 PMCID: PMC6247052 DOI: 10.1002/cam4.1807] [Citation(s) in RCA: 45] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2018] [Revised: 08/19/2018] [Accepted: 09/09/2018] [Indexed: 12/14/2022] Open
Abstract
Collagen triple helix repeat containing (CTHRC1), which was identified as a cancer-related factor, is a promigratory protein involved in multiple processes, including vascular remodeling, antifibrosis, metabolism, bone formation, and cancer. In this study, we aimed to investigate the clinical significance and possible role of CTHRC1 in the process of epithelial-mesenchymal transition (EMT) in colorectal cancer (CRC). Here, we revealed that CTHRC1 mRNA and protein levels are both upregulated in CRC tissues compared with those of paired noncancerous tissues. Moreover, the overexpression of CTHRC1 correlated with poor prognosis in patients with CRC (especially colon cancer). Furthermore, we showed that CTHRC1 induced EMT and promoted cell motility in CRC cells. Importantly, we demonstrated that CTHRC1 promoted EMT by activating transforming growth factor-β (TGF-β) signaling, revealing a possible effective therapeutic treatment for patients with CRC.
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Affiliation(s)
- Shujuan Ni
- Department of PathologyFudan University Shanghai Cancer CenterShanghaiChina
- Department of OncologyShanghai Medical College, Fudan UniversityShanghaiChina
- Institute of PathologyFudan UniversityShanghaiChina
| | - Fei Ren
- Department of PathologyFudan University Shanghai Cancer CenterShanghaiChina
- Department of OncologyShanghai Medical College, Fudan UniversityShanghaiChina
- Institute of PathologyFudan UniversityShanghaiChina
| | - Midie Xu
- Department of PathologyFudan University Shanghai Cancer CenterShanghaiChina
- Department of OncologyShanghai Medical College, Fudan UniversityShanghaiChina
- Institute of PathologyFudan UniversityShanghaiChina
| | - Cong Tan
- Department of PathologyFudan University Shanghai Cancer CenterShanghaiChina
- Department of OncologyShanghai Medical College, Fudan UniversityShanghaiChina
- Institute of PathologyFudan UniversityShanghaiChina
| | - Weiwei Weng
- Department of PathologyFudan University Shanghai Cancer CenterShanghaiChina
- Department of OncologyShanghai Medical College, Fudan UniversityShanghaiChina
- Institute of PathologyFudan UniversityShanghaiChina
| | - Zhaohui Huang
- Wuxi Cancer InstituteAffiliated Hospital of Jiangnan UniversityWuxiChina
| | - Weiqi Sheng
- Department of PathologyFudan University Shanghai Cancer CenterShanghaiChina
- Department of OncologyShanghai Medical College, Fudan UniversityShanghaiChina
- Institute of PathologyFudan UniversityShanghaiChina
| | - Dan Huang
- Department of PathologyFudan University Shanghai Cancer CenterShanghaiChina
- Department of OncologyShanghai Medical College, Fudan UniversityShanghaiChina
- Institute of PathologyFudan UniversityShanghaiChina
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17
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Chernyshov SV, Shelygin YA, Kashnikov VN, Maynovskaya OA, Rybakov EG. [Risk factors of regional lymph node metastases in pT1 colorectal cancer]. Khirurgiia (Mosk) 2018:4-9. [PMID: 30199045 DOI: 10.17116/hirurgia20180824] [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] [Indexed: 11/17/2022]
Abstract
AIM To identify risk factors of lymph node metastases in patients with pT1 rectal cancer. MATERIAL AND METHODS There were 43 patients aged 62.3±11.3 years with pT1 rectal cancer who underwent mesorectal excision in 2012 - 2018. There were 34 (64%) females and 19 (36%) males. RESULTS Histological examination revealed SM1-2 in 22/43 (51%) cases, SM3 - in 21/43 (49%) cases. Lymph node metastases were identified in specimens with submucosal invasion: SM3 - in 8/21 (38.1%) cases and SM1-2 - in 3/22 (13.6%) cases (p=0.08). Logistic regression confirmed lymphovascular invasion (p=0.005) and mucosal and/or poorly differentiated carcinoma (p=0.014) as independent predictors of lymph node metastases. CONCLUSION Lymphovascular invasion and poorly differentiated carcinoma are indications for transabdominal mesorectal excision.
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Affiliation(s)
- S V Chernyshov
- Ryzhikh State Research Center of Coloproctology of Healthcare Ministry of Russia, Moscow, Russia
| | - Yu A Shelygin
- Ryzhikh State Research Center of Coloproctology of Healthcare Ministry of Russia, Moscow, Russia; Russian Medical Academy of Continuing Professional Education of Healthcare Ministry of Russia, Moscow, Russia
| | - V N Kashnikov
- Ryzhikh State Research Center of Coloproctology of Healthcare Ministry of Russia, Moscow, Russia
| | - O A Maynovskaya
- Ryzhikh State Research Center of Coloproctology of Healthcare Ministry of Russia, Moscow, Russia
| | - E G Rybakov
- Ryzhikh State Research Center of Coloproctology of Healthcare Ministry of Russia, Moscow, Russia
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18
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The significance of tumor budding in T1 colorectal carcinoma: the most reliable predictor of lymph node metastasis especially in endoscopically resected T1 colorectal carcinoma. Hum Pathol 2018; 78:8-17. [DOI: 10.1016/j.humpath.2018.02.001] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2017] [Revised: 01/27/2018] [Accepted: 02/01/2018] [Indexed: 12/16/2022]
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19
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Jung CK, Jung SH, Yim SH, Jung JH, Choi HJ, Kang WK, Park SW, Oh ST, Kim JG, Lee SH, Chung YJ. Predictive microRNAs for lymph node metastasis in endoscopically resectable submucosal colorectal cancer. Oncotarget 2017; 7:32902-15. [PMID: 27096956 PMCID: PMC5078061 DOI: 10.18632/oncotarget.8766] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2015] [Accepted: 03/28/2016] [Indexed: 12/19/2022] Open
Abstract
Accurate prediction of regional lymph node metastasis (LNM) in endoscopically resected T1-stage colorectal cancers (CRCs) can reduce unnecessary surgeries. To identify miRNA markers that can predict LNM in T1-stage CRCs, the study was conducted in two phases; (I) miRNA classifier construction by miRNA-array and quantitative reverse transcription PCR (qRT-PCR) using 36 T1-stage CRC samples; (II) miRNA classifier validation in an independent set of 20 T1-stage CRC samples. The expression of potential downstream target genes of miRNAs was assessed by immunohistochemistry. In the discovery analysis by miRNA microarray, expression of 66 miRNAs were significantly different between LNM-positive and negative CRCs. After qRT-PCR validation, 11 miRNAs were consistently significant in the combined classifier construction set. Among them, miR-342-3p was the most significant one (P=4.3×10-4). Through logistic regression analysis, we developed a three-miRNA classifier (miR-342-3p, miR-361-3p, and miR-3621) for predicting LNM in T1-stage CRCs, yielding the area under the curve of 0.947 (94% sensitivity, 85% specificity and 89% accuracy). The discriminative ability of this system was consistently reliable in the independent validation set (83% sensitivity, 64% specificity and 70% of accuracy). Of the potential downstream targets of the three-miRNAs, expressions of E2F1, RAP2B, and AKT1 were significantly associated with LNM. In conclusion, this classifier can predict LNM more accurately than conventional pathologic criteria and our study results may be helpful to avoid unnecessary bowel surgery after endoscopic resection in early CRC.
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Affiliation(s)
- Chan Kwon Jung
- Department of Hospital Pathology, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea
| | - Seung-Hyun Jung
- Department of Microbiology, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.,Integrated Research Center for Genome Polymorphism, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.,Cancer Evolution Research Center, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea
| | - Seon-Hee Yim
- Integrated Research Center for Genome Polymorphism, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea
| | - Ji-Han Jung
- Department of Hospital Pathology, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea
| | - Hyun Joo Choi
- Department of Hospital Pathology, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea
| | - Won-Kyung Kang
- Department of Surgery, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea
| | - Sung-Won Park
- Integrated Research Center for Genome Polymorphism, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.,Cancer Evolution Research Center, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea
| | - Seong-Taek Oh
- Department of Surgery, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea
| | - Jun-Gi Kim
- Department of Surgery, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea
| | - Sug Hyung Lee
- Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.,Cancer Evolution Research Center, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea
| | - Yeun-Jun Chung
- Department of Microbiology, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.,Integrated Research Center for Genome Polymorphism, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea
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20
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Cappellesso R, Luchini C, Veronese N, Lo Mele M, Rosa-Rizzotto E, Guido E, De Lazzari F, Pilati P, Farinati F, Realdon S, Solmi M, Fassan M, Rugge M. Tumor budding as a risk factor for nodal metastasis in pT1 colorectal cancers: a meta-analysis. Hum Pathol 2017; 65:62-70. [PMID: 28438617 DOI: 10.1016/j.humpath.2017.04.013] [Citation(s) in RCA: 64] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2017] [Revised: 03/29/2017] [Accepted: 04/05/2017] [Indexed: 01/04/2023]
Abstract
Worldwide, colorectal cancer (CRC) screening programs have significantly increased the detection of submucosal (pT1) adenocarcinoma. Completion surgery may be indicated after endoscopic excision of these potentially metastasizing early cancers. However, the postsurgical prevalence of nodal implants does not exceed 15%, leading to questions concerning the clinical appropriateness of any post-endoscopy surgery. Eastern scientific societies (Japanese Society for Cancer of the Colon-Rectum, in particular) include tumor budding (TB), defined as the presence of isolated single cancer cells or clusters of fewer than 5 cancer cells at the tumor invasive front, among the variables that must be included in histologic reports. In Western countries, however, no authoritative endorsements recommend the inclusion of TB in the histology report because of the heterogeneity of definitions and measurement methods as well as its apparent poor reproducibility. To assess the prognostic value of TB in pT1 CRCs, this meta-analysis evaluated 41 studies involving a total of 10137 patients. We observed a strong association between the presence of TB and risk of nodal metastasis in pT1 CRC. In comparing TB-positive (684/2401; 28.5%) versus TB-negative (557/7736; 7.2%) patients, the prevalence of nodal disease resulted in an odds ratio value of 6.44 (95% confidence interval, 5.26-7.87; P<.0001; I2 = 30%). This increased risk of regional nodal metastasis was further confirmed after accounting for potential confounders. These results support the priority of histologically reporting TB in any endoscopically removed pT1 CRC to direct more appropriate patient management.
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Affiliation(s)
- Rocco Cappellesso
- Department of Medicine, Surgical Pathology Unit, University of Padova, Padova 35121, Italy
| | - Claudio Luchini
- University and Hospital Trust of Verona, Verona 37129, Italy; Department of Pathology, Santa Chiara Hospital, Trento 38122, Italy
| | - Nicola Veronese
- National Research Council, Neuroscience Institute, Aging Branch, Padova 35100, Italy; Institute of Clinical Research and Education in Medicine (IREM), Padova 35121, Italy
| | - Marcello Lo Mele
- Department of Medicine, Surgical Pathology Unit, University of Padova, Padova 35121, Italy
| | | | - Ennio Guido
- Gastroenterology Unit, S. Antonio Hospital, Padova 35128, Italy
| | | | | | - Fabio Farinati
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova 35128, Italy
| | - Stefano Realdon
- Digestive Endoscopy Unit, Veneto Institute of Oncology IOV-I.R.C.S.S, Padova 35128, Italy
| | - Marco Solmi
- Department of Neurosciences, University of Padova, Institute for Clinical Research and Education in Medicine, Padova Local Unit, National Health Care System, Padova 35128, Italy
| | - Matteo Fassan
- Department of Medicine, Surgical Pathology Unit, University of Padova, Padova 35121, Italy.
| | - Massimo Rugge
- Department of Medicine, Surgical Pathology Unit, University of Padova, Padova 35121, Italy
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21
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Barresi V, Reggiani Bonetti L, Ieni A, Caruso RA, Tuccari G. Poorly Differentiated Clusters: Clinical Impact in Colorectal Cancer. Clin Colorectal Cancer 2017; 16:9-15. [DOI: 10.1016/j.clcc.2016.06.002] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2016] [Revised: 06/06/2016] [Accepted: 06/10/2016] [Indexed: 12/15/2022]
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22
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Ichimasa K, Kudo SE, Miyachi H, Kouyama Y, Ishida F, Baba T, Katagiri A, Wakamura K, Hayashi T, Hisayuki T, Kudo T, Misawa M, Mori Y, Matsudaira S, Kimura Y, Kataoka Y. Patient gender as a factor associated with lymph node metastasis in T1 colorectal cancer: A systematic review and meta-analysis. Mol Clin Oncol 2017; 6:517-524. [PMID: 28413659 DOI: 10.3892/mco.2017.1172] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2016] [Accepted: 01/11/2017] [Indexed: 12/27/2022] Open
Abstract
Approximately 10% of patients with T1 colorectal cancer have lymph node metastases (LNM), requiring node dissection along with surgical resection. Patient gender was recently reported to affect the occurrence of LNM. The aim of the present study was to assess whether patient gender was predictive of LNM in T1 colorectal cancer. Public databases, including PubMed, EMBASE and the Cochrane Central Register of Controlled Trials were searched, using key terms related to 'T1 colorectal cancer' and 'lymph node'. All relevant studies reporting the adjusted odds ratio or risk ratio of LNM in relation to patient gender were included. The quality of the studies was classified according to the Quality in Prognostic Studies tool. A random-effects model was used and the quality of the evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation approach. The initial database search identified 2,492 publications; of those, 36 studies reported unadjusted results. Of the 36 studies, 4 reported adjusted results and fulfilled the inclusion criteria for this meta-analysis: 3 studies were graded as having a moderate risk of bias, and 1 had a low risk of bias. The present meta-analysis demonstrated that female gender was associated with increased risk of LNM (risk ratio=2.45, 95% confidence interval: 1.03-3.88). The I2 statistic was 0.901, classified as very low (+OOO) and was downgraded by the risk of bias, inconsistency and publication bias. In conclusion, female gender was found to be correlated with LNM in patients with T1 colorectal cancer.
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Affiliation(s)
- Katsuro Ichimasa
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama, Kanagawa 224-8503, Japan
| | - Shin-Ei Kudo
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama, Kanagawa 224-8503, Japan
| | - Hideyuki Miyachi
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama, Kanagawa 224-8503, Japan
| | - Yuta Kouyama
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama, Kanagawa 224-8503, Japan
| | - Fumio Ishida
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama, Kanagawa 224-8503, Japan
| | - Toshiyuki Baba
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama, Kanagawa 224-8503, Japan
| | - Atsushi Katagiri
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama, Kanagawa 224-8503, Japan
| | - Kunihiko Wakamura
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama, Kanagawa 224-8503, Japan
| | - Takemasa Hayashi
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama, Kanagawa 224-8503, Japan
| | - Tomokazu Hisayuki
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama, Kanagawa 224-8503, Japan
| | - Toyoki Kudo
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama, Kanagawa 224-8503, Japan
| | - Masashi Misawa
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama, Kanagawa 224-8503, Japan
| | - Yuichi Mori
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama, Kanagawa 224-8503, Japan
| | - Shingo Matsudaira
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama, Kanagawa 224-8503, Japan
| | - Yui Kimura
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama, Kanagawa 224-8503, Japan
| | - Yuki Kataoka
- Hospital Care Research Unit, Hyogo Prefectural Amagasaki General Medical Center, Amagasaki, Hyogo 660-8550, Japan
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23
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Tumor budding in colorectal cancer--ready for diagnostic practice? Hum Pathol 2015; 47:4-19. [PMID: 26476568 DOI: 10.1016/j.humpath.2015.08.007] [Citation(s) in RCA: 157] [Impact Index Per Article: 15.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2015] [Revised: 07/30/2015] [Accepted: 08/13/2015] [Indexed: 02/06/2023]
Abstract
Tumor budding is an important additional prognostic factor for patients with colorectal cancer (CRC). Defined as the presence of single tumor cells or small clusters of up to 5 cells in the tumor stroma, tumor budding has been likened to an epithelial-mesenchymal transition. Based on well-designed retrospective studies, tumor budding is linked to adverse outcome of CRC patients in 3 clinical scenarios: (1) in malignant polyps, detection of tumor buds is a risk factor for lymph node metastasis indicating the need for colorectal surgery; (2) tumor budding in stage II CRC is a highly adverse prognostic indicator and may aid patient selection for adjuvant therapy; (3) in the preoperative setting, presence of tumor budding in biopsy material may help to identify high-risk rectal cancer patients for neoadjuvant therapy. However, lack of consensus guidelines for standardized assessment still limits reporting in daily diagnostic practice. This article provides a practical and comprehensive overview on tumor budding aimed at the practicing pathologist. First, we review the prognostic value of tumor budding for the management of colon and rectal cancer patients. Second, we outline a practical, evidence-based proposal for the assessment of tumor budding in the daily sign-out. Last, we summarize the current knowledge of the molecular characteristics of high-grade budding tumors in the context of personalized treatment approaches and biomarker discovery.
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Fasoli R, Nienstedt R, De Carli N, Monica F, Guido E, Valiante F, Armelao F, de Pretis G. The management of malignant polyps in colorectal cancer screening programmes: A retrospective Italian multi-centre study. Dig Liver Dis 2015; 47:715-9. [PMID: 25986044 DOI: 10.1016/j.dld.2015.04.011] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2014] [Revised: 04/04/2015] [Accepted: 04/18/2015] [Indexed: 12/11/2022]
Abstract
BACKGROUND Although recognition of colorectal malignant polyps is increasing, treatment plans lack the evidence of randomised trials. AIM To retrospectively evaluate presentation, management and outcomes of screen-detected colorectal malignant polyps, with special focus on the role of histological factors in therapeutic decision-making. METHODS We retrospectively analysed data regarding malignant polyps detected during faecal immuno-chemical test-based screening programmes in five centres in North-Eastern Italy between April 2008 and April 2013. RESULTS 306 malignant polyps in 306 patients were included; 72 patients underwent surgery directly (23.6%). Of 234 patients treated endoscopically, 133 subsequently underwent radicalisation surgery (56.8%) and in 17 there was evidence of residual disease (12.8%). Involved, unsafe (<1mm) or invaluable resection margins and sessile morphology represented the most frequent determinants of subsequent surgery. The mean number of nodes harvested during radicalisation surgery was 7.1±6.4 (range 0-29). Histological diagnosis was re-evaluated according to new guidelines in 125 cases (41%); in 18 this led to modification of the risk class (14.4%). CONCLUSIONS Although the rate of surgical treatment following endoscopic resection is similar to other studies, residual disease at surgery was lower than most international series. Adhering to the new histological reporting system and respecting guidelines on node harvesting may favourably influence prognosis.
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Affiliation(s)
- Renato Fasoli
- Provincial Department of Gastroenterology and Digestive Endoscopy, Santa Chiara Hospital, Trento, Italy.
| | - Richard Nienstedt
- Provincial Department of Gastroenterology and Digestive Endoscopy, Santa Chiara Hospital, Trento, Italy
| | | | - Fabio Monica
- Gastroenterology and Digestive Endoscopy Unit, Bassano del Grappa Hospital, Bassano del Grappa, VI, Italy
| | - Ennio Guido
- Gastroenterology and Digestive Endoscopy Unit, Sant'Antonio Hospital, Padova, Italy
| | - Flavio Valiante
- Gastroenterology and Digestive Endoscopy Unit, Santa Maria del Prato Hospital, Feltre, BL, Italy
| | - Franco Armelao
- Provincial Department of Gastroenterology and Digestive Endoscopy, Santa Chiara Hospital, Trento, Italy
| | - Giovanni de Pretis
- Provincial Department of Gastroenterology and Digestive Endoscopy, Santa Chiara Hospital, Trento, Italy; Provincial Department of Gastroenterology and Digestive Endoscopy, Santa Maria del Carmine Hospital, Rovereto, TN, Italy
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25
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Wang LM, Guy R, Fryer E, Kartsonaki C, Gill P, Hughes C, Szuts A, Perera R, Chetty R, Mortensen N. The Ueno method for substaging pT1 colorectal adenocarcinoma by depth and width measurement: an interobserver study. Colorectal Dis 2015; 17:674-81. [PMID: 25620664 DOI: 10.1111/codi.12910] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2013] [Accepted: 10/25/2014] [Indexed: 02/08/2023]
Abstract
AIM Early pT1 polyp colorectal cancers (CRCs) present challenges for accurate pathology substaging. Haggitt and Kikuchi stages depend on polyp morphology and are often difficult to apply due to suboptimal orientation or fragmentation, or absence of the muscularis propria in polypectomy or submucosal resection specimens. European guidelines for quality assurance suggest using Ueno's more objective approach, using depth and width measurements beyond muscularis mucosae. We have investigated interobserver variation using Ueno's approach. METHOD Ten consecutive pT1 polyp CRCs were identified and the slides assessed by six gastrointestinal pathologists for depth and width of invasion. A further 60 polyps were studied by a group of specialist and general pathologists. Agreement was assessed by analysis of variance. A polyp CRC is classified as high risk if it has a depth ≥ 2000 μm or a width ≥ 4000 μm and low risk with a depth < 2000 μm or a width < 4000 μm. Concordance for the dichotomized values was assessed using the kappa statistic. RESULTS The intraclass correlation coefficient (ICC) for depth was 0.83 and for width 0.56 in the 10-polyp group. The ICC for the 60-polyp CRCs was 0.67 for depth and 0.37 for width. In both groups, when polyp CRCs are divided into high- and low-risk categories based on depth, there was substantial and moderate agreement (κ = 0.80 and 0.47) but only fair agreement when based on width (κ = 0.34 and 0.35). CONCLUSION Ueno's method has the advantage of being independent of polyp morphology. Our study shows better concordance for depth measurement and reproducibility in nonfragmented specimens, with poorer agreement when based on width.
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Affiliation(s)
- L M Wang
- Department of Cellular Pathology, John Radcliffe Hospital, University of Oxford, Headington, Oxford, UK
| | - R Guy
- Department of Colorectal Surgery, Churchill Hospital, University of Oxford, Headington, Oxford, UK
| | - E Fryer
- Department of Cellular Pathology, John Radcliffe Hospital, University of Oxford, Headington, Oxford, UK
| | - C Kartsonaki
- CR-UK/MRC Oxford Institute for Radiation Oncology, Department of Oncology, John Radcliffe Hospital, University of Oxford, Headington, Oxford, UK
| | - P Gill
- Department of Cellular Pathology, John Radcliffe Hospital, University of Oxford, Headington, Oxford, UK
| | - C Hughes
- Department of Cellular Pathology, John Radcliffe Hospital, University of Oxford, Headington, Oxford, UK
| | - A Szuts
- Department of Cellular Pathology, John Radcliffe Hospital, University of Oxford, Headington, Oxford, UK
| | - R Perera
- Department of Cellular Pathology, John Radcliffe Hospital, University of Oxford, Headington, Oxford, UK
| | - R Chetty
- Department of Cellular Pathology, John Radcliffe Hospital, University of Oxford, Headington, Oxford, UK
| | - N Mortensen
- Department of Colorectal Surgery, Churchill Hospital, University of Oxford, Headington, Oxford, UK
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Molecular profiling of tumour budding implicates TGFβ-mediated epithelial-mesenchymal transition as a therapeutic target in oral squamous cell carcinoma. J Pathol 2015; 236:505-16. [DOI: 10.1002/path.4550] [Citation(s) in RCA: 101] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2015] [Revised: 04/20/2015] [Accepted: 04/25/2015] [Indexed: 11/07/2022]
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27
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Gulluoglu M, Yegen G, Ozluk Y, Keskin M, Dogan S, Gundogdu G, Onder S, Balik E. Tumor Budding Is Independently Predictive for Lymph Node Involvement in Early Gastric Cancer. Int J Surg Pathol 2015; 23:349-58. [PMID: 25911564 DOI: 10.1177/1066896915581200] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND The most important prognostic factor for early gastric cancer (EGC) is the lymph node status. It is important to predict early lesions without lymph node metastasis (LNM) before proceeding to radical surgery in locally excised lesions. Tumor budding is a feature known to be related to aggressive tumor behavior in several solid tumors. We aimed to assess the predictive value of tumor budding for LNM in pT1a and pT1b gastric cancer. METHODS We retrospectively investigated radical gastrectomy specimens for of 126 EGC patients and assess the possible relation between the clinicopathologic features, including age, gender, tumor location, tumor size, macroscopic tumor type, histologic differentiation, depth and width of submucosal invasion, lymphovascular invasion, and tumor budding with lymph node involvement. RESULTS Among the 126 EGCs, 38 were stages as pT1a and 88 as pT1b. LNM rate in pT1a tumors was 13% whereas it was 33% in pT1b tumors. Tumor budding was the only factor significantly and independently related to LNM in pT1a patients. Female gender and tumor budding were found to be independent risk factors in pT1b group. Other clinicopathologic features were not related to LNM. CONCLUSION Based on these results, we suggest that budding is a promising parameter to assess for prediction of LNM in EGC removed by endoscopic surgery, and to decide on the appropriate surgical approach.
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Affiliation(s)
- Mine Gulluoglu
- Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Gulcin Yegen
- Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Yasemin Ozluk
- Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Metin Keskin
- Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Serap Dogan
- Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | | | - Semen Onder
- Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Emre Balik
- Faculty of Medicine, Istanbul University, Istanbul, Turkey
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28
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Wang Y, Zhuo C, Shi D, Zheng H, Xu Y, Gu W, Cai S, Cai G. Unfavorable effect of small tumor size on cause-specific survival in stage IIA colon cancer, a SEER-based study. Int J Colorectal Dis 2015; 30:131-7. [PMID: 25392257 DOI: 10.1007/s00384-014-2056-y] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/25/2014] [Indexed: 02/04/2023]
Abstract
BACKGROUND We sought to determine the prognostic role of tumor size on cause-specific survival (CSS) of patients with stage IIA colon cancer. METHODS Surveillance, Epidemiology and End Results (SEER) database was utilized to identify patients with stage IIA colorectal cancer (examined lymph nodes ≥12) diagnosed from 1988 to 2003. The prognostic effect of tumor size on CSS was evaluated by univariate and multivariate analyses. RESULTS A total of 8775 patients were enrolled in the analysis. The median follow-up time was 109 months. As determined by minimal P value method, tumor sizes of 2.5 and 6.0 cm were used as optimal cutoff value to divide the cohort. The 8-year CSS of colon cancer with tumor sizes ≤2.5, 2.6-6.0, and >6.0 cm was 81.6, 86.2, and 86.7% respectively (P = 0.003). In the multivariate analysis of colon cancer, using ≤2.5-cm tumors as reference, decreased hazard ratio (HR) of CSS was observed in 2.6-6.0 cm (HR, 0.736; 95% confidence interval (CI), 0.599-0.905; P = 0.004) and >6.0 cm (HR, 0.770; 95% CI, 0.619-0.958; P = 0.019) tumors. CONCLUSIONS In stage IIA colon cancer, small tumor size represented a subset with decreased CSS. Further studies are merited to validate the unfavorable prognostic role of small tumor size in stage IIA colon cancer.
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Affiliation(s)
- Yuwei Wang
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, 270 Dong An Road, Shanghai, 200032, China
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Alamo P, Gallardo A, Di Nicolantonio F, Pavón MA, Casanova I, Trias M, Mangues MA, Lopez-Pousa A, Villaverde A, Vázquez E, Bardelli A, Céspedes MV, Mangues R. Higher metastatic efficiency of KRas G12V than KRas G13D in a colorectal cancer model. FASEB J 2014; 29:464-76. [PMID: 25359494 DOI: 10.1096/fj.14-262303] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Although all KRas (protein that in humans is encoded by the KRas gene) point mutants are considered to have a similar prognostic capacity, their transformation and tumorigenic capacities vary widely. We compared the metastatic efficiency of KRas G12V (Kirsten rat sarcoma viral oncogene homolog with valine mutation at codon 12) and KRas G13D (Kirsten rat sarcoma viral oncogene homolog with aspartic mutation at codon 13) oncogenes in an orthotopic colorectal cancer (CRC) model. Following subcutaneous preconditioning, recombinant clones of the SW48 CRC cell line [Kras wild-type (Kras WT)] expressing the KRas G12V or KRas G13D allele were microinjected in the mouse cecum. The percentage of animals developing lymph node metastasis was higher in KRas G12V than in KRas G13D mice. Microscopic, macroscopic, and visible lymphatic foci were 1.5- to 3.0-fold larger in KRas G12V than in KRas G13D mice (P < 0.05). In the lung, only microfoci were developed in both groups. KRas G12V primary tumors had lower apoptosis (7.0 ± 1.2 vs. 7.4 ± 1.0 per field, P = 0.02), higher tumor budding at the invasion front (1.2 ± 0.2 vs. 0.6 ± 0.1, P = 0.04), and a higher percentage of C-X-C chemokine receptor type 4 (CXCR4)-overexpressing intravasated tumor emboli (49.8 ± 9.4% vs. 12.8 ± 4.4%, P < 0.001) than KRas G13D tumors. KRas G12V primary tumors showed Akt activation, and β5 integrin, vascular endothelial growth factor A (VEGFA), and Serpine-1 overexpression, whereas KRas G13D tumors showed integrin β1 and angiopoietin 2 (Angpt2) overexpression. The increased cell survival, invasion, intravasation, and specific molecular regulation observed in KRas G12V tumors is consistent with the higher aggressiveness observed in patients with CRC expressing this oncogene.
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Affiliation(s)
- Patricia Alamo
- Oncogenesis and Antitumor Drug Group, Biomedical Research Institute Sant Pau, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; CIBER de Bioingeniería, Biomateriales y Nanomedicina, Barcelona, Spain
| | - Alberto Gallardo
- CIBER de Bioingeniería, Biomateriales y Nanomedicina, Barcelona, Spain; Department of Pathology, Clínica Girona, Girona, Spain
| | - Federica Di Nicolantonio
- Department of Oncology, University of Torino, Torino, Italy; Candiolo Cancer Institute-Fondazione del Piemonte per l'Oncologia, Istituto Di Ricovero e Cura a Carattere Scientifico, Torino, Italy
| | - Miguel Angel Pavón
- Oncogenesis and Antitumor Drug Group, Biomedical Research Institute Sant Pau, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; CIBER de Bioingeniería, Biomateriales y Nanomedicina, Barcelona, Spain
| | - Isolda Casanova
- Oncogenesis and Antitumor Drug Group, Biomedical Research Institute Sant Pau, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; CIBER de Bioingeniería, Biomateriales y Nanomedicina, Barcelona, Spain
| | - Manuel Trias
- CIBER de Bioingeniería, Biomateriales y Nanomedicina, Barcelona, Spain; Departments of General and Digestive Surgery
| | | | - Antonio Lopez-Pousa
- CIBER de Bioingeniería, Biomateriales y Nanomedicina, Barcelona, Spain; Medical Oncology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Antonio Villaverde
- CIBER de Bioingeniería, Biomateriales y Nanomedicina, Barcelona, Spain; Institut de Biotecnologia i de Biomedicina, and
| | - Esther Vázquez
- CIBER de Bioingeniería, Biomateriales y Nanomedicina, Barcelona, Spain; Institut de Biotecnologia i de Biomedicina, and
| | - Alberto Bardelli
- Department of Oncology, University of Torino, Torino, Italy; Candiolo Cancer Institute-Fondazione del Piemonte per l'Oncologia, Istituto Di Ricovero e Cura a Carattere Scientifico, Torino, Italy; Department de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, Barcelona, Spain; and FIRC Institute of Molecular Oncology, Milan, Italy
| | - María Virtudes Céspedes
- Oncogenesis and Antitumor Drug Group, Biomedical Research Institute Sant Pau, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; CIBER de Bioingeniería, Biomateriales y Nanomedicina, Barcelona, Spain
| | - Ramón Mangues
- Oncogenesis and Antitumor Drug Group, Biomedical Research Institute Sant Pau, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; CIBER de Bioingeniería, Biomateriales y Nanomedicina, Barcelona, Spain;
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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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31
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Koelzer VH, Zlobec I, Lugli A. Tumor budding in the clinical management of colon and rectal cancer. COLORECTAL CANCER 2014. [DOI: 10.2217/crc.14.21] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
SUMMARY Morphological features of the tumor microenvironment are emerging as powerful prognostic indicators for colorectal cancer (CRC). The presence of peritumoral budding (PTB), defined as the presence of single tumor cells or small clusters of up to five cells in the tumor stroma ahead of the invasive front, is a hallmark of aggressive disease biology. Presence of PTB strongly correlates with adverse clinicopathological features and is recognized as an additional adverse prognostic factor by the Union for International Cancer Control. Recent studies have also characterized intratumoral budding (ITB) in biopsy material as a prognostic indicator in the preoperative setting. This paper provides a comprehensive overview on the role of PTB and ITB in the clinical management of colon and rectal cancer.
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Affiliation(s)
- Viktor H Koelzer
- Clinical Pathology Division, Institute of Pathology, University of Bern, Murtenstrasse 31, CH-3010 Bern, Switzerland
- Translational Research Unit, Institute of Pathology, University of Bern, Murtenstrasse 31, CH-3010 Bern, Switzerland
| | - Inti Zlobec
- Translational Research Unit, Institute of Pathology, University of Bern, Murtenstrasse 31, CH-3010 Bern, Switzerland
| | - Alessandro Lugli
- Clinical Pathology Division, Institute of Pathology, University of Bern, Murtenstrasse 31, CH-3010 Bern, Switzerland
- Translational Research Unit, Institute of Pathology, University of Bern, Murtenstrasse 31, CH-3010 Bern, Switzerland
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Wang ZX, Zheng YF, Liang Y, Xu JX. Pulmonary metastases of colorectal carcinoma: Clinical characteristics, metastatic features, therapeutic methods and prognosis. Shijie Huaren Xiaohua Zazhi 2014; 22:2513-2517. [DOI: 10.11569/wcjd.v22.i17.2513] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To explore the clinical characteristics, metastatic features, therapeutic methods and prognosis in patients with pulmonary metastases of colorectal carcinoma.
METHODS: The clinical data of 120 patients with pulmonary metastases of colorectal cancer were retrospectively analyzed. The clinical parameters of the patients, treatment methods and the factors affecting prognosis were analyzed.
RESULTS: In patients with pulmonary metastases of colorectal carcinoma, the 6-mo, 1-, 2-, 3-, and 5-year survival rates were 78%, 44%, 26%, 19% and 16%, respectively, with an overall median overall survival (OS) period of 18.0 mo. Pulmonary symptoms, sex, age, single or multiple pulmonary metastases, the presence or absence of liver metastases, mediastinal and/or hilar lymph node involvement were not significant prognostic factors of OS (P > 0.05). Univariate analysis showed that factors significantly predicting a poor prognosis included primary tumor site (P = 0.017), vessel invasion (P = 0.024) and high T stage (P = 0.008). However, none of these were prognostic factors on multivariate analysis. There was a trend of better survival in patients submitted to metastasectomy compared with those submitted to chemotherapy alone, although there was no statistical difference (median OS: 33.0 mo vs 18.0 mo, P = 0.128). Among 153 patients who underwent radical colorectal resection, 82 had pulmonary metastases in two years after surgery, with a median disease free interval (DFI) of 20.0 mo. The factors that affected DFI included primary tumor site, morphotype, differentiation degree, T stage and N stage (P < 0.05). T stage was an independent predictive factor of DFI (P = 0.019).
CONCLUSION: T stage is an independent predictor of DFI, showing that the tumor with strong ability of invasion tend to cause lung metastasis more commonly.
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Barresi V, Branca G, Ieni A, Reggiani Bonetti L, Baron L, Mondello S, Tuccari G. Poorly differentiated clusters (PDCs) as a novel histological predictor of nodal metastases in pT1 colorectal cancer. Virchows Arch 2014; 464:655-62. [PMID: 24771119 DOI: 10.1007/s00428-014-1580-z] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2014] [Revised: 03/24/2014] [Accepted: 04/09/2014] [Indexed: 12/15/2022]
Abstract
The practical use of histological factors such as submucosal (SM) invasion depth, poor differentiation, presence of lymphovascular invasion (LVI) and tumour budding to establish the risk of nodal dissemination in pT1 colorectal cancer (CRC) is limited by their low standardization and high inter-observer variability. It was recently suggested that the presence in CRC histological sections of poorly differentiated clusters (PDCs), defined as ≥5 cancer cells with no gland formation, may predict the metastatic potential of CRC. In addition, PDC assessment was shown to be more reproducible than the evaluation of the other aforementioned histological predictors. Hence, in this study, we investigated and compared the predictive value of PDC and other histological parameters on the risk of nodal involvement in pT1 CRC. The presence of PDC, SM invasion depth ≥1,000 μm and LVI was significantly associated with N+ status in pT1 CRC (P < 0.0001). Among these parameters, SM invasion depth had the highest sensitivity to identify N+ pT1 CRC but with the lowest specificity. When the analysis was restricted to CRCs with SM invasion depth ≥1,000 μm, the presence of PDC was the only independent risk factor for nodal metastases and allowed the identification of 87.5 % of N+ cancers. In conclusion, in this study, we demonstrate that the presence of PDC is associated with the metastatic potential of pT1 CRC. The combination of this parameter with SM invasion depth may allow identifying most of the pT1 CRC with nodal metastases.
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Affiliation(s)
- Valeria Barresi
- Department of Human Pathology "Gaetano Barresi", University of Messina, 98125, Messina, Italy,
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Ryu HS, Kim WH, Ahn S, Kim DW, Kang SB, Park HJ, Park YS, Lee CH, Lee HS. Combined morphologic and molecular classification for predicting lymph node metastasis in early-stage colorectal adenocarcinoma. Ann Surg Oncol 2014; 21:1809-16. [PMID: 24562932 DOI: 10.1245/s10434-014-3539-3] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2013] [Indexed: 01/05/2023]
Abstract
BACKGROUND Identifying reliable predictors of lymph node (LN) metastasis is clinically important, particularly for optimizing treatments for early colorectal cancer (ECC) patients. This study evaluated risk-predictive models of LN metastasis using several pathologic and molecular ECC parameters. METHODS Tissue specimens from 179 patients with histologically confirmed ECC were enrolled. A total of 20 clinicopathological characteristics, including tumor budding, micropapillary structure, and mucinous differentiation, and 22 protein expressions related to cancer invasion in central and invasive front areas were evaluated for their predictive value for LN metastasis. RESULTS Alongside conventional histopathological parameters, tumor budding and mucinous differentiation at the invasive front of ECCs and micropapillary structure were found to be independent predictive factors for LN metastasis. Immunohistochemical expressions of CXCL12 and p38-MAPK at the invasive front were also found to be associated with regional LN metastasis in ECC. Analytic logistic models, using combinations of statistically independent parameters, revealed their abilities to predict LN metastasis in ECC. Further, receiver operating characteristic analysis using combinations of 6 or 7 independent variables represented predictive performances (area under curve of 0.956 or 0.960, respectively) for LN metastasis in ECC. CONCLUSIONS The combined histomorphologic and molecular factors tested here might be able to predict for LN metastasis in ECC.
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Affiliation(s)
- Han Suk Ryu
- Department of Pathology, Seoul National University Hospital, Seoul, South Korea
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Christophi C, Nguyen L, Muralidharan V, Nikfarjam M, Banting J. Lymphatics and colorectal liver metastases: the case for sentinel node mapping. HPB (Oxford) 2014; 16:124-30. [PMID: 23869986 PMCID: PMC3921007 DOI: 10.1111/hpb.12118] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2012] [Accepted: 03/21/2013] [Indexed: 12/12/2022]
Abstract
BACKGROUND Hepatic resection remains the treatment of choice for patients with colorectal liver metastases (CLM). Indications for hepatic resection have been extended to include extrahepatic lymph node groups, resulting in increased survival benefits. The identification of specific lymph pathways and involved nodes is necessary to support the development of guidelines for a more focused approach to the management of this disease. The feasibility of sentinel node mapping should be investigated to define specific lymphatic groups involved in CLM. METHODS Scientific papers published from 1950 to 2012 were sought and extracted from the MEDLINE, PubMed and University of Melbourne databases. RESULTS Several studies have reported microscopic lymph node involvement in 10-15% of patients undergoing hepatic resection for CLM in which no macroscopic involvement was evident. In retrospect, over 80% of lymphadenectomies are proven unnecessary. Traditional imaging modalities have limited predictive value in detecting lymph node involvement. Sentinel node mapping has proved an extremely accurate tool in detecting lymph node involvement and can identify patients in whom lymphadenectomy may be beneficial. CONCLUSIONS Current imaging techniques are inadequate to detect microscopic lymph node involvement in patients with resectable CLM. The use of sentinel node mapping is proposed to identify nodal groups involved and provide management strategies.
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Affiliation(s)
- Christopher Christophi
- Christopher Christophi, Department of Surgery, University of Melbourne, Austin Hospital, Lance Townsend Building Level 8, Studley Road, Heidelberg, Vic 3084, Australia. Tel: + 61 3 9496 5492. Fax: + 61 3 9458 1650. E-mail:
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Caputo D, Caricato M, La Vaccara V, Taffon C, Capolupo GT, Coppola R. T1 colorectal cancer: poor histological grading is predictive of lymph-node metastases. Int J Surg 2013; 12:209-212. [PMID: 24378911 DOI: 10.1016/j.ijsu.2013.12.012] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2013] [Accepted: 12/19/2013] [Indexed: 12/23/2022]
Abstract
INTRODUCTION After complete local excision of pT1 colorectal cancers, prediction of the absence of lymph-node involvement represents an interesting perspective in order to avoid unnecessary additional radical surgery, reducing morbidity, mortality and costs of care. We aimed to identify independent risk factors predictive of nodal involvement in pT1 colorectal cancer patients. METHODS Data regarding depth of submucosal invasion, histological grading, tumour budding and lymphovascular invasion in a consecutive series of 48 pT1 surgically resected colorectal cancers have been retrospectively collected and related to the nodal status. RESULTS A 12.5% rate of nodal involvement has been found. The poor differentiation was found as the only independent predictor of nodal metastases in pT1 colorectal cancer (p = 0.01). CONCLUSIONS Poor differentiation was the only independent significant predictor of nodal involvement in pT1 colorectal tumours. Our and literature's data confirm that risk factors must be prospectively collected and reported; further genetic and epigenetic predictive factors have to be investigated in order to carefully evaluate the needing of major surgery for pT1 colorectal cancer.
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Affiliation(s)
- Damiano Caputo
- Department of General Surgery, University Campus Bio-Medico di Roma, Via Alvaro del Portillo, 200, 00128 Rome, Italy.
| | - Marco Caricato
- Department of General Surgery, University Campus Bio-Medico di Roma, Via Alvaro del Portillo, 200, 00128 Rome, Italy
| | - Vincenzo La Vaccara
- Department of General Surgery, University Campus Bio-Medico di Roma, Via Alvaro del Portillo, 200, 00128 Rome, Italy
| | - Chiara Taffon
- Department of Pathology, University Campus Bio-Medico di Roma, Via Alvaro del Portillo, 200, 00128 Rome, Italy
| | - Gabriella Teresa Capolupo
- Department of General Surgery, University Campus Bio-Medico di Roma, Via Alvaro del Portillo, 200, 00128 Rome, Italy
| | - Roberto Coppola
- Department of General Surgery, University Campus Bio-Medico di Roma, Via Alvaro del Portillo, 200, 00128 Rome, Italy
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Abstract
Evidence has now accumulated that colonoscopy and removal of polyps, especially during screening and surveillance programs, is effective in overall risk reduction for colon cancer. After resection of malignant pedunculated colon polyps or early stage colon cancers, long-term repeated surveillance programs can also lead to detection and removal of asymptomatic high risk advanced adenomas and new early stage metachronous cancers. Early stage colon cancer can be defined as disease that appears to have been completely resected with no subsequent evidence of involvement of adjacent organs, lymph nodes or distant sites. This differs from the clinical setting of an apparent “curative” resection later pathologically upstaged following detection of malignant cells extending into adjacent organs, peritoneum, lymph nodes or other distant sites, including liver. This highly selected early stage colon cancer group remains at high risk for subsequent colon polyps and metachronous colon cancer. Precise staging is important, not only for assessing the need for adjuvant chemotherapy, but also for patient selection for continued surveillance. With advanced stages of colon cancer and a more guarded outlook, repeated surveillance should be limited. In future, novel imaging technologies (e.g., confocal endomicroscopy), coupled with increased pathological recognition of high risk markers for lymph node involvement (e.g., “tumor budding”) should lead to improved staging and clinical care.
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Beheshti A, Pinzer BR, McDonald JT, Stampanoni M, Hlatky L. Early tumor development captured through nondestructive, high resolution differential phase contrast X-ray imaging. Radiat Res 2013; 180:448-54. [PMID: 24125488 DOI: 10.1667/rr13327.1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
Although a considerable amount is known about molecular dysregulations in later stages of tumor progression, much less is known about the regulated processes supporting initial tumor growth. Insight into such processes can provide a fuller understanding of carcinogenesis, with implications for cancer treatment and risk assessment. Work from our laboratory suggests that organized substructure emerges during tumor formation. The goal here was to examine the feasibility of using state-of-the-art differential phase contrast X-ray imaging to investigate density differentials that evolve during early tumor development. To this end the beamline for TOmographic Microscopy and Coherent rAdiology experimenTs (TOMCAT) at the Swiss Light Source was used to examine the time-dependent assembly of substructure in developing tumors. Differential phase contrast (DPC) imaging based on grating interferometry as implemented with TOMCAT, offers sensitivity to density differentials within soft tissues and a unique combination of high resolution coupled with a large field of view that permits the accommodation of larger tissue sizes (1 cm in diameter), difficult with other imaging modalities.
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Affiliation(s)
- A Beheshti
- a Center of Cancer Systems Biology, GRI, Tufts University School of Medicine, Boston, Massachusetts
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Grizzi F, Celesti G, Basso G, Laghi L. Tumor budding as a potential histopathological biomarker in colorectal cancer: hype or hope? World J Gastroenterol 2012; 18:6532-6536. [PMID: 23236225 PMCID: PMC3516222 DOI: 10.3748/wjg.v18.i45.6532] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2012] [Revised: 10/12/2012] [Accepted: 11/11/2012] [Indexed: 02/06/2023] Open
Abstract
Colorectal cancer (CRC), the third most commonly diagnosed type of cancer in men and women worldwide is recognized as a complex multi-pathway disease, an observation sustained by the fact that histologically identical tumors may have different outcome, including various response to therapy. Therefore, particularly in early and intermediate stage (stages II and III, respectively) CRC, there is a compelling need for biomarkers helpful of selecting patients with aggressive disease that might benefit from adjuvant and targeted therapy. Histopathological examination shows that likely other solid tumors the development and progression of human CRC is not only determined by genetically abnormal cells, but also by intricate interactions between malignant cells and the surrounding microenvironment. This has led to reconsider the features of tumor microenvironment as potential predictive and prognostic biomarkers. Among the histopathological biomarkers, tumor budding (i.e., the presence of individual cells and small clusters of tumor cells at the tumor invasive front) has received much recent attention, particularly in the setting of CRC. Although its acceptance as a reportable factor has been held back by a lack of uniformity with respect to qualitative and quantitative aspects, tumor budding is now considered as an independent adverse prognostic factor in CRC that may allow for stratification of patients into risk categories more meaningful than those defined by tumor-node-metastasis staging alone, and also potentially guide treatment decisions, especially in T2-T3 N0 (stage II) CRCs.
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