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Lino-Silva LS, Zepeda-Najar C, Caro-Sánchez CH, Herrera-Gómez Á, Salcedo-Hernández RA. Prognostic significance of tumor budding in melanoma. Melanoma Res 2022; 32:318-323. [PMID: 35797486 DOI: 10.1097/cmr.0000000000000839] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Cutaneous melanoma is an aggressive neoplasm with growing incidence and continuous research is undertaken for novel prognostic factors. This current research aims to determine if tumor budding is an independent factor that correlates with the survival of patients with melanoma. A total of 742 cases of melanoma were evaluated. A receiver operating curve (ROC) was performed to analyze tumor budding impact on survival, identifying a cutoff point associated with death. Subsequently, two groups of participants were created based on that result. Participants within the two groups were compared for clinicopathologic characteristics and survival analysis. Also, a multivariate analysis was performed. Of the total, 447 (60.2%) melanomas occurred in women and 295 in men. The mean age was 57.5 years + 15.75. The most common location was in acral areas (68.2%) followed by trunk (16.7%) and head and neck (15.1%). At presentation, 142 cases (19.1%) presented as stage I, 307 (41.4%) as stage II, 269 (36.3%) as stage III, and 24 (3, 2%) in stage IV. Regarding tumor budding, 586 (79%) cases showed tumor budding (at least one bud in 0.785 mm 2 ), with a median of 5. From the ROC curve, 4.5 tumor buds/0.785 mm 2 was the best cutoff point for correlation with death, grouping the series in low budding (0-4 buds/0.785 mm 2 ) and high budding ( > 5 buds/0.785 mm 2 ). Cases with high tumor budding were associated with older age, acral location, advanced clinical stages, ulceration, recurrence, and death. High tumor budding was associated with a significant decrease in 5-year overall survival (94.4% vs. 55.5%, P < 0.001). In the multivariate analysis, the factors remaining as independent predictors of survival were acral location, clinical stage IV, recurrence during clinical follow-up, and high tumor budding. High tumor budding (>5 buds in 0.785 mm 2 ) independently correlates with 5-year overall survival rates and is associated with older age, acral location, advanced clinical stages, ulceration, recurrence, and death.
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Affiliation(s)
| | - César Zepeda-Najar
- Surgical Oncology, Hospital Angeles Tijuana, Tijuana, Baja California Norte
| | | | - Ángel Herrera-Gómez
- Surgical Oncology, Instituto Nacional de Cancerología, Tlalpan, Mexico City, Mexico
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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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Lino-Silva LS, Salcedo-Hernández RA, Gamboa-Domínguez A. Tumour budding in rectal cancer. A comprehensive review. Contemp Oncol (Pozn) 2018; 22:61-74. [PMID: 30150882 PMCID: PMC6103233 DOI: 10.5114/wo.2018.77043] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2018] [Accepted: 04/03/2018] [Indexed: 12/18/2022] Open
Abstract
A unique and fundamental characteristic of malignant neoplastic cells is their ability to invade other tissues and metastasise. The first step in this process is the dissociation of some of these cells from the tumour invasion front, named tumour budding (TB). This phenomenon has become increasingly relevant in recent years due to its association with adverse clinicopathological characteristics and with the epithelial-mesenchymal transition. TB has been studied by mixing colon with rectal tumours, but it is clinically important to differentiate these types of tumours. A review in two databases without language restriction was performed from 1950 to 2017 about TB with an emphasis on rectal cancer. We present various aspects of TB, from its terminology and evaluation to its molecular aspects, through its clinical associations. TB is associated with adverse clinicopathological features, like lymphovascular invasion, lymph node metastasis, and decreased survival. More studies of the clinicopathological, molecular, and epidemiological characteristics of TB in rectal cancer are needed.
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Athanasakis E, Xenaki S, Venianaki M, Chalkiadakis G, Chrysos E. Newly recognized extratumoral features of colorectal cancer challenge the current tumor-node-metastasis staging system. Ann Gastroenterol 2018; 31:525-534. [PMID: 30174388 PMCID: PMC6102465 DOI: 10.20524/aog.2018.0284] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2018] [Accepted: 03/13/2018] [Indexed: 12/12/2022] Open
Abstract
One of the most common malignant tumors in humans, colorectal cancer has been extensively studied during the past few decades. Staging colorectal cancer allows clinicians to obtain precise prognostic information and apply specific treatment procedures. Apart from remote metastases, the depth of tumor infiltration and lymph node involvement have traditionally been recognized as the most important factors predicting outcome. Variations in the molecular signature of colorectal cancer have also revealed differences in phenotypic aggressiveness and therapeutic response rates. This article presents a review of the extratumoral environment in colorectal surgery.
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Affiliation(s)
- Elias Athanasakis
- Department of General Surgery, University Hospital of Heraklion Crete, Greece
| | - Sofia Xenaki
- Department of General Surgery, University Hospital of Heraklion Crete, Greece
| | - Maria Venianaki
- Department of General Surgery, University Hospital of Heraklion Crete, Greece
| | - George Chalkiadakis
- Department of General Surgery, University Hospital of Heraklion Crete, Greece
| | - Emmanuel Chrysos
- Department of General Surgery, University Hospital of Heraklion Crete, Greece
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Systematic review and meta-analysis of the impact of tumour budding in colorectal cancer. Br J Cancer 2016; 115:831-40. [PMID: 27599041 PMCID: PMC5046217 DOI: 10.1038/bjc.2016.274] [Citation(s) in RCA: 169] [Impact Index Per Article: 18.8] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2016] [Revised: 07/20/2016] [Accepted: 08/01/2016] [Indexed: 12/27/2022] Open
Abstract
Background: Tumour budding is a histological finding in epithelial cancers indicating an unfavourable phenotype. Previous studies have demonstrated that it is a negative prognostic indicator in colorectal cancer (CRC), and has been proposed as an additional factor to incorporate into staging protocols. Methods: A systematic review of papers until March 2016 published on Embase, Medline, PubMed, PubMed Central and Cochrane databases pertaining to tumour budding in CRC was performed. Study end points were the presence of lymph node metastases, recurrence (local and distal) and 5-year cancer-related death. Results: A total of 7821 patients from 34 papers were included, with a mean rate of tumour budding of 36.8±16.5%. Pooled analysis suggested that specimens exhibiting tumour budding were significantly associated with lymph node positivity (OR 4.94, 95% CI 3.96–6.17, P<0.00001), more likely to develop disease recurrence over the time period (OR 5.50, 95% CI 3.64–8.29, P<0.00001) and more likely to lead to cancer-related death at 5 years (OR 4.51, 95% CI 2.55–7.99, P<0.00001). Conclusions: Tumour budding in CRC is strongly predictive of lymph node metastases, recurrence and cancer-related death at 5 years, and its incorporation into the CRC staging algorithm will contribute to more effective risk stratification.
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Petrelli F, Pezzica E, Cabiddu M, Coinu A, Borgonovo K, Ghilardi M, Lonati V, Corti D, Barni S. Tumour Budding and Survival in Stage II Colorectal Cancer: a Systematic Review and Pooled Analysis. J Gastrointest Cancer 2016; 46:212-8. [PMID: 25994502 DOI: 10.1007/s12029-015-9716-1] [Citation(s) in RCA: 59] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
PURPOSE Tumour budding is defined as the presence of isolated or small clusters of malignant cells at the invasive edge of the tumour. It is considered a negative prognostic factor in colorectal cancer (CRC) and is associated with a poor outcome and adverse pathological features. Here, we report a meta-analysis of the association of tumour budding and survival in stage II CRC patients. METHODS PubMed, EMBASE, Web of Science and SCOPUS were searched for studies that assessed the relationship between tumour budding and 5-year overall survival (OS) in stage II CRC patients. Published data were extracted and used to compute odds ratios (ORs) for death at 5 years and hazard ratios (HRs) for survival amongst patients with respect to the extent of tumour budding, using multivariate analysis. Data were pooled using the Mantel-Haenszel random effect model. RESULTS We analysed 12 studies that included a total of 1652 patients. High-grade budding was associated with worse OS at 5 years (OR for death, 6.25; 95 % confidence interval [CI], 4.04-9.67; P < 0.00001). The absolute difference in 5-year OS was -25 % (95 % CI, -18- - 33 %, P < 0.00001). It was particularly noteworthy that the presence of high-grade budding was associated with an increased risk of death (HR for death, 3.68; 95 % CI, 2.16-6.28, P < 0.00001). CONCLUSIONS Tumour budding is associated with worse survival in stage II CRC, in particular in pT3N0M0 patients. It could therefore potentially be used when deciding whether to administer adjuvant chemotherapy in high-risk node negative CRC patients.
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Affiliation(s)
- F Petrelli
- Department of Oncology, Division of Medical Oncology, Azienda Ospedaliera Treviglio, Treviglio, BG, Italy,
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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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Jayasinghe C, Simiantonaki N, Kirkpatrick CJ. Histopathological features predict metastatic potential in locally advanced colon carcinomas. BMC Cancer 2015; 15:14. [PMID: 25603809 PMCID: PMC4307171 DOI: 10.1186/s12885-015-1013-7] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2014] [Accepted: 01/06/2015] [Indexed: 01/08/2023] Open
Abstract
Background Metastatic dissemination can exist before a pathologically and clinically detectable manifestation. The structural heterogeneity of colon cancer (CC) in histological sections with respect to the morphology of tumor aggressiveness and composition of the tumor microenvironment raises the question of whether the microscopical tumor architecture enables a discrimination of groups with different metastatic potential. This would result in an assessment of the prognosis and provision of an ancillary tool for the therapeutic management after surgery, beside the estimation of the local tumor extent. Methods In order to identify predictive biomarkers for metastasis of locally advanced CC, which can easily be integrated into the pathologist’s daily routine diagnostic activity, we determined tumor budding, peritumoral inflammation, extent of desmoplasia and necrosis, density of macro- and microvascular blood vessels and functional state of lymphatics in the tumor center, invasive margin and tumor-free surrounding tissue in 86 non-metastatic, lymphogenous-metastatic and haematogenous-metastatic, subserosa-invasive CC. Results Features influencing nodal metastasis in the univariate analysis included high tumor budding (p = 0.004), high large vessel density in the subserosa (p = 0.043), abundant desmoplasia (p = 0.049), non-finger-like desmoplastic pattern (p = 0.051) and absent lymphocellular intratumoral inflammation (p = 0.084). In the multivariate analysis, with the exception of large vessel density, these pathomorphological features were independent risk factors for lymphogenous metastasis (p = 0.023, p = 0.017, p = 0.037, p = 0.012, respectively) with a good discrimination ability (AUC of 0.853). Features associated with distant metastasis in the univariate analysis included high tumor budding (p = 0.002), low intratumoral small vessel density (p = 0.013), absent lymphocellular intratumoral inflammation (p = 0.048) and abundant necrosis (p = 0.073). In the multivariate analysis only tumor budding was an independent predictor for haematogenous metastasis (p = 0.007) with a good discrimination ability (AUC of 0.829). Conclusions Thus, mainly tumor budding but also the described structural characteristics of the peritumoral tissue appears to reflect the metastatic potential of locally advanced CC and therefore should be stated in pathological reports.
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Affiliation(s)
- Caren Jayasinghe
- Institute of Pathology, Johannes Gutenberg University, Langenbeckstr. 1, 55101, Mainz, Germany. .,Department of Pathology, Laboratory Medicine Cologne, Geibelstr. 2, 50931, Cologne, Germany.
| | - Nektaria Simiantonaki
- Institute of Pathology, Johannes Gutenberg University, Langenbeckstr. 1, 55101, Mainz, Germany. .,Institute of Pathology Essen-Mitte, Am Deimelsberg 34a, 45276, Essen, Germany.
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Landau MS, Hastings SM, Foxwell TJ, Luketich JD, Nason KS, Davison JM. Tumor budding is associated with an increased risk of lymph node metastasis and poor prognosis in superficial esophageal adenocarcinoma. Mod Pathol 2014; 27:1578-1589. [PMID: 24762549 PMCID: PMC4209206 DOI: 10.1038/modpathol.2014.66] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2013] [Revised: 02/25/2014] [Accepted: 02/25/2014] [Indexed: 12/18/2022]
Abstract
The treatment approach for superficial (stage T1) esophageal adenocarcinoma critically depends on the pre-operative assessment of metastatic risk. Part of that assessment involves evaluation of the primary tumor for pathologic characteristics known to predict nodal metastasis: depth of invasion (intramucosal vs submucosal), angiolymphatic invasion, tumor grade, and tumor size. Tumor budding is a histologic pattern that is associated with poor prognosis in early-stage colorectal adenocarcinoma and a predictor of nodal metastasis in T1 colorectal adenocarcinoma. In a retrospective study, we used a semi-quantitative histologic scoring system to categorize 210 surgically resected, superficial (stage T1) esophageal adenocarcinomas according to the extent of tumor budding (none, focal, and extensive) and also evaluated other known risk factors for nodal metastasis, including depth of invasion, angiolymphatic invasion, tumor grade, and tumor size. We assessed the risk of nodal metastasis associated with tumor budding in univariate analyses and controlled for other risk factors in a multivariate logistic regression model. In all, 41% (24 out of 59) of tumors with extensive tumor budding (tumor budding in ≥3 20X microscopic fields) were metastatic to regional lymph nodes, compared with 10% (12 out of 117) of tumors with no tumor budding, and 15% (5 out of 34) of tumors with focal tumor budding (P<0.001). When controlling for all pathologic risk factors in a multivariate analysis, extensive tumor budding remains an independent risk factor for lymph node metastasis in superficial esophageal adenocarcinoma associated with a 2.5-fold increase (95% CI=1.1-6.3, P=0.039) in the risk of nodal metastasis. Extensive tumor budding is also a poor prognostic factor with respect to overall survival and time to recurrence in univariate and multivariate analyses. As an independent risk factor for nodal metastasis and poor prognosis after esophagectomy, tumor budding should be evaluated in superficial (T1) esophageal adenocarcinoma as a part of a comprehensive pathologic risk assessment.
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Affiliation(s)
- Michael S. Landau
- Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA
| | - Steven M. Hastings
- Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA
| | - Tyler J. Foxwell
- Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA
| | - James D. Luketich
- Department of Cardiothoracic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA
| | - Katie S. Nason
- Department of Cardiothoracic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA
| | - Jon M. Davison
- Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA
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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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Homma Y, Hamano T, Otsuki Y, Shimizu S, Kobayashi Y. Total number of lymph node metastases is a more significant risk factor for poor prognosis than positive lateral lymph node metastasis. Surg Today 2014; 45:168-74. [PMID: 24831659 DOI: 10.1007/s00595-014-0913-5] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2013] [Accepted: 02/14/2014] [Indexed: 12/20/2022]
Abstract
PURPOSE Lateral lymph nodes (LLNs) along the iliac vessels are an important indicator of local recurrence; however, we are unaware of any study that investigates whether the number of LLN metastases influences the prognosis of patients with lower rectal cancer. METHOD We analyzed retrospectively the records of 154 patients who underwent radical resection of T1-4 lower rectal adenocarcinoma at a single institution. RESULTS Among the 88.3 % of patients who underwent LLN dissection, 13 (8.4 %) had LLN metastasis. The Cox proportional hazard model indicated that sex, histological grade, lymphatic or venous invasion, and LLN metastasis were not significantly associated with tumor recurrence, whereas tumor depth and more than three lymph node metastases were risk factors for recurrence (p = 0.002 and p = 0.02, respectively). Of the 13 patients with LLN metastasis, 6 whose mesenteric lymph nodes (MLNs) had been well dissected and examined did not have MLN metastasis. CONCLUSIONS The presence of one or two LLN metastases in patients who have undergone LLN dissection with surgery for lower rectal cancer is not associated with poor prognosis. The number of LLN metastases is a more significant risk factor for poor prognosis.
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Affiliation(s)
- Yoichiro Homma
- Department of Colorectal Surgery, Seirei Hamamatsu General Hospital, Naka-ku Sumiyoshi 2-12-12, Hamamatsu, Shizuoka, 430-8558, Japan,
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Peng JY, Li ZN, Wang Y. Risk factors for local recurrence following neoadjuvant chemoradiotherapy for rectal cancers. World J Gastroenterol 2013; 19:5227-5237. [PMID: 23983425 PMCID: PMC3752556 DOI: 10.3748/wjg.v19.i32.5227] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2013] [Revised: 06/14/2013] [Accepted: 07/18/2013] [Indexed: 02/06/2023] Open
Abstract
Local recurrence (LR) has an adverse impact on rectal cancer treatment. Neoadjuvant chemoradiotherapy (nCRT) is increasingly administered to patients with progressive cancers to improve the prognosis. However, LR still remains a problem and its pattern can alter. Correspondingly, new risk factors have emerged in the context of nCRT in addition to the traditional risk factors in patients receiving non-neoadjuvant therapies. These risk factors are decisive when reviewing treatment options. This review aims to elucidate the distinctive risk factors related to LR of rectal cancers in patients receiving nCRT and to clarify their clinical significance. A search was conducted on PubMed to identify original studies investigating patients with rectal cancer receiving nCRT. Outcomes of interest, especially potential risk factors for LR in patients with nCRT, were then analyzed. The clinical importance of these risk factors is discussed. Remnant cancer cells, lymph-nodes and tumor response were found to be major risk factors. Remnant cancer cells decide the status of resection margins. Local excision following nCRT is promising in ypT0-1N0M0 cases. Dissection of lateral lymph nodes should be considered in advanced low-lying cancers. Although better tumor response resulted in a relatively lower recurrence rate, the evidence available is insufficient to justify a non-operative approach in clinical complete responders to nCRT. LR cannot be totally avoided by current multidisciplinary approaches. The related risk factors resulting from nCRT should be considered when making decisions regarding treatment selection.
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Liang F, Cao W, Wang Y, Li L, Zhang G, Wang Z. The prognostic value of tumor budding in invasive breast cancer. Pathol Res Pract 2013; 209:269-75. [PMID: 23561623 DOI: 10.1016/j.prp.2013.01.009] [Citation(s) in RCA: 79] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2012] [Revised: 12/27/2012] [Accepted: 01/27/2013] [Indexed: 12/11/2022]
Abstract
We investigated the prognostic value of tumor budding in 160 cases of operable invasive ductal carcinoma, not otherwise specified (IDC-NOS). The number of buds was counted in H&E slides with a maximal invasive margin in a 0.950mm(2) field of vision (200×). According to a cut-off score selected by ROC analysis, the cohort was dichotomized into a low (0-7 budding foci, 107 cases, 66.9%) and a high-grade budding group (8 or more budding foci, 53 cases, 33.1%). The inter-observer test showed a good reproducibility with 0.717 as the К value. High-grade budding was significantly associated with the presence of lymphovascular invasion (LVI) (P=0.001), larger tumor size (P=0.014), and worse clinical outcome (P<0.001). By immunohistochemical staining, budded cells at the margin displayed epithelial mesenchymal transition (EMT)-like molecular phenotype and decreased proliferative activity. Survival analyses revealed that tumor budding (HR 4.275, P<0.001) together with tumor size (HR 2.468, P=0.002), node status (HR 2.362, P<0.001), and LVI status (HR 1.910, P=0.035) was the independent prognostic factor in IDC-NOS. In conclusion, tumor budding is a reproducible, significant, and independent histopathological prognostic factor in IDC-NOS.
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Affiliation(s)
- Fenli Liang
- Center for Cancer Research, First Affiliated Hospital of Xi'an Jiaotong University, 710061 Xi'an, China
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Kim JC, Yu CS, Lim SB, Kim CW, Kim JH, Kim TW. Abdominoperineal resection and low anterior resection: comparison of long-term oncologic outcome in matched patients with lower rectal cancer. Int J Colorectal Dis 2013; 28:493-501. [PMID: 23053680 DOI: 10.1007/s00384-012-1590-8] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/23/2012] [Indexed: 02/04/2023]
Abstract
PURPOSE The current study aimed to compare the oncologic outcome and pattern of metastasis after abdominoperineal resection (APR) and low anterior resection (LAR) treating lower rectal cancer. METHODS A total of 804 patients undergoing curative resection (R0) were enrolled prospectively. The APR and LAR groups (n = 402, respectively) were matched for gender, age, and stage, for a retrospectively comparative analysis. RESULTS In a multivariate analysis with potential variables, APR itself was not a risk factor for increased local recurrence (LR) or reduced survival (P = 0.243-0.994). Circumferential resection margin (CRM) involvement as an operation-related risk was 1.6-fold more frequent in the APR group and was significantly associated with LR and systemic recurrence (OR, 2.487-4.017; P < 0.01). Circumferential margin positivity (CRM+) was concurrently correlated with advanced stage, larger tumor (long diameter, >4 cm), and longer sagittal midpelvic diameter (>10 cm) in a multivariate analysis (P < 0.001-0.05). The site of metastasis did not differ between the two groups, with the exception of lung metastasis which was more frequent in the APR group (APR vs. LAR: 15.9 vs. 10 %, P = 0.015). In the APR group, CRM+ and the presence of an infiltrating tumor were correlated with disease-free survival (hazard ratio (HR), 1.644 and 1.654, respectively), whereas elevated serum carcinoembryonic antigen and LVI+ were correlated with overall survival (HR, 1.57 and 1.671, respectively), in a multivariate analysis with potential variables (P < 0.05). CONCLUSIONS When performed with appropriate skill to achieve R0 resection, APR can be used safely without impairing oncological outcome, although sphincter-preserving surgery should remain the preferred option.
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Affiliation(s)
- Jin C Kim
- Department of Surgery, University of Ulsan College of Medicine, and Institute of Innovative Cancer Research, Asan Medical Center, 86 Asanbyeongwon-gil, Songpa-gu, 138-736 Seoul, South Korea.
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Abstract
INTRODUCTION In patients with metastatic colorectal cancers, multimodal management and the use of biological agents such as monoclonal antibodies have had major positive effects on survival. The ability to predict which patients may be at 'high risk' of distant metastasis could have major implications on patient management. Histomorphological, immunohistochemical or molecular biomarkers are currently being investigated in order to test their potential value as predictors of metastasis. AREAS COVERED Here, the author reviews the clinical and functional data supporting the investigation of three novel promising biomarkers for the prediction of metastasis in patients with colorectal cancer: tumor budding, Raf1 kinase inhibitor protein (RKIP) and metastasis-associated in colon cancer-1 (MACC1). EXPERT OPINION The lifespan of most potential biomarkers is short as evidenced by the rare cases that have successfully made their way into daily practice such as KRAS or microsatellite instability (MSI) status. Although the three biomarkers reviewed herein have the potential to become important predictive biomarkers of metastasis, they have similar hurdles to overcome before they can be implemented into clinical management: standardization and validation in prospective patient cohorts.
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Affiliation(s)
- Inti Zlobec
- University of Bern, Institute of Pathology L414, Translational Research Unit (TRU), Bern, Switzerland.
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Additional colectomy after colonoscopic polypectomy for T1 colon cancer: a fine balance between oncologic benefit and operative risk. Int J Colorectal Dis 2012; 27:1473-8. [PMID: 22454048 DOI: 10.1007/s00384-012-1464-0] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/09/2012] [Indexed: 02/04/2023]
Abstract
PURPOSE The treatment of early-stage colorectal cancers removed endoscopically depends on histopathologic findings. This study aimed to assess the benefit-risk balance for patients who underwent additional surgery after endoscopic resection of a T1 carcinoma with unfavorable histology. METHODS From 2000 to 2010, 64 consecutive patients were included in this retrospective study. Specimens resected after endoscopic polypectomy showed at least one of the following unfavorable factors: no free margin, lymphovascular invasion, poorly differentiated grade, SM2-3 involvement (submucosal invasion greater than 300 μm from the muscularis mucosae), tumor budding, sessile morphology, and piecemeal resection. The main objective was to assess the benefit-risk balance of an oncological resection performed after the polypectomy. Oncological benefit was measured by the lymph node metastasis rate and the persistence of a residual adenocarcinoma on the specimen. The risk was measured by the occurrence of severe complications of grade III-IV or death. The associations between these end points and clinicopathologic variables were evaluated by univariate analysis and logistic regression. RESULTS Five patients (7.8 %) had lymph node metastases and two (3.1 %) had residual carcinomas. Eight patients (12.5 %) had grade III-IV morbidity. There were no deaths. Oncological benefit was associated by logistic regression analysis with patients who presented multiple criteria (≥2) that led to surgery (p = 0.031). The benefit-risk balance was favorable only for those patients. CONCLUSIONS Additional surgery is required for patients who present multiple adverse histological criteria. If only one criterion is selected, the indication should be discussed, especially for patients with multiple comorbidities.
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Abstract
Tumor 'budding', loosely defined by the presence of individual cells and small clusters of tumor cells at the invasive front of carcinomas, has received much recent attention, particularly in the setting of colorectal carcinoma. It has been postulated to represent an epithelial-mesenchymal transition. Tumor budding is a well-established independent adverse prognostic factor in colorectal carcinoma that may allow for stratification of patients into risk categories more meaningful than those defined by TNM staging, and also potentially guide treatment decisions, especially in T1 and T3 N0 (Stage II, Dukes' B) colorectal carcinoma. Unfortunately, its universal acceptance as a reportable factor has been held back by a lack of definitional uniformity with respect to both qualitative and quantitative aspects of tumor budding. The purpose of this review is fourfold: (1) to describe the morphology of tumor budding and its relationship to other potentially important features of the invasive front; (2) to summarize current knowledge regarding the prognostic significance and potential clinical implications of this histomorphological feature; (3) to highlight the challenges posed by a lack of data to allow standardization with respect to the qualitative and quantitative criteria used to define budding; and (4) to present a practical approach to the assessment of tumor budding in everyday practice.
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Zlobec I, Borner M, Lugli A, Inderbitzin D. Role of intra- and peritumoral budding in the interdisciplinary management of rectal cancer patients. Int J Surg Oncol 2012; 2012:795945. [PMID: 22900161 PMCID: PMC3415098 DOI: 10.1155/2012/795945] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2012] [Accepted: 06/23/2012] [Indexed: 01/30/2023] Open
Abstract
The presence of tumor budding (TuB) at the invasive front of rectal cancers is a valuable indicator of tumor aggressiveness. Tumor buds, typically identified as single cells or small tumor cell clusters detached from the main tumor body, are characterized by loss of cell adhesion, increased migratory, and invasion potential and have been referred to as malignant stem cells. The adverse clinical outcome of patients with a high-grade TuB phenotype has consistently been demonstrated. TuB is a category IIB prognostic factor; it has yet to be investigated in the prospective setting. The value of TuB in oncological and pathological practice goes beyond its use as a simple histomorphological marker of tumor aggressiveness. In this paper, we outline three situations in which the assessment of TuB may have direct implications on treatment within the multidisciplinary management of patients with rectal cancer: (a) patients with TNM stage II (i.e., T3/T4, N0) disease potentially benefitting from adjuvant therapy, (b) patients with early submucosally invasive (T1, sm1-sm3) carcinomas at a high risk of nodal positivity and (c) the role of intratumoral budding assessed in preoperative biopsies as a marker for lymph node and distant metastasis thus potentially aiding the identification of patients suitable for neoadjuvant therapy.
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Affiliation(s)
- Inti Zlobec
- Institute of Pathology, University of Bern, Murtenstrasse 31, 3010 Bern, Switzerland
| | - Markus Borner
- Department of Oncology, Hospital Centre Biel, 2502 Bienne, Switzerland
| | - Alessandro Lugli
- Institute of Pathology, University of Bern, Murtenstrasse 31, 3010 Bern, Switzerland
- Clinical Pathology Division, Institute of Pathology, University of Bern, Murtenstrasse 31, 3010 Bern, Switzerland
| | - Daniel Inderbitzin
- Department of Visceral and Transplantation Surgery, Inselspital-Bern University Hospital, 3010 Bern, Switzerland
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Analysis of risk factors for lymph nodal involvement in early stages of rectal cancer: when can local excision be considered an appropriate treatment? Systematic review and meta-analysis of the literature. Int J Surg Oncol 2012; 2012:438450. [PMID: 22778940 PMCID: PMC3388331 DOI: 10.1155/2012/438450] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2012] [Revised: 04/15/2012] [Accepted: 04/17/2012] [Indexed: 02/08/2023] Open
Abstract
Background. Over the past ten years oncological outcomes achieved by local excision techniques (LETs) as the sole treatment for early stages of rectal cancer (ESRC) have been often disappointing. The reasons for these poor results lie mostly in the high risk of the disease's diffusion to local-regional lymph nodes even in ESRC. Aims. This study aims to find the correct indications for LET in ESRC taking into consideration clinical-pathological features of tumours that may reduce the risk of lymph node metastasis to zero. Methods. Systematic literature review and meta-analysis of casistics of ESRC treated with total mesorectal excision with the aim of identifying risk factors for nodal involvement. Results. The risk of lymph node metastasis is higher in G ≥ 2 and T ≥ 2 tumours with lymphatic and/or vascular invasion. Other features which have not yet been sufficiently investigated include female gender, TSM stage >1, presence of tumour budding and/or perineural invasion. Conclusions. Results comparable to radical surgery can be achieved by LET only in patients with T(1) N(0) G(1) tumours with low-risk histological features, whereas deeper or more aggressive tumours should be addressed by radical surgery (RS).
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Märkl B, Arnholdt HM. Prognostic significance of tumor budding in gastrointestinal tumors. Expert Rev Anticancer Ther 2011; 11:1521-33. [PMID: 21999126 DOI: 10.1586/era.11.156] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Tumor budding describes the presence of single tumor cells or small tumor cell clusters at the invasion front of carcinomas. It is currently thought to be the result of epithelial-mesenchymal transformation. Tumor budding can be appreciated histologically during routine evaluation of malignant polyps or surgical specimens of malignant tumors. Many studies have been published assessing cancers in all locations from the esophagus to the rectum, almost always reporting similar results. This seems especially remarkable as a generally accepted definition of how budding must be evaluated is still lacking. Regardless of the location, tumor budding generally is associated with nodal metastases and aggressive behavior, and it is mostly independent from other adverse factors. While the prognostic value of tumor budding is evident, especially in stage II colorectal cancers, it still has no therapeutic implications. This is owing to the heterogeneity of the performed studies and the lack of oncological studies, which are urgently needed.
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Affiliation(s)
- Bruno Märkl
- Institute of Pathology, Stenglinstrasse 2, 86156 Augsburg, Germany.
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