Photomicrography of tumor cell budding. An isolated single cancer cell and a cluster composed of fewer than five cancer cells are identified at the invasive front of the tumor (H&E, × 200).

Photomicrography of tumor cell budding. An isolated single cancer cell and a cluster composed of fewer than five cancer cells are identified at the invasive front of the tumor (H&E, × 200).

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The objective of the current study was to identify the clinicopathological risk factors affecting recurrence after a curative resection for stage I colorectal cancer. We retrospectively studied 434 patients who underwent a curative resection for stage I colorectal cancer between January 1999 and December 2004. Postoperative oral chemotherapy was pe...

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... Some studies showed that tumors with LVI have a higher likelihood of advanced T stage or tumor budding and infiltrating or poorly differentiated histology [17]. LVI has also been suggested as a risk factor for micrometastases or skip metastasis [18], and these may explain the metastatic potential of LVI, even in patients without LN metastases. Distant metastasis tended to be more dominant than local recurrence in colon cancer. ...
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Recurrence can still occur even after radical resection of stage I colorectal cancer (CRC). This study aimed to identify subgroups with a high risk for recurrence in the stage I CRC. We retrospectively reviewed prospectively collected data of 1952 patients with stage I CRC after radical resection between 2002 and 2017 at our institute. 1398 (colon, 903 (64.6%), rectum, 495 (35.4%)) were eligible for analysis. We analyzed the risk factors for recurrence and survival. During the follow-up period (median: 59 months), 63 (4.6%) had a recurrence. The recurrence rate of rectal cancer was significantly higher than that of colon cancer (8.5% vs. 2.3%). Left-sided tumors, T2, tumor size >5 cm, and lymphovascular invasion were independent risk factors of colon cancer recurrence. Male, preoperative carcinoembryonic antigen (CEA) ≥2.5 ng/mL, and harvested lymph nodes (LNs) <12 were independently associated with recurrence of rectal cancer. Recurrence affected OS (5-year OS: 97.1% vs. 67.6%). Despite curative resection, survival sharply decreased with recurrence. The risk factors for recurrence were different between colon and rectal cancer. Patients with a higher risk for recurrence should be candidates for more aggressive surveillance, even in early-stage CRC.
... The 5-year recurrence rate of resected stage I NSCLC has been reported to be as high as 35-40%, demonstrating that the presence of micrometastases is a common phenomenon [18]. This is particularly staggering when compared with 5-year recurrence statistics for other types of stage I cancers, including breast cancer (3.1%) [19] and colon cancer (4.6%) [20]. In a randomized prospective trial of patients with stage I lung cancer undergoing lobectomy versus segment or wedge resection, it was shown that patients who had lobectomy developed less locoregional recurrence [21]. ...
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There remains a critical need for improved staging of non-small-cell lung cancer, as recurrence and mortality due to undetectable metastases at the time of surgery remain high even after complete resection of tumors currently categorized as 'early stage.' A 14-gene quantitative PCR-based expression profile has been extensively validated to better identify patients at high-risk of 5-year mortality after surgical resection than conventional staging - mortality that almost always results from previously undetectable metastases. Furthermore, prospective studies now suggest a predictive benefit in disease-free survival when the assay is used to guide adjuvant chemotherapy decisions in early-stage non-small-cell lung cancer patients.
... There is mounting evidence of the prognostic importance of TB in CRC and other malignancies [4,[21][22][23]. Numerous studies have shown TB to be a strong and independent predictor of local lymph node metastases in pT1 colorectal cancer [6,[24][25][26][27][28][29][30][31][32][33][34][35][36][37] and of recurrence and survival in stage II colorectal cancer [4,5,[38][39][40][41][42][43][44]. Thus, TB strongly influences (neo-) adjuvant therapy decisions and stage II colorectal cancer patients with high-grade tumor budding may be considered for adjuvant therapy [3,7,15,16]. ...
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Purpose: Evaluation of tumor budding in colorectal cancer (CRC) may help to predict the tumors' metastatic potential and patients with an aggressive tumor, although not yet metastasized at time of surgery might benefit from adjuvant therapy. Methods: The degree of intratumoral tumor budding (ITB) was classified as low, intermediate, and high grade according to the recommendations of the International Tumor Budding Consensus Conference (ITBCC) 2016 on H&E and pankeratin-stained TMA sections from 1262 CRC, no special type (NST), including 655 stage II CRC and was correlated to clinicopathological data and overall survival. Results: Results show that higher ITB rates are significantly linked to higher tumor grade and stage, positive nodal status, lymphovascular invasion (P < 0.0001 each), absence of peritumoral lymphocytes, infiltrating type invasive tumor margin, left-sided cancer localization, and mismatch-repair proficient cancers (P < 0.05 each). In a cohort of 655 stage II CRC, ITB was associated with lymphovascular invasion (P = 0.0459) and adverse clinical outcome (P < 0.0001). In a multivariate analysis including tumor stage, tumor grade, lymphovascular invasion, ITB, and tumor localization, only low tumor stage (P = 0.0022) and absence of lymphovascular invasion (P = 0.0043) showed independent prognostic significance. Conclusion: In conclusion, our findings argue towards a clinical utility of ITB as a prognostic biomarker in stage II colorectal cancer to define patients who might benefit from adjuvant therapy. ITB might be used as additional or surrogate marker in CRC in which peritumoral tumor budding is difficult to assess.
... 8 In addition, in a multivariate analysis conducted on the clinicopathologic factors, the gross appearance of the tumor was identified as an independent factor affecting recurrence (P-value ¼ 0.020). 9 ...
... In addition to degree of differentiation, gross tumor morphology has been found to be an important prognostic variable. 8 Keum et al. 9 who retrospectively studied 434 patients in their study suggested that the location of the tumor (P-value ¼ 0.009), T stage (P-value ¼ 0.010), and gross findings (P-value ¼ 0.017) are significant in the univariate analysis of the clinicopathologic factors affecting recurrence. In addition, on multivariate analysis, gross finding of the tumor (P-value ¼ 0.020) was identified as an independent factor affecting recurrence. ...
... Gross morphologically fungating/ulcerofungating lesions had 3.9% recurrence, and ulceroinfiltrative/infiltrative lesions had 10.9% recurrence rate. 9 In addition, in our study, the ulceroinfiltrative/infiltrative lesions are more common in the rectum than in the colon and ulceroinfiltrative/infiltrative lesions are known to have poor prognosis and more recurrence than the proliferative or fungative lesions. ...
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Background Clinical presentation of colorectal cancers (CRCs) also depends on the gross tumor morphology. This has also been found to be an important prognostic variable. Objectives The objective of this study was to evaluate the influence of gross tumor morphology on clinicopathological profile of CRCs in Kashmiri population. Methods This 5-year study is a prospective (2 yrs) and retrospective (3 yrs) study conducted from 2011 to 2016 in the Colorectal Surgery Division at Sher-i-Kashmir Institute of Medical Sciences (SKIMS), Srinagar, Kashmir, India. Parameters studied were age, sex, site of lesion, clinical presentations, gross tumor morphology, and histopathology of the lesion. Results A total of 930 patients with CRC were included. Infiltrative variety was the most common morphology in patients aged 15–25 years and patients older than 75 years (P-value <0.0001). Gross tumor morphology of CRC had no relation with the sex of the patient, patient demographics, dietary habit, and smoking history. There was statistically significant correlation between the gross tumor morphology and bleeding per rectum (P/R). The most common type of tumor leading to pallor was proliferative (51.7%). All the 20 patients with ulceroinfiltrative growth in our study had poorly differentiated histology, and a majority of patients (58.2%) with proliferative lesions had well-differentiated adenocarcinoma. Among 149 patients in our study with poorly differentiated histology, 76 (51%) had infiltrative lesion (P-value<0.0001). Conclusion Different morphological types of CRC vary with respect to clinical presentation. Microscopically, degree of differentiation also varies in different gross morphological types. We concluded that clinical presentation of CRCs also depends on the gross tumor morphology and, in turn, the gross tumor morphology is an important prognostic variable.
... Keum et al [30] concluded that high risk factors for recurrence include rectal cancer, T2 stage and an infiltrative growth pattern. However, this study only looked at patients who underwent resection for stage I colorectal cancer which may explain their finding of T2 stage compared with ours of T4 stage. ...
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AIM To evaluate prognostic pathological factors associated with early metachronous disease and adverse long-term survival in these patients. METHODS Clinical and histological features were analysed retrospectively over an eight-year period for prognostic impact on recurrent disease and overall survival in patients undergoing curative resection of a primary colorectal cancer. RESULTS A total of 266 patients underwent curative surgery during the study period. The median age of the study cohort was 68 year (range 26 to 91) with a follow-up of 7.9 years (range 4.6 to 12.6). Resection was undertaken electively in 225 (84.6%) patients and emergency resection in 35 (13.2%). Data on timing of surgery was missing in 6 patients. Recurrence was noted in 67 (25.2%) during the study period and was predominantly early within 3 years (82.1%) and involved hepatic metastasis in 73.1%. Emergency resection (OR = 3.60, P = 0.001), T4 stage (OR = 4.33, P < 0.001) and lymphovascular invasion (LVI) (OR = 2.37, P = 0.032) were associated with higher risk of recurrent disease. Emergency resection, T4 disease and a high lymph node ratio (LNR) were strong independent predictors of adverse long-term survival. CONCLUSION Emergency surgery is associated with adverse disease free and long-term survival. T4 disease, LVI and LNR provide strong independent predictive value of long-term outcome and can inform surveillance strategies to improve outcomes.
... Numerous studies, as well as four meta-analyses, have shown tumor budding to be a strong and independent predictor of local lymph node metastases in pT1 colorectal cancer. [15][16][17][31][32][33][60][61][62][63][64][65][66][67][68] The ITBCC group therefore strongly recommends the reporting of tumor budding in pT1 colorectal cancer along with other histopathologic predictors of lymph node metastasis, such as poor differentiation, lymphovas- cular invasion and depth/level of submucosal invasion. 16 However, some stage II colorectal cancer patients show worse survival than stage III colorectal cancer patients who receive adjuvant chemotherapy. ...
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Tumor budding is a well-established independent prognostic factor in colorectal cancer but a standardized method for its assessment has been lacking. The primary aim of the International Tumor Budding Consensus Conference (ITBCC) was to reach agreement on an international, evidence-based standardized scoring system for tumor budding in colorectal cancer. The ITBCC included nine sessions with presentations, a pre-meeting survey and an e-book covering the key publications on tumor budding in colorectal cancer. The 'Grading of Recommendation Assessment, Development and Evaluation' method was used to determine the strength of recommendations and quality of evidence. The following 10 statements achieved consensus: tumor budding is defined as a single tumor cell or a cell cluster consisting of four tumor cells or less (22/22, 100%). Tumor budding is an independent predictor of lymph node metastases in pT1 colorectal cancer (23/23, 100%). Tumor budding is an independent predictor of survival in stage II colorectal cancer (23/23, 100%). Tumor budding should be taken into account along with other clinicopathological features in a multidisciplinary setting (23/23, 100%). Tumor budding is counted on H&E (19/22, 86%). Intratumoral budding exists in colorectal cancer and has been shown to be related to lymph node metastasis (22/22, 100%). Tumor budding is assessed in one hotspot (in a field measuring 0.785 mm(2)) at the invasive front (22/22, 100%). A three-tier system should be used along with the budding count in order to facilitate risk stratification in colorectal cancer (23/23, 100%). Tumor budding and tumor grade are not the same (23/23, 100%). Tumor budding should be included in guidelines/protocols for colorectal cancer reporting (23/23, 100%). Members of the ITBCC were able to reach strong consensus on a single international, evidence-based method for tumor budding assessment and reporting. It is proposed that this method be incorporated into colorectal cancer guidelines/protocols and staging systems.Modern Pathology advance online publication, 26 May 2017; doi:10.1038/modpathol.2017.46.
... Numerous studies, as well as four meta-analyses, have shown tumor budding to be a strong and independent predictor of local lymph node metastases in pT1 colorectal cancer. [15][16][17][31][32][33][60][61][62][63][64][65][66][67][68] The ITBCC group therefore strongly recommends the reporting of tumor budding in pT1 colorectal cancer along with other histopathologic predictors of lymph node metastasis, such as poor differentiation, lymphovas- cular invasion and depth/level of submucosal invasion. 16 However, some stage II colorectal cancer patients show worse survival than stage III colorectal cancer patients who receive adjuvant chemotherapy. ...
Article
594Background: Tumor budding, defined as single tumor cells or small clusters of four or less tumor cells at the invasive front, has been shown to be a strong and independent prognostic factor in colorectal cancer (CRC). However, widespread reporting of tumor budding has been held back largely due to a lack of consensus on scoring methods. 23 experts from the United States, Canada, Japan and Europe participated at the International Tumor Budding Consensus Conference (ITBCC), held in April 2016 in Bern, Switzerland, and agreed on a set of recommendations for assessing and reporting tumor budding in CRC. The aim of this study was to validate the method proposed by ITBCC in the clinically relevant scenario of Stage II CRC. Methods: In 151 Stage II CRC patients, tumor budding was assessed on scanned H&E-stained slides in a single hot spot measuring 0.785mm2. Cutoffs as defined by ITBCC were used: Low (Bd1): 0-4 buds, intermediate (Bd2): 5-9 buds, high (Bd3): ≥ 10 buds. Statistical analysis for associations wi...
... Infiltrative growth pattern at the tumour margin is associated with shorter patient survival in colorectal cancer (Cianchi et al, 2007;Karamitopoulou et al, 2015;Keum et al, 2012;Morikawa et al, 2012;Zlobec et al, 2009Zlobec et al, , 2007. Infiltrative growth pattern has been associated with specific tumour subtype; that is, microsatellitestable (MSS) and BRAF-mutated colorectal cancer Roman et al, 2010). ...
... Colorectal cancer is a heterogeneous group of cancers with various histological and molecular phenotypes that differ in disease progression (Morikawa et al, 2011). Infiltrative growth pattern at the tumour margin and lymph node metastasis are reliable histological indicators of higher colorectal cancer mortality (Cianchi et al, 2007;Keum et al, 2012;Morikawa et al, 2012;Zlobec et al, 2009Zlobec et al, , 2014Zlobec et al, , 2007. Considering that the effects of adjuvant therapy may differ according to tumour molecular features (Jonker et al, 2014;Liao et al, 2012), identifying tumour infiltration and metastasis-associated molecular markers is important for targeted therapy. ...
Article
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Background: Loss of CDH1 (E-cadherin) expression in cancer cells may promote cell migration and invasion. Therefore, we hypothesised that loss of CDH1 expression in colorectal carcinoma might be associated with aggressive features and clinical outcome. Methods: Utilising molecular pathological epidemiology database of 689 rectal and colon cancer cases in the Nurses' Health Study and the Health Professionals Follow-up Study, we assessed tumour CDH1 expression by immunohistochemistry. Multivariate logistic regression analysis was conducted to assess association of CDH1 loss with tumour growth pattern (expansile-intermediate vs infiltrative) and lymph node metastasis and distant metastasis, controlling for potential confounders including microsatellite instability, CpG island methylator phenotype, LINE-1 methylation, and PIK3CA, BRAF and KRAS mutations. Mortality according to CDH1 status was assessed using Cox proportional hazards model. Results: Loss of tumour CDH1 expression was observed in 356 cases (52%), and associated with infiltrative tumour growth pattern (odds ratio (OR), 2.02; 95% confidence interval (CI), 1.23-3.34; P=0.006) and higher pN stage (OR, 1.73; 95% CI, 1.23-2.43; P=0.001). Tumour CDH1 expression was not significantly associated with distant metastasis or prognosis. Conclusions: Loss of CDH1 expression in colorectal cancer is associated with infiltrative tumour growth pattern and lymph node metastasis.British Journal of Cancer advance online publication 7 January 2016 doi:10.1038/bjc.2015.347 www.bjcancer.com.
... Komori et al [97] 2010 111 (0) Ueno et al [46] H&E SMd, SMw, L, V, TB, area of SM invasion, histologic type at deepest invasion TB, Histological type Tateishi et al [98] 2010 322 (0) Ueno et al [46] H&E 32.9% G, SMd, L, V, TB, disruption of muscularis mucosae TB (multivariate), L1, G Ueno et al [99] 2010 296 (67) Ueno et al [63] H&E 11.8% G, SMd, SMw, L, V, TB, size, TuConf, growth pattern, adenoma component, extent of poorly differentiated component, cribriform pattern, extent of mucin-producing component TB, SMd, SMw, LVI, cribriform pattern, extent of poorly differentiated component, extent of mucin-producing component, grade of leastdifferentiated component Akishima-Fukasawa et al [100] 2011 111 (0) Ueno et al [63] H&E 50.5% G, SMd, SMw, L, V, TB, TuConf, border, disruption of muscularis mucosae, neutrophil infiltration in cancer cells, fibrotic cancer-type stroma, LInf, Crohn-like reaction, microscopic abscess formation TB, SMd, G, L1, border, disruption of muscularis mucosa, neutrophil infiltration in cancer cells, fibrotic cancer-type stroma, Crohn-like reaction, microscopic abscess formation Keum et al [101] 2012 434 (0) Ueno et al [46] H&E 40% in patients with recurrence Age, sex, G, L, V, TB, location, size, border, TuConf, annularity, poorly differentiated component, myxoid cancer stroma, infiltration level in muscularis propria TB found in all 20 patients with recurrence ...
... DTAV is regarded as the most important factor for the determination of anal preserving surgery methods by the majority of researchers (22,23). Colorectal cancer has the particular biological characteristic of upwards growth along the intestinal wall (24). However, the downward growth is generally within 2.0 cm and growth of >2.0 cm presents in only 3% of cases (25,26). ...
Article
The aim of the present study was to identify the factors associated with the use of sphincter-preserving resection (SPR) surgery for the treatment of low rectal cancer. A total of 330 patients with histopathologically confirmed low rectal cancer were divided into two groups, namely the abdominoperineal resection (APR) and sphincter-preserving (SP) groups. For SPR factor analysis, the χ2 test was performed as the univariate analysis, while a logistic regression test was conducted as the multivariate analysis. Of the 330 patients, 192 cases (58.18%) received SPR surgery and 138 cases (41.82%) underwent an APR. Univariate analysis results revealed that the sphincter-preserving factor was significantly associated with age, gender, ethnicity, body mass index (BMI), total infiltrated circumference, distance of the tumor from the anal verge (DTAV), depth of invasion and tumor grade (P<0.05). However, there were no statistically significant associations with family medical history, diabetes history, venous tumor embolism, growth type, tumor length, lymphatic metastasis and level of preoperative carcinoembryonic antigen (P>0.05). Multivariate analysis indicated that the sphincter-preserving factor was strongly associated with DTAV and the depth of invasion, with significant statistical difference (P<0.05). Therefore, selecting SPR surgery for patients with low rectal cancer is dependent on age, gender, ethnicity, BMI, the total infiltrated circumference, DTAV, depth of invasion and tumor grade. In addition, DTAV and the depth of invasion are independent risk factors for the selection of SPR surgery.