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

      Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
      Springer Nature

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          Abstract

          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.

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          Most cited references59

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          Japanese Society for Cancer of the Colon and Rectum (JSCCR) Guidelines 2014 for treatment of colorectal cancer

          Colorectal cancer is a major cause of death in Japan, where it accounts for the largest number of deaths from malignant neoplasms among women and the third largest number among men. Many new methods of treatment have been developed during recent decades. The Japanese Society for Cancer of the Colon and Rectum Guidelines 2014 for treatment of colorectal cancer (JSCCR Guidelines 2014) have been prepared as standard treatment strategies for colorectal cancer, to eliminate treatment disparities among institutions, to eliminate unnecessary treatment and insufficient treatment, and to deepen mutual understanding among health-care professionals and patients by making these guidelines available to the general public. These guidelines have been prepared as a result of consensuses reached by the JSCCR Guideline Committee on the basis of careful review of evidence retrieved by literature searches and taking into consideration the medical health insurance system and actual clinical practice in Japan. They can, therefore, be used as a guide for treating colorectal cancer in clinical practice. More specifically, they can be used as a guide to obtaining informed consent from patients and choosing the method of treatment for each patient. As a result of the discussions of the Guideline Committee, controversial issues were selected as clinical questions, and recommendations were made. Each recommendation is accompanied by a classification of the evidence and a classification of recommendation categories, on the basis of consensus reached by Guideline Committee members. Here we present the English version of the JSCCR Guidelines 2014.
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            Risk factors for an adverse outcome in early invasive colorectal carcinoma.

            Various histologic findings exist for managing patients with malignant polyps. Our goal was to determine the criteria for a conservative approach to patients with locally excised early invasive carcinoma. In 292 early invasive tumors (local resection followed by laparotomy [80 tumors, group A], local resection only [41 tumors, group B], and primarily laparotomy [171 tumors, group C], potential parameters for nodal involvement were analyzed. The status of the endoscopic resection margin also was examined for the risk for intramural residual tumor. Unfavorable tumor grade, definite vascular invasion, and tumor budding were the combination of qualitative factors that most effectively discriminated the risk for nodal involvement in patients in groups A-C. The nodal involvement rate was 0.7%, 20.7%, and 36.4% in the no-risk, single-risk, and multiple-risks group, respectively. Thirty-two and 9 patients from group B were assigned to the no-risk and one-risk group, respectively; extramural recurrence occurred in 2 patients with risk factors. Considering quantitative risk parameters for submucosal invasion (i.e., width > or =4000 microm or depth > or =2000 microm), nodal involvement (including micrometastases) was not observed in the redefined no-risk group that accounted for about 25% of the patients from groups A and C. An insufficiency of endoscopic resection could be evaluated most precisely based on the coagulation-involving tumor, rather than the 1-mm rule for the resection margin. Provided that the criterion of sufficient excision is satisfied, the absence of an unfavorable tumor grade, vascular invasion, tumor budding, and extensive submucosal invasion would be the strict criteria for a wait-and-see policy.
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              Correlations between lymph node metastasis and depth of submucosal invasion in submucosal invasive colorectal carcinoma: a Japanese collaborative study.

              Depth of submucosal invasion (SM depth) in submucosal invasive colorectal carcinoma (SICC) is considered an important predictive factor for lymph node metastasis. However, no nationwide reports have clarified the relationship between SM depth and rate of lymph node metastasis. Our aim was to investigate the correlations between lymph node metastasis and SM depth in SICC. SM depth was measured for 865 SICCs that were surgically resected at six institutions throughout Japan. For pedunculated SICC, the level 2 line according to Haggitt's classification was used as baseline and the SM depth was measured from this baseline to the deepest portion in the submucosa. When the deepest portion of invasion was limited to above the baseline, the case was defined as a head invasion. For nonpedunculated SICC, when the muscularis mucosae could be identified, the muscularis mucosae was used as baseline and the vertical distance from this line to the deepest portion of invasion represented SM depth. When the muscularis mucosae could not be identified due to carcinomatous invasion, the superficial aspect of the SICC was used as baseline, and the vertical distance from this line to the deepest portion was determined. For pedunculated SICC, rate of lymph node metastasis was 0% in head invasion cases and stalk invasion cases with SM depth <3000 micro m if lymphatic invasion was negative. For nonpedunculated SICC, rate of lymph node metastasis was also 0% if SM depth was <1000 micro m. These results clarified rates of lymph node metastasis in SICC according to SM depth, and may contribute to defining therapeutic strategies for SICC.
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                28548122
                10.1038/modpathol.2017.46

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