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Recently, we demonstrated that the intratumoural density of CD3+ and CD8+ T cells is independently prognostic and associated with lymph node (LN) harvest and LN size in node-negative colon cancer. We assumed that FOXP3+ T cells (Tregs) could be inversely associated with these LN features. Therefore, we performed a retrospective immunohistochemical analysis using an already well-characterised collection of stage I/II colon cancer cases. Receiver operating characteristic analysis revealed the optimal cut-off for predicting cancer-related death to be 70 FOXP3+ Tregs/mm 2 at the invasion front. Other than T-stage, none of the relevant histopathological parameters were associated with the density of FOXP3+ cells. In particular, no relation to LN size and count were found. Cancer-specific survival was significantly improved in cases with high densities (115 vs 86 months; p=0.026) in univariable but not in multivariable analysis. In contrast to other cancers, FOXP3+ T cells are associated with a favourable outcome., Competing Interests: Competing interestsNone declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Background: Stage migration is an accepted explanation for the association between lymph node (LN) yield and outcome in colon cancer. To investigate whether the alternative thesis of immune response is more likely, we performed a retrospective study., Methods: We enrolled 239 cases of node negative cancers, which were categorized according to the number of LNs with diameters larger than 5 mm (LN5) into the groups LN5-very low (0 to 1 LN5), LN5-low (2 to 5 LN5), and LN5-high (≥6 LN5)., Results: Significant differences were found in pT3/4 cancers with median survival times of 40, 57, and 71 months (P = .022) in the LN5-very low, LN5-low, and LN5-high groups, respectively. Multivariable analysis revealed that LN5 number and infiltration type were independent prognostic factors., Conclusions: LN size is prognostic in node negative colon cancer. The correct explanation for outcome differences associated with LN harvest is probably the activation status of LNs., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objectives: We postulated that lymph node (LN) harvest and LN size are influenced by immunologic effects., Methods: To investigate this hypothesis, we performed a retrospective analysis of 170 node-negative colon cancer cases to evaluate the density of intratumoral T lymphocytes (ITLs). CD3- and CD8-positive T cells were counted using a digital system., Results: The ITL density was significantly increased in cases with sufficient LN harvest and high numbers of LNs larger than 5 mm (LN5). High ITL numbers were associated with improved cancer-specific survival. The analysis of the immune score revealed a significantly different cancer-specific outcome (P = .024), with no cancer-related death in the group with the highest score. The immune score and tumor budding were independently prognostic., Conclusions: ITL density is independently prognostic and associated with LN harvest and LN size. The immune response is very likely the true explanation for the known prognostic effect of the LN harvest in colon cancer., (© American Society for Clinical Pathology, 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Lymph node retrieval in colorectal cancer can be improved by using advanced histopathological techniques like methylene blue-assisted lymph node dissection, which results in a doubling or even tripling of the lymph node count in comparison with conventional lymph node dissection techniques. However, it is not clear whether the established lymph node staging systems are suitable for predicting patients' prognoses under these circumstances., Objective: The aim of this study was to determine whether the current lymph node staging systems are suitable when advanced dissection methods are used., Design: This is a retrospective cohort study., Setting and Patients: We formed a study group (methylene blue-assisted lymph node dissection) of 293 patients and a control group (conventional lymph node dissection) of 232 patients, each with node-positive cases. Conventional pN staging according to the International Union Against Cancer, seventh edition, and lymph node ratio were applied., Main Outcome Measures: Overall survival was compared by using the different staging systems in a uni- and multivariable fashion., Results: The lymph node ratio values were reduced in the advanced methylene blue-assisted lymph node dissection group in comparison with the conventional lymph node dissection group (0.1 vs 0.3, p < 0.001). Although pN staging proved to be reliable, the cutoff values for lymph node ratio staging had to be adapted. The new cutoffs (0.07, 0.15, and 0.34) were prognostic. However, multivariable analysis revealed pN staging and vascular invasion, but not lymph node ratio, as independently prognostic in the methylene blue-assisted lymph node dissection group., Limitations: The study group and historical control group are not perfectly balanced because the case number in the stage III subgroup of the control group is small., Conclusions: pN staging proved to be a robust prognostic marker in colorectal cancer under the circumstances of improved lymph node harvest. After adaptation of the cutoff values, lymph node ratio is also prognostic but not superior to pN staging.

Lymph node staging is of paramount importance for prognosis estimation and therapy stratification in colorectal cancer. A high number of harvested lymph nodes is associated with an improved outcome. Methylene blue-assisted lymph node dissection effectively improves the lymph node harvest and ensures sufficient staging. Now, the effect on node positivity rate and stage-related outcome was investigated. The study cohort with advanced lymph node dissection consisted of 669 colorectal cancer cases of all stages, which were collected between 2007 and 2012. A historical collection of 663 cases investigated with conventional techniques between 2002 and 2004 served as control. Lymph node harvest was dramatically improved in the study group with mean lymph node numbers of 34 ± 17 vs 13 ± 5 (P<0.001) and sufficient staging rates of 98% vs 62% (P<0.001). However, neither the rate of nodal positive cases (37% vs 37%; P = 0.98) nor the rate of N2 cases differed between the two groups (14% vs 13%; P = 0.80). Furthermore, no differences were found concerning the outcome in both groups. The advanced lymph node dissection technique guarantees adequate histopathological lymph node staging in virtually all cases of colorectal cancer and is therefore extremely helpful. The hypothesis that it also provides a higher sensitivity in detecting metastases, however, could be not proved.

Background: Exact lymph node (LN) staging is crucial for prognosis estimation and treatment stratification in gastric cancer. Recently, a new concept for improving LN harvest and the accuracy of LN staging was introduced. It combines methylene blue-assisted lymph node dissection (MBLND) with a new ex vivo sentinel lymph node (evSLN) mapping technique. The purpose of this study was to investigate these techniques in a prospective and randomized manner., Methods: A total of 50 patients with proven or suspicious gastric cancer were enrolled. Twenty-five patients each were randomized to the conventional technique (Unstained) or MBLND (Methylene). In 46 cases, additional evSLN mapping with black ink as a marker dye was performed., Results: Methylene blue-assisted lymph node dissection was associated with a highly significantly improved LN harvest (36 ± 10 vs. 21 ± 10; P < 0.001). The biggest differences were seen in LNs ≤ 6 mm. In contrast to the conventional technique, neither partial gastrectomy nor preoperative chemotherapy influenced LN harvest in the methylene group. The evSLN detection rate, sensitivity, and accuracy were 87, 81, and 93%, respectively. Isolated tumor cells were detected after immunohistochemical staining in 3 of 17 cases (18%). The probability of carrying a metastasis was two times higher in evSLNs compared to non-evSLNs (44 vs. 23%; P < 0.001)., Conclusions: Methylene blue-assisted lymph node dissection is a highly effective method of improving the LN harvest in gastric cancer. Further application of evSLN mapping is feasible and has the potential to heighten the sensitivity of metastasis detection.