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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.

Background: We recently introduced ex vivo, intra-arterial methylene blue injection as a simple method to improve the lymph node (LN) harvest in gastrointestinal cancer. We now combined it with a novel ex vivo sentinel lymph node (evSLN) mapping technique., Methods: evSLN mapping was performed by subserosal (n = 20) or submucosal (n = 30) India ink injection. Subsequently, methylene blue was injected intra-arterially to enhance visibility of all LNs to improve the overall LN harvest. Manual LN dissection was carried out after fixing overnight. evSLNs nodes were identified by detecting carbon particles during histological examination. In primary node-negative cases, all detected LNs were step sectioned and immunohistochemically stained for pan-cytokeratin., Results: India ink injection was easy to perform. Methylene blue injection failed in 1 case. The mean lymph node harvest was 42 ± 18 LNs, and the SLN detection rate was 78%. The sensitivity for detecting metastases was 75%. The mean SLN number was 3 ± 1. LN metastases were found in 20 of 47 malignant cases (43%). Skip metastases occurred in 4 cases. Of these cases, 3 showed involvement of at least 1 entire LN. True upstaging (N0 → N1mi) was found in 1 of 23 cases (4%) within a SLN after advanced evaluation., Conclusions: Combination of methylene blue technique and ex vivo sentinel mapping is feasible, easy to perform, and cost effective. It guarantees an optimal LN harvest and has the potential to heighten the sensitivity of metastasis detection.

Purpose: The American Joint Committee on Cancer recommends examination of a minimum of 12 lymph nodes in rectal cancer for accurate staging. Despite this, several studies have demonstrated that nodal harvest is highly variable and often inadequate. This study was designed to determine if staining the nodes with methylene blue dye produced a better and more accurate harvest in comparison with standard pathologic lymph node dissection., Methods: Fifty patients with primary resectable rectal cancer were randomly assigned to undergo a standard nodal harvest or a harvest after ex vivo injection of the inferior mesenteric artery with methylene blue. A fat clearance technique was subsequently used to identify the maximum possible number of lymph nodes and metastasis., Results: The average lymph node harvest was 30 +/- 13.5 in the stained group and 17 +/- 11 in the unstained group (P < 0.001). At least 12 nodes were identified in every case in the stained group. In the unstained group, 7 of 25 cases (28 percent) did not meet the minimum criteria of 12 nodes (P < 0.01). Among the pathologists for the stained group, no difference was found in the harvest (P < 0.05), but variability was detected between the pathologists in the unstained group (P = 0.6). After fat clearance, one case in the unstained group was upstaged, whereas no cases in the stained group were upstaged., Conclusions: Staining the lymph nodes with methylene blue dye is an accurate staging technique and reliably produces an adequate harvest.

Aims: Lymph node (LN) stage is still the strongest prognostic marker in potentially curable gastric cancer. Accuracy of histopathological lymph node assessment depends on the number of investigated LNs and detection rate of metastases and micrometastases. The aim was to perform a feasibility study employing intra-arterial methylene blue injection - a novel method to improve LN harvest - and ex vivo sentinel LN mapping., Methods and Results: A total of 33 cases were enrolled, including 14 retrospective cases that served as a control group. The methylene group showed a highly significant improved mean LN harvest compared with unstained cases, with 38 +/- 14 versus 21 +/- 10 LNs (P < 0.001), respectively. The detection rate of ex vivo sentinel mapping was 88%. No skip metastases occurred., Conclusion: Both techniques have the potential to improve the accuracy of histopathological LN staging and can be combined successfully.

Recently, we introduced ex vivo intra-arterial methylene blue injection into the inferior mesenteric artery as a novel method to improve lymph node (LN) harvest in rectal cancer. We have now adapted this method to the other segments of the colon. A total of 60 cases were enrolled. Primary LN dissection was followed by fat clearance and a secondary dissection. The mean +/- SD primary LN harvest differed highly significantly with 35 +/- 18 and 17 +/- 10 LNs in the methylene blue-stained and unstained groups, respectively. Primary insufficient LN harvest occurred in 8 cases of the unstained group and in only 1 case of the methylene blue-stained group (P = .0226). After secondary dissection, upstaging was seen exclusively in the unstained group. The time/LN ratio differed significantly with 0.9 and 0.6 min/LN in the unstained and methylene blue-stained groups, respectively. Intraarterial methylene blue injection is recommended as a routine technique in the histopathologic study of colon cancer.

Adequate lymph node assessment in colorectal cancer is crucial for prognosis estimation and further therapy stratification. However, there is still an ongoing debate on required minimum lymph node numbers and the necessity of advanced techniques such as immunohistochemistry or PCR. It has been proven in several studies that lymph node harvest is often inadequate under routine analysis. Lymph nodes smaller than 5 mm are especially concerning as they can carry the majority of metastases. These small, but affected lymph nodes may escape detection in routine analysis. Therefore, fat-clearing protocols and sentinel techniques have been developed to improve accuracy of lymph node staging. We describe a novel and simple method of ex vivo methylene blue injection into the superior rectal artery of rectal cancer specimens, which highlights lymph nodes and makes them easy to detect during manual dissection. Initially, this method was developed for proving accuracy of total mesorectal excision. We performed a retrospective study comparing lymph node recovery of 12 methylene blue stained and an equal number of unstained cases. Lymph node recovery differed significantly with average lymph node numbers of 27+/-7 and 14+/-4 (P<0.001) for the methylene blue and the unstained group, respectively. The largest difference was found in size groups between 1 and 4 mm causing a shift in size distribution toward smaller nodes. Metastases were confirmed in 21 and 19 lymph nodes occurring in five and four cases, respectively. Hence, we conclude that methylene blue injection technique improves accuracy of lymph node staging by heightening the lymph node harvest in rectal resections. In our experience, it is a very simple time and cost effective method that can be easily established under routine circumstances.