The clinical significance of lymph node size in colon cancer.

To date, the clinical value of lymph node size in colon cancer has been investigated only in a few studies. Only in radiological diagnosis is lymph node size routinely recognized, and nodes ≥10 mm in diameter are considered pathologic. However, the few studies regarding this topic suggest that lymph node size is not a reliable indicator of metastatic disease. Moreover, we hypothesized that increasing lymph node size is associated with favorable outcome. By performing a morphometric study, we investigated the clinical significance of lymph node size in colon cancer in terms of metastatic disease and prognosis. A cohort of 237 cases with excellent lymph node harvest (mean lymph node count: 33±17) was used. The size distribution in node-positive and -negative cases was almost identical. In all, 151 out of the 305 metastases detected (49.5%) were found in lymph nodes with diameters ≤5 mm. Only 25% of lymph nodes >10 mm showed metastases. Minute lymph nodes ≤1 mm were involved only very rarely (2 of 81 cases). In 67% of the cases, the largest positive lymph node was <10 mm. The prognostic relevance of lymph node size was investigated in a subset of 115 stage I/II cases. The occurrence of ≥7 lymph nodes that were >5 mm in diameter was significantly associated with better overall survival. Our data show that lymph node size is not a suitable factor for preoperative lymph node staging. Minute lymph nodes have virtually no role in correct histopathological lymph node staging. Finally, large lymph nodes in stage I/II disease might indicate a favorable outcome.

Combination of ex vivo sentinel lymph node mapping and methylene blue-assisted lymph node dissection in gastric cancer: a prospective and randomized study.

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.

A new concept for the role of ex vivo sentinel lymph nodes in node-negative colorectal cancer.

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 â†’ 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.

Shape is not associated with the origin of pericolonic tumor deposits.

Pericolonic tumor deposits (PTDs) are associated with an adverse outcome in colorectal cancer. According to the International Union Against Cancer they are classified as N1 or V1/V2 depending on their shape. This recommendation, however, is not well supported by the literature. To elucidate the origin of PTDs, we performed a histomorphologic study of 69 PTDs, which were found in 7 of 21 colorectal specimens using the whole-mount step-section technique. Depending on the origin, the nodules were classified as venous invasions, lymphatic invasions, nerve sheath infiltrations, free PTDs, and continuous growth in 18 (26%), 3 (4%), 6 (9%), 34 (49%), and 8 (12%) of 69 PTDs, respectively. Polycyclic and oval-round shapes were identified in all categories. Continuous growth was found only within the inner third of the adhering fat, whereas the other morphologic features were found in all regions. The data of this study do not support PTD classification on the basis of their shape.

Shift from cytoplasmic to nuclear maspin expression correlates with shorter overall survival in node-negative colorectal cancer.

Maspin has been characterized as a potent tumor suppressor in many in vitro and in vivo studies. In contrast, in stage III colon cancer, an association with shorter overall survival as well as sensitivity to chemotherapy was found for cases with nuclear maspin expression. Because 20% of node-negative colorectal cancer cases show a fatal clinical course, we hypothesized that immunohistochemical maspin expression could be of help to identify higher-risk cases. Therefore, we analyzed survival in a study employing 156 cases of stage I/II colorectal cases. Immunohistochemical cytoplasmic and/or nuclear maspin expression was found in 72% and 48% of the cases, respectively. Significant correlations between cytoplasmic expression and high tumor grade (P < .01) and between nuclear expression and tumor budding (P < .001) were shown. No differences concerning overall survival and immunohistochemical maspin expression were found when the complete collective was analyzed. However, evaluation of the pT3 cases revealed a highly significant worse mean overall survival of cases with a combination of nuclear expression and cytoplasmic loss of maspin compared to cases with the opposite expression pattern nuclear loss and cytoplasmic expression (mean overall survival 40 versus 63 months, respectively; P < .001). The other possible combinations (complete positive and complete negative) showed intermediate mean overall survival times with 54 and 49 months, respectively. Our findings suggest a compartment-dependent function of maspin in colorectal cancer, which can be useful in identifying stage II cases with a higher risk for fatal outcome with a possible benefit from adjuvant chemotherapy.

Methylene blue-assisted lymph node dissection in colon specimens: a prospective, randomized study.

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.