A novel insight of sentinel lymph node concept based on 1-3 positive nodes in patients with pT1-2 gastric cancer

<p>Abstract</p> <p>Background</p> <p>Sentinel node (SN) biopsy has been practiced in gastric cancer in recent years, and many studies focused on the distribution of solitary lymph node metastasis (SLM) to assess the pattern of SN. In fact, there is usually more than one SN existing in gastric cancer. The distribution of SNs needs to be further re-evaluated.</p> <p>Methods</p> <p>A total of 289 patients in pT1-2 stage with 1-3 positive nodes confined to same compartment were included in this study with informed consents. The primary lesion was solitary (≤ 5.0 cm in diameter) and D2 or D3 lymph node dissection had been performed. The location of metastatic lymph nodes was analyzed retrospectively.</p> <p>Results</p> <p>Most positive nodes occurred in N1 compartment, with frequency of 79.6% to 85.7% based on site of tumor. In the lower third of stomach, no. 6 was the most common metastatic site and no. 3 was the second; the order was reversed for SLM. With increasing depth of tumor invasion, a progressively augmented nodal involvement was shown. Nearly a half appeared transverse metastasis when the tumor located at the lesser or greater curvature. Among skip metastasis, no. 7, 8a, 9 and 11p were the most common metastatic sites and the prognosis was as similar as that of patients with N1 involved only.</p> <p>Conclusions</p> <p>The 1-3 positive nodes in the same compartment should be possible SNs, and most of which are restricted in N1 in pT1-2 gastric cancer. Transversal and 2 stations lymph node metastasis are common.</p

Different significance between intratumoral and peritumoral lymphatic vessel density in gastric cancer: a retrospective study of 123 cases

<p>Abstract</p> <p>Background</p> <p>Patients with gastric cancer in China have worse outcome and poorer prognosis. Tumor-induced lymphangiogenesis plays a crucial role in metastasis and tumor progression. The intratumoral and peritumoral lymphatics were supposed to have different biological effects. Three major growth factors, vascular endothelial growth factor- (VEGF)-A, VEGF-C and VEGF-D, are involved in the activation process via their receptors (VEGFRs). The purpose of current study is to investigate the significant difference between intratumoral and peritumoral lymphatic vessel density (LVD) in gastric cancer and their correlations with lymphangiogenetic growth factors.</p> <p>Methods</p> <p>Intratumoral LVD (I-LVD) and peritumoral LVD (P-LVD) of 123 patients with primary gastric cancer were assessed after staining with D2-40, and confirmed by double staining with D2-40/CD34. Proliferative activity of lymphatics endothelium was evaluated by double staining with D2-40/Ki-67. The associations were analyzed between I-LVD/P-LVD and the expression level of VEGF-A, VEGF-C, VEGF-D and the receptor VEGFR-3, which was measured by immunohistochemistry (IHC). The correlations of I-LVD and P-LVD with patient prognosis were also valued.</p> <p>Results</p> <p>(1) The peritumoral lymphatics (PTLs) were relatively enlarged with dilated lumen compared with the intratumoral lymphatics (ITLs). Increased P-LVD was significantly higher than I-LVD (<it>P </it>< 0.05). (2) P-LVD was found significantly associated with lymph node metastasis (LNM) (<it>P </it>< 0.001), lymphatic vessel invasion (LVI) (<it>P </it>< 0.001), VEGF-C (<it>P </it>= 0.003), VEGF-D expression level (<it>P </it>= 0.005) and VEGFR-3 expression level (<it>P </it>< 0.001) in peritumoral tissues, despite no significant association was found between above variants with I-LVD. However, increased I-LVD was demonstrated to be associated with decreased tumor volume (<it>P </it>< 0.001). Neither I-LVD nor P-LVD was correlated with VEGF-A expression (<it>P </it>> 0.05). (3) Proliferative activity of lymphatics endothelium was observed in PTLs, in spite of ITLs. (4) Increased P-LVD, but not I-LVD, was indicated to be an independent risk factor for lymph node metastasis by multivariate logistic regression analysis, and was related to worse disease-free survival and overall survival.</p> <p>Conclusions</p> <p>PTLs play roles in gastric cancer progression. Increased P-LVD, but not I-LVD, was significantly associated with VEGF-C/-D/VEGFR-3 system, and could be an independent risk factor for lymph node metastasis and a prognostic factor in gastric cancer.</p

Detection of sentinel and non-sentinel lymph node micrometastases by complete serial sectioning and immunohistochemical analysis for gastric cancer

<p>Abstract</p> <p>Background</p> <p>We investigated the presence and distribution of the sentinel and the non-sentinel node micrometastases using complete serial sectioning and immunohistochemical staining (IHC), to inspect whether lymph node micrometastases spread to the sentinel lymph nodes first.</p> <p>Methods</p> <p>A total of 35 patients, who underwent gastrectomy with a sentinel lymph node biopsy for gastric cancer, were enrolled in this study. Total of 1028 lymph nodes of 35 patients having gastric cancer without metastasis of lymph node by permanent section with hematoxylin and eosin staining (H&E) were selected. There were 252 sentinel nodes and the other 776 were non-sentinel nodes. All nodes were sectioned serially and stained alternately with H&E and IHC. Lymph node micrometastases was defined as proving to be positive first either the IHC or the complete serial sectioning.</p> <p>Results</p> <p>Micrometastases were detected in 4 (11%) of the 35 patients, 6 (0.58%) of 1028 nodes. Of these 4 patients, 3 had micrometastases exclusively in sentinel nodes, and the other had micrometastasis in both sentinel and non-sentinel nodes. There was no patient who had the micrometasitases only in non-sentinel nodes.</p> <p>Conclusion</p> <p>These results support the concept that lymph node micrometastasis of gastric cancer spreads first to sentinel nodes.</p

Agarose Spot as a Comparative Method for in situ Analysis of Simultaneous Chemotactic Responses to Multiple Chemokines

yesWe describe a novel protocol to quantitatively and simultaneously compare the chemotactic responses of cells towards different chemokines. In this protocol, droplets of agarose gel containing different chemokines are applied onto the surface of a Petri dish, and then immersed under culture medium in which cells are suspended. As chemokine molecules diffuse away from the spot, a transient chemoattractant gradient is established across the spots. Cells expressing the corresponding cognate chemokine receptors migrate against this gradient by crawling under the agarose spots towards their centre. We show that this migration is chemokine-specific; meaning that only cells that express the cognate chemokine cell surface receptor, migrate under the spot containing its corresponding chemokine ligand. Furthermore, we show that migration under the agarose spot can be modulated by selective small molecule antagonists present in the cell culture medium