• Journal of Breast Cancer
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• v.21 no.4
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• pp.447-452
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• 2018

Purpose: The recent trend in breast cancer treatment is to minimize axillary dissection. However, no pattern of axillary metastasis has been precisely established. The purpose of this study was to evaluate the metastatic lymphatic pattern using near-infrared fluorescence imaging with indocyanine green (ICG) in breast cancer with cytologically proven axillary metastasis. Methods: This was a prospective single-center study. We evaluated 147 patients with breast cancer involving cytologically proven axillary metastasis, and compared physiological and nonphysiological lymphatic metastasis. Results: We performed lymphatic mapping for 64 patients who exhibited level II lymphatic flow on near-infrared fluorescence imaging with ICG, and found that all had axillary metastasis: 51 patients who did not receive neoadjuvant chemotherapy (NAC) and 13 patients post-NAC. Of patients who did not receive NAC, 32 had physiological lymphatic metastasis and 19 had nonphysiological lymphatic metastasis. The risk factors for nonphysiological lymphatic metastasis were age ${\geq}55$ years, high Ki-67 index (>20%), and perinodal extension in both univariate and multivariate analysis (p<0.05). Conclusion: Patients with identified risk factors in cytologically-proven axillary metastasis who did not receive NAC may have nonphysiological lymphatic metastasis.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.36 no.3
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• pp.85-93
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• 2014

Purpose: Nodal metastasis is the main prognostic factor in the patients with oral squamous cell carcinoma (OSCC). We investigated the association between tumor-associated lymphatics and OSCC characteristics. Methods: Thirty-four specimens were used for the immunohistochemical staining with the antibody for vascular endothelial growth factor (VEGF)-C, VEGF-D, VEGF receptor (VEGFR)-3, phosphorylated VEGFR-3, D2-40, and matrix metallproteinases (MMPs). We observed the distribution of the lymphangiogenic factors and quantified the degree of expression. We determined lymphatic vessel density (LVD) and lymphatic vessel dilatation with D2-40 immunostaining. We assessed the association of LVD or lymphatic vessel dilatation with tumor progression or tumor differentiation. Results: OSCC cells expressed lymphangiogenic ligands. Lymphangiogenic receptor, VEGFR-3, was expressed and activated in some tumor cells as well as in tumor-associated endothelial cells. LVD was not associated with tumor size or nodal status, but lymphatic vessel dilatation was higher in tumors with nodal metastasis, and also higher in poorly differentiated tumors. In stromal area of OSCC, MMP-1 and MMP-10 were up-regulated and the basement membrane of tumor-associated endothelial cells was destroyed by these collagenases. Conclusion: In the primary tumors with nodal metastasis, especially in poorly differentiated OSCC, tumor cells invaded the dilated lymphatic vessels via ruptured sites. MMP-1 and MMP-10 are important in the lysis of the glycocalyx inside the tumor-associated lymphatic endothelial cells.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.5
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• pp.2221-2224
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• 2014

Objective: To explore the relationship between expressions of cell adhesion molecules CD44 v6 and E-cadherin (E-cad) and lymphatic metastasis in non-small cell lung cancer (NSCLC). Materials and Methods: Eightyseven tissue samples obtained from patients with primary NSCLC were collected in our hospital from Dec., 2007 to Dec., 2012, and the expressions of CD44 v6 and E-cad gene proteins in these samples were detected by immunohistochemical method. Results: In the tissue without lymphatic metastasis, the positive expression rate of CD44 v6 was significantly lower, whereas the normal expression rate of E-cad was notably higher than that with lymphatic metastasis (55.6% vs. 78.4%, 47.2% vs. 21.6%), and both differences had statistical significance (P<0.05). Besides, CD44 v6 and E-cad expressions had a significant correlation in the NSCLC tissue with lymphatic metastasis (P<0.05). Conclusions: The positive expression of CD44 v6 and abnormal expression of E-cad may play a very important role in promoting lymphatic metastasis of NSCLC, with synergistic effect. Hence, detection of CD44 v6 and E-cad expressions is conductive to judging the lymphatic metastasis in NSCLC.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.28 no.1
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• pp.7-15
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• 2002

The present study was carried out to evaluate the correlation of metastasis and prognostic factors in squamous cell carcinoma of head and neck. Examination was performed on a series of thirty-seven patients who were confirmed to squamous cell carcinoma and its lymphatic metastasis by pathologist. Correlations of metastasis and other factors such as angiogenesis, histologic grading, and p53 expression and ras oncogene were studied. The depth of tumors was around 1 to 27mm. Twenty cases were more than 10mm deep, of which seventeen cases were shown lymphatic metastasis. Total score of histologic grading including keratinization, nuclear atypia, growth pattern and intensity of inflammation was ranged from 5 to 10 points. Of these factors, nuclear atypia with intensity of inflammation, and nuclear atypia with growth pattern was correlated with nuclear atypia each. For angiogenesis, number of new-formed vessels were counted 13 to 58 each. Twenty-eight cases were shown to lymphatic metastasis. No correlation with histologic grading and lymphatic metastasis was found. The results of immunohistochemical staining for p53 and ras oncogene revealed that positive cases were 16 and 22, negative for 21 and 15 each. However, both were not correlated with histologic grading and lymphatic metastasis. These results were revealed that angiogenesis was not correlated with lymphatic metastasis of squamous cell carcinoma arising in head and neck. Nuclear atypia with intensity of inflammation and dysplasia with growth pattern were correlated with histologic grading, which suggested that more careful and adequate advice is needed for effective treatment.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.3079-3083
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• 2013

Objective: To investigate the effects of endostar, a recombined humanized endostatin, plus cisplatin on the growth, lymphangiogenesis and lymphatic metastasis of the Lewis lung carcinoma (LLC) in mice. Methods: A tumor model were established in C57BL/6 mice by intravenious transplantation of LLC cells. Then the mice were randomized to receive administration with NS, endostar, cisplatin, or endostar plus cisplatin. After the mice were sacrificed, tumor multiplicity, tumor size and lymph node metastasis were assessed. Then the expression of vascular endothelial growth factor-c (VEGF-C) and podoplanin were determined by immunohistochemical staining. Results: Endostar plus cisplatin significantly suppressed tumor growth. lymphatic metastasis and prolonged survival time of the mice without obvious toxicity. The inhibition of lymphatic metastasis was associated with decreased microlymphatic vessel density (MLVD) and expression of VEGF-C. Conclusions: Endostar combined with cisplatin was more effective to suppress tumor growth and lymphatic metastasis than either agent alone. Thus this may provide a rational alternative for lung carcinoma treatment.

• Journal of Gastric Cancer
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• v.13 no.3
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• pp.192-195
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• 2013

Gastrointestinal stromal tumor is a rare tumor which arises from the whole gastrointestinal tracts and most of it is detected in the stomach. It is uncommon with small intestine originated gastrointestinal stromal tumor and more uncommon with lymphatic metastasis. We experienced an unusual case of the small bowel gastrointestinal stromal tumor during experimental autopsy. Two primary tumors with central necrosis were detected in the ileum. The sizes of each tumor were $6.1{\times}3.4{\times}4.0$ cm and $3.7{\times}4.2{\times}3.2$ cm. There was extensive lymphatic metastasis on the greater omentum and mesenteric, iliac lymph nodes were also involved. With histologic findings, the eosinophilic spindle cells were densely distributed. Immunohistochemical findings were CD117 (-), CD34 (+), desmin (-), and S-100 protein (-). Therefore, we diagnosed the tumors as small bowel gastrointestinal stromal tumors with broad lymph node mestasis.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.1
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• pp.583-587
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• 2013

This study aimed to investigate tumor microvessel density (MVD) and lymphatic vessel density (LVD) using the Chalkley method as predictive markers for the risk of axillary lymph node metastasis and their relationship to other clinicopathological parameters in primary breast cancer cases. Forty two node-positive and eighty node-negative breast cancers were immunostained for CD34 and D2-40. MVD and LVD were counted by the Chalkley method at x400 magnification. There was a positive significant correlation of the MVD with the tumor size, coexisting ductal carcinoma in situ (DCIS) and lymph node metastases (P<0.05). In multivariate analysis, the MVD (2.86-4: OR 5.87 95%CI 1.05-32; >4: OR 20.03 95%CI 3.47-115.55), lymphovascular invasion (OR 3.46, 95% CI 1.13-10.58), and associated DCIS (OR 3.1, 95%CI 1.04-9.23) independently predicted axillary lymph node metastasis. There was no significant relationship between LVD and axillary lymph node metastasis. However, D2-40 was a good lymphatic vessel marker to enhance the detection of lymphatic invasion compared to H and E staining. In conclusion, MVD by the Chalkley method, lymphovascular invasion and associated DCIS can be additional predictive factors for axillary lymph node metastases in breast cancer. No relationship was identified between LVD and clinicopathological variables, including axillary lymph node metastasis.

• Journal of Gastric Cancer
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• v.10 no.4
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• pp.162-167
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• 2010

Purpose: The incidence of lymph node metastasis has been reported to range from 2.6 to 4.8% in early stage gastric cancer with mucosal invasion (T1a cancer). Lymph node metastasis in early stage gastric cancer is known as an important predictive factor. We analyzed the prediction factors of lymph node metastasis in T1a cancer. Materials and Methods: A total of 9,912 patients underwent radical gastrectomy due to gastric cancer from October 1994 to July 2006 in the Department Of Surgery at Samsung Medical Center. We did a retrospective analysis of 2,524 patients of these patients, ones for whom the cancer was confined within the mucosa. Results: Among the 2,524 patients, 57 (2.2%) were diagnosed with lymph node metastasis, and of these, cancer staging was as follows: 41 were N1, 8 were N2, and 8 were N3a. Univariate analysis of clinicopathological factors showed that the following factors were significant predictors of metastasis: tumor size larger than 4 cm, the presence of middle and lower stomach cancer, poorly differentiated adenocarcinoma and signet-ring cell carcinoma, diffuse type cancer (by the Lauren classification), and lymphatic invasion. Multivariate analysis showed that lymphatic invasion and tumor larger than 4 cm were significant factors with P<0.001 and P=0.024, respectively. Conclusions: The frequency of lymph node metastasis is extremely low in early gastric cancer with mucosal invasion. However, when lymphatic invasion is present or the tumor is larger than 4 cm, there is a greater likelihood of lymph node metastasis. In such cases, surgical treatments should be done to prevent disease recurrence.

• Journal of Gastric Cancer
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• v.13 no.2
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• pp.93-97
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• 2013

Purpose: Endoscopic submucosal dissection has recently been practiced on a differentiated type of early gastric cancer. However, there is no clear evidence for endoscopic treatments of signet ring cell carcinoma. The aim of this study is to identify the predictive clinicopathological factors for lymph node metastasis in signet ring cell carcinoma for assisting endoscopic submucosal dissection trials. Materials and Methods: A total of 186 patients with early signet ring cell carcinoma who underwent radical curative gastrectomy between January 2001 and September 2009 were enrolled in this study. Retrospective reviews of their medical records are being conducted. Several clinicopathologic factors were being investigated in order to identify predictive factors for lymph nodes metastasis: age, gender, tumor size, type of operation, tumor location, gross type, ulceration, Lauren's classification, depth of invasion, and lymphatic invasion. Results: The lymph node metastasis rate for signet ring cell carcinoma was 4.3% (n=8). Of the 186 lesions with early signet ring cell carcinoma, 91 (48.9%) tumors were larger than 15 mm in size and 40 (21.5%) showed submucosal invasions in the resection specimens. In multivariate analysis, only the lymphatic invasion (P<0.0001) showed an association with lymph node metastasis. To evaluate cutoff values for tumor sizes in the presence of lymph node metastasis, early signet ring cell carcinomas with lymphatic invasions were excluded. In the absence of lymphatic invasion, mucosal cancer with tumor sizes <15 mm had no lymph node metastasis. Conclusions: Endoscopic submucosal dissection can be performed on patients with early signet ring cell carcinoma limited to the mucosa and less than 15 mm.

• Journal of Gastric Cancer
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• v.1 no.2
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• pp.113-118
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• 2001

Purpose: The common features of brain metastases from gastric cancer are unknown because brain metastasis is an uncommon pattern of metastasis. The purpose of this study was to investigate the clinical features of and the prognosis for patients with brain metastases after a curative resection for gastric cancer. Materials and Methods: Twenty-one (21) cases of patients with brain metastases of gastric cancer, who had been treated at the Department of Surgery, Yonsei University College of Medicine, were assessed retrospectively. Results: The mean age was $55.8\pm9.6$ years (range: $34\~70$ years), and the male-to-female ratio was 2.5 : .1. The most common neurologic symptom was headache ($38.5\%$), and no patient was free from the neurologic symptoms. The incidence of parenchymal metastasis (PM: $76.2\%$) was higher than that of leptomeningeal metastasis (LM: $19.0\%$). Patients with gastric cancer and brain metastasis showed high rates of blood and lymphatic vessel invasion (lymphatic vessel invasion: $85.7\%$; blood vessel invasion: $80.9\%$). According to Lauren's classification, the incidence of intestinal types was 14/21 ($66.7\%$), that of diffuse types was 3/21 ($14.3\%$) and that of mixed types was 4/21 ($19.0\%$). The mean interval between the gastrectomy and the diagnosis of brain metastasis was $24.7\pm4.0$ months (PM: 26.8 months; LM: 20.3 months). The median period of survival after diagnosis of brain metastasis was 2 months for paren chymal metastasis and 0 months for leptomeningeal metastasis. Conclusion:.. During a follow-up period, patients with neurologic symptoms should be suspected of having brain metastasis. Early diagnosis and treatment is the only hope to prolong survival in such patients.