• Asian Pacific Journal of Cancer Prevention
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• v.15 no.12
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• pp.4893-4896
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• 2014

Background: Recent reports have shown that C-X-C chemokine receptor 4 (CXCR4) plays an important role in metastasis. Despite a clear understanding of the protein's structure and properties, its functional role remains elusive. We conducted the present study to evaluate the expressions of CXCR4 in pancreatic cancer, and to investigate its relationship with clinicopathological parameters, especially perineural invasion(PNI). Materials and Methods: The association between CXCR4 expression and perineural invasion was determined by immunohistochemistry in pancreatic cancer patients (n=51). Results: CXCR4 expression was correlated with the existence of PNI and the type of PNI (p=0.042, p=0.040). TIMP-2 expression was also correlated with the existence, the pathway and degree of PNI (p=0.000, p=0.006, p=0.000). Conclusions: Our results suggest an association between PNI and expression of CXCR4 and TIMP-2 in pancreatic cancer. CXCR4 may promote the occurrence of PNI in pancreatic cancer cells by decreasing the inhibition of TIMPs on MMP.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.33 no.2
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• pp.81-93
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• 2007

Purpose: Adenoid cystic carcinoma (ACC) is a relatively rare tumor that arises in glandular tissues of the head and neck region and sometimes has a protracted clinical course with perineural invasion and delayed onset of distant lung metastasis. Treatment failure of salivary ACC is most often associated with perineural and hematogenous tumor spread. However, very little has been known about the cellular and molecular mechanisms of perineural invasion and hematogenous distant metastasis of parotid ACC. This study was designed to develop an orthotopic tumor model of parotid adenoid cystic carcinoma in athymic nude mice. Experimental Design: A melanoma cell line was injected into the parotid gland of athymic mice to determine whether such implantation was technically feasible. A parotid ACC cell line was then injected into the parotid gland or the subcutaneous tissue of athymic mice at various concentrations of tumor cells, and the mice were thereafter followed for development of tumor nodule. The tumors were examined histopathologically for perineural invasion or regional or distant lung metastasis. We used an oral squmous cell carcinoma cell line as control. Results: Implantation of tumor(melanoma) cell suspension into the parotid gland of nude mice was technically feasible and resulted in the formation of parotid tumors. A parotid ACC cell line, ACC3 showed no significantly higher tumorigenicity, but showed significantly higher lung metastatic potential in the parotid gland than in the subcutis. In contrast, mucosal squmous cell carcinoma cell line doesn’t show significantly higher lung metastatic potential in the parotid gland than in the subcutis. The ACC tumor established in the parotid gland seemed to demonstrate perineural invasion of facial nerve, needs further study. Conclusion: An orthotopic tumor model of salivary ACC in athymic nude mice was successfully developed that closely recapitulates the clinical situations of human salivary ACC. This model should facilitate the understanding of the cellular and molecular mechanisms of tumorigenisis and metastasis of salivary ACC and aid in the development of targeted molecular therapies of salivary ACC.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3149-3152
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• 2012

Objective: The prognostic significance of perineural invasion (PNI) in gastric cancer has been previously investigated but not clearly clarified. The objective of our study was to investigate the role of PNI as prognostic factor in patients undergoing curative surgical resection and without distant metastasis in comparison with other clinicopathological factors. Methods: Between 2001 and 2010, 287 cases of gastric adenocarcinoma underwent radical gastrectomy recorded in hospital based registries. PNI was assessed as positive when cancer cells were seen in the perinerium or neural fascicles intramurally. Categorical and continuous variables were summarized using descriptive statistics and compared using chi-square and Mann-Whitney U tests, respectively. Cancer related survival rates were estimated by the Kaplan-Meier method. Results: PNI was positive in 211 of 287 cancers (73%), with a positive relation to lymph node metastases and advanced stage (p=0.0001, p=0.0001, respectively), mural invasion, and lymphatic and blood vessel invasion (p=0.0001, p=0.0001, respectively). The median survival of the PNI positive patients was significantly shorter than that of their PNI negative counterparts (24.1 versus 38.2 months, p=0.008). In the multivariate analysis, we detected PNI was an independent prognostic factor (p=0.025, HR=1.21, 95% CL 1.08-2.3) along with classical clinicopathological variables such as lymph node involvement (p=0.001), pT stage (p=0.03), and LVI (p=0.017), but not age, gender, tumour localization, stage, histologic type, and surgery procedure. Conclusions: PNI positivity in gastric cancers was related mural invasion, lymph node involvement, advanced stage and lymphatic and venous blood vessels. The presence of PNI appeared as an independent prognostic factor on survival on multivariate analysis, not influenced by tumor stage, lymph node metastases and other classical factors.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.22
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• pp.9687-9692
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• 2014

Background: Biliary tract cancers are rare, and surgical resection is the standard treatment at early stages. However, reports on the benefits of adjuvant treatment following surgical resection are conflicting. This study aimed to evaluate the factors affecting survival and adjuvant treatments in patients with surgically treated biliary tract cancers. Materials and Methods: Patient clinical features, adjuvant treatments, and efficacy and prognostic factor data were evaluated. Survival analyses were performed using SPSS 15.0. Results: The median overall survival was 30.7 months (95% confidence interval [CI], 18.4-42.9 months). Median survival was 19 months (95% CI, 6-33) for patients treated with fluorouracil based chemotherapy and 53 months (95% CI, 33.2-78.8) with gemcitabine based chemotherapy(p=0.033). On univariate analysis, poor prognostic factors for survival were galbladder localization, perineural invasion, hepatic invasion, a lack of adjuvant chemoradiotherapy treatment, and a lack of lymph node dissection. On multivariate analysis, perineural invasion was a poor prognostic factor (p=0.008). Conclusions: Biliary tract cancers generally have poor prognoses. The main factors affecting survival are tumour localization, perineural invasion, hepatic invasion, adjuvant chemoradiotherapy, and lymph node dissection. Gemcitabine-based adjuvant chemotherapy is more effective than 5-fluorouracil-based chemotherapy.

• Journal of Gastric Cancer
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• v.1 no.2
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• pp.77-82
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• 2001

Purpose: The most important prognostic factors in gastric cancer are depth of invasion and lymph node metastasis. Therefore, the prognosis for serosa and lymph node negative gastric cancer is favorable. However, there is no general agreement on the prognostic factors in this subset of patients. This study was undertaken to evaluate the prognostic significances of venous invasion (VI), lymphatic invasion (LI), and perineural invasion (NI) in T1 and T2 gastric cancer without lymph node involvement. Materials and Methods: We retrospectively evaluated 206 patients with T1 and T2, lymph node negative gastric cancer who underwent a curative resection from 1989 to 1993 at Kangnam St. Mary's Hospital, Seoul, Korea. The Chi-square test was used to determine the statistical significance of differences, and the Kaplan-Meier method was used to calculate survival rates. Significant differences in the survival rates were assessed using the log-rank test, and the Cox regression method was used to evaluate independent prognostic significance. Results: The rate of VI, LI and NI correlated well with the depth of tumor invasion. The rates of VI (+) for T1 vs T2 was $0\%\;vs\;5.1\%$, of LI (+) was $5.6\%\;vs\;26.8\%$, and of NI (+) was $1.6\%\;vs\;26.8\%$ in NI (+). There were 13 recurrent cases, 10 cases out of the 13 were T2 gastric cancers, and the recurrence rate was higher in LI (+) and NI (+) cases than in LI (-) and NI (-) cases. The 5-year survival rates were $93.4\%$ in LI (-) cases, $77.4\%$ in LI (+) cases, $92.5\%$ in NI (-) cases, $74\%$ in NI(+) cases, $95.9\%$ in LI (-) NI (-) cases, and $73.9\%$ in LI (+) NI (+) cases. Multivariate analysis demonstrated that simultaneous LI and NI was the only significant factor influencing the prognosis. Conclusion: These results suggest that simultaneous lymphatic and perineural invasion may be an independent prognostic factor in patients with T1 and T2 gastric cancer without lymph node metastasis.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.3151-3154
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• 2013

Introduction: Colorectal cancers are in the top of the cancer-related causes of death in the world and lymph node metastasis is accepted as the primary prognostic factor. In this study, correlations of FGF19 staining pattern with local invasion and lymph node metastasis in a series of colorectal cancers were investigated. Methods: This studyincluded 81 colorectal cancer patients who underwent surgery in our hospital with no evidence of preoperative radiological distant metastasis. Routine pathological examination of the resection material was performed in order to identify vascular, perineural and serosal infiltration, regional lymph node metastasis and the degree of differentiation. Tumor tissue samples were stained with an immunohistochemistry method for FGF 19 evaluation and the staining pattern was statistically compared with the above mentioned characteristics of the tumors. Results: The patient population consisted of 47 females and 34 males with a median age of 70 years. In 40 patients regional lymph nodes were positive and 51%, 32% and 38% had serosal, perineural and vascular invasion. While 64 cases were moderately-differentiated, 11 cases were well-differentiated and 6 poorlydifferentiated, there was no association with FGF 19 staining, including intensity. Conclusion: No evidence of significant statistically correlation was found between FGF 19 staining pattern and serosal, perineural, vascular invasion, lymph node involvement and degree of differentiation.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.9
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• pp.5133-5139
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• 2013

Background: Perineural invasion (PNI) has been reported as one of the sources of locoregional recurrence in resected pancreatic cancer (PC). However the impact of PNI in resected pancreatic cancer remains controversial. The purpose of this study was to determine the association between PNI status and clinical outcomes. Methods: Publications were identified which assessed prognostic significance of PNI status in resected pancreatic cancer up to February 2013. A meta-analysis was performed to clarify the association between PNI status and clinical outcomes. Results: A total of 21 studies met the inclusion criteria, covering 4,459 cases. Analysis of these data showed that intrapancreatic PNI was correlated with reduced overall survival only in resected pancreatic ductal adenocarcinoma (PDAC) patients (HR=1.982, 95%CI: 1.526-2.574, p=0.000). Extrapancreatic PNI was correlated with reduced overall survival in all resected pancreatic cancer patients (HR=1.748, 95%CI: 1.372-2.228, p=0.000). Moreover, intrapancreatic PNI status may be associated with tumor recurrence in all resected pancreatic cancer patients (HR=2.714, 95%CI: 1.885-3.906, p=0.000). Conclusion: PNI was an independent and poor prognostic factor in resected PDAC patients. Moreover, intrapancreatic PNI status may be associated with tumor recurrence.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.15
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• pp.6287-6293
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• 2014

Background: Invasion of breast cancer cells into blood and lymphatic vessels is one of the most important steps for metastasis. In this study the prognostic relevance of lymphangiogenesis and lymphovascular invasion (LVI) in breast cancer patients was evaluated in terms of survival. Materials and Methods: This retrospective study concerned 518 breast cancer patients who were treated at Department of Surgical Oncology, Saroj Gupta Cancer Centre and Research Institute, Kolkata-700063, West Bengal, India, a reputed cancer centre and research institute of eastern India between January 2006 and December 2007. Results: The median overall survival and disease free survival of the patients were 60 months and 54 months respectively. As per Log-rank test, poor overall as well as disease free survival pattern was observed for LVI positive patients as compared with LVI negative patients (p<0.01). Also poor overall as well as disease free survival pattern was observed for perineural invasion (PNI) positive patients as compared to PNI negative patients (p<0.01). Conclusions: From this study it is evident that LVI and PNI are strongly associated with outcome in terms of disease free as well as overall survival in breast cancer patients. Thus LVI and PNI constitute potential targets for treatment of breast cancer patients. We advocate incorporating their status into breast cancer staging systems.

• Archives of Craniofacial Surgery
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• v.24 no.5
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• pp.211-217
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• 2023

Background: Oral cavity cancers, the second most common type in India, are responsible for 10% of the overall cancer burden. With a recurrence rate of 30% to 40% and a 5-year survival rate of 50%, these malignancies account for substantial morbidity and mortality. Despite advances in treatment modalities, survival rates following treatment completion have not improved significantly. The present study aimed to establish specific epidemiological and pathological factors responsible for recurrence after treatment completion in buccal mucosa cancers. Methods: A retrospective analysis of the data of 116 patients treated for biopsy-proven cancers of the buccal mucosa was undertaken 1 year after treatment completion. Factors such as age, sex, education, lymphovascular invasion, extranodal extension (ENE), perineural invasion, depth of invasion, and pathological margin status were compared between patients who presented with recurrence and those who did not. Statistical significance was set at p< 0.05. Results: Of the 116 patients, 40 (34.5%) developed a recurrent disease within 1 year. The mean age of the study population was 43.3 years, and males constituted 91.4% of the included patients. Ipsilateral buccal mucosa was the commonest site of disease recurrence. Neck node metastasis, ENE, and margins of resection < 5 mm were significantly related to the recurrence of disease. However, surprisingly, lymphovascular invasion, perineural invasion, and depth of invasion > 10 mm did not show statistically significant associations. Conclusion: Neck node metastasis, ENE, and margins of resection < 5 mm were the histopathological factors associated with recurrence in cancers of the buccal mucosa.

• Journal of Gastric Cancer
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• v.10 no.2
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• pp.55-62
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• 2010

Purpose: We evaluated the clinicopathological charicterics and prognostic impacts of lymphatic vessel invasion in gastric cancer without lymph node involvement. Materials and Methods: Among 1,795 patients who underwent gastric surgery with gastric cancer at the department of surgery, Hanyang university college of medicine from June 1992 to March 2009, we retrospectively evaluated 890 patients with lymph node negative gastric cancer. Results: The lymphatic vessel invasion correlated significantly with tumor stage, age, tumor size, perineural invasion and operation method. The survival rates were only significantly different between the patients with and without lymphatic vessel invasion in patients with stage Ia (P=0.036). Univariate and multivariate analysis demonstrated that blood vessel invasion and preoperative serum CEA level were significant factor influencing the survival rate in lymph node negative gastric cancer patients with lymphatic invasion. Conclusions: In patients with lymph node negative gastric cancer, the survival rate is significantly lower in those with lymphatic vessel invasion than in those without. Especially, in patients with stage Ia gastric cancer, the survival rates is significantly different between those with and those without lymphatic vessel invasion. Blood vessel invasion and preoperative serum CEA level is an adverse prognostic indicator in patients with stage Ia gastric cancer with lymphatic invasion. Thus we should consider further adjuvant therapies in case of need and need to show more concern to identify gastric cancer patients early at risk for recurrence.