• Journal of Ginseng Research
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• 제43권1호
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• pp.68-76
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• 2019

Background: In colorectal cancer (CRC), 40-60% of patients develop metastasis. The epithelial-mesenchymal transition (EMT) is a pivotal and intricate process that increases the metastatic potential of CRC. The aim of this study was to investigate the effect of Korean Red Ginseng extract (RGE) on colorectal metastasis through inhibition of EMT and the metastatic abilities of CRC cells. Methods: To investigate the effect of RGE on the metastatic phenotypes of CRC cells, CT26 and HT29 cells were evaluated by using an adhesion assay, a wound-healing assay, an invasion assay, zymography, and real-time reverse transcription-polymerase chain reaction. Western-blot analysis was conducted to elucidate the molecular mechanisms of RGE, which showed an inhibitory effect on the transforming growth factor-${\beta}1$ ($TGF-{\beta}1$)-induced EMT in HT29 cells. Additionally, the antimetastatic effect of RGE was evaluated in a mouse model of lung metastasis injected with CT26 cells. Results: RGE decreased the adhesion and migration ability of the CT26 cells and TGF-${\beta}1$-treated HT29 cells. The invasion ability was also reduced by RGE treatment through the inhibition of matrix metalloproteinase-9 expression and activity. Moreover, RGE suppressed the TGF-${\beta}1$-induced EMT via TGF-${\beta}1$/Smad-signaling-mediated Snail/E-cadherin expression in HT29 cells and lung tissue in CT26 tumor-bearing mice. Conclusion: Our results demonstrated that RGE inhibited colorectal lung metastasis through a reduction in metastatic phenotypes, such as migration, invasion, and the EMT of CRC cells.

• Asian Pacific Journal of Cancer Prevention
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• 제16권9호
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• pp.3703-3708
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• 2015

Background: The neutrophil-to-lymphocyte ratio (NLR) is a strong predictor of mortality in patients with colorectal, lung, gastric cancer, pancreatic and metastatic renal cell carcinoma. We here evaluated whether preoperative NLR is an independent prognostic factor for non-metastatic renal cell carcinoma (RCC). Materials and Methods: Data from 327 patients who underwent curative or palliative nephrectomy were evaluated retrospectively. In preoperative blood routine examination, neutrophils and lymphocytes were obtained. The predictive value of NLR for non-metastatic RCC was analyzed. Results: The NLR of 327 patients was $2.72{\pm}2.25$. NLR <1.7 and NLR ${\geq}1.7$ were classified as low and high NLR groups, respectively. Chi-square test showed that the preoperative NLR was significantly correlated with the tumor size (P=0.025), but not with the histological subtype (P=0.095)and the pT stage (P=0.283). Overall survival (OS) and disease-free survival (DFS) were assessed using the Kaplan-Meier method. Effects of NLR on OS (P=0.007) and DFS (P=0.011) were significant. To evaluate the independent prognostic significance of NLR, multivariate COX regression models were applied and identified increased NLR as an independent prognostic factor for OS (P=0.015), and DFS (P=0.019). Conclusions: Regarding patient survival, an increased NLR represented an independent risk factor, which might reflect a higher risk for severe cardiovascular and other comorbidities. An elevated blood NLR may be a biomarker of poor OS and DFS in patients with non-metastatic RCC.

• Journal of Chest Surgery
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• 제39권11호
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• pp.838-843
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• 2006

배경: 폐는 대장암의 가장 흔한 복강 외 전이 장소이며, 폐 전이는 대장암의 근치적 수술 후 약 10%에서 발생된다고 알려져 있다. 폐 전이에 대한 수술 후 5년 생존율은 $9{\sim}47%$로 다양하게 보고되고 있으나 국내에서는 대장암의 폐 전이에 대한 임상연구가 미흡한 상태이다. 이에 저자들은 대장암의 근치적 수술 후 폐 전이가 발생한 환자에서 폐 절제술을 시행하고 그 결과를 후향적으로 분석하였다. 대상 및 방법: 대상 환자는 1996년 7월부터 2003년 12월까지 대장암의 폐 전이로 폐절제술을 시행 받은 61명을 대상으로 하였다. 연구는 대장암 병기, 폐 전이의 위치, 폐절제술의 방법, 전이된 폐 결절의 수와 크기, 재발, 생존 등을 조사하여 그 예후 인자를 알아보고자 하였다. 결과: 환자들의 평균 3년, 5년 생존율은 각각 61%, 41%였다. 단변량 및 다변량 분석에서 통계학적으로 유의한 예후 인자는 없었다. 환자들의 평균 무병 기간은 17개월이었다. 수술 후 재발은 폐가 가장 흔한 위치였고, 이 중 3명의 환자에서 재수술을 시행하여 2명은 현재까지 생존해 있다. 결론: 대장암의 근치적 수술 후 폐 전이 발생 시 수술적응이 되는 경우 폐절제술을 시행하는 것이 좋은 결과를 기대할 수 있는 적절한 치료방법이라고 생각한다.

• Asian Pacific Journal of Cancer Prevention
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• 제17권8호
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• pp.4071-4075
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• 2016

Background: FDG PET/CT is at an equivocal stage to recommend for staging of colorectal cancer as compared to contrast-enhanced CT (ceCT). This study was intended to evaluate the value of FDG PET/ceCT in colorectal cancer staging as compared to ceCT alone. Materials and Methods: PET/ceCT was performed for 61 colorectal cancer patients who were prospectively enrolled in the study. Three patients were excluded due to loss to follow-up. PET/ceCT findings and ceCT results alone were read separately. The treatment planning was then determined by tumor board consensus. The criteria for T staging were determined by the findings of ceCT. Nodal positive by PET/ceCT imaging was determined by visual analysis of FDG uptake greater than regional background blood pool activity. The diagnostic accuracy of T and N staging was determined only in patients who received surgery without any neoadjuvant treatment. Results: Of 58 patients, there were 40 with colon cancers including sigmoid cancers and 18 with rectal cancers. PET/ceCT in pre-operative staging detected bone metastasis and metastatic inguinal lymph nodes (M1a) that were undepicted on CT in 2 patients (3%), clearly defined 19 equivocal lesions on ceCT in 18 patients (31%) and excluded 6 metastatic lesions diagnosed by ceCT in 6 patients (10%). These resulted in alteration of management plan in 15 out of the 58 cases (26%) i.e. changing from chemotherapy to surgery (4), changing extent of surgery (9) and avoidance of futile surgery (2). Forty four patients underwent surgery within 45 days after PET/CT. The diagnostic accuracy for N staging with PET/ceCT and ceCT alone was 66% and 48% with false positive rates of 24% (6/25) and 76% (19/25) and false negative rates of 47% (9/19) and 21% (4/19), respectively. All of the false negative lymph nodes from PET/ceCT were less than a centimeter in size and located in peri-lesional regions. The diagnostic accuracy for T staging was 82%. The sensitivity of the peri-lesional fat stranding sign in determining T3 stage was 94% and the specificity was 54%. Conclusions: Our study suggested promising roles of PET/ceCT in initial staging of colorectal cancer with better diagnostic accuracy facilitating management planning.

• Journal of Digestive Cancer Research
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• 제1권1호
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• pp.29-35
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• 2013

복막암종증(Peritoneal carcinomatosis)은 복강내에 암세포가 파종되어 벽쪽 복막과 내장쪽 복막 표면에 악성세포가 축적되는 상태로 정의할 수 있으며, 이것은 암성복수와도 관련 있다. 일반적으로 복막암종증은 원발암의 전이성 암과 유사하게 치료하나 같은 원발암의 다른 장기로의 전이암과는 달리 예후가 좋지 않다. 보존적 치료만 했을 경우 복막암종증 환자의 중앙생존기간은 3-6개월이다. 복막암종증은 예후가 좋지 않고 치료 방법이 제한적이어서 일선에서 치료하는 내과 의사에겐 여전히 어려운 과제이기도 하다. 최근에 이와 관련된 치료 방법이 많이 연구되어 육안적 병소제거술 및 복막절제술(cytoreductive surgery with peritonectomy)과 함께 조기 수술 후 복강내 화학요법(early postoperative intraperitoneal chemotherapy, EPIC) 또는 수술 중 복강내 온열화학요법(hyperthermic intraperitoneal chemotherapy, HIPEC)을 시행하여 생존율을 향상시키고 있다. 본 논문에서는 복막암종증의 전반적인 특징, 증상, 예후 및 진단과 수술적 방법, 항암 화학요법 등의 치료법에 대하여 알아보고자 한다.

• Asian Pacific Journal of Cancer Prevention
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• 제17권2호
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• pp.603-608
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• 2016

Background: The investigation of mutation patterns in oncogenes potentially can make available a reliable mechanism for management and treatment decisions for patients with colorectal cancer (CRC). This study concerns the rate of KRAS and BRAF genes mutations in Iranian metastatic colorectal cancer (mCRC) patients, as well as associations of genotypes with clinicopathological features. Materials and Methods: A total of 1,000 mCRC specimens collected from 2008 to 2012 that referred to the Mehr Hospital and Partolab center, Tehran, Iran enrolled in this cross sectional study. Using HRM, Dxs Therascreen and Pyrosequencing methods, we analyzed the mutational status of KRAS and BRAF genes in these. Results: KRAS mutations were present in 33.6% cases (n=336). Of KRAS mutation positive cases, 85.1% were in codon 12 and 14.9% were in codon 13. The most frequent mutation at KRAS codon 12 was Gly12Asp; BRAF mutations were not found in any mCRC patients (n=242). In addition, we observed a strong correlation of KRAS mutations with some clinicopathological characteristics. Conclusions: KRAS mutations are frequent in mCRCs while presence of BRAF mutations in these patients is rare. Moreover, associations of KRAS genotypes with non-mucinous adenocarcinoma and depth of invasion (pT3) were remarkable.

• Asian Pacific Journal of Cancer Prevention
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• 제15권21호
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• pp.9277-9281
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• 2014

Purpose: To investigate clinicopathological features in patients with recurrent colorectal cancer within 1 year and more than 1 year after curative resection. Materials and Methods: We retrospectively evaluated 103 patients with disease recurrence before versus after 1 year of resection. Thirty-two patients (31%) were diagnosed with recurrence less than 1 year after curative resection for colorectal cancer (early recurrence) and 71 (69%) after more than 1 year (non-early recurrence). Results: The early recurrence group displayed a significantly lower overall survival rate for both colon cancer (p=0, 01) and rectal cancer (p<0.001). Inadequate lymph node dissection was a significant predictor for early relapse. There were no statistically significant differences in clinicopathological variables such as age, sex, primary tumor localization, stage, depth of invasion, lymphovascular invasion and perineural invasion between the early and non-early recurrence groups. However, a K-ras mutation subgroup was significantly associated with early recurrence (p<0.001). Conclusions: Poor survival is associated with early recurrence for patients undergoing resection for non-metastatic colorectal cancer, as well as K-ras mutation.

• Asian Pacific Journal of Cancer Prevention
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• 제15권6호
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• pp.2647-2650
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• 2014

Background: Colorectal cancers(CRC) are the third most common cancer in the western world, with surgery preferred for management of non-metastatic disease and post surgical treatment usually arranged according to the TNM staging system. However, there is still prognostic variation between patients who have the same stage. It is increasingly recognized that variations within disease course and clinical outcome in colorectal cancer patients are influenced by not only oncological characteristics of the tumor itself but also host response factors. Recent studies have shown correlation between the inflammatory response and clinical outcomes in various cancers. The neutrophil/lymphocyte ratio (NLR) has been described as a marker for immune response to various stimuli including cancer. Material-Methods: Two hundred eighty-one CRC patients were included in our retrospective analysis, separated into two groups according to a cut-off value for the NLR. Patient data including age, gender, vertical penetration, anatomic location, and differentiation of the tumor, TNM stage, survival rate, and disease-free survival were analyzed for correlations with the NLR. Results: Using ROC curve analysis, we determined a cut-off value of 2.2 for NLR to be best to discriminate between patient survival in the whole group. In univariate analysis, high pretreatment NLR (p=0.001, 95%CI 1.483-4.846), pathologic nodal stage (p<0.001, 95%CI 1.082-3.289) and advanced pathologic TNM stage (p<0.001, 95%CI 1.462-4.213) were predictive of shorter survival. In multivariate analysis, advanced pathologic TNM stage (p=0.001, 95%CI 1.303-26.542) and high pretreatment NLR (p=0.005, 95%CI 1.713-6.378) remained independently associated with poor survival. Conclusions: High pre-treatment NLR is a significant independent predictor of shorter survival in patients with colorectal cancer. This parameter is a simple, easily accessible laboratory value for identifying patients with poorer prognosis.

• Asian Pacific Journal of Cancer Prevention
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• 제15권13호
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• pp.5365-5369
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• 2014

Background: The lymph node ratio (LNR) has been shown to be an important prognostic factor for colorectal cancer. However, studies focusing on the prognostic impact of LNR in rectal cancer patients who received neoadjuvant chemoradiotherapy (CRT) followed by curative resection have been limited. The aim of this study was to investigate LNR in rectal cancer patients who received neoadjuvant chemoradiotherapy (CRT) followed by curative resection. Materials and Methods: A total of 131 consecutive rectal cancer patients who underwent neoadjuvant CRT and total mesorectal excision were included in this study. Patients were divided into two groups according to the LNR (${\leq}0.2$ [n=86], >0.2 [n=45]) to evaluate the prognostic effect on overall survival (OS) and disease-free survival (DFS). Results: The median number of retrieved and metastatic lymph node (LN) was 14 (range 1-48) and 2 (range 1-10), respectively. The median LNR was 0.154 (range 0.04-1.0). In multivariate analysis, LNR was shown to be an independent prognostic factor for both overall survival (hazard ratio[HR]=3.778; 95% confidence interval [CI] 1.741-8.198; p=0.001) and disease-free survival (HR=3.637; 95%CI 1.838-7.195; p<0.001). Increased LNR was significantly associated with worse OS and DFS in patients with <12 harvested LNs, and as well as in those ${\geq}12$ harvested LNs (p<0.05). In addition, LNR had a prognostic impact on both OS and DFS in patients with N1 staging (p<0.001). Conclusions: LNR is an independent prognostic factor in ypN-positive rectal cancer patients, both in patients with <12 harvested LNs, and as well as in those ${\geq}12$ harvested LNs. LNR provides better prognostic value than pN staging. Therefore, it should be used as an additional prognostic indicator in ypN-positive rectal cancer patients.

• Journal of Chest Surgery
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• 제48권6호
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• pp.447-451
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• 2015

This report describes the case of a 57-year-old man with an anterior mediastinal tumor. Four years previously, he underwent laparoscopic anterior resection for sigmoid colon cancer. Thirty months after that procedure, bilateral pulmonary metastasectomy was performed. Twelve months later, follow-up computed tomography revealed a 1-cm pulmonary nodule on the upper lobe of the right lung and a solid mass on the anterior mediastinum, and the patient was also observed to have an elevated serum carcinoembryonic antigen (CEA) level. Repeated pulmonary nodule resection and total thymectomy were performed. Immunohistochemical staining of the anterior mediastinal tumor revealed adenocarcinoma, and his serum CEA level returned to normal after the operation. These findings strongly suggested metastatic thymic adenocarcinoma from a colorectal cancer.