• Asian Pacific Journal of Cancer Prevention
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• 제14권9호
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• pp.5375-5378
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• 2013

Background: This study was undertaken to evaluate the surgical outcomes of patients with stage IA2 cervical cancer treated with radical hysterectomy. Data for 58 patients who underwent modified radical hysterectomy or radical hysterectomy with pelvic lymphadenectomy between January 2003 and December 2012 at Chiang Mai University Hospital were retrospectively reviewed. The analysis included clinico-pathological risk factors (nodal metastasis, parametrial involvement), adjuvant treatment, 5-year disease-free survival and 5-year overall survival. All pathologic slides were reviewed by a gynecologic pathologist. Follow-up methods included at least cervical cytology and colposcopy with directed biopsy if indicated. Univariate analysis was performed to identify factors associated with median survival. At the median follow up time of 73 months, the 5-year disease-free survival and the 5-year overall survival were 97.4% and 97.4%, respectively. Two (3.4%) patients had pelvic lymph node metastases. In a univariate analysis, there was no statistically significant association between survival and prognostic factors such as age, histological cell type, lymph-vascular space invasion, vaginal margin status and lymph node status. Surgical and survival outcomes of women with stage IA2 cervical cancer are excellent. No parametrial involvement was detected in our study. Patients with stage IA2 cervical cancer may be treated with simple or less radical hysterectomy with pelvic lymphadenectomy.

• Asian Pacific Journal of Cancer Prevention
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• 제16권17호
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• pp.7975-7979
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• 2015

Purpose: This study aimed to explore the value of IHC4 in predicting pathological response after neoadjuvant chemotherapy in patients with hormonal receptor (HR)-positive breast cancer (BC). Materials and Methods: In this retrospective exploratory study, data for 68 HR-positive BC patients who received neoadjuvant chemotherapy were recorded. IHC4 scores were calculated based on estrogen receptors/progesterone receptors, Ki-67 and HER2 status. Logistic and ordinal regression analyses in addition to likelihood ratio test were used to explore associations of IHC4 scores and other clinico-pathological parameters with pathological complete response (pCR) and pathological stage. Results: Taking the 25th percentile as the cut-off, a lower IHC4 score was associated with an increased probability of pCR (low; 52.9% vs. High; 21.6%, OR=4.1, 95% CI=1.28-13.16, p=0.018) and a lower pathological stage (OR=3.9, 95% CI=1.34-11.33, p=0.012). When the IHC4 score was treated as a continuous variable, a lower score was again associated with an increased probability of pCR (OR=1.010, 95% CI=1.001-1.018, p=0.025) and lower pathological stage (OR=1.009, 95% CI=1.002-1.017, P=0.008). Lower clinical stage was associated with a better pCR rate that was of borderline significance (P=0.056). When clinical stage and IHC4 score were incorporated together in a logistic model, the likelihood ratio test gave a P-value of 0.004 after removal of the IHC4 score and 0.011 after removal of the stage, indicating a more significant predictive value of the IHC4 score for pCR. Conclusions: This study suggests that the IHC4 score can predict pathological response to neoadjuvant chemotherapy in HR-positive BC patients. This finding now needs to be validated in a larger cohort of patients.

• Asian Pacific Journal of Cancer Prevention
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• 제15권7호
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• pp.3057-3063
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• 2014

Background: Anaplastic lymphoma kinase (ALK) gene rearrangement in non-small cell lung cancer (NSCLC) has been intensively studied. The gold standard for ALK detection is FISH, but this is not routinely conducted in clinical practice, so that the IHC method has a role. The aim of this study was to identify the incidence of ALK rearrangement and risk or prognostic factors for ALK positivity using both of IHC and FISH methods. Materials and Methods: From January 2008 to December 2012, 267 completely resected NSCLC patients in Chiang Mai University Hospital were enrolled in this study. Clinical and pathological variables and outcomes of treatment were retrospectively reviewed. IHC and FISH were used to evaluate ALK rearrangement. Sensitivity and specificity of IHC were analyzed. Multivariable analysis was used to identify clinico-pathological correlations with positive results of IHC and clinical outcomes. Results: Twenty-two (8.2%) of 267 specimens were IHC-positive for ALK with intense cytoplasmic staining, whereas only 10 (3.8%) were FISH-positive. Sensitivity, specificity and the positive likelihood ratio with IHC were 80.0%, 94.9%, and 15.8 respectively. Age less than 55 years (RR 4.4, 95%CI 1.78-10.73, p value=0.001) and presence of visceral pleural invasion (VPI) (RR 2.9, 95%CI 1.21-6.78, p value =0.017) were identified as risk factors for ALK rearrangement with FISH. There were no statistically significant differences in other clinical and pathological variables. ALK rearrangement was not a prognostic factor for tumor recurrence or overall survival. Conclusions: The incidences of ALK positivity in completely resected NSCLCs in northern Thailand were 8.2% by IHC and 3.8% by FISH. IHC with mouse monoclonal, Ventana D5F3 antibody can be used as a screening tool before FISH method because of high specificity and high positive likelihood ratio. Age less than 55 years and VPI are risk factors for ALK positivity.

• Asian Pacific Journal of Cancer Prevention
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• 제13권3호
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• pp.837-846
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• 2012

Breast cancer (BCa) is the leading type of cancer in Mexican women. Genetic factors, such as single nucleotide polymorphisms (SNP) of P450 system, have been reported in BCa. In this report, and for the first time in the literature, we analyzed the rs3735684 (7021 G>A), rs11553651 (15016 G>T) and rs56195291 (60020 C>G) polymorphisms in the CYP2W1, 4F11 and 8A1 genes in patients with BCa and in healthy Mexican women to identify a potential association between these polymorphisms and BCa risk. Patients and controls were used for polymorphism analysis using an allelic discrimination assay with TaqMan probes and confirmed by DNA sequencing. Links with clinic-pathological characteristics were also analyzed. Statistical analysis was performed using the standard ${\chi}^2$ or Fisher exact test statistic. No significant differences were observed in the distributions of CYP2W1 (OR 8.6, 95%CI 0.43-172.5 P>0.05; OR 2.0, 95%CI 0.76-5.4, P>0.05) and CYP4F11 (OR 0.3, 95%CI 0.01-8.4 P>0.05) genotypes between the patients and controls. Only the CYP8A1 CC genotype was detected in patients with BCa and the controls. All polymorphism frequencies were in Hardy-Weinberg Equilibrium (HWE) in the controls (P>0.05). We found a significant association between BCa risk and smoking, use of oral contraceptives or hormonal replacement therapy (HRT), obesity, hyperglycemia, chronic diseases, family history of cancer and menopausal status in the population studied (P<0.05). Tobacco, oral contraceptive or HRT, chronic diseases and obesity or overweight were strongly associated with almost eight, thirty-five, nine and five-fold increased risk for BCa. Tobaco, obesity and hyperglycemia significantly increased the risk of BCa in the patients carrying variant genotypes of CYP2W1 (P<0.05). These results indicate that the CYP2W1 rs3735684, CYP4F11 rs11553651 and CYP8A1 rs56195291 SNPs are not a key risk factor for BCa in Mexican women. This study did not detect an association between the CYP2W1, 4F11 and 8A1 genes polymorphisms and BCa risk in a Mexican population. However, some clinico-pathological risk factors interact with CYP2W1 genotypes and modifies susceptibility to BCa.

• Journal of Chest Surgery
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• 제39권11호
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• pp.828-837
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• 2006

배경: 악성종양에서 신생혈관 생성 및 당분해의 증가는 저산소 상태의 미세환경을 나타내며, 이는 종양의 침습성, 전이 및 환자의 예후와 관련이 있는 것으로 알려져 있다. Hypoxia-inducible factor 1(HIF-1)는 당원 수송체, 당분해 효소, 혈관내피세포 성장인자 등의 유전자의 전사를 활성화한다고 알려져 있다. 그리고 HIF-1의 전사 활성도는 HIF-$1{\alpha}$ 아단위의 표현이 조절되는 정도에 의존한다. 비소세포 폐암에서 HIF-$1{\alpha}$의 발현이 혈관 생성능, 종양세포 증식능 및 이상형 p53의 축적 등 종양의 생물학적 특성에 미치는 영향과 환자의 수술 후 예후와의 관계를 규명하고자 한다. 대상 및 방법: 1997년부터 1999년까지 비소세포 폐암으로 진단받고 전폐절제술 혹은 폐엽절제술을 시행 받은 59명의 폐암 환자들에서 얻어진 파라핀 조직 블록을 대상으로 하였다. ABC(avidin-biotin complex) 방법에 기초한 면역조직화학검사를 이용하여 암조직과 정상조직에서 HIF-$1{\alpha}$, VEGF(vascular endothelial growth factor), p53 단백의 발현을 조사하고, Ki-67의 발현을 이용한 증식지수를 측정하였다. HIF-$1{\alpha}$ 발현과 환자의 생존기간을 포함한 임상적-병리학적 변수들과의 상관관계, VEGF, p53의 발현과 증식지수와의 상관관계를 분석하였다. 결과: HIF-$1{\alpha}$의 과발현은 40.7%(24예/59예)였다. HIF-$1{\alpha}$의 과발현은 병리학적 TNM병기(p=0.004), T병기(p=0.020), N병기(p=0.004), 림프관/혈관 침범(p=0.019) 등과 관련이 있었다. 또 혈관내피세포 성장인자의 발현(p<0.001) 및 이상형의 p53의 발현(p=0.040)과 관련성이 있었다. Kaplan-Meier 생존분석에서 HIF-$1{\alpha}$의 과발현이 있는 환자의 5년 생존울은 22%로 HIF-$1{\alpha}$의 저발현 환자의 5년 생존율 61%에 비해 불량한 생존율을 보였고, 단변량분석과 다변량분석에서 HIF-$1{\alpha}$의 발현은 불량한 예후를 나타내는 인자로 관찰되었다. 결론: 이상의 결과로 비소세포 폐암 환자에서 HIF-$1{\alpha}$의 과발현은 종양내 신생혈관의 생성과 림프절 전이와 관련이 있는 표지자로 여겨지며, 수술 후 불량한 예후를 나타내었다.

• Asian Pacific Journal of Cancer Prevention
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• 제14권9호
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• pp.5095-5099
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• 2013

Background: The overall incidence of breast cancer in South Asian countries, including Nepal, is low compared to Western countries. However, the incidence of breast cancer among young women is relatively high. Breast cancer in such cases is characterized by a relatively unfavorable prognosis and unusual pathological features. The aim of this study was to investigate clinico-pathological and biological characteristics in younger breast cancer patients (<40 years) and compare these with their older counterparts. Materials and Methods: Nine hundred and forty four consecutive female breast cancer patients, admitted to the Department of Surgery, Tribhuvan University Teaching Hospital, Kathmandu, Nepal between November 1997 and October 2012, were retrospectively analyzed. Results: Out of the 944 female breast cancer patients, 263 (27.9%) were <40 years. The mean age was $34.6{\pm}5.0$ years among younger patients compared to $54.1{\pm}9.9$ for those ${\geq}40$ years. The mean age at menarche was also significantly lower ($13.5{\pm}1.5$ vs $14.2{\pm}1.5$ years p=0.001) while the mean duration of symptoms was significantly longer (7.6 vs 6.5 months p=0.004). Family history of breast cancer was evident in 3.0% of the young women versus 0.3% in the older one. Mammography was performed less frequently in younger patients (59.7%), compared to older (74.4%), and was of diagnostic benefit in only 20% of younger patients compared to 85% of older ones. At diagnosis, the mean tumor diameter was significantly larger in young women ($5.0{\pm}2.5$ vs $4.5{\pm}2.4cm$, p=0.005). Axillary lymph nodes were positive in 73% of younger patients and 59% of older patients. In the younger group, the proportion of stage III or IV disease was higher (55.1% vs 47.1%, $p{\leq}0.05$). The proportion of breast conserving surgery was higher in young patients (25.1% vs 8.7%) and a higher proportion of younger patients receive neoadjuvant chemotherapy (9.9% vs 2.8%). The most common histological type was ductal carcinoma (93.1% vs 86%). The proportion of histological grade II or III was higher in younger patients (55.9% vs 24.5%). Similarly, in the younger group, lymphatic and vascular invasion was more common (63.2% vs 34.3% and 39.8% vs 25.4%, respectively). Patients in the younger age group exhibited lower estrogen and/or progesterone receptor positivity (34.7% vs 49.8%). Although statistically not significant, the proportion of triple negative tumors in younger age group was higher (22.4% vs 13.6%). Conclusions: Breast cancer in young Nepalese women represents over one quarter of all female breast cancers, many being diagnosed at an advanced stage. Tumors in young women exhibit more aggressive biological features. Hence, breast cancer in young women is worth special attention for earlier detection.

• Annals of Surgical Treatment and Research
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• 제95권5호
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• pp.286-296
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• 2018

Purpose: Sentinel lymph node (SLN) biopsy (SLNB) is widely accepted for staging of melanoma patients. It has been shown that clinico-pathological features such as Breslow thickness, ulceration, age, and sex are better predictors of relapse and survival than SLN status alone. The aims of this study were to evaluate the long-term (10-year) prognostic impact of SLNB and to determine predictive factors associated with SLN metastasis, relapse, and melanoma specific mortality (MSM). Methods: This was a prospective observational study on 289 consecutive patients with primary cutaneous melanoma who underwent SLNB from January 2000 to December 2007, and followed until January 2014, at an Italian academic hospital. Results: SLN was positive in 64 patients (22.1%). The median follow-up was 116 months (79-147 months). Tenyear disease-free survival and melanoma specific survival were poor in patients with positive SLN (58.7% and 66.4%, respectively). Only the increasing Breslow thickness resulted independently associated to an increased risk of SLN metastasis. Cox regression analysis showed that a Breslow thickness >2 mm was an independent predictor of relapse, and male sex and Breslow thickness >2 mm was a predictor of MSM. At 10 years, SLN metastasis was not significantly associated to either relapse or MSM. Conclusion: After the fifth year of follow-up, SLN metastasis is not an independent predictive factor of relapse or mortality which are mainly influenced by the characteristics of the primary tumor and of the patient. Patients with a Breslow thickness >2 mm regardless of the SLN status should be considered at high risk for 10-year relapse and mortality.

• 대한세포병리학회지
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• 제3권1호
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• pp.1-11
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• 1992

췌-담도 및 배터 팽대부 주위의 암은 조기진단이 어려워 처음 발견시 질병이 상당히 진행되어 있어, 근치술은 물론 생검진단도 수행하기가 어려운 경우가 흔히 있다. 과거 이런 환자들의 진단 방법의 하나로 십이지장에서 담즙을 얻어 세포병리 검사가 시도 되었었으나, 이 경우 얻어진 담즙에 위액 및 췌액이 섞여 있어 변성을 쉽게 초래하고, 염증세포들이 많이 섞여 있을 뿐만 아니라 주위의 염증으로 비정형 세포변화를 초래하여 진단이 어려운 경우가 흔히 있었다. 최근 이런 환자들에 있어 수반되는 증상인 폐색성 황달의 완화와 방사선학적 진단을 위해 경피 경간 담도 조영술 및 담즙배출술이 시행되고 있는데, 이때 비교적 세포형태가 잘 유지된 담즙을 반복 채취하여 세포 병리검사가 시행된다. 저자들은 이 방법으로 얻어진 담즙의 세포 병리학적 진단 성적을 검토하여 다음과 같은 결과를 얻었다. 총 검체는 148명 환자의 275 검체로 이들의 세포 병리학적 진단은 선암 30예 (20.3%) 편평상피 세포암 1예 (0.75%), 전이성 소 세포암 1예 (0.7%), 선조성 비후 8예 (5.4%) 비정형 6예 (4.1 %), 간 흡충증 17예 (11.5), 양성 질환 57예 (38.5%)였고 28명 (18.9%)에서는 부적합 검체가 의뢰 되었었다. 그중 105명에서 의무기록의 확인이 가능하였는데 이들의 임상진단은 99명에서는 악성 질환 이었고 6명에서는 총 담관 결석과 협착과 같은 양성 질환 이었다. 담즙 세포 병리검사에서의 이들 악성 진단율은 23.2%이었다. 이들 악성 질환을 담도 유래의 종양과(1군)부근 림프절의 전이성암, 췌장암, 배터 팽대부 주위암 등의 외인성으로 담도를 압박하는 종양(2군)으로 나누어 보면 악성 진단율은 각각 37%와 11.6%로 현저한 차이가 있었다. 이들중 조직학적 진단이 가능 하였던 9예의 경우 세포 병리 진단율은 각각 50%(1군)와 20%(2군)로 역시 현저한 차이가 있었다 임상진단이 양성 질환 이었던 예들은 전예에서 세포 병리학적으로 양성으로 진단되어 담즙 세포 병리검사의 임상진단과의 일치율은 27.6%, 특이도는 100%이었다. 이상으로 이 담즙세포 검사의 악성 진단율은 그리높지 않으나, 경피 경간 담즙 배출술로 환자의 증상을 완화 시키면서 부수적으로 진단도 얻을 수 있는 유용한 방법이라 하겠고, 그중 담도유래의 종양군에서 외인성으로 담도를 압박하게 되는 종양군에 비해 현저히 높은 진단율을 보였다.

• Tuberculosis and Respiratory Diseases
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• 제63권1호
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• pp.31-41
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• 2007

연구배경: 폐암의 병인에 기여하거나 예후를 결정하는 인자에 대해서는 매우 다양한 인자와 다양한 상호 관계로 인하여 특히 유전자의 역할에 대해서는 결정적으로 알려진 것이 없어 앞으로 더 많은 연구가 필요한 실정이다. 이에 따라 본 연구에서는 COX-2, MMP-9, p53가 비소세포폐암에서 어떻게 발현되는지 세포면역학적으로 알아보고 임상 특성과 예후와 상관관계를 알아보고자 하였다. 대상 및 방법: 91명의 비소세포폐암을 대상으로 하여 후향적으로 임상특성을 고찰하고 COX-2, MMP-9, p53의 유전자 표현을 세포면역학적 방법을 통하여 검사하였다. 임상특성과 유전자 표현 패턴의 상관관계와 생존에 대한 예후인자로서의 역할에 대하여 조사하였다. 결 과: 1) 편평상피세포암에서는 흡연자과 남자가 우세한 비율을 차지하였으며 남자에서 흡연의 비율이 유의하게 높았다. 2) 전체 대상 환자에서 생존에 영향을 미치는 결정적인 인자는 근치적 절제술의 시행여부와 병기로 나타났다. 3) COX-2의 발현은 편평상피세포암 보다 선암에서 더 유의하게 높게 발현되었다. 4) COX-2, MMP-9, p53의 발현이 모두 되지 않는 비율은 선암에 비해 편평상피세포암에서 더 흔하게 관찰되었다. 5) p53돌연변이가 있으면서 COX-2와 MMP-9은 발현이 되지 않는 비소세포폐암환자의 생존기간이 다른 발현 양상을 보이는 경우에서의 생존기간보다 더 연장되어 보였다(생존기간의 중앙값; 165.6주). 6) COX-2의 발현과 MMP-9의 발현 사이에는 유의한 상관관계가 있었다. 7) 폐암을 근치적으로 절제한 환자의 경우에 COX-2의 발현은 유의한 예후인자였다. MMP-9는 근치적 절제술을 받지 못한 환자군에서 유의한 예후인자로 작용하였다.

• Journal of Gastric Cancer
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• 제10권1호
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• pp.19-25
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• 2010

목적: 복강경하 보조 위 절제술이 위암 치료에 사용되기 위해서는 기술적인 측면 외에 수술적 치료와 관계하는 영양학적 및 면역학적 요소가 함께 고려되어야 한다. 이에 본 연구에서는 조기위암 환자에서 복강경하 위아전절제술의 영양학적 및 면역학적 측면에서의 안정성에 대해 알아 보고자 본 연구를 시행하였다. 대상 및 방법: 2006년 4월부터 2009년 5월까지 조기위암으로 복강경하 위아전절제술을 시행한 87예와 개복 위아전절제술을 시행한 30명의 환자를 대상으로 임상 정보와 혈청학적 검사를 후향적으로 비교 분석하였다. 결과: 두 군 간의 술 전 임상병리학적 요인에는 차이가 없었으며, 복강경하 위아전절제술군에서 총 백혈구수는 개복군에 비해 술 후 1일째와 3일째 더 증가 정도가 낮았으며(P=0.001, P=0.008), CRP는 술 후 1일째와 3일째에서 증가 정도의 차이를 보이지 않았으나(P=0.632, P=0.139), 술 후 5일째의 감소 정도는 통계학적 차이를 보였다(P<0.001). T4/T8 ratio는 복강경하 위아전절제술군에서 술 후 3일째 감소 정도가 적었으나(P=0.003), Albumin의 감소 정도는 통계학적 차이를 보이지 않았다(P=0.157). 결론: 복강경 위아전절제술은 개복 위절제술에 비해 Albumin을 이용해 비교한 영양학적 측면에서 장점은 없었으나, 술 후 총 백혈수의 증가, CRP 감소, 및 T4/T8 ratio 감소 등의 전신 면역 및 염증 반응에서 우월함을 알 수 있었다.