• Asian Pacific Journal of Cancer Prevention
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• v.16 no.18
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• pp.8397-8403
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• 2016

Background: Breast cancer (BCa) is the most common malignancy in Mexican women. A set of histopathological markers has been established to guide BCa diagnosis, prognosis and treatment. Nevertheless, in only a few Mexican health services, such as that of the Secretariat of National Defense (SEDENA for its acronym in Spanish), are these markers commonly employed for assessing BCa. The aim of this study was to explore the association of Ki67, TP53, HER2/neu, estrogenic receptors (ERs) and progesterone receptors (PRs) with BCa risk factors. Materials and Methods: Clinical histories provided background patient information. Immunohistochemical (IHC) analysis was conducted on 48 tissue samples from women diagnosed with BCa and treated with radical mastectomy. The Chi square test or Fisher exact test together with the Pearson and Spearman correlation were applied. Results: On average, patients were $58{\pm}10.4$ years old. It was most common to find invasive ductal carcinoma (95.8%), histological grade 3 (45.8%), with a poor Nottingham Prognostic Index (NPI; 80.4%). ERs and PRs were associated with smoking and alcohol consumption, metastasis at diagnosis and Ki67 expression (p<0.05). PR+ was also related to urea and ER+ (p<0.05). Ki67 was associated with TP53 and elevated triglycerides (p<0.05), and HER2/neu with ER+, the number of pregnancies and tumor size (p<0.05). TP53 was also associated with a poor NPI (p<0.05) and CD34 with smoking (p<0.05). The triple negative status (ER-/PR-/HER2/neu-) was related to smoking, alcohol consumption, exposure to biomass, number of pregnancies, metastasis and a poor NPI (p<0.05). Moreover, the luminal B subty was associated with histological type (p=0.007), tumor size (p=0.03) and high cholesterol (p=0.02). Conclusions: Ki67, TP53, HER2/neu, ER and PR proved to be related to several clinical and pathological factors. Hence, it is crucial to determine this IHC profile in women at risk for BCa. Certain associations require further study to understand physiological/biochemical/molecular processes.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.11
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• pp.4549-4553
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• 2015

Background: Colorectal carcinoma (CRC) is one of the major causes of cancer death worldwide. Data from the literature indicate differences between the proliferation rate of endothelial cells relative to the morphology growth type, possibly due to origin of specimens (autopsy material, surgery fragments) or quantification methods. Vascular endothelial growth factor (VEGF) is a factor that stimulates the proliferation of endothelial cells. It is expressed in more than 90% of cases of metastatic CRC. Aim: The aim of this study was to evaluate the endothelial cell proliferation and VEGF expression in primary tumors and corresponding liver metastases. Materials and Methods: Our study included 24 recent biopsies of primary tumors and corresponding liver metastases of CRC cases. CD34/Ki67 double immunostaining and RNA scope assay for VEGF were performed. Results: In the primary tumors analysis of VEGFmRNA expression indicated no significant correlation with differentiation grade, proliferative and non-proliferative vessels in the intratumoral and peritumoral areas. In contrast, in the corresponding liver metastases, VEGFmRNA expression significantly correlated with the total number of non-proliferative vessels and total number of vessels. CD34/Ki67 double immunostaining in the cases with poorly differentiated carcinoma indicated a high number of proliferating endothelial cells in the peritumoral area and a low number in the intratumoral area for the primary tumor. Moderately differentiated carcinomas of colon showed no proliferating endothelial cells in the intratumoral area in half of the cases included in the study, for both, primary tumor and liver metastasis. In well differentiated CRCs, in primary tumors, a high proliferation rate of endothelial cells in the intratumoral area and a lower proliferation rate in the peritumoral area were found. A low value was found in corresponding liver metastasis. Conclusions: The absence of proliferative endothelial cells in half of the cases for the primary tumors and liver metastases in moderately differentiated carcinoma suggest a vascular mimicry phenomenon. The mismatch between the total number of vessels and endothelial proliferation in primary tumors indicate that a functional vascular network is already formed or the existence of some mechanisms influenced by other angiogenic factors.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.7
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• pp.3643-3646
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• 2016

Management of eyelid cancers is based on surgery and/or radiotherapy (RT). The treatment objective is to control tumors with acceptable functional and esthetic outcomes. The aim of this study was to evaluate the results of radiation therapy in management of epithelial eyelid cancers, reviewing retrospectively the clinical records of patients treated in our institution from January 1989 to December 2013. We focused on clinical and histological features, treatment characteristics, tolerance and disease control. One hundred and eight patients (62 men and 46 women) were enrolled, with a mean age of 61 years [ranges 15-87]. The most frequent tumor location was the inner canthus (42.6%). Median tumor size was 21 mm [ranges 4-70]. Histological type was basal cell carcinoma in 88 cases (81.5%), squamous cell carcinoma in 16 (14.8%) and sebaceous carcinoma in 4 (3.7%). Radiation therapy was exclusive in 67 cases (62%) and post-operative for positive or close margins in the remaining cases. Kilovoltage external beam radiotherapy (KVRT) was used in 63 patients (58.3%) and low-dose-rate interstitial brachytherapy in 37 (34.3%). Eight (7.4%) were treated with cobalt or with a combination of KVRT-cobalt, KVRT-electron beams, KVRT-brachytherapy or cobalt-electron beams. The total delivered radiation doses were 70 Gy (2 Gy/fraction) in 62 patients (57.4%), 66 Gy (2 Gy/fraction) in 37 (34.3%) and 61.2 Gy (3.4Gy/fraction) in 9 (8.3%). After a median follow-up of 64 months, we noted 10 cases of local recurrences(9.2%): 7 after exclusive and 3 after post-operative RT. No local recurrence occurred in patients treated with brachytherapy. Actuarial 5-year local recurrence-free rate, disease-free survival and overall survival were respectively 90%, 90% and 97%. T-stage was found to be a significant factor for recurrence (p=0.047). All acute radiation-related reactions were scored grade I or II. Delayed effects were eye watering in 24 cases (22.2%), eye dryness in 19 (17.6%), unilateral cataract in 7 (6.4%) and ectropion in 4 (3.7%). Radiation therapy and especially brachytherapy is an efficient treatment of eyelid cancers, allowing eye conservation and functional preservation with good local control rates and acceptable toxicity.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.18
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• pp.7959-7964
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• 2014

The significance of the single hormone receptor positive phenotype of breast cancer is still poorly understood. The use of hormone therapy has been found to be less effective for this type, which has a survival outcome midway between double positive and double negative phenotypes. The aim of this study was to investigate differences in patient and tumor characteristics and survival between double-receptor positive (ER+PR+), double receptor negative (ER-PR-) and single receptor positive (ER+PR- and ER-PR+) breast cancer in an Asian setting. A total of 1,992 patients with newly diagnosed stage I to IV breast cancer between 2003 and 2008, and where information on ER and PR were available, were included in this study. The majority of patients had ER+PR+ tumors (n=903: 45.3%), followed by 741 (37.2%) ER-PR-, 247 (12.4%) ER+PR-, and 101 (5.1%) ER-PR+ tumors. Using multivariate analysis, ER+PR- tumors were 2.4 times more likely to be grade 3 compared to ER+PR+ tumors. ER+PR- and ER-PR+ tumors were 82% and 86% respectively less likely to be grade 3 compared with ER-PR- tumors. ER-PR+ tumours were associated with younger age. There were no survival differences between patients with ER+PR+ and ER-PR+ tumors. However, ER+PR- tumors have poorer survival compared with ER+PR+ tumours. ER-PR- tumours had the worst survival. Adjuvant hormonal therapy with tamoxifen was found to have identical survival advantage in patients with ER+PR+ and ER-PR+ tumors whereas impact was slightly lower in patients with ER+PR- tumors. In conclusion, we found ER+PR- tumors to be more aggressive and have poorer survival when compared to ER+PR+ tumors, while patients with ER-PR+ tumours were younger, but had a similar survival to their counterparts with ER+PR+ tumours.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.9
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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.

• Tuberculosis and Respiratory Diseases
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• v.82 no.3
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• pp.227-233
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• 2019

Background: Programmed death-ligand 1 (PD-L1), a transmembrane protein, binds to the programmed death-1 (PD-1) receptor, and anti-PD-1 therapy enables immune responses against tumors. This study aimed to assess clinical characteristics of PD-L1 expression using immunohistochemistry among Korean patients with lung cancer. Methods: We retrospectively reviewed the data of patients with pathologically proven lung cancer from a single institution. PD-L1 expression determined by Tumor Proportion Score (TPS) was detected using 22C3 pharmDx (Agilent Technologies) and SP263 (Ventana Medical Systems) assays. Results: From July 2016 to July 2017, 267 patients were enrolled. The main histologic type was adenocarcinoma (69.3%). Most participants were smokers (67.4%) and had clinical stage IV disease (60.7%). In total, 116 (42%) and 58 (21%) patients had TPS ${\geq}1%$ and ${\geq}50%$, respectively. The patients were significantly older in TPS ${\geq}1%$ group than in TPS <1% group ($64.83{\pm}9.38years$ vs. $61.73{\pm}10.78years$, p=0.014), not in TPS ${\geq}50%$ cutoff value ($64.69{\pm}9.39$ vs. $62.36{\pm}10.51$, p=0.178). Regarding histologic grade, higher proportions of poorly differentiated tumor were observed in the TPS ${\geq}1%$ (40.8% vs. 25.8%, p=0.020) and TPS ${\geq}50%$ groups (53.2% vs. 27.2%, p=0.004). Among 34 patients examined with 22C3 and SP263 assays, 27 had positive results in both assays, with a cutoff of TPS ${\geq}1%$ (r=0.826; 95% confidence interval, 0.736-0.916). Conclusion: PD-L1 expression, defined as TPS ${\geq}1%$, was related to older age and poorly differentiated histology. There was a similar distribution of PD-L1 expression in both 22C3 and SP263 results.

• Radiation Oncology Journal
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• v.13 no.1
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• pp.69-78
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• 1995

Seventy four patients with soft tissue sarcomas treated by postoperative radiotherapy in the Department of Therapeutic Radiology, Seoul National University Hospital between August 1979 and September 1990 were analyzed. The follow-up Period ranged from 3 to 145 months with a median of 51 months. Liposarcoma and malignant fibrous histiocytoma(MFH) constituted $54\%$ of the cases and the histologic grades of tumors are as follows: grade I, 23 cases; grade II, 17 cases; grade III, 24 cases: unknown grade, 10 cases. The patients were treated by marginal(17 cases), wide(55 cases) or compartmental(2 cases) excision followed by Postoperative radiotherapy. The total radiation doses were 4200-8820 cGy (median 6000 cGy), 180-200 cGy daily. 5 times per week. Of 74 Patients, 35 ultimately failed. The local control was $62.2\%$ at 5 years and cumulative risk of distant metastasis was $22,3\%$ at 5 years. The overall survival and disease free survival were $72.3\%$, and $53.3\%$ at 5 years, respectively. Survival after appearance of metastasis was $15.1\%$ at 3 years. Patients with liposarcoma experienced better local control than those with other histologic type and tumor grade and surgical resection margin significantly correlated with local recurrence, distant metastasis and overall survival on univariate analysis. In conclusion, re-excision is needed for patients with positive surgical resection margin to improve local control and further therapeutic measures using effective chemotherapy should be explored in the hope of improving overall survival.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.7
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• pp.3335-3341
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• 2014

Background: Severe toxicity is commonly observed in cancer patients receiving irinotecan (CPT-11) UDPglucuronosyltransferase1A1 (UGT1A1) catalyzes the glucuronidation of the active metabolite SN-38 but the relationship between UGT1A1 and severe toxicity remains unclear. Our study aimed to assess this point to guide clinical use of CPT-11. Materials and Methods: 89 cancer patients with advanced disease received CPT-11-based chemotherapy for at least two cycles. Toxicity, including GI and hematologic toxicity was recorded in detail and UGT1A1 variants were genotyped. Regression analysis was used to analyse relationships between these variables and tumor response. Results: The prevalence of grade III-IV diarrhea was 10.1%, this being more common in patients with the TA 6/7 genotype (5 of 22 patients, 22.7%) (p<0.05). The prevalence of grade III-IV neutropenia was 13.4%and also highest in patients with the TA 6/7 genotype (4 of 22 patients; 18.2%) but without significance (p>0.05). The retreatment total bilirubin levels were significantly higher in TA6/7 patients (mean, $12.75{\mu}mol/L$) with compared to TA6/6 (mean, $9.92{\mu}mol/L$) with p<0.05. Conclusions: Our study support the conclusion that patients with a $UGT1A1^*28$ allele (s) will suffer an increased risk of severe irinotecan-induced diarrhea, whether with mid-or low-dosage. However, the $UGT1A1^*28$ allele (s) did not increase severe neutropenia. Higher serum total bilirubin is an indication that patients UGT1A1 genotype is not wild-type, with significance for clinic usage of CPT-11.

• Radiation Oncology Journal
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• v.29 no.4
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• pp.260-268
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• 2011

Purpose: To evaluate the treatment outcome and prognostic factor after postoperative radiotherapy in retroperitoneal sarcoma. Materials and Methods: Forty patients were treated with surgical resection and postoperative radiotherapy for retroperitoneal sarcoma from August 1990 to August 2008. Treatment volume was judged by the location of initial tumor and surgical field, and 45-50 Gy of radiation was basically delivered and additional dose was considered to the high-risk area. Results: The median follow-up period was 41.4 months (range, 3.9 to 140.6 months). The 5-year overall survival (OS) was 51.8% and disease free survival was 31.5%. The 5-year locoregional recurrence free survival was 61.9% and distant metastasis free survival was 50.6%. In univariate analysis, histologic type (p = 0.006) was the strongest prognostic factor for the OS and histologic grade (p = 0.044) or resection margin (p = 0.032) had also effect on the OS. Histologic type (p = 0.004) was unique significant prognostic factor for the actuarial local control. Conclusion: Retroperitoneal sarcoma still remains as a poor prognostic disease despite the combined modality treatment including surgery and postoperative radiotherapy. Selective dose-escalation of radiotherapy or combination of effective chemotherapeutic agent must be considered to improve the treatment result especially for the histopathologic type showing poor prognosls.

• Radiation Oncology Journal
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• v.22 no.1
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• pp.11-16
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• 2004

Purpose: To evaluate the survival rate, local failure rate and patterns of failure, and analyze the prognostic factors affecting local relapse of ductal carcinoma in situ treated with breast conserving surgery and radiotherapy Materials and Methods: From June 1995 to December 2001, 96 patients with ductal carcinoma in situ treated with breast conserving surgery and radiotherapy were retrospectively analyzed. The operations were either local or wide excision in all patients, with an axillary lymph node dissection performed in some patients. Radiation dose to the whole breast was 50.4 Gy, over 5 weeks, with 1.8 Gy daily fractions, with additional doses ($10\~14$ Gy) administered to the primary tumor bed in some patients with close ($\leq$2 mm) or positive resection margin. The median follow-up period was 43 months (range $10\~102$ months). Results: The 5-year local relapse free survival and overall survival rates were 91 and $100\%$ respectively. Local relapse occurred in 6 patients ($6.3\%$). Of the 6 recurrences, one was invasive ductal cell carcinoma. With the exception of one, all patients recurred 2 years after surgery. There was no regional recurrence or distant metastasis. Five patients with local recurrence were salvaged with total mastectomy, and are alive with no evidence of disease. One patient with recurrent invasive ductal cell carcinoma will receive salvage treatment. On analysis of the prognostic factors affecting local relapse, none of the factors among the age, status of resection margin, comedo type and nuclear grade affected local relapse. Operation extent also did not affect local control (p=0.30). In the patients with close resection margin, boost irradiation to the primary tumor bed did not affect local control (p=1.0). Conclusions: The survival rate and local control of the patients with ductal carcinoma in situ treated with breast conserving surgery and radiotherapy were excellent. Close resection margin and boost irradiation to the primary tumor bed did not affect local relapse, but further follow-up with much more patients is needed.