• Title/Summary/Keyword: Invasive carcinoma

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The genomic landscape associated with resistance to aromatase inhibitors in breast cancer

  • Kirithika Sadasivam;Jeevitha Priya Manoharan;Hema Palanisamy;Subramanian Vidyalakshmi
    • Genomics & Informatics
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    • v.21 no.2
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    • pp.20.1-20.10
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    • 2023
  • Aromatase inhibitors (AI) are drugs that are widely used in treating estrogen receptor (ER)-positive breast cancer patients. Drug resistance is a major obstacle to aromatase inhibition therapy. There are diverse reasons behind acquired AI resistance. This study aims at identifying the plausible cause of acquired AI resistance in patients administered with non-steroidal AIs (anastrozole and letrozole). We used genomic, transcriptomic, epigenetic, and mutation data of breast invasive carcinoma from The Cancer Genomic Atlas database. The data was then separated into sensitive and resistant sets based on patients' responsiveness to the non-steroidal AIs. A sensitive set of 150 patients and a resistant set of 172 patients were included for the study. These data were collectively analyzed to probe into the factors that might be responsible for AI resistance. We identified 17 differentially regulated genes (DEGs) among the two groups. Then, methylation, mutation, miRNA, copy number variation, and pathway analyses were performed for these DEGs. The top mutated genes (FGFR3, CDKN2A, RNF208, MAPK4, MAPK15, HSD3B1, CRYBB2, CDC20B, TP53TG5, and MAPK8IP3) were predicted. We also identified a key miRNA - hsa-mir-1264 regulating the expression of CDC20B. Pathway analysis revealed HSD3B1 to be involved in estrogen biosynthesis. This study reveals the involvement of key genes that might be associated with the development of AI resistance in ER-positive breast cancers and hence may act as a potential prognostic and diagnostic biomarker for these patients.

The Prognostic Value of Oligo-Recurrence Following Esophagectomy for Esophageal Cancer

  • Minsang Kang;Woojung Kim;Chang Hyun Kang;Kwon Joong Na;Samina Park;Hyun Joo Lee;In Kyu Park;Young Tae Kim
    • Journal of Chest Surgery
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    • v.56 no.6
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    • pp.403-411
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    • 2023
  • Background: The concept of oligo-recurrence has not been generally applied in esophageal cancer. This study aimed to determine the prognostic significance of the number of recurrences in esophageal cancer. Methods: Patients with squamous cell carcinoma who underwent curative esophagectomy with R0 or R1 resection and who experienced a confirmed recurrence were included. The study included 321 eligible participants from March 2001 to December 2019. The relationship between the number of recurrences and post-recurrence survival was investigated. Results: The mean age was 63.8±8.1 years, and the majority of the participants (97.5%) were men. The median time to recurrence was 10.7 months, and the median survival time after recurrence was 8.8 months. Multiple recurrences with simultaneous local, regional, and distant locations were common (38%). In terms of the number of recurrences, single recurrences were the most common (38.3%) and had the best post-recurrence survival rate (median, 17.1 months; p<0.001). Patients with 2 or 3 recurrences showed equivalent survival to each other and longer survival than those with 4 or more (median, 9.4 months; p<0.001). In the multivariable analysis, the significant predictors of post-recurrence survival were body mass index, minimally invasive esophagectomy, N stage, R0 resection, post-recurrence treatment, and the number of recurrences (p<0.05). Conclusion: After esophagectomy, the number of recurrences was the most significant risk factor influencing post-recurrence survival in patients with esophageal cancer. In esophageal cancer, oligo-recurrence can be defined as a recurrence with three or fewer metastases. More intensive treatment might be recommended if oligo-recurrence occurs.

Inhibition of Adrenergic Agonists-induced Metastatic Ability of Liver Cancer Cells by Ethanol Extract of Premature Citrus Unshiu Peel (청피 에탄올 추출물이 스트레스성 카테콜아민으로 유도한 간암세포의 전이를 억제하는 효과 및 기전 연구)

  • Shin-Hyung Park
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.38 no.1
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    • pp.10-15
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    • 2024
  • Previous studies have highlighted the pivotal role of the β-adrenergic receptor (β-AR) signaling pathway in stimulating cancer metastasis induced by chronic stress. According to the theory of traditional Korean medicine, chronic stress can induce Qi stagnation. Based on the traditional role of premature citrus unshiu peel in moving Qi, we hypothesized that an ethanol extract of premature citrus unshiu peel (EPCU) can attenuate chronic stress-induced cancer progression. In this study, we investigated the potential role of EPCU on modulating the adrenergic agonists-induced metastatic properties of liver cancer cells. Our findings revealed that adrenergic agonists, including norepinephrine (NE), epinephrine (E), and isoproterenol (ISO), augmented the migratory capacity of Hep3B human hepatocellular carcinoma cells, which was completely abrogated by EPCU treatment in a concentration-dependent manner. Consistently, EPCU inhibited the E-induced invasive property of Hep3B cells in a dose-dependent manner. These results suggest that EPCU efficiently attenuates adrenergic agonists-induced metastatic abilities of liver cancer cells. As a molecular mechanism, EPF suppressed the phosphorylation of major components of β-AR signaling pathway, including Src, signal transducer and activator of transcription 3 (STAT3) and ERK, induced by E treatment. Taken together, our results demonstrate that EPCU impedes the adrenergic agonists-driven metastatic potential of cancer cells by inhibiting β-AR signaling pathway. This study provides basic evidence supporting the probable use of premature citrus unshiu peel to prevent metastasis in liver cancer patients under chronic stress.

Human in-vivo 31P MR Spectroscopy of Benign and Malignant Breast Tumors

  • Jeong Mi Park;Jae Hyung Park
    • Korean Journal of Radiology
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    • v.2 no.2
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    • pp.80-86
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    • 2001
  • Objective: To assess the potential clinical utility of in-vivo 31P magnetic resonance spectroscopy (MRS) in patients with various malignant and benign breast lesions. Materials and Methods: Seventeen patients with untreated primary malignant breast lesions (group I), eight patients with untreated benign breast lesions (group II) and seven normal breasts (group III) were included in this study. In-vivo 31P MRS was performed using a 1.5 Tesla MR scanner. Because of the characteristics of the coil, the volume of the tumor had to exceed 12 cc (3×2×2 cm), with a superoinferior diameter at least 3 cm. Mean and standard deviations of each metabolite were calculated and metabolite ratios, such as PME/PCr, PDE/PCr, T-ATP/PCr and PCr/T-ATP were calculated and statistically analyzed. Results: Significant differences in PME were noted between groups I and III (p=0.0213), and between groups II and III (p=0.0213). The metabolite ratios which showed significant differences were PME/PCr (between groups II and III) (p=0.0201), PDE/PCr (between groups I and III, and between groups II and III) (p=0.0172), T-ATP/PCr (between groups II and III) (p=0.0287), and PCr/T-ATP (between groups II and III) (p=0.0287). There were no significant parameters between groups I and II. Conclusion: In-vivo 31P MRS is not helpful for establishing a differential diagnosis between benign and malignant breast lesions, at least with relatively large lesions greater than 3 cm in one or more dimensions.

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What are the Appropriate Surgery and Postoperative Surveillance for Intraductal Papillary Mucinous Neoplasm?

  • Ideno, Noboru;Nakata, Kohei;Nakamura, Masafumi
    • Journal of Digestive Cancer Research
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    • v.9 no.1
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    • pp.8-18
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    • 2021
  • Although many guidelines for pancreatic cystic neoplasms focus on the management of intraductal papillary mucinous neoplasm of the pancreas (IPMN) at the highest oncological risk, there are many issues that surgeons need to consider at the time to plan the surgical procedures based on characteristics of IPMN subtypes, such as multiplicity of branch duct-IPMN (BD-IPMN) and intraductal spreading of main duct-IPMN (MD-IPMN). For multifocal BD-IPMN, partial pancreatectomy would be selected to remove BD-IPMN with predictors of malignancy, while the other lesions without risk factors can be left, although total pancreatectomy might be considered if the patients have a strong family history of pancreatic cancer. Partial pancreatectomy would be also adequate procedure for MD-IPMN if negative surgical margin for high-grade dysplasia or invasive carcinoma were achieved. It has become to be well-known that patients with BD-IPMN are at increased risk for developing not only IPMN-associated pancreatic ductal adenocarcinoma (PDAC) but also PDAC independent from the IPMN. Hence, the detection of a concomitant PDAC is also an important focus for strategies after resection of BD-IPMNs. Our recent analysis of patients after partial pancreatectomy for MD-IPMN with negative surgical margin identified an unexpected recurrence pattern, which we called "monoclonal skip" recurrence. MD-IPMN seems to be disseminated in the pancreatic ductal systems and MD-IPMN with identical genetic background was detected in the remnant pancreas even in a long time after index surgery. We proposed strategies of postoperative surveillance based on characteristics and natural history of each morphological subtype.

Assessment of risks for breast cancer in a flight attendant exposed to night shift work and cosmic ionizing radiation: a case report

  • Dong Joon Park;Sungkyun Park;Seong Won Ma;Hoekyeong Seo;Sang Gil Lee;Kyung-Eun Lee
    • Annals of Occupational and Environmental Medicine
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    • v.34
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    • pp.5.1-5.10
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    • 2022
  • Background: Some epidemiological studies have estimated exposure among flight attendants with and without breast cancer. However, it is difficult to find a quantitative evaluation of occupational exposure factors related to cancer development individually in the case of breast cancer in flight attendants. That is, most, if not all, epidemiological studies of breast cancer in flight attendants with quantitative exposure estimates have estimated exposure in the absence of individual flight history data. Case presentation: A 41-year-old woman visited the hospital due to a left breast mass after a regular check-up. Breast cancer was suspected on ultrasonography. Following core biopsy, she underwent various imaging modalities. She was diagnosed invasive ductal carcinoma of no special type (estrogen receptor positive in 90%, progesterone receptor positive in 3%, human epidermal growth factor receptor 2/neu equivocal) with histologic grade 3 and nuclear grade 3 in the left breast. Neoadjuvant chemotherapy was administered to reduce the tumor size before surgery. However, due to serious chemotherapy side effects, the patient opted for alternative and integrative therapies. She joined the airline in January, 1996. Out of all flights, international flights and night flights accounted for 94.9% and 26.2, respectively. Night flights were conducted at least four times per month. Moreover, based on the virtual computer program CARI-6M, the estimated dose of cosmic radiation exposure was 78.81 mSv. There were no other personal triggers or family history of breast cancer. Conclusions: This case report shows that the potentially causal relationship between occupational harmful factors and the incidence of breast cancer may become more pronounced when night shift workers who work continuously are exposed to cosmic ionizing radiation. Therefore, close attention and efforts are needed to adjust night shift work schedules and regulate cosmic ionizing radiation exposure.

Results of Radiation Therapy for Carcinoma of the Uterine Cervix (자궁경부암의 방사선치료 성적)

  • Lee Kyung-Ja
    • Radiation Oncology Journal
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    • v.13 no.4
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    • pp.359-368
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    • 1995
  • Purpose : This is a retrospective analysis for pattern of failure, survival rate and prognostic factors of 114 patients with histologically proven invasive cancer of the uterine cervix treated with definitive irradiation. Materials and Methods : One hundred fourteen patients with invasive carcinoma of the cervix were treated with a combination of intracavitary irradiation using Fletcher-Suit applicator and external beam irradiation by 6MV X-ray at the Ewha Womans University Hospital between March 1982 and Mar 1990. The median age was 53 years(range:30-77 years). FIGO stage distribution was 19 for IB, 23 for IIA, 42 for IIB, 12 for IIIA and 18 for IIIB. Summation dose of external beam and intracavitary irradiation to point A was 80-90 Gy(median:8580 cGy) in early stage(IB-IIA) and 85-100 Gy(median:8850 cGy) in advanced stage(IIB-IIIB). Kaplan-Meier method was used to estimate the survival rate and multivariate analysis for progrostic factors was performed using the Log likelihood for Weibull Results : The pelvic failure rates by stage were $10.5{\%}$ for IB. $8.7{\%}$ for IIA, $23.8{\%}$ for IIB, $50.0{\%}$ for IIIA and $38.9{\%}$ for IIIB. The rate of distant metastasis by stage were $0{\%}$ for IB, $8.7{\%}$ for IIA, $4.8{\%}$ for IIB. $0{\%}$ for IIIA and $11.1{\%}$ for IIIB. The time of failure was from 3 to 50 months and with median of 15 months after completion of radiation therapy. There was no significant coorelation between dose to point A($\leq$90 Gy vs >90 Gy) and pelvic tumor control(P>0.05). Incidence rates of grade 2 rectal and bladder complications were $3.5{\%}$(4/114) and $7{\%}$(8/114), respectively and 1 patient had sigmoid colon obstruction and 1 patient had severe cystitis. Overall 5-year survival rate was $70.5{\%}$ and disease-free survival rate was $53.6{\%}$. Overall 5-year survival rate by stage was $100{\%}$ for IB, $76.9{\%}$ for IIA, $77.6{\%}$ for IIB $87.5{\%}$ for IIIA and $69.1{\%}$ for IIIB. Five-rear disease-free survival rate by stage was $81.3{\%}$ for IB, $67.9{\%}$ for IIA, $46.8{\%}$ for IIB, $45.4{\%}$ for IIIA and $34.4{\%}$ for IIIB. The prognostic factors for disease-free survival rate by multivariate analysis was performance status(p= 0.0063) and response rate after completion of radiation therapy(p= 0.0026) but stage, age and radiation dose to point A were not siginificant. Conclusion : The result of radiation therapy for early stage of the uterine cervix cancer was relatively good but local control rate and survival rate in advanced stage were poor inspite of high dose irradiation to point A above 90 Gy. Prospective randomized studies are recommended to establish optimal tumor doses for various stages and volume of carcinoma of uterine cervix, And ajuvant chemotherapy or radiation-sensitizing agents must be considered to increase the pelvic control and survival rate in advanced cancer of uterine cervix.

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A Method to Quantify Breast MRI for Predicting Tumor Invasion in Patients with Preoperative Biopsy- Proven Ductal Carcinoma in Situ (DCIS) (유방 자기공명영상법을 이용한 수술 전 관상피내암으로 진단된 환자의 침윤성 유방암을 예측하는 정량적 분석법)

  • Ko, Myung-Su;Kim, Sung Hun;Kang, Bong Joo;Choi, Byung Gil;Song, Byung Joo;Cha, Eun Suk;Kiraly, Atilla Peter;Kim, In Seong
    • Investigative Magnetic Resonance Imaging
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    • v.17 no.2
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    • pp.73-82
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    • 2013
  • Purpose : To determine the quantitative parameters of breast MRI that predict tumor invasion in biopsy-proven DCIS. Materials and Methods: From January 2009 to March 2010, 42 MRI examinations of 41 patients with biopsy-proven DCIS were included. The quantitative parameters, which include the initial percentage enhancement ($E_1$), peak percentage enhancement ($E_{peak}$), time to peak enhancement (TTP), signal enhancement ratio (SER), arterial enhancement fraction (AEF), apparent diffusion coefficient (ADC) value, long diameter and the volume of the lesion, were calculated as parameters that might predict invasion. Univariate and multivariate analyses were used to identify the parameters associated with invasion. Results: Out of 42 lesions, 23 lesions were confirmed to be invasive ductal carcinoma (IDC) and 19 lesions were confirmed to be pure DCIS. Tumor size (p = 0.003; $6.5{\pm}3.2$ cm vs. $3.6{\pm}2.6$ cm, respectively) and SER (p = 0.036; $1.1{\pm}0.3$ vs. $0.9{\pm}0.3$, respectively) showed statistically significant high in IDC. In contrast, E1, Epeak, TTP, ADC, AEF and volume of the lesion were not statistically significant. Tumor size and SER had statistically significant associations with invasion, with an odds ratio of 1.04 and 22.93, respectively. Conclusion: Of quantitative parameters analyzed, SER and the long diameter of the lesion could be specific parameter for predicting invasion in the biopsy-proven DCIS.

A Study For Optimizing Input Waveforms In Radiofrequency Liver Tumor Ablation Using Finite Element Analysis (유한 요소 해석을 이용한 고주파 간 종양 절제술의 입력 파형 최적화를 위한 연구)

  • Lim, Do-Hyung;NamGung, Bum-Seok;Lee, Tae-Woo;Choi, Jin-Seung;Tack, Gye-Rae;Kim, Han-Sung
    • Journal of Biomedical Engineering Research
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    • v.28 no.2
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    • pp.235-243
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    • 2007
  • Hepatocellular carcinoma is significant worldwide public health problem with an estimated annually mortality of 1,000,000 people. Radiofrequency (RF) ablation is an interventional technique that in recent years has come to be used for treatment of the hepatocellualr carcinoma, by destructing tumor tissues in high temperatures. Numerous studies have been attempted to prove excellence of RF ablation and to improve its efficiency by various methods. However, the attempts are sometimes paradox to advantages of a minimum invasive characteristic and an operative simplicity in RF ablation. The aim of the current study is, therefore, to suggest an improved RF ablation technique by identifying an optimum RF pattern, which is one of important factors capable of controlling the extent of high temperature region in lossless of the advantages of RF ablation. Three-dimensional finite element (FE) model was developed and validated comparing with the results reported by literature. Four representative Rf patterns (sine, square, exponential, and simulated RF waves), which were corresponding to currents fed during simulated RF ablation, were investigated. Following parameters for each RF pattern were analyzed to identify which is the most optimum in eliminating effectively tumor tissues. 1) maximum temperature, 2) a degree of alteration of maximum temperature in a constant time range (30-40 second), 3) a domain of temperature over $47^{\circ}C$ isothermal temperature (IT), and 4) a domain inducing over 63% cell damage. Here, heat transfer characteristics within the tissues were determined by Bioheat Governing Equation. Developed FE model showed 90-95% accuracy approximately in prediction of maximum temperature and domain of interests achieved during RF ablation. Maximum temperatures for sine, square, exponential, and simulated RF waves were $69.0^{\circ}C,\;66.9^{\circ}C,\;65.4^{\circ}C,\;and\;51.8^{\circ}C$, respectively. While the maximum temperatures were decreased in the constant time range, average time intervals for sine, square, exponential, and simulated RE waves were $0.49{\pm}0.14,\;1.00{\pm}0.00,\;1.65{\pm}0.02,\;and\;1.66{\pm}0.02$ seconds, respectively. Average magnitudes of the decreased maximum temperatures in the time range were $0.45{\pm}0.15^{\circ}C$ for sine wave, $1.93{\pm}0.02^{\circ}C$ for square wave, $2.94{\pm}0.05^{\circ}C$ for exponential wave, and $1.53{\pm}0.06^{\circ}C$ for simulated RF wave. Volumes of temperature domain over $47^{\circ}C$ IT for sine, square, exponential, and simulated RF waves were 1480mm3, 1440mm3, 1380mm3, and 395mm3, respectively. Volumes inducing over 63% cell damage for sine, square, exponential, and simulated RF waves were 114mm3, 62mm3, 17mm3, and 0mm3, respectively. These results support that applying sine wave during RF ablation may be generally the most optimum in destructing effectively tumor tissues, compared with other RF patterns.

Usefulness of the $UBC^{TM}$ (Urinary Bladder Cancer) Test Compared to Urinary Cytology for Transitional Cell Carcinoma of the Bladder in Patients with Hematuria (혈뇨 환자의 방광암 진단에서 $UBC^{TM}$ (Urinary Bladder Cancer) 검사의 유용성)

  • Gil, Myung-Cheol;Kang, Do-Young;Seong, Youl-Koon;Jung, Se-Il;Kwon, Hyon-Young;Jung, Gyung-Woo;Kim, Duk-Kyu;Roh, Mee-Sook;Hwang, Tae-Ho;Yoon, Jin-Han
    • The Korean Journal of Nuclear Medicine
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    • v.35 no.3
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    • pp.192-197
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    • 2001
  • Purpose: Urinary cytology and cystoscopic exam are effective methods for diagnosis of transitional cell carcinoma(TCC). But the former shows drawbacks such as the need for a well-trained examiner, and wide imprecision related to the variability of microscopic exam; the latter is an invasive method. $UBC^{TM}$ test detects the epitope on specific cytokeratin fragments released from epithelium of bladder cancer by immunoradiometric assay. We compared $UBC^{TM}$ test with urinary cytology for diagnosis of TCC to evaluate the utility of $UBC^{TM}$ test. Materials and Methods: Eighty-four patients with hematuria were included in our study. $UBC^{TM}$ tests (IDL Biotech, Sweden) were assayed in mid-stream urine according to the ordinary assay protocol. Nineteen patients were confirmed as TCC by cystoscopic examination and underwent transurethral resection (Group A). Other patients had various benign urinary tract conditions (Group B). Samples were considered positive as the $UBC^{TM}$ concentration was greater than $12{\mu}g/L$. Results: $UBC^{TM}$ levels were significantly different between group A ($95.9{\pm}166.4\;{\mu}g/L$) and group B ($19.2{\pm}85.6{\mu}g/L$) (P<0.001). Sensitivity for diagnosis of TCC was 89.5% (17/19) in UBC test and 47.4% (9/19) in cytology (p<0.05). Specificity for diagnosis of TCC was 81.5% (53/65) in $UBC^{TM}$ test and 100% (65/65) in cytology. $UBC^{TM}$ test was significantly more sensitive in stage Ta, $T_1$ tumors (84.6 vs 38.5%, p<0.05) and in grade I (83.3% vs 16.7%, p<0.05) than cytology. $UBC^{TM}$ test showed a tendency to be more sensitive as the grade was higher (83.3% in Grade I, 90% in Grade II and 100% in Grade III). Conclusion: $UBC^{TM}$ test could be a useful method in distinguishing TCC from other benign genitourinary diseases. Moreover, $UBC^{TM}$ test could be an especially valuable marker for diagnosis of TCC in patients with early TCC of low grade TCC compared to urinary cytology. Therefore, mbined use of $UBC^{TM}$ test in association with cytology is helpful to overcome the limited sensitivity of cytology.

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