• Asian Pacific Journal of Cancer Prevention
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• v.16 no.14
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• pp.5993-5999
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• 2015

Background: Molecular testing for human papillomavirus (HPV) is the most objective and reproducible of all cervical cancer screening tests and also less demanding in terms of training and quality assurance. However, there is an impending need for cost effective molecular HPV testing methods with sampling ease, easy storage measures and minimum turn around times suitable for a low resource setting. Objective : Our aim was to evaluate the feasibility of using a fast transfer analysis (FTA) mini elute cartridge for cervical sampling to identify high risk HPV by real time PCR and to compare molecular HPV testing and Pap cytology testing to predict histologically confirmed cervical precancer (CIN 2+ lesions) in a cervical cancer prevention program. Materials and Methods: This was conducted as a pilot study (n=200) on women sampled using FTA mini elute cartridges, genotyped by two different real time PCR assays, detecting 13 high risk HPV (HR HPV) species, including HPV16 along with its physical DNA status. Results obtained from each of the tests were compared and analysed using suitable statistical tests. Results: With FTA mini elute cartridge samples HR HPV positivity was seen in 48/200 (24%). Of these, presence of HPV 16 DNA was observed in 28/48 (58.3%) women. High risk HPV was positive in 20% (37/185) of women with benign cytology and 73.3% (11/15) of women with abnormal cytology findings. A very significant correlation (${\chi}^2=22.090$ ; p=0.000) was observed between cytology and HR HPV findings showing an increasing trend of HR HPV prevalence in 50% (1/2) of LSIL, 75% (3/4) of HSIL and 100% (3/3) of SCC. Of the CIN 2+ lesions identified by histopathology, 88.9% (8/9) had HR HPV. A significant association (${\chi}^2=11.223$ ; p=0.001) of HR HPV and histopathologically confirmed CIN 2+ lesions was found. Sensitivity of the two tests were comparable but specificity of Pap testing was better (90.7% vs 70.4%) to predict histopathologically diagnosed cervical precancers. Conclusions: The current study explored the feasibility of using a FTA mini elute cartridge for cervical sampling for the first time in India as a part of a community based cervical cancer prevention program. We suggest that FTA based sampling is suitable and feasible for real time based HPV testing. Molecular HR HPV testing can be more sensitive and useful to identify high risk women requiring Pap testing which is more specific to detect histologically confirmed cervical precancer.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.5
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• pp.2251-2255
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• 2014

Background: The aim of this study was to evaluate 10 years of false positive urine cytology records, along with follow-up histologic and cytologic data, to determine the significance of suspicious urine cytology findings. Materials and Methods: We retrospectively reviewed records of urine samples harvested between January 2002 and December 2012 from voided and catheterized urine from the bladder. Among the 21,283 urine samples obtained during this period, we located 1,090 eligible false positive findings for patients being evaluated for the purpose of confirming urothelial carcinoma (UC). These findings were divided into three categories: atypical, indeterminate, and suspicious of malignancy. Results: Of the 1,090 samples classified as false positive, 444 (40.7%) were categorized as atypical, 367 (33.7%) as indeterminate, and 279 (25.6%) as suspicious of malignancy. Patients with concomitant UC accounted for 105 (23.6%) of the atypical samples, 147 (40.1%) of the indeterminate samples, and 139 (49.8%) of the suspicious of malignancy samples (p<0.0001). The rate of subsequent diagnosis of UC during a 1-year follow-up period after harvesting of a sample with false positive urine cytology initially diagnosed as benign was significantly higher in the suspicious of malignancy category than in the other categories (p<0.001). The total numbers of UCs were 150 (33.8%) for atypical samples, 213 (58.0%) for indeterminate samples, and 199 (71.3%) for samples categorized as suspicious of malignancy. Conclusions: Urine cytology remains the most specific adjunctive method for the surveillance of UC. We demonstrated the clinical value of dividing false positive urine cytology findings into three categories, and our results may help clinicians better manage patients with suspicious findings.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.5
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• pp.1949-1953
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• 2014

Background: CA125 and HE4 are used in calculating Risk of Malignancy Algorithm (ROMA); and Risk of Malignancy Index (RMI). However, studies showed that normal levels of CA125, and HE4 differ among ethnicities such as between Asians and Caucasians, thus affecting the accuracy of the RMI score and ROMA in predicting ovarian malignancy. This study aimed to determine whether new or modified cutoff values for Ca125, HE4, the RMI score, and ROMA resulted in a better prediction of malignancy compared with the previous or standard ones. Materials and Methods: Serum level of CA125 and HE4 from 128 patients with diagnosis of ovarian tumor that had been collected before surgery at Cipto Mangunkusumo General Hospital (CMH) in Jakarta from November 2010 until May 2011 were reviewed and analysed. The standard cutoff values of these biomarkers, RMI, and ROMA were modified by using logistic regression model. The modified cutoff values were compared to the standard cutoff values in terms of sensitivity, specificity, and accuracy. Results: The modified cutoff value of CA125, HE4, RMI score and ROMA were 165.2 U/mL, 103.4 pM, 368.7, 28/54. The sensitivity and specificity of the modified cutoff values CA125, HE 4, RMI score and ROMA in differentiating benign from malignant and borderline were 67% and 75,4%; 73.1% and 85.2%; 73.1% and 80.3%; and 77.6% and 86.9%. While the sensitivity and specificity of the standard cutoff value of CA125; HE4; RMI score; and ROMA were 91% and 24.6%; 83.6% and 65%; 80.6% and 65.6%; and 91.0% and 42.6%. The accuracy of modified cutoff values compared with standard cutoff values were: 71.2% vs 59.3%, 78.9% vs 75% vs, 76.5% vs 73.4%, and 82% vs 67.9%. Conclusions: The new or modified cutoff values of Ca125, HE4, RMI score and ROMA resulted in higher accuracy compared to the previous or standard ones, at the cost of reduced sensitivity.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.13
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• pp.5355-5358
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• 2014

Background: To assess the role of sonographic endometrial thickness and hysteroscopic polyp size in predicting premalignant and malignant polyps in postmenopausal women. Materials and Methods: A total of 328 postmenopausal women with abnormal uterine bleeding and thickened endometrium underwent operative hysteroscopy due to detection of endometrial polyps were included in this retrospective study. Preoperative endometrial thickness measured by transvaginal ultrasonography and polyp size on hysteroscopy were noted. Hysteroscopic resection with histology was performed for endometrial polyps. Endometrial thickness and polyp size were evaluated on the basis of final diagnosis established by histologic examination. Receiver operator characteristic curves were calculated to assess the sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy of endometrial thickness and polyp size for detecting pemalignant and malignant polyps. Results: Premalignant and malignant polyps were identified in 26 (7.9%) of cases. Sonographic measurement showed a greater endometrial thickness in cases of premalignant and malignant polyps when compared to benign polyps. On surgical hysteroscopy, premalignant and malignant polyps were also larger. Endometrial thickness demonstrated a sensitivity of 53.8%, specificity of 85.8%, PPV of 24.6% and NPV of 95.6% at a cut-off limit of 11.5 mm with diagnostic accuracy of 83.2%. Polyp size has a diagnostic accuracy of 94.8% with a sensitivity of 92.3%, specificity of 95.0%, PPV of 61.5% and NPV of 99.3% at a cut-off point of 19.5mm. Conclusions: Endometrial thickness measured by transvaginal ultrasonography is not sufficient in predicting premalignant and malignant endometrial polyps in postmenopausal women with abnormal uterine bleeding and thickened endometrium. Polyp size on hysteroscopy is a more accurate parameter, because of better sensitivity and specificity. However, while polyp size ${\geq}19.5mm$ seems to have a great accuracy for predicting premalignancy and malignancy, histologic evaluation is still necessary to exclude premalignant and malignant polyps.

• Progress in Medical Physics
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• v.16 no.4
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• pp.183-191
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• 2005

The utilization of PET has been increased so fast since the usefulness of the PET has been proved in various clinical and research fields. Among the many applications, the PET Is especially useful in oncology and most of the clinical PET scans are peformed for the oncologic examination Including the different diagnosis of malignant and benign tumors and assessment of the treatment effects and recurrent tumors. As the PET-CT scanners are widely available, there is Increasing interest in the application of the PET Images to the radiation treatment planning. Although the CT images are conventionally used for the target volume determination in the radiation treatment planning, there are fundamental limitation In use of only the anatomical information. Therefore, the volume determination of the functionally active tumor region using the PET would be important for the treatment planning. However, the accurate determination of the tumor boundary is not simple in PET due to the relatively low spatial resolution of the currently available PET scanners. In this study, computer simulations were peformed to study the relationship between the lesion size, PET resolution, lesion to background ratio and the threshold of Image Intensity to determine the true tumor volume.

• Journal of Yeungnam Medical Science
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• v.15 no.1
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• pp.114-124
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• 1998

We analyzed the mammographic (n=21) findings (location, margin, shape, cluster microcalcifications, size, multiplicity) and ultrasonographic (n=12) findings (shape, border, internal echo, boundary echo, posterior echo, lateral echo, width/depth ratio) to evaluate specific radiologic findings of histopathologically proved uncommon breast cancer. The mammographic findings (n=21) are as follow; 1) single; 16, multiple; 5 2) margin (smooth; 13, irregular; 4, spiculated; 4) 3) shape (round and ovoid; 9, lobulated; 8, irregular; 4) 4) cluster micro calcifications (abscent; 20, present; 1) 5) size (1-3cm; 18, 3-5cm; 2, 5cm> ; 1) 6) location (UOQ; 13, UIQ; 4, LIQ; 3, LOQ; 1). The ultrasonographic findings (n=12) are as follow; 1) shape (round to oval; 5, lobulated; 5, irregular; 2) 2) border (smooth even; 9, rough uneven; 3) 3) internal echo (fine homogeneous; 5, coarse heterogeneous; 7) 4) boundary echo (regular fine; 4, irregular thick; 8) 5) posterior echo (enhanced; 11, no change; 1) 6) lateral echo (marked; 7, nonexistent; 5) 7) width/depth ratio (1.5> ; 1, 1.0-1.5; 7, 1.0< ; 4). Uncommon breast cancer show benign nature on mammogram, but malignant nature on ultrasonogram (especially boundary echo, internal echo, width/depth ratio).

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.2255-2258
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• 2016

Background: Awareness about prostate cancer has increased in the community, and prostate cancer screening examinations, including prostate specific antigen (PSA) assays, are now widely available. Prior to the PSA era, up to 27% of prostate cancers were detected incidentally at the time of transurethral resection of prostate (TURP). After PSA testing became widely available, the incidence of incidentally detected carcinoma prostate in TURP specimens without prior diagnosis reduced to 5-13%. However, the incidence of incidentally detected carcinoma prostate has been reported to vary across the globe since various factors can influence the identification of this malignancy in TURP specimens. In this paper, we focus on rates of incidentally detected prostate cancer in TURP specimens in our hospital and correlate it with various parameters. Materials and Methods: This retrospective study of histopathological findings of biopsy specimens was conducted for patients undergoing TURP during a period of 5 years from April 2010. The inclusion criteria were patients diagnosed with benign prostatic hyperplasia (BPH) (digital rectal examination (DRE) not showing any abnormally hard areas and normal age adjusted PSA values). Patients with elevated PSA, abnormal DRE, documented urinary tract infection and proved adenocarcinoma prostate (CaP) were excluded from the study. The total weight of prostatectomy specimen, occurrence of carcinoma prostate in the chips, percentage of total tissue resected showing malignancy and Gleason's scores were recorded. Results: A total of 597 patients belonging to the inclusion criteria were studied. The incidence of occult CaP in the study group was 5.2 % (31/597). Out of these, 8 belonged to T1a and 23 belonged to T1b stages. The age group 70 - 79 years had the maximum incidence of occult CaP. It was observed that the clinical grading of prostate did not have a bearing on the incidence of occult CaP whereas the weight of resected specimen correlated with the incidence of CaP. The incidence of occult CaP was greater with low volume prostates (<20 g). (P=0.15). Conclusions: The rate of incidentally detected adenocarcinoma prostate in patients undergoing TURP for clinically diagnosed BPH was found to be only 5.2 % in our study which is low when compared with similar studies done elsewhere. The age of the patient and weight of the resected specimen correlated with incidence of occult prostate cancer. The clinical grading of prostate by DRE however, demonstrated no correlation.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.1943-1948
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• 2012

Introduction: Prostate cancer in Indonesia is the $3^{rd}$ ranking cancer among males and the $5^{th}$ rank for their cancer mortality. Prognostic markers that can identify aggressive prostate cancer in early stages and help select appropriate therapy to finally reduce the mortality are therefore urgently needed. It has been suggested that stem cells in the prostate gland have a role in initiation, progression, and metastasis of cancer, although controversy continues to exist. Maintenance of normal stem cell or reserve cell populations in several epithelia including prostate has been shown to be regulated by p63 and alteration of p63 expression is considered to have an oncogenic role in prostate cancer. We hypothesize that the expression of cytoplasmic aberrance of p63 is associated with high ALDH1A1 expression as a cancer stem cell marker, thus leading to progression of prostate cancer. Methods: Using a cross-sectional study during two years (2009-2010), a total of 79 paraffin embedded tissues of benign prostatic hyperplasia, PIN prostatic intraepithelial neoplasia, low and high Gleason score prostate cancer were investigated using immunohistochemistry. Associations between cytoplasmic p63 and ALDH1A1, as well as with pathological diagnosis, were analyzed by Chi-Square test using SPSS 15.0. Links of both markers with cell proliferation rate (KI-67) and apoptotic rate (cleaved caspase 3) were also analyzed by Kruskal-Wallis test. Results: The mean age of patient at the diagnosis is 70.0 years. Cytoplasmic aberrance of p63 was associated with ALDH1A1 expression (p<0.001) and both were found to have significant relationships with pathological diagnosis (including Gleason score), (p=0.006 and p<0.001 respectively). Moreover, it was also found that higher levels of cytoplasmic p63 were significantly associated with the frequency of proliferating cells and cells undergoing apoptosis in prostate cancers (p=0.001 and p=0.016 respectively). Conclusion: p63 cytoplasmic aberrance is associated with high ALDH1A1 expression. These components are suggested to have an important role in prostate cancer progression and may be used as molecular markers.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.2835-2838
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• 2013

Background: Prostate cancer features a substantial incidence and mortality burden, similarly to breast cancer, and it ranks among the top ten specific causes of death in males. Objective: To explore the situation of prostate cancer in a healthy population cohort in Eastern Nepal. Materials and Methods: This study was conducted in the Department of General Surgery at B. P. Koirala Institute of Health Sciences, Dharan, Nepal from July 2010 to June 2011. Males above 50 years visiting the Surgical Outpatient Department in BPKIHS were enrolled in the study and screening camps were organized in four Teaching District Hospitals of BPKIHS, all in Eastern Nepal. Digital rectal examination (DRE) was conducted by trained professionals after collecting blood for assessment of serum prostatic specific antigen (PSA). Trucut biopsies were performed for all individuals with abnormal PSA/DRE findings. Results: A total of 1,521 males more than 50 years of age were assessed and screened after meeting the inclusion criteria. The vast majority of individuals, 1,452 (96.2%), had PSA ${\leq}4.0$ ng/ml. Abnormal PSA (>4 ng/ml) was found in 58 (3.8%). Abnormal DRE was found in 26 (1.72%). DRE and PSA were both abnormal in 26 (1.72%) individuals. On the basis of raised PSA or abnormal DRE 58 (3.84%) individuals were subjected to digitally guided trucut biopsy. Biopsy report revealed benign prostatic hyperplasia in 47 (3.11%) and adenocarcinoma prostate in 11 (0.73%). The specificity of DRE was 66.0%with a sensitivity of 90.9% and a positive predictive value of 38.5%. The sensitivity of PSA more than 4ng/ml in detecting carcinoma prostate was 100% and the positive predictive value for serum PSA was 19.0% Conclusions: The overall cancer detection rate in this study was 0.73% and those detected were locally advanced. Larger community-based studies are highly warranted specially among high-risk groups.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.7
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• pp.3437-3445
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• 2016

Background: There is an increasing concern in the role of microRNA (miRNA) in the pathogenesis of bone metastasis (BM) secondary to prostate cancer (CaP). In this exploratory study, we hypothesized that the expression of vinculin (VCL) and chemokine X3C ligand 1 (CX3CL1) might be down-regulated in clinical samples, most likely due to the post-transcriptional modification by microRNAs. Targeted genes would be up-regulated upon transfection of the bone metastatic prostate cancer cell line, PC3, with specific microRNA inhibitors. Materials and Methods: MicroRNA software predicted that miR-21 targets VCL while miR-29a targets CX3CL1. Twenty benign prostatic hyperplasia (BPH) and 16 high grade CaP formalin-fixed paraffin embedded (FFPE) specimens were analysed. From the bone scan results, high grade CaP samples were further classified into CaP with no BM and CaP with BM. Transient transfection with respective microRNA inhibitors was done in both RWPE-1 (normal) and PC3 cell lines. QPCR was performed in all FFPE samples and transfected cell lines to measure VCL and CX3CL1 levels. Results: QPCR confirmed that VCL messenger RNA (mRNA) was significantly down-regulated while CX3CL1 was up-regulated in all FFPE specimens. Transient transfection with microRNA inhibitors in PC3 cells followed by qPCR of the targeted genes showed that VCL mRNA was significantly upregulated while CX3CL1 mRNA was significantly down-regulated compared to the RWPE-1 case. Conclusions: The down-regulation of VCL in FFPE specimens is most likely regulated by miR-21 based on the in vitro evidence but the exact mechanism of how miR-21 can regulate VCL is unclear. Up-regulated in CaP, CX3CL1 was found not regulated by miR-29a. More microRNA screening is required to understand the regulation of this chemokine in CaP with bone metastasis. Understanding miRNA-mRNA interactions may provide additional knowledge for individualized study of cancers.