Background: Cholangiocarcinoma (CHCA) is serious public health problem in Thailand, especially in the northeastern and northern regions. CHCA is known as one of the most aggressive malignant tumors associated with local invasion and a high rate of metastasis. A crucial step in the invasion process is the proteolytic degradation of the extracellular matrix (ECM) and basal membranes, for which several studies have shown a critical role played by matrix metalloproteinase-11 (MMP-11). Objective: This study aim to detect MMP-11 expression in CHCA specimens and any correlation with survival time. Materials and Methods: A retrospective analysis was conducted of 30 patients with CHCA in Rajvithi hospital, who had undergone immunohistochemical staining of MMP-11. Relationships between clinicopathological data and MMP-11 expression in CHCA specimens were analyzed by the ${\chi}^2$ test or Fisher's exact test. The estimated survival and the survival differences were analyzed by the Kaplan-Meier method and the log-rank test, respectively. Results: MMP-11 expression was found in 15 specimens (50%). The overall mean survival time is 237.0 days (95% CI 135.4-338.5, SD 271.9). Specimens with a positive MMP-11 had an average survival time of 136.7 days (95%CI 50.3-223.1, SD 156.0). Survival differences was signficant for the positive and negative MMP-11(p=0.022), but not well differentiated tumor and moderate to poor differentiated tumor (p=0.755), CA19-9 level of >1,000 and <1,000 (p=0.488), and between advanced and non-advanced staging (p=0.388). Conclusions: The positive MMP-11 expression indicates poor prognosis in CHCA specimens.
Cholangiocarcinoma (CCA) is the bile duct cancer which constitutes one of the important public health problems in Thailand with high mortality rate, especially in the Opisthorchis viverrini (a parasite risk factor for CCA) endemic area of the northeastern region of the country. This study aimed to identify potential biomarkers from the plasma peptidome by CCA patients. Peptides were isolated using 10 kDa cut-off filter column and the flow-through was then used as a peptidome for LC-MS/MS analysis. A total of 209 peptides were obtained. Among these, 15 peptides were concerned with signaling pathways and 12 related to metabolic, regulatory, and biosynthesis of secondary metabolite pathways. Five exclusive peptides were identified as potential biomarkers, i.e. ETS domain-containing transcription factor ERF (P50548), KIAA0220 (Q92617), phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform 1 (P42338), LP2209 (Q6XYC0), and casein kinase II subunit alpha (P19784). Three of these biomarkers are signaling related molecules. A combination of these biomarkers for CCA diagnosis is proposed.
Background: The aim of this study was to analyze the patterns of relapse and survival outcomes in Northern Thai women with recurrent endometrial cancer (EC). Materials and Methods: Medical records were abstracted from EC patients who underwent primary surgery from 1999 to 2012. Data on clinicopathologic variables, sites of first recurrence, time to relapse of disease, and overall survival (OS) was analyzed. Associations between the clinicopathological variables and the rates of disease recurrence were determined. Results: Among 1,204 reviewed records, 42 eligible patients were identified with recurrent disease. The median age was 55 years and the median follow-up time was 26.0 months. The median times to recurrence (TTR) after completion of the initial treatment in the group of local relapse (LR) and distant/combined sites of recurrence (DCSR) was 6.6 (95% CI=4.6 to 8.6 months) and 16.9 months (95% CI=5.6 to 28.2 months), respectively (p=0.36). The 2-year survival and 3-year survival probability in the group of LR was 54.2% (95% CI=27.2 to 81.3%) and 34.7% (95% CI=9.2 to 60.2%), compared to 50.4% (95% CI=41.1 to 59.7%) and 42.1% (95%CI= 24.1 to 60.1%) for those with DCSR. Distant recurrence was the most frequent pattern of relapse. Overall survival was not significantly different in patients with local relapse when compared to those with DCSR (p=0.69). Conclusions: Patients with recurrence of EC after primary treatment had a worse prognosis and clinical aggressiveness. LR and DCSR occurred most during the first three years. The common sites of relapses were vaginal cuff, pelvis, and lungs. No significant clinicopathological predictor for survival outcomes was identified.
MicroRNAs directly and indirectly influence many biological processes such as apoptosis, cell maintenance, and immune responses, impacting on tumor genesis and metastasis. They modulate gene expression at the posttranscriptional level and are associated with progression of liver disease. Hepatocellular carcinoma (HCC) is a cancer which mostly occurs in males. There are many factors affect HCC development, for example, hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV), co-infection, environmental factors including alcohol, aflatoxin consumption and host-related factors such as age, gender immune response, microRNA and single nucleotide polymorphisms (SNPs). Chronic infection with the hepatitis B virus is the major factor leading to HCC progression since it causes the liver injury. At present, there are many reports regarding the association of SNPs on miRNAs and the HCC progression. In this research, we investigated the role of miR-149 (rs2292832) and miR-101-1 (rs7536540) with HCC progression in Thai population. The study included 289 Thai subjects including 104 HCC patients, 90 patients with chronic hepatitis B virus infection (CHB) and 95 healthy control subjects. The allele and genotype of rs2292832 and rs7536540 polymorphisms were determined by TaqMan real-time PCR assay. Our results revealed no significant association between miR-149 (rs2292832) and miR-101-1 (rs7536540) and the risk of HCC in our Thai population. However, this research is the first study of miR-149 (rs2292832) and miR-101-1 (rs7536540) in HCC in Thai populations and the results need to be confirmed with a larger population.
Opisthorchis viverrini (OV)-induced cholangiocarcinoma (CCA) is an important cancer in the Great Mekong region, particularly in Thailand. Limitations of treatment options and the lack of an effective diagnostic tool for early detection of CCA are major concerns for the control of this type of cancer. The aim of the study was to investigate anti-CCA activity of the ethanolic extract of Atractylodes lancea (Thunb.) DC., and the applicability of positron emission tomography-computed tomography (PET-CT) as a tool for detection and monitoring the progression of CCA in Opisthorchis viverrini (OV)/dimethylnitrosamine (DMN)-induced CCA hamsters. Male Syrian hamsters were used for toxicity tests and anti-CCA activity evaluation. Development of CCA was induced by initial feeding of 50 metacercariae of OV, followed by drinking water containing 12.5 ppm of DMN in hamsters. The ethanolic extract of A. lancea (Thunb.) DC. was administered orally for 30 days. PET-CT was performed every 4 weeks after initiation of CCA using 18F-fluorodeoxyglucose ($^{18}F-FDG$). Results from the present study suggest that the ethanolic extract of A. lancea (Thunb.) DC. rhizome exhibited promising anti-CCA activity and safety profile in the OV/DMN-induced hamster model. To successfully apply PET-CT as a tool for early detection of tumor development and progression, modification of radiolabeling approach is required to improve its specificity for CCA cells.
Purpose: The incidence of colorectal cancer (CRC) has been increasing in Asian countries including Thailand. Double contrast barium enema (DCBE) is one of the investigation tools used in CRC screening. This study aimed to determine the incidence of colorectal neoplasm detected at screening by DCBE in Thai people. Methods: The computerized radiology database of screening DCBE in Thai adults between June 2009 and October 2011 at the Faculty of Medicine, Siriraj Hospital, was reviewed. DCBE examination performed in a surveillance program after curative CRC resection or the removal of colorectal polyps was also considered as a screening DCBE. Results: A total of 819 screening DCBEs performed during this 28-month period were analyzed. The mean age of patients was $59.8{\pm}13.6$ years. Of the total, 467 (57%) were male. A family history of CRC and a previous history of curative CRC resection or polyp removal were noted in 34 patients (4%) and 124 patients (15%), respectively. A total of 31 patients (3.8%; 95%CI = 2.7%-5.3%) were reported to have colorectal polyp or mass demonstrated on DCBE. Of these, follow-up endoscopy was performed in 20 cases (65%). According to pathological results, the incidence of advanced adenoma and CRC detected at screening DCBE was 0.7% (95%CI = 0.3%-1.6%; n=6) and 0.4% (95%CI = 0.1%-1.1%; n=3), respectively. Conclusions: The screening DCBE performed in Thai adults had a diagnostic yield of 0.7% for advanced adenoma and 0.4% for CRC.
Intestinal parasitic infections (IPIs) are still important to the health of Thai rural residents. IPIs are the cause of many chronic diseases with, for example, opisthorchiasis resulting in progression to cholangiocarcinoma (CCA). This cross-sectional study in a prospective cohort study aimed to examine the prevalence and co-infection of intestinal parasites among Northeastern Thai rural residents, recruited into the Khon Kaen Cohort Study (KKCS), and who were residing in areas of high-risk for developing CCA. On recruitment, subjects had completed questionnaires and provided fecal samples for IPI testing using the formalin ethyl acetate concentration technique. Data on selected general characteristics and the results of the fecal tests were analysed. IPI test results were available for 18,900 of cohort subjects, and 38.50% were found to be positive for one or more types of intestinal parasite. The prevalence of Opisthorchis viverrini (O. viverrini) infection was the highest (45.7%), followed by intestinal flukes (31.9%), intestinal nematodes (17.7%), intestinal protozoa (3.02%), and intestinal cestodes (1.69%). The pattern of different infections was similar in all age groups. According to a mapping analysis, a higher CCA burden was correlated with a higher prevalence of O. viverrini and intestinal flukes and a greater intensity of O. viverrini. Both prevention and control programs against liver fluke and other intestinal parasites are needed and should be delivered simultaneously. We can anticipate that the design of future control and prevention programmes will accommodate a more community-orientated and participatory approach.
Background: Acceptability of self-sampling HPV testing is confirmed worldwide. However, some cultural differences may affect this question. Therefore, this study was conducted to evaluate the acceptability of self-sampling HPV testing in Thai women. Materials and Methods: One hundred women aged 30-65 years with an intact cervix were included in this study. The participants were asked to do the Pap test by physicians and then brush type self-sampling instruments were assigned for self-collection and finally completed a questionnaire for acceptability evaluation. The questionnaire contains 2 parts. Part one covered general information of the participants and part two is the acceptability questions. Results: Mean age was 40.6 years. The incidence of high risk HPV detection in this study was 16%. The most common reason for doing Pap smear was for annual checkup. On the topic of ease of use, 85 % of the subjects agreed. Most of the participants (82%) reported that they felt less pain. However, reliability of the result was not satisfactory because 37% of the participants hesitated to rely on the results of the test. According to the price, if the price is less than 1,000 Baht (32.59 Baht = 1USD), 82% of the subjects would use it for their next screening. Conclusions: The acceptability of self-sampling device in this study is quite good but the reliability of the test was questioned by some of the participants. Moreover, the price of the test in Thailand may also influence the acceptability of the test.
Background: Time to colposcopy (TC) after abnormal Pap smears was evaluated for influence on cytohistologic correlation (CHC). Materials and Methods: This retrospective study assessed the correlation between TC and CHC of women who had abnormal Pap smears. Colposcopic chart review included participants from 2010-2013 who attended a colposcopic clinic, Thammasat University Hospital, Thailand. Results: Four hundred and sixty cases who had abnormal Pap smears were recruited. Pap reports were atypical smears with low grade squamous intraepithelial lesion (SIL), high grade SIL and cancer at 339, 114 and 7 cases, respectively. One hundred and twenty four patients underwent loop electrosurgical excision procedure (LEEP). A half of the cases were colposcopically examined within 1-2 months after abnormal Pap collection. CHC was 88 percent and not affected at all by TC. Subjects who attended cervical cancer screening from affiliated health providers had shorter TC than those screened in our tertiary hospital. Conclusions: Time to colposcopy with abnormal Pap smears conducted at Thammasat University Hospital had a highest frequency of 42 days, in line with the literature. Length of TC does not affect the correlation between Pap and histopathologic reports. A longer waiting period for colposcopy did not alter progression or regression of the disease.
Spirogyra neglecta, a freshwater green alga, is a local food in the northern and northeastern parts of Thailand. This investigation explored the anticarcinogenicity of S neglecta and its possible cancer chemopreventive mechanisms in rats divided into 14 groups. Groups 1 and 10 served as positive and negative control groups, respectively. Groups 1-9 were intraperitoneally injected with diethylnitrosamine (DEN) once a week for 3 weeks. Groups 10-14 received normal saline instead. One week after the last DEN injection, groups 2-5 were administered for 9 consecutive weeks various doses of S neglecta extract (SNE) and dried S neglecta (SND), mixed with basal diet. Groups 6-9 and 11-14 similarly were administered various doses of SNE and SND starting from the first week of the experiment. Administration of SNE and SND was not associated with formation of glutathione-Stransferase placental form (GST-P) positive foci in rat liver. SNE and SND during initiation phase significantly reduced the number of GST-P positive foci in rats injected with DEN. The number of GST-P also diminished in groups treated with SNE and SND after injection with DEN, except for the low dose extract group. SNE showed stronger anticarcinogenic potency than SND. Furthermore, SNE also decreased the number of Ki-67 positive cells. However, the numbers of TUNEL-positive cells in the liver of the SNE-treated groups were not statistically different from the controls. The GST activity in 50 mg/kg bw of SNE and 1% of SND groups was significantly increased as compared to the positive control. In conclusion, Spirogyra neglecta (Hassall) K$\ddot{u}$tzing showed cancer chemopreventive properties at the early stages of diethylnitrosamine-induced hepatocarcinogenesis in rats. Possible inhibitory mechanisms include enhancement of the activities of some detoxifying enzymes and/or suppression of precancerous cells.
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