Sanguanchoke Luanratanakorn

Up-Regulation of miR-21 Is Associated with Cervicitis and Human Papillomavirus Infection in Cervical Tissues

MicroRNA-21 (miR-21) is recognized as an oncomir and shows up-regulation in many types of human malignancy. The aim of this study was to investigate the association of miR-21 expression associated with HPV infection in normal and abnormal cervical tissues. Cervical tissue samples with different cytological or histopathological grades were investigated for HPV by PCR and for miR-21 and programmed cell death, protein 4 (PDCD4) expression using quantitative real-time PCR (qRT-PCR). Laser capture microdissection (LCM) of stromal and epithelial tissues and in situ hybridization (ISH) using locked nucleic acid (LNA) probes were performed on a subset of fixed specimens. Cell line experiments were conducted on fibroblasts stimulated in culture media from HeLa cells, which were then assessed for miR-21, PDCD4, IL-6 and α-SMA expression by qRT-PCR. Twenty normal cervical cell, 12 cervicitis, 14 cervical intraepithelial neoplastic I (CIN I), 22 CIN II-III and 43 cervical squamous cell carcinoma (SCC) specimens were investigated. miR-21 levels were significantly lower in normal than in abnormal tissues. The expression of miR-21 in HPV negative normal cytology was significantly lower than in HPV positive samples in abnormal tissue and SCC. The miR-21 expression was significantly higher in HPV negative cervicitis than HPV negative normal cells. LCM and ISH data showed that miR-21 is primarily expressed in the tumor-associated stromal cell microenvironment. Fibroblasts treated with HeLa cell culture media showed up-regulated expression of miR-21, which correlated with increased expression of α-SMA and IL-6 and with down-regulation of PDCD4. These results demonstrate that miR-21 is associated with HPV infection and involved in cervical lesions as well as cervicitis and its up-regulation in tumor-stroma might be involved in the inflammation process and cervical cancer progression.

Elevated preoperative platelet to lymphocyte ratio associated with decreased survival of women with ovarian clear cell carcinoma.

This study was conducted to establish whether the preoperative platelet to lymphocyte ratio (PLR) is predictive of survival of women with ovarian clear cell carcinoma (OCCC). A PLR > 300 was deemed elevated. Progression-free survival (PFS) was estimated using the Kaplan-Meier method. Cox proportional hazard analysis was used to determine the independent effect of PLR. Thirty-six patients were reviewed. Elevated PLRs were more commonly noted in patients with an advanced vs an early stage of disease (88.9% vs 11.1%). Women with elevated PLR carried a higher rate of disease progression during primary therapy than that those in the normal PLR group (44.4 vs 22.2%). The median PFS for patients with elevated PLR was notably worse than that for patients with normal PLR (10 vs 34 months). Despite the impact of elevated PLR on PFS, it was found to be marginally significant when controlling for commonly applied prognostic markers. It, however, trended toward significance (HR=4.76; 95%CI, 0.95-23.8). In conclusion, an elevated PLR appears to be directly associated with adverse survival rather than being a surrogate for other indicators of a poor prognosis. PLR may be a useful biomarker for predicting survival of women with OCCC and merits further large-scale studies.

Weekly gemcitabine and cisplatin concurrent with pelvic irradiation for primary therapy of cervical cancer: report of the first seven cases in Thai women

PurposeThe aim of this study was to evaluate the compliance, response, and side effects of weekly gemcitabine (125 mg/m2) given concomitantly with standard weekly cisplatin (40 mg/m2) and pelvic radiotherapy for primary treatment of cervical cancer stage IB2–IVA in the first seven Thai cases.Materials and methodsWeekly gemcitabine at a dose of 125 mg/m2 was given concomitantly with cisplatin at 40 mg/m2 for six cycles with concurrent radiotherapy in primary therapy of stage IB2–IVA cervical cancer. Radiation consisted of 5000 cGy in 25 daily fractions combined with brachytherapy to take point A to about 8600 cGy.ResultsUsing weekly gemcitabine at a dose of 125 mg/m2 with cisplatin at a dose of 40 mg/m2, five of seven patients demonstrated a dose-limiting toxicity (DLT). DLTs consisted of nephrotoxicity in three cases and bone marrow suppression in two cases. Only one of seven patients could go through six cycles. All 5 living patients had a clinically complete response.ConclusionsWeekly gemcitabine at a dose of 125 mg/m2 with cisplatin at a dose of 40 mg/m2 given concurrently with primary pelvic radiotherapy resulted in an excellent response but unacceptable toxicities for Thai women. The trial protocol was changed by reducing the cisplatin dosage to 20 mg/m2.

Srinagarind Hospital experience in concurrent chemoradiation for 100 patients with stage IB2 to IVA uterine cervical cancer.

PurposeThe aim of this study was to determine responses, acute adverse effects, and survival outcomes of women with stage IB2 to IVA treated with weekly cisplatin concurrent with pelvic irradiation at Srinagarind Hospital.Materials and methodsThe medical records of 100 women with cervical cancer stage IB2 to IVA who were treated with weekly cisplatin 40 mg/m2 concurrent with pelvic radiotherapy at Srinagarind Hospital between January 2003 and June 2006 were reviewed and analyzed.ResultsDuring the study period, 100 women were eligible for analysis, with a mean age of 46 years (range 24–60 years). Distribution according to International Federation of Gynecology and Obstetrics (FIGO) staging was IB2 1.0%, IIB 47.0%, IIIB 51.0%, and IVA 1.0%, respectively. A total of 86 patients received five or more cycles of weekly cisplatin. Grade 3 and 4 hematologic toxicities were found in 6.0%. The overall response rate was 97.0%. Complete response was achieved in 86 patients (86.0%) and partial response in 11 patients (11.0%). Stable disease was found in 1 patient (1.0%) but no progressive disease was found. Progression-free survival and overall survival rate were 69.6% and 96.1%, respectively.ConclusionWeekly cisplatin (40 mg/m2) concurrent with pelvic irradiation for locally advanced cervical cancer was effective with acceptable toxicity in Thai women.

Contraceptive practices and pregnancy intendedness among pregnant adolescents

Background Adolescent pregnancy is a major health problem in many developing countries. Objective To assess contraceptive practices and pregnancy intendedness in pregnant adolescents. Materials and methods This study was prospectively conducted from September 2013 to June 2014. All consecutively pregnant women between 15 and 19 years old attending the Antenatal Clinic at Srinagarind Hospital and the Khon Kaen Branch of the Planned Parenthood Association of Thailand were invited for participation. Face-to-face interviews by trained interviewers using standardized questionnaires were carried out. Logistic regression was used to determine an adjusted odds ratio (aOR) and 95% confidence interval (CI) of independent predictors. Results Two hundred participants were enrolled. Mean age was 17.2 years. One hundred and eighteen (59.0%) were currently in school. Seventy-five (37.5%) participants had never used any contraceptive methods. Of the 125 participants who had ever used contraception, regular use of contraceptives was reported in only 21 participants (16.8%). Only two participants (1.0%) had ever used an intrauterine device or implant. Participants’ age was a significant independent factor associated with non-use of contraceptives (aOR, 6.42; 95% CI, 2.94–14.04). Of the 200 participants, 132 (66.0%) declared that the pregnancy was unintended. Significant independent factors predicting unintended pregnancy were educational status (aOR, 6.17; 95% CI, 3.27–13.75) and participants’ age (aOR, 5.76; 95% CI, 2.42–13.70). Conclusion Non-use and use of contraceptive methods with high failure rates were major reasons leading to adolescent pregnancies. Participants’ age was an independent factor predicting non-use of contraceptives. Educational status and age of the participants were significant factors predicting unintended pregnancy.

Association of antibody to E2 protein of human papillomavirus and p16INK4A with progression of HPV-infected cervical lesions

Human papillomavirus (HPV) E2 and L1 proteins are expressed in cervical cells during the lytic stage of infection. Overexpression of p16INK4A is a biomarker of HPV-associated cervical neoplasia. This study investigated antibodies to HPV16 E2, HPV16 L1, and p16INK4A in sera from women with no squamous intraepithelial lesion (No-SIL) of the cervix, low-grade SIL, high-grade SIL, and cervical squamous cell carcinoma (SCC). HPV DNA was detected by polymerase chain reaction. Anti-E2, -L1, and -p16INK4A antibodies in sera were determined by western blot. Among 116 samples, 69 (60%) were HPV DNA-positive. Percentages seropositive for anti-E2, -L1, and -p16INK4A antibodies were 39.6, 22.4, and 23.3%, respectively. Anti-E2 antibody was significantly correlated with HPV DNA-positive cases. Eighty-seven women (75%) were regarded as infected with HPV, having at least one positive result from HPV DNA, L1, or E2 antibody. Antibody to p16INK4A was associated with HPV infection (odds = 5.444, 95% CI 1.203–24.629, P = 0.028) and precancerous cervical lesions (odds = 5.132, 95% CI 1.604–16.415, P = 0.006). Interestingly, the concurrent detection of anti-E2 and -p16INK4A antibodies was significantly associated with HPV infection (odds = 1.382, 95% CI 1.228–1.555, P = 0.044). These antibodies might be good candidate biomarkers for monitoring HPV-associated cervical lesion development to cancer.

High-grade Cervical Histopathology in Women with Atypical Glandular Cell Cytology

This study was undertaken to evaluate the prevalence of underlying significant lesions among women referred for colposcopy after atypical glandular cell (AGC) smears and the associated risks. The present study reviewed data from women with AGC smears undergoing colposcopy at the Colposcopy Clinic, Faculty of Medicine, Khon Kaen University, Thailand between January 2001 to December 2014. Significant lesions included cervical intraepithelial neoplasia grade 2-3, adenocarcinoma in situ, endometrial hyperplasia, and cancer. During the study period, 170 women with AGC cytology were reviewed. The mean age was 45.7 years. Thirty-eight women (22.4%) were postmenopausal. Eighteen smears (10.6%) were further subclassified as AGC-favor neoplasia (AGC-FN). In total, significant lesions were noted in 27 women (15.9%; 95%CI, 7.8%-18.3%). Thirteen women (7.6%, 95%CI, 4.1%-12.7%) were found to have cervical cancer or endometrial cancer. Two variables were independently associated with an increased risk of significant histopathology results: level of educational attainment (secondary level or lower versus bachelor degree or higher) and types of AGC (AGC versus AGC- FN). Women who had low level of education and those with AGC-FN were at the higher risk of significant lesions (OR, 3.16; 95%CI 1.10-9.11 and OR, 4.62; 95%CI, 1.54-13.85, respectively). In conclusion, the rate of significant lesions among women referred for colposcopy after AGC smears is considerably high. Low education and smear subtypes appear independently associated with a higher risk of significant lesions.

Is Age an Independent Predictor of High-Grade Histopathology in Women Referred for Colposcopy after Abnormal Cervical Cytology?

This study was conducted to determine whether advancing age is an independent predictor of increased risk of high-grade pathologies among women referred for colposcopy after abnormal cervical cytology. Medical records were reviewed for women with abnormal cervical cytology who underwent colposcopy at Khon Kaen University Hospital. Logistic regression was used to determine the independent impact of age on the risk of high-grade pathologies. Mean age of the women was 42.8 years. Of 482 women, 97 (20.1%) were postmenopausal, and 92 (19.1%) were nulliparous. The rate of high-grade pathologies included cervical intraepithelial neoplasia 2-3, 99 (20.5%), adenocarcinoma in situ, 4 (0.8%), cervical cancer, 30 (6.2%), and endometrial cancer, 1 (0.2%). The prevalence of significant lesions was 26.9% (95% CI, 23.1%-31.2%). In total, 31 women had cancers (6.4%; 95% CI, 4.4%-9.0%). When controlling for smear types and parity, age was noted to be a significant independent predictor of high-grade histopathology. Women older than 35-40 years were approximately 2 times as likely to have severe histopathology as the younger women. This study illustrates the substantial risk of underlying significant lesions especially invasive cancer in Thai women with abnormal cervical cytology. Age was a significant independent factor predicting the risk of high-grade pathologies.

Wound Complications after Laparotomy for Endometrial Cancer

This study was conducted to determine the incidence of wound complications after laparotomy for endometrial cancer and significant predictors of risks. Medical records of patients with endometrial cancer undergoing laparotomy for surgical staging at Srinagarind Hospital, Khon Kaen University between January 2007 and December 2013 were reviewed. Intravenous antibiotic prophylaxis was routinely given 30 minutes before surgery. The primary endpoint was wound complications (including seroma, hematoma, separation, or infection) requiring additional medical and/or surgical management within 4 weeks of laparotomy. During the study period, 357 patients with complete medical records were reviewed. The mean age was 56.9 years. Wound complications were observed in 28 patients (7.84%, 95% CI, 5.27% to 11.14%). Body mass index (BMI) ≥ 30 kg/m2, diabetes mellitus (DM), and prior abdominal surgery were observed as significant independent factors predicting an increased risk of wound complications with adjusted odds ratios (95% CIs) of 2.96 (1.23-7.16), 2.43 (1.06-5.54), and 3.05 (1.03-8.98), respectively. In conclusion, the incidence of wound complications after laparotomy for endometrial cancer was 7.8%. Significant independent predictors of risk included BMI, DM and prior abdominal surgery.