Aim: To determine utility of the frozen section (FS) in the operative management of endometrial pre-malignant lesions. Materials and Methods: We retrospectively analyzed patients who underwent abdominal hysterectomy with preoperative diagnosis of complex atypical endometrial hyperplasia (CAEH) and simple endometrial hyperplasia (SEH) between May 2007 and December 2013. Frozen and paraffin section (PS) results were compared. Sensitivity, specificity, the positive predictive value (PPV), the negative predictive value (NPV) and the accuracy in predicting EC on FS were evaluated with 95% confidence intervals (CIs) for each parameter. The correlation between FS and PS was calculated as an ${\kappa}$ coefficient. Results: Among 143 preoperatively diagnosed CAEH cases, 60 (42%) were malignant and 83 (58%) were benign in PS; and among 60 malignant cases diagnosed in PS, 43 (71%) were "malignant" in FS. Sensitivity, specificity, PPV and NPV for FS were 76%, 100%, 100% and 87.5%, respectively. Conclusions: We found that FS is reliable and applicable in the management of endometrial hyperplasias. It is important that the pathologist should be experienced because FS for endometrial pre-malignant lesions has significant inter-observer variability. The other conclusion is that patients with the diagnosis of EH, especially those who are postmenopausal, should undergo surgery where FS investigation is available.
Background: To determine the frequency of dysplastic lesions in the endocervical curettage (ECC) specimens of women with ASC-US and LSIL Pap and to evaluate the possible factors associated with high grade dysplasia in those ECC specimens. Materials and Methods: Two hundred and sixty patients with ASC-US and LSIL cytologic smears who underwent an ECC at the time of colposcopic examination during January 2010 and December 2012 were reviewed. Demographic and clinicopathologic data were collected. Multivariate analysis using binary logistic regression was used to identify factors that might be associated with high grade endocervical dysplasia. Results: The frequency of endocervical dysplasia was 7.7% (20 out of 260 patients). Cervical intraepithelial neoplasia (CIN) 1 and CIN 2-3 lesions in the endocervical canal were observed in 12 and 8 patients, respectively. No microinvasive or invasive cervical cancers were identified. There was no difference in the frequency of high grade endocervical dysplasia between the patients with satisfactory and unsatisfactory colposcopic examinations (1.4% vs 5.1%, respectively, p=0.087). A multivariate logistic regression analysis demonstrated a significant association between high grade CIN on ectocervical biopsy as well as LSIL cytologic smears and high grade dysplasia in endocervical canal (OR=0.046, 95%CI=0.007-0.288; p=0.001 and OR=0.154, 95%CI=0.025-0.942; p=0.043, respectively). Conclusions: The frequency of high grade endocervical dysplasia in women with ASC-US and LSIL cytologic smears was low. Therefore, routine performance of ECC in those women is debatable. High grade ectocervical dysplasia and LSIL cytologic smears may be used as predictors for high grade dysplasia in endocervical canal and ECC in these patients is reasonable.
Aim: To evaluate the operative, oncologic and obstetric outcomes of the loop electrosurgical excision procedure (LEEP) in cases with cervical neoplasia. Materials and Methods: A retrospective cohort study was conducted on patients who were suspected of cervical neoplasia and therefore undergoing LEEP at Siriraj Hospital, Mahidol University, Thailand, during 1995-2000. Outcome measures included operative complications in 407 LEEP patients and long-term outcomes in the 248 patients with cervical intraepithelial neoplasia (CIN) who were treated with only LEEP. Results: There were 407 patients undergoing LEEP; their mean age was $39.7{\pm}10.5$ years. The histopathology of LEEP specimens revealed that 89 patients (21.9%) had lesions ${\leq}CIN$ I, 295 patients (72.5%) had CIN II or III, and 23 patients (5.6%) had invasive lesions. Operative complications were found in 15 patients and included bleeding (n=9), and infection (n=7). After diagnostic LEEP, 133 patients underwent hysterectomy as the definite treatment for cervical neoplasia. Of 248 CIN patients who had LEEP only, seven (2.8%) had suffered recurrence after a median of 16 (range 6-93) months; one had CIN I, one had CIN II, and five had CIN III. All of these recurrent patients achieved remission on surgical treatment with re-LEEP (n=6) or simple hysterectomy (n=1). A significant factor affecting recurrent disease was the LEEP margin involved with the lesion (p=0.05). Kaplan-Meier analysis showed 5-year and 10-year disease-free survival (DFS) estimates of 99.9%. Twelve patients became pregnant a total of 14 times, resulting in 12 term deliveries and two miscarriages - one of which was due to an incompetent cervix. Conclusions: LEEP for patients with cervical neoplasia delivers favorable surgical, oncologic and obstetric outcomes.
Metastatic gestational trophoblastic neoplasia (GTN) is an uncommon cancer. The principal treatment consists of chemotherapy with or without surgery or radiotherapy. We here retrospectively reviewed the outcomes of metastatic GTN treated at our institute between January, 1999 and December, 2013. Sixty-three patients met the criteria. The median age was 30.0 years and almost 90% were referral cases. Nearly 40% of the studied patients presented with vaginal bleeding while 22.2% were asymptomatic. The most common antecedent pregnancy was hydatidiform mole (57.1%) followed by term pregnancy (20.6%). The median interval time from antecedent pregnancy to the development of GTN was three months and the median pretreatment B-hCG was 58,274 mIU/ml. Stage III (74.6%) was the most common staging followed by stage IV (20.6%) and stage II (4.8%). The most frequent surgery was hysterectomy (31.7%). Thoracotomy and craniotomy were performed in three and two patients, respectively. The most common first line chemotherapy regimen was methotrexate and folinic acid (36.5%) followed by EMA (etoposide, methotrexate, actinomycin D) (34.9%), EMACO (etoposide, methotrexate, actinomycin D, cyclophosphamide, vincristine) (17.5%) with the remission rate of 66.7%. Nearly one-third of the patients were given a subsequent chemotherapy regimen after failure with the first line therapy and showed a final response rate of 73.0%. However, in stage IV, the response to first line treatment was only 38.5%. In conclusion, the outcomes of metastatic GTN were poor especially with the higher stages.
Toll-like receptor 4 (TLR4) has been implicated in cell proliferation and apoptosis in several types of cancer. In this study, the impact of TLR4 activation on apoptotic cell death in gynecologic cancers induced by lipopolysaccharide (LPS) was investigated. Cervical cancer cell lines were produced from isolated surgical specimens supplied by Paik Hospital. The primary cultures of normal myometrium and gynecologic cancers, including cervical, endometrial, and ovarian cancers, were used to examine the differences in morphological characteristics between normal and cancerous cells. A reverse transcription polymerase chain reaction analysis was used to determine the relative expression levels of TLR4 gene involved in apoptosis-associated signaling in cervical cancer cells. The cancer cell colonies showed a tendency to reach high levels of confluency compared with normal cells. In addition, an enhanced growth rate and loss of contact inhibition were observed in gynecologic cancer cells compared with normal cells (doubling times of 16.6 hr vs. 26 hr, respectively). The expression level of ITGA5, an alpha-5 integrin marker, was upregulated in normal myometrial cells, but this tendency was not exhibited in cervical cancer cells. Furthermore, p53 tumor suppressor gene expression was upregulated, whereas TLR4 and caspase-3 gene expressions were downregulated in cervical cancer cells. Notably, the expression levels of TLR4 and caspase-3 were increased significantly in LPS-treated cancer cells compared with those in non-LPS-treated cells. These results suggest that the TLR4-mediated caspase-dependent apoptotic signaling pathway could be suggested as a therapeutic target for the treatment of gynecologic cancers, including cervical cancers.
Objective: The aims of this study were to explore Turkish women's knowledge, behavior and beliefs related to cervical cancer and screening. Methods: The study was performed in two cities in the East of Turkey between September 2009 and April 2010, with a sampling group of 387 women. Data were collected by means of an interview form with the Health Belief Model Scale for Cervical Cancer and Pap Smear Test - Turkish Version. Results: Women in the research group were found to have poor knowledge, inadequate health behavior and low/medium level false beliefs regarding cervical cancer screening. There was relation between health beliefs and characteristics of women and particularly education (F = 10.80, p = 0.01). Similarly, it was found that Pap smear barriers were influenced by demographic characteristics and that women with low-level education (p = 0.001), divorced women (p = 0.05), women with low-income(p = 0.05), women who gave their first birth when they were 18 or younger (p = 0.05) and women not applying any contraceptive method at all (p = 0.01) were determined to have negative Pap smear barriers. Conclusions: Primarily the knowledge, attitudes and beliefs of women in the target group should be evaluated to increase their participation in cervical cancer screening and to prepare effective education strategies.
Objective: Cervical cancer is one of the most common malignant tumors. Our previous results showed that long non-coding RNA (lncRNA) XLOC_006390 plays an important role in cervical cancer. In this study, we have explored the mechanism of action of lncRNA XLOC_006390. Methods: LncRNA XLOC_006390 was proposed to exercise its function as a competing endogenous RNA (ceRNA), and its potential targeted miRNAs was predicted through the database LncBase Predicted v.2. Two miRNAs, miR-331-3p, and miR-338-3p, were chosen for the study. Expression of miRNAs and lncRNA in cervical cancer cells and tissues was detected by reverse transcription polymerase chain reaction. To determine the correlation, silencing of XLOC_006390, over-expression of miR-331-3p, and miR-338-3p was performed in SiHa and Caski cell lines, respectively. Results: Based on the interactive effect between miRNA and lncRNA, miR-331-3p and miR-338-3p were significantly downregulated in cervical cancer cells and tissues, and their expression levels were negatively related to that of lncRNA. Our results also showed that the expression of miR-331-3p target gene NRP2, miR-338-3p target genes PKM2, EYA2 was significantly downregulated when the XLOC_006390 was knocked down. Further, XLOC_006390 was found to facilitate cervical cancer tumorigenesis and metastasis by downregulating miR-331-3p and miR-338-3p expression. Conclusion: Taken together, our study demonstrated that XLOC_006390 may serve as a ceRNA and reversely regulates the expression of miR-331-3p and miR-338-3p, thus facilitating cervical cancer tumorigenesis and metastasis.
Kim, Do-Hoon;Cho, Chi-Heum;Kwon, Sun Young;Ryoo, Nam-Hee;Jeon, Dong-Seok;Lee, Wonmok;Ha, Jung-Sook
Journal of Gynecologic Oncology
/
v.29
no.6
/
pp.90.1-90.12
/
2018
Objective: We performed small-scale mutation and large genomic rearrangement (LGR) analysis of BRCA1/2 in ovarian cancer patients to determine the prevalence and the characteristics of the mutations. Methods: All ovarian cancer patients who visited a single institution between September 2015 and April 2017 were included. Sanger sequencing, multiplex ligation-dependent probe amplification (MLPA), and long-range polymerase chain reaction (PCR) were performed to comprehensively study BRCA1/2. The genetic risk models BRCAPRO, Myriad, and BOADICEA were used to evaluate the mutation analysis. Results: In total, 131 patients were enrolled. Of the 131 patients, Sanger sequencing identified 16 different BRCA1/2 small-scale mutations in 20 patients (15.3%). Two novel nonsense mutations were detected in 2 patients with a serous borderline tumor and a large-cell neuroendocrine carcinoma. MLPA analysis of BRCA1/2 in Sanger-negative patients revealed 2 LGRs. The LGRs accounted for 14.3% of all identified BRCA1 mutations, and the prevalence of LGRs identified in this study was 1.8% in 111 Sanger-negative patients. The genetic risk models showed statistically significant differences between mutation carriers and non-carriers. The 2 patients with LGRs had at least one blood relative with breast or ovarian cancer. Conclusion: Twenty-two (16.8%) of the unselected ovarian cancer patients had BRCA1/2 mutations that were detected through comprehensive BRCA1/2 genetic testing. Ovarian cancer patients with Sanger-negative results should be considered for LGR detection if they have one blood relative with breast or ovarian cancer. The detection of more BRCA1/2 mutations in patients is important for efforts to provide targeted therapy to ovarian cancer patients.
Background: Pelvic exenteration is a procedure which includes enbloc resection of pelvic organs followed by surgical reconstruction. Aims include both cure and palliation but data for pelvic exenteration in Thailand are very limited. Objective: This study was conducted to evaluate characteristics of patients, operative procedure outcomes and complications. Materials and Methods: This retrospective review covered all of the charts of exenteration patients during January 2002 to December 2011. Baseline characteristic of the patients were collected as well as details of clinical results. Results: A total of 13 cases of pelvic exenteration were included. Most underwent total pelvic exenteration (9 cases) and the remainder posterior and anterior exenteration. Their primary cancers were ovarian, cervical and vulva. Mean operative time was 532 minutes (SD 160.2, range 270-750) and estimated blood loss was 2830 ml (1850, 1000-8000). Mean tumor size was 7.33 cm (3.75, 4-15). Mean hospital stay was 35.2 days (29.8, 13-109). The most common post operative complication was urinary tract infection. Overall disease free survival with a negative surgical margin was significantly better than in positive surgical margin patients (p=0.014). Conclusions: Surgical margin was the most significant prognostic factor for disease free survival, in line with earlier studies.
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