Human papillomavirus prevalence, genotype distribution, and prognostic factors of vaginal cancer.

We aimed to investigate human papillomavirus (HPV) prevalence and genotype distribution and prognostic factors in vaginal cancer (VC). VC patients who received treatment between 1989 and 2020 were retrospectively reviewed. L1 general polymerase chain reaction (PCR) followed by HPV Blot (King Car, I-Lan, Taiwan) and E6 type-specific-PCR were performed for genotyping firstly. P16 and p53 immunohistochemistry staining was performed. Univariate and multivariate analyses identified predictors of clinical outcomes.79 VC patients were eligible for analysis. 73 patients (92.4%) were squamous cell carcinoma (SCC) and 6 (7.6%) as non-SCC. The median follow-up time was 134.3 months (range 0.9-273.4). Among nine initially HPV-negative cases, seven were identified as being positive through HPV16/18/45/52/58 whole-genome amplification followed by Sanger sequencing (WGASS). HPV DNA sequences were detected in 98.6% of SCC and 83.3% of non-SCC, respectively, with HPV16 (49.4%), HPV52 (15.2%) and HPV58 (8.9%) being predominant. Patients with paraaortic lymph node (LN) metastasis had a 5-year cancer-specific survival (CSS) rate of 0%. Multivariate analysis revealed that only p16 and stage were significantly correlated with prognosis. Variables with strong correlations (p16- and HPV-positivity, LN metastasis and stage), were included in models 2-5 alternatively. Stage III/IV (hazard ratio [HR] = 3.64-4.56) and LN metastasis (HR = 2.81-3.44) were significant negative predictors of CSS, whereas p16-positivity (HR = 0.29-0.32) and HPV-positivity (HR = 0.14) were related to better prognosis. In conclusion, 97.5% of VCs were HPV-positive with WGASS. Stage III/IV and LN metastasis were significant negative predictors, whereas p16- and HPV-positivity were significantly associated with better prognosis.

Detection and prognostic significance of isolated tumor cells and micrometastases in pelvic lymph nodes of patients with early ovarian clear cell carcinoma.

BACKGROUND/PURPOSE: Ovarian clear cell carcinoma (OCCC) accounts for approximately 18% of all epithelial ovarian malignancies in Taiwan and portends a poor prognosis. Here, we sought to investigate whether immunohistochemistry with an anti-pan-cytokeratin antibody cocktail (AE1/AE3) can be used as an adjunct to hematoxylin and eosin (H&E) staining for improving the detection of isolated tumor cells (ITCs) and micrometastasis to pelvic lymph nodes (LNs). We also assessed whether these lesions may predict disease recurrence. METHODS: Pelvic lymphadenectomy specimens were obtained from 197 patients with stage 1 OCCC who had undergone surgery between 2000 and 2018 from Linkou and Kaohsiung Chang Gung Memorial Hospital. Immunohistochemical staining with AE1/AE3 was applied to a total of 1186 slides. Clusters of metastatic tumor cells, detected immunohistochemically, were classified as ITCs (clusters with diameters of ≤0.2 mm) or micrometastases (tumor cell clusters of >0.2 but ≤2.0 mm). We also assessed the diameter of metastases in patients with positive lymph nodes (stage IIIA1, n = 3, 7 positive nodes). RESULTS: Clusters with a positive AE1/AE3 staining were identified in five (2.53%) of the 197 patients (ITCs, n = 3; micrometastasis, n = 2). Four patients had no evidence of disease recurrence but a patient recurred at follow-up. Metastatic foci of patients with stage IIIA1 disease were all >2.0 mm in size. CONCLUSION: Immunohistochemical staining with AE1/AE3 can identify micrometastasis or ITCs in LNs missed on routine H&E staining. The role of micrometastasis in predicting recurrent OCCC and implementing on treatment strategies requires further investigation.

Is maternal serum inhibin A a good predictor in preterm labor? - Experience from a community hospital in Taiwan.

BACKGROUND: We aimed to determine whether inhibin A could be a reliable and accurate predictor of preterm birth, and discuss the possible pathogenic processes of inhibin A leading to preterm birth. METHODS: A retrospective cohort study was conducted on consecutive singleton pregnant women who underwent the second-trimester quad screen test at a gestational age of 15-20 weeks at Keelung Chang-Gung Memorial Hospital from March 2011 to May 2015. Data including maternal characteristics and pregnancy outcomes were collected from an electric medical record database. Data regarding pregnancy terminations before a gestational age of 24 weeks and regarding pregnancies that involved chromosomal or congenital anomalies were excluded from this analysis. One-way analysis of variance was used to compare second-trimester α-fetoprotein, human chorionic gonadotropin, unconjugated estriol, and inhibin A in women with preterm deliveries versus those with term deliveries. RESULTS: Although a total of 935 women with singleton pregnancies were enrolled, pregnancy outcome and complete maternal data were obtained from only 770 (82.3%)of them. In total, 687 (89.2%) women delivered at or after 37 weeks of gestation and 83 (10.8%) women delivered before 37 weeks of gestation. The results showed that the inhibin A level was significantly increased in the preterm labor group (p = 0.009). A cutoff inhibin A value above 2.25 was identified statistical significantly in the preterm labor group. CONCLUSIONS: From our results, an inhibin A level above 2.25 multiples of the median in the quad screen test may be associated with preterm labor afterward. Closely monitoring for uterine contractions or cervical length measurement in the second trimester may be indicated in patients with unexplained elevated inhibin A levels.

Primary signet ring cell carcinoma of the cervix: A case report with review of the literature.

OBJECTIVE: Primary cervical signet ring cell carcinoma (PCSRCC) is extremely rare. In this paper, we describe a Case presenting with PCSRCC. CASE REPORT: The 48-year-old woman visited the gynecological department because of postmenopausal bleeding. A cervical mass was discovered through pelvic examination, and the biopsy results indicated a poorly differentiated adenocarcinoma with a signet ring cell pattern. Colonoscopy revealed external compression of the rectum without intraluminal mucosal lesions. Abdominal computed tomography revealed a suspicious malignant lesion at the cervicorectal junction and multiple metastases. Debulking surgery was performed and the final pathology report documented a FIGO stage IVb PCSRCC involving multiple sites. CONCLUSION: Complete tumor survey and staging are critical to differentiate primary from metastatic signet cell carcinoma of the cervix. Immunohistochemical studies cannot provide precise information. Because cases are rare, it is difficult to determine the proper treatment guidelines and prognosis.

[Adenovirus vector encoding human KDR elicits immunity against hepatocellular carcinomas in mice].

OBJECTIVE: To investigate the effect of adenovirus vector encoding human vascular endothelial growth factor receptor-2 (hVEGFR-2 or hKDR) on breaking the immune tolerance and inducing immunity against murine hepatocellular carcinomas. METHODS: Human and mouse KDR cDNA were cloned from human umbilical vein endothelial cells (HUVEC) and C57BL/6 mouse embryo cells respectively using RT-PCR, and then Ad hKDR and Ad mKDR were constructed. Seven days after immunization of the mice with Ad hKDR or Ad mKDR, an analysis of cytotoxic activity of antigen-specific cytotoxic T lymphocytes (CTL) was made by lactate dehydrogenase (LDH) release assay, in which splenocytes of the immunized mice acted as effectors and Hepa 1-6/mKDR cells as the targets. In addition, the survival of the mice immunized with Hepa 1-6 hepatoma cells was checked. RESULTS: Seven days after immunization, the 6 h killing activities of CTL elicited by the Ad hKDR were 84.3%+/-6.7%, 71.5%+/-5.2%, and 44.6%+/-4.7% at the ratio of the effectors:targets (E:T) of 100:1, 50:1, and 25:1, respectively. Correspondingly, the CTL activities by Ad mKDR were 65.2%+/-6.1%, 46.7%+/-5.0%, and 22.6%+/-3.7%. Sixty percent of the Ad hKDR-immunized mice with 5*10(6) Hepa 1-6 hepatoma cells were still alive two months after the inoculation, whereas just 40% of the Ad mKDR-immunized mice with 2*10(6) Hepa 1-6 cells survived two months. When CD8+ or CD4+ T lymphocytes were deleted in the mice the above mentioned CTL activities and protection of the mice from tumors disappeared. CONCLUSION: Adenovirus vector-mediated xenogeneic KDR can effectively break the immune tolerance to hepatocellular carcinomas in an animal model and induce a strong antigen-specific T cell response, which is dependent on CD8+ and CD4+ T cells.

Primary signet ring cell carcinoma of the cervix: A case report with review of the literature.

OBJECTIVE: Primary cervical signet ring cell carcinoma (PCSRCC) is extremely rare. In this paper, we describe a case presenting with PCSRCC. CASE REPORT: The 48-year-old woman visited the gynecological department because of postmenopausal bleeding. A cervical mass was discovered through pelvic examination, and the biopsy results indicated a poorly differentiated adenocarcinoma with a signet ring cell pattern. Colonoscopy revealed external compression of the rectum without intraluminal mucosal lesions. Abdominal computed tomography revealed a suspicious malignant lesion at the cervicorectal junction and multiple metastases. Debulking surgery was performed and the final pathology report documented a FIGO stage IVb PCSRCC involving multiple sites. CONCLUSION: Complete tumor survey and staging are critical to differentiate primary from metastatic signet cell carcinoma of the cervix. Immunohistochemical studies cannot provide precise information. Because cases are rare, it is difficult to determine the proper treatment guidelines and prognosis.