Review of the literature on combined oral contraceptives and cancer.

Millions of women have given preference to the use of combined oral contraceptives (COCs) since its introduction in the 1960s. Both oestrogens and progestogens can regulate proliferation and it is plausible these effects may contribute to carcinogenesis. We aimed to review the accumulated knowledge to date to appreciate the modifying effects combined oral contraceptives may have on carcinogenesis. Our methodology involved a review of the current published literature, paying attention to studies published in the last 20 years. It has been noted that the overall cancer odds do not change with the use of COCs. Increased risk for breast cancer with COC use is not consistently backed in the literature; the results range from no increase in risk to a 20%-30% elevation in risk, and the risk seems to be temporary, limited to recent or current regular COC use. Also, diagnosed breast cancer cases seem to be clinically advanced in ever-users compared to never-users. Data show that the ongoing and prolonged use of COCs may provide diminished risk for endometrial, colorectal and ovarian cancers. Although studies do not clearly support increased risk with COC use in high-risk groups, such as women with family history of cancer or BRCA carriers, local and international guidelines are available for clinical decision-making. For cervical cancer, COCs seem to enhance the risk with more than 5 years of use, and in many studies, this enhanced risk diminishes after discontinuation and restores to those of never-users within 10 years. The relationship between COC use and liver malignancy risk assessments has provided conflicting findings. Some studies have suggested that hormonal contraceptives may increase the risk of not only hepatocellular carcinoma but also intrahepatic cholangiocarcinoma. Combined oral contraceptives are safe and effective and the effects are reversible. Patients who pursue family planning should be warned of possible carcinogenic outcomes, but it should also be explained that-in addition to sexual health advantages-preferring COCs may also decrease the risks of endometrial, colorectal and ovarian cancers.

OPEC study: An international multicenter study of ovarian preservation in endometrial cancers.

OBJECTIVE: To evaluate the feasibility and oncological safety of ovarian preservation in early stage endometrial adenocarcinoma (EC) patients aged 40 and below. METHODS: A total of 11 institutions from eight countries participated in the study. 169 of 5898 patients aged ≤40 years were eligible for the study. Patients with EC treated between March 2007 and January 2019 were retrospectively assessed. RESULTS: The median duration of follow-up after EC diagnosis was 59 months (4-187). Among 169 participants, ovarian preservation surgery (OPS) was performed in 54 (31.9%), and BSO was performed in 115 (68.1%) patients. Although patients younger than 30 years of age were more likely to have OPS than patients aged 30 to 40 years (20.4% vs. 9.6%, P = 0.021), there was no significant difference by the mean age. There were no other relevant baseline differences between OPS and BSO groups. The Kaplan-Meier analysis revealed no difference in either the overall survival (P = 0.955) or recurrence-free survival (P = 0.068) among patients who underwent OPS, and BSO. CONCLUSION: OPS appears to be safe without having any adverse impact on survival in women aged ≤40 years with FIGO Stage I EC.

Impact of Human Papillomavirus on Wnt/Beta-Catenin Signaling in Morphological Inconspicuous Cervicovaginal Cells.

INTRODUCTION: The aim of this study was to identify early changes in the Wnt/beta-catenin signaling pathway in high-risk human papillomavirus (HPV) infected cervicovaginal cells and to correlate these changes with cell proliferation, apoptosis, and autophagic processes. METHODS: We evaluated 91 cervicovaginal smears of women with (n = 41) and without (n = 50) HPV-DNA. Smears were stained against beta-catenin, c-myc, secreted frizzled-related protein 4 (sFRP4), cleaved caspase-3, and the autophagy markers Beclin-1 and light chain 3B. In addition, sFRP-1, -2, -3, -4, -5 mRNA levels were determined by quantitative reverse transcription-PCR in primary keratinocytes and FaDu cells expressing HPV16-E6, -E7, or -E6E7. RESULTS: Our data indicated that the Wnt/beta-catenin signaling is activated in HPV (+) cervicovaginal cells that can already be detected in cells with no obvious changes in cellular morphology (HPV [+]/cyto [-]). These cells also had significantly higher sFRP4 levels when compared to HPV-negative samples. In primary keratinocytes, sFRP4 was found to be absent and sFRP1 and sFRP2 to be repressed in the presence of HPV16-E6 and E7. Interestingly, sFRP4 is expressed in FaDu cells and can be upregulated in the presence of E6E7. Curiously, SFRP4 expression correlated with an increase in the level of autophagic markers in HPV (+)/cyto (-) smears. CONCLUSION: In conclusion, the activation of the Wnt/beta-catenin signaling pathway and upregulation of sFRP4, paralleled by an activation of the autophagic pathway may represent predisposing cellular factors early after HPV infection which need to be further determined in larger study.

Endocervical polyps in high risk human papillomavirus infections.

OBJECTIVES: Human papillomavirus (HPV) positive patients with and without endocervical polyps is compared with respect to HPV genotypes and presence of pre-invasive diseases. To our knowledge, this is the first and largest report in the literature examining the endocervical polyps in HPV positive cases. MATERIAL AND METHODS: Clinicopathological data for the first one million screening patients (n = 1060 992) from around the entire country during 2015 and 2016 were targeted for this research. Colposcopy, colposcopic surgical diagnostic procedures and final pathology results of 3499 patients with high-risk (HR) HPV-positive were obtained from reference colposcopy centers. Patients with endocervical polyps (n = 243 [6.9 %]) were accepted as experimental arm while patients without any endocervical polyp (n = 3256 [93.1%]) were regarded as the control group. Age, HPV genotype, Pap smear abnormality, and final pathological results were compared between two groups using Student's t-test and cross-tabulation chi-square test. RESULTS: The incidence of endocervical polyp was found to be 6.9 % in HR HPV-positive women. The most common HPV genotypes observed in both groups were HPV 16 or 18. Abnormal cytology reports (≥ ASC-US) were not significantly different between both groups. However, with respect to final pathological diagnosis, patients with endocervical polyp had significantly lower numbers of pre-invasive diseases (31.3% vs 44.2%; p < 0.10). CONCLUSIONS: Endocervical polyps may be more common in patients with HR HPV infections. HPV 18 is observed significantly more, in the HR HPV positive endocervical polyp group. Patients with endocervical polyps do not have increased risk for preinvasive cervical diseases.

Impact of clinicopathological variables on laparoscopic hysterectomy complications, a tertiary center experience.

OBJECTIVES: To analyze intraoperative and postoperative complications according to Clavian-Dindo Classification (CDC) and evaluate the influence of clinicopathological features on the feasibility and safety of total laparoscopic hysterectomy (TLH) in patients that underwent surgery in a tertiary center. MATERIAL AND METHODS: We retrospectively reviewed the database of 469 patients that underwent surgery for patients who underwent extra facial TLH from 2013 to 2020. RESULTS: A total of 86 (18.3%) peri-postoperative complications were observed. The incidence of intraoperative complications was 2% (n = 10). The overall conversion rate to open surgery was 1.9% (n = 9). A total of 76 postoperative complications were observed in 61 patients (14.3%). The incidence of minor (Grade I [n = 16, 3.4%] and II [n = 42, 8.9%]) and major complications (Grade III [n = 15, 3.2%], IV [n = 2, 0.4%] and V [n = 1, 0.2 %]) were 12.3% and 3.8%, respectively. A higher BMI and performing surgery at the first step of learning are found to be associated with intraoperative and postoperative complications (p < 0.05). Postoperative complications related to having a history of the cesarean section, additional comorbidities, and uterine weight ≥ 300 g (p < 0.05). CONCLUSIONS: The implementation of TLH by experienced surgeons appears to have remarkable advantages over open surgery. However, the risk factor for complications should be taken into account by surgeons in the learning curve in selecting the appropriate patient for surgery.

Serum markers for the early diagnosis of intestinal anastomotic leak after gyne-oncological operations.

OBJECTIVE: To analyse the serum markers for the early diagnosis of intestinal anastomotic leak (AL) after the gyne-oncological operations. METHODS: Between September 2017 and March 2021, patients with an intestinal anastomosis performed during the gyne-oncological surgeries were identified from a tertiary centre in Turkey. As the local guideline of the clinic, all these patients were followed by measuring serum samples including procalcitonin (PCT) and C-reactive protein (CRP) on postoperative day (POD) 1 through the day of discharge or the day of re-operation for AL. RESULTS: 12.5% (5/40) of the patients suffered an AL and 4 of them were re-operated. The mean albumin values on POD 3-4 and the mean platelet values on POD 1 were lower in the AL group (P < .05). Although it was not statistically significant (P > .05), median PCT values (ng/mL) on POD 8-10 were higher in the AL group compared with no leak group. The best cut-off point for PCT on POD 9 was determined to be 0.11 ng/mL (AUC: 0.917, Sensitivity = 100.0%, specificity = 66.7%, positive predictive value = 66.7%, negative predictive value = 100.0%). CONCLUSION: Serum PCT and CRP concentrations were not found to be helpful for the early diagnosis of AL in patients operated for gyne-oncological malignancies. Low levels of albumin and platelets in the first days after the operation may be clue for a possible AL.

Anxiety, depression and concerns of pregnant women during the COVID-19 pandemic.

PURPOSE: In December 2019, the emerging of a novel coronavirus (COVID-19) has influenced the whole world. The current pandemic also triggers several psychological changes. Uncertainties and changes in health practices may cause anxiety, depression, and concerns on vulnerable populations such as pregnant. This study aims to survey the pregnant women to capture the psychological impact and perceptions during the pandemic. METHODS: A total of 297 pregnant women aged ≥ 18 years were enrolled in May 2020. We evaluated the hard-copy survey included questions about demographic and clinical information of patients, 95% confidence intervals of a COVID-19-related questionnaire in a Likert scale and 14-item Hospital Anxiety and Depression Scale (HADS). RESULTS: A total of 297 pregnant women were included in this study with a mean age of 27.64. Most patients (82.5%) had concerns about infecting their babies during delivery. The fear of infection of the fetus during delivery revealed elderly age and having anxiety as the unique significant risk factors. Mean HADS-A and HADS-D scores were 7.94 (± 4.03) and 7.23 (± 3.84), respectively. Multivariate analysis showed having anxiety was associated with a high HADS-D score and concern about the inability to reach obstetrician, and being in advanced age, having a high HADS-A score, and concern about the inability to reach obstetrician demonstrated significant effects on HADS-D score. CONCLUSION: We conclude that in future pandemics, communications and reassurance of the patients should be prioritized upon their routine ante-natal care to avoid increased levels of anxiety and even depression.

Neuroendocrine carcinoma of the endometrium: A very rare gynecologic malignancy.

OBJECTIVE: To investigate the clinicopathologic characteristics, prognostic factors, outcome, and treatment of the neuroendocrine carcinoma (NEC) of the endometrium. MATERIALS AND METHODS: We retrospectively reviewed the clinicopathologic and survival data of 10 patients who underwent surgery for NEC. The patients were collected between 1999 and 2017 from four referral centers in Turkey. RESULTS: The median age of patients was 67 years (range: 34-75 years). The NEC of endometrium consist of 9 cases with small cell carcinoma (SC) NEC (two with mixed histotypes), and one with a large cell (LC) NEC. According to FIGO 2009 criteria, 70 % (7/10) of patients had advanced stage (III and IV) disease. All patients except one underwent surgical staging, eight patients received platinum-based chemotherapy (CTX) and of 6 those were additionally treated with radiotherapy (RT). Four patients died of disease ranging from 2 to 10 months and six were alive 12-72 months with no evidence of disease. In addition, 4 SC NEC cases raised in polypoid features had no evidence of disease from 24 to 72 months. DISCUSSION: NEC of the endometrium is a rare disease with poor prognosis, which frequently diagnosed in advanced stages. The main treatment modality was the administration of platinum-based CTX as an adjuvant to surgery or surgery and RT. Our result suggests that the polypoid feature of the tumor might be one of the best predictors for the prognosis of SC NEC.

Adnexal masses in patients with colorectal cancer.

OBJECTIVE: To evaluate the clinicopathological features and outcomes of patients undergone surgery for benign and metastatic adnexal masses during the surveillance of colorectal cancer (CRC). METHODS: A single institute retrospective study involving 90 patients diagnosed with CRC that undergone surgery at Hacettepe University Hospital between 2000-2018. Clinicopathological and survival data was obtained from hospital records. RESULTS: Elevated blood levels of CEA (HR, 1.23; 95 % CI: 1.03-1.24; p = 0.01), adnexal masses larger than 5 cm (HR, 3.296; 95 % CI: 1.527-7.076; p = 0.002), bilaterality of adnexal mass (HR, 2.200; 95 % CI: 2.464-11.969; p = 0.001) and high PCI score (HR, 0.150; 95 % CI: 0.044-0.479; p = 0.01) were found to be significantly associated with ovarian metastasis. There was a significant difference in overall survival (OS), with respect to complete and incomplete resection in adnexal surgery of ovarian metastasis (46.6 vs. 29.6 months; p = 0.004). The median survival time was 32.8 months for patients with ≤ 24 months interval time to adnexal metastasis surgery, and 48.5 months for patients with >24 months interval time to adnexal metastasis surgery (p = 0.001). CONCLUSION: This study showed that numerous clinicopathological variables such as bilaterality and size of adnexal mass, serum blood levels of CEA and PCI score may have a significant impact on the prediction and management of ovarian masses diagnosed during CRC surveillance. Complete resection and interval time to adnexal surgery is significantly associated with OS.

Retrospective Analysis of Pure Ovarian Immature Teratoma in Patients Aged 15-39 Years: A Turkish Multicenter Study.

Purpose: To evaluate the clinicopathological characteristics and surgical outcomes in patients with pure ovarian immature teratomas (POITs). Materials and Methods: In this multicenter study, a retrospective review was made of the databases of six Gynecology Oncology Departments in Turkey to identify patients with POITs who had undergone surgery between 1993 and 2019. Results: Evaluation was made of 48 patients with a median age at diagnosis of 22.5 years (range, 15-37 years). In 40 (83%) patients, stage I was determined and in eight patients, an advanced stage (IIIB, IIIC, and IVB) was determined. Tumors were found to be grade I in 17 (35.4%) cases, grade II in 12 (25%), and grade III in 19 (39.6%). Fertility-sparing surgery was applied to 42 (87.5%) patients and radical surgery to 6 (12.5%). The median follow-up was 60 months (range, 3-246 months). Recurrence was seen in seven patients, all with grade III tumors. In the final pathological examination of recurrent tumors, mature teratoma was reported in five patients, and immature teratoma in one patient. Salvage surgery was not performed in one patient as the tumor was unresectable and so a regimen of bleomycin, etoposide, and cisplatin (BEP) was administered. Conclusion: POITs are rare tumors seen at a young age, and benign or malignant relapse can be seen in these tumors. In this cohort, the malignant recurrence rate was 4.1%, and the benign recurrence rate was 10.4%. All the recurrences were in grade III tumors. Benign recurrences can be treated with surgery alone and the malignant group should be treated with surgery followed by chemotherapy.

Perspectives, fears and expectations of patients with gynaecological cancers during the COVID-19 pandemic: A Pan-European study of the European Network of Gynaecological Cancer Advocacy Groups (ENGAGe).

BACKGROUND: The impact of the COVID-19 pandemic on European gynaecological cancer patients under active treatment or follow-up has not been documented. We sought to capture the patient perceptions of the COVID-19 implications and the worldwide imposed treatment modifications. METHODS: A patient survey was conducted in 16 European countries, using a new COVID-19-related questionnaire, developed by ENGAGe and the Hospital Anxiety & Depression Scale questionnaire (HADS). The survey was promoted by national patient advocacy groups and charitable organisations. FINDINGS: We collected 1388 forms; 592 online and 796 hard-copy (May, 2020). We excluded 137 due to missing data. Median patients' age was 55 years (range: 18-89), 54.7% had ovarian cancer and 15.5% were preoperative. Even though 73.2% of patients named cancer as a risk factor for COVID-19, only 17.5% were more afraid of COVID-19 than their cancer condition, with advanced age (>70 years) as the only significant risk factor for that. Overall, 71% were concerned about cancer progression if their treatment/follow-up was cancelled/postponed. Most patients (64%) had their care continued as planned, but 72.3% (n = 892) said that they received no information around overall COVID-19 infection rates of patients and staff, testing or measures taken in their treating hospital. Mean HADS Anxiety and Depression Scores were 8.8 (range: 5.3-12) and 8.1 (range: 3.8-13.4), respectively. Multivariate analysis identified high HADS-depression scores, having experienced modifications of care due to the pandemic and concern about not being able to visit their doctor as independent predictors of patients' anxiety. INTERPRETATION: Gynaecological cancer patients expressed significant anxiety about progression of their disease due to modifications of care related to the COVID-19 pandemic and wished to pursue their treatment as planned despite the associated risks. Healthcare professionals should take this into consideration when making decisions that impact patients care in times of crisis and to develop initiatives to improve patients' communication and education.

Expression levels of maternal plasma microRNAs in preeclamptic pregnancies.

The present study aimed to identify the differential expression profiles of microRNAs in the plasma between patients with preeclampsia (PE) and healthy pregnancies using quantitative real-time PCR. The expression profiles of 32 miRNAs in maternal plasma from 31 patients with PE and 32 healthy pregnancies were evaluated. The expression levels of eight miRNAs including miR-210, miR-375, miR-197-3p, miR-132-3p, miR-29a-3p, miR-328, miR-24-3p, and miR-218-5p were significantly upregulated and the expression levels of three miRNAs, including miR-302b-3p, miR-191-5p, and miR-17-5p, were significantly downregulated in patients with preeclampsia when compared to healthy pregnant women. In conclusion, we identified 11 miRNAs that may be potential biomarkers for non-invasive diagnosis and a pivotal role in the prediction of PE. Considering the small cohort of patients, further studies with larger samples from different gestational stages are necessary to confirm our findings.IMPACT STATEMENTWhat is already known on this subject? The alterations in the release pattern of placenta-specific miRNAs detected in maternal serum have been found to be associated with pregnancy-related complications such as preeclampsia (PE).What do the results of this study add? In the present study, the release pattern of seven miRNAs had consistency and two of them had inconsistency with previous researches. Moreover, two novel miRNAs were also defined to demonstrate the interrelationship between PE and miRNAs.What are the implications of these findings for clinical practice and/or future research? The identification of 11 miRNAs that may be potential biomarkers for non-invasive diagnosis and a pivotal role in the prediction of PE. Considering the small cohort of patients, further studies with larger samples from different gestational stages are necessary to confirm our findings.

Cytoreductive surgery including distal pancreatectomy with splenectomy in advanced stage ovarian cancer: Two centers analysis.

OBJECTIVE: Complex procedures such as distal pancreatectomy and splenectomy (DPS) may be required for R0 resection in patients with ovarian cancer (OC). These procedures can increase survival and cause serious morbidity. We aimed to present our experience in this field. MATERIALS AND METHODS: Thirteen patients who underwent DPS for OC between January 2004 and July 2018 in two centers (Hacettepe University Hospital, Etlik Hospital) were evaluated. Statistical analysis was performed using SPSS. RESULTS: The mean operative time was 310 min (220-570 min). None of the patients required transfusion. No perioperative mortality was observed. The mean postoperative hospital stay was 12 days (ranging from 8 to 33 days). The number of patients with early postoperative complications was four (30.7%). One of these patients was complicated by intestinal perforation, one with pancreatic fistula, one with pneumonia and the other with atelectasis. Other complications were observed conservatively. Ten patients underwent 6 cycles of platinum-based chemotherapy postoperatively. The median value of the postoperative chemotherapy period was 20 days (range 11-47 days). The median follow-up period was 46 months (2-144 months). Ten patients had recurrence. Eleven patients died of disease. Two patients are stil alive. Disease-free (DFS) and overall (OS) survival were 16 and 63 months, respectively. CONCLUSION: DPS for cytoreductive surgery is a procedure that increases morbidity, but most of the complications can be treated conservatively. Considering the increase in survival, it is considered to be a valuable procedure in upper abdominal disease.

The relationship between the presence of HPV infection and biofilm formation in cervicovaginal smears.

PURPOSE: To demonstrate and understand the association of HPV infection and biofilm formation. METHODS: The study consisted of cervicovaginal samples of 72 women who were evaluated at the colposcopy unit. Papanicolaou staining was used for cytological examination while "Crystal Violet Binding" assay was performed to detect biofilm formation. RESULTS: HPV-DNA was positive in 55.5% (n = 40) of the patients. The biofilm formation rate was statistically significantly higher in the HPV-positive women (45%) compared to HPV-negative women (21.9%) (P < 0.05). There was a statistically significant relationship between the presence of single HPV and "high-risk HPV" types and biofilm formation (P < 0.05). Biofilm formation was found in 80% of women with abnormal smear demonstrating atypical epithelial cells (P < 0.05). CONCLUSION: Biofilm formation is more frequent at the cervicovaginal microbiota of patients with HPV infection. This finding is especially important in cases with atypical epithelial cells at their cervicovaginal smears.

Using a pessary during radiotherapy in reducible pelvic organ prolapse and vaginal cancer: a case report and review of the literature.

PURPOSE: Primary vaginal cancer and pelvic organ prolapse (POP) combination is extremely rare. Although definitive chemoradiotherapy (CRT) and brachytherapy (BT) is the standard treatment for advanced stage primary vaginal cancer, there is a limited data about the treatment of primary vaginal cancer combined with POP due to its rarity. In addition, radiotherapy (RT) process may be difficult in these cases and often result in more toxicity. CASE PRESENTATION: In this case report, we present a 77-year-old woman with a diagnosis of primary vaginal cancer associated with POP, who was treated with definitive CRT using a pessary to restore vaginal anatomy for optimal radiation. Following CRT, complete response was observed and vaginal cuff BT was performed. The patient tolerated the treatment very well and is still alive without disease at 10-months follow-up. CONCLUSIONS: Combined primary vaginal cancer and POP is an extremely rare clinical entity, with only a few cases reported in the literature. When applying CRT in these cases, critical organ doses may be higher than expected due to the downward descent of the pelvic organs. Especially in elderly patients, a pessary can be used as a non-surgical procedure to restore the anatomy for symptom relief during definitive CRT. Additionally, it allows tumors to be targeted more precisely.

Vulvar Epidermoid Cyst and Type 2 Radical Genital Mutilation.

About 100 million women are estimated to be circumcised globally. Various rates of complications have been encountered, especially after circumcision, such as bleeding, infection, shock, menstrual irregularity, difficulty in urination or common urinary tract infections, inguinal pain, difficulty in sexual intercourse, and genital circumcision scar especially at the vulvar region, and cystic or solid character mass in short and long term. Furthermore, the maternal-fetal morbidity and mortality increase due to bleeding and fistula, which develop after prolonged labor, travail, and difficult labors. Our aim in this paper was to discuss a 42-year-old multiparous female case who had undergone type 2 radical genital mutilation (circumcision) when she was 7 years of age, along with the literature, which has been evaluated for the gradually growing mass at the left inguinal canal region in the last 10 years and diagnosed as epidermoid inclusion cyst developing secondary to postcircumcision surgical ground trauma, since there was no other case found in the literature search that had been circumcised at such an early age and developing after circumcision at such advanced age, and, therefore, this is suggested to be the first case on this subject.

Complications and outcomes of repeat cesarean section in adolescent women.

AIM: The evaluation of the effect of repeat cesarean sections in adolescent pregnancies on the morbidity, obstetric and perinatal results. MATERIALS AND METHODS: We reviewed the patient file and hospital records of patients who underwent at least one cesarean section among adolescent age group pregnant women who gave birth at our clinic between January 2010 and May 2013. The patients were divided into two groups as the patients who underwent the second cesarean section (116 patients) and those who underwent the third cesarean section (36 patients). The demographic data, maternal data and obstetric and perinatal results of the patients were evaluated. RESULTS: A significant difference was present between the patients in the evaluation of the total number of examinations during pregnancy (P = 0.001), total maternal weight gain during pregnancy (P = 0.006), and the first examination gestational age (P = 0.006) and all values were less favorable in the third cesarean group. The gestational week at birth (P < 0.001), birth weight (P < 0.001), and APGAR score (P < 0.001) in the group with the third cesarean section were statistically significantly lower than the second cesarean section. The third cesarean cesarean was found to cause a significant risk increase for placenta accreta risk in adolescent pregnancies (P = 0.042). CONCLUSION: The increasing number of cesarean sections in the adolescent group is seen to be a significant risk factor for low gestational week of birth, low birth weight and related morbidities. The most important reason for the increased morbidity with increasing cesarean sections in the adolescent age has been defined as placenta accreta.