Management of cervical cancer during pregnancy.

Cervical cancer (CC) is the most common gynaecological cancer during pregnancy. The rarity of the disease and lack of randomised control studies have prevented the establishment of treatment guidelines. The management of CC mainly follows the guidelines for the non-pregnant disease state, expert opinions and limited case reports. Although the management of CC diagnosed during pregnancy appears to be a significant dilemma for the patients and specialists, the prognosis of CC is not influenced by pregnancy. The treatment decision should be made collaboratively with a multidisciplinary team consisting of an obstetrician, gynaecologist, oncologist and paediatrician. The concerns of the patient should be taken into account.

Prevalence of genital warts in reproductive-aged Turkish women presenting at gynecology outpatient clinics for any reason.

The objective of this multicenter descriptive study was to calculate the frequency of genital warts among Turkish women aged 15-49 years, who visited outpatient gynecology clinics for a variety of reasons. The study was conducted in February 2011 to collect data for a minimum of 154 patients at each center, and the total sample size reached 2,967 women (95.1% completion rate). Oral informed consents were obtained. A questionnaire including data on socio-demographic characteristics and reasons for admission was administered, and a pelvic examination was performed. The overall point prevalence was 35% (95% CI = 3.1%-4.0%), correcting for sampling design, with the highest rates observed in the 15 to 19-year-old group. The odds of having a genital wart was 1.82 times (95% CI = 0.99-3.33) higher among non-pregnant participants than in pregnant women (p = 0.051). The overall point prevalence of genital warts among reproductive-aged women attending gynecology outpatient clinics for any reason in Turkey was 35%.

Fetal loss in threatened abortion after demonstration of fetal cardiac activity in a low socioeconomic population.

This study was conducted to determine the incidence and risk factors of fetal loss in threatened abortion after ultrasonographic detection of fetal cardiac activity in a low socioeconomic population. A total of 202 women with singleton pregnancies who presented with vaginal bleeding in which fetal heart activity was ultrasonographically demonstrated between 5 and 14 weeks' gestation were included. Pregnancies with fetal abnormalities were excluded from the study. All cases were followed-up with respect to pregnancy outcomes. A total of 54 of 202 pregnancies (26.7%) resulted in fetal loss before 20 weeks' gestation. The mean fetal heart rate (FHR) and cervical length values were lower in spontaneous abortions than in viable pregnancies (121.2 +/- 13.3 vs 143.5 +/- 12.4 and 41 +/- 6.0 vs. 34.8 +/- 6.1, respectively; p < 0.001). A receiver operating characteristic (ROC) curve analysis revealed an area under the curve of 0.88 for FHR and 0.77 for cervical length. A FHR value <130 b.p.m. was 81.4% sensitive, 85.1% specific and a cervical length value <40 mm was 80.8% sensitive, 54.7% specific for determination of fetal loss before 20 weeks' gestation. Fetal loss was observed in about one-quarter of pregnancies admitted with threatened abortion in a low socioeconomic population. Bradycardia and short cervix were found to be significant risk factors affecting the pregnancy outcome in women presenting with vaginal bleeding, in whom fetal cardiac activity was documented.

Identification of point mutations and large rearrangements in the BRCA1 gene in 667 Turkish unselected ovarian cancer patients.

OBJECTIVE: The aim of this study was to evaluate the prevalence and spectrum of a known founder mutation, 5382insC and large genomic rearrangements (LGRs) in BRCA1 in ovarian cancer patients in Turkey. The additional aim was to determine the genetic testing strategy in Turkish breast/ovarian cancer family. METHODS: Six hundred and sixty-seven ovarian cancer patients from five large geographical regions in Turkey, 61 of which had family history of breast/ovarian cancer, were tested for the mutation 5382insC by mutagenically separated polymerase chain reaction and direct sequencing of the entire coding sequence and the splicing sites. Additionally, multiplex ligation-dependent probe amplification (MLPA) was performed for large mutational scanning of BRCA1 gene in unselected ovarian cancer. RESULTS: In this study, BRCA1 point mutations were observed in 1% of all patients and 9.8% of familial cases: 5382insC, unique novel missense variant-G1748S and unclassified splice site variant IVS20+5A>T. 5382insC was observed in two patients. However, G1748S, previously unreported, was found in four patients and thus led to the conclusion that this mutation may be unique to Turkey. A splice site variant, IVS20+5A>T, was detected in three patients, with two of them including G1748S and IVS20+5A>T, together. Using MLPA, six different distinct LGRs in BRCA1 were observed: the deletion of E1A-1B-2, E11, E17-19, E18 and E18-19 and duplication of E5-9. The prevalence of LGRs in this study was 40.9% among patients with family history. The deletion of E1A-1B-2 was the common mutation, and patients with this deletion were referred to us from four different geographical regions in Turkey. Therefore, it was hypothesized that this deletion covering E1-2 is common in Turkey. CONCLUSION: LGRs in BRCA1 were strongly associated with positive family history among the Turkish population. On the basis of these findings, it can be recommended that a low-cost screening for LGRs in BRCA1 may be the first-line mutation detection method in families with strong breast/ovarian cancer history in Turkey.

Power Doppler properties of endometrial polyps and submucosal fibroids: a preliminary observational study in women with known intracavitary lesions.

OBJECTIVES: To compare power Doppler flow mapping characteristics of endometrial polyps and submucosal fibroids and analyze whether two different power Doppler characteristics, single-vessel pattern and rim-like vessel pattern, can help to differentiate these focal endometrial lesions. METHODS: Patients suspected of having endometrial polyps or submucosal fibroids on sonohysterography were examined prospectively by transvaginal B-mode and power Doppler sonography. Single-vessel pattern and rim-like vessel pattern were considered to be characteristic of endometrial polyps and submucosal fibroids, respectively. Suspected diagnoses of the lesions according to vascular Doppler characteristics were compared with the final diagnosis following histopathological examination. RESULTS: Included in the final analysis were 49 patients with histological confirmation of the type of endometrial lesion: 32 with endometrial polyps and 17 with submucosal fibroids. Power Doppler signals were observed in 47 of these; they were not observed in two patients with endometrial polyps. Of the 32 with endometrial polyps, 26 (81.3%) endometrial polyps showed a single-vessel pattern, three (9.4%) showed a multiple-vessel pattern and one (3.1%) showed a scattered-vessel pattern. Of the 17 with submucosal fibroids, 12 (70.6%) showed a rim-like vessel pattern, three (17.6%) showed a multiple-vessel pattern and two (11.8%) showed a single-vessel pattern. Single-vessel pattern was associated with two false-positive cases, but there were no false-positive cases for rim-like vessel pattern. The sensitivity, specificity and positive and negative predictive values for single-vessel pattern in diagnosing endometrial polyps were 81.2%, 88.2%, 92.9% and 71.4% and for rim-like pattern in diagnosing submucosal fibroids they were 70.6%, 100%, 100% and 86.5%, respectively. CONCLUSIONS: Power Doppler blood flow mapping is a valuable tool in the diagnosis of focal endometrial pathology and is useful in distinguishing submucosal fibroids and endometrial polyps.

Radiotherapy in the adjuvant setting of cervical carcinoma: treatment, results, and prognostic factors.

To evaluate the efficacy of postoperative radiotherapy and to investigate prognostic factors for early-stage cervical cancer patients. From December 1993 to December 2001, 141 patients with stage I-II cervical cancer without para-aortic lymph node (LN) metastases and treated by surgery and postoperative radiotherapy (RT) were included in this study. Indications for postoperative external RT were based on pathologic findings, including LN metastasis, positive surgical margins, parametrial involvement, pT2 tumor, and presence of any two minor risk factors like lymphvascular space involvement, deep stromal invasion, and tumor diameter between 2-4 cm. Sixty-six (47%) patients received RT alone, whereas 59 (42%) were treated with RT and concomitant chemotherapy (CT), and 16 received neoadjuvant CT. Patients with positive vaginal margins also received 27.5 Gy high-dose rate vaginal cuff brachytherapy in five fractions. Median follow-up time was 55 months. The actuarial 5-year overall (OS), disease-free (DFS), locoregional recurrence-free (LRFS), and distant metastases-free (DMFS) survival rates are 70%, 68%, 77%, and 88%, respectively. Univariate and multivariate analyses revealed that level and number of metastatic LNs and concomitant CT were unique significant prognostic factors for OS, DFS, and LRFS. Endometrial involvement, on the other hand, was proven to be significant for DFS and DMFS. Patients with less than three LN metastases or having only obturator LN involvement showed similar prognosis with their counterparts having no LN metastases. On the other hand, patients with either common iliac LN or more than three LN metastases had significantly worse outcome. Our results indicate that level and number of metastatic LNs are the most important prognostic factors determining the survival rates, and patients with upper lymphatic involvement or more than three metastatic LNs seem to need more effective treatment approaches.

Results with EMA/CO (etoposide, methotrexate, actinomycin D, cyclophosphamide, vincristine) chemotherapy in gestational trophoblastic neoplasia.

The aim of this study was to evaluate the efficacy and toxicity of EMA/CO (etoposide, methotrexate, actinomycin D, cyclophosphamide, vincristine) regimen for the treatment of high-risk gestational trophoblastic neoplasia (GTN). Thirty-three patients with high-risk GTN, scored according to World Health Organization, received 159 EMA/CO treatment cycles between 1994 and 2004. Twenty-three patients were treated primarily with EMA/CO, and 10 patients were treated secondarily after failure of single agent or MAC (methotrexate, actinomycin D, cyclophosphamide, or clorambucile) III chemotherapy. Adjuvant surgery and radiotherapy were used in selected patients. Survival, response, and toxicity were analyzed retrospectively. The overall survival rate was 90.9% (30/33). Survival rates were 91.3% (21/23) for primary treatment and 90% (9/10) for secondary treatment. Six (18.2%) of 33 patients had drug resistance. Four of them underwent surgery for adjuvant therapy. Three of these patients with drug resistance died. Survival and complete response to EMA/CO were influenced by liver metastasis, antecedent pregnancy, and histopathologic diagnosis of choriocarcinoma. Survival rate was also affected by blood group. The treatment was well tolerated. The most severe toxicity was grade 3-4 leukopenia that occurred in 24.3% (8/33) of patients and 6.9% (11/159) of treatment cycles. Febrile neutropenia occurred in one patient (3%). EMA/CO regimen is highly effective for treatment of high-risk GTN. Its toxicity is well tolerated.

Recurrent partial hydatidiform mole: a report of a patient with three consecutive molar pregnancies.

Hydatidiform mole (HM) is the most common form of gestational trophoblastic neoplasia and is characterized by atypical hyperplastic trophoblasts and hydropic villi. Recurrence of HM is extremely rare. Here, we report the case of a patient with three consecutive partial HMs without normal pregnancy. A 28-year-old woman with gravida 3, para 0, was referred to our hospital with a diagnosis of an invasive mole in December 2003. She had three consecutive molar pregnancies in 2000, 2001, and 2003. All three molar pregnancies were evacuated by suction curettage and the patient was followed by serial beta-human chorionic gonadotropin levels. All three moles were histologically confirmed as partial moles. In the first two molar events no additional treatment after evacuation was required, but in the last event, the beta-human chorionic gonadotropin levels increased and an invasive mole was suspected. Diagnostic workup ruled out an invasive mole and choriocarcinoma. Karyotypic analysis of the patient and her husband was normal. The patient required chemotherapy for treatment of persistent disease. Recurrent partial HM is a very rare clinical disorder. Repetitive molar pregnancy is not an indication for chemotherapy, but persistent disease does require chemotherapy.

A phase II study of gemcitabine plus carboplatin in platinum-sensitive, recurrent ovarian carcinoma.

OBJECTIVES: Gemcitabine and carboplatin each have demonstrated effectiveness without increased neurotoxicity in pretreated patients with ovarian cancer. We evaluated the efficacy and safety of gemcitabine plus carboplatin in patients with recurrent ovarian cancer in a multicenter phase II study. METHODS: Women with histologically proven measurable or evaluable epithelial ovarian cancer (any FIGO) who relapsed > or =6 months after discontinuation of first-line, platinum-containing therapy received gemcitabine 1000 mg/m(2) on days 1 and 8 and carboplatin AUC 4 on day 1 (after gemcitabine) every 21 days for up to six cycles. RESULTS: Of the 40 enrolled/evaluable patients, 6 (15%) had complete response and 19 (47.5%) had partial response (PR), including one patient with PR in nonmeasurable disease (PRNM), for an overall response rate of 62.5% (95% CI, 45.8-77.3%). The median duration of response was 7.8 months (95% CI, 6.7-10.0), the median time to progressive disease was 9.6 months (95% CI, 8.5-11.0), and the median time to treatment failure was 9.3 months (95% CI, 8.2-10.4). The main grade 3/4 toxicities were neutropenia (78% of patients), leukopenia (30%), thrombocytopenia (18%), and anemia (15%); no grade 4 nonhematologic toxicities occurred, and grade 3 nonhematologic toxicities were mild. CONCLUSIONS: The combination of gemcitabine and carboplatin is active and feasible in platinum-sensitive patients with recurrent ovarian cancer. This regimen is undergoing further evaluation in a large phase III trial.

Primary fallopian tube carcinoma: a retrospective multicenter study.

PURPOSE: This retrospective multicenter study aimed to assess the survival and prognostic factors of primary fallopian tube carcinoma. METHODS: The medical records of 29 patients with fallopian tube carcinoma from two centers were reviewed for age, stage, surgical intervention, relapse and survival. RESULTS: The mean age of the patients was 56 years (range, 37-76). Six patients were in Stage I (20.7%), eight cases in Stage II (27.6%), nine cases in Stage III (31%) and two cases in Stage IV (6.9%). Data on stage was not available in four cases (13.8). Fifteen patients underwent lymph node evaluation. The median follow-up was 29 months (range, 3-122). The median survival was 95 months with a 5-year survival rate of 69.7%. The median progression-free survival was 76 months with a 5-year survival rate of 51.8%. CONCLUSION: Age, stage and lymphadenectomy were found to be significant prognostic factors on overall survival.

Adding concurrent low dose continuous infusion of cisplatin to radiotherapy in locally advanced cervical carcinoma: a prospective randomized pilot study.

The tolerability and efficacy of the continuous infusion of cisplatin during radiotherapy was studied by tumour response, survival and pelvic control, in carcinoma of the cervix. 44 patients with stage IIB-IIIB cervical carcinoma were prospectively randomized into two groups: radiation alone (control group) versus radiation plus cisplatin (study group). While there was no significant difference in diarrhoea and urinary complication scores, emesis and appetite changes were significantly greater in the study group. Tumour responses were no different at the end of the treatment and 3 months after completion of treatment. After 40 months median follow-up, 40/44 patients were assessed (one had a second primary tumour and three were lost to follow-up). Persistent disease was found in 3 patients: one in the study arm and two in the control arm. Recurrence was seen in 10 patients in the first 2 years. 5-year pelvic control rates were; 69.4% and 63.9% (p=0.7), survival rates were 52.0% and 48.9% (p=0.7) and disease-free survival rates were 67.5% and 58.7% (p=0.3) for the control and the study groups, respectively. Although the continuous infusion of cisplatin during radiotherapy was well tolerated, this additional treatment did not appear to show an improvement in pelvic control, survival, or disease-free survival.

Comparison of hepatocyte growth factor levels of epithelial ovarian cancer cyst fluids with benign ovarian cysts.

Hepatocyte growth factor (HGF) is known to take role in oncogenesis and tumoral behavior of the tumors of the organs that contain mesenchymal and epithelial cells together. This study aims to compare HGF levels in cyst fluids of epithelial ovarian cancer and benign ovarian cysts and look for the role of HGF in ovarian carcinogenesis. Twenty-four consecutive patients with ovarian cancer and 34 with benign cysts of ovary were recruited prospectively at Gynecologic Oncology Departments of SSK Ankara Maternity Hospital and Hacettepe University School of Medicine between 2001 and 2002. Cyst fluids were collected during primary staging in cancer patients and during laparatomy for benign patients. HGF levels were measured by enzyme-linked immunosorbent assay method. Median HGF levels of the benign ovarian cysts and epithelial ovarian tumoral fluids were found as 3822 pg/ml (85-15,253 pgr/ml) and 12,962 pgr/ml (4136-16,025 pgr/ml), respectively. Malign cyst fluids have higher HGF levels when compared with benign ovarian cysts (P < 0.01). This finding suggests that HGF may take a paracrine role in oncogenic differentiation and tumoral development of epithelial ovarian cancers. Mechanisms that take role in HGF secretion and the answers of the neighboring epithelial cells to HGF during tumoral development need to be investigated.

Comparison of HGF (hepatocyte growth factor) levels of epithelial ovarian cancer cyst fluids with benign ovarian cysts.

Hepatocyte growth factor (HGF) is known to take a role in oncogenesis and tumoral behavior of the tumors of the organs that contain both mesenchymal and epithelial cells. This study compares HGF levels in cyst fluids of epithelial ovarian cancer and benign ovarian cysts to look for the role of HGF in ovarian carcinogenesis. Twenty-four consecutive patients with ovarian cancer and 34 with benign ovarian cysts were recruited prospectively at the Gynecologic Oncology Departments of SSK Ankara Maternity Hospital and Hacettepe University School of Medicine between 2001 and 2002. Cyst fluids were collected during primary staging in cancer patients and during laparatomy for benign patients. HGF levels were measured by ELISA method. Median HGF levels of the benign ovarian cysts and epithelial ovarian tumoral fluids were found to be 3822 pg/ml (85-15253 pg/ml) and 12962 pg/ml (4136-16025 pg/ml), respectively. Malignant cyst fluids have higher HGF levels when compared with benign ovarian cysts (P < 0.01). This finding suggests that HGF may take a paracrine role in oncogenic differentiation and tumoral development of epithelial ovarian cancers. Mechanisms that take a role in HGF secretion and the responses of neighboring epithelial cells to HGF during tumoral development need to be investigated.

Primary choriocarcinoma of the uterine cervix in a postmenopausal patient: a case report.

BACKGROUND: Primary cervical choriocarcinoma seen in a postmenopausal patient is a very rare entity. CASE: Primary choriocarcinoma of the uterine cervix was diagnosed in a 54-year-old woman. She had admitted to our clinic with vaginal bleeding and had been postmenopausal for 1 year at the time of diagnosis. A cervical tumoral mass was seen in her pelvic examination and cervical biopsy revealed squamous cell carcinoma of the cervix. Pelvic examination under anesthesia was done and patient was accepted as FIGO Stage IIA. Type III hysterectomy with bilateral salphingoopherectomy and bilateral pelvic-paraaortic lymph node dissection was carried out. Postoperative pathological evaluation of the surgical specimen showed that case was a primary choriocarcinoma of the cervix. CONCLUSION: This is one of the few reported cases of cervical choriocarcinoma in a postmenopausal patient. The most appropriate theory for the development of this tumor is metaplastic differentiation of the tumor from another histologic type.

Neoadjuvant chemotherapy or primary surgery in advanced epithelial ovarian carcinoma.

Neoadjuvant chemotherapy has been proposed as an alternative approach to conventional surgery as initial management of bulky ovarian cancer, with the goal of performing adequate debulking in the interval surgery. Two hundred five consecutive patients with advanced ovarian cancer were divided into two groups. Neoadjuvant chemotherapy followed by interval surgery was performed in 45 of 205 patients. The remaining 158 patients received primary surgery plus adjuvant chemotherapy. Optimal cytoreductive surgery rates were significantly higher in the neoadjuvant CT group (P<0.001). In multivariate analysis, only residual tumor diameter and appendix involvement were found to affect total survival significantly in both groups. Five-year survival and median survival were not statistically different when all patients treated conventionally were compared with all patients treated with neoadjuvant chemotherapy. Primary chemotherapy followed by interval debulking surgery in a selected group of patients does not appear to worsen prognosis, but it permits less aggressive surgery and improves patients' quality of life.

Significance of serum and peritoneal fluid lactate dehydrogenase levels in ovarian cancer.

We investigated prospectively whether the detection of serum lactate dehydrogenase (LDH) and/or peritoneal fluid LDH levels may serve as a reliable biochemical marker in discriminating ovarian carcinoma from benign ovarian tumors. In this series, postoperatively 20 of 50 patients had a diagnosis of ovarian cancer while the remaining 30 patients had benign ovarian tumor. No significant difference in peritoneal fluid LDH levels was observed between patients with ovarian cancer and benign ovarian tumor (p > 0.05). Serum LDH levels in ovarian cancer patients were significantly higher than those in patients with benign ovarian tumor (p < 0.05). Statistically significant differences were not observed in LDH levels of different histological types of ovarian cancer and different stages of the disease. Serum LDH levels presented diagnostic accuracy with high specificity and may have a potential use as a biochemical marker.

Benefit of adjuvant radiotherapy in surgically staged stage I-II endometrial carcinoma.

AIMS AND BACKGROUND: This study was performed to determine the treatment outcomes and patterns of failure following external beam therapy in patients with pathological stage I-II endometrial carcinoma. STUDY DESIGN: Eighty-three patients with stage I-II endometrial carcinoma surgically staged who were found to have high risk factors and who received postoperative radiation therapy are the subject of this report. High risk factors were: histologic grade II-III, depth of myometrial invasion (DMI) > or =1/2, stage II, poor prognostic histology (clear cell, papillary serous cell) and lymphovascular invasion. RESULTS: Recurrences were observed in six patients. The recurrences were located in the vagina (1), lung (2), liver (1), and paraaortic lymph nodes (1). Five of the six recurrences were stage IC and II. The overall survival (OS), cause-specific survival (CSS) and disease-free survival (DFS) at five years were 82.9%, 85.0% and 81.3%, respectively. DMI, grade, age and cervical stromal invasion had a significant impact on CSS. CONCLUSION: Adjuvant radiotherapy decreases the rate of relapse in pathologically staged high-risk stage I-II endometrial carcinoma patients. After reviewing the other studies on this subject we conclude that vaginal cuff brachytherapy alone could be used in stage IA grade III and stage IB grade I-II patients because the recurrence rate is low; pelvic radiotherapy + vaginal cuff brachytherapy should be used for stage IC-II disease. Distant metastases occurred in five of our patients and represent a significant type of failure.

Accuracy of frozen section diagnosis in borderline ovarian malignancy.

This study was conducted to determine the accuracy of frozen section diagnosis in borderline ovarian tumors. Thirty-three patients were evaluated on the basis of frozen sections between February 1992 and December 1997. Frozen section diagnosis and final diagnosis were divided into three categories: for frozen section diagnosis: 1 = benign, 2 = borderline, 3 = 'at least' borderline, and for final diagnosis: 1 = benign, 2 = borderline, 3 = cancer. Three patients with a benign diagnosis according to their frozen sections were reclassified as borderline in the final diagnosis and all of them were of the mucinous type. The frozen section diagnosis of tumors of borderline malignancy was inaccurate in 3 of 23 patients. Four of 7 patients with at least borderline according to their frozen section diagnosis had invasive cancer at the final diagnosis. The correlation between frozen section diagnosis and final pathological examination was 72.7% (24/33). We found 9% (2/22) inaccurate results in the serous type and 36.6% (4/11) in the mucinous type. The sensitivity and specificity of frozen section diagnosis were found to be 86.95 and 57.14%, respectively. We concluded that frozen section evaluation in identifying a borderline ovarian malignancy is accurate enough to exclude the presence of a benign pathology.

Prognostic factors in stage IB-IIA cervical carcinomas treated with postoperative radiotherapy.

PURPOSE: This study investigated the prognostic significance of age, stage, tumor size, pelvic lymph node metastasis (PLM), surgical margin invasion, overall radiotherapy time (ORT), and interval between radiotherapy and surgery (IRS) in stage IB-IIA cervical carcinoma. METHOD AND MATERIALS: 100 patients treated with radical hysterectomy and postoperative radiotherapy were evaluated retrospectively. RESULTS: The 5-yr overall survival (OS), disease-free survival (DFS), and pelvic control rate (PC) were 83.6%, 82.8%, and 91.8%, respectively. PLM (p=0.008), IRS (p=0.01), ORT (p=0.007), and tumor size (p=0.028) were found to be significant on PC. PLM (p=0.04), ORT (p=0.04), and IRS (p=0.001) were significant on OS. PLM was significant (p=0.04) and IRS was marginally significant (p=0.06) on DFS. After multivariate analysis, PLM was significant on OS, DFS and PC. Recurrences were seen in 14 patients. CONCLUSION: According to this study PLM, IRS, and ORT are the most important prognostic factors. Recurrences outside the radiation volume leads to treatment failure.