Factors affecting sonographic preoperative local staging of endometrial cancer.

OBJECTIVES: To identify major factors in the under- and overestimation of cervical and myometrial invasion by endometrial cancer at preoperative staging by ultrasound. METHODS: This prospective study involved all patients with histologically confirmed endometrial cancer referred consecutively for surgical staging between January 2009 and December 2011. All patients underwent transvaginal ultrasound examination, obtaining metric and perfusion data, and the results were compared with final histology: myometrial invasion was defined at histology in the final pathology report as being either < or ≥ 50%, while cervical stromal invasion was reported as being either present or absent, and sonographic over-/underestimation was determined relative to these. RESULTS: Enrolled prospectively into the study were 210 patients. The proportion of cases with sonographic underestimation, relative to final histology, of myometrial invasion (i.e. false-negative estimation of no or superficial invasion < 50%) and of cervical invasion (i.e. false-negative finding of absence of stromal invasion) was comparable: 8.6% (n = 18) and 10.5% (n = 22), respectively. Myometrial invasion was overestimated by ultrasound (i.e. false-positive estimation of deep invasion ≥ 50%) in 15.7% (n = 33) of cases, and cervical invasion was overestimated (i.e. false-positive finding of presence of stromal invasion) in 4.8% (n = 10) of cases. These outcomes correspond to positive and negative predictive values of 67.6% (95% CI, 57.7-76.6) and 83.3% (95% CI, 74.9-89.8), respectively, for the subjective assessment of myometrial invasion, and 60.0% (95% CI, 38.2-79.2) and 88.1% (95% CI, 82.5-92.4), respectively, for that of cervical stromal invasion. The staging error in subjective assessment was not related to body mass index (BMI), to the position of the uterus in the pelvis or to image quality. Cervical and myometrial invasion were more often underestimated in well-differentiated endometrial cancers that were smaller in size, with thick minimum tumor-free myometrium and lower perfusion, and more often overestimated in moderately and poorly differentiated cancers that were larger in size, with thin minimum tumor-free myometrium and richer perfusion. CONCLUSION: The accuracy of subjective assessment of myometrial and cervical invasion by ultrasound was significantly influenced by tumor size, density of tumor vascularization, tumor vessel architecture and histological grading, while it was not significantly affected by BMI, uterine position and image quality.

Transrectal ultrasound and magnetic resonance imaging in the evaluation of tumor size following neoadjuvant chemotherapy for locally advanced cervical cancer.

OBJECTIVES: To assess the accuracy of magnetic resonance imaging (MRI) and transrectal ultrasound (TRUS) in the evaluation of tumor size and in the detection of residual tumor following neoadjuvant chemotherapy (NACT) in patients with cervical cancer. METHODS: This was a prospective study involving 42 women with locally advanced histologically confirmed cervical cancer referred for NACT. Clinical examination, TRUS and MRI were performed before and after NACT. The tumor volume was calculated using three standardized diameters (anteroposterior, laterolateral and craniocaudal) that were measured using both TRUS and MRI. Thereafter patients underwent surgical treatment and the same tumor measurements were taken by a pathologist using a fixed surgical specimen. Tumor volumes were calculated from tumor dimensions using the ellipsoid formula, and data obtained from both imaging methods were compared with pathological results as the gold standard. RESULTS: Twelve cases were excluded from the study owing to disease progression (these patients were referred for primary radiotherapy) or inability to perform MRI, leaving data from 30 patients for the final analysis. On average, tumor volume decreased after NACT by 84.6 and 87.1% as measured by MRI and TRUS, respectively. The agreement between measurements obtained by MRI and histology did not reach significance (intraclass correlation coefficient, 0.344 (95% CI, -0.013 to 0.610), P = 0.059), while agreement between TRUS and histology was statistically significant (intraclass correlation coefficient, 0.795 (95% CI, 0.569-0.902), P < 0.001). The accuracy of residual tumor detection (for non-microscopic tumors > 5 mm3 in volume) reached 77% for both MRI and TRUS. The sensitivity of TRUS was, however, lower than that of MRI (83 vs. 96%). The positive predictive values were similar for the two methods. CONCLUSIONS: TRUS should be considered as an accurate diagnostic method in the evaluation of tumor volume after NACT in patients with cervical cancer and may constitute a reliable alternative imaging method to MRI.

[The rational preoperative diagnosis of ovarian tumors - imaging techniques and tumor biomarkers (review)]. / Racionální predoperacní diagnostika benigních a maligních ovariálních nádoru - zobrazovací metody, nádorové markery.

The majority of patients who suffer from an early-stage or advanced-stage of ovarian cancer complain about symptoms, mainly gastrointestinal ones. The pelvic examination in ovarian cancer detection is limited by the adnexal position in the pelvis and frequent extraovarian spread of disease. Recently, any reliable tumor biomarker (CA 125 and/or HE4), which can be used in differential diagnosis between benign and malignant ovarian tumors, does not exist. According the results of the largest multicenter International Ovarian Trial Analysis (IOTA), ultrasound if performed by an experienced sonologist is an ideal diagnostic method in differential diagnosis between benign and malignant ovarian tumors. The experienced examiner is also able to detect extraovarian tumor spread and to assess tumor operability. Magnetic resonance imaging (MRI) is used only to complement ultrasound in cases when high tissue resolution is needed. Computed tomography (CT) is a useful method for detection of extraovarian spread, especially in cases when an ultrasound examiner experienced in abdominal scanning is not available. Similarly, fusion of positron emission tomography with CT (PET/CT) is a highly accurate method for the detection of abdominal and extraabdominal tumor spread, but its use is limited by cost and the low availability of this method. On the other hand, PET/CT is not recommended for primary ovarian cancer detection because of its lower sensitivity in comparison to ultrasound and its high false positive rates as well.

Sentinel lymph node status in patients with locally advanced cervical cancers and impact of neoadjuvant chemotherapy.

OBJECTIVES: Neoadjuvant chemotherapy (NAC) is used in locally advanced cervical cancers with the aim to decrease the size of the tumor and to allow for less radical surgery. Despite of the fact that the high response rate of the tumor has been well established, the impact of NAC on sentinel lymph node (SN) detection and status has not been explored to date. METHODS: Our study included 82 patients with locally advanced cervical cancers (FIGO IB1 >3 cm, IB2, IIA2 and selected IIB) out of which 51 patients were referred to SN biopsy prior to NAC and 31 patients to radical surgical procedure including SN biopsy after three courses of "dose density" NAC. In both groups, the prevalence of macrometastases, micrometastases and isolated tumor cells (ITC) in SN was compared. RESULTS: The total of 179 SNs was evaluated. SN detection rate in the whole cohort reached 87.8% per patient and 60.9% bilaterally, without significant difference between both groups. In the group with upfront SN biopsy prior to NAC the prevalence of macrometastases, micrometastases and ITC amounted to 43.1% (22/51), 7.8% (4/51) and 7.8% (4/51) respectively. In the group with SN biopsy after previous NAC, macrometastases were detected in 22.6 (7/31) of patients in SN, whereas there was only one micrometastasis and no ITC detected in that group. CONCLUSIONS: Neoadjuvant chemotherapy did not influence the detection rate of SNs, yet it was associated with significantly reduced prevalence of metastatic involvement of SNs, especially almost completely eliminating low volume disease.

Ultrasonographic appearance of metastatic non-gynecological pelvic tumors.

OBJECTIVE: To describe the ultrasound (sonomorphologic and vascular) characteristics of metastatic non-gynecological pelvic tumors, and to identify ultrasound characteristics typical of the most common non-gynecological pelvic tumors. METHODS: In 92 patients with a pelvic mass who had undergone ultrasound examination with subsequent surgery or tru-cut biopsy revealing a metastatic non-gynecological tumor origin, we analyzed retrospectively the sonomorphologic and vascular parameters. All parameters were evaluated for the whole group of non-gynecological tumors as well as separately for each specific tumor type. The findings were compared with those from 100 women with epithelial ovarian cancer. RESULTS: We found that CA 125, size of tumor, echogenicity, homogeneity of solid portion, mobility, and presence of ovarian crescent sign, parenchymal metastases and suspicious necrosis were individual statistically significant discriminators (P < 0.01) between the metastatic non-gynecological tumor group and the epithelial ovarian cancer group. CONCLUSIONS: Metastatic non-gynecological tumors in the pelvis have a significantly different sonomorphologic pattern compared with primary epithelial ovarian cancer. This pattern is dependent on the primary origin of the tumor. Doppler parameters, however, cannot differentiate between primary ovarian cancer and metastatic non-gynecological tumors.

Outcomes of pregnant patients with Pap smears classified as atypical glandular cells.

OBJECTIVES: The incidence of cervical cancers increases with age. Due to the trend of increasing age of first pregnancy, abnormal Pap smears including those classified as atypical glandular cells (AGC) are being found more often in early pregnancy. Once invasive cancer is excluded, conservative management of squamous intraepithelial lesions (SIL) in pregnancy is considered safe; however, optimal management of AGC is not well established. The aim of our study was to evaluate the outcome of patients with AGC diagnosed from smears during pregnancy. METHODS: The study included 17 patients referred to us in early pregnancy with Pap smears reported as AGC: 11 not otherwise specified (AGC-NOS), five favour neoplasia (AGC-FN) and one adenocarcinoma in situ (AIS). Thirty-one with high-grade SIL (HSIL) Pap smears confirmed on punch biopsy in early pregnancy comprised a control group. Human papillomavirus (HPV) positivity was found in seven patients with persistent AGC-NOS (including all four who had CIN3 postpartum). All the women were initially examined by expert colposcopy and those with AGC-FN or AIS smears also by transrectal ultrasound to exclude invasive endocervical cancer. Follow-up controls were carried out every 8-12 weeks and, if there were no signs of progression, revaluation was scheduled 6-8 weeks after delivery. RESULTS: The mean age of the women was 31.4 years. Conization in one patient in the study group was performed in the 16th week of pregnancy due to colposcopic signs of microinvasive squamous cell cancer confirmed on histology. Progression to invasive cancer was not found in any of the other 16 patients in the study group or in the control group. Cervical intraepithelial neoplasia or AIS was confirmed postpartum by conization or punch biopsy in 47.1% (8/17) of patients in the study group and, in 77.4% (24/31) of patients in the control group. CONCLUSIONS: Conservative management of women with AGC in pregnancy is safe where invasive cancer is excluded. As histological verification of glandular pre-cancerous lesions by punch biopsy is not reliable and the postpartum regression rate cannot be determined precisely, conization should be performed in all cases with AGC-FN or AIS. Triage of persistent AGC-NOS with HPV testing is useful in distinguishing significant underlying lesions.

[Transabdominal ultrasound examination in gynecology]. / Transabdominální ultrazvukové vysetrení v gynekologii.

OBJECTIVE: To present structured guidelines to transabdominal ultrasound examination in gynecology. SUBJECT: Practical guide. SETTING: Oncogynecological Center, Department of Obstetrics and Gynecology, Charles University in Prague - First Faculty of Medicine and General Faculty Hospital, Prague. SUBJECT AND METHOD: After having gone over the now-a-days literature and summarized our experience, we present description of normal and more frequent and common pathological findings on transabdominal ultrasound. CONCLUSION: Entire examination takes usually a couple of minutes, but gives much more information to distinguish between potential causes of patient's difficulties and allows for focusing an adequate diagnostic and therapeutic management.

[Ultrasound-guided minimally invasive interventions in gynecologic oncology]. / Minimálne invazivní výkony pod ultrazvukovou kontrolou v onkogynekologii.

OBJECTIVE: To present our experience with ultrasound-guided minimally invasive interventions in gynecologic oncology. SUBJECT: Original paper. SETTING: Oncogynecological Center, Department of Obstetrics and Gynecology, Charles University in Prague - First Faculty of Medicine and General Faculty Hospital, Prague. SUBJECT AND METHOD: We provide minimally invasive punction interventions under ultrasound guidance using either abdominal or vaginal probe in three indication groups - diagnostics (tru-cut biopsy), therapy (punction drainage of lymphocyst) and palliation (insertion of permanent peritoneal catheter). CONCLUSION: Ultrasound-guided minimally invasive interventions represent a group of accessible and relatively simple methods useful in many indications, not only in gynecologic oncology. Adoption of these methods allows to broadening the spectrum of interventions offered and decreasing patient's stress.

[Hereditary susceptibility to endometrial cancer]. / Dedicná dispozice ke vzniku karcinomu endometria.

OBJECTIVE: To present up-to-date knowledge concerning field of hereditary susceptibility to endometrial cancer as a part of hereditary non-polyposis colorectal cancer (Lynch syndrome). SUBJECT: Review. SETTING: Oncogynecological Center, Department of Obstetrics and Gynecology, Charles University in Prague, First Faculty of Medicine and General Faculty Hospital, Prague. SUBJECT AND METHOD: After having gone over the now-a-days literature and summarized our experience with management of high risk women of Lynch syndrome families we present up-to-date overview of this field problematics. CONCLUSION: Although endometrial cancer arising due to germ-line susceptibility account for a small part of these malignancies only, they represent disease with clearly defined and detectable serious risk factor. Management approach for these women is now defined and allows for early detection or lowering the risk. Educated gynecologist, as a field specialist, has good chance to identify women at risk and manage them in an appropriate way.

Ultrasound-guided tru-cut biopsy of abdominal and pelvic tumors in gynecology.

OBJECTIVE: To analyze the safety, adequacy and accuracy of tru-cut biopsy and to evaluate factors potentially affecting adequacy. METHODS: We analyzed retrospectively a group of patients who had undergone tru-cut biopsy for either primary suboptimally operable tumors, recurrence or suspected non-genital or secondary tumor. Tru-cut biopsy was performed either transvaginally or transabdominally, using an automatic biopsy gun with disposable needle and needle guide attached to the probe. The adequacy, i.e. obtaining a sample sufficient for identification of the origin of the tumor and performance of immunohistochemistry; accuracy, i.e. agreement between biopsy and final postoperative histology; and safety, as determined by complication rate, were assessed. Variables potentially influencing adequacy were analyzed using the orthogonal projections to latent structure method. RESULTS: A total of 195 biopsies were performed on 190 patients. An adequate sample was obtained in 178 (91.3%) biopsies. The final histology was not in agreement with the result from tru-cut biopsy in two out of 118 patients who underwent subsequent surgery (accuracy 98.3%). There were complications in two cases out of the 195 biopsies performed (1.0%). Ascites, elevated CA 125, primary suboptimal operable tumor, serous epithelial ovarian cancer histology, carcinomatosis and vaginal approach were significant positive predictors for the achievement of an adequate sample, while recurrence as an indication, non-serous and non-ovarian histotypes and transabdominal approach were negative predictors. CONCLUSION: Ultrasound-guided tru-cut biopsy is an efficient, minimally invasive, accurate and safe diagnostic method in the management of advanced, recurrent or atypical abdominal and pelvic tumors of probable non-genital origin, where unnecessary laparotomy or laparoscopy can be avoided. The adequacy of tru-cut biopsy is mainly influenced by indication group, histology, site of biopsy and approach. Our analysis can help in counseling the patient before the procedure and helps to explain the possible causes of failure of the procedure.

Late morbidity following nerve-sparing radical hysterectomy.

OBJECTIVES: Nerve-sparing (NS) modification of radical hysterectomy (RH) has been developed with the main purpose of improving the quality of life after radical surgical treatment of early-stage cervical cancer. Although the procedure has been discussed for almost 30 years, there are only limited data available on late morbidity. The aim of the study was to prospectively evaluate the morbidity of patients before and 6 months after NS RH and compare that with the morbidity in patients following different types of parametrectomy without nerve sparing. METHODS: Multiple parameters were assessed prospectively using 20-item self-reported questionnaire, focusing on three main areas of morbidity: bladder, sexual, and anorectal functions. Excluded were patients treated with adjuvant radiotherapy. RESULTS: Enrolled were women following NS RH (N=32), type C RH (N=19), and type D RH (N=21). Nine parameters significantly deteriorate in the whole group after the treatment: defecation straining (p=0.03), defecation regularity (p=0.0006), defecation frequency (p=0.02), need to use laxatives (p<0.001), flatulence incontinence (p<0.001), urinary incontinence (p<0.001), nocturia (p=0.002), loss of bladder sensation (p=0.04), and straining to void (p<0.001). There were significant differences (p<0.05) between groups following NS and type C or D RH in changes of following parameters: defecation regularity, receptivity to sexual activity, urinary incontinence, nocturia, and straining to void, while no differences were found between type C and D RH. Minimal changes were observed in any of 10 parameters of sexual functions. CONCLUSIONS: Our results confirmed a significant negative impact of RH on bladder and anorectal functions. Autonomic nerve preservation significantly improved morbidity 6 months after treatment.

[Use of transrectal ultrasound and magnetic resonance imaging in the staging of early-stage cervical cancer]. / Vyuzití transrektálního ultrazvukového vysetrení a magnetické rezonance ve stagingu casných stadií zhoubného nádoru delozního hrdla.

OBJECTIVE: The goal of this study was to compare the accuracy of magnetic resonance imaging (MRI)--a standard method--and transrectal ultrasound (TRUS) in the staging and determination of significant prognostic parameters in early-stage cervical cancer. The following prognostic parameters were evaluated: identification of residual tumor in the cervix after cone-biopsy, tumor volume, and early parametrial infiltration. DESIGN: Prospective study. SETTING: Oncogynecological Center, Department of Obstetrics and Gynecology, General Faculty Hospital of Charles University, Prague. METHODS: Patients referred to Oncogynecological Center from January 2004 to February 2006, in whom early-stage cervical cancer (T1a1-T2a) was diagnosed by clinical examination, were prospectivelly enrolled in the study. Only those patients who were examined by both MRI and TRUS with following surgical treatment were included. Imaging results were compared with pathology findings. RESULTS: Data from 95 patients were evaluated. The accuracy of tumor detection in 95 patients was 93.7% for TRUS and 83.2% for MRI (P < or = 0.006). In small tumors (< or = 1 cm3), the accuracy of tumor detection by TRUS was 90.5% and 81.1% by MRI (P < or = 0.049). The accuracy of parametrial infiltration detection by TRUS and MRI was 98.9% and 94.7%, respectively (P < or = 0.219). The accuracy was not influenced by body mass index values. CONCLUSION: Our results show TRUS achieving comparable or even higher accuracy than the more commonly used MRI in staging of early-stage cervical cancer.

[Ultrasound-guided intervention in the treatment of abdomino-pelvic advanced tumors]. / Význam intervencní ultrasonografie v l écbe pokrocilých abdomino-pelvických nádoru.

OBJECTIVE: The goal of this study was to evaluate the accuracy and safety of ultrasound-guided tru-cut biopsy in advanced abdomino-pelvic tumors in a sufficiently large cohort. DESIGN: Prospective study. SETTING: Oncogynecological Center, Department of Obstetrics and Gynecology, General Faculty Hospital of Charles University, Prague. METHODS: Patients indicated for tru-cut biopsy were those with primarily inoperable tumors, with advanced tumors and compromised performance status preventing a primary surgical procedure, and with recurrent pelvic tumors requiring histological verification. All were referred to the Oncogynecological Center between January 2005 and June 2007. Tru-cut biopsy was taken either from pelvic tumor or from its metastatic sites transvaginally or transabdominally under ultrasound guidance. Sample adequacy was evaluated. RESULTS: Altogether, 119 patients were referred for tru-cut biopsy during a study period. Only 4 cases were found unsuitable for tru-cut biopsy and the patients were referred for laparoscopy instead. Samples were obtained transvaginally in 67 patients (58.3%) and transabdominally in 48 patients (41.7%). The biopsy was taken from pelvic tumor in 59 patients (51.3%), omental cake in 14 patients (12.2%), from peritoneal visceral or parietal carcinomatosis in 37 patients (32.2%) and from other localities in 5 patients (4.3 %). The diagnostic adequacy of ultrasound-guided tru-cut biopsy reached 94.8% (95% CI, 94.17-99.40%). There were only two tru-cut biopsy-related complications: The first case involved bleeding from tumor in a patient with mild thrombocytopenia that required laparotomy; in the second case, diagnostic laparoscopy was indicated after a minor bleeding occurred in the biopsy site on ultrasound, however, no significant pelvic bleeding was confirmed by the procedure. CONCLUSION: Ultrasound-guided tru-cut biopsy is a safe, reliable, fast, and cost-effective diagnostic method for histological verification of both advanced primary and recurrent abdomino-pelvic tumors. It can be performed in an outpatient setting without the need for general anesthesia, causing a minimal discomfort to the patient in comparison with laparoscopy or laparotomy. The risk of complications is low and the main advantage is the acquirement of a sample adequate for further immunohistochemical examination, which is a necessary requirement for the choice of optimal oncological treatment.

[Molecular characterization of epithelial ovarian borderline tumors with respect to clinical management and prognosis]. / Molekulární charakteristiky borderline ovariálních tumoru ve vztahu k biologickému chování nádoru.

OBJECTIVE: To analyze up-to-data knowledge in the field of molecular characterization of epithelial ovarian borderline tumors with respect to clinical management and prognosis. DESIGN: Review. SETTING: Oncogynecological Center, Department of Obstetrics and Gynecology, Charles University in Prague, First Faculty of Medicine, and General Faculty Hospital, Prague. METHODS: Based on literature search and own experimental data in the field of molecular biology of ovarian cancer and borderline tumors of ovary, we summarize up-to-date knowledge of molecular differences and specific features of BTO with respect to implementation of these knowledge into the clinical management. RESULTS AND CONCLUSION: We suppose that spectrum of genomic changes (i.e. genetic and epigenetic) causing tumor transformation is limited and these changes take place in stem or progenitor cell. Analysis of genomic changes can help to define certain subtypes of BTO and, correlated to clinical characteristics, to identify subtypes with different biological behavior. Such molecular typing of BTO allows to individualize treatment.

[Inactivation of BRCA1, BRCA2 and p53 genes in sporadic ovarian cancer]. / Inaktivace genu BRCA1, BRCA2 a p53 u sporadického karcinomu vajecníku.

OBJECTIVE: To analyze loss of heterozygosity (LOH), loss of expression and somatic mutations of BRCA1, BRCA2 and p53 genes in sporadic epithelial ovarian cancer samples. DESIGN: Original paper. SETTING: Oncogynecologic center, Clinic of Obstetrics and gynecology, First Faculty of Medicine, Charles University in Prague and General Teaching Hospital, Prague. MATERIAL AND METHODS: We used genomic DNA and total RNA from peripheral blood and fresh frozen tumor as a template for LOH, loss-of-expression and mutation analyses. RESULTS: LOH in at least one region was found in 60% of tumors. Majority of these alterations occurred not solely, but in conjunction with other region deletions. CONCLUSION: Our study confirms high frequency of somatic alteration of BRCA1, BRCA2 and p53 genes in sporadic epithelial ovarian cancer.

[Detection of HPV DNA in lymph nodes in early stages cervical cancers]. / Stanovení DNA HPV v lymfatických uzlinách u casných stadií karcinomu delozního hrdla.

OBJECTIVE: Review recent knowledge concerning significance of detection of DNA HPV in regional lymph nodes in cervical cancer patients. TYPE OF THE STUDY: Literature review. SETTING: Department of Obstetrics and Gyneacology, 1st Faculty of Medicine, Charles University and General Teaching Hospital, Prague. RESULTS: Metastatic involvement of pelvic lymph nodes is the most important prognostic parameter in early stages cervical cancer. Still, almost 20% of patients with negative pelvic nodes experience recurrence. Detection of HPV DNA in lymph nodes might be a marker of occult metastatic involvement. However, published data are limited, mostly due to inconsistent methodology. Only 3 prospective studies evaluating HPV from fresh or frozen tissue were published till now, all other retrospective studies extracted HPV DNA from paraffin embedded samples. A few papers showed correlation between HPV DNA and metastatic involvement of pelvic lymph nodes. DNA HPV identification in histopatology-negative nodes was considered as a risk factor for recurrence. Presence of DNA HPV 18 in histopathology-negative pelvic nodes was described as a poor prognostic factor; however prognostic significance of individual genotype is still unclear. CONCLUSION: Detection of high risk HPV DNA in regional lymph nodes is a good candidate for prognostic parameter in early stages cervical cancers. The group of women with both absence of metastatic involvement and negative HPV DNA evaluation of regional lymph node should represent a cohort of patients with particularly good prognosis.