Technetium-99m-sestamibi scintigraphy in gynecological cancer imaging.

A new diagnostic method, technetium-99m-sestamibi scintigraphy, and its potential use in gynecological oncology is described. The biochemical mechanisms of uptake and retention of technetium-99m-sestamibi in neoplastic cells are presented and the grounds for the potential use of the tracer in predicting the response to first-line chemotherapy in ovarian cancer patients are discussed. Based on the available literature data and on our own studies, the sensitivity and specificity of technetium-99m-sestamibi scintigraphy in ovarian cancer diagnosis are assessed, and the current place of this method among other functional imaging methods applied in gynecological oncology is discussed. Technetium-99m-sestamibi scintigraphy seems to provide an attractive alternative method to the expensive PET imaging, and can be easily performed in most hospitals. However, further studies in a larger series of patients are necessary before this method is widely applied.

Color Doppler assessment of blood flow in endometrial cancer.

OBJECTIVE: To determine the location and intensity of angiogenesis as well as selected flow parameters by transvaginal color Doppler (TVCD) and to evaluate the relation of myometrial invasion, histological grading, lymph nodes, and omental and adnexal metastasis on blood flow characteristics in endometrial cancer. METHODS: Transvaginal colour Doppler and pulsed Doppler ultrasound were performed on 90 women with endometrial cancer. The degree of invasion as well as adnexal, omental, and pelvic lymph node metastasis was evaluated. Location of the blood vessels (peripheral, central, mixed) and vascular density as well as selected Doppler blood flow indices: PSV, RI of neoplastic infiltration was assessed. RESULTS: The median age of the 90 women was 63.3 +/- 12.3 years (range 32 to 86 years); of these 92.2% were postmenopausal. Cancer concerned only the endometrium (E), with superficial (S) and deep infiltration (D) established in 14.4%, 45.6% and 40%, respectively. The histological maturity was as follows: G1 - 17.6%, G2 - 66.7%, G3 - 16.6% of cases. Adnexal, omental and lymph node metastasis was found in 12.2%, 3.3% and 16.6%, respectively. Abnormal low impedance and high velocity flow (mean RI 0.38 +/- 0.09, PSV 20.45 +/- 9.6 cm/sec) were found in 88.9% of cases. In types E, S, D in 61.5%, 92.7% and 94.4%, respectively (p = 0.003). Differences in RI and PSV between groups with high and low vascular density were statistically significant (p = 0.005 and 0.001, respectively). In all cases peripheral and mixed vascularity were found more frequently (p < 0.05). A positive significant correlation between vascular density increase and surgicopathological stage of cancer was found more frequently (p < 0.005). There were significant differences in vascular density, Doppler blood flow indices and vascular location in each type of histological malignancy (p < 0.05). No significant differences in each flow parameter in hematogenous-adnexal/omental metastatic and non metastatic cases were found, whereas pelvic lymph node involvement and vascular density were shown to be statistically significant (p < 0.02). There were significant differences in vascular density in lymph-node positive cases whereas the remaining flow parameters did not differ. CONCLUSIONS: These results suggest that TVCD evaluation of endometrial cancer is a reliable method for assessing endometrial angiogenesis. Our results indicate that blood flow rates correspond with increased angiogenesis in endometrial cancers, and might potentially be used as a good prediction factor for tumor progression and metastasis in affected women. Preoperative ultrasound examination should be seen as an important tool in the establishment of individualized treatment programs for women with endometrial cancer.

Diagnostic value of the photodynamic method in the evaluation of lesions of the uterine cervix.

The purpose of this study was to assess the efficacy of the photodynamic diagnosis (PDD) method in the diagnosis of lesions of the uterine cervix, as well as to establish its place and efficacy among currently available diagnostic techniques. In the case of lesions located on the cervix, the projected aim of the study was intended to be realised by performing a detailed comparative analysis of the examination results of the following: PDD, cytology, colposcopy and testing for the presence of viruses, as compared with histological evaluation of performed biopsies.

Possibilities and limitation of endoscopic procedures in oncological gynaecology.

In cases of gynaecological cancer, the use of endoscopic techniques, in spite of becoming more frequent, is very controversial. Mainly, the potential risk of dissemination, which worsens the patient prognosis and leads to consequent adjuvant therapy is of concern. Based on data from the literature the authors present the advantages and disadvantages of using hysteroscopy in patients suffering from endometrial malignancy. According to the references and personal experience, the diagnostic and therapeutic value of laparoscopy in cases of cervical, endometrial and ovarian cancer are discussed.

Diagnostic value of the PDD method in evaluation of vulvar lesions.

The purpose of this study was to evaluate the efficiency of photodynamic diagnostics (PDD), a method used in the diagnosis of vulvar lesions, and to determine its position and efficacy among diagnostic techniques generally used up to now. The projected purpose of the study in cases of vulvar lesions was realised by performing a detailed comparative analysis of sensitivity, specificity and diagnostic efficacy of PDD and vulvoscopy, as compared with histological evaluation of excised lesions.

TP53 status determines clinical significance of ERBB2 expression in ovarian cancer.

ERBB2 expression has been found in 19 to 44% of ovarian carcinomas; however, its predictive value has not been demonstrated, and trastuzumab has not found clinical application in ovarian cancer patients. We evaluated clinical significance of ERBB2 expression in relation to TP53 accumulation in ovarian carcinoma patients treated with platinum-based regimens. Immunohistochemical analysis with CB11 and a novel NCL-CBE356 antibody (against the internal and external domains of ERBB2, respectively) was performed on 233 tumours (FIGO stage IIB-IV); the US Food and Drug Administration-approved grading system with 0 to 3+ scale was used for evaluation, and the results were analysed by the Cox and logistic regression models. In all, 42% of the tumours expressed (category 1+, 2+ or 3+) either CB11 or CBE356 or both (CB11/CBE356 parameter). Associations between ERBB2 expression and clinical factors were observed only if tumours with staining category 1+ were grouped together with tumours showing staining categories 2+ and 3+. CB11/CBE356 parameter had a better predictive value than CB11 alone. CB11/CBE356 expression was negatively associated with platinum sensitivity (PS) in the TP53(-) group (P=0.022) and with disease-free survival (DFS) in the TP53(+) group (P=0.009). Our results may suggest that trastuzumab should be given postoperatively to patients with TP53(-)/ERBB2(+) ovarian carcinomas to enhance PS, and after completion of chemotherapy to patients with complete remission and TP53(+)/ERBB2(+) carcinomas to extend DFS time (in total to 30.4% of all patients analysed). Thus, novel criteria for ovarian cancer patient inclusion for clinical trials with trastuzumab should be considered and tested.

The importance of fine needle aspiration biopsy and sonographic evaluation of parametria in cervical cancer.

OBJECTIVE: The aim of study was to estimate of the value of fine needle aspiration biopsy (FNAB) and transvaginal ultrasonography (TVS) in the preoperative assessment of the parametria in cervical cancer. We compared parametrial infiltration before and postoperatively by histopathology to verified and confirmed staging of disease. Correct staging qualification, especially evaluation of the parametrium, is very useful in choosing an adequate method of treatment, and thereby in patient survival. MATERIAL AND METHOD: 52 women (median age 56 years, range 33-85) with cervical cancer in Stage Ib and 49 (median age 51, range 36-71) in Stage II and III, were included in the study. Assessment of parametrial invasion before treatment was performed by fine needle aspiration biopsy (FNAB) with endovaginal ultrasound assistance. The sonographic evaluation of parametria was performed by Siemens Sonoline Versa Pro with a transvaginal 7 MHz mechanical transducer with a biopsy guide and 21-gauge needle. The probe was covered with a disposable latex sheath filled with ultrasound gel. The aspirated material was placed on a glass slide, fixed in 95% alcohol and submitted to cytologic evaluation. All of the patients with cervical cancer in Stage Ib underwent a Wertheim-Meigs hysterectomy. The preoperative findings were compared with data obtained by histopathology findings. Moreover, in the whole group of 101 patients a comparison of FNAB and sonography was performed. The sensitivity, specificity and diagnostic accuracy of this method were evaluated. RESULTS: Parametrial involvement assessed postoperatively by histopathology, in clinical Stage Ib cervical cancer was found in eight of 52 cases (15.4%). FNAB of parametrial involvement in the operated group was accurate in 14 of 18 (accuracy--83%, sensitivity--78%, specificity--84%, PPV--50%, NPV--95%). Sonographic assessment of parametrial involvement was correct in 12 of 18 cases (accuracy--58%, sensitivity--67%, specificity--56%, PPV--24%, NPV--89%). In the whole group of patients (operated and non-operated), sonographic evaluation of parametria verified by FNAB was correct in 104 of 202 cases (accuracy--78%, sensitivity--71%, specificity--86%, PPV--84%, NPV--74%). CONCLUSIONS: FNAB and TVS assessment of the parametria are very useful methods in confirmation of neoplastic infiltration. Correct preoperative diagnosis may improve staging, treatment and indirectly, survival of patients with cervical cancer.

P21WAF1, P27KIP1, TP53 and C-MYC analysis in 204 ovarian carcinomas treated with platinum-based regimens.

BACKGROUND: The prognostic and predictive value of cell cycle regulatory proteins in ovarian cancer has not been established. We evaluated the clinical and biological significance of P21(WAF1), P27(KIP1), C-MYC, TP53 and Ki67 expressions in ovarian cancer patients. MATERIALS AND METHODS: Immunohistochemical analysis was performed on 204 ovarian carcinomas of International Federation of Gynecology and Obstetrics (FIGO) stage IIB to IV treated with platinum-based chemotherapy. Multivariate analysis with Cox and logistic regression models was performed in the whole group, and in the TP53-negative and TP53-positive subgroups. RESULTS: High P21(WAF1) labeling index (LI) was an independent positive predictor of platinum-sensitive response (P = 0.02). Overall survival was positively influenced by P21(WAF1) LI (P = 0.02) or by P21(WAF1) plus P27(KIP1) LI (P = 0.004) in the TP53-negative group only. Ki67 LI showed borderline association with disease-free survival (P = 0.05). Growth fraction was negatively associated with P21(WAF1) and P27(KIP1) indices in the TP53-negative group (P = 0.023 and 0.008, respectively), and these associations were borderline or lost in the TP53-positive group. Endometrioid and clear cell carcinomas differed from other carcinomas by having a low incidence of TP53 accumulation, a high incidence of C-MYC overexpression (70%) and a low median Ki67 LI (all with P <0.001). CONCLUSIONS: We have shown an independent predictive value of P21(WAF1) LI in ovarian carcinoma patients. The prognostic value of P21(WAF1) and P21(WAF1) plus P27(KIP1) LI was determined by TP53 status. A high frequency of C-MYC overexpression in endometrioid and clear cell carcinomas may suggest its role in the development of these tumor types.

The value of ultrasonography in preoperative assessment of selected prognostic factors in endometrial cancer.

OBJECTIVE: To determine the efficiency of transabdominal and transvaginal ultrasonography (TAS and TVS) in the assessment of myometrial invasion, cervical involvement, pelvic lymph nodes, adnexal and omental metastases (preoperative staging) of endometrial cancer. METHODS: Transabdominal and transvaginal 2D, ultrasound were performed on 90 women to classify myometrial invasion, cervical involvement, pelvic lymph nodes and adnexal metastases in endometrial cancer. According to this 13 type E (invasion involving the endometrium), 41 type S (superficial, of less than 50% of myometrial infiltration), 36 type D (deep infiltration) and 22 cervical involvement were identified. There were 15 G1, 60 G2 and 15 G3 cases. Adnexal, omental and lymph-node metastases were found in 11, two and 15 cases, respectively. Endometrial cancer was diagnosed on the basis of dilatation and curettage. The degree of invasion was evaluated preoperatively. Ultrasonographic findings were compared to surgical staging and histopathology of the surgical specimen. RESULTS: The median age of the 90 women was 63.3 +/- 12.3 years (range 32 to 86 years). The median thickness of malignant endometrium was 19.5 +/- 9.6 (range 7 to 54 mm). In type E the median thickness was 11.76 +/- 4.2, in type S 17.3 +/- 7.6, in type D 24.8 +/- 9.8 and in cases with cervical involvement 23.2 +/- 11 mm. Myometrial invasion evaluated by TVS was accurate in 76 of 90 cases (accuracy 84.4%). In type E sensitivity was 92.3%, specificity 87.0%, positive and negative predictive value, respectively, 63.1% and 98.6%. In type S these values were respectively: 78.0%, 93.9%, 91.4%, 80.0% and in type D--88.9%, 92.6%, 88.9% and 100.0%. Tumor extension to the cervix was properly assessed in 19 of 22 women in which it was present (sensitivity 86.4%, specificity 85.3%, positive predictive value 85.5%, negative predictive value 95.1%). Adnexal metastasis was correctly diagnosed in 8 of 11 cases in which it was present (sensitivity 72.7%, specificity 97.5%, positive predictive value 80%, negative predictive value 96.3%), and lymph-node metastasis in only 5 of 15 cases (sensitivity 33.3%, specificity 100%, positive predictive value 100%, negative predictive value 88.2%). CONCLUSION: These results suggest that 2D TAS and TVS evaluation of endometrial cancer are reliable methods for preoperative assessment of selected prognostic factors, e.g. myometrial invasion, cervical involvement and adnexal metastases. However in assessing lymph-node metastases, TVS with its low sensitivity, did not provide additional information. Preoperative ultrasound examination should be speculated as an important tool in the establishment of different surgical choices which can be made after a correct pretreatment prognosis.

The effectiveness of hysteroscopic polypectomy in cases of female infertility.

The authors, based on their own material, evaluated the value of hysteroscopic treatment of endometrial polyps in a group of infertile women. Polypectomy was performed in 25 patients using either endoscopic microscissors or electric loop. Follow-up hysteroscopy was performed after two months as an integral part of the treatment. All the patients were observed for 12 months. The primary intrauterine investigation was complete in all patients without regard to kind of instrument which was confirmed by second-look hysteroscopy. About 80% of the patients who underwent surgery conceived. Restoration of reproductive ability did not depend on the size of the removed lesion.

Hysteroscopy in cases of cervical polyps.

To assess the usefulness of hysteroscopy in cases of cervical polyps, we studied 78 patients with a lesion found during a routine gynecological examination. All women were referred for diagnostic hysteroscopy followed by endoscopic polypectomy. In 83.3% of the cases intrauterine investigation confirmed primary diagnosis - a polyp peduncle in the cervical canal. Sixty-five of those lesions were the only pathologic condition, and six (7.7%) were associated with an endometrial polyp. In the remaining 16.7% of examined patients, primary polyps identified as cervical polyps appeared to be endometrial. All women admitted to the study were successfully treated by hysteroscopy. Our results suggest that endoscopic evaluation of the uterine cavity in women with cervical polyps can clarify the initial diagnosis. Hysteroscopy allows not only a precise visualisation of the polyp peduncle but also gives the possibility to identify and treat concurrent asymptomatic intrauterine pathological conditions.

Evaluation of clinical significance of TP53, BCL-2, BAX and MEK1 expression in 229 ovarian carcinomas treated with platinum-based regimen.

In cell line studies, BCL-2, BAX, as well as novel MEK1 protein levels have strong influence on ovarian cancer response to cisplatin-based chemotherapy. However, such associations have not been demonstrated clinically. We evaluated prognostic/predictive significance of these proteins with regard to TP53 status. Immunohistochemical analysis was performed on 229 ovarian carcinomas FIGO stage IIB-IV treated with platinum-based chemotherapy; the results were analysed by the Cox and logistic regression models. Clinical parameters (residual tumour size, patient age, FIGO stage) were the only indicators of overall survival (OS) and the strongest predictors of complete remission (CR). On the other hand, BAX expression was the strongest (P=0.005) or the only (in FIGO IIIC, P=0.02) prognostic indicator of disease-free survival (DFS) in the TP53(+) group. TP53(+) and TP53(-) ovarian carcinomas differed in clinical and molecular prognostic and predictive factors. Another novel finding is that CR was negatively influenced by high BAX expression in all patients group (P=0.047) and by BCL2 expression in the TP53(-) group (P=0.05). High MEK1 expression was associated with endometrioid and clear cell carcinomas (P=0.049); its loss was found with advancing FIGO stage (P=0.002). Our results suggest that binomial TP53 status divides ovarian carcinomas into two biologically distinct groups. BAX expression is an important factor of DFS in the TP53(+) group. BCL-2 and BAX, but not MEK1 expressions have predictive value in ovarian cancer patients treated with platinum-based chemotherapy.

Preoperative discrimination between malignant and benign adnexal masses with transvaginal ultrasonography and colour blood flow imaging.

BACKGROUND: Ovarian cancer is one of the causes of death in women, and in about 70% of cases is recognized only in advanced stages. This study was undertaken to evaluate distinctive values of transvaginal and color Doppler ultrasonography in differentiating malignant and benign adnexal masses through analysis of ultrasonic morphological features of malignancy and estimation of location and intensification of angiogenesis as well as values of resistance of flow in examined masses. PATIENTS AND METHODS: 329 women with malignant and benign adnexal masses underwent ultrasonographic and colour Doppler examination 1-5 days before surgery (laparotomy, laparoscopy) thus allowing histological verification of diagnosis. The ultrasonographic structure was assessed using a morphological scoring system devised by Sassone, Jain and Benacerraf. Regions showing vasculature, especially within septae and solid parts of tumours were examined by means of transvaginal colour Doppler. Location and intensification of angiogenesis as well as resistance index (RI) were investigated. Sensitivity, specificity, PPV and NPV of both techniques were assessed. Statistical analysis of obtained data were based on the Student's t test; p < 0.05 level was considered significant. RESULTS: Postoperatively 255 (77.5%) benign and 74 (22.5%) malignant tumours were seen. In the group of benign masses the average age of women was 42.6+/-12.3 and in the malignant it was 53.1+/-12.6 (p<0.0001). The transverse dimension of benign lesions was 77.2+/-19, whereas for malignant it was 107.0+/-31 (p<0.0001). Benign tumours in 63.0% were cystic, in 26.0% mixed cystic-solid and in 11.0% solid echostructures while in malignant they were respectively, 6.8%, 56.8% and 36.4% (p<0.0001). Doppler flow within the tumour was 74.5% in benign and 98.6% in malignant masses (p<0.0001). In benign lesions homogenous superficial or peripheral vasculature was visualized, and in the majority of cases (82.7%) it was of medium intensification. However in malignant central, peripheral or mixed vascularisation. in the majority intensified character was found. Average value of the resistance index in all benign masses amounted to 0.77+/-0.14, however in malignant it was 0.39+/-0.07 (p<0.0001). CONCLUSIONS: We contend that complete ultrasonographic estimation of ovarian neoplasms outside the qualification of structural details should include Doppler analysis of vasculature parameters. Most important is the qualification of resistance of flow, and location and intensification of vascularisation in examined masses which permit the differentiation of malignant and benign lesions. Preoperatively recognizing malignant processes with colour Doppler ultrasonography shows higher accuracy, specificity and PPV.

Spontaneous apoptosis in ovarian carcinomas: a positive association with p53 gene mutation is dependent on growth fraction.

Changes in cell survival contribute to tumour development, influence tumour biology and its response to chemotherapy. p53 gene alterations should negatively affect apoptosis by impaired p53-dependent apoptotic response. We looked for associations between spontaneous apoptosis, p53 gene mutation, p53 protein accumulation, growth fraction, bcl-2 expression and histological parameters in 64 ovarian, four tubal and three peritoneal carcinomas. Apoptotic cells were detected with the TUNEL method. p53 gene variants were detected by the single-strand conformation polymorphism and were sequenced directly. P53, Ki-67 and bcl-2 protein expressions were detected immunohistochemically. A weighed multiple logistic regression model was applied. Apoptotic index (AI) ranged 0.02-0.18 (mean 0.11); proliferation index (PI) ranged 3-90% (mean 54%). p53 gene mutations were present in 51, p53 protein accumulation in 46, and diffuse bcl-2 expression in 29 of 71 tumours. The AI was positively associated with the presence of p53 gene mutation (P = 0.011). However, the PI included into the analysis did positively influence the AI (P = 0.02) and diminished the association with p53 gene mutation (P = 0.082). The AI was negatively associated with good histological differentiation (P = 0.0006), the serous tumour type (P = 0.002), and diffuse bcl-2 expression (P = 0.025). Strong bcl-2 expression was associated with endometrioid tumour type (P = 0.002). FIGO stage and p53 protein accumulation were the only parameters that influenced overall survival time. Thus, our results suggest that histological tumour type and grade are major determinants of spontaneous apoptosis in ovarian carcinomas; p53 alterations do not adversely but rather positively affect spontaneous apoptosis by increasing growth fraction. This, in turn, suggests p53-independency of spontaneous apoptosis in ovarian carcinomas.

[Preoperative evaluation of the invasiveness of myometrial and pelvic lymph nodes in patients with endometrial cancer]. / Przedoperacyjna diagnostyka glebokosci naciekania miesnia macicy oraz przerzutów do wezlów chlonnych miednicy u chorych na raka endometrium.

Transvaginal sonography (TVS), computed tomography (CT) and magnetic resonance imaging (MRI) were used for preoperative diagnosis of myometrial and pelvic lymph nodes invasion in patients with endometrial cancer. Results of examinations were compared with histopathological findings. Sensitivity, specificity, efficacy, positive and negative prognostic values of these imaging techniques were compared. TVS and MRI had similar efficacy in the evaluation of depth of myometrial invasion (78.8% vs 67.6%). In the evaluation of deep invasion TVS in spite of lower sensitivity had higher specificity and positive prognostic value. Efficacy of all methods for evaluation of lymph nodes metastases was similar (80-82%), but TVS had higher positive prognostic value than MRI. CT in comparison with TVS and MRI was less useful in the diagnosis of myometrial invasion.

[Preoperative evaluation of cervical involvement in endometrial cancer]. / Mozliwosc przedoperacyjnej oceny zajecia szyjki macicy przez proces nowotworowy u chorych na raka endometrium.

Usefulness of fractionated curettage, histeroscopy, transvaginal sonography and MR-imaging in the preoperative diagnosis of cervical involvement of endometrial cancer was studied. Sensitivity, specificity, efficacy, positive and negative prognostic value of above-mentioned examinations were compared. None of examinations was adequate for diagnosis of presence of cervical invasion because of their low positive prognostic values. Negative prognostic value of all examinations was high. MR-imaging and transvaginal sonography had the highest efficacy and comparatively high sensitivity and specificity. Authors suggest, that transvaginal sonography--considering its simplicity and relative cheapness--should be obligatory in the diagnosis of endometrial cancer advancement.

Fractional curettage, hysteroscopy and imaging techniques: transvaginal sonography (TVS), magnetic resonance imaging (MRI) and computed tomography (CT) in the diagnosis of cervical canal involvement in cases of endometrial carcinoma.

The value of preoperative diagnostic procedures (FC, hysteroscopy, TVS, MRI, CT) used to evaluate cervical canal involvement in cases of endometrial carcinoma was assessed. The results of these diagnostic methods were compared to postoperative pathologic examination results. Evaluation of the cervix by CT was limited. High NPV of the rest of the methods together with their negative results allowed us to exclude cervical infiltration with a high probability. Alas, none of them was adequate to confirm the presence of cervical involvement because of their low PPV which ranged from 8.3% (hysteroscopy) to 50% (MRI). Among all these diagnostic procedures TVS was relatively efficient (77.8%), specific (78%), sensitive (75%) and inexpensive. This method is preferable in the evaluation of possible cervical infiltration.

Transvaginal colour flow imaging in assessment of ovarian tumor neovascularization.

Localization and intensity of angiogenesis in benign and malignant ovarian neoplasms recorded by color Doppler transvaginal ultrasound has been assessed. Increased intratumoral angiogenesis has been affirmed in 60% of malignant and only in 9% of benign lesions.