Prediction of cervical infiltration in Stage II endometrial cancer by different preoperative evaluation techniques (D&C, US, CT, MRI).

OBJECTIVE: Our clinical practice for FIGO Stage II endometrial cancer consists of Wertheim's radical hysterectomy as first choice of treatment. The evaluation of patients is based on D&C. The accuracy of this preoperative staging method is examined here. METHODS: Twenty-nine patients with endometrial cancer with suspected cervical involvement (FIGO Stage II) based on endocervical curettage underwent Wertheim's radical hysterectomy between January 1, 1989 and December 31, 2001 at the Gynaecological Department of the National Institute of Cancer, Budapest, Hungary. In all cases surgico-pathological staging was performed to examine the accuracy of preoperative D&C and to find out whether radical surgery was necessary in all patients and how the preoperative evaluation of patients should be improved. RESULTS: Out of 29 patients who underwent Wertheim's hysterectomy the pathological examination found primary cervical cancer in two patients. These two patients were eliminated from further evaluation. Out of the remaining 27 patients only eight (29.6%) had cervical involvement of endometrial cancer documented by a pathologic review on the hysterectomy specimen. Extrauterine disease was documented in one of the patients with cervical infiltration (1/8) and in one in the cervix-negative group (1/19). Ovarian spread was found in the first case and ovarian infiltration with penetration of the tumour into the parametric tissue in the second case. According to the FIGO classification 18 (66.6%) patients had less extensive disease and two (7.4%) had more extensive disease. Only 26% of the patients (7/27) had surgical findings consistent with the Stage II disease. CONCLUSION: We can conclude that "overtreatment" seems to have occurred in 19 patients, whose cervical infiltration by endometrial cancer could not be proved by pathological staging. It can also be assessed that understaging took place in two cases, which can be explained by two reasons; we did not make use of preoperative imaging techniques since US was applied in six patients, CT in 16 and the most accurate, MRI, on three patients only. The other possible reason, which can point out the bad efficacy of the imaging techniques as well, could be that a major part of the patients received preoperative AL treatment, which could also have influenced the cervical progression. This is possible, but has not been proved. The difference in the number of cervical infiltrations in the group of patients who received preoperative radiotherapy and in the group where they did not, is not significant (p = 0.9742), and infiltration of the endometrium was present in all cases. In the future, proper selection of imaging modalities can improve the staging of gynaecological disorders and preclude unnecessary procedures. In endometrial cancer cases US, especially with the use of TVUS, is often considered to be the primary imaging approach. However, in patients where ultrasound is suboptimal, where there is a large tumour present or the result of imaging studies will directly influence the choice of therapy and guide therapy planning then the higher accuracy of MRI warrants its use. CT is of use in the later stages of disease; differentiation between Stage I and II is difficult and CT is limited in the assessment of myometrial invasion.

Freeze dried ondansetron: first observations with the fast dissolving oral antiemetic Zofran Zydis for the prophylaxis of the cisplatin-induced emesis in gynecological cancer patients.

Oral antiemetics are seldom taken by patients (women, children or those having tumors of the buccal area, mouth or esophagus), who find it difficult to swallow. In addition to anatomical reasons, the side effects of cytostatics require medication. Fast dissolving ondansetron is a new preparation, which instantaneously disintegrates and disperses in the saliva. The purpose of this paper was to evaluate the antiemetic effectivity of the product Zofran Zydis. Thirty six patients treated with cisplatin (50 mg/m2) in 55 chemotherapy courses were given 2x8 mg fast dissolving ondansetron in a prospective non randomised study. 75% complete response and 11% major response rates were found. Authors conclude that fast dissolving ondansetron is a new and effective preparation that enriches the panel of available supporting drugs.

[Does the addition of an anxiolytic drug improve the anti-emetic effectiveness of the steroid and granisetron combination in the prophylaxis of cisplatin-induced vomiting?]. / Fokozható-e a szteroid és granisetron antiemeticus kombináció hatékonysága anxiolyticus szer hozzáadásával a cisplatin okozta hányás profilaxisában?

Authors evaluated two forms of antiemetic therapy in 129 courses of 51 gynecological cancer patients treated with cisplatin chemotherapy of moderately or highly emetic dose (50-100 mg/m2) in a prospective, non randomized study. The patients received granisetron (3 mg, intravenously) and methylprednisolone (100 mg, orally) in the group A. An additional anxiolytic drug (alprazolam or meprobamate or diazepam) or droperidol with known sedative characteristics (1 ml, intravenously) was given in the combination of the group B. 80.3% and 73.5% complete responses were achieved in groups A and B, respectively (p = 0.4084). No differences were found in the side effects of the two antiemetic combinations. Authors conclude the addition of an anxiolytic drug does not improve the antiemetic effectivity of the granisetron-methylprednisolone combination in the first 24 hours of cisplatin chemotherapy.

[Human papillomavirus and cervical cancer: genetic background of the neoplastic process]. / Humán papillomavírus és méhnyakrák: a tumoros folyamat kialakulásának genetikai háttere.

In a 2-year period, 136 HPV positive cytological samples of the cervix uteri were analyzed at the Department of Molecular Pathology, National Institute of Oncology, Hungary. Comparison with the international data obtained from the literature revealed that the Hungarian epidemiological data bore closest resemblance to the European ones except some differences. The HPV18 is rather seldom encountered in this country. Similarly low occurrence was noted only in Japan. However, the 14.1% occurrence rate of HPV58 in Hungary is by far higher than that in any other country in this analysis except Japan where this virus is of similarly high frequency. In Hungary, the incidence of HPV59 is relatively high just like in Central and South America. HPV33 and HPV66 infections occur in a significantly higher number with Hungary than in any of the countries studied. In our study The European type variant of HPV16 (E-V-350G) occurred in 2/10 CIN II-III cases. The authors also compared the various clinico-pathological grouping of HPV types published, and identified several inconsistencies. Viruses considered to have high risk occurred in intact epithelium, CIN I-II-III and carcinoma alike. The general tendency was, however, that certain viruses correlated with specific clinico-pathological entities. At present there is no reason to include the PCR-based HPV typing in the mass screening of cervical cancers. HPV typing and physical state of the virus can reasonable be determined if the cervical cytology is suspect for HPV infection or even control examination after "loop" conisation. Negative cytology completed with negative HPV-DNA test means the lack of cancer risk even in the case of a previously removed CIN or carcinoma. However, a positive HPV test detected after conisation associated with negative cytology finding indicates a risk of 70% of the development of CIN within 2 years.

Side-effects of paclitaxel therapy in ovarian cancer patents.

OBJECTIVE: Since premedication with H1, H2 receptor antagonists and steroids fewer side-effects of paclitaxel (PTXL) chemotherapy have been published. The authors summarize the literature and their own experience. MATERIALS AND METHODS: 23 patients with stage III ovarian cancer were treated with second-line chemotherapy of PTXL and carboplatin (CRB) with the doses of 175 mg/m2, 3 h and AUC 5 mg/ml x min, respectively. The side-effects of treatment are evaluated in a prospective non-randomized study. RESULTS: Rare toxicity in hemoglobin (G0-15%, G1-62%, G2-12% and G4-4%) and leukocyte levels (G0-35%, G1-25%, G2-29%, G3-11% and G4-0%) were detected. There was no definite change found in platelet count (G0-89.5%, G1-10.5%), and moreover in 15.8% of the patients the controlled platelet count was higher than the normal laboratory range. Liver enzymes, serum creatinine and carbamide levels in each case were within the normal range (G0). One patient complained of severe neuropathy (nervus oculomotorius paresis), and another one developed severe ECG abnormalities CONCLUSIONS: When suitable premedication is applied few side-effects of PTXL therapy are reported.

Allelic imbalance and microsatellite instability in BRCA1 associated breast and ovarian tumors.

We have investigated the involvement of microsatellite instability (MSI) and allelic imbalance (AI) at chromosome 13q and 17 in 41 breast and 41 ovarian carcinomas and their association with BRCA1 and BRCA2 gene mutations. MSI was detected in 20% of ovarian and 7% of breast tumors. AI at the BRCA1 locus was detected in 59% and 32% of ovarian and breast tumors, respectively. At the BRCA2 locus, AI rates were 49% and 44% for ovarian and breast tumors, respectively. Germline BRCA1 mutations, identified in 5 (12%) ovarian tumors and in one (2%) breast tumor were not associated with MSI. In only 2/5 BRCA1 positive tumors loss of the wild-type allele was observed. We conclude that BRCA1 mutation status is not associated with MSI and that MSI found in a fraction of ovarian tumors may reflect possible mutations in one of the DNA mismatch repair genes.

[Second-line chemotherapy with paclitaxel for ovarian cancer]. / Kiújult petefészekrák második vonalú kemoterápiás kezelése paclitaxellel.

The authors summerize the results of second-line combination chemotherapy with paclitaxel (175 mg/m2, 3h) and carboplatin (AUC 5 mg/ml.min) in patients with recurrent epithelial ovarian cancer. The paclitaxel/carboplatin therapy was applied in 57 patients in 297 courses (median course/patient was 5, range 2, 12). Complete response (CR) was found in 3 patients (3/57 = 5%), however the tumorous process progressed after some time. The median progression free interval (PFI) was found to be 15 (range 3,130) weeks, with an average of 24.3 +/- 26.5 weeks. The authors conclude, that second-line paclitaxel combination therapy produces poorer results than the first-line treatment. These results, which are similar to the literature data have led to the agreement: paclitaxel can be applied in ovarian cancer patients only in first-line chemotherapy in Hungary from the year 2000.

[Prognostic value of cell heterogeneity in cervical cancer determined by digital image analyzer of DNA content]. / A cervixdaganatok citometriai heterogenitásának vizsgálata sejtenkénti DNS-analízissel, a daganatheterogenitás prognosztikai értékének meghatározása céljából.

Frequency and prognostic value of cell heterogeneity in FIGO 1a-2a cervical cancer was examined, in 66 of patients underwent Wertheim type hysterectomy between 1989 and 1995 in National Institute of Cancer, Budapest, Hungary. A newly developed DNA image analyses (DNACE) was used in paraffin embedded tissues after enzymatic hydrolyses for evaluation of the DNA content in cervical cancer. In 30.3% of examined tissues (20/66) two subgroups was found. There was significant differences in the DNA indexes (DI) between the subgroups (p = 0.0001). In the remaining 69.7% of the cases only one subgroup was present. The frequency of two subgroups was higher between aneuploid (78.4%), or hyperploid (81.5%) type cervical cancer, however there was no significant difference between the two groups. On the other hand there was significant difference in the presence of two subgroups between the well and less differentiated cervical cancer. The frequency was higher between the less differentiated groups (p = 0.02). Looking at the prognostic value of subgroups, there was no significant correlation between the heterogeneity of cervical cancer and FIGO stage, or lymph node metastasis (p = 0.6855), or vascular/lymphatic space infiltration (p = 0.2558), or invasiveness of cancer (0.0823). There was neither significant value found between the outcome of disease and the number of subgroups present (p = 0.8738). It is though that the present of cellular heterogeneity in cervical cancer is connected with the differentiation of the cancer cells, and can be a good prognostic value in the anticipation of the aggressiveness of cervical cancer. Looking at the present result, there was no significant connection between the heterogeneity of cervical cancer and the outcome of the disease, so further examination should be done.

Prevalence of founder BRCA1 and BRCA2 mutations among breast and ovarian cancer patients in Hungary.

We have investigated the impact of BRCA1 and BRCA2 mutations that were frequently identified among Hungarian high-risk breast-ovarian cancer families (Ramus et al., 1997b, AJHG), on the development of breast and ovarian cancer in the general Hungarian population. The prevalence of 3 BRCA1 mutations (185delAG, 300T-->G and 5382insC) and 2 BRCA2 mutations (6174delT and 9326insA) was evaluated in a hospital-based consecutive series of 500 female breast cancer patients and 90 ovarian cancer patients, not selected for age at diagnosis or family history of cancer, as well as in 350 controls. Among breast cancer patients, 3.6% (18/500) carried a founder mutation: 9 BRCA1 300T-->G, 7 BRCA1 5382insC, 1 BRCA1 185delAG and 1 BRCA2 9326insA. Among ovarian cancer patients, 11% (10/90) carried a founder mutation: 5 BRCA1 185delAG, 4 BRCA1 300T-->G and 1 BRCA1 5382insC. One control carried a mutation, BRCA1 5382insC. Inherited breast cancer was more frequent among women with younger age at diagnosis: 6.1% of women younger than age 50 but 2.4% of women diagnosed at age 50 or older carried one of the founder mutations. There was no association between mutation status and age at diagnosis of ovarian cancer. Three of 23 medullary breast cancers were inherited (p = 0.038). Carrier status was also associated with a non-significant trend toward advanced tumor stage at diagnosis. These mutations could be evaluated among all ovarian cancer patients and breast cancer patients younger than age 60 and of Hungarian ancestry.

[Detection of human papillomavirus infection by the nucleic acid hybridization method (a multicenter study)]. / Human papillomavírus-fertözés kimutatás nukleinsav hibridizációs módszerrel (multicentrikus tanulmány).

The human papillomaviruses (HPV) are regarded as one of the important agents of cervical carcinoma. A multicentre study was organized to determine the prevalence of HPV in the fertile female population in Hungary. Parallel with the clinical sample collection, a questionnaire interview was performed to acquire data on the life style, socioeconomic status, sexual practice, etc. 1200 women were examined colposcopically and cervix samples were collected for cytology and the detection of HPV DNA. 17.4% of the samples were HPV-infected. 3.9% of the patients had acquired low-risk, and 10.1% 10.2% high-risk HPV types; 3.4% of the women were at the same time infected with both low-risk and high-risk HPV types. Simultaneously performance of cytology and the HPV hybrid capture assay contribute to recognise and treat the precancerous status and risk factors.

Candida guilliermondii var. guilliermondii infection in infertile women.

The sera of 263 women--217 infertile and 46 pregnant--were examined by various serological methods (precipitation test, agglutination, indirect immunofluorescence) to detect Candida guilliermondii var. guilliermondii (C.g.) infection. The precipitation reaction was performed with extracellular C. guilliermondii antigen, the agglutination reaction was employed parallel with C. albicans. In the infertile group 122 (56.2%) proved to be C.g. positive, while in the fertile 11 women (23.9%) proved to be so, the level of significance being p less than 0.0001 between the two groups. A one-month ketoconazole treatment (one tablet, 200 mg/day) was adequate for eliminating the C.g. infection. In a few cases hystological examinations were also performed according to Gomori-Grocott and yeast cells could be detected in the stroma of the ovary. IgA, IgG, IgM, Gc-globulin, transferrin and ferritin determinations were carried out before and after the ketoconazole treatment, and there were significant differences in the IgM and transferrin levels between the infected and non-infected groups. The authors achieved 5 pregnancies of 56 treated women in 6 months.

[A microbiology clinic in outpatient gynecologic service]. / Klinikai mikrobiológiai ambulancia a nögyógyászati járóbeteg-ellátásban.

The authors report on their experiences gained at the sexually transmitted disease clinic they established at the First Department of Obstetrics and Gynecology of Semmelweis Medical University. A total of 456 patients presenting with signs and symptoms of lower genital tract infection have been examined in one year. The investigation of patients included aerobic and anaerobic culture of vaginal bacteria, vaginal smear and the identification of sexually transmitted Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasmatales and Gardnerella vaginalis. The authors conclude that a sexually transmitted disease clinic is appropriate to contribute to the prevention of horizontal and vertical spread of the sexually transmitted bacterial infections.

The serum protein content of human follicular fluid and its correlation with the maturity of oocytes.

The authors determined, by an immunochemical method, the alpha-1-antitrypsin, Gc globulin, prealbumin, albumin, haemopexin, transferrin, haptoglobin, IgA, IgG, ceruloplasmin, alpha-2-macroglobulin contents of 98 follicular fluids, 10 peritoneal fluids and 24 blood sera. Out of these proteins analysed, change in the concentration of alpha-1-antitrypsin showed correlation with the maturity and fertilisation of the oocyte. The alpha-1-antitrypsin content was 1.6 +/- 0.26 g/l in the case of mature oocytes, and 3.1 +/- 1.12 g/l in the case of immature ones. Fertilisation was also concomitant of low alpha-1-antitrypsin levels.

Changes of serum proteins in patients with malignant gynaecological tumours.

The changes of 13 serum proteins in 53 ovarian tumour patients were studied by the radial immunodiffusion method from the beginning of treatment, during the course of disease. As to the course of the disease, in 6 of them characteristic and significant changes were observed. These were prealbumin, alpha 1-anti-trypsin, orosomucoid, coeruloplasmin, transferrin and haptoglobin. Although the differences could be evaluated as an average of investigations, the value of the examinations is greatly reduced by the very high scatter of the individual values.

The significance of neopterin determination as a tumour marker in ovarian cancer.

The neopterin level of 164 urine samples of ovarian cancer patients was determined by high pressure liquid chromatography. Parallelly, the serum levels of CA 125, CEA and of lipid bound sialic acid were also determined. A good correlation was found both with CA 125 and with lipid-bound sialic acid. There was a closer correlation with the latter both in the patients showing remission and in the active tumour carriers. In patients with negative tumour markers (TM) in the sera examined, a tumour-free state was confirmed in 87.5% by neopterin determinations. Accordingly, authors recommend neopterin determination in patients who face a critical decision.

The importance of polyamine determination in monitoring malignant gynaecological tumours.

By thin-layer chromatography, the serum polyamine levels together with those of CA 125, CEA, lipid-bound sialic acid and urinary neopterine were determined in 56 ovarian cancer patients. A correlation was found in the group of clinically active tumour carriers between the clinical finding and the results of polyamine determination only where other tumour markers were suggestive of complete remission.

Significance of CEA, AFP, SP1 and HCG as tumor markers in ovarian carcinoma.

The significance of CEA, AFP, HCG and SP1 determinations in 85 patients with ovarian cancer were analyzed from the point of view of evaluation of the clinical status of the patients. On the basis of the trials it was stated that a satisfactory correlation between the extension of the tumor and the serum CEA level was observed in 26.6% of the cases. The efficiency of monitoring by systematic CEA tests was found to be 17.3%. The determination of AFP and HCG is useful only in cases of tumors with specific histological structures and in problems of differential diagnostics. The testing of SP1 is of no value in clinical practice.