Jerzy A. Jakowicki

A randomized comparison between monofilament and multifilament tapes for stress incontinence surgery

Our objective was to compare monofilament and multifilament tapes positioned without tension at the midurethra for postoperative complications and cure rate. One hundred patients with stress urinary incontinence were randomly allocated into two study groups. Using identical surgical methodology, 50 patients had a monofilament tape inserted at the midurethra using the TVT delivery instrument, and another 50 a multifilament tape using the IVS delivery instrument. The only significant difference between the groups was in the incidence of postoperative urinary retention (p=0.023). Ten patients from the monofilament group required longer than normal (‘normal’ means to the morning of the next day) catheterization, in contrast to only two from the multifilament group. The clinical efficacy of both procedures was equally high. Conclusions were that both tapes appear to be equally effective in the surgical treatment of SUI. The higher incidence of postoperative urinary retention in the monofilament group was most likely caused by the elastic feature of this tape.

Female urinary stress incontinence in terms of connective tissue biochemistry

The role of connective tissue in the aetiology of female stress incontinence has been investigated. Collagen content and extractability as well as estrogen receptor concentration in vesico-vaginal fascia were measured after small tissue biopsies had been obtained during vaginal repair surgery in cases of urinary incontinence. The mean concentration of estrogen receptor in vesico-vaginal fascia among incontinent women was 49.4 +/- 14.8 fmol/mg of protein as compared to 29.6 +/- 13.1 in continent control group (P < 0.03; t-test). The mean hydroxyproline concentration in vesico-vaginal fascia of incontinent women was 13.8 +/- 2.6 micrograms/mg wet weight, whereas in the control group it was significantly higher 20.6 +/- 2.4 (P < 0.001). The role of connective tissue components in the aetiology of female stress incontinence is discussed.

The Efficacy and Safety of the Tension-Free Vaginal Tape Procedure Do Not Depend on the Method of Analgesia

OBJECTIVE The original tension-free vaginal tape (TVT) method, described by Ulmsten et al., routinely uses local anaesthesia during the procedure. Since the anaesthetic effect after local application of lidocaine hydrochloride was not always satisfactory we decided to introduce the spinal anaesthesia during this operation. The aim of the present study was to compare local and spinal anaesthesia with respect to their efficacy and safety in the TVT procedure. METHODS 103 women, with objectively confirmed stress urinary incontinence, were randomised into the study. Sixty-seven women were anaesthetised locally and 36 patients spinally. All TVT procedures were performed as originally described. Objective assessment of the influence of anaesthesia on intra-abdominal pressure at rest and during the cough test was done using a rectal catheter and a central venous pressure manometer. The efficacy of the TVT procedure was based on a gynaecological examination with a cough test and a three-degree subjective scale: complete cure, improvement or failure. RESULTS The success of the TVT procedure performed under local anaesthesia is comparable with that achieved under spinal analgesia (p=0.42). The number of complications that occurred in the two groups does not differ significantly (p=0.57). CONCLUSIONS Spinal anaesthesia impairs the ability to cough effectively during the TVT procedure. However, the efficacy and safety of the operations performed under this type of anaesthesia are comparable with the efficacy and safety of operations done under local anaesthesia.

Expression of TGF-β type I and II receptors in normal and cancerous human endometrium

Transforming growth factor-beta (TGF-beta) belongs to a superfamily of structurally related polypeptides involved in various biological processes, including cell growth, proliferation and differentiation, angiogenesis, apoptosis, and extracellular matrix remodeling. We tried to define the different expression patterns of the TGF-beta receptors by investigating the female reproductive organs during the menstrual cycle and endometrial tumorigenesis, because their role in these processes is still unclear. In this study, we examined the expression of the TGF-beta type I and type II receptors in normal (n=13) and carcinomatous (n=42) endometrial tissue specimens using reverse transcriptase polymerase chain reaction and immunological (Western blot and enzyme linked immunosorbent assay) methods. Two uncommon female genital tract tumors, rhabdomyosarcoma of the uterine cervix and uterine carcinosarcoma, were also included. There were no significant differences between normal and cancerous endometrial tissues regarding the TGF-beta receptors mRNA levels. However, we observed a markedly low TGF-beta type I receptor protein level (P<0.028; Mann-Whitney-U test), while the malignant endometrium showed a significantly higher TGF-beta type II receptor protein level (P<0.007; Mann-Whitney-U test) than the normal endometrium. Moreover, significantly elevated TGF-beta receptor type II protein level was noted when depth of myometrial invasion of endometrial carcinomas was considered (P<0.05; Mann-Whitney-U test). In contrast to uterine carcinosarcoma, in which no detectable mRNA for TGF-beta type II receptor was found, we noted expression of both TGF-beta receptors in rhabdomyosarcoma of the uterine cervix. However, neither rhabdomyosarcoma of the uterine cervix nor uterine carcinosarcoma displayed TGFbetaRI and TGFbetaRII protein expression. This observation corroborates the complexity of the deregulation of TGF-beta receptor expression in human endometrial cancer.

Loss of heterozygosity of the retinoblastoma gene is correlated with the altered pRb expression in human endometrial cancer

Abstract. The retinoblastoma (Rb) gene was the first tumor suppressor gene to be discovered; however, data on the influence of Rb inactivation on endometrial carcinogenesis are scarce. We investigated 46 paired primary human endometrial carcinomas and normal tissues to assess the frequency of loss of heterozygosity (LOH) in Rb and 20 tumor pairs to detect the frequency of p53 LOH. Moreover, expression of the retinoblastoma protein (pRb) was assessed immunohistochemically. Of 44 informative cases 8 showed loss of one allele in at least one Rb marker; Rb LOH frequency thus reached 18%. Two omental metastases of endometrial origin showed a heterogeneity pattern similar to that of the primary tumors. We did not find a significant correlation between Rb LOH and patient age, clinical stage, histological grade or muscle invasion of the tumor. Nevertheless, Rb LOH was demonstrated at early (stage I, 5/27, 18%) and advanced (stages II–IV; 3/9, 33%) clinical stages of the neoplasm, suggesting that LOH at the Rb locus occurs before the clonal expansion of the tumor. There was a significant correlation between Rb LOH and weak/absent pRb expression. We noted a single case of p53 LOH at intron 1, but no tumor showed both alterations simultaneously. Our data suggest that LOH at the Rb locus plays a role in the oncogenesis of a subset of uterine neoplasms and corresponds with the altered expression of the pRb.

Immunohistochemical Analysis of MIB-1 Proliferative Activity in Human Endometrial Cancer. Correlation with Clinicopathological Parameters, Patient Outcome, Retinoblastoma Immunoreactivity and K-Ras Codon 12 Point Mutations

To test the prognostic utility of MIB-1 in human endometrial neoplasias, the proliferative activities of fifty-two endometrial carcinomas obtained from Polish women were assessed. We also investigated the relationship between the MIB-1 Proliferative Index and the well-known clinicopathological features of cancer (clinical stage, histological type, histological grade, depth of myometrial invasion), patients age, overall survival, retinoblastoma immunostaining and K-ras codon 12 point mutations. The mean MIB-1 Proliferation Index was 43.8%, with a median of 36.0%. Due to the great intratumour heterogeneity of the immunoreaction, the Index ranged from 0% to 98%. A significant relationship was noted between MIB-1 expression and histological grading (p=0.0004) and myometrial invasion of cancer (p=0.01). Multivariate Cox regression demonstrated that the clinical stage was the only independent prognostic factor during follow-up (p=0.025). There was a tendency towards a poorer outcome for women with a Proliferative Index of >31% than for patients whose Index was ≤ 31%; the difference, however, did not reach significance (p=0.25; log-rank test). Interestingly, uterine cancers lacking retinoblastoma protein expression had a mean MIB-1 Proliferation Index that was nearly twice as high as in those neoplasias that stained positively for retinoblastoma (70.33% and 42.14%, respectively; p=0.09; Mann-Whitney-U test). There were no significant differences between K-ras codon 12 point mutation-positive and -negative endometrial carcinomas regarding the proliferative activity of the cancer (mean Indexes 47.6% and 43.8%, respectively; p=0.66, Mann-Whitney-U test). Our data support the view that MIB-1 proliferative activity was significantly increased with a decrease of the histological grading and with the myometrial invasion of human endometrial cancer.

Expression of the cell-cycle regulatory proteins (pRb, cyclin D1, p16INK4A and cdk4) in human endometrial cancer: correlation with clinicopathological features

AbstractIntroduction. Derailments of the control mechanisms in the G1/S phase of the cell cycle play a fundamental role in the initiation and progression of cancer. However, only a few reports have addressed the issue of simultaneously occurring abnormalities of Rb-pathway components in malignant endometrial tumors.Methods. Currently, we assessed the expression of cell-cycle regulatory proteins (pRb, cyclin D1, p16INK4A and cdk4) in 48 sporadic endometrial cancers, and investigated these tumors for a possible relationship between aberrant protein staining and clinicopathological variables of cancer and RB-LOH.Results. There was abnormal pRb, cyclin D1, p16INK4A and cdk4 immunoreactivity in 2%, 50%, 6% and 25% of cases, respectively. Altogether, 33 of 48 (69%) endometrial malignant tumors showed abnormal expression of at least one Rb-pathway protein immunohistochemically. However, there was significant correlation neither between the cell-cycle regulators nor between the frequency of pRb, p16INK4A and cyclin D1 abnormalities and clinicopathological variables of cancer, but a significant correlation did exist between cdk4 staining and the clinical stage of disease (P<0.05, Fishers exact test). Moreover, an inverse relationship was also demonstrated between cdk4 expression and patient age (r=-0.367; P=0.01). However, none of the cell-cycle regulatory proteins, except for pRb, was related to loss of heterozygosity at locus 13q14.Conclusion. As a conclusion, derailments of the Rb-pathway components, cyclin D1 and cdk4 in particular, seems to participate in the endometrial cancer development in humans. Overexpression of cdk4 was related to the progression of neoplastic disease and corresponds with age of onset, suggesting a major role of altered cdk4 immunoreactivity in the progression of endometrial cancer.

K-ras exon 2 point mutations in human endometrial cancer

In the present study, we screened for the K-ras exon 2 point mutations in a group of 87 gynecological neoplasms (82 endometrial carcinomas, four carcinomas of the uterine cervix and one uterine carcinosarcoma) using the non-isotopic PCR-SSCP-direct sequencing techniques. Direct sequencing analysis revealed CAA-->CAC (Gln-->His) K-ras codon 61 point mutations in two (2.4%) of the 82 endometrial carcinomas mentioned above. These two cases were endometrial endometrioid carcinomas at an early clinical stage of disease (stage IB and IC due to FIGO). Those endometrial carcinomas that showed K-ras exon 2 point mutations revealed a strong positivity for heterogeneous nuclear retinoblastoma protein staining; none of these, however, have had the K-ras codon 12 point mutation. In addition, there were no K-ras gene point mutations in three endometrial carcinomas lacking the Rb protein immunohistochemically. None of the cervical carcinomas tested had K-ras gene point mutations, whereas one carcinosarcoma harbored K-ras codon 61 point mutation (CAA-->CAC). In conclusion, our data support the view that K-ras exon 2 point mutations are rare events in human endometrial cancer. Rb and K-ras gene abnormalities may occur independently of each other during endometrial carcinogenesis in humans.

RB protein expression in human endometrial carcinomas--an immunohistochemical study.

The aim of the current study was to investigate the immunohistochemical expression of the retinoblastoma protein (pRB) in formalin-fixed, paraffin-embedded specimens obtained from 62 patients suffering from endometrial cancer. The avidin-biotin-peroxidase detection system with microwave pretreatment and the mouse anti-human NCL-RB1 monoclonal antibody were used. Heterogeneous nuclear immunostaining for the pRB was generally observed in the glandular cells in 59 out of 62 (95%) endometrial carcinomas, while stromal components were unreactive. In one case of stage Ic endometrioid adenocarcinoma, a small percentage of glandular cells (5%) stained positively with the anti-RB antibody, while two other tumors (stage IIa adenosquamous carcinoma and stage IIIa endometrioid adenocarcinoma) were pRB negative. In the cases with concomitant hyperplastic and neoplastic endometrial lesions, pRB immunoreaction was heterogeneous in the hyperplastic endometrial cells and in the adjacent neoplastic endometrium. Moreover, eight cases of endometrial carcinoma harboring K-ras codon 12 gene point mutation overexpressed pRB (more than 80% of glandular endometrial cells were positive) immunohistochemically, while none of three pRB negative slides had a K-ras gene alteration. Our data support the view that the pRB is expressed in most of the human endometrial neoplasms, but the lack of pRB immunoreactivity may correspond with the retinoblastoma gene rearrangements in a subset of advanced endometrial carcinomas.

Serum leptin concentrations in women taking oral contraceptives

OBJECTIVES To investigate serum leptin concentrations in women taking oral contraceptives containing the same gestagen and different doses of ethinyl estradiol. STUDY DESIGN 30 women received tablets containing 20 microg of ethinyl estradiol (EE) and 150 microg of desogestrel (DSG) (Mercilon) whereas another group of 30 women received 30 microg of EE and 150 microg of DSG (Marvelon). Serum leptin concentrations were estimated using a Leptin RIA kit (Linco Research USA) after an overnight fast on the first day of the cycle prior to the onset of therapy as well as after the 3rd and 6th treated cycles. RESULTS In both groups a positive correlation between serum leptin and body mass index (BMI) was found (r=0.56; P<0.001 and r=0.67; P<0.001). The initial serum leptin concentration in the Mercilon group was 7.62+/-8.46 ng/ml. This value was not statistically different from values after 3 months (9.31 8.23 ng/ml) and after 6 months (10.53+/-8.03 ng/ml) of treatment. Very similar results were found in patients receiving Marvelon: 8.81+/-6.56 ng/ml initially; 11.62+/-11.16 ng/ml at 3 months, and 10.38+/-7.32 ng/ml at 6 months. The statistical analysis did not reveal any significant difference at each investigated time point in either study group. CONCLUSIONS Modern low dose OC containing third generation gestagen and low dose of ethinyl estradiol, does not have any influence on serum leptin or BMI, and therefore does not exert a significant influence on body energy metabolism.