Rapid reduction of leiomyoma volume during treatment with the GnRH antagonist ganirelix.

OBJECTIVE: To assess maximal volume reduction of leiomyomas and uterus and the duration of treatment required to reach these reductions with daily GnRH antagonist treatment. DESIGN: Prospective, open-label study. SETTING: Large teaching hospital in The Netherlands. POPULATION: Premenopausal women with symptomatic fibroids, who were scheduled for surgery. METHODS: Twenty women were treated with daily 2 mg of subcutaneous ganirelix. Prior to the first injection and weekly during treatment, the volume of leiomyomas and the uterus were assessed by ultrasound (USS) and serum hormones were measured. Prior to treatment and when maximal size reduction was observed by USS, the volume of the leiomyomas and the uterus were also assessed by magnetic resonance imaging (MRI). MAIN OUTCOME MEASURES: Leiomyoma and uterine size reduction, time to maximal reduction. RESULTS: One woman was excluded from the study due to incorrect administration dose of ganirelix. Data on the remaining 19 women (average age 39 years) with subserosal (n= 9), submucosal (n= 7), intramural (n= 10) and transmural (n= 1) leiomyomas were evaluated. Baseline leiomyoma volumes ranged from small (3-4 mL) to large (>1000 mL). The median duration of treatment up to maximal leiomyoma size reduction was 19 days (range 1-65 days). The maximal size reduction in leiomyomas measured by USS was -42.7% (-77.0% to 14.1%) and -29.2% (-62.2% to 35.6%) by MRI. Comparable uterine size reductions of -46.6% (-78.6% to -6.1%) and -25.2% (-63.6% to 28.9%) were observed by USS and MRI. During the first three weeks of treatment, 8 out of 19 women reported adverse events related to the induced hypoestrogenic state. Most of these events resolved within one week after treatment was discontinued. CONCLUSION: Daily treatment with 2 mg of ganirelix results in rapid reduction of leiomyoma and uterine volume in premenopausal women with minor side effects. If longer-acting GnRH antagonists become available, pretreatment with GnRH antagonist should be preferred over GnRH agonists prior to surgery.

Localization and staging of cervical intraepithelial neoplasia using double ratio fluorescence imaging.

A phase zero evaluation of a new fluorescence imaging technique for diagnosing cervical intraepithelial neoplasia (CIN) was performed. The fluorescence imaging prototype performed quantitative imaging of Protoporphyrin induced by a topically applied aminolevulinic acid using double ratio (DR) fluorescence imaging technique developed by our group. A total of 38 patients were in the protocol, with 16 colposcopically selected for biopsy. Fluorescence images of these 16 patients were taken, 19 sites were biopsied, and the disease was staged histopathologically. DR fluorescence imaging of the cervix using our general purpose prototype appeared to be cumbersome but feasible. In four cases strongly localized fluorescent hotspots were observed at the location where the disease was colposcopically visible. In the other cases the fluorescence showed a more diffuse multifocal image. The value of the DR determined at the site of biopsy correlated in a statistically significant way with the histopathologically determined stage of the disease [Spearman rank correlation, r=0.881, p<0.001 (confidence interval 0.7044-0.9552)]. This suggests that noninvasive staging of CIN using this technique is feasible. We believe that the results of this study justify the development of a dedicated device that combines regular white light colposcopy with DR fluorescence imaging.

Decrease in the number of abdominal hysterectomies after introduction of laparoscopic hysterectomy.

STUDY OBJECTIVE: To compare two 3-year periods before and after laparoscopic hysterectomy was introduced into our resident training program. DESIGN: Retrospective analysis (Canadian Task Force classification II-2). SETTING: Teaching hospital in the Netherlands. PATIENTS: Women undergoing hysterectomy from 1992 to 1994 and 1995 to 1997. INTERVENTION: Abdominal, vaginal, and laparoscopic hysterectomies. MEASUREMENTS AND MAIN RESULTS: Laparoscopic hysterectomy significantly (p<0.002) reduced the number of abdominal hysterectomies. CONCLUSION: To reduce the number of abdominal hysterectomies, it is essential that the laparoscopic procedure be taught to residents.

Urogenital Chlamydia trachomatis serovars in men and women with a symptomatic or asymptomatic infection: an association with clinical manifestations?

To determine whether certain Chlamydia trachomatis serovars are preferentially associated with a symptomatic or an asymptomatic course of infection, C. trachomatis serovar distributions were analyzed in symptomatically and asymptomatically infected persons. Furthermore, a possible association between C. trachomatis serovars and specific clinical symptoms was investigated. C. trachomatis-positive urine specimens from 219 asymptomatically infected men and women were obtained from population-based screening programs in Amsterdam. Two hundred twenty-one C. trachomatis-positive cervical and urethral swabs from symptomatically and asymptomatically infected men and women were obtained from several hospital-based departments. Serovars were determined using PCR-based genotyping, i.e., restriction fragment length polymorphism analysis of the nested-PCR-amplified omp1 gene. The most prevalent C. trachomatis serovars, D, E, and F, showed no association with either a symptomatic or asymptomatic course of infection. The most prominent differences found were (i) the association of serovar Ga with symptoms in men (P = 0.0027), specifically, dysuria (P < 0.0001), and (ii) detection of serovar Ia more often in asymptomatically infected people (men and women) (P = 0.035). Furthermore, in women, serovar K was associated with vaginal discharge (P = 0.002) and serovar variants were found only in women (P = 0.045).

Monitoring of Chlamydia trachomatis infections after antibiotic treatment using RNA detection by nucleic acid sequence based amplification.

AIM: To investigate the value of RNA detection by nucleic acid sequence based amplification (NASBA) for the monitoring of Chlamydia trachomatis infections after antibiotic treatment. METHODS: Cervical smears (n = 97) and urine specimens (n = 61) from 25 C trachomatis positive female patients were analysed for the presence of C trachomatis 16S ribosomal RNA (rRNA) by NASBA and C trachomatis plasmid DNA by the polymerase chain reaction (PCR) before and up to five weeks after antibiotic treatment. RESULTS: Chlamydia trachomatis RNA was found in all cervical smears taken before antibiotic treatment (n = 24) and in two smears taken one week after antibiotic treatment; no C trachomatis RNA was detected after two weeks or more. In contrast, C trachomatis DNA was found in all such specimens before treatment, and 21 of 25, six of 21, and five of 20 smears were found to be positive at one, two, and three weeks after treatment, respectively. After four weeks, only one of six smears was positive, and this smear had been negative in the two preceding weeks. Of the 61 urine samples investigated, C trachomatis DNA and C trachomatis RNA were found in all before treatment (n = 15), whereas one week after treatment four of 15 were C trachomatis DNA positive and C trachomatis RNA was detected in one sample only. CONCLUSIONS: These data show that RNA detection by NASBA can be used successfully to monitor C trachomatis infections after antibiotic treatment. Furthermore, it might be possible to use urine specimens as a test of cure because neither C. trachomatis DNA or RNA could be detected two weeks or more after treatment.

Abdominal wall metastases after surgical resection of an immature teratoma of the ovary.

In this case report the diagnostic process is discussed leading to a rather late correct diagnosis of immature teratoma. The authors advice preoperative determination of alpha-fetoprotein in all women with ovarian tumours under 40 years of age. The limitations for pathologists to assess immaturity within a teratoma are stressed.

RNA amplification by nucleic acid sequence-based amplification with an internal standard enables reliable detection of Chlamydia trachomatis in cervical scrapings and urine samples.

In the present study, the suitability of RNA amplification by nucleic acid sequence-based amplification (NASBA) for the detection of Chlamydia trachomatis infection was investigated. When comparing different primer sets for their sensitivities in NASBA, use of both the plasmid and omp1 targets resulted in a detection limit of 1 inclusion-forming unit (IFU), while the 16S rRNA appeared to be the most sensitive RNA target for amplification (10(-3) IFU). In contrast, for DNA amplification by PCR, the plasmid target was optimal (10(-2) IFU), which is 10 times less sensitive than rRNA NASBA. To exclude false negativity in NASBA detection because of inhibition of amplification and/or inefficient sample preparation, an internal standard was developed. The internal control was added prior to sample preparation. This 16S rRNA NASBA with an internal control was compared with a plasmid DNA PCR by using a group of C. trachomatis-negative (n = 41) and -positive (n = 37) cervical scrapings, as determined by enzyme immunoassay (EIA). In addition, urine samples from the EIA-positive women were tested (n = 17). Both NASBA and PCR assays were able to detect C. trachomatis in all EIA-positive cervical scrapings, the corresponding urine samples, and two samples from the EIA-negative group. The internal NASBA standard was found clearly in all EIA-negative samples. In conclusion, these results indicate that detection of C. trachomatis by RNA amplification by NASBA with an internal standard is a suitable and highly sensitive detection method, with potential use in the diagnosis of urogenital C. trachomatis infections with cervical scrapings as well as urine specimens.

Effects of ketoprofen and mesosalpinx infiltration on postoperative pain after laparoscopic sterilization.

OBJECTIVE: To determine whether preoperative ketoprofen and mesosalpinx infiltration, either alone or in combination, favorably influence postoperative recovery after outpatient laparoscopic sterilization. METHODS: In a double-blind, randomized, placebo-controlled study, 20 women received 100 mg of oral ketoprofen preoperatively, and each mesosalpinx was infiltrated with 5 mL of saline plus epinephrine 1:200,000; 20 women were given oral ketoprofen, and each mesosalpinx was infiltrated with 5 mL of bupivacaine 0.5% with epinephrine 1:200,000; and 20 women received a placebo capsule with mesosalpinx infiltration. Pain was assessed by a visual analogue scale and a self-assessment 11-point scale; outcome was assessed by discharge time, consumption of analgesics, incidence of nausea and vomiting, and the number of postoperative days to full recovery. RESULTS: Pain ratings in the ketoprofen-only group were significantly higher than in the two other groups (P < .001). Preoperative ketoprofen alone provided insufficient postoperative pain relief, necessitating the use of opiates and peripheral analgesics. Nausea and vomiting were highest in these subjects, as was intake of peripheral analgesics at home. Times to discharge were also the longest in this group (median 385 minutes, range 260-510) and differed significantly from both other groups (P < .001). It took 4-13 days to recover. In contrast, women with only a mesosalpinx block ambulated and recovered sooner, but times to discharge were still prolonged (median 240 minutes, range 105-375). Recovery usually occurred by the fourth postoperative day. The combination of preoperative ketoprofen and mesosalpinx block resulted in the shortest times to discharge (median 190 minutes, range 80-330), the least consumption of peripheral analgesics, and the lowest incidence of nausea and vomiting. Recovery occurred by the fourth postoperative day. CONCLUSION: Mesosalpinx infiltration has a favorable effect on postoperative recovery after day-surgery laparoscopic sterilization. Still better results can be obtained with a multimodal analgesic approach, combining mesosalpinx infiltration with preoperative ketoprofen.

The connective tissue of the adult female pelvic region. A microscopical analysis.

Using special histological criteria, structures found during blunt dissection of the adult female pelvic region could be recognized in 0.7-0.8 cm thick transparent histologically stained serial sections of this region, as connective tissue ribbons. The connective tissue in the adult female pelvic region reveals an orderly constructed system of coherent connective tissue ribbons. These ribbons form a skeleton which borders several separate functional areas. Areas for the locomotive system of the leg areas containing the pelvic vessels and viscera are separated by an area of adipose tissue. This area is again bordered by a connective tissue ribbon. In the fossa ischiorectalis also connective tissue ribbons are found, bordering areas filled with adipose tissue. These connective tissue ribbons interconnect the musculus levator ani, the epidermis, the musculus obturatorius internus, and the musculus gluteus maximus. The architecture found in the sections has a bilateral symmetry and possesses interindividual uniformity. The three-dimensional architecture of this system of connective tissue ribbons will be described in a next article.

The connective tissue of the adult female pelvic region. A musculo-fibrous apparatus.

From histologically stained transparent 0.7-0.8 cm thick serial sections of adult female pelves transparent glass-plate reconstructions of the connective tissue septa system were prepared. The analysis of these reconstructions revealed a bilateral symmetry and an interindividual uniformity of the connective tissue system and the adipose tissue components lying in between. The connective tissue system separating different functional compartments in the retroperitoneal space in order to envelop the muscles, the bones, the vessels and the viscera, forms a substaining system interwoven with the connective tissue elements of the musculus levator ani and perforating the muscle, and continues into the connective tissue system in the fossa ischiorectalis upto the fascia perinei superficialis is reached. The fasciae of the pelvic muscles, the sacro-tuberal and sacro-spinal ligaments and the ligaments of the uterus appear to be completely involved in this system of connective tissue septa. The connective tissue system links the pelvic viscera up to the muscular and bony parts of the locomotive systems of the trunk and the legs, giving a rise to a functional entity. The formulation of the hypothesis of this entity raised new questions about the structure of the different connective tissue septa in the female pelvic region.

Histological aspects of connective tissue septa in the adult female pelvic region.

From very thick 7-8 cm thick sections of adult female specimine parts of the connective tissue septa system were isolated and their relationships to muscles, viscera and vessels were studied histologically. Following the identification of an integrated system of pelvic connective tissue septa as described in previous articles biomechanical views were formulated. The consideration of these views led to new questions concerning the correlation of the structure of the connective tissue septa at different places in the entire pelvic region. The septa appeared to continue uninterrupted into the fascia and the perimysium of the muscles. The interrelationships of the connective tissue fibres, the adipose tissue and the vessels is described. The adventitia of the pelvic veins are firmly attached to the connective tissue septa. The groundsubstance of the adipose tissue appeared to contain hydrophilic acid mucopolysaccharides. The arteries were found close to the septa but not attached to them freely embedded in the adipose tissue. The connective tissue septa appeared to be built as multi-layered, "puff-pastry"-like arranged structures. The possible functional aspects of the interrelationships of the connective tissue septa system with the vascular system are discussed.

The connective tissue of the female fetal pelvic region.

The spatial architecture of the female fetal pelvic region was studied with a blunt dissection technique and reconstructed from 60 mu serial thick sections of complete fetal pelves. From the analysis of these reconstructions could be concluded that the connective tissue in the fetal female pelvic region is organized into a bilateral symmetric and interindividual constant system of septa. This system of connective tissue was found continuous from the retroperitoneal space through the musculus levator ani into the fossa ischiorectalis.