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Chlamydia trachomatis infections (CTI) are the most common sexually transmitted infections.1 CTI in women may cause pelvic inflammatory disease (PID) and subsequently result in tubal factor infertility and ectopic pregnancy.2 Finally, CTI in pregnancy may cause neonatal conjunctivitis and pneumonia.3 Approximately 70% of the CTI in women are asymptomatic. The prevalence in asymptomatic obstetric and gynaecological patients in Europe ranges from 0.8 to 4.8%.4,5 Intrauterine manipulations such as curettage and a hysterosalpingogram in women with a CTI may cause PID as well.6 In the Netherlands there are no general policies for intrauterine manipulations. We would like to establish general policies to prevent intra-abdominal CTI. Therefore, information about the clinical aspects of CTI, patient characteristics, and data on the prevalence of CTI in an outpatient department of obstetrics and gynaecology are needed. From June 1996 to September 1997, new patients attending the outpatient department of obstetrics and gynaecology of the Westeinde Hospital were requested to participate in the study. Approval was obtained by the ethics committee. The Westeinde Hospital is an inner city hospital, with a high percentage of patients of different ethnic origin. After informed consent a questionnaire was completed and a gynaecological examination was performed. For detection of CTI two methods were used: 1. A probe hybridisation assay from a urethral, an endocervical and an anorectal swab (PACE 2 assay) (Gen-Probe). Swabs were analysed within 24 hours according to Gen-Probe’s packet insert instructions. 2. Amplification of CT-rRNA by transcription mediated amplification (TMA) in urine samples with the …

To analyse local tumour parameters of early cervical cancer that might be of prognostic significance for tumour relapse in the pelvis.Retrospective.Data were collected from 308 patients who underwent radical hysterectomy and pelvic lymphadenectomy in the years 1984-1996 in the Leiden University Medical Centre, the Netherlands. Treatment policies and operating staff were the same during the study period. The existence of relapse was studied by physical, gynaecological, laboratory and, if indicated, radiological examination.Data on 294 patients were available for analysis. Their mean age was 45 years (range: 21-82). Postoperative radiation treatment was given to 119 patients (40%). Mean follow-up duration was 36 months (range: 1-136). Recurrences had developed in 46 patients (15.6%), 29 of whom had died. The calculated overall 5-year survival rate was 83%; 91% for those with negative and 53% for those with positive pelvic nodes. The calculated recurrence-free-5-year survival rate was 75% for the entire group, 83% for the patients without and 47% for those with lymph node metastases. When more than one lymph node region was affected, 5-year disease free survival was 19% and when lymph node metastasis occurred bilaterally, it was 22%. Multivariate analysis revealed that lymph node involvement (hazard ratio: 4.4), parametrial involvement (5.5), tumour size30 mm (4.6) and depth of invasion10 mm (5.1) were independent factors of prognostic significance for disease free survival. The current indications for adjuvant treatment might be extended with infiltration depth. The number and the bilaterality, if any, of affected lymph node stations might be indication for additional adjuvant therapy.

The correlation between human papillomavirus (HPV) infection and tumor prognosis in 159 Russian women with cervical carcinoma was investigated. The presence of various HPV types was correlated with the histologic parameters of the carcinomas and with their immunoreactivity with antibodies to p53, Ki-67-Ag, and bcl-2.Formalin fixed, paraffin embedded tissue specimens representing 159 cases of International Federation of Gynecology and Obstetrics Stage I and II were used. HPV DNA was detected by polymerase chain reaction (PCR) using a general primer set that targets the L1 region and synthesizes a product of only 65 base pairs. The HPV types were determined by direct sequencing and compared with known HPV types.All 159 carcinomas were positive for HPV. HPV 16 (64.8%) was most frequently found, followed by HPV 18 (10.7%) and HPV 45 (8.2%). In 6 patients (3.8%), HPV types could not been further classified, and these cases were therefore categorized as HPV X. Although a trend was noted toward poorer prognosis for women with carcinomas harboring HPV types 16, 18, and 45 than for patients with carcinomas harboring HPV types 31, 33, 35, 52, 56, 58, and 68, the differences were not statistically significant. The prevalence of adenocarcinoma and adenosquamous carcinoma was higher among HPV 18 positive patients than among patients with the other known HPV types (P=0.0002).The rate of HPV positivity in these 159 cervical carcinomas was 100%. These findings challenge the assumption that HPV negative cervical carcinomas exist. This high rate might be attributed to the use of a new broad-spectrum HPV PCR test. HPV typing in cervical carcinoma was not significantly related to clinical outcome. HPV 18 was significantly more frequently found in adenocarcinoma and adenosquamous carcinoma. The possibility of classifying HPV 45 as an oncogenic high risk type should be considered.

Human papillomavirus (HPV) infection and p53 abnormalities might both play a role in the carcinogenesis of subtypes of squamous cell carcinoma of the vulva. In this study, the authors investigated the prevalence of and the relationship between p53 overexpression and HPV infection in patients with vulvar carcinoma.Immunohistochemical methods for the detection of p53 protein and consensus primer polymerase chain reaction (PCR) were used, followed by direct sequencing of the PCR product for the evaluation of HPV subtype infection. Sixty-six patients with squamous cell carcinoma of the vulva were available for this study.DO7, an anti-p53 monoclonal antibody, showed p53 overexpression in 35 carcinomas (53%). Consensus primer PCR showed HPV infection in 12 carcinomas (18%). No significant association was observed between p53 overexpression or HPV infection and tumor subtype. Approximately 57% of the HPV negative carcinomas and 33% of the HPV positive carcinomas had p53 overexpression. With regard to the patients with DO7 positivity inor =50% of the nuclei only, significantly more HPV negative carcinomas were DO7 positive compared with HPV positive carcinomas (41% vs. 0%, respectively; P = 0.018). No relation was found between either HPV infection or p53 overexpression and disease free survival.p53 overexpression is common in both HPV positive and HPV negative carcinomas of the vulva. These findings indicate that these two both play a role in the pathogenesis of vulvar carcinoma, but do not influence disease free survival.

To compare the analgetic efficacy and side-effects of Naproxen and Tramadol following the outpatient VABRA aspiration or hysterosalpingography.Ninety-one patients from the gynaecology clinics of two university hospitals and one municipal-teaching hospital.Multicentre double blind randomized clinical trial. Computerised randomisation, stratification per-centre.Semiquantitative assessment of the two drugs was performed by the patient and the gynaecologist using a 1- to 6-point scale. Pain, stress and well-being was scored by the patient using the visual analog scale (VAS) and the verbal description scale (VDS), ranging from 0 (good) to 100 (bad). Side-effects during the first 24 h postoperatively were recorded by the patient in a diary.The analgetic efficacy (pain, stress and well-being) of Naproxen and Tramadol was identical. Subjective assessment by the patient and the doctor also revealed no differences between Naproxen and Tramadol. Side-effects of Tramadol, however, were significantly more severe than those of Naproxen and this phenomenon was responsible for a lower ability to proceed with normal activities in the Tramadol group.Tramadol is a good alternative for Naproxen at outpatient VABRA or HSG procedures when Naproxen is contra-indicated.

The clinical value of pretreatment serum concentrations of cytokeratin 19 fragments, measured by Cyfra 21-1, was compared with tissue polypeptide antigen (TPA) and squamous cell carcinoma antigen (SCC-Ag) in 78 patients with squamous cell cervical cancer.Serum levels were compared with tumor stage, size, lymph node status, parametrial involvement, and prognostic data. The clinical performance of the different tests was evaluated by their receiver operating characteristic (ROC) curves.Serum levels of all markers were related significantly to tumor stage and size. Elevated serum levels of these markers were not found to be predictive for the presence of lymph node metastases. In contrast, a positive relation was found between quantitative serum Cyfra 21-1, TPA, and SCC-Ag levels and the presence of either lymph node metastases or parametrial involvement (i.e., extracervical disease). An elevated, i.e. positive, serum Cyfra 21-1 level was related significantly to the presence of extracervical disease (P = 0.020). The clinical performance of each serum marker in predicting lymph node metastases or parametrial involvement appeared to be similar as expressed by their ROC curves. In the univariate analysis, Cyfra 21-1, TPA, and SCC-Ag showed prognostic value with respect to disease free interval and survival. Elevated serum levels were associated with a poor prognosis. However, after adjusting for tumor stage and size, none of these markers remained statistically significant.Cyfra 21-1 may be of additional value in assessing stage of disease, tumor size, and the presence of extracervical disease in patients with cervical cancer. Determining its value during follow-up warrants further study.

The objective of this study was to investigate the prognostic significance of serum antibodies to human papillomavirus (HPV)-16 peptides in patients with squamous cell cervical cancer.Pretreatment sera from 78 patients and 198 control women were tested by an enzyme-linked immunosorbent assay technique for reactivity with HPV-16 E4 (E401p) and E7 (E701p) synthetic peptides. The presence and serum level of these antibodies were correlated with tumor stage, histologic features, and prognostic parameters.The median follow-up was 65 months (range, 6-97 months). Antibodies to E401p peptide were found in 5 of the 198 (3%) control subjects, 4 of the 43 (9%) patients with low tumor stage (International Federation of Gynecology and Obstetrics [FIGO] Ia, Ib, IIa), and 7 of the 35 (20%) patients with advanced tumor stage (FIGO IIb, III, IVa). Antibodies to E701p were found in 25 (13%), 11 (26%), and 11 (31%) women, respectively. The differences between patients and control subjects were significant (P0.002). Seropositivity against these peptides showed no correlation with tumor stage. Antibody levels to both peptides were significantly higher in patients compared with control subjects (P0.05). Furthermore, antibody levels to E401p were higher in patients with advanced tumor stage versus patients with low tumor stage (P = 0.0097). Such a relation was not found for anti-E701p antibodies. In the univariate analysis, a high level of anti-E701p antibodies was associated with a shorter disease free interval (P = 0.012) and poor survival (P = 0.049). However, this variable possessed no prognostic value after adjusting for FIGO stage and tumor size.The authors' findings indicate that the prognostic significance of serum antibodies to the HPV-16 E4 and E7 peptides used in this study of patients with cervical cancer is limited.

In a group of 316 conizations performed from January 1984 to July 1991, 68 patients (22%) revealed no free margins of cervical intraepithelial neoplasia (CIN). They were divided into two groups with: 'negative follow-up' [normal cytology or less than two smears suggesting CIN I (class IIIa)] and 'positive follow-up' [at least two smears suggesting CIN I or one smear suggesting CIN II (class IIIb) or worse]. Forty-five patients (66%) fulfilled the criteria of negative follow-up. All patients with CIN I at the cone margin (18) were found in this group. The other 23 patients were in the positive follow-up group. Patients with positive follow-up were significantly younger (p = 0.04). Intervention after incomplete cone biopsy was necessary in approximately 10% (7/68) of cases. Cytology was thereby a reliable indicator for residual disease. Higher grade of CIN involved at the cone margin predicted a higher chance of positive follow-up. Semiquantitative measurement of CIN in the cone specimen showed a severe involvement of CIN II and CIN III in the positive follow-up group. In sum, our study showed that CIN I at the margin of the cone biopsy has no clinical significance. However, CIN II or III at the margin needs a careful cytologic follow-up, and appropriate action should be taken in case of cytologic abnormalities.

In to order to investigate the prevalence of HPV related parameters in sexually non-active women, smears of 75 virgins were microscopically reviewed for alterations caused by HPV i.e. koilocytosis, parakeratosis and multinucleinization. In none of these smears were the mentioned parameters seen together, so the diagnosis of HPV infection could not be assessed. In an age-matched control population consisting of 75 sexually active women smears were reviewed. In this group 10 smears (13%) were found positive for HPV infection, well in accordance with literature.

The results of a prospective study of laparoscopic management of ovarian cysts are discussed. This technique of minimally invasive surgery was introduced at the department of Gynaecology of the Leiden University Medical Centre in 1991. Only premenopausal women with unilocular ovarian cysts smaller than 10 cm in diameter and with sonographically benign characteristics were included in this study. In a period of one year, 25 cystectomies and one ovariectomy were performed. 88% of the cysts were initially treated with hormone therapy. Mean age of the patients was 30 years (range: 21-54), average size of the cysts was 6 cm (range: 4-10) and mean operating time was 80 minutes (range: 35-120), there were no complications during operation or in the postoperative period. No laparotomies had to be performed. Three times (11.5%) pathological specimen examination revealed a corpus luteum cyst. The other 23 were non-functional cysts. No carcinoma was detected. The results of this minimally invasive surgery for removal of ovarian cysts are encouraging. Morbidity compared with the conventional cystectomy by laparotomy is low as appears from a shorter hospital stay and quicker recovery. Cystectomy of the ovary, compared with laparoscopic aspiration and fenestration, has a better therapeutic effect and the histological evaluation is more reliable. Persistent, unilocular ovarian cysts, which fulfill the criteria used in our study, are best treated by laparoscopic removal instead of laparotomy.

The serum vitamin B12 levels were determined in 44 asymptomatic patients at least one year after completion of pelvic irradiation for a gynaecological tumour. Ten patients (23%) were found to have decreased levels of serum vitamin B12, of which six (14%) were assumed to be caused by malabsorption due to radiation damage to the terminal ileum as no other reason for a lower vitamin B12 level could be detected. Neither the radiation dose or volume nor the manifestation of acute or late radiation side effects appeared to be correlated with the finding of decreased levels of vitamin B12. It is concluded that even in asymptomatic patients who received pelvic irradiation, serum vitamin B12 levels can serve as a marker for radiation enteropathy. It is advocated to check vitamin B12 levels prior to the radiation treatment as well as during the follow-up of these patients.

The prognosis of patients with early ovarian cancer is good as compared with that of patients with advanced disease. However, there are no methods for predicting prognosis of early ovarian cancer, on which treatment decisions can be based.The prognostic significance of DNA flow cytometric and morphometric analysis was evaluated in 64 surgically treated patients with well-differentiated early-stage (International Federation of Gynecology and Obstetrics [FIGO] Stage IA, IB, IC, and IIA) epithelial ovarian cancer. The extent of the well-defined staging procedure was assessed strictly in every patient.Only five patients died of recurrent ovarian cancer; all of these patients belonged to the inaccurately staged group. No significant relationship was found between clinicopathologic characteristics, such as menopausal status, FIGO stage, histologic cell type, and 5-year disease-free survival rate. Forty-two of the tumors had a mitotic activity index (MAI) of less than 30, and 43 of the tumors showed a volume percentage epithelium (VPE) of less than 65. Neither as a single parameter nor in combination did MAI and VPE correlate significantly with disease-free survival. Thirty-two tumors (50%) were DNA diploid, 15 were considered wide-CV-diploid, and 17 were aneuploid. Nearly 90% of the tumors showed DNA indices (DI) of 1.40 or less. The 5-year disease-free survival rate was significantly lower (61%) for patients with DI greater than 1.40 than for those with DI of 1.40 or less (96%) (P0.005). From the total number of five patients who died of their disease, three had tumors with DI in the tetraploid range.

One hundred consecutive radical hysterectomies performed in a Dutch oncology centre during a five and a half year period between 1984 and 1990, were analysed. The operations were performed in a uniform manner by the same three surgeons. Surgical mortality was nil. Mean operating time was 4 hours and mean blood loss amounted to 1200 ml. One patient developed a vesicovaginal fistula. Long lasting urinary symptoms occurred in 32% of patients, sex problems in 13%. The latter situation was encountered significantly more frequently when surgery was combined with radiotherapy. Eighty-two of the 100 patients had a primary cervical carcinoma and were analysed further. Distribution according to stage was as follows: stage IA: 3, IB: 64, IIA: 13, IIB: 2. Postoperative external and intracavitary pelvic radiation was given in 34 patients (41%). Three-year survival of these patients amounted to 86%. One-third of patients had a large primary tumour (diameter greater than 4 cm). Three-year survival rate in this subgroup of patients was 78%. Lymph node metastases were found in 14 patients (17%). Three-year survival rates for patients with and without lymph node metastases were 64% and 94%, respectively (p less than 0.0001). Results and complications of this series were compared with the current literature data and found to be comparable and sometimes even better than recent literature data. These findings may serve to advocate further centralisation of this kind of surgery in oncological centres in the Netherlands.

Objective To see whether surgical adhesiolysis would improve pelvic pain in women with pelvic adhesions. Design Randomized clinical trial comparing surgery (adhesiolysis) with no surgery with final analysis of results after 9–12 months. Setting Department of Gynecology, Leiden University Medical Center, the Netherlands. Subjects 48 women known by laparoscopy to have stage II-IV pelvic adhesions. Interventions Midline laparotomy and surgical adhesiolysis. Main outcome results Pelvic pain assessed by the McGill pain score, subjective pain assessment and disturbance of daily activities. Results 24 women were randomly allocated to undergo surgical adhesiolysis and 24 to a control group who did not have surgery. After 9–12 months there were no significant differences between the two groups overall with regard to pelvic pain. A subgroup of women with severe, vascularized and dense adhesions involving bowel (stage IV) had significantly less pelvic pain after adhesiolysis for two of the three methods of assessment. Conclusions Adhesiolysis for the treatment of pelvic pain is not indicated in women with light or moderate degree pelvic adhesions. It may be beneficial in those with severe adhesions involving the intestinal tract.

One hundred six patients with chronic pelvic pain were randomly allocated to one of two treatment groups. In the standard-approach group, organic causes of pelvic pain were excluded first and diagnostic laparoscopy was routinely performed. If no somatic cause could be found, attention was given to other causes such as psychological disturbances. In the second group an integrated approach was chosen. From the beginning equal attention was devoted to somatic, psychological, dietary, environmental, and physiotherapeutic factors. In this group, laparoscopy was not routinely performed. Both groups were similar with respect to clinical characteristics of the patients and the severity of their pain as assessed by various pain parameters. Postcoital pain was reported by 27% of the patients. Twenty percent of the patients had had negative sexual experiences such as childhood sexual abuse or rape. Evaluation of the pain 1 year after the institution of treatment revealed that the integrated approach improved pelvic pain significantly more often than the standard approach for three out of four pain parameters (P less than .01). Laparoscopy played no important role in the treatment of pelvic pain. It is concluded that equal attention to both organic and other causative factors from the beginning of therapy is more likely to result in a reduction of pelvic pain than is a standard approach.

The first ten applications of an absorbable polyglycolic-acid mesh to keep small bowel from descending into the pelvis during postoperative radiation treatment, are described. Two of the ten patients developed mild symptoms of (sub)ileus that could be treated conservatively. In two patients GI tract series revealed that a small bowel loop had slipped outside the sling and had descended into the pelvis. To prevent this condition an interlocked running suture to adjust the mesh is recommended. It is concluded that this intestinal sling procedure is a feasible surgical method causing only mild postoperative complaints or no symptoms at all. The sling procedure is effective to keep the small bowel out of the pelvis following surgery in patients who may require postoperative radiation treatment for pelvic malignancy.

Patients with well-differentiated epithelial ovarian cancer Stages Ia, Ib, Ic, and IIa (FIGO 1976) were observed after surgical treatment without adjuvant therapy. Careful surgical staging was required, and the extent of the staging procedure was assessed in each individual patient. There were 107 patients entered in the study by nine Dutch oncology centers. Of these 107, 21 did not fulfill all of the inlet criteria of the study and were excluded. Central pathologic review was performed in the remaining 86 cases, revealing that there was borderline tumor in seven patients, moderately or poorly differentiated tumor in nine patients, and tumor of nonepithelial histologic cell type in one patient. In two cases, no material for histologic review was available. After exclusion of these 19 cases, 67 patients were further analyzed. None of these 67 patients was lost during the follow-up period that ranged from 19 to 99 months (mean, 50 months). Tumor recurrence was found in four patients after 11, 25, 34, and 34 months of follow-up, all of whom died shortly after diagnosis of the recurrence without satisfactory response to secondary treatment. For the patients who underwent the most extensive staging procedure, disease-free 5-year survival was 100%. For the patients who were inaccurately staged, disease-free 5-year survival was 88%. It was concluded that well-differentiated early stage (Ia-IIa) ovarian cancer carries an excellent prognosis after surgical treatment and complete surgical staging, with the possible exception of patients with Stage Ic disease with malignant peritoneal washings. Furthermore, it was considered that the application of more objective and consistent ways of assessing tumor grade should be encouraged. Surgical staging should be regarded as the golden standard in defining subsets of low-risk patients and should be included and clearly defined in future trials on early ovarian cancer.

Laparoscopic findings in 200 asymptomatic, healthy women having a sterilization were recorded; 148 patients (74%) had no abnormality and 52 patients had abnormalities comprising pelvic adhesions (14%), uterine fibromyomas (5%), endometriosis (3%) and ovarian or parovarian cysts (2%).To place diagnostic laparoscopy in perspective, laparoscopic findings in 200 consecutive healthy women having laparoscopic sterilization by clips or rings were recorded. The subjects all had regular menses and a normal pelvic exam. 148 had no pathology on laparoscopy. 52 remaining women had adhesions (28, 14%), hydrosalpinx (3), ovarian cyst (3), endometriosis (5), fibromyomas (10, 5%), parovarian cyst (1), benign bladder tumor (1), and carcinoid bowel tumor (1). 43% of the adhesions were moderate or severe; 26% were associated with history of appendectomy; 68% were located outside the small pelvis. These findings are comparable to those published in 2 other series. They are relevant to management to patients complaining of chronic pain or infertility.

In 30 patients whose last cervical smear had lacked endocervical cells, two new samples were collected, one with a cotton-tipped applicator and the other with the recently developed Cytobrush cervical brush. With the cotton swab, no endocervical cells were present in the repeat smears of 21 patients, as compared with only 3 Cytobrush smears lacking endocervical cells; the difference is statistically significant (P less than .001). Quantitatively, the cellular yield with the Cytobrush was larger. It is concluded that the use of the cervical brush to collect material for cervical smears is more effective and provides a higher yield of cells than the use of the conventional cotton swab. The importance of the presence of endocervical cells in a smear as evidence that the transformation zone has been properly sampled is also discussed.

Case reports are presented for 2 patients in whom copper-containing IUDs had penetrated through the uterine wall into the abdominal cavity. It is pointed out with reference to reports in the literature that laparoscopic removal is frequently impossible and may also be dangerous because of the marked peritoneal reaction surrounding the copper part of the IUD. The results could be adhesions and infiltration. A scheme is proposed for the treatment of patients who are suspected of perforation by a copper-containing IUD. Authors' modified)

In 130 high-risk patients for cervical pathology paired smears were obtained with a wooden spatula and a Cytobrush. The Cytobrush was useful in lowering the amount of inadequate smears (2 vs 22%, p less than or equal to 0.01), and detected more abnormal cytology in combination with the spatula compared to the spatula smear alone (27 vs 35%, p less than or equal to 0.05). In 6 cases, adequate false-negative spatula smears, containing endocervical cells, were corrected by the Cytobrush. It is concluded that the Cytobrush is useful in lowering the amount of inadequate smears and false-negative cytology, while there is little evidence of false-positive cytology. The use of the wooden spatula/Cytobrush-combination is recommended in high risk populations.

Solitary nonspecific decelerations in fetal heart rate occurring in three patients during antepartum cardiotocography are described. The decelerations were nonspecific in that they were neither variable nor late nor associated with maternal hypotension. All occurred in pregnancies complicated by hypertension and placental insufficiency. In the three patients described, the fetus lived for at least three days after the first nonspecific deceleration was observed. Although solitary nonspecific decelerations may indicate may indicate danger to the fetus from placental insufficiency, these decelerations should not be considered as an indication for immediate delivery.

A 24-year-old Vietnamese boat refugee went to a physician to have her IUD removed. There was no control thread, and X-rays showed an IUD of unknown type in situ. The IUD could not be removed with a Wilbaut hook, so curettage was performed to extract the IUD, which could not be identified. It is possible that other Vietnamese refugees are using the same type of IUD.