Laparoscopically assisted vaginal and abdominal hysterectomy: comparison of postoperative pain, fatigue and systemic response. A case-control study.

BACKGROUND AND OBJECTIVE: Laparoscopic and open surgery have been compared with conflicting results regarding their systemic responses. The sensitivity of biochemical markers that are used to discriminate between the stress responses to different types of surgery varies from study to study. We wanted to evaluate the stress response and the sensitivity of clinical and biochemical stress markers in patients undergoing laparoscopically assisted vaginal or abdominal hysterectomy. METHODS: We performed a case-control study with patients undergoing laparoscopically assisted vaginal hysterectomy (n=20) or abdominal hysterectomy (n=20). Pain scores were assessed at rest and during coughing, and active leg elevation and fatigue scores using a visual analogue scale. In 10 patients of each group, haematocrit, white cell count, C-reactive protein, glucose, cortisol, adrenocorticotrophic hormone, beta-endorphin immunoreactivity, interleukin-6 and urine excretion of epinephrine and norepinephrine were measured preoperatively and during the first 44 postoperative hours. RESULTS: The most sensitive symptoms and markers of the systemic response were pain scores during mobilization, fatigue scores, C-reactive protein and interleukin-6 (P < 0.01 in all comparisons). Pain scores at rest, and all other laboratory markers of the systemic response, did not discriminate between the two types of surgery. CONCLUSION: Follow-up of postoperative pain scores during mobilization and fatigue levels might be an easy tool for the evaluation of postoperative recovery. Using an identical anaesthetic technique, the neuroendocrine response was of the same magnitude after both types of surgery.

GnRH analogues and uterine leiomyomas. Effect of hormone replacement therapy on cell proliferation.

Cell proliferation in uterine leiomyomas treated preoperatively with either nafarelin (400 microg/day) for 3 months (7 patients) or nafarelin plus hormone (oestradiol + norethisterone) add-back therapy (6 patients) was investigated by automatic image analysis of frozen tissue sections using immunohistochemistry with anti-proliferating cell nuclear antigen antibody. GnRHa therapy decreased cell proliferation in leiomyomas to a level corresponding to the situation previously seen in postmenopausal leiomyomas. However, there was no consistent correlation between cell proliferation and shrinkage of leiomyomal size. The hormone add-back therapy moderated the influence of GnRHa on cell proliferation and completely blocked a decrease in size of leiomyomas in our patients.

Cytokine production profiles in the peritoneal fluids of patients with malignant or benign gynecologic tumors.

BACKGROUND: Cytokines play a key role in the regulation of cells of the immune system and also have been implicated in the pathogenesis of malignant diseases. Some cytokines have been shown to have potential in the diagnosis of cancer. METHODS: A total of 111 patients with ovarian, cervical, or endometrial carcinomas or benign ovarian or uterine tumors were enrolled on the study, and the levels of interleukin (IL)-2, IL-4, IL-6, IL-10, interferon (IFN)-gamma, granulocyte-colony stimulating factor (G-CSF), granulocyte-macrophage-colony stimulating factor (GM-CSF), macrophage-colony stimulating factor (M-CSF), and tumor necrosis factor (TNF)-alpha were measured by cytokine specific, enzyme-linked immunoadsorbent assays. In addition, ratios of IL-2, IL-4, and IFN-gamma production were studied to characterize the type of T-cell response that occurred in the peritoneal cavities of the patients. RESULTS: High levels of M-CSF (mean for all patients, 26,050 pg/mL) and G-CSF (mean for all patients, 20,267 pg/mL) were observed in virtually all patients, but no significant differences between the study groups were observed. Similarly, no differences in the levels of IL-2, IL-4, IL-10, IFN-gamma, GM-CSF, or TNF-alpha were found. However, IL-6 levels were significantly higher in patients with ovarian carcinoma (mean +/- standard error of the mean [SEM]: 5572 +/- 1266) or benign tumors (mean +/- SEM: 4474 +/- 2008) than in those with cervical (mean +/- SEM: 1222 +/- 546) or endometrial carcinoma (mean +/- SEM: 1977 +/- 616). A predominantly Th1 type cytokine profile, irrespective of the diagnosis, was observed in patients with gynecologic tumors. CONCLUSIONS: With the exception of IL-6, the cytokine synthesis profiles in the peritoneal fluids of patients with benign and malignant gynecologic tumors were found to be similar. These results suggest that cytokine production in these patients is a result of nonspecific inflammation rather than a specific response against the tumor cells, and that skewing of cytokine synthesis toward either the Th1 or the Th2 phenotype is not the underlying mechanism resulting in the malignant process in women with gynecologic tumors.

Impaired ovarian function and risk factors for atherosclerosis in premenopausal women.

OBJECTIVES: The aim of the study was to obtain information on the possible relationship between impaired ovarian function and risk factors for cardiovascular disease. MATERIAL AND METHODS: Serum lipid levels, plasma fibrinolytic potential and histological and biochemical changes in the intima of the uterine artery were investigated in premenopausal women with irregular menstrual cycles, and the results were compared with those from regularly menstruating women. In addition, the same parameters were studied in postmenopausal women on hormone replacement therapy (HRT) and in postmenopausal women who had never used HRT. In total 64 patients undergoing hysterectomy for benign reasons were included the study. RESULTS: Plasma fibrinogen concentration was significantly higher in irregularly menstruating women as compared with women with regular cycles. In women with irregular cycles thickened or sclerotic arterial intima was a significantly more common finding as compared with regularly menstruating women. A significant positive correlation was observed between plasma fibrinogen concentration and intimal esterified cholesterol content in women with thickened or sclerotic uterine artery. CONCLUSIONS: These data suggest an important role for normal ovarian function in the prevention of atherosclerosis.

Increased levels of interleukin-6 and interleukin-10 in the peritoneal fluid of patients with endometriosis.

OBJECTIVE: The levels of interleukin-2, interleukin-4, interleukin-5, interleukin-6, interleukin-10, and granulocyte-macrophage colony-stimulating factor were measured in the peritoneal fluid of 15 patients with endometriosis to characterize the type of immune response that occurs at the site of endometriosis. STUDY DESIGN: Cytokine levels in peritoneal fluid obtained during laparoscopy from 15 patients and 12 controls undergoing tubal ligation were determined by enzyme-linked immunosorbent assay. RESULTS: The mean levels of interleukin-6 in patients with endometriosis and controls were 797 +/- 407 pg/ml and 133 +/- 38 pg/ml, respectively (p < 0.02). Similarly, the mean concentration of interleukin-10 in peritoneal fluids of patients with endometriosis was significantly higher than that of controls (241 +/- 38 vs 128 +/- 21, p < 0.05). The levels of interleukin-2, interleukin-4, interleukin-5, and granulocyte-macrophage colony-stimulating factor were not significantly different between the two study groups. CONCLUSIONS: The levels of interleukin-6 and interleukin-10 are increased in the peritoneal fluids of patients with endometriosis, suggesting enhanced macrophage activity in these patients. Increased interleukin-6 and interleukin-10 production may partially contribute to the disturbed immune regulation observed in patients with endometriosis.

Detection of serum antibodies to Chlamydia trachomatis in patients with chlamydial and nonchlamydial pelvic inflammatory disease by the IPAzyme Chlamydia and enzyme immunoassay.

A novel serological test, IPAzyme Chlamydia (Savyon Diagnostics Ltd., Beer Sheva, Israel), was compared with an enzyme immunoassay (EIA) for the ability to detect serum immunoglobulin G and A antibodies in the diagnosis of acute chlamydial pelvic inflammatory disease. In comparison with cell culture, which is the "gold standard," IPAzyme Chlamydia and EIA exhibited sensitivities of 63 and 68% and specificities of 76 and 87%, respectively. Thus, IPAzyme Chlamydia offers no advantages over the EIA, and neither serological test can be recommended for the diagnosis of acute Chlamydia trachomatis infection. So far, conventional cell culture remains the most reliable diagnostic test for chlamydial pelvic inflammatory disease.

Demonstration of tumor necrosis factor-alpha in preovulatory follicular fluid: its association with serum 17 beta-estradiol and progesterone.

In the present study we have measured the concentrations of interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) in preovulatory follicular fluid (FF) samples obtained from patients undergoing ovulation induction with human menopausal gonadotropin/human chorionic gonadotropin. In 13 of the 24 (54%) FF samples obtained from 20 patients, TNF-alpha was detected. In contrast, IL-1 beta was observed in none of the 16 samples assessed. In the samples with detectable levels of TNF-alpha, the mean concentration was 40.1 pg/ml (range 20-74 pg/ml). In addition, we found an association between the presence of TNF-alpha in the FF and the serum level of 17 beta-estradiol (E2) and progesterone (P). The E2 and P levels were significantly lower in patients with detectable levels of TNF-alpha in FF than in patients with no detectable TNF-alpha in FF. In summary, the present study shows the presence of TNF-alpha and the absence IL-1 beta in hyperstimulated human preovulatory FF. In addition, our results show an association between the presence of TNF-alpha in FF and low E2 and P levels in serum, suggesting a role for TNF-alpha in the regulation of human steroidogenesis.

The effect of ciprofloxacin and doxycycline plus metronidazole on lower genital tract flora in patients with proven pelvic inflammatory disease.

Alterations in the lower genital tract flora were studied during antimicrobial treatment of 36 women with acute pelvic inflammatory disease (PID). Sixteen women received ciprofloxacin, and 20 received doxycycline plus metronidazole. Both regimes eradicated Chlamydia trachomatis in all cases and Neisseria gonorrhoeae in all except one in which combination treatment failed because of resistance of the organism to tetracycline. Both regimes eradicated Mycoplasma hominis in all cases, while ciprofloxacin was somewhat less effective than combination treatment against Ureaplasma urealyticum. Ciprofloxacin was less effective than combination treatment against Gardnerella vaginalis. The incidence of Candida infection increased equally in both groups, although symptoms necessitating antifungal treatment were rare.

C-reactive protein in assessing antimicrobial treatment of acute pelvic inflammatory disease.

Serial serum C-reactive protein (CRP) determinations were used in the evaluation of antimicrobial treatment of acute pelvic inflammatory disease (PID) as proven by laparoscopy and endometrial biopsy or microbiologic findings in the upper genital tract in 36 women. Sixteen patients were treated with ciprofloxacin and 20 with doxycycline plus metronidazole. The mean CRP levels did not differ significantly in patients with severe and moderate salpingitis in comparison with mild salpingitis on admission or during treatment, nor was there any significant difference between the mean CRP levels in patients with acute chlamydial/gonococcal and nonchlamydial/nongonococcal PID. The mean CRP levels decreased by the third day of treatment in all treatment groups, and the decrease by the sixth day of treatment was significant (P less than .05), reflecting the clinical response to therapy faster than did serial ESR determinations. After the documentation of acute PID, serial serum CRP determinations were a useful predictor of the short-term response to antimicrobial therapy.

Antigen specific serum antibody response to Chlamydia trachomatis in patients with acute pelvic inflammatory disease.

Sera from 35 patients with acute pelvic inflammatory disease (PID) with and without Chlamydia trachomatis confirmed by culture and sera from 19 control patients with neither evidence of pelvic infection nor C trachomatis infection were studied for the presence of serum IgG, IgA, and IgM antibodies to C trachomatis using enzyme immunoassay (EIA) and immunoblotting techniques. There was no correlation between the antibody concentrations in the EIA and the spread of chlamydial infection, as determined by cervical, endometrial, and laparoscopic sampling for chlamydia. The immunoblot analysis showed antibodies to the major outer membrane protein (MOMP) of C trachomatis elementary bodies in all patients who had had C trachomatis isolated. Reactivity was also frequently observed against the 68, 62, 60, 45, and 31 kilodalton antigens. About 20 antigenic polypeptides were identified. Differences in antibody prevalence to specific chlamydial antigens, however, were not related to the site of chlamydial isolation or serum antibody concentrations observed with the EIA. The results indicate that patients with PID with and without upper genital tract infection with C trachomatis cannot be differentiated by reactivity of sera to specific chlamydial polypeptide antigens. The determination of a specific serum IgA antibody response by EIA was the most effective single test to discriminate between patients with and without acute chlamydial infection.

A case-control study of uterine endometrial cancer in Japanese and Finn.

The difference between the endometrial cancer incidence in Japanese and Finnish women (lower and higher incidence, respectively), was evaluated on the basis of data from cases of endometrial cancer, cervical cancer and benign gynecological disease in both countries. The comparison took into account the various personal and clinical characteristics of these cases. In endometrial cancer, Japanese and Finnish women had similar characteristics except for the age at first delivery, the age at last delivery and obesity. However, obesity in postmenopausal women in the two countries was similar. Common factors in the two countries included few pregnancies and deliveries, nullipara and single women. In cervical cancer, no difference between the characteristics of Japanese and Finnish women was found except that Japanese women had a higher frequency of pregnancy. In benign diseases, characteristics were similar to those of endometrial cancer in Finnish women, but this was not the case in Japanese women. These facts may indicate the number of Finnish women with endometrial cancer risk factors is greater than the number of Japanese women with these risk factors. This was thought to account for the difference in the incidence of endometrial cancer.

Transvaginal ultrasound in the diagnosis and treatment of tubo-ovarian abscess.

Transvaginal ultrasound showed tubo-ovarian abscess in 10 patients admitted for acute pelvic inflammatory disease, and transvaginal ultrasound-guided aspiration of tubo-ovarian abscess was performed under antimicrobial treatment. Only light sedation was required and the procedure was well tolerated by the patients. The short-term recovery of all patients was quick and uncomplicated. This new technique is a useful alternative for the diagnosis and treatment of tubo-ovarian abscess.

Laparoscopic diagnosis and treatment of acute pyosalpinx.

We diagnosed acute pyosalpinx in eight patients with laparoscopy. The pus was aspirated through the laparoscope in five cases, and antimicrobial treatment was started intravenously thereafter. The short-term recovery was uncomplicated. Laparoscopic treatment of acute pyosalpinx, in contrast to radical surgery, preserves reproductive potential and ovarian function.

Serologic evidence for the role of Chlamydia trachomatis, Neisseria gonorrhoeae, and Mycoplasma hominis in the etiology of tubal factor infertility and ectopic pregnancy.

The authors used enzyme immunoassay to determine the prevalence of serum antibodies to the sexually transmitted disease (STD) organisms Chlamydia trachomatis, Neisseria gonorrhoeae, and Mycoplasma hominis among 104 infertile women undergoing in vitro fertilization. Altogether, 55 (72%) out of 76 women with tubal abnormalities tested positive for one or more STD organisms, compared with only 6 (21%) out of 28 infertile women with normal tubes (P less than .001). The authors obtained positive test results for C. trachomatis, N. gonorrhoeae, and M. hominis in 40%, 14%, and 37% of the patients with tubal abnormalities, respectively; of women without tubal abnormalities, the test results were 7%, 0%, and 14%, respectively. Out of 20 patients with a history of ectopic pregnancy, the authors obtained positive findings for C. trachomatis, N. gonorrhoeae, and M. hominis in 8 (40%), 1 (5%), and 7 (35%), respectively. These results indicate an independent role for all three STD organisms in the etiology of tubal factor infertility and ectopic pregnancy following both symptomatic and asymptomatic pelvic inflammatory disease (PID). The correlation between positive mycoplasmal serology and secondary infertility and tubal abnormalities may suggest a link between M. hominis infections during pregnancy and delivery complications and consequent development of tubal factor infertility.

Serum CA 125 in acute pelvic inflammatory disease.

Serum levels of CA 125 and other selected tumour markers were measured in 31 patients with proven pelvic inflammatory disease (PID). Ten (32%) of the patients had elevated CA 125, one (4%) had elevated CEA, and none had elevated CA 15-3, AFP or beta 2-microglobulin. Compared to patients with normal CA 125, patients with elevated CA 125 were older, more often users of intrauterine contraceptive devices, had longer duration of symptoms, higher erythrocyte sedimentation rates, and more often had an adnexal mass on pelvic examination. There was a correlation between CA 125 levels and the severity of adnexal inflammation as defined by laparoscopy. Isolation of specific micro-organisms from the upper genital tract was not associated with elevated CA 125. In most women serum levels of CA 125 decreased during treatment. PID should be considered as a major cause of positive CA 125 findings among young women.

Removal of an intrauterine device and the treatment of acute pelvic inflammatory disease.

The effect of removing intrauterine devices on the resolution of acute pelvic inflammatory disease was retrospectively studied in 186 hospital inpatients. In 105 patients the intrauterine device was left in place and in 81 it was removed on admission. The demographic and clinical findings in the two groups were similar. No differences were found between the two groups in their short-term response to treatment, except that when an intrauterine device was removed the time in hospital was more often prolonged.

Chlamydial salpingitis and perihepatitis after tubal occlusion.

Chlamydia trachomatis was isolated from the distal part of the tube in a patient with salpingitis and perihepatitis 14 months after laparoscopic tubal occlusion. This suggests that chlamydial infection can spread by the lymphatic or hematogenous routes.

Class specific antibody response to gonococcal infection.

An enzyme immunoassay was used to determine IgM, IgG, and IgA antibodies to gonococcal pili in 68 patients with uncomplicated gonorrhoea, 35 women with pelvic inflammatory disease, and in 115 normal controls. A clear difference in response rate in all three antibody classes between patients with gonorrhoea and healthy controls was evident. Among women with gonorrhoea, the magnitude of antibody response was higher than among men with gonorrhoea, especially in the IgM class. No major differences were found in the overall distribution of serological findings between women with uncomplicated gonorrhoea and those with gonococcal pelvic inflammatory disease. Among this last group, however, high IgM antibody levels in acute phase sera were significantly associated with the isolation of Neisseria gonorrhoeae in the upper genital tract.

The relation between serum sex steroid levels and plasma cell infiltrates in endometritis.

We measured serum levels of progesterone and estradiol among 35 patients with endometritis confirmed by endometrial biopsy. The onset of symptoms took place predominantly in the proliferative phase of the cycle. A negative correlation was found between the serum progesterone levels and the histopathologic severity of plasma cell endometritis. Our results suggest that the hormonal status contributes to the immune response and susceptibility to endometrial infection.