Transvaginal ultrasound assessment of myometrial and cervical stromal invasion in women with endometrial cancer: interobserver reproducibility among ultrasound experts and gynecologists.

OBJECTIVES: To assess interobserver reproducibility among ultrasound experts and gynecologists in the prediction by transvaginal ultrasound of deep myometrial and cervical stromal invasion in women with endometrial cancer. METHODS: Sonographic videoclips of the uterine corpus and cervix of 53 women with endometrial cancer, examined preoperatively by the same ultrasound expert, were integrated into a digitalized survey. Nine ultrasound experts and nine gynecologists evaluated presence or absence of deep myometrial and cervical stromal invasion. Histopathology from hysterectomy specimens was used as the gold standard. RESULTS: Compared with gynecologists, ultrasound experts showed higher sensitivity, specificity and agreement with histopathology in the assessment of cervical stromal invasion (42% (95% CI, 31-53%) vs 57% (95% CI, 45-68%), P < 0.01; 83% (95% CI, 78-86%) vs 87% (95% CI, 83-90%), P = 0.02; and kappa, 0.45 (95% CI, 0.40-0.49) vs 0.58 (95% CI, 0.53-0.62), P < 0.001, respectively) but not of deep myometrial invasion (73% (95% CI, 66-79%) vs 73% (95% CI, 66-79%), P = 1.0; 70% (95% CI, 65-75%) vs 69% (95% CI, 63-74%), P = 0.68; and kappa, 0.48 (95% CI, 0.44-0.53) vs 0.52 (95% CI, 0.48-0.57), P = 0.11, respectively). Though interobserver reproducibility (in the context of test proportions 'good' and 'very good', according to kappa) regarding deep myometrial invasion did not differ between the groups (experts, 34% vs gynecologists, 22%, P = 0.13), ultrasound experts assessed cervical stromal invasion with significantly greater interobserver reproducibility than did gynecologists (53% vs 14%, P < 0.001). CONCLUSION: Preoperative ultrasound assessment of deep myometrial and cervical stromal invasion in endometrial cancer is best performed by ultrasound experts, as, compared with gynecologists, they showed a greater degree of agreement with histopathology and greater interobserver reproducibility in the assessment of cervical stromal invasion.

Preoperative sexual function in women with rectal cancer.

BACKGROUND: Even though sexual dysfunction has been reported after rectal cancer treatment, information on preoperative sexual function is scarce, particularly in female patients. AIMS: To describe preoperative sexual function in women with rectal cancer, and to analyse potential sources of bias. METHODS: The Female Sexual Function Index (FSFI) was administered to women with newly diagnosed non-metastatic rectal cancer, irrespective of whether they were sexually active or not. FSFI total and domain scores were calculated for women with complete responses to the corresponding items. Data were compared for those who did and did not complete all the FSFI domains, and for women in the study cohort, and those who were eligible for inclusion but not included. RESULTS: Sexual inactivity was common. Mean FSFI total score was low (16.4 ± 10.6 SD) among the women who completed all six FSFI domains. The proportion of women who had a partner was higher in this group compared with those who did not complete all the domains (49 of 57 vs 7 of 25, p < 0.001). Eighty-two of the 157 women eligible for inclusion were included. Included women were younger (p = 0.002) and had less co-morbidity than those who were not included (p = 0.025). CONCLUSIONS: The low FSFI total score indicates sexual dysfunction. However, the use of FSFI in both women who are and who are not sexually active complicates interpretation of the data and may result in an information bias hampering internal validity. External validity may be limited by selection bias.

Epidemiology and prognosis of ovarian metastases in colorectal cancer.

BACKGROUND: National guidelines for prophylactic oophorectomy in women with colorectal cancer are lacking. The aim of this population-based cohort study was to report on the prevalence, incidence and prognosis of ovarian metastases from colorectal cancer, providing information relevant to the discussion of prophylactic oophorectomy. METHODS: All 4566 women with colorectal cancer in Stockholm County during 1995-2006 were included and followed until 2008. Prospectively collected data regarding clinical characteristics, treatment and outcome were obtained from the Regional Quality Registry. RESULTS: The prevalence of ovarian metastases at the time of diagnosis of colorectal cancer was 1.1 per cent (34 of 3172) among women with colonic cancer and 0.6 per cent (8 of 1394) among those with rectal cancer (P = 0.105). After radical resection of stage I-III colorectal cancer, metachronous ovarian metastases were found during follow-up in 1.1 per cent (22 of 1971) with colonic cancer and 0.1 per cent (1 of 881) with rectal cancer (P = 0.006). Survival in patients with ovarian metastases was poor. CONCLUSION: Ovarian metastases from colorectal cancer are uncommon.

The safety and efficacy of MenoTreat, a new balloon device for thermal endometrial ablation.

BACKGROUND: An evaluation of the performance and safety of the prototype of a new device, MemoTreat (Atos Medical) for thermal endometrial balloon ablation in patients with menorrhagia. The evaluation was performed at four Swedish hospitals. METHODS: In total 51 consecutive, premenopausal patients, suffering from menorrhagia due to benign causes and not responding to conventional treatment, were treated between March 1997 and March 1998. The treatment entailed heated (85 degrees C) sterile saline circulated in a uterine balloon at a treatment pressure of 200 mmHg for 11 minutes. The procedure was performed mainly under general anesthesia and no pre-treatment endometrial thinning was performed. A validated pictorial assessment technique was used to evaluate changes in menstrual blood loss before and after treatment. Changes in quality of life and severity of dysmenorrhea were also evaluated. Data analysis was based on the 'intention to treat' method. RESULTS: The success rate in terms of a 50% reduction in menstrual bleeding was 84.3% at 6 months after treatment. Five patients became amenorrheic. The quality of life assessment showed substantial improvement and the severity of dysmenorrhea was markedly reduced. No intra-operative treatment complications occurred and the post-treatment morbidity was similar to that reported for other similar treatment methods. CONCLUSIONS: MenoTreat significantly reduced menstrual bleeding in menorrhagic patients, with a concomitant improvement in quality of life. The findings in this study resulted in a redesigned device with a thinner balloon catheter, improved cervical protection and treatment temperatures kept at a constant level.

The effect of lignocaine on sperm phagocytosis in the peritoneal fluid from women with or without endometriosis.

The study was undertaken to investigate a possible mechanism for reducing the phagocytosis of spermatozoa by leukocytes in the peritoneal fluid from women suffering from endometriosis. Peritoneal fluids were collected during laparoscopy from women undergoing laparoscopic sterilization or from women under investigation for cause of infertility where the laparoscopic findings were endometriosis. Prepared spermatozoa from one healthy man were incubated in vitro with peritoneal fluid with or without lignocaine. Samples from the incubations were studied daily and the number of viable and dead spermatozoa were counted. The number of free spermatozoa, not adhered to leukocytes, was significantly increased when incubated in human peritoneal fluid supplemented with lignocaine. Thus lignocaine contributes to increasing the number of free spermatozoa and maintaining the possibility of fertilizing an oocyte. For patients with endometriosis, treatment with lignocaine might be a means of increasing the chances of conception. A clinical study is in progress to evaluate this effect in vivo and to search for alternative methods of assisting the fertilization process.

Follow up of hysteroscopic surgery for menorrhagia.

OBJECTIVE: A retrospective study of short and long term results of transcervical endomyometrial resection for menorrhagia. MATERIAL AND METHODS: Patient data were collected from all 104 premenopausal women who had undergone a transcervical endomyometrial resection due to severe menorrhagia in 1990-95. Almost 40% had submucous fibromas that were resected together with the endometrium. A questionnaire about gynecological symptoms was mailed to all 104 women. Ninety-seven (93%) women answered the questionnaire. RESULTS: The mean follow-up period was 29 months. The following short-term complications were encountered: fluid overload in four, one uterine perforation and one major bleeding. The long-term complications included: three hematometra and one pregnancy ending in a spontaneous abortion. Glandular hyperplasia of the endometrium without atypia was found in two cases, and adenomyosis in 31 (29%) cases. Twenty-one women (21%) became amenorrhoic after the treatment, whereas forty-nine (51%) had minimal menstrual bleeding. Eleven women (11%) suffered from dysmenorrhea. Due to dysmenorrhea and/or persistent menorrhagia thirteen (12.5%) underwent a hysterectomy, generally within one year after the resection. The histological examinations showed adenomyosis in three cases, fibromas in four and fibromas and adenomyosis in three cases. CONCLUSIONS: In our hands hysteroscopic transcervical endomyometrial resection was a safe and effective treatment for menorrhagia in spite of the fact that amenorrhea was not always achieved. However, dysmenorrhea appeared in 11% of the women. The reason for this remains to be studied. Correct selection criteria is important to get optimal results and reduce the treatment failure.

Hysteroscopy provides proof of trophoblastic tumors in three cases with negative color Doppler images.

Color Doppler sonography has replaced pelvic arteriography as well as real-time ultrasound in the assessment of patients with gestational trophoblastic disease. In about 25% of patients in whom human chorionic gonadotropin (hCG) levels are suggestive of trophoblastic disease, there will be no evidence of abnormal vessels in the uterus. In these cases it is assumed that hCG was produced by metastatic lesions. We present here three cases in which color Doppler examination was negative and where myometrial biopsies containing tumor were obtained by means of hysteroscopy. The fact that color Doppler, in its present form, does not detect small areas of trophoblastic tumor might also have implications for other kinds of tumors. Knowledge of the exact microscopic diagnosis in molar patients with persistent disease may have an impact on management.

Endometrial stromal sarcoma diagnosed by operative hysteroscopy.

A 33 year old, para-2 woman had a 'submucous myoma' diagnosed in the uterine fundus during a diagnostic hysteroscopy because of dysfunctional bleeding. After pretreatment with a gonadotrophin-releasing hormone (GnRH) agonist for 3 months, the myoma was resected through a resectoscope. Histological examination showed features of low-grade stromal sarcoma although no complete diagnostic certainty was reached. Due to the age of the patient and her wish to preserve fertility, it was decided not to perform extensive surgery but to perform hysteroscopy again in a follow-up visit after 3 months. Since the myoma had by this time recurred in the same place, it was decided to perform a total abdominal hysterectomy. The subsequent histopathological examination confirmed the growth of a low-grade stromal sarcoma. Following this diagnosis, the ovaries were removed laparoscopically and were found to be free of tumour.

The utilization rate and pregnancy outcome of multifetal pregnancy reduction in the Nordic countries.

OBJECTIVE: To review the utilization rate and pregnancy outcome of multifetal pregnancy reductions (MFR) in the Nordic countries during the period January 1986-June 1992. STUDY DESIGN: All centers offering assisted conception in Denmark, Finland, Norway and Sweden were retrospectively surveyed by means of a questionnaire with regard to the number and methods used for MFR, pregnancy loss and the outcomes of the pregnancies. The response rate was 100%. RESULTS: During the period studied, 185 births of triplets or higher multiples occurred in Sweden, 120 in Finland and 102 in Denmark. MFR was performed in 42 women (Sweden 26, Finland 10, Denmark 6) but not in Norway at all. This gives an estimated average utilization rate of 1/7 multiple births of three or more in Sweden, 1/17 in Denmark and 1/12 in Finland. The most frequently used method was intracardiac or intrathoracic injection of a potassium chloride solution in gestational weeks 9-12. One pregnancy was reduced from seven to four fetuses, two from five to three, 10 from five to two, one from four to three, 17 from four to two, one from four to one, five from three to two, four from three to one and one from two to one. Nine (21%) pregnancies terminated in a spontaneous abortion within one week (n = 2) to several weeks (n = 7) after the procedure. Of the remaining 33 (79%) pregnancies which continued to delivery, two fetuses died in utero in the second trimester, three infants died perinatally and one child had transverse limb reduction defects. A successful pregnancy defined by the discharge home of at least one infant occurred in 79% of the cases. CONCLUSION: This study gives national estimates on the utilization rate of MFR. Although MFR is performed more frequently in Sweden than in Denmark and Finland, the overall figures remain low in the Nordic countries. The incidence of pregnancy loss in this study is somewhat higher than in several larger reported series, probably reflecting the learning curve of the procedure. It seems reasonable that MFR should be performed in only a few centers in the Nordic countries.

Hysteroscopy in gestational trophoblastic diseases.

Hysteroscopic evaluations were performed in eight women with gestational trophoblastic diseases. Seven of the eight patients had abnormal hysteroscopic findings and biopsies were obtained from the endometrium and adjacent myometrium. Five patients had histopathological proof of tumour. This preliminary report shows the feasibility of the method. The potential risks involved are discussed. A correct histopathological diagnosis in patients evaluated for gestational trophoblastic diseases may be useful in order to tailor the treatment.

Physical and mental development in 4-6-year-old triplets.

A total of 21 families with complete sets of triplets, born within 200 km of Stockholm, were invited to participate in a follow-up study with the aim of assessing the physical and mental development of their triplets at 4-6 years of age. Four families declined to participate in the study and thus the study group consisted of 17 sets of triplets who were born at 33-36 gestational weeks from 1986 to 1989. Mean birth weight was 2104 g (range 1310-2670 g) for the boys and 1882 g (range 1290-2590 g) for the girls. At birth, none of the 51 triplets showed any malformations. No asphyxia or other major complications were noted to have occurred at delivery. The children were examined in their homes with a neurological examination and the Griffiths mental development scales (GMDS). No major physical disabilities were found. In a group of triplets born small for dates, the total GMDS score and most of the subscale scores were significantly lower than for their siblings. In contrast to what has been found in singletons and twins, the differences in mental development between triplet boys and girls were not significant. On the whole, physical and mental development did not differ from what has been found in twins and singletons of the same age and with the same birth weight.

Multifetal pregnancy reduction in Sweden. Utilization rate and pregnancy outcome (1986-1992)

All departments of Obstetrics and Gynecology, as well as all private clinics in Sweden offering assisted conception, were surveyed by means of a questionnaire to determine the utilization rate and outcome of multifetal pregnancy reduction (MFR) for the period 1 January 1986 to 30 June 1992. The response rae was 100%. Multifetal reduction was performed in 26 women, giving an average utilization rate of 1/7 multiple births of three or more for the entire period. Of the various techniques used, intracardiac or intrathoracic injection of a potassium chloride solution was predominant. The experience of each center with multifetal reductions varied between one and six procedures. In this series, the overall complete pregnancy loss was 27% (n = 7). In 73% (n = 19) of women the pregnancy continued to delivery. One fetus died in utero in the second trimester, one child died from a subtentorial hemorrhage perinatally, and one child had a malformation of the right foot and hand. It seems necessary to limit MFR to a few centers in Sweden in order to maintain and increase the experience of the operators involved, and to decrease the fetal loss rate associated with the procedure. However, the ultimate goal is to make these procedures unnecessary when methods of avoiding excessive ovulation are refined and by limiting the number of replaced embryos in IVF-treatment.

Cervical ripening with mifepristone (RU 486) in first trimester abortion. An electron microscope study.

Mifepristone (RU 486) is a steroid that binds to the progesterone receptor and acts as a progesterone antagonist. It has been used clinically to terminate an early pregnancy. In the present investigation, the effects of mifepristone on the fine structure of the cervix were evaluated in two groups of women undergoing a first trimester abortion, using a triple-blind randomized protocol. In group I (n = 18), a cervical biopsy was taken after two doses of 100 mg mifepristone or placebo orally 24 and 12 h before vacuum aspiration. In group II (n = 20), cervical biopsies were taken before and after two doses of 100 mg mifepristone or placebo orally 48 and 36 h before vacuum aspiration. Smooth muscle cells, fibroblasts and an extracellular matrix with large bundles of collagen fibrils were the main structural components in all cervical biopsies. In group I, an increased number of mast cells and signs of new blood capillary formation and collagenolysis were observed in several of the biopsies after mifepristone treatment (67% correctly classified). In group II, the effects were less evident and in most of the cases (70%) no definite differences were noted between the biopsies taken before and after mifepristone treatment. Nevertheless, mifepristone treatment had induced softening in the cervical tissue, as judged by the decrease in resistance to mechanical dilatation.

Production of 12-hydroxyeicosatetraenoic acid in early pregnant uterine cervix--lack of correlation to mifepristone-induced cervical ripening. A double-blind randomized biomechanical and biochemical study.

The regulation of cervical ripening in pregnancy may involve arachidonic acid metabolites. We studied the formation of lipoxygenase products in cervical biopsies from twenty nulliparous women requesting a first trimester abortion. The patients were randomly allocated to receive either 100 mg of the progesterone antagonist mifepristone (RU 486) or placebo 48 and 36 hours before surgery. A capacity to produce significant amounts of 12-HETE and material co-chromatographing with leukotrienes was observed in the cervical tissue. No qualitative or quantitative relationship to mifepristone-induced cervical ripening was found. Although our data suggest a large variation of 12-HETE production it remains to clarify its role in the cervix.