DNA ploidy in curettage specimens identifies high-risk patients and lymph node metastasis in endometrial cancer.

BACKGROUND: Preoperative risk stratification is essential in tailoring endometrial cancer treatment, and biomarkers predicting lymph node metastasis and aggressive disease are aspired in clinical practice. DNA ploidy assessment in hysterectomy specimens is a well-established prognostic marker. DNA ploidy assessment in preoperative curettage specimens is less studied, and in particular in relation to the occurrence of lymph node metastasis. METHODS: Curettage image cytometry DNA ploidy in relation to established clinicopathological variables and outcome was investigated in 785 endometrial carcinoma patients prospectively included in the MoMaTEC multicentre trial. RESULTS: Diploid curettage status was found in 72.0%, whereas 28.0% were non-diploid. Non-diploid status significantly correlated with traditional aggressive postoperative clinicopathological features, and was an independent predictor of lymph node metastasis among FIGO stage I-III patients in multivariate analysis (OR 1.94, P=0.033). Non-diploid status was related to shorter disease-specific survival (5-year DSS of 74.4% vs 88.8% for diploid curettage, P<0.001). When stratifying by FIGO stage and lymph node status, the prognostic effect remained. However, in multivariate regression analysis, preoperative histological risk classification was a stronger predictor of DSS than DNA ploidy. CONCLUSIONS: Non-diploid curettage is significantly associated with aggressive clinicopathological phenotype, lymph node metastasis, and poor survival in endometrial cancer. The prognostic effect was also observed among subgroups with (presumably) less aggressive traits, such as low FIGO stage and negative lymph node status. Our results indicate curettage DNA ploidy as a possible supplement to existing parameters used to tailor surgical treatment.

A discordant histological risk classification in preoperative and operative biopsy in endometrial cancer is reflected in metastatic risk and prognosis.

INTRODUCTION: In endometrial cancer, tissue for histological evaluation is obtained preoperatively (endometrial biopsy) and operatively (hysterectomy specimen). We investigated if a discordant risk classification based on preoperative and operative biopsy is reflected in metastatic risk and prognosis. PATIENTS AND METHODS: One thousand three hundred and seventy-four patients were prospectively included in a multicentre setting (Molecular Markers for Treatment of Endometrial Cancer (MoMaTEC) study). Preoperative and operative specimens were classified as high risk if non-endometrioid histology or endometrioid grade 3; otherwise low risk. Disease specific survival differences were calculated by means of Kaplan-Meier and Cox proportional hazard models. RESULTS: Discordant risk was found in 207 (16%) cases. Lymph node metastases were detected in 7% and 23% of patients with concordant low and high risk respectively versus 14% and 20% in the discordant groups (p<0.001). Five-year disease specific survival in the discordant groups proved intermediate (75-80%) to concordant low (94%) or high (58%) risk. Both operative and preoperative biopsy high-risk results have independent prognostic impact on disease specific survival with adjusted hazard ratios of 2.4 (95% confidence interval (95% CI) 1.5-3.9) and 2.1 (95% CI 1.3-3.2) respectively by Cox analysis. CONCLUSIONS: Discordant risk in preoperative biopsy and hysterectomy identifies an intermediate group with respect to disease spread and prognosis. Preoperative biopsy results remain important also with the hysterectomy histology available.

Sublingual nitroglycerin for management of retained placenta.

OBJECTIVE: The aim of the study was to investigate the effect of sublingual nitroglycerin for management of retained placenta and to assess possible adverse effects of the treatment. METHOD: Twenty-four women were randomly selected to receive either 1 mg nitroglycerin or placebo tablets sublingually if intravenous oxytocin and controlled umbilical cord traction had failed to expel the placenta. Success rate for delivery of placenta, blood pressure, pulse rate, blood loss, and various side effects were examined. RESULT: All 12 women in the nitroglycerin group had successful delivery of placenta, while removal of placenta was successful in only one of the 12 women in the placebo group. No adverse effects of clinical importance were registered. CONCLUSION: Sublingual nitroglycerin for treatment of retained placenta seems to be effective without causing serious adverse effects. However, the definite clinical value needs to be evaluated in larger series of patients.

Validation of a six-task simulation model in minimally invasive surgery.

BACKGROUND: The content validity of currently available inanimate simulation models is questionable, because some tasks seem too far from clinical reality. The aim of this study was to validate a simulation model with six tasks commonly used in clinical practice (6-TSM) for the acquisition of psychomotor skills in minimally invasive surgery (MIS). METHODS: This was a prospective randomized trial comparing the 6-TSM to a previously described three-task training method (3-TTM). All first, second, and third postgraduate year surgical residents were eligible. The 6-TSM included clipping and dividing of a vessel, excision of lesion, appendectomy, mesh repair, suturing perforation, and hand-sewn anastomosis. The outcome measures of 6-TSM included accuracy error, tissue damage, sliding knot, leak, operating time, and dangerous movements. After completion of training, 6-TSM and 3-TTN residents were tested by the Minimally Invasive Surgical Trainer-Virtual Reality (MIST-VR). Criterion-related and construct validity, responsiveness, test-retest, and interrater reliability were assessed. RESULTS: During six months, 17 residents underwent training with the 6-TSM or the 3-TTM as allocated. The mean duration of training with 6-TSM and 3-TTM was similar (7.8 vs 8.1 h). The criterion-related validity of the 6-TSM was shown by significantly increased skill improvement in the 6-TSM residents, as compared with the 3-TTM residents at MIST-VR. Construct validity the of 6-TSM was shown by the finding that the experts' baseline was superior to the residents' baseline. The responsiveness of the 6-TSM was shown by the significantly increased skill improvement of the 6-TSM residents in sliding knot, leak, and operating time. The test-retest reliability of the 6-TSM was good (> 0.80), except for accuracy error and dangerous movements (Cronbach's intraclass correlation coefficient alpha: 0.57, p < 0.0001; 0.62, p < 0.0001, respectively). The interrater reliability of the 6-TSM was good (>0.80) except for leak (Kendall's concordance coefficient tau_b:0.76, p = 0.06 for hand-sewn anastomosis) and dangerous movements (tau_b:0.72, p = 0.08 for suturing perforation and tau_b:0.68, p = 0.10 for hand-sewn anastomosis). The perresident cost for 6-TSM was 769 dollars. CONCLUSIONS: The 6-TSM is a valid and reliable learning tool for surgical residents' acquisition of laparoscopic motor skills.

Treatment of ectopic pregnancy by local injection of hypertonic glucose: a randomized trial comparing administration guided by transvaginal ultrasound or laparoscopy.

OBJECTIVE: To study local treatment of ectopic pregnancy by injection of hyperosmolar (50%) glucose, guided either by transvaginal ultrasound or by laparoscopy. METHODS: Eighty women were randomized, 39 into the sonography and 41 into the laparoscopy group. Criteria for inclusion were 1) ectopic pregnancy < or = 4 cm seen by transvaginal ultrasound, 2) hCG < or = 3000 IU/l, and 3) little or no intraabdominal bleeding. In the sonography group, patients were treated by one skilled ultrasound investigator, whereas injections by laparoscopy were performed by several colleagues. The former group were offered a second glucose injection if hCG levels were rising. Those successfully treated were offered hysterosalpingography (HSG) for evaluation of tubal patency. RESULTS: Twenty-nine (74.4%) women were successfully treated in the sonography group by one single injection, compared to 21 (51.2%) in the laparoscopy group. Eight women in the sonography group received a second glucose injection because of a rising hCG, increasing the success rate in this group to 82.1% (32 of 39 women). Six patients in the laparoscopy group were not injected due to technical difficulties during the operation, and the success rate for those injected were 60% (21 of 35 women). The overall success rate was 66.3%. Of the 28 women investigated by HSG, both tubes were normal in 19 (67.8%), and in 25 patients (89.3%) the treated tube was open. CONCLUSIONS: Local injection of hyperosmolar glucose guided by transvaginal ultrasound by one skilled investigator is an effective treatment for ectopic pregnancy. Most women preserve tubal patency after treatment.

[Childbirth preparation classes--parenteral education on the right track? An evaluation study based on questionnaires sent to women in Sogn and Fjordane]. / Svangerskapskurs--foreldreutdanning på rett veg? Ei brukarevaluering frå kvinner i Sogn og Fjordane.

Three hundred and fifteen women were sent a questionnaire within 8 months after delivery. They were interviewed about various aspects of pregnancy, delivery and the postpartum period. The response rate was 82%. This paper deals with the women's experience of childbirth preparation classes. Eighty per cent reported that such classes were available. Of this eighty per sent, 50% had attended such classes. Women having their first baby were more likely to attend. Forty-three per cent of the attending women found the classes very beneficial whereas 50% reported little and 7% no benefit from the childbirth education. The results indicate that in the women's view the classes are not especially important in ante-natal care. Furthermore, the quality of the classes seems to be inadequate.

On the specificity of prostaglandin and steroid induced inhibition of 3H-proline incorporation in the human follicular wall.

Experiments were carried out to elucidate whether the previously reported inhibitory effect of prostaglandin (PG) E2 on 3H-proline incorporation into total protein of specimens from the isolated preovulatory human follicular wall could be exerted also by other prostanoids. Moreover, investigations were designed to explore if the previously documented inhibitory effect of steroids on 3H-proline incorporation could be mediated by endogenously formed PGs. Tissue specimens from the apical wall of follicles were incubated in the presence of PGF2 alpha, 6-keto-PGF1 alpha, progesterone (P) or 17 beta-estradiol (E2). The steroids were added alone or in combination with the PG synthetase blockers, indomethacin or 5, 8, 11, 14-eicosatetraynoic acid. Following incubation with 3H-proline for 2-4 h, the incorporated radioactivity was determined. PGF2 alpha and 6-keto-PGF1 alpha had no effect on 3H-proline incorporation. Both P and E2 induced a significant decrease of 3H-proline incorporation in preovulatory follicles, whereas similar effects in unripe follicles were statistically significant only for P. The steroid effects were not influenced when blockers of PG synthesis were added concomitantly. It is concluded that among the "classical" PGs PGE2 has a unique effect on collagen metabolism in the human follicular wall. E2 and especially P have a similar inhibitory effect on collagen formation as reflected by measurements of 3H-proline incorporation, an effect which does not appear to be primarily mediated by endogenous PGs.

Oxytocin in human follicular fluid and its possible role in the ovulatory process as studied in vitro.

Oxytocin immunoreactivity was determined in follicular fluid from human follicles at different stages of development. The concentration of oxytocin was highest in pre-ovulatory follicles. The measured oxytocin was found to co-elute with synthetic oxytocin in an h.p.l.c. system. The influence of oxytocin on the incorporation of [3H]proline into isolated human follicular wall was studied in vitro. Oxytocin induced a decrease of radiolabelling in both unripe and pre-ovulatory follicles, indicating an inhibitory effect on collagen synthesis. This effect of oxytocin was not affected by indomethacin. An oxytocin analogue, 1-deamino-2-D-Tyr(OEt)-4-Thr-8-Orn-vasotocin, did not inhibit the incorporation of [3H]proline. The pre-ovulatory augmentation of oxytocin concentration in follicular fluid might reflect a physiological role for oxytocin in the ovulatory process. This assumption is strengthened by the observation that oxytocin may influence follicular collagen metabolism in vitro and by this means participate in the regulation of follicular rupture in the human.

Interaction between prostaglandin E2 and noradrenalin on collagen synthesis in human cervical tissue during pregnancy.

The effects of prostaglandin E2 (PGE2) and noradrenalin (NA) on the incorporation of [3H]proline in cervical tissue of pregnant women were investigated. NA inhibited the incorporation in early as well as in term pregnancy. PGE2 counteracted the NA-effect in the former group of patients but did not affect the influence of NA at term. The results demonstrate an interaction between PGE2 and NA and point to a hitherto unknown effect of NA in the regulation of cervical connective tissue metabolism.

Hormonal effects on collagenolytic activity in the isolated human ovarian follicular wall.

Tissue pieces from the wall (i.e. tunica albuginea with adjacent theca externa) of human follicles were incubated with and without various hormones and their potential influence upon the collagenolytic activity was evaluated. Following incubation the collagenase activity was determined in the incubation medium by measurement of the hydrolytic activity against the synthetic peptide 2,4-dinitrophenyl-Pro-Gln-Gly-Ile-Ala-Gly-Gln-D-Arg-OH. Stimulated collagenolytic activity was seen in the presence of relaxin and oxytocin whereas prostaglandin E2, prostaglandin F2 alpha, progesterone and 17 beta-estradiol were without effect. It is concluded that the stimulated collagenolytic activity induced by relaxin and oxytocin may be of importance for the degradation of collagen which occurs prior to follicular rupture.

Vaginitis emphysematosa in a renal transplant patient.

Transplant surgery is now a widely established practice and the associated immunosuppressive treatment is followed by various complications. The present report on vaginitis emphysematosa in a woman with renal transplantation indicates that even this benign condition may have a connection with immunosuppressive therapy.

The influence of prostaglandin E2 and oxytocin on the incorporation of [3H]proline and [3H]glucosamine in the human amnion.

Fetal membranes were obtained in connection with 1st-trimester abortion and vaginal delivery or elective caesarean section at term. Pieces of the isolated amnion membrane were incubated in vitro with [3H]proline or [3H]glucosamine in the presence of prostaglandin (PG) E2 or oxytocin. PGE2 reduced the labelling with [3H]proline in the 1st trimester and in membranes obtained at vaginal delivery, whereas an increase of incorporation was observed before start of labour. Oxytocin reduced [3H]proline labelling at any stage. In membranes from vaginally delivered women both oxytocin and PGE2 stimulated the incorporation of [3H]glucosamine, whereas oxytocin diminished radiolabelling in the other experimental groups. Regarding the radiolabelling with [3H]proline and [3H]glucosamine as reflecting the de novo formation of collagen and proteoglycans, respectively, it is suggested that both PGE2 and oxytocin, by their influence on connective tissue metabolism, may regulate the tensile properties of the fetal membranes.

Influence of progesterone, androstenedione and oestradiol-17 beta on the incorporation of [3H]proline in the human follicular wall.

The incorporation of proline, a precursor for collagen specific hydroxyproline, is regarded to reflect the metabolism of collagen. In vitro experiments were carried out to investigate the influence of sex steroids on the incorporation of [3H]proline into the human follicular wall. Tissue pieces from the apical wall of follicles at different stages of development were incubated in the presence of the steroids and [3H]proline, and the tissue bound radioactivity was determined. Progesterone induced a decrease of radiolabelling in both unripe and pre-ovulatory follicles. Androstenedione caused a similar effect but only in pre-ovulatory follicles. The influence of oestradiol-17 beta on the incorporation of [3H]proline was less pronounced with a tendency towards a decrease of radiolabelling in both types of follicles. It is suggested that the observed biochemical changes induced by sex steroids are of importance for connective tissue remodelling preceding human follicular rupture.

Influence of prostaglandin E2 on proteoglycan synthesis in the human ovarian follicle wall.

The effect of prostaglandin (PG) E2 on the incorporation of 3H-glucosamine in the human follicular wall was investigated in vitro. Follicles were obtained from women undergoing sterilization via minilaparotomy. Tissue pieces of the follicular wall were incubated in the presence of PGE2 and 3H-glucosamine and the tissue-bound radioactivity was determined. PGE2 induced a significant increase of radiolabelling in the apex of the mature follicle wall but did not significantly affect the incorporation in other parts of the wall, nor in the wall of less developed follicles. The incorporation of glucosamine, a precursor of glucosaminoglycans, is regarded to reflect the synthesis of proteoglycans. The demonstrated increase in the incorporation of 3H-glucosamine in the apical wall of the mature follicle in response to PGE2 indicates that PG-mediated stimulation of proteoglycan synthesis is of importance for follicular rupture.

Collagen synthesis inhibition by PGE2 within the human follicular wall--one possible mechanism underlying ovulation.

Follicular wall specimens were taken from various parts of human preovulatory follicles as well as from less developed follicles. The tunica albuginea was isolated and incubated for 2 h in Krebs Ringer bicarbonate buffer containing 3H-proline in the presence or absence of PGE2 (0.1 microgram/ml). Following incubation the incorporated radioactivity was determined and related to the protein content of each strip. PGE2 had a specific effect on the incorporation of 3H-proline into protein in the follicular wall. In the apical part of the preovulatory follicle a significantly decreased incorporation was registered, indicating a reduced net synthesis of collagen. However, PGE2 was without effect on specimens derived from the non-apical parts of the preovulatory follicles as well as from the less developed follicles. It is suggested that the registered biochemical changes induced by PGE2 are of importance for the process of human ovulation.