Accuracy of transvaginal ultrasound versus MRI in the PreOperative Diagnostics of low-grade Endometrial Cancer (PODEC) study: a prospective multicentre study.

AIM: To investigate if the diagnostic accuracy of transvaginal ultrasound (TVUS) performed by gynaecologists is sufficient for preoperative assessment of low-grade endometrial cancer (EC) compared to magnetic resonance imaging (MRI). MATERIALS AND METHODS: MRI and TVUS performed by gynaecologists were assessed at the participating centres. The MRI examinations were interpreted by two radiologists at the tertiary centre. Deep myometrial and cervical stroma invasion were visually assessed and compared to postoperative histopathology. RESULTS: Two hundred and fifty-nine patients were included. There was a statistically significant difference in specificity assessing deep myometrial invasion between MRI and TVUS (MRI 0.88, TVUS 0.68). There was no difference in sensitivity (MRI 0.73, TVUS 0.68). When assessing cervical stroma infiltration, MRI had a higher specificity (MRI 0.96, TVUS 0.90), but there was no difference in sensitivity (MRI 0.41, TVUS 0.32). CONCLUSION: MRI has higher specificity than TVUS performed by gynaecologists for assessing deep MI and CSI in low-grade EC, but similar sensitivities. The use of TVUS as a first-line test, rather than MRI, may be supported by this study in centres where access to MRI may be limited.

Impact of lymphadenectomy and lymphoedema on health-related quality of life 1 year after surgery for endometrial cancer. A prospective longitudinal multicentre study.

OBJECTIVE: To assess the impact of lymphadenectomy and lymphoedema of the lower limbs (LLL) on health-related quality of life (HRQoL) 1 year after surgery for endometrial cancer (EC). DESIGN: Prospective longitudinal cohort multicentre study. SETTING: Departments of obstetrics and gynaecology at four university hospitals, six central hospitals and four county hospitals in Sweden. POPULATION: Two-hundred-and-thirty-five women with early stage EC were included; 116 with high-risk EC underwent surgery including lymphadenectomy (+LA), and 119 with low-risk EC had surgery without lymphadenectomy (-LA). METHODS: The generic SF-36 and EQ-5D-3L and the lymphoedema-specific LYMQOL questionnaire were used to assess HRQoL. LLL was assessed by systematic circumferential measurements of the legs enabling volume estimation, clinical evaluation and patient-reported perception of leg swelling. All assessments were carried out on four occasions; preoperatively, and 4-6 weeks, 6 months and 1 year postoperatively. MAIN OUTCOME MEASURE: HRQoL scores. RESULTS: No significant differences were seen in HRQoL between the +LA and -LA groups 1 year postoperatively. Irrespective of method of determining LLL, women with LLL were significantly more affected in the LYMQOL domains Function, Appearance/body image and Physical symptoms, but not in the domain Emotion/mood, than women without LLL. No such differences were seen in the generic HRQoL or in the LYMQOL global score between the groups with and without LLL. CONCLUSIONS: Lymphadenectomy did not seem to affect generic HRQoL adversely. Irrespective of the method of measuring, LLL affected the lymphoedema-specific HRQoL negatively, mainly in physical domains, but had no impact on the generic HRQoL. TWEETABLE ABSTRACT: Lymphoedema has impact on lymphoedema-specific, but not on generic, HRQoL, 1 year after surgery for EC.

Asparaginase-like protein 1 expression in curettage independently predicts lymph node metastasis in endometrial carcinoma: a multicentre study.

OBJECTIVE: Correct preoperative identification of high-risk patients is important to optimise surgical treatment and improve survival. We wanted to explore if asparaginase-like protein 1 (ASRGL1) expression in curettage could predict lymph node metastases and poor outcome, potentially improving preoperative risk stratification. DESIGN: Multicentre study. SETTING: Ten hospitals in Norway, Sweden and Belgium. POPULATION: Women diagnosed with endometrial carcinoma. METHODS: ASRGL1 expression in curettage specimens from 1144 women was determined by immunohistochemistry. MAIN OUTCOME MEASURES: ASRGL1 status related to disease-specific survival, lymph node status, preoperative imaging parameters and clinicopathological data. RESULTS: ASRGL1 expression had independent prognostic value in multivariate survival analyses, both in the whole patient population (hazard ratio (HR) 1.63, 95% CI 1.11-2.37, P = 0.012) and in the low-risk curettage histology subgroup (HR 2.54, 95% CI 1.44-4.47, P = 0.001). Lymph node metastases were more frequent in women with low expression of ASRGL1 compared with women with high ASRGL1 levels (23% versus 10%, P < 0.001), and low ASRGL1 level was found to independently predict lymph node metastases (odds ratio 2.07, 95% CI 1.27-3.38, P = 0.003). CONCLUSIONS: Low expression of ASRGL1 in curettage independently predicts lymph node metastases and poor disease-specific survival. TWEETABLE ABSTRACT: Low ASRGL1 expression in curettage predicts lymph node metastasis and poor survival in endometrial carcinoma.

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.

Revision of FIGO surgical staging in 2009 for endometrial cancer validates to improve risk stratification.

OBJECTIVE: Correct staging is a cornerstone in cancer treatment. The FIGO surgical staging for endometrial cancer was revised in 2009. We have evaluated if the revision improved stratification with respect to prognosis in a large prospective multicenter setting. METHODS: 1268 endometrial cancer patients have been prospectively recruited in the MoMaTEC study for the investigation of clinical and histopathological data. RESULTS: Restaging from FIGO 88 to FIGO 09 criteria increased the number of stage I cases from 932 to 979. The majority of the non-endometrioid tumors, down-staged to FIGO 09 stage I, were of serous histology. One third of the patients classified as stage II tumors based on FIGO 88 criteria (FIGO88 IIA) were down-staged to FIGO 09 IA (53%) and FIGO 09 IB (47%). The histological subtype for these cases was mainly endometrioid (86.1%) and high/intermediate grade (77.7%). Patients with FIGO 88 stages IA, IB, IIA and IIIA with positive cytology only, showed similar survival. In Cox multivariate survival analysis adjusting for histopathological variables we found that the revised FIGO 09 criteria improved prognostication. For FIGO stage I patients the adjusted HR was 3.9 (p=0.01, CI 1.35-11.36) for FIGO IB compared to FIGO IA. The independent prognostic impact for the FIGO 09 staging was also confirmed in a subset analysis of patients not subjected to lymphadenectomy and for the endometrioid subgroup. CONCLUSIONS: The FIGO 2009 staging system has improved prediction of prognosis, and is less complex, compared to earlier versions. Careful assessment of myometrial invasion seems particularly important for patients not subjected to lymphadenectomy.

Fertility after autologous ovine uterine-tubal-ovarian transplantation by vascular anastomosis to the external iliac vessels.

BACKGROUND: Transplantation of the uterus has been suggested as a treatment of uterine factor infertility. This study investigates whether the sheep uterus can resume its capacity to harbour normal pregnancies after autotransplantation by vascular anastomosis. METHODS: From 14 ewes, the uterus, excluding one uterine horn, was isolated along with its oviduct and ovary and preserved ex vivo and then transplanted back with end-to-side anastomosis of the vessels of the graft to the external iliac vessels. After recovery, the ewes underwent surgical examination and serum progesterone measurements to ascertain healing and ovarian activity. Afterwards, five autotransplanted and five control ewes were placed with a ram for mating. Caesarean sections were performed before the estimated term of pregnancy and data on fetal measures were compared. RESULTS: Of the 14 ewes, seven survived surgery with ovarian activity intact and grafts showing normal appearance. Mating occurred in four of five transplanted ewes and in five out of five controls, and three transplanted animals and five control animals conceived. In one transplanted ewe, torsion of the uterus was observed after spontaneous initiation of labour. Foeti from transplanted mothers were comparable in size to those of controls. CONCLUSIONS: Despite the encountered complications, this is the first report to demonstrate fertility and pregnancies going to term after autotransplantation of the uterus in an animal of a comparable size to the human.

Uterus transplantation in the baboon: methodology and long-term function after auto-transplantation.

BACKGROUND: Techniques for uterus transplantation (UTx) have been developed in rodent/domestic animals towards future clinical introduction of UTx to treat uterine factor infertility. The aim of this study was to extend the UTx research into a non-human primate species by developing surgical techniques for uterus retrieval and transplantation in the baboon. METHODS: Female baboons (n = 15) underwent surgery, with the initial five animals used for studies of pelvic vascular anatomy. Retrieval surgery included isolation of the ovarian veins and the uterine arteries together with the anterior branches of the internal iliacs. The utero-tubal-ovarian specimen was removed, flushed and kept ex vivo for 2 h when the two arterial ends and two venous ends were anastomosed side-to-side to construct one arterial and one venous end. These were, at auto-transplantation, anastomosed end-to-side to the external iliacs and the animals (n = 10) were evaluated concerning cyclicity and later by laparoscopy/laparotomy. RESULTS: The total duration of organ retrieval, backtable preparation and transplantation was around 6 h with an overall ischaemic time of the specimen of about 3 h. One animal died due to cardiomyopathy. Five out of the nine surviving animals resumed cyclicity, as a sign of re-established ovarian function. Only two out of these five animals exhibited resumed menstruation, indicating re-established ovarian and uterine function. Laparoscopy confirmed normal-sized uteri in these two animals. CONCLUSIONS: This study demonstrates the feasibility of UTx by vascular anastomosis in a non-human primate species. The low success rate demonstrates the complexity involved in UTx surgery and the need for further methodological developments.

Vaginal sacrospinous colpopexy and laparoscopic sacral colpopexy for vaginal vault prolapse.

BACKGROUND: Vaginal sacrospinous colpopexy (VSC) and laparoscopic sacral colpopexy (LSC) both correct vault prolapse. The present study compares the perioperative course and long-term results of VSC and LSC. METHODS: This retrospective study of post-hysterectomy vault prolapse involved 111 patients operated with either VSC (n=51) or LSC (n=60). The median time for the postoperative follow-up visit was 33.6 (range: 13-60) months for the LSC group and 38.4 (range: 7-108) months for the VSC group. Prolapse grade as well as the patient's satisfaction was recorded at the follow-up visit. RESULTS: Operation time was significantly shorter in the VSC group (median: 62 min) compared to the LSC group (median: 129 min). The rate of perioperative complications was low in both groups. There were 3 laparotomies in the LSC group, due to perioperative complications. The inpatients days were similar, with 3.7 days (1-18) and 4.0 days (2-21) in the VSC and the LSC group, respectively. Surgery for the recurrence of vault prolapse at any time before the follow-up visit did not occur in the VSC group, but occurred in 7 patients in the LSC group. At the follow-up visit, there was no recurrence of vault prolapse in either group. The subjective success rate was 82% in the VSC and 78% in the LSC group. CONCLUSIONS: This study indicates that VSC and LSC are two equally effective surgical procedures to correct vaginal vault prolapse, but the LSC technique requires a longer operating time.

Microwave radiation enhances teratogenic effect of cytosine arabinoside in mice.

Impregnated Swiss mice were irradiated 2 h daily on days 1-18 of gestation in nonthermal (1 or 10 mW/cm2) or thermogenic (40 mW/cm2) 2,450-MHz microwave (MW) fields. On the 19th day of pregnancy all dams were killed to check the number of resorptions. Living fetuses were isolated, weighed and checked for the presence of macroscopically visible malformations of skeleton and cleft palate (CP) and/or lip (CLP). Some of the pregnant mice in each group were injected intraperitoneally on the 9th day of gestation with 10 mg/kg of cytosine arabinoside (ara-C), a well-known teratogen resulting under the above conditions in the appearance of about 15% (42 of 354) of resorbed implantation points and the development of CP or CLP in about 30% (96 of 312) of fetuses. Exposure to nonthermal MW fields during pregnancy did not lead to resorptions or detectable malformations; however, the body mass of 19-day fetuses was significantly lower than in sham-irradiated controls. MW hyperthermia (40 mW/cm2) applied during pregnancy led to an increased number of resorptions - about 25% (37 of 157) compared to 2% (6 of 306) in controls. Significant enhancement of the teratogenic potency of ara-C was observed after combined exposure to both ara-C and MWs during pregnancy. In dams treated with ara-C alone about 20% (62 of 358) resorptions and about 30% (91 of 296) fetuses with CL or CLP were found; additional exposure in MW fields (10 mW/cm2), not resulting per se in resorptions or detectable malformations, increased the numbers to 45% (213 of 448) of resorptions and to 70% (167 of 235) fetuses with CL or CLP.+

[Are microwaves a co-teratogen? Experimental model concept and its verification]. / Czy mikrofale sa koteratogenem--koncepcja modelu doswiadczalnego i jego sprawdzenie.

Microwave radiation does not result in development of congenital malformations in mice until hyperthermia is evoked. However, in the literature it is well established that certain environmental and occupational factors not being teratogenic per se may enhance and/or influence potency of established teratogens. As concerns the microwave radiation there are results suggesting cocarcinogenic properties of this radiation. In view of the above we set the hypothesis that microwave radiation may also interfere with teratogenic potency of the established teratogens. For the experiment we selected cytosine arabinoside (ara-C) under the trade name of Cytosar, produced by the Upjohn Co. The scheme of our experiment included injection of pregnant mice with 10 mg per kg of are-C on various days of gestation and further also irradiation in microwaves fields at power density of 10 mW/cm2. After checking the teratogenic potency of ara-C in further study on combination of ara-C and microwaves all the mice from the experimental groups were injected on the 9th day of gestation. The significant increase of the incidence of both malformations and resorptions was observed after combined action of are-C and microwaves. We conclude that the experimental pattern of teratogenic action of are-C can be used widely in experiments on combination with other environmental and occupational factors.

Effects of microwave exposure in utero on embryonal, fetal and postnatal development of mice.

Pregnant Swiss mice were repetitively exposed during various periods of gestation to 2,450 MHz continuous wave microwave radiation. Irradiations were conducted daily in an anechoic chamber at a power density of 10 (subthermal) or 40 mW/cm2 (thermal) for 2 h/day, 7 sessions/week. Thermal exposures to microwaves resulted in significant inhibition of the embryonal and fetal development in utero, accompanied by an increased incidence of intrafetal bleedings, resorptions and deaths of fetuses. Moreover, nonspecific resistance to viral and bacterial infections was markedly depressed in pups of dams irradiated for the whole period of gestation with thermal doses of microwaves. No such effects were found following exposure of pregnant mice to 10 mW/cm2 power density of radiation. The results suggest that the observed effects of microwave exposure in the course of pregnancy are thermal in nature.

[Effect of 2450 MHz microwaves on the fertility of Swiss female mice]. / Badanie wplywu mikrofal 2450 MHz na plodnosc samic myszy szczepu "Swiss".

The effect of repeated expositions to 2450 cm2 microwaves at power densities of 10 or 40 mW/cm2 on fecundity of female Swiss mice was investigated. After microwave irradiations during whole pregnancy mice were allowed to have offsprings. On the day of birth litters were inspected, the number of pups noted. 30 days later female mice were mated with males for the second time and after delivery the litters were controlled, offsprings were counted. The size of first and second litters were compared. The size of second litters of irradiated animals were compared with controls. We concluded, that microwave repetitive exposure of female mice in presented conditions does not result in impaired fecundity measured as a litter size.

[Clinical value of the fetoplacental ratio]. / Ocena wartosci klinicznej wskaznika poplodowo-plodowego.

Scientific interest in the placenta derives not only from its enormous diversity of form and function but also from the unique metabolic, endocrine and immunologic properties. The steady increase in size and weight of the placenta throughout pregnancy has been investigated in the large number of studies. The data obtained from weighing the placenta vary considerably, depending upon how the placenta is prepared. If membranes and mass of the cord are left attached and adherent maternal blood clot is not removed, the weight is increased by nearly 50 percent. In our study we tried to asses the value of the feto-placental ratio and to correlate the weight of placenta with the other data obtained during pregnancy and labour and with outcome of pregnancy. A group of 1010 patients was assessed. The data obtained these patients were correlated with the length of pregnancy, the body weight of the baby and the status of the newborn estimated by Apgar score in 1 and 5 min. The feto-placental ratio was significantly affected by the length of pregnancy and the status of the newborn. Another comparisons were made with the medical illnesses during pregnancy, i. g. H--Gestosis, renal diseases and the cholestasis of pregnancy.

[Environmental and occupational factors in the development of congenital malformations]. / Czynniki srodowiskowe i zawodowe jako przyczyna powstawania wad wrodzonych.

Teratology has grown from a little known discipline to a discipline embracing a vast accumulation of literature on experimental studies in many animal forms. Emphasis has shifted from preoccupation with descriptions of anatomical defects to concern about subtle and interacting causative factors. The aim of this work is to assemble a source of facts, concepts, methods and references within the broad scope of teratology. Our review summarizes reports of teratogenic effects in mammals. The major intent of this work, however, has been to introduce into a field of teratology. Special attention has been paid to the relation of animal studies to the problem in man and to the interactions between teratogens and environmental variables. We present a number of illustrative examples of various kinds of interactions that may occur and their possible significance. Striking degrees of potentiative interactions have been demonstrated in laboratory animals when two or more compounds were used simultaneously at doses at or below the threshold level for teratogenicity of the same compound when applied singly. We propose the name coteratogenesis for the agents which are not teratogenic but which aggravate teratogenicity of the other factors known as teratogens.