Identifying safe diagnostic algorithms for sentinel lymph node mapping in high-risk endometrial cancer: The SENTIREC-endo study.

INTRODUCTION: It is unclear if sentinel node (SLN) mapping can replace pelvic- (PLD) and paraaortic lymphadenectomy (PALD) for high-risk endometrial cancer (EC). A diagnostically safe surgical algorithm, taking failed mapping cases into account, is not defined. We aimed to investigate the diagnostic accuracy of SLN mapping algorithms in women with exclusively high-risk EC. METHODS: We undertook a prospective national diagnostic cohort study of SLN mapping in women with high-risk EC from March 2017 to January 2023. The power calculation was based on the negative predictive value (NPV). Women underwent SLN mapping, PLD and PALD besides removal of suspicious and any FDG/PET-positive lymph nodes. Accuracy analyses were performed for five algorithms. RESULTS: 170/216 included women underwent SLN mapping, PLD and PALD and were included in accuracy analyses. 42/170 (24.7%) had nodal metastasis. The algorithm SLN and PLD in case of failed mapping, demonstrated a sensitivity of 86% (95% CI 74-100) and an NPV of 96% (95% CI 91-100). The sensitivity increased to 93% (95% CI 83-100) and the NPV to 98% (95% CI 94-100) if PLD was combined with removal of any PET-positive lymph nodes. Equivalent results were obtained if PLD and PALD were performed in non-mapping cases; sensitivity 93% (95% CI 83-100) and NPV 98% (95% CI 95-100). CONCLUSION: SLN-mapping is a safe staging procedure in women with high-risk EC if strictly adhering to a surgical algorithm including removal of any PET-positive lymph nodes independent of location and PLD or PLD and PALD in case of failed mapping.

The SENTIREC-endo study - Risks and benefits of a national adoption of sentinel node mapping in low and intermediate risk endometrial cancer.

OBJECTIVE: The SENTIREC-endo study aims to investigate risks and benefits of a national protocolled adoption of sentinel lymph node (SLN) mapping in women with early-stage low-grade endometrial cancer (EC) with low- (LR) and intermediate-risk (IR) of lymph node metastases. METHODS: We performed a national multicenter prospective study of SLN-mapping in women with LR and IR EC from March 2017-February 2022. Postoperative complications were classified according to Clavien-Dindo. Lymphedema was assessed as a change score and as incidence of swelling and heaviness evaluated by validated patient-reported outcome measures at baseline and three months postoperatively. RESULTS: 627 women were included in the analyses; 458 with LR- and 169 with IR EC. The SLN detection rate was 94.3% (591/627). The overall incidence of lymph node metastases was 9.3% (58/627); 4.4% (20/458) in the LR- and 22.5% (38/169) in the IR group. Ultrastaging identified 62% (36/58) of metastases. The incidence of postoperative complications was 8% (50/627) but only 0.3% (2/627) experienced an intraoperative complication associated with the SLN procedure. The lymphedema change score was below the threshold for clinical importance 4.5/100 CI: (2.9-6.0), and the incidence of swelling and heaviness was low; 5.2% and 5.8%, respectively. CONCLUSION: SLN mapping in women with LR and IR EC carries a very low risk of early lymphedema and peri- and postoperative complications. The national change in clinical practice contributed to a more correct treatment allocation for both risk groups and thus supports further international implementation of the SLN technique in early stage, low grade EC.

Can the dynamic spectral imaging (DSI) color map improve colposcopy examination for precancerous cervical lesions? A prospective evaluation of the DSI color map in a multi-biopsy clinical setting.

BACKGROUND: Colposcopy serves as a subjective examination of the cervix with low sensitivity to detect cervical intraepithelial dysplasia (CIN) grade 2 or worse (CIN2 +). Dynamic spectral imaging (DSI) colposcopy has been developed to provide an objective element to cervix examinations and has been proven to increase sensitivity of detecting CIN2 + . We aimed to assess the performance of the DSI color map and compared it to histological diagnoses of cervical biopsies in determining the CIN grade present. METHODS: Women were included in a consecutive, prospective manner at Randers Regional Hospital, Denmark. Women were eligible to participate if they were referred for colposcopy due to abnormal cervical smear (threshold: ≥ ASCUS) or follow-up after previously diagnosed CIN. All women had four biopsies taken, one directed by colposcopists alone prior to viewing the DSI color map, one directed by the worst color on the respective DSI color map, and two additional biopsies. All biopsies were analyzed separately. We calculated sensitivity, specificity, positive predictive values, and negative predictive values (NPVs) with 95% confidence intervals (CIs). RESULTS: A total of 800 women were recruited. Of these, 529 (66.1%) were eligible for inclusion. The sensitivity of the DSI color map was found to be 48.1% (95% CI 41.1-55.1) in finding CIN grade 2 or worse (CIN2 +) when compared to the histological diagnosis of the DSI directed biopsy. This was 42.5% (95% CI 36.7-48.5) when compared to the final histological diagnosis of all four cervical biopsies and with an NPV of 53.5% (95% CI 50.5-56.5). CONCLUSION: The worst color indicated by the DSI map might not consistently reflect the true grade of cervical dysplasia present. Thus, even though the DSI color map indicates low-grade changes, colposcopists should still consider taking biopsies from the area as high-grade changes might be present. TRIAL REGISTRATION: NCT04249856, January 31 2020 (retrospectively registered).

Dynamic Spectral Imaging Colposcopy Versus Regular Colposcopy in Women Referred With High-Grade Cytology: A Nonrandomized Prospective Study.

OBJECTIVE: The aim of the study was to evaluate the sensitivity of dynamic spectral imaging (DSI) colposcopy compared with regular colposcopy for women referred with high-grade cervical cytology. METHODS: In a prospective, nonrandomized, multicenter study, we included women referred for colposcopy at hospital gynecology clinics with high-grade cytology. Women were examined using either a regular or DSI colposcope. In both groups, colposcopists located 1 area viewed as most suspicious. In the DSI group, this was done before viewing the DSI map. Subsequently, an area was chosen based on the worst color of the DSI map, and further additional biopsies were taken. All women had 4 cervical biopsies taken, all analyzed separately. The main outcome was sensitivity to find cervical intraepithelial neoplasia grade 2 or worse (CIN2+). RESULTS: A total of 261 women were examined using DSI colposcopy, and 156 women were examined using regular colposcopy. The sensitivity for finding CIN2+ when using the DSI technology as an adjunctive technology was found to be 82.2% (95% CI = 75.9-87.4), based on an average of 1.4 biopsies. This was corresponding in sensitivity to 2 biopsies taken using regular colposcopy (80.3%; 95% CI = 72.3-86.8). There was no difference in sensitivity for CIN+ between the groups when 3 or more biopsies were taken. CONCLUSIONS: We found that the DSI colposcope may help direct biopsy placement; however, the improvement is based on small differences in needed biopsies and the clinical significance of this may be small. Multiple biopsies were still superior.

Accuracy of colposcopy-directed biopsy vs dynamic spectral imaging directed biopsy in correctly identifying the grade of cervical dysplasia in women undergoing conization: A methodological study.

INTRODUCTION: Dynamic spectral imaging (DSI) colposcopy has previously been found to improve sensitivity of CIN2+ detection. The aim of this study was to compare the histological diagnosis of colposcopic-directed biopsies (CDB) with that of DSI-directed biopsies in women undergoing conization, using the histological diagnosis of the conization specimen as gold standard. MATERIAL AND METHODS: Women referred for colposcopy were included in a prospective cohort study at Randers Regional Hospital, Denmark, from January 2016 to February 2019. All women had four cervical punch biopsies taken. The first biopsy was taken from the area that appeared most abnormal by conventional colposcopy (ie, CDB) and the second biopsy from the area that appeared most abnormal using the DSI map. An additional two biopsies were taken either from other visible lesions or as random biopsies. Biopsies were analyzed separately. If any biopsies revealed cervical dysplasia of such a degree that excisional treatment was recommended, the patient was referred for conization. Subsequently, we compared the histological diagnosis of CDB and DSI-directed biopsies with that of the cone biopsy. RESULTS: A total of 573 women were enrolled, 170 of which underwent conization. In women with an adequate colposcopy and representative biopsies (n = 124) there was an overall agreement rate between the worst biopsy diagnosis (of any four) and the conization diagnosis in 95.2% (95% CI 89.8-98.2) of women. CDB diagnosis agreed with the cone diagnosis in 80.6% (95% CI 72.6-87.2) of women. DSI-directed biopsy agreed with the cone diagnosis in 83.9% (95% CI 76.2-89.9) of women. The difference in detection rate between the CDB and the DSI-directed biopsy was, however, not significant (P = .54). Taking four biopsies increases the detection rate of cervical dysplasia to 95.2%, which was a significant increase from both CDB alone (P = .0008) and DSI-directed biopsy alone (P = .0053). CONCLUSIONS: We found no significant difference in the ability to identify the cervical dysplasia grade between CDB and DSI-directed biopsies. A higher detection rate of cervical dysplasia was achieved with four biopsies than with one CDB biopsy or one DSI-directed biopsy.

Ultrasound Scoring of Endometrial Pattern for Fast-track Identification or Exclusion of Endometrial Cancer in Women with Postmenopausal Bleeding.

STUDY OBJECTIVE: To evaluate the risk of endometrial cancer (REC) scoring system for the prediction of high and low probability of endometrial cancer (EC) in women with postmenopausal bleeding (PMB). DESIGN: A prospective study (Canadian Task Force classification II-1). SETTING: An academic hospital. PATIENTS: Nine hundred fifty consecutive patients with PMB underwent transvaginal ultrasonography (TVS) and REC scoring between November 2013 and December 2015. INTERVENTIONS: Obstetrics and gynecology residents supervised by trained physicians scored endometrial patterns according to the previously established REC scoring system. The reference standard was endometrial samples, endometrial thickness (ET, 4-4.9 mm), operative hysteroscopy or hysterectomy (ET ≥5 mm), and 1-year follow-up in all patients presenting with ET <4 mm. Diagnostic performance for the prediction of probability of malignancy was assessed using the REC scoring system. MEASUREMENTS AND MAIN RESULTS: The area under the receiver operating characteristic curve of the TVS REC scoring system was 97% (95% confidence interval [CI], 95%-98%) for the prediction of malignancy. In 656 patients with ET ≥4 mm, REC scoring effectively predicted a high probability of malignancy with sensitivity (95% confidence interval) of 92% (95% CI, 87%-95%) and specificity of 94% (95% CI, 91%-96%). An REC score of 0 was present in 206 (32%) patients with ET ≥4 mm and was associated with a low negative likelihood ratio of 0.026 for EC. There were only 7 patients with EC/atypical hyperplasia among these 206 patients. CONCLUSION: The REC scoring system identified or ruled out most ECs, clearly showing that more specific image analysis at first-line TVS can accelerate the diagnosis of EC in patients with PMB and may allow for improved selection of second-line strategies in patients with ET ≥4 mm.

Preoperative prediction of high-risk endometrial cancer by expert and non-expert transvaginal ultrasonography, magnetic resonance imaging, and endometrial histology.

OBJECTIVE: To identify women with high-risk endometrial cancers using expert and non-expert transvaginal ultrasonography (TVS) and MRI. STUDY DESIGN: Myometrial involvement was prospectively evaluated in patients with atypical hyperplasia or endometrial cancer on ultrasound by non-experts at first visit (non-expert-TVS: n = 266) and experts (expert-TVS: n = 188) at second visit. MRI (n = 175) was performed when high-risk cancer was suspected on non-expert-TVS. Preoperatively, high-risk cancer was defined as myometrial involvement ≥50 %, or preoperative unfavorable tumor histology (grade 3 endometrioid, non-endometrioid tumors, or tumor in cervical biopsies) obtained by endometrial sampling or hysteroscopic biopsies. Preoperative evaluations were compared with final histopathology obtained at surgery, high-risk cancer being defined as unfavorable tumor histology or patients with FIGO stage ≥1b. RESULTS: Preoperative unfavorable tumor histology was seen in 64 women and correctly identified 63 of 128 high-risk cancers. Preoperative diagnosis of unfavorable tumor histology or myometrial involvement ≥50 %, i.e. judged high-risk, had an area under the curve (AUC), sensitivity, and specificity of 79.5 %, 93.8 %, 65.2 % on non-expert-TVS; 85.5 %, 84.4 %, 86.5 % on expert-TVS, and 85.4 %, 89.6 %, 81.2 % on MRI. AUC values were not significantly different between MRI and expert-TVS, but lower on non-expert-TVS (p < 0.02). However, sensitivity was highest on non-expert-TVS, where a low cutpoint for myometrial involvement was used (included potentially deep and difficult evaluations) in contrast to an exact cutpoint of myometrial involvement ≥50 % used on expert-TVS and MRI. The highest AUC, 88.6 %, was seen when MRI was performed in patients with myometrial involvement ≥50 %, determined on non-expert TVS. Sensitivity was reduced to 85.9 %, while specificity increased to 91.3 %. Thus, MRI was needed for risk classification in only 104 (39 %) patients. CONCLUSION: Diagnostically, expert-TVS and MRI were comparable and superior to non-expert-TVS. However, non-expert-TVS classified all patients with unclear myometrial involvement ≥50 %, and thereby only misdiagnosed 6.2 % of high-risk cases. Non-expert-TVS combined with MRI when myometrial involvement was ≥50 % on non-expert-TVS was a simple and effective method comparable with expert imaging to identify low- and high-risk cancer and select patients for SLND. Addition of MRI to the diagnostic regimen was needed in only 39 % of our patients.

[Screening for Down's syndrome can cause both security and anxiety].

Most women experience periods of increased anxiety and worry during pregnancy, and in many cases it is an appropriate response to a novel situation of change and transition. Women participate in screening for Down's syndrome in order to receive a general reassurance of the health of their baby. Generally, a screen-negative result does increase pregnant women's feelings of reassurance. A screen-positive result generates uncertainty and anxiety, however this anxiety declines to normal levels following a normal diagnostic result.

[A qualitative study of pregnant women's choice of nuchal translucency measurement]. / En kvalitativ undersøgelse af gravides valg af nakkefoldskanning.

INTRODUCTION: In 2004, The Danish National Board of Health introduced new guidelines for prenatal screening and diagnosis. Subsequently, all pregnant women in Denmark have been offered a maternal serum screening and a nuchal translucency measurement (NTM). The results are combined to a single risk estimate of carrying a Down syndrome child. All pregnant women are also offered a late second trimester scan for fetal abnormalities. Pregnant woman should be fully informed to enable them to make an informed choice. We explored the role of information in the pregnant women's understanding and decision-making for the NTM. MATERIALS AND METHODS: 26 consenting pregnant women were interviewed after their first visit to their GP and again after the late ultrasound scan. Our results are mainly based on the first interviews and the 24 participants who chose to have a NTM. RESULTS: The pregnant women consider a fetal scan as an attractive routine procedure during pregnancy. Apart from the information about prenatal examinations given by the GP, the pregnant women do not subsequently seek further information. The most important motives for wanting to have the NTM are 1) assurance, 2) choice, 3) expectations of the scan being a happy event, and 4) the idea that the examinations are approved by the Danish health care system. DISCUSSION: The decision to have a NTM is motivated by expectations that exceed the specific medical aim of the examination and the content of the information provided. The pregnant women believe in a link between knowledge and anxiety, and therefore do not wish to "know too much". Our results show that the pregnant woman's conception of the information provided and her motives for having a NTM are based on strategies and rationales that hinder an informed choice.

Informed consent: providing information about prenatal examinations.

BACKGROUND: Choice in prenatal care has moved on from a paternalistic approach, to increased patient autonomy and informed decision-making. This review summarises the existing literature on the information of pregnant women about prenatal examinations. The extent to which information about Down syndrome and screening tests empowers informed decision-making are investigated, as are different ways of expressing a risk estimate. RESULTS: Knowledge scores can be improved and decisional conflict reduced by group counselling, individual sessions, and by use of leaflets. None of the interventions leads to a raise in anxiety scores or influence uptake rates. Satisfaction with information provided was found unrelated to level of knowledge, but associated with having expectations for information met. Information on Down syndrome is missing (13-21%), or restricted (13%), limitations of screenings tests rarely mentioned, and written materials often insufficient. Women experience risk expressed as proportions or relative risk ratio significantly higher than percentage, number needed to treat, or absolute risk reduction. More women correctly understand relative risk reduction compared to absolute risk reduction and number needed to treat (60 versus 42 and 30%). Using medical words rather than lay terms significantly alter risk perception. CONCLUSIONS: Information can increase the level of knowledge and reduce decisional conflict, without raising anxiety scores. A clarification of the women's expectations seems paramount to obtain a perception of good information and informed consent. The information provided about Down syndrome and screening tests does not empower an informed consent based on relevant knowledge.

Informed consent: attitudes, knowledge and information concerning prenatal examinations.

BACKGROUND: Providing women with information enabling an informed consent to prenatal examinations has been widely recommended. OBJECTIVE: The primary purpose of this review is to summarise the current knowledge of the pregnant woman's expectations and attitudes concerning prenatal examinations, as well as the knowledge possessed by pregnant women undergoing prenatal examinations. Second, we explore their reasons for accepting or declining available screening tests. RESULTS: More than 90% of the pregnant women expressed a positive attitude toward screening procedures in pregnancy. Most often (70-96%), the pregnant women were found knowledgeable about the procedural and practical aspects, but were more seldom (31-81%) able to correctly identify the purpose of tracing fetal malformations. Some 29-65% were not familiar with the existence of a false negative result, and 30-43% were found unaware of the possibility of a false positive result. The risk of miscarriage in relation to amniocentetesis [AC] is unknown to 11-53%. Uptake rates are associated with attitudes toward prenatal examinations, but no knowledge of the test offered. A total of 88% considered their health care provider an important source of information, and 57% stated that this information has influenced their decision. CONCLUSIONS: Pregnant women favor prenatal examinations, but the choice of participation does not seem to be based on insight to enable full informed consent. Health care providers are perceived as an essential source of information.