The 10-year results after national introduction of pelvic lymph node staging in Danish intermediate-risk endometrial cancer patients not given postoperative radiotherapy.

The 10-year results after national introduction of pelvic lymph node staging in Danish intermediate-risk endometrial cancer patients not given postoperative radiotherapy. Gitte Ørtoft; Claus Høgdall; Estrid S Hansen; Margit Dueholm. OBJECTIVE: To prepare for the national introduction of sentinel node staging, we evaluated the consequences of the previous national decision to introduce lymph node staging in intermediate-risk endometrial cancer patients (grade 1/2 with > 50% or grade 3 with < 50% myometrial invasion) by determining the number of patients upstaged by lymphadenectomy and whether upstaging affected the survival and recurrence patterns of non-staged patients and patients with and without lymph node metastases. STUDY DESIGN: In a national cohort study, 2005-12, 1294 stage I-IV patients who should have been offered lymphadenectomy were progressively registered. The number of patients upstaged by lymphadenectomy, 10-year survivals were evaluated by Kaplan-Meier analysis and adjusted Cox regression. RESULTS: This study demonstrates that it takes time to introduce lymphadenectomy at a national level, as indicated by the increasing number of cases staged per year, from 12% in 2005 to 74% in 2012. Pelvic lymphadenectomy was performed in 43.8% (567/1294) and lymph node metastases were found in 13.6% (77/567). As 54 patients had further dissemination outside the uterine body, only 23 patients (6%) were upstaged from stage I to IIIC. Compared to lymph node-negative patients, the 77 patients with lymph node metastasis had significantly lower overall, (55% versus 68%), disease-specific (64% versus 86%), and progression-free survival (51% versus 77%), mainly due to non-local recurrences including a high number of paraaortic recurrences. In 873 final stage I intermediate-risk patients, 10-year survival and recurrence rates were not significantly lower in non-staged as compared to lymph node-negative patients (overall survival 62% versus 70%: disease-specific survival: 90% versus 90%, progression-free survival: 81% vs 83%), probably due to the low number of patients upstaged from stage I to stage IIIC. CONCLUSION: Lymph node metastases were present in 13.6% of patients with intermediate-risk who underwent pelvic lympadenectomy, and these patients had a lower 10-year survival than lymph node-negative patients. Because lymphadenectomy upstaged only 6% from stage I to stage IIIC, survival and recurrence rates were not significantly compromised in non-staged as compared to lymph node-negative intermediate-risk stage I patients. Sentinel node staging has now been implemented in Danish intermediate-risk endometrial cancer patients.

Survival and recurrence in stage II endometrial cancers in relation to uterine risk stratification after introduction of lymph node resection and omission of postoperative radiotherapy: a Danish Gynecological Cancer Group Study.

OBJECTIVE: To evaluate survival and recurrence in stage II endometrial cancer in relation to uterine risk stratification. Outcome for stage II was compared before and after the introduction of lymph node (LN) resection and omission of all postoperative radiotherapy. METHODS: The cohort consisted of 4,380 endometrial carcinoma patients radically operated (no visual tumor, all distant metastasis removed) (2005-2012) including 461 stage II. Adjusted Cox regression was used to compare survival and actuarial recurrence rates. RESULTS: Uterine risk factors (low-, intermediate-, and high-) were the strongest predictors of survival and recurrence in stage II. Stage II low-risk having a prognosis comparable to low-risk stage I (grade 1-2, <50% myometrial invasion), whereas cervical invasion significantly increased the risk of recurrence and decreased cancer-specific survival in intermediate- and high-risk compared to the corresponding stage I risk groups. In 355 cases of 708 with cervical stromal invasion, LN-resection showed 27.9% with LN metastasis and upstaged 18.1% from stage II to IIIC resulting in longer survival and lower recurrence in LN-resected compared to non-LN resected stage II. Radical as compared to simple hysterectomy did not alter survival. Treatment with external beam radiotherapy decreased local recurrence without affecting survival. CONCLUSION: Uterine risk groups are the strongest predictors for survival and recurrence in stage II patients and should be considered when advising adjuvant therapy. LN-resected stage II had increased survival and decreased recurrence. Omitting radiotherapy increase vaginal recurrence without affecting survival.

The effect of transcervical endometrial resection on clinical symptoms related to intrinsic adenomyosis and junctional zone changes.

OBJECTIVES: To assess the effect of transcervical endometrial resection on clinical symptoms related to histopathological findings of the junctional zone. STUDY DESIGN: This prospective study took place at a university hospital. Premenopausal women suffering from abnormal uterine bleeding and/or pelvic pain and scheduled for transcervical endometrial resection were enrolled (n = 112). Histopathological findings of the endomyometrial biopsies were categorized as follows: Adenomyosis of the inner myometrium (intrinsic adenomyosis): ≥ 2 mm myometrial invasion without contact to the basal endometrium, serrated junctional zone: > 3 mm myometrial invasion with contact to the basal endometrium and linear junctional zone: No or marginal myometrial invasion (≤ 3 mm) with contact to the basal endometrium. All study participants received a baseline and two follow-up questionnaires (6 and 18 months after surgery) regarding symptom severity, health-related quality of life and pelvic pain. Data regarding reintervention surgery was obtained from the National Database Patoweb. The rate of reintervention surgery and the improvement in symptom severity, health-related quality of life and pelvic pain were correlated to histopathological findings. RESULTS: Twenty-four patients had intrinsic adenomyosis, 31 had serrated junctional zone and 57 had linear junctional zone. Fifteen patients (13%) underwent reintervention surgery; three (20%) within 6 months, nine (60%) between 6-18 months and three (20%) > 18 months after transcervical endometrial resection. Reintervention surgery was more common in women with intrinsic adenomyosis compared to women without (33% (95% CI: 16-55) vs 8% (95% CI: 3-16)) (p-value: < .05). Nine patients (38%) with intrinsic adenomyosis were asymptomatic based on low symptom severity score, high health-related quality of life and no pelvic pain at 18 months follow-up. Patients with linear junctional zone had a higher improvement in symptom severity and health-related quality of life than patients with intrinsic adenomyosis or serrated junctional zone at 6 months follow-up after surgery (p-value < .05). However, there was no significant difference in pelvic pain reduction. CONCLUSION: The effect of transcervical endometrial resection may depend upon the degree of junctional zone changes, and patients with intrinsic adenomyosis are more likely to undergo reintervention surgery than patients with either linear or serrated junctional zone. However, intrinsic adenomyosis may also be successfully treated with endometrial resection.

Lymph-vascular space invasion (LVSI) as a strong and independent predictor for non-locoregional recurrences in endometrial cancer: a Danish Gynecological Cancer Group Study.

OBJECTIVE: To evaluate the effect of lymph-vascular space invasion (LVSI) on location of recurrences in Danish patients with endometrial cancer. METHODS: This national cohort study (2005-2012) included 4,380 radically operated patients (no visual tumor, all distant metastasis removed). LVSI status was recorded in 3,377 (77.1%). In stage I patients, 2.6% received adjuvant radiotherapy and 1.4% adjuvant chemotherapy. Adjusted Cox regression was used to compare actuarial recurrence rates. RESULTS: LVSI was present in 18.7% of 3,377 patients with known LVSI status. Of these, 7.6% stage I patients with LVSI experienced an isolated locoregional and 19.4% a non-locoregional recurrence. Compared to no LVSI, 5-year recurrence rate was higher (25.5% vs. 8.5%) in patients with LVSI and the frequency of distant recurrences was strikingly higher (stage I: 15.2% vs. 2.7%), the effect being similar across International Federation of Gynecology and Obstetrics stages and histological types. In intermediate-risk stage I patients with LVSI, 8.0% experienced an isolated locoregional recurrence compared to 20.1% with non-locoregional recurrence, giving these patients a seriously adverse risk of survival. A separate analysis in patients with recurrences demonstrated that those with LVSI had significantly more distant recurrences (55.4% vs. 29.9%) and fewer isolated vaginal recurrences (24.3% vs. 42.8%) than patients with no LVSI. CONCLUSION: LVSI is a strong independent risk factor for the development of non-locoregional recurrences even in intermediate-risk stage I endometrial cancer. The non-locoregional recurrence pattern suggests a future focus for optimization of postoperative treatment in these patients.

Location of recurrences in high-risk stage Iendometrial cancer patients not given postoperative radiotherapy: A Danish gynecological cancer group study.

OBJECTIVES: To study recurrence rates in Danish high-risk stage I endometrial cancers not given radiotherapy in accordance with the decision of the Danish Gynecological Cancer Group. METHODS: This prospective national cohort study includes all 4707 endometrial carcinomas diagnosed from 2005 to 2012. Of these, 623 patients had grade 3 endometroid adenocarcinoma with >50% myometrial invasion or serous/clear/undifferentiated carcinoma (with any depth of invasion). In 305 patients with high-risk stage I on final pathology, 14.1% received adjuvant external beam radiotherapy and 9.6% adjuvant chemotherapy. No patients received brachytherapy. 5-year Kaplan-Meier survival estimates and actuarial recurrence rates were calculated, and adjusted Cox regression analysis used for comparison. Recurrence rates were compared with historical Danish population data (DEMCA 98-99). RESULTS: For non-irradiated patients, 5-year overall survival, cancer-specific survival, and progression-free survival rates in high-risk stage I patients were 65%, 78%, and 73%, respectively. For non-irradiated patients, isolated local recurrences were uncommon (vaginal 3.1%, pelvic 0.4%). Death was mainly due to a high occurrence of non-local recurrences, with 8.8% experiencing a first recurrence in the abdominal cavity (outside the field where radiation traditionally have been given) and 13.0% a distant metastasis outside the abdominal cavity. Grade 3 tumors with >50% myometrial invasion seem to be characterized by a different pattern of recurrences, with significantly more isolated vaginal recurrences (7.9% vs 2.2%) and fewer total number of abdominal recurrences (7.9% vs 15.3%) as compared with unfavorable tumor types. CONCLUSION: Isolated vaginal and pelvic recurrences were rare (3-5%) in patients with a final pathologic diagnosis of high-risk stage I endometrial cancer even after the Danish Gynecological Cancer Group decided to omit all types of postoperative radiotherapy and introduce lymph node staging.

Two- and three-dimensional transvaginal ultrasonography for diagnosis of adenomyosis of the inner myometrium.

RESEARCH QUESTION: How diagnostically accurate is two-dimensional (2D-TVS) compared with three-dimensional transvaginal ultrasonography (3D-TVS) in diagnosing adenomyosis of the inner myometrium. What is the most accurate combination of ultrasonographic features? DESIGN: Premenopausal women (n = 110) scheduled for hysterectomy or transcervical resection of the endomyometrium owing to abnormal uterine bleeding were consecutively enrolled. All participants had real-time 2D-TVS and, later, blinded off-line 3D-TVS to diagnose adenomyosis. Results were compared with a detailed histopathological examination of the inner myometrium as gold standard. RESULTS: Prevalence of adenomyosis of the inner myometrium was 29%. For 2D-TVS and 3D-TVS, respectively, the diagnostic accuracy was sensitivity 72% (95% CI 53 to 86) and 69% (95% CI 50 to 84); specificity 76% (95% CI 65 to 85) and 86% (95% CI 76-93); and area under the curve (AUC) 0.74 (95% CI 0.7 to 0.8) and 0.77 (95% CI 0.7 to 0.9). Specificity of 3D-TVS was not statistically significantly better than 2D-TVS; the difference between them almost reached statistical significance (P = 0.06). The most accurate three-dimensional feature was junctional zone irregularity (JZmax-JZmin ≥5mm) (AUC: 0.78). A combination of two or more two-dimensional and two or more three-dimensional features was highly accurate (AUC: 0.77). CONCLUSIONS: For diagnosing adenomyosis of the inner myometrium, 3D-TVS offers a high accuracy similar to 2D-TVS. Identification of junctional zone irregularity with 3D-TVS may be beneficial to diagnosis. Two or more two-dimensional features and two or more three-dimensional features combined may give a more objective diagnosis, and may be useful for clinical practice and future research.

The effect of introducing pelvic lymphadenectomy on survival and recurrence rates in Danish endometrial cancer patients at high risk: a Danish Gynecological Cancer Group study.

OBJECTIVES: To evaluate the rate of survival and recurrence related to the introduction of pelvic lymphadenectomy in Danish high-risk endometrial cancer patients. STUDY DESIGN: Data on 713 high-risk patients defined as grade 3 with >50% myometrial invasion or serous/clear/undifferentiated carcinomas stage I-IV endometrial cancer patients diagnosed from 2005 to 2012 were retrieved from the Danish Gynecological Cancer Database. Of these, 305 were high-risk stage I. Five year Kaplan-Meier survival estimates and actuarial recurrence rates were calculated, and adjusted Cox used for comparison. Findings were compared with earlier Danish results. RESULTS: Lymphadenectomy in 390 radically operated high-risk patients resulted in upstaging of 31 patients from stage I to IIIC and 19 patients from stage II to IIIC corresponding to 12.8%. Upstaging from stage I to IIIC had a cancer-specific survival of 77%, almost comparable to lymph node-negative high-risk stage I patients (81%). Lymphadenectomy patients had a significant higher overall survival as compared with non-lymph node resected for all patients, but not for stage I patients. Lymphadenectomy, however, did not significantly affect cancer-specific survival, progression-free survival, recurrence rate or risk of local, distant, or lymph node recurrence. When the survival of high-risk stage I patients was compared with earlier Danish results, a small improvement in overall survival (7%) and cancer-specificsurvival (8%) was demonstrated. CONCLUSION: Only a small number of high-risk patients were upstaged from stage I to III due to lymphadenectomy. These patients showed a surprisingly good survival possibly due to correct stage identification and subsequent relevant adjuvant therapy. However, even though introduction of lymphadenectomy in the Danish high-risk population seems to increase overall survival, no significant change in cancer-specific survival, progression-free survival or recurrence patterns was demonstrated.

Inter-rater agreement in the diagnosis of adenomyosis by 2- and 3-dimensional transvaginal ultrasonography.

OBJECTIVES: To assess the inter-rater agreement of 2-dimensional (2D) and 3-dimensional (3D) transvaginal ultrasonography (TVUS) in the diagnosis of adenomyosis. METHODS: This prospective study included premenopausal women (n = 96) with heavy menstrual bleeding, menstrual pain, or both who were scheduled for hysterectomy or transcervical resection of the endometrium. All women underwent real-time 2D TVUS and subsequently offline 3D TVUS, which was blinded to 2D TVUS, by a single expert rater and a single nonexpert rater for the diagnosis of adenomyosis based on standardized pattern recognition and junctional zone measurements. Three-dimensional TVUS was done on a computer with 3D volumes recorded during 2D TVUS by both raters. The expert rater reported the image quality of all 3D volumes (n = 192). Inter-rater agreement (Cohen's κ) was assessed for both techniques, and the improvement over time was assessed for 2D TVUS. RESULTS: Diagnosis of adenomyosis showed good (κ = 0.69) and poor (κ = 0.21) inter-rater agreement with 2D and 3D TVUS, respectively (P < .05). The agreement with 2D TVUS improved over time. The agreement with 3D TVUS was slightly better for expert-recorded 3D volumes (κ = 0.40), which also had better image quality (P < .05). The most reproducible 2D and 3D features were anechoic lacunae (κ = 0.52) and junctional zone irregularity (κ = 0.27), respectively. CONCLUSIONS: Standardized pattern recognition during real-time 2D TVUS may result in good agreement between expert and nonexpert raters for the diagnosis of adenomyosis. Offline 3D TVUS is less reproducible, and junctional zone measurements do not improve the inter-rater agreement. The low inter-rater agreement may be related to a lack of experience and low image quality of nonexpert-recorded 3D volumes.

Assessment of myometrial invasion in endometrial cancer using three-dimensional ultrasound and magnetic resonance imaging.

INTRODUCTION: Preoperative knowledge of myometrial invasion in endometrial cancer is important for surgical planning. This study aimed to assess the diagnostic efficiency of two-dimensional (2D) and three-dimensional (3D) transvaginal ultrasonography (TVS) with and without saline infusion (SIS) and magnetic resonance imaging (MRI) for assessment of myometrial invasion in endometrial cancer. MATERIAL AND METHODS: 110 women with atypical endometrial hyperplasia or endometrial adenocarcinoma underwent preoperative 2D- and 3D-TVS with and without SIS and MRI. Offline 3D-TVS measurement was performed of the minimal tumor-free margin in relation to myometrial thickness expressed as deep (≥ 50%) myometrial invasion and subjective impression of cervix involvement. The quality of images was also evaluated. Diagnostic efficiencies were calculated for myometrial and cervical involvement for each method. The pathologist's final diagnosis served as the reference standard. RESULTS: For myometrial involvement, MRI showed greater accuracy than 3D-TVS or 2D-TVS (83, 71 and 75%, respectively). The efficiency of 3D-TVS was not superior to 2D-TVS and did not improve with SIS. The sensitivities of 2D-TVS and 3D-TVS were similar to that of MRI, and the efficiency of 3D-TVS improved when volumes of inadequate quality (39%) were excluded. For evaluating cervical involvement, the accuracy of 3D-TVS was 85%, comparable to the results of 2D-TVS (80%) and MRI (85%). The results did not improve when saline was added. CONCLUSION: 3D-TVS or 3D-SIS was not more efficient than 2D-TVS or MRI for assessment of myometrial invasion in endometrial cancer. 3D-TVS assessment without 2D-TVS was impeded by difficulties in obtaining 3D-TVS volumes of sufficient quality.

A 30-year experience in using oral methotrexate as initial treatment for gestational trophoblastic neoplasia regardless of risk group.

BACKGROUND: Treatment of postmolar gestational trophoblastic neoplasia (GTN) is often stratified according to FIGO score using methotrexate (MTX) for low-risk patients and first-line multi-agent chemotherapy (e.g. EMA-CO) for high-risk patients. In contrast, oral MTX may be given as first-line therapy to all GTN patients regardless of risk group. The aim was to examine the efficacy of oral MTX and a response-adapted treatment policy, which has been used for three decades at Aarhus University Hospital (AUH). MATERIAL AND METHODS: Seventy-one consecutive postmolar GTN patients treated 1981-2011 were included. Data were obtained from medical records, using histopathology and human choriogonadotropin (hCG) to verify the diagnosis. All patients received oral MTX as first-line chemotherapy. Second- and third-line chemotherapy was given according to response. RESULTS: Sixty-four (90%) patients were retrospectively categorized as FIGO low-risk disease, whereas seven patients (10%) had high-risk disease. Complete response to first-line oral MTX chemotherapy was observed in 35/71 (49%) patients, while 62/71 (87%) had complete remission on MTX (first-line) and/or MTX plus dactinomycin (second-line), without the use of multi-agent therapy. Nine patients (13%) received third-line multi-agent chemotherapy, six low-risk (67%) and three high-risk (33%) patients. There were no recurrences and no patients died as a consequence of toxicity or disease. CONCLUSION: Fifty percent of all patients can be cured on oral MTX alone. By adding dactinomycin, about 90% are cured without use of multi-agent chemotherapy. The use of oral MTX as initial treatment can minimize the number of patients receiving multi-agent chemotherapy.

Toward four-dimensional image-guided adaptive brachytherapy in locally recurrent endometrial cancer.

PURPOSE: To evaluate clinical outcome and feasibility of a four-dimensional image-guided adaptive brachytherapy concept in patients with locally recurrent endometrial cancer. METHODS AND MATERIALS: Forty-three patients with locally recurrent endometrial cancer were included. Treatment consisted of conformal external beam radiotherapy followed by a boost using pulsed-dose-rate brachytherapy (BT). Large tumors were treated with MRI-guided interstitial BT. Small tumors were treated with CT-guided intracavitary BT. The planning aim (total external beam radiotherapy and BT) for high-risk clinical target volume was D90 > 80 Gy, whereas constraints for organs at risk were D2cc ≤ 90 Gy for bladder and D2cc ≤ 70 Gy for rectum, sigmoid, and bowel in terms of equivalent dose in 2 Gy fractions. RESULTS: Median high-risk clinical target volume was 18 cm(3) (range, 0-91). D90 was 82 Gy (range, 77-88). D2cc to bladder, rectum, and sigmoid were 67 Gy (range, 50-81), 67 Gy (range, 51-77), and 55 Gy (range, 44-68), respectively. Median followup was 30 months (6-88). Two-year local control rate was 92% (standard error [SE], 5). Disease-free survival rate and overall survival rate was 59% (SE, 8) and 78% (SE, 7), respectively. Patients with low- to intermediate-risk for recurrence had a 2-year disease-free survival rate of 72% (SE, 9) compared with 42% (SE, 12) in patients with high risk for recurrence (p = 0.04). Late morbidity Grade 3 was recorded in 5 (12%) patients. CONCLUSIONS: Four-dimensional image-guided adaptive brachytherapy is feasible in locally recurrent endometrial cancer. Local control rate is good. Systemic control remains a problem in patients with high risk for recurrence.

Valid and complete data on endometrial cancer in the Danish Gynaecological Cancer Database.

INTRODUCTION: It is a comparative register study designed for data validation of surgery, pathology and recurrence for endometrial cancer in the Danish Gynaecological Cancer Database (DGCD) in the 2005-2009 period. The main outcomes were completeness of the data registered in the DGCD, agreement concerning data reported and comparability between the DGCD and a definite reference. MATERIAL AND METHODS: DGCD data on women with endometrial cancer or adenomatous hyperplasia supplemented with patient charts for data on recurrence were retrieved and compared with a definite reference (the pathology report and clinical journals). RESULTS: The completeness of data on pathology and surgery reported to the DGCD was 97.3%. The comparability between the DGCG and the definite reference was 94.4%. The agreement for the reported data in the DGCD was 88.3%. For recurrence, the comparability was 94.5% and the agreement was 71.6%. Completeness could not be determined due to the design of the database, where recurrence is composed of optional variables only. CONCLUSION: The data on endometrial cancer registered in the DGCD regarding surgery and pathology are valid and complete, and they provide a solid base for research. Due to the relatively infrequent incidence of recurrences, and the fact that these are rarely entered into the database when they do occur, agreement concerning recurrence is low. Based on this study, the DGCD cannot alone provide information on recurrence that will give a reliable foundation for research. FUNDING: Funding was provided by the Health Research Fund of the Region of Central Jutland and the Department of Gynaecology and Obstetrics, Aarhus University Hospital. TRIAL REGISTRATION: not relevant.

Ovarian carcinoma histotype determination is highly reproducible, and is improved through the use of immunohistochemistry.

AIMS: To assess the variation in ovarian carcinoma type diagnosis among gynaecological pathologists from Nordic countries, and whether a rationally designed panel of immunohistochemical markers could improve diagnostic reproducibility. METHODS AND RESULTS: Eight pathologists from four countries (Sweden, Denmark, Norway, and Finland) received an educational lecture on the diagnosis of ovarian carcinoma type. All tumour-containing slides from 54 ovarian carcinoma cases were independently reviewed by the participants, who: (i) determined type purely on the basis of histology; (ii) indicated whether they would apply immunohistochemistry in their routine practice; and (iii) determined type after reviewing the staining results. The results for six markers (WT1, p53, p16, HNF-1ß, ARID1A, and progesterone receptor) were determined for all 54 cases, by staining of a tissue microarray. The median concordance with central review diagnosis was 86%, and significantly improved to 90% with the incorporation of immunostaining results (P = 0.0002). The median interobserver agreement was 78%, and significantly improved to 85% with the incorporation of immunostaining results (P = 0.0002). CONCLUSIONS: Use of the immunostaining results significantly improved both diagnostic accuracy and interobserver agreement. These results indicate that ovarian carcinoma type can be reliably diagnosed by pathologists from different countries, and also demonstrate that immunohistochemistry has an important role in improving diagnostic accuracy and agreement between pathologists.

Preoperative staging of endometrial cancer using TVS, MRI, and hysteroscopy.

OBJECTIVES: To evaluate the accuracy of different preoperative modalities for staging of endometrial cancer to restrict extensive surgery to patients at high risk of metastatic disease. SETTING: Aarhus University Hospital. POPULATION: 156 women referred in 2006-2011 because of atypical endometrial hyperplasia (G0) or endometrial cancer. METHODS: Patients were offered preoperative transvaginal ultrasonography (TVS), magnetic resonance imaging (MRI), and hysteroscopic-directed biopsies from the uterine tumor and cervix. Final pathology of the removed uterus was the reference standard. Patients were divided into low risk (<50% myometrial invasion, and grades 0, 1, 2, and no cervical invasion) or high risk (all others). MAIN OUTCOME MEASURES: Accuracy, sensitivity, specificity, positive/negative predictive value. RESULTS: Patients were aged 32-88 years, with a mean body mass index of 29. At final pathology 81% had cancer and 19% G0 or no residual tumor; 54% were high risk. Hysteroscopy-directed biopsies had a higher accuracy (92%) than endometrial biopsy (58%) for differentiating G0 from cancer (p < 0.001); grade 3 tumor identification had similar accuracy (93 vs. 92%). Deep myometrial invasion was estimated with higher accuracy by MRI (82%) than TVS (74%) (p < 0.02). For cervical involvement, hysteroscopy-directed biopsies had higher accuracy (94%) than MRI (84%,) and TVS (80%) (p < 0.02). Accuracy for identifying high-risk women was highest (83%) using a combination of MRI and hysteroscopic-directed biopsies, compared with TVS and endometrial biopsy (72%) (p < 0.05). CONCLUSION: Preoperative staging with MRI and hysteroscopy-directed biopsy can identify eight of 10 women with high risk of lymph node metastases and spare eight of 10 low-risk women extended surgery.

The risk of persistent trophoblastic disease after hydatidiform mole classified by morphology and ploidy.

OBJECTIVE: Hydatidiform mole can be classified by histopathologic characteristics and by genetic constitutions and most complete moles are diploid, whereas most partial moles are triploid. We investigated the concordance between these two classifications, characterized moles with conflicting classifications, and compared the ability of the two classifications to discriminate between patients with and without a substantial risk of persistent trophoblastic disease. METHODS: 294 cases of consecutively collected hydropic placentas clinically suspected of hydatidiform mole made the basis of this retrospective study. We determined the ploidy and reviewed the original histopathologic material in all cases. Data on possible chemotherapy were collected for each patient. RESULTS: 270 of the conceptuses were histopathologically classified as hydatidiform mole. Among the 24 conceptuses classified as non-molar miscarriage, 20 were triploids, 2 were diploid androgenetic and 2 were diploid biparental. In 23% of the conceptuses, the histopathologic and genetic classifications were conflicting. 5% of the patients with hydropic placentas classified as partial mole encountered persistent trophoblastic disease; however, the genome was diploid in all these moles. None of 131 patients with a triploid hydropic gestation encountered persistent trophoblastic disease. CONCLUSION: As full concordance between the histopathologic and the genetic classifications was not found, we believe that features beyond the genetic constitution influence the development of morphologic features in hydatidiform moles. We recommend that gestations suspected of hydatidiform mole are subjected to histopathologic examination. If hydatidiform change and trophoblastic hyperplasia are identified, the ploidy should be used to identify patients with a high risk of persistent trophoblastic disease.

Predictors of low risk of persistent trophoblastic disease in molar pregnancies.

OBJECTIVE: To search for predictive factors for low risk of persistent trophoblastic disease in patients with molar pregnancies. METHODS: A total of 270 consecutively collected, histologically confirmed hydatidiform moles were classified by ploidy using karyotyping and flow cytometry. The parental origin of the genome was determined by analysis of microsatellite polymorphisms. Data on clinical features and pathology reports were collected for each patient. RESULTS: The observed frequency of persistent trophoblastic disease in patients with triploid moles was 0 of 105, (95% confidence interval 0-2.8%), whereas 28 of 162 patients with diploid molar pregnancies developed persistent trophoblastic disease (P < .001). Patients with a diploid mole and an initial hCG level lower than 49,000 units per liter did not develop persistent trophoblastic disease (P = .03). CONCLUSION: The risk of persistent trophoblastic disease after a triploid mole is very low. By combining the present data with data from published studies with valid ploidy assessment, the frequency of persistent trophoblastic disease in patients with triploid moles is 0 of 196 (95% confidence interval 0-1.5%). We suggest that the surveillance program for patients with triploid molar pregnancies is shortened. Initial hCG less than 49,000 units per liter is a possible predictor of low risk of persistent trophoblastic disease in women with diploid molar pregnancies, but this observation needs confirmation in larger studies.

Accuracy of magnetic resonance imaging and transvaginal ultrasonography in the diagnosis, mapping, and measurement of uterine myomas.

OBJECTIVE: The purpose of this study was to evaluate and compare the accuracy of magnetic resonance imaging and transvaginal ultrasonography in myoma diagnosis, mapping, and measurement. STUDY DESIGN: This was a double-blind study of 106 consecutive premenopausal women who underwent hysterectomy for benign reasons. Myomas (total, 257) were exactly mapped by magnetic resonance imaging and transvaginal ultrasonography; in each patient, we counted correctly identified myomas with pathologic position as true value. RESULTS: The presence of myomas was detected with the same high level of precision by both methods (magnetic resonance imaging: sensitivity, 0.99; specificity, 0.86; transvaginal ultrasonography: sensitivity, 0.99; specificity, 0.91). The mean number of correctly identified myomas was significantly higher by magnetic resonance imaging than by transvaginal ultrasonography (mean difference, 0.51 +/- 1.03; P <.001), a difference that narrowed to 0.08 +/- 0.76 (P =.60) in 26 patients with 1 to 4 myomas and uterine volumes <375 mL. Magnetic resonance imaging and transvaginal ultrasonography myoma diameter measurements had equal and high accuracies in patients with 1 to 4 myomas. CONCLUSION: Transvaginal ultrasonography is as efficient as magnetic resonance imaging in detecting myoma presence, but its capacity for exact myoma mapping falls short of that of magnetic resonance imaging, especially in large (>375 mL) multiple-myoma (>4) uteri.