Deciphering signaling pathways in hematopoietic stem cells: the molecular complexity of Myelodysplastic Syndromes (MDS) and leukemic progression.

Myelodysplastic Syndromes, a heterogeneous group of hematological disorders, are characterized by abnormalities in phosphoinositide-dependent signaling, epigenetic regulators, apoptosis, and cytokine interactions within the bone marrow microenvironment, contributing to disease pathogenesis and neoplastic growth. Comprehensive knowledge of these pathways is crucial for the development of innovative therapies that aim to restore normal apoptosis and improve patient outcomes.

Blinatumomab differentially modulates peripheral blood and bone marrow immune cell repertoire: A Campus ALL study.

Blinatumomab is the first bi-specific T-cell engager approved for relapsed or refractory B-cell precursor acute lymphoblastic leukaemia (B-ALL). Despite remarkable clinical results, the effects of blinatumomab on the host immune cell repertoire are not fully elucidated. In the present study, we characterized the peripheral blood (PB) and, for the first time, the bone marrow (BM) immune cell repertoire upon blinatumomab treatment. Twenty-nine patients with B-ALL received blinatumomab according to clinical practice. Deep multiparametric flow cytometry was used to characterize lymphoid subsets during the first treatment cycle. Blinatumomab induced a transient redistribution of PB effector T-cell subsets and Treg cells with a persistent increase in cytotoxic NK cells, which was associated with a transient upregulation of immune checkpoint receptors on PB CD4 and CD8 T-cell subpopulations and of CD39 expression on suppressive Treg cells. Of note, BM immune T-cell subsets showed a broader post-treatment subversion, including the modulation of markers associated with a T-cell-exhausted phenotype. In conclusion, our study indicates that blinatumomab differentially modulates the PB and BM immune cell repertoire, which may have relevant clinical implications in the therapeutic setting.

The baseline comorbidity burden affects survival in elderly patients with acute myeloid leukemia receiving hypomethylating agents: Results from a multicentric clinical study.

BACKGROUND: In older patients with acute myeloid leukemia (AML), the definition of fitness, prognosis, and risk of death represents an open question. METHODS: In the present study, we tested the impact on survival of disease- and patient-related parameters in a large cohort of elderly AML patients homogeneously assigned to treatment with hypomethylating agents (HMAs). RESULTS: In 131 patients with a median age of 76 years, we confirmed that early response (<0.001) and biology-based risk classification (p = 0.003) can select patients with better-predicted survival. However, a full disease-oriented model had limitations in stratifying our patients, prompting us to investigate the impact of baseline comorbidities on overall survival basing on a comorbidity score. The albumin level (p = 0.001) and the presence of lung disease (p = 0.013) had a single-variable impact on prognosis. The baseline comorbidity burden was a powerful predictor of patients' frailty, correlating with increased incidence of adverse events, especially infections, and predicted overall survival (p < 0.001). CONCLUSION: The comorbidity burden may contribute to impact prognosis in addition to disease biology. While the therapeutic armamentarium of elderly AML is improving, a comprehensive approach that combines AML biology with tailored interventions to patients' frailty is likely to fully exploit the anti-leukemia potential of novel drugs.

Donor selection for adoptive immunotherapy with NK cells in AML patients: Comparison between analysis of lytic NK cell clones and phenotypical identification of alloreactive NK cell repertoire.

Natural killer (NK) cell-based adoptive immunotherapy in leukemia patients is an emerging field of interest based on clinical evidence of efficacy and safety. Elderly acute myeloid leukemia (AML) patients have been successfully treated with NK cells from HLA-haploidentical donors, especially when high amounts of alloreactive NK cells were infused. The aim of this study was comparing two approaches to define the size of alloreactive NK cells in haploidentical donors for AML patients recruited in two clinical trials with the acronym "NK-AML" (NCT03955848), and "MRD-NK". The standard methodology was based on the frequency of NK cell clones capable of lysing the related patient-derived cells. The alternative approach consisted of the phenotypic identification of freshly derived NK cells expressing, as inhibitory receptors, only the inhibitory KIR(s) specific for the mismatched KIR-Ligand(s) (HLA-C1, HLA-C2, HLA-Bw4). However, in KIR2DS2+ donors and HLA-C1+ patients, the unavailability of reagents staining only the inhibitory counterpart (KIR2DL2/L3) may lead to an underestimated identification of the alloreactive NK cell subset. Conversely, in the case of HLA-C1 mismatch, the alloreactive NK cell subset could be overestimated due to the ability of KIR2DL2/L3 to recognize with low-affinity also HLA-C2. Especially in this context, the additional exclusion of LIR1-expressing cells might be relevant to refine the size of the alloreactive NK cell subset. We could also associate degranulation assays, using as effector cells IL-2 activated donor peripheral blood mononuclear cells (PBMC) or NK cells upon co-culture with the related patient target cells. The donor alloreactive NK cell subset always displayed the highest functional activity, confirming its identification accuracy by flow cytometry. Despite the phenotypic limitations and considering the proposed corrective actions, a good correlation was shown by the comparison of the two investigated approaches. In addition, the characterization of receptor expression on a fraction of NK cell clones revealed expected but also few unexpected patterns. Thus, in most instances, the quantification of phenotypically defined alloreactive NK cells from PBMC can provide data similar to the analysis of lytic clones, with several advantages, such as a shorter time to achieve the results and, perhaps, higher reproducibility/feasibility in many laboratories.

Impact of infectious comorbidity and overall time of hospitalization in total outpatient management of acute myeloid leukemia patients following venetoclax and hypomethylating agents.

Venetoclax (VEN) and hypomethylating agent (HMAs) regimens are emerging as the standard of care for unfit for chemotherapy acute myeloid leukemia (AML) patients, but the safety and feasibility of a total outpatient management have not been fully investigated. Fifty-nine AML patients with active disease received VEN and HMAs. Nineteen out of 59 (32.2%) patients received the first cycle as inpatients, whereas 40/59 (67.8%) patients were treated in the outpatient setting. No significant differences were observed with regard to incidence of adverse events (AEs), including tumor lysis syndrome (TLS), and the 30-day and 60-day mortality was comparable. Notably, an infectious prophylaxis inspired to that adopted during intensive chemotherapy resulted in a low infection rate with a reduced bacterial infections incidence in out- versus hospitalized patients (p < .0001). The overall time of hospitalization was significantly shorter in patients who received a total outpatient treatment as compared to those who received the first cycle as inpatients (5.9 vs. 39.7 days, p < .0001). Despite the adopted differences in treatment management, the efficacy was similar. These data indicate that a total outpatient management of VEN and HMAs is feasible in AML patients without negatively impacting on treatment efficacy and may yield pharmacoeconomic and quality-of-life benefits.

Long-Term Outcome After Adoptive Immunotherapy With Natural Killer Cells: Alloreactive NK Cell Dose Still Matters.

Recently, many reports were published supporting the clinical use of adoptively transferred natural killer (NK) cells as a therapeutic tool against cancer, including acute myeloid leukemia (AML). Our group demonstrated promising clinical response using adoptive immunotherapy with donor-derived alloreactive KIR-ligand-mismatched NK cells in AML patients. Moreover, the antileukemic effect was correlated with the dose of infused alloreactive NK cells ("functional NK cell dose"). Herein, we update the results of our previous study on a cohort of adult AML patients (median age at enrollment 64) in first morphological complete remission (CR), not eligible for allogeneic stem cell transplantation. After an extended median follow-up of 55.5 months, 8/16 evaluable patients (50%) are still off-therapy and alive disease-free. Overall survival (OS) and disease-free survival (DFS) are related with the dose of infused alloreactive NK cells (≥2 × 105/kg).

Adenomyosis and endometriosis in adolescents and young women with pelvic pain: prevalence and risk factors.

AIM: To evaluate the prevalence of ultrasound diagnosis of adenomyosis and endometriosis in young women complaining of pelvic pain and to find the symptoms and clinical characteristics associated with these diseases in young women. METHODS: Cross-sectional study, including 100 young women (14-24 years) with a history of chronic pelvic pain. Women were asked detailed medical hystory and pain symptoms scores (Visual Analogue Scale) and underwent gynecological examination and ultrasound evaluation. RESULTS: The prevalence of endometriosis and adenomyosis in young women amounted to 25.0% and 46.0%, respectively. A significant correlation was found between ovarian endometriosis and adenomyosis. Dysmenorrhea and dyspareunia were risk factors for adenomyosis. Dyschezia, dyspareunia, chronic pelvic pain, presence of sonographic soft markers suggestive of pelvic adhesions, being a worker and having a previous surgery were risk factors for endometriosis. Young women (20-24 years) had a higher incidence of both adenomyosis and endometriosis than adolescents (14-19 years). CONCLUSIONS: Our outcomes strengthen the hypothesis of a progressive and common course of the natural history of endometriosis, which initially may manifest with symptoms, then with signs of pelvic adhesions and finally as adenomyosis, ovarian endometriomas or deep infiltrating endometriosis.

Question Mark Sign and Transvaginal Ultrasound Uterine Tenderness for the Diagnosis of Adenomyosis: A Prospective Validation.

OBJECTIVES: To evaluate the diagnostic accuracy of the classic ultrasound (US) signs of adenomyosis, the question mark sign and transvaginal ultrasound (TVUS) uterine tenderness, in the diagnosis of adenomyosis. METHODS: This was a prospective study including 78 patients waiting for hysterectomy for uterine benign diseases and undergoing preoperative US examinations to evaluate all criteria for US diagnosis of adenomyosis as reported by the consensus statement of the Morphological Uterus Sonographic Assessment group. A US diagnosis of adenomyosis was made in the presence of 2 or more Morphological Uterus Sonographic Assessment features. Moreover, the question mark sign and TVUS uterine tenderness were evaluated. Ultrasound features were compared with the histologic examination, which was considered the reference standard for the diagnosis of adenomyosis. The Cohen κ coefficient was used to measure the accordance between US and histologic results. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of each US feature were calculated. RESULTS: The prevalence of adenomyosis in the sample was 33.3%. The sensitivity, specificity, PPV, NPV, and accuracy of TVUS in the diagnosis of adenomyosis were 77%, 96%, 91%, 89%, and 90%, respectively. Myometrial heterogeneity was the most frequently encountered feature (100%) but showed low specificity (7%). The question mark sign and TVUS uterine tenderness showed sensitivity, specificity, PPV, NPV, and accuracy of 41%, 96%, 83%, 77%, and 69% and 69%, 65%, 66%, 81%, and 67%. CONCLUSIONS: The question mark sign and TVUS uterine tenderness are useful tools for the diagnosis of adenomyosis.

Computed Tomography-Colonography With Intravenous Contrast Medium and Urographic Phase for the Evaluation of Pelvic Deep Infiltrating Endometriosis of Intestinal and Urinary Tract.

OBJECTIVES: The aim of this study was to evaluate the diagnostic accuracy of a specific protocol of computed tomography-colonography with intravenous contrast medium and urographic phase, which combined simultaneously the study of the intestinal and urinary tract, in the preoperative evaluation of women with deep infiltrating endometriosis (DIE) of anterior and posterior pelvic compartments. METHODS: We retrospectively analyzed 73 women who underwent 74 computed tomography-colonography with intravenous contrast medium and urographic phase examinations for strong clinical suspicion of DIE. All the women had surgical confirmation. RESULTS: Computed tomography-colonography with intravenous contrast medium and urographic phase in detecting DIE rectosigmoid involvement had a sensitivity of 82.3% and a specificity of 66.7%, while in detecting DIE urinary tract involvement had a sensitivity of 45.9% and a specificity of 78.4%. CONCLUSIONS: Computed tomography-colonography with intravenous contrast medium and urographic phase is a useful technique for the preoperative planning of selected women with DIE, in particular, for the detection of sigmoid colon and bladder lesions especially when performed with a dose reduction protocol.

Intra- and Inter-Rater Agreement Describing Myometrial Lesions Using Morphologic Uterus Sonographic Assessment: A Pilot Study.

OBJECTIVES: To evaluate the intra- and inter-rater agreement for myometrial lesions using Morphologic Uterus Sonographic Assessment terminology. METHODS: Thirteen raters with high (n = 6) or medium experience (n = 7) assessed 30 3-dimensional ultrasound clips with (n = 20) and without (n = 10) benign myometrial lesions. Myometrial lesions were reported as poorly or well defined and then systematically evaluated for the presence of individual features. The clips were blindly assessed twice (at a 2-month interval). Intra- and inter-rater agreements were calculated with κ statistics. RESULTS: The reporting of poorly defined lesions reached moderate intra-rater agreement (κ = 0.49 [high experience] and 0.47 [medium experience]) and poor inter-rater agreement (κ = 0.39 [high experience] and 0.25 [medium experience]). The reporting of well-defined lesions reached good to very good intra-rater agreement (κ = 0.73 [high experience] and 0.82 [medium experience]) and good inter-rater agreement (κ = 0.75 [high experience] and 0.63 [medium experience]). Most individual features associated with ill-defined lesions reached moderate intra- and inter-rater agreement among highly experienced raters (κ = 0.41-0.60). The least reproducible features were myometrial cysts, hyperechoic islands, subendometrial lines and buds, and translesional flow (κ = 0.11-0.34). Most individual features associated with well-defined lesions reached moderate to good intra- and inter-rater agreement among all observers (κ = 0.41-0.80). The least reproducible features were a serosal contour, asymmetry, a hyperechoic rim, and fan-shaped shadows (κ = 0.00-0.35). CONCLUSIONS: The reporting of well-defined lesions showed excellent agreement, whereas the agreement for poorly defined lesions was low, even among highly experienced raters. The agreement on identifying individual features varied, especially for features associated with ill-defined lesions. Guidelines on minimum requirements for features associated with ill-defined lesions to be interpreted as poorly defined lesions may improve agreement.

Short-term histopathological effects of dienogest therapy on ovarian endometriomas: in vivo, nonrandomized, controlled trial.

Ovarian endometriosis is a common gynecological disorder. To date, progestins are recommended as the first-line medical treatment for symptomatic ovarian endometriosis. The aim of this study was to evaluate the main histopathological effects of short-term dienogest therapy in patients with ovarian endometriomas scheduled for surgery. A prospective, nonrandomized controlled trial, including 70 symptomatic women with single ovarian endometriotic cyst (diameter between 30-50 mm) was conducted. Women scheduled for surgery were divided into two groups, depending on the treatment established at enrollment: 36 women received progestin therapy with dienogest (P group) and 34 women received no therapy (C group). At histopathological examination necrosis, inflammation, decidualization, glandular atrophy and angiogenesis were blindly evaluated. At tissue level, decidualization was significantly more frequent in P group compared to C group (p = .001). A nonsignificant tendency (p = .29) towards a slight decreased inflammation in P group was found. No significant differences were observed between the two groups in terms of necrosis, glandular atrophy and angiogenesis. The study suggests that high decidualization rate and the tendency to reduced inflammatory reaction in the short-term administration of dienogest might contribute to its therapeutic efficacy.

Comparison of transvaginal sonography and computed tomography-colonography with contrast media and urographic phase for diagnosing deep infiltrating endometriosis of the posterior compartment of the pelvis: a pilot study.

PURPOSE: To compare the diagnostic accuracy of transvaginal sonography (TVS) and computed tomography-colonography with contrast media and urographic phase (CTCU) in the preoperative detection of deep infiltrating endometriosis (DIE). MATERIALS AND METHODS: Forty-seven patients with clinical suspicion of DIE underwent preoperative TVS and CTCU. Imaging data were compared with histopathologic analysis. Sensitivity, specificity, positive and negative predictive values and test accuracies of the two modalities were calculated. RESULTS: For diagnosing intestinal DIE, TVS and CTCU had a sensitivity of 98 and 71%, specificity of 33 and 50%, positive predictive value of 91 and 91%, negative predictive value of 67 and 20%, accuracy of 89 and 68%, respectively. For diagnosing ureteral DIE, TVS and CTCU had a sensitivity of 10 and 60%, specificity of 94.8 and 70.2% on the right; sensitivity of 28.5 and 57.1%, specificity of 96.3 and 76.9% on the left, respectively. CONCLUSION: TVS should be regarded as an accurate, radiation-free first-line diagnostic modality for patients with suspicion of posterior endometriosis. CTCU should be regarded as a complementary imaging modality, particularly for sigmoid or ureteral endometriosis.

Does exist a correlation between endometriosis and thrombophilic disorders? A pilot study.

OBJECTIVE: At present, there is growing evidence of the existence of a genetic predisposition in both thrombophilic disorders and endometriosis. The aim of our study was to evaluate for the first time the prevalence of some thrombophilic disorders in patients with endometriosis. MATERIALS AND METHODS: We conducted a retrospective study on 138 patients with endometriosis and 278 healthy control women. All women were subjected to a blood examination testing for thrombophilic screening and the variables examinated were: hyperhomocysteinemia, factor V Leiden and factor II prothrombin G20210A mutations in heterozygosis and homozigosis. RESULTS: A significant reduced prevalence (p < 0.05) of factor V Leiden mutation in endometriosis patients was found, whereas no significant differences (p = NS) for factor II and hyperhomocysteinemia were observed. CONCLUSION: Our preliminary data do not show any association between thrombophilic condition and endometriosis. Before assuming hormonal therapies, a thrombophilic plasmatic screening seems to be unnecessary in patients affected by endometriosis.

New Laparoscopic Technique of Hysteropexy for Uterine Retrodisplacement: Bologna Technique.

STUDY OBJECTIVE: To show a new laparoscopic technique of hysteropexy for uterine retrodisplacement (retroversion and/or retroflexion). DESIGN: Narrated step-by-step explanation of the Bologna hysteropexy technique using descriptive text and an educational video. SETTING: Tertiary referred center of minimally invasive gynecology, Sant'Orsola Hospital, Bologna University. INTERVENTIONS: The Bologna hysteropexy is proposed as an additional procedure after surgical laparoscopic interventions for benign gynecologic disease. The technique consists of 2 semicontinuous absorbable sutures (Biosyn monofilament no. 1 [Covidien, Mansfield, MA] with 2/3 inch diameter needle, 36 mm) suspending the uterus to the anterior abdominal wall, through the plication and shortening of round ligaments. A knot is tied intracorporeally between the 2 free ends of the semicontinuous sutures, drawing a V shape figure and resulting in uterine ventrosuspension. CONCLUSION: The Bologna technique hysteropexy is simple and quick to perform. It is effective in suspending the uterus in anteverted and anteflexed positions at 6-month ultrasound follow-up. No perioperative complications were recorded. It can be done with a standard surgical suture-passer and does not add additional cost to surgery. Furthermore, an absorbable suture is desirable for fertile women.

Adenomyosis: What the Patient Needs.

A panel of experts in the field of endometriosis expressed their opinions on management options in a 28-year-old patient, attempting pregnancy for 1 year, with severe cyclic pelvic pain and with clinical examination and imaging techniques suggestive of adenomyosis. Many questions this paradigmatic patient may pose to the clinician are addressed, and all clinical scenarios are discussed. A decision algorithm derived from this discussion is also proposed.

Conversion in endometrial cancer patients scheduled for laparoscopic staging: a large multicenter analysis: conversions and endometrial cancer.

BACKGROUND: Data on patients with endometrial cancer converted to laparotomy are totally lacking. The aim of the present study was to evaluate surgical and oncological outcomes in patients with endometrial cancer scheduled for laparoscopic staging but converted to laparotomy. METHODS: Data of consecutive patients who had undergone surgery for staging endometrial cancer in seven Italian centers were reviewed. Patients' characteristics and surgical and oncological data were noted and analyzed according to surgery, i.e. laparotomy, laparoscopy, and laparoscopy converted to laparotomy. RESULTS: Seventy-one out of 512 (13.9 %) patients scheduled to laparoscopy were converted to laparotomy for reasons related to anesthesiology [38/71 (53.5 %)] or surgery [33/71 (46.5 %)]. The conversion rate varied among stages [41/460 (8.9 %), 13/27 (48.1 %), 17/25 (68.0 %) in patients with stage I, II, and endometrial cancers, respectively]. Significant (P < 0.05) differences among groups were detected in patients' age, body mass index and previous pelvic surgery, and in the distribution of stages and histotype of endometrial cancers. The Kaplan-Meier procedure showed that the cumulative probability of first recurrence (P = 0.089, 0.590 and 0.084 for stage I, II and III, respectively) and of death (P = 0.108, 0.567 and 0.372 for stage I, II and III, respectively) categorized by stages did not attain statistical significance by log-rank testing after correction for confounding factors. CONCLUSIONS: The surgical and oncological outcomes of converted patients are no different from those of patients staged successfully with laparoscopy or with laparotomy. The conversion to laparotomy should be not considered per se a complication.

The role of ovarian suspension in endometriosis surgery: a randomized controlled trial.

STUDY OBJECTIVE: A very high percentage of patients with severe pelvic endometriosis develop adhesions after laparoscopic surgery. The objective of this trial was to evaluate the role of ovarian suspension performed during surgery for severe endometriosis on ovarian adhesions and postoperative pelvic pain. DESIGN: A randomized controlled trial (Canadian Task Force classification I). SETTING: The tertiary care University Hospital of Bologna, Bologna, Italy. PATIENTS: Eighty patients with ovarian and posterior deep infiltrating endometriosis were included in the study. INTERVENTIONS: Patients underwent laparoscopic surgery for endometriosis and were randomized sequentially into 2 groups: transient ovarian suspension was performed in the treatment group (n = 40), whereas in the control group (n = 40) ovaries were left free in the pelvis. Symptom intensity (dysmenorrhea, chronic pelvic pain, dyspareunia, dyschezia, and dysuria) were ranked using a visual analog scale. Postsurgical ovarian adhesions were evaluated using transvaginal ultrasonographic scans performed by an ultrasound operator who was blinded to the details of the operative procedure and women's randomization allocation. Complications, lesion localization, endometrioma diameter, and surgery time were recorded. MEASUREMENTS AND MAIN RESULTS: At follow-up, a significantly lower rate of ultrasound-detectable ovarian adhesions with the uterus and the bowel was observed in the treatment group, respectively (46.7% vs 77.3%, p = .003 and 26.7% vs 68.2%, p < .0005). Patients in the control group showed a higher percentage of fixed ovaries with moderate and severe adhesions than the treatment group, respectively (56.8% vs 28.9%, p = .003 and 20.5% vs 8.9%, p = .110). No differences between the 2 groups were found regarding complications and pelvic pain. CONCLUSION: Ovarian suspension seems to be an additional effective surgical procedure associated with an increased ovarian mobility in women treated for severe endometriosis. Moreover, it is feasible, safe, simple, and fast. Hence, it should be routinely used during laparoscopic surgery for endometriosis.

Women with deep infiltrating endometriosis: sexual satisfaction, desire, orgasm, and pelvic problem interference with sex.

INTRODUCTION: Endometriosis is a chronic and progressive condition of women of reproductive age. It is strongly associated with a significant reduction of quality of life (QOL) and sexual function. AIMS: This study aims to objectively evaluate sexual function in women with deep infiltrating endometriosis (DIE) and to study the impact of endometriosis symptoms and type of lesion on patient's sexual function. METHODS: This is a cross-sectional study in a tertiary care university hospital. It included 182 patients with preoperative clinical and ultrasound diagnosis of DIE who were referred to our center from 2008 to 2011. MAIN OUTCOME MEASURES: A sexual activity questionnaire, the Sexual Health Outcomes in Women Questionnaire (SHOW-Q) was used to collect data pertaining to satisfaction, orgasm, desire, and pelvic problem interference with sex. Short Form 36 (SF-36) was used to evaluate QOL. Demographic and clinical characteristics were assessed: age, body mass index, parity, ethnicity, postsecondary education, employment, smoking, history of surgical treatment, and hormonal contraception. Patients were asked about pain symptoms (dysmenorrhea, dyspareunia, dyschezia, chronic pelvic pain, and dysuria) using a visual analog scale. RESULTS: The mean values obtained on the different scales of the SHOW-Q showed poor sexual function (mean SHOW-Q total score 56.38 ± 22.74). Satisfaction was the dimension most affected (mean satisfaction score 55.66 ± 34.55), followed by orgasm (mean orgasm score 56.90 ± 33.77). We found a significant correlation between the SF-36 scores and the SHOW-Q scores (P < 0.0001). Sexual dysfunction and deterioration of QOL seem to be correlated. Analyzing the impact of symptoms and lesions on sexual function, we found that dyspareunia and vaginal DIE nodules significantly affect sexual activity (P < 0.05). CONCLUSION: The results of this study demonstrated that women with DIE have a sexual function impairment, correlated with the overall well-being decrease. Moreover, the presence of dyspareunia and vaginal endometriotic lesions seems to be involved in sexual dysfunction.

A prospective blinded comparison of the accuracy of transvaginal sonography and frozen section in the assessment of myometrial invasion in endometrial cancer.

OBJECTIVE: To compare the accuracy of preoperative transvaginal sonography (TVS) and intraoperative frozen section (FS) in the assessment of myometrial invasion of endometrial carcinoma, having the definitive histological examination as gold standard. METHODS: 155 consecutive women (mean age 63 years, range 32-88) diagnosed as having endometrial carcinoma were prospectively evaluated at TVS in order to preoperatively stage the disease. All the patients subsequently underwent complete surgical staging including total abdominal hysterectomy, bilateral oophorectomy, pelvic and lumboaortic lymphadenectomy. After removal of the uterus, intraoperative FS was performed by pathologists with special interest in gynaecologic oncology in a predefined, standardized manner. Sensitivity, specificity, positive and negative predictive values were calculated for both modalities as regards neoplastic invasion of the myometrium. RESULTS: Overall, 131 women (84.5%) had an endometrioid adenocarcinoma, 8 (5.2%) an adenosquamos carcinoma, 7 (4.5%) a serous papillary carcinoma, 4 (2.6%) a clear cell carcinoma, 3 (1.9%) a mixed type carcinoma, 1 (0.6%) a carcinosarcoma, and 1 (0.6%) a mesodermal mixed malignant tumor. Sensitivity, specificity, positive and negative predictive values and accuracy for TVS in the evaluation of myometrial infiltration were: 75%, 89%, 86%, 79% and 81%. Corresponding features for FS were: 92%, 92%, 89%, 94% and 92%. The diagnostic performance of FS was higher than that of TVS (Cohen's K value: 0.841; p<0.0005). CONCLUSION: Intraoperative FS performed better than preoperative TVS in the assessment of myometrial invasion by endometrial cancer. Despite being time consuming, FS can be regarded as a useful modality in order to decide whether to perform lymphadenectomy in cases with poor visualization of the endometrium at TVS and when TVS gives inconclusive results.