Alimentary nickel (Ni) may result in allergic contact mucositis (ACM), whose prevalence is >30% and may present with IBS-like and extra-intestinal symptoms. These symptoms are also frequent in endometriosis, and Ni allergic contact dermatitis has already been observed in endometriosis. Therefore, intestinal and extra-intestinal symptoms in endometriosis may depend on a Ni ACM, and a low-Ni diet could improve symptoms. We studied the prevalence of Ni ACM in endometriosis and focused on the effects of a low-Ni diet on gastrointestinal, extra-intestinal, and gynecological symptoms. We recruited 84 women with endometriosis, symptomatic for gastrointestinal disorders. Thirty-one out of 84 patients completed the study. They underwent Ni oral mucosa patch test (omPT), questionnaire for intestinal/extra-intestinal/gynecological symptoms, and a low-Ni diet. Clinical evaluation was performed at baseline (T0) and after three months (T1). Twenty-eight out 31 (90.3%) patients showed Ni omPT positive results, with Ni ACM diagnosis, whereas three out of 31 (9.7%) patients showed negative Ni omPT. After three months of low-Ni diet, all gastrointestinal, extra-intestinal and gynecological symptoms showed a statistically significant reduction. Ni ACM has a high prevalence in endometriosis and a low-Ni diet may be recommended in this condition to reduce gastrointestinal, extra-intestinal and gynecological symptoms.

Objective This study aimed to evaluate the prevalence of concurrent endometrial cancer in patients pre-operatively diagnosed with atypical endometrial hyperplasia undergoing hysterectomy. Additionally, we assessed the occurrence of high to intermediate-risk and high-risk tumors according to the ESGO-ESTRO-ESP classification. The study also compared surgical outcomes and complications between patients undergoing simple hysterectomy and those undergoing hysterectomy with sentinel lymph node biopsy. Methods In this multicenter retrospective study, patients with a pre-operative diagnosis of atypical endometrial hyperplasia were identified and divided into two groups: Group 1, which included patients treated with total hysterectomy with or without bilateral salpingo-oophorectomy, and Group 2, where sentinel lymph node biopsy was incorporated into the standard surgical treatment. Results Among 460 patients with atypical endometrial hyperplasia, 192 received standard surgical management (Group 1) and 268 underwent sentinel lymph node biopsy (Group 2). A total of 47.2% (95% CI 42.6% to 51.7%) of patients were upgraded to endometrial cancer on final histopathological examination. High to intermediate-risk and high-risk tumors constituted 12.3% and 9.2% in Group 2 and 7.4% and 3.7% in Group 1. Lymph node metastases were identified in 7.6% of patients with concurrent endometrial cancer who underwent nodal assessment with at least unilateral mapping. Of the 12 sentinel lymph node metastases, 75.0% were micrometastases, 16.7% macrometastases, and 8.3% isolated tumor cells. No significant differences were found in estimated blood loss, operative time, and intra-operative and post-operative complications between the two groups. The rate of patients undergoing sentinel lymph node biopsy doubled every 2 years (OR 2.010, p<0.001), reaching 79.1% in the last 2 years. Conclusion This study found a prevalence of concurrent endometrial cancer of 47.2%, and sentinel lymph node biopsy provided prognostic and therapeutic information in 60.8% of cases. It also allowed for the adjustment of adjuvant therapy in 12.3% of high to intermediate-risk patients without increasing operative time or complication rates.

Objective To evaluate the diagnostic performance of the one-step nucleic acid amplification (OSNA) method for the detection of sentinel lymph node (SLN) metastases in women with apparent early-stage endometrial cancer compared with standard ultrastaging. Methods Prospective, multicentric, interventional study. Patients with apparent early-stage endometrial cancer who underwent primary surgical staging with SLN mapping were included. SLNs were serially sectioned with 2 mm slices perpendicular to the longest axis of the node: the odd slices were submitted to ultrastaging, whereas the even slices were submitted to the OSNA analysis. Diagnostic performance was calculated taking ultrastaging as referral standard. Results Three-hundred and sixteen patients with 668 SLNs were included. OSNA assay detected 22 (3.3%) positive SLNs, of which 17 (2.5%) were micrometastases and 5 (0.7%) macrometastases, whereas ultrastaging detected 24 (3.6%) positive SLNs, of which 15 (2.2%) were micrometastases and 9 (1.3%) macrometastases (p=0.48). Regarding negative SLNs, OSNA detected 646 (96.7%) negative nodes, including 8 (1.2%) isolated tumor cells, while ultrastaging detected 644 (96.4%) negative nodes with 26 (3.9%) isolated tumor cells. Specificity of OSNA was 98.4% (95% CI 97.5 to 99.4), accuracy was 96.7% (95% CI 95.4 to 98.1), sensitivity was 50% (95% CI 30.0 to 70.0), while negative predictive value was 98.1% (95% CI 97.1 to 99.2). Discordant results were found in 22 SLNs (3.3%) corresponding to 20 patients (6.3%). These were 10 (1.5%) false-positive SLNs (all micrometastases): one (0.1%) of these was a benign epithelial inclusion at ultrastaging. There were 12 (1.8%) false-negative SLNs of OSNA, of which 9 (1.3%) were micrometastases and 3 (0.5%) macrometastases. Overall, 17/668 (2.5%) benign epithelial inclusions were detected at ultrastaging. Conclusion The OSNA method had high specificity and high accuracy in detecting SLN metastasis in apparent early-stage endometrial cancer. The advantage of the OSNA method could be represented as the possibility to analyze the entire lymph node thus eliminating sampling bias.

Endometrial cancer (EC) is the most diagnosed gynecologic malignancy, and its incidence and mortality are increasing. The prognosis is highly dependent on the disease spread. Surgical staging includes retroperitoneal evaluation to detect potential lymph node metastases. In recent years, systematic lymphadenectomy has been replaced by sentinel lymph node (SLN) biopsy and ultrastaging, allowing for the detection of macrometastases, micrometastases, and isolated tumor cells (ITCs). Micrometastases and ITCs have been grouped as low-volume metastases (LVM). The reported prevalence of LVM in studies enrolling more than one thousand patients with apparent early-stage EC ranges from 1.9% to 10.2%. Different rates of LVM are observed when patients are stratified according to disease characteristics and their risk of recurrence. Patients with EC at low risk for recurrence have low rates of LVM, while intermediate- and high-risk patients have a higher likelihood of being diagnosed with nodal metastases, including LVM. Macro- and micrometastases increase the risk of recurrence and cause upstaging, while the clinical significance of ITCs is still uncertain. A recent meta-analysis found that patients with LVM have a higher relative risk of recurrence [1.34 (95% CI: 1.07–1.67)], regardless of adjuvant treatment. In a retrospective study on patients with low-risk EC and no adjuvant treatment, those with ITCs had worse recurrence-free survival compared to node-negative patients (85.1%; CI 95% 73.8–98.2 versus 90.2%; CI 95% 84.9–95.8). However, a difference was no longer observed after the exclusion of cases with lymphovascular space invasion. There is no consensus on adjuvant treatment in ITC patients at otherwise low risk, and their recurrence rate is low. Multi-institutional, prospective studies are warranted to evaluate the clinical significance of ITCs in low-risk patients. Further stratification of patients, considering histopathological and molecular features of the disease, may clarify the role of LVM and especially ITCs in specific contexts.

Literature is inconsistent with respect to clinical value of lymphovascular space invasion (LVSI) semiquantitative assessment. We aim to investigate the prognostic role of LVSI extent in stage I endometrioid endometrial carcinomas (ECs) classified by immunohistochemistry (IHC) analysis. Patients with stage I endometrioid EC undergone primary surgery were retrospectively included. Following World Health Organization definition for LVSI pathologic evaluation, subjects were divided into: LVSI-negative; LVSI-focal; LVSI-substantial. An IHC-based model was utilized to classify patients into: p53-aberrant (p53abn); mismatch repair deficient (MMRd); mismatch repair proficient with positive estrogen receptors (MMRp-ERpos); and mismatch repair proficient with negative estrogen receptors (MMRp-ERneg). 2091 subjects were included and divided into: 78.0 % (n:1631) LVSI-negative, 10.6 % (n:221) LVSI-focal, and 11.4 % (n:239) LVSI-substantial. Presence of LVSI (any extent) was associated with older age, larger tumor size and deeper myometrial infiltration. Patients with LVSI-substantial presented with higher incidence of grade 3 tumors, p53abn and MMRd status. Conversely, most LVSI-negative and LVSI-focal cases were MMRp-ERpos. At multivariable regression, LVSI-substantial was independently associated with reduced 5-year disease-free survival (DFS) and overall-survival (OS). LVSI-negative and LVSI-focal groups had similar DFS (p = 0.42) and OS (p = 0.09), whereas comparison with LVSI-substantial demonstrated significantly poorer outcomes for patients with substantial invasion. These findings were confirmed in sub-analyses of cases with grade 1-2 endometrioid and myometrial infiltration, and in the MMRp-ERpos cohort. In stage I endometrioid ECs, LVSI-focal was not associated with reduced oncologic outcomes compared to LVSI-negative. In contrast, LVSI-substantial was associated with aggressive clinicopathologic and molecular features and behaved as an independent prognostic factor for reduced survival. Our results were further confirmed in two low-risk EC settings: grade 1-2 with myometrial infiltration, and the MMRp-ERpos group.