Sentinel node mapping decreases the risk of failed detection of isolated positive para-aortic lymph node in endometrial cancer.

BACKGROUND: Isolated positive para-aortic lymph node metastasis in endometrial cancer is an uncommon event, ranging from 1% to 3%. OBJECTIVE: Our aim was to evaluate the impact of sentinel lymph node (SLN) mapping on the risk of isolated positive para-aortic lymph node metastasis. METHODS: We retrospectively evaluated a series of 426 patients who underwent SLN mapping with at least one SLN detected from January 2013 to December 2021 (SLN group) compared with a historical series of 209 cases who underwent a systematic pelvic and para-aortic lymphadenectomy between June 2007 and April 2015 (LND group). Isolated para-aortic lymph node metastasis recurrences were included in the SLN group analysis. RESULTS: In the SLN group, 168 cases (39.4%) had backup systematic lymphadenectomy, and 56 (13.1%) had positive lymph nodes compared with 34 (16.3%) in LND group (p=0.18). The SLN group had higher rates of minimally invasive surgeries (p<0.001) and presence of lymphovascular space invasion (p<0.001). Moreover, SLN group had fewer other uterine risk factors, such as high-grade tumors (p<0.001), and deep myometrial invasion (p<0.001). We found that SLN mapped outside the pelvis at pre-sacral, common iliac areas, and para-aortic regions in 2.8% (n=12), 11.5% (n=49), and 1.6% (n=7) of cases, respectively. Overall, 52 (12.2%) patients had positive SLNs, and 3 (5.7%) positive SLNs were found outside the pelvis-one in the pre-sacral region, one in the common iliac area, and one in the para-aortic region. An isolated para-aortic lymph node was found in only 2 (0.5%) cases in the SLN group compared with 7 (3.3%) cases in the LND group (p=0.004). CONCLUSIONS: SLN protocol accurately predicts lymph node status and may decrease the risk of failed identification of isolated para-aortic lymph node metastasis compared with systematic lymphadenectomy.

Efficacy of articaine anesthesia with needle-free/Comfort-in method and conventional needle injection in dental patients with irreversible pulpitis: a randomized clinical trial.

OBJECTIVE: To assess the anesthetic efficacy of articaine with the needle-free/Comfort-in™ method compared to the conventional needle method. To assess pain during anesthesia application, onset of anesthesia and patient`s self-reported quality of life-related to oral health after the dental emergency appointment. MATERIALS AND METHODS: This parallel, randomized clinical trial was conducted by a single operator/dentist in the state of Maranhao, northeast of Brazil. Included participants were adult dental patients with one molar (maxillary) or premolar (maxillary or mandibular) tooth diagnosed with symptomatic irreversible pulpitis. The primary outcome was the anesthetic efficacy, measured using a combination of electrical and cold pulp tests (cold + EPT) and the Numerical Rating Scale (NRS). Secondary outcomes were pain during anesthesia application, onset of anesthesia, and patient`s quality-of-life (measured with the OHIP-14). RESULTS: 62 patients were randomized in the anesthesia needle-free group and Comfort-in group (34.26 ± 10.786 × 33.29 ± 8.399 years old, respectively). The group of patients in the Comfort-in group had 71.0% success. Patients from the Comfort-in group reported statistically lower pain during the anesthesia application than patients from the conventional group (2.13 ± 2.172 × 6.03 ± 3.146 NRS scores, respectively) as well as immediately after the anesthetic procedure. Patients self-reported negative impact in quality of life was similar between groups before (p > 0.05) and after (p > 0.05) the dental emergency. CONCLUSIONS: Comfort-in™ had similar efficacy to the conventional needle method. CLINICAL RELEVANCE: This trial showed that it is possible to anesthetize patients with tooth pulpits without using needles to provide comfort mainly to anxious patients.

Can mismatch repair status be added to sentinel lymph node mapping algorithm in endometrioid endometrial cancer?

OBJECTIVE: To evaluate the relation between mismatch repair (MMR) status and the risk of lymph node metastasis in endometrial cancer, and whether this additional data can be incorporated to current SLN (sentinel lymph node) algorithm. METHODS: We included a series of 332 women that underwent SLN mapping ± systematic lymphadenectomy from January 2013 to December 2021. Protein expressions of MLH1, MSH2, MSH6, PMS2 were examined by immuno-histochemistry and considered MMRd (deficient) when at least one protein was not expressed. RESULTS: MMRd was noted in 20.8% of cases and correlated to grade 3 (p = 0.018) and presence of lymphovascular space invasion (p = 0.032). Moreover, MMRd was an independent risk factor for lymph node metastasis (OR 2.76, 95% CI 1.36-5.62). Notably, 21.7% (15/69) cases with MMRd had lymph node metastasis compared to 9.5% (25/263) of cases with MMRp (proficient) (p = 0.005). The overall and bilateral SLN detection rates were 91.9% and 75.9%, respectively. Of the 80 (24%) cases of non-bilateral SLN detection, 66.2% had low-grade tumors (G1/G2) and myometrial invasion <50%. Considering MMR status an independent prognostic factor for lymph node metastasis, a systematic lymphadenectomy (side specific or bilateral) would forgo in 53.7% (43/80) of cases with non-bilateral detection, representing 13% (43/332) of all endometroid tumors. CONCLUSION: MMR status was independently related to lymph node metastasis in endometrioid EC. Moreover, MMR status may help to select patients that can forgo systematic lymphadenectomy in case of undetected SLN.

Does sentinel node mapping impact morbidity and quality of life in endometrial cancer?

OBJECTIVES: To evaluate the prevalence of post-operative complications and quality of life (QoL) related to sentinel lymph node (SLN) biopsy vs systematic lymphadenectomy in endometrial cancer. METHODS: A prospective cohort included women with early-stage endometrial carcinoma who underwent lymph node staging, grouped as follows: SLN group (sentinel lymph node only) and SLN+LND group (sentinel lymph node biopsy with addition of systematic lymphadenectomy). The patients had at least 12 months of follow-up, and QoL was assessed by European Organization for Research and Treatment of Cervical Cancer Quality of Life Questionnaire 30 (EORTC-QLQ-C30) and EORTC-QLQ-Cx24. Lymphedema was also assessed by clinical evaluation and perimetry. RESULTS: 152 patients were included: 113 (74.3%) in the SLN group and 39 (25.7%) in the SLN+LND group. Intra-operative surgical complications occurred in 2 (1.3%) cases, and all belonged to SLN+LND group. Patients undergoing SLN+LND had higher overall complication rates than those undergoing SLN alone (33.3% vs 14.2%; p=0.011), even after adjusting for confound factors (OR=3.45, 95% CI 1.40 to 8.47; p=0.007). The SLN+LND group had longer surgical time (p=0.001) and need for admission to the intensive care unit (p=0.001). Moreover, the incidence of lymphocele was found in eight cases in the SLN+LND group (0 vs 20.5%; p<0.001). There were no differences in lymphedema rate after clinical evaluation and perimetry. However, the lymphedema score was highest when lymphedema was reported by clinical examination at 6 months (30.1 vs 7.8; p<0.001) and at 12 months (36.3 vs 6.0; p<0.001). Regarding the overall assessment of QoL, there was no difference between groups at 12 months of follow-up. CONCLUSIONS: There was a higher overall rate of complications for the group undergoing systematic lymphadenectomy, as well as higher rates of lymphocele and lymphedema according to the symptom score. No difference was found in overall QoL between SLN and SLN+LND groups.

Open Versus Minimally Invasive Radical Hysterectomy in Cervical Cancer: The CIRCOL Group Study.

PURPOSE: To analyze the survival outcomes of patients in a Brazilian cohort who underwent minimally invasive surgery (MIS) compared with open surgery for early stage cervical cancer. METHODS: A multicenter database was constructed, registering 1280 cervical cancer patients who had undergone radical hysterectomy from 2000 to 2019. For the final analysis, we included cases with a tumor ≤ 4 cm (stages Ia2 to Ib2, FIGO 2018) that underwent surgery from January 2007 to December 2017. Propensity score matching was also performed. RESULTS: A total of 776 cases were ultimately analyzed, 526 of which were included in the propensity score matching analysis (open, n = 263; MIS, n = 263). There were 52 recurrences (9.9%), 28 (10.6%) with MIS and 24 (9.1%) with open surgery (p = 0.55); and 34 deaths were recorded, 13 (4.9%) and 21 (8.0%), respectively (p = 0.15). We noted a 3-year disease-free survival (DFS) rate of 88.2% and 90.3% for those who received MIS and open surgery, respectively (HR 1.32; 95% CI: 0.76-2.29; p = 0.31) and a 5-year overall survival (OS) rate of 91.8% and 91.1%, respectively (HR 0.80; 95% CI: 0.40-1.61; p = 0.53). There was no difference in 3-year DFS rates between open surgery and MIS for tumors ≤ 2 cm (95.7% vs. 90.8%; p = 0.16) or > 2 cm (83.9% vs. 85.4%; p = 0.77). Also, the 5-year OS between open surgery and MIS did not differ for tumors ≤ 2 cm (93.1% vs. 93.6%; p = 0.82) or > 2 cm (88.9% vs. 89.8%; p = 0.35). CONCLUSIONS: Survival outcomes were similar between minimally invasive and open radical hysterectomy in this large retrospective multicenter cohort.

Vulvovaginal candidiasis and asymptomatic vaginal colonization in Portugal: Epidemiology, risk factors and antifungal pattern.

Vulvovaginal candidiasis (VVC) has been identified as a global issue of concern due to its clinical, social and economic implications. The emerging relevance of VVC makes it crucial to increase the knowledge on its epidemiological and etiological features in order to improve its prevention and treatment. Thus, this study aimed to reveal the incidence, microbiology, antifungal pattern and risk factors of VVC in Portugal. For that, high vaginal samples were collected from 470 symptomatic and asymptomatic participants; Candida spp. were identified with molecular techniques and their antifungal susceptibility was analyzed with E-tests. The results revealed an incidence of VVC among women with vulvovaginitis of 74.4%. Furthermore, 63.7% of asymptomatic women were colonized with Candida spp. Importantly, women with history of recurrent vaginal infections, those who use over-the-counter antifungals, oral contraceptive pills and non-cotton underwear were found to be at significantly higher risk of developing VVC. Candida albicans was the most common species (59%), followed by Candida glabrata (27%), in a total of eight distinct species, with similar distribution among colonized and infected participants. Of note, various isolates, especially of the most common species, showed low susceptibility towards fluconazole. In contrast, only few isolates showed low susceptibility towards caspofungin. Overall, this study suggests that the identification of species causing VVC and their antifungal susceptibility are urgently needed in clinical practice in order to improve the decision for the most adequate treatment. It also suggests that avoiding certain risk behaviors may prevent the development of VVC. LAY SUMMARY: Vaginal candidiasis (VVC) is a relevant infection worldwide. In this study, we identified several risk behaviors that may promote VVC and concluded that vaginal microbiologic analyses are urgently required in clinical practice in order to improve the prevention and treatment of this disease.

Sentinel lymph node mapping versus sentinel lymph node mapping with systematic lymphadenectomy in endometrial cancer: an open-label, non-inferiority, randomized trial (ALICE trial).

BACKGROUND: Growing evidence suggest that sentinel lymph node (SLN) biopsy in endometrial cancer accurately detects lymph node metastasis. However, prospective randomized trials addressing the oncological outcomes of SLN biopsy in endometrial cancer without lymphadenectomy are lacking. PRIMARY OBJECTIVES: The present study aims to confirm that SLN biopsy without systematic node dissection does not negatively impact oncological outcomes. STUDY HYPOTHESIS: We hypothesized that there is no survival benefit in adding systematic lymphadenectomy to sentinel node mapping for endometrial cancer staging. Additionally, we aim to evaluate morbidity and impact in quality of life (QoL) after forgoing systematic lymphadenectomy. TRIAL DESIGN: This is a collaborative, multicenter, open-label, non-inferiority, randomized trial. After total hysterectomy, bilateral salpingo-oophorectomy and SLN biopsy, patients will be randomized (1:1) into: (a) no further lymph node dissection or (b) systematic pelvic and para-aortic lymphadenectomy. MAJOR INCLUSION AND EXCLUSION CRITERIA: Inclusion criteria are patients with high-grade histologies (endometrioid G3, serous, clear cell, and carcinosarcoma), endometrioid G1 or G2 with imaging concerning for myometrial invasion of ≥50% or cervical invasion, clinically suitable to undergo systematic lymphadenectomy. PRIMARY ENDPOINTS: The primary objective is to compare 3-year disease-free survival and the secondary objectives are 5-year overall survival, morbidity, incidence of lower limb lymphedema, and QoL after SLN mapping ± systematic lymphadenectomy in high-intermediate and high-risk endometrial cancer. SAMPLE SIZE: 178 participants will be randomized in this study with an estimated date for completing accrual of December 2024 and presenting results in 2027. TRIAL REGISTRATION NUMBER: NCT03366051.

Revealing Candida glabrata biofilm matrix proteome: global characterization and pH response.

Candida glabrata is a clinically relevant human pathogen with the ability to form high recalcitrant biofilms that contribute to the establishment and persistence of infection. A defining trait of biofilms is the auto-produced matrix, which is suggested to have structural, virulent and protective roles. Thus, elucidation of matrix components, their function and modulation by the host environment is crucial to disclose their role in C. glabrata pathogenesis. As a major step toward this end, this study aimed to reveal, for the first time, the matrix proteome of C. glabrata biofilms, to characterize it with bioinformatic tools and to study its modulation by the environmental pH (acidic and neutral). The results showed the presence of several pH-specific matrix proteins (51 acidic- and 206 neutral-specific) and also proteins commonly found at both pH conditions (236). Of note, several proteins related to mannan and ß-glucan metabolism, which have a potential role in the delivery/organization of carbohydrates in the matrix, were found in both pH conditions but in much higher quantity under the neutral environment. Additionally, several virulence-related proteins, including epithelial adhesins, yapsins and moonlighting enzymes, were found among matrix proteins. Importantly, several proteins seem to have a non-canonical secretion pathway and Pdr1 was found to be a potential regulator of matrix proteome. Overall, this study indicates a relevant impact of environmental cues in the matrix proteome and provides a unique resource for further functional investigation of matrix proteins, contributing to the identification of potential targets for the development of new therapies against C. glabrata biofilms.

Impact of Sentinel Node Mapping in Decreasing the Risk of Lymphocele in Endometrial Cancer.

OBJECTIVE: Due to the growing evidence of sentinel lymph node (SLN) mapping in endometrial cancer (EC), our aim was to evaluate the impact of SLN mapping and other clinical-pathological variables in the risk of developing lymphocele. METHODS: We retrospectively analyzed a series of patients with ECs who underwent lymph node staging with SLN mapping with or without systematic pelvic ± para-aortic lymphadenectomy from November 2012 to January 2020. The lymphocele diagnosis was performed by computed tomography or magnetic resonance imaging. RESULTS: Of 348 patients included, 178 underwent SLN mapping only and 170 underwent SLN mapping and systematic lymphadenectomy (46.5% pelvic only; 53.5% pelvic and para-aortic). Seventy-three (21%) patients had open surgery and 275 (79%) had a minimally invasive approach. After a median follow-up of 25.4 months, the overall prevalence of lymphocele was 8.6% (n = 30), with 29 cases in a pelvic location. Lymphocele was found in 3.4% (n = 6/178) of patients submitted to SLN mapping only, compared with 14.1% (n = 24/170) among those who underwent SLN with lymphadenectomy (p = 0.009). Among those patients with lymphocele, seven (23.3%) were symptomatic and five (16.6%) required drainage. All symptomatic cases occurred in lymphoceles larger than 4 cm (p = 0.001). Neither resected lymph node count nor the type of systematic lymphadenectomy were related to the presence of lymphocele. Systematic lymphadenectomy was the only factor that emerged as a risk factor for the presence of lymphocele in multivariate analysis (odds ratio 3.68, 95% confidence interval 1.39-9.79; p = 0.009). CONCLUSIONS: Our data suggest that SLN mapping independently decreases the risk of lymphocele formation compared with full lymphadenectomy in EC.

Predictive Factors for Residual Disease After Conization in Cervical Cancer.

OBJECTIVE: The aim of this study was to evaluate predictive factors for the presence of residual disease after conization followed by definitive surgery in cervical cancer, and suggest a margin distance threshold that could predict residual disease. METHODS: We retrospectively analyzed a series of 42 patients with early-stage cervical cancer who underwent primary conization before definitive surgical treatment from March 2009 to May 2020. All conization specimens were reviewed for endocervical, ectocervical, and radial margins. Cases with residual disease in magnetic resonance imaging before definitive surgery were excluded. RESULTS: Thirty-three (78.6%) patients underwent hysterectomies and 9 (21.4%) trachelectomies ± lymph node staging. Twelve (28.6%) cases were stage IA1, 5 (11.8%) cases were stage IA2, 13 (31%) cases were stage IB1, 11 (26.2%) cases were stage IB2, and 1 (2.4%) case was stage IIIC1 [International Federation of Gynecology and Obstetrics (FIGO) 2019]. We found residual disease in 17 (40.4%) surgical specimens. Of the 20 patients with negative margins, there were still 3 (15%) cases with residual disease. Conversely, residual disease was identified in 14 (63.6%) of the 22 patients with positive cone margins (p = 0.001). Tumor size [odds ratio (OR) 1.71, 95% confidence interval (CI) 1.02-1.33] and positive endocervical margin status (OR 33.6, 95% CI 3.85-293.3) were related to a higher risk of residual disease in multivariate analysis. Notably, all patients with tumors larger than 2 cm had residual disease, in contrast to 29.4% in lesions up to 2 cm (p = 0.002). CONCLUSION: We found that tumor size and positive margin were predictive factors for residual disease. We could not suggest a reliable minimum margin distance threshold that could predict residual disease.