An umbrella review of reviews on challenges to meaningful adolescent involvement in health research.

BACKGROUND: Less than 1% of studies on child and adolescent health report the involvement of adolescents in health research. This is attributed to barriers experienced by researchers and adolescents in the engagement process. To address this under-involvement of adolescents, we first need a better understanding of the factors that hinder adolescent involvement in health research. OBJECTIVE: We conducted an umbrella review of reviews to consolidate the review-level evidence on the barriers to meaningful involvement of adolescents in health research. METHODS: We preregistered this umbrella review of reviews with PROSPERO (CRD42021287467). We searched 11 databases; Google Scholar; and PROSPERO; supplemented by a hand search of the reference lists of eligible reviews, relevant journals, websites of 472 organisations, and input from experts. This resulted in the inclusion of 99 review articles exploring adolescent involvement in studies on adolescent physical or mental health, which were narratively synthesised. Adolescent coresearchers were engaged at all stages of the review. RESULTS: We found that adolescent involvement in health research is impeded by several challenges experienced by researchers and adolescents. Some challenges experienced by researchers were organisational issues which included limited resources, gatekeeping and paying adolescents. Some barriers were related to a lack of preparedness among researchers and included a lack of awareness of adolescent involvement, the need for training and guidance, and negative attitudes towards participatory research. There were also barriers around how adolescents can be involved, such as researchers finding it challenging to adapt to new methods, issues with recruitment and retention of adolescents, inclusiveness and accessibility. There were also challenges specific to adolescents, such as adolescents' skills and expertise, training, motivations and study goals. Finally, barriers related to the ethical involvement of adolescents included issues with power dynamics, confidentiality, safety and protection of adolescents. Some of the barriers reported by adolescents included tokenistic involvement, inaccessibility of adolescent involvement, and their competing demands. CONCLUSION: Researchers may find this review useful in understanding and planning for potential challenges of involving adolescents in research. Despite many identified barriers to adolescent engagement, few mitigation strategies were identified to address these barriers. There is a clear need to establish best practices for meaningful adolescent involvement in health research. PUBLIC AND PATIENT INVOLVEMENT IN THE REVIEW: Adolescents were involved at multiple stages of this umbrella review of reviews. They reviewed the protocol, screened 25% of the articles at title and abstract screening stage, screened 10% of full-text articles, and worked on data analysis. They also helped plan and conduct a participatory workshop with an adolescent advisory group to discuss the challenges experienced by adolescents in health research.

Elevation of circulating neutrophil extracellular traps in endometrial cancer: Poor prognostic value of cell-free double-stranded DNA.

OBJECTIVE: Neutrophils produce neutrophil extracellular traps (NETs) by releasing nuclear contents into the extracellular environment. NETs are associated with systemic inflammation and cancer development and progression. We aimed to investigate whether NET markers are associated with the prognosis of endometrial cancer. METHODS: Circulating levels of three NET markers (histone-DNA complex, cell-free double-stranded DNA (dsDNA), and neutrophil elastase) were measured in 98 patients with endometrial cancer who underwent surgery as primary treatment between January 2015 and June 2018 and 45 healthy women. Area under the receiver operating characteristic curve (AUC) analyses were conducted to investigate the diagnostic and prognostic utility of the markers for endometrial cancer. RESULTS: Patients with endometrial cancer showed significantly higher levels of the three NET markers than those in healthy controls. In discriminating endometrial cancer patients from healthy controls, the three NET markers showed AUC values in the following order: cell-free dsDNA (0.832; 95 % CI, 0.760-0.889), histone-DNA complex (0.740; 95 % CI, 0.660-0.809), and neutrophil elastase (0.689; 95 % CI, 0.607-0.764), comparable to those of CA-125 (0.741; 95 % CI, 0.659-0.813). Multivariate analysis adjusting for FIGO stage, histology, and lymphovascular space invasion, and lymph node involvement revealed that cell-free dsDNA level (cutoff: 95.2 ng/mL) was an independent prognostic marker for poor progression-free (adjusted HR, 2.75; 95 % CI, 1.096.92; P = 0.032) and overall survival (adjusted HR, 11.51; 95 % CI, 2.0664.22; P = 0.005) for patients with endometrial cancer. CONCLUSION: High levels of circulating NET markers were observed in patients with endometrial cancer. Cell-free dsDNA levels may play a role as prognostic markers for endometrial cancer.

Patient-reported outcomes of treatment and adverse effects following acute lymphoblastic leukemia: a low- and middle-income country cross-sectional study.

INTRODUCTION: The scenario of adult patients with acute lymphoblastic leukemia treated in Brazil has not been well described yet. METHODS: Four hundred patients diagnosed with acute lymphoblastic leukemia from 1981 to 2019, registered in the Brazilian lymphoma and leukemia association (ABRALE) or their caregivers were interviewed by telephone to evaluate patient-reported perceptions of diagnosis, treatment and adverse effects. RESULTS: Overall, 203 were male with a mean age of 15.7 years and median follow-up of 6.2 years. Main presenting symptoms were fever (39 %), bleeding/ecchymosis (38 %), intense fatigue (30 %), and musculoskeletal pain (28 %). The proportion of patients diagnosed within one week of symptoms onset differed between public (17.9 %) and private healthcare (31.1 %; p-value = 0.019). Additionally, diagnostic difficulties were higher in public care: 35 % versus 22.6 % (p-value = 0.034). Only 36 patients were able to report their treatment protocols; from a list of eight reported protocols, the most common were the Brazilian Childhood Cooperative Group for Treatment of Acute Lymphoblastic Leukemia in Children (GBTLI - 10/27.8 %) and Berlin-Frankfurt-Münster (BFM - 8/22.2 %). Seventy patients (17.5 %) required treatment modification, 37.1 % due to severe adverse effects; 21.7 % received short treatment duration (≤6 months) and 16 % proceeded to allogeneic hematopoietic stem cell transplantation with 17/64 (27 %) reporting difficulties in this step, characterized as >3 months delay. Indication for transplantation was related to minimal residual disease and cranial radiotherapy; 41.7 % reported treatment-related adverse effects (range: 1-6), in particular: mood disorders (26.3 %), neurologic deficit (13.8 %), cognitive/memory impairment (12 %), and lung disease (15 %). Risk factors for adverse effects were age, indication of transplantation and living in a large city. Treatment disparities such as diagnostic and transplantation delays remain challenges in these patients. CONCLUSIONS: Urgent interventions are needed to optimize healthcare and reduce adverse effects, especially in adolescent and young adult patients.

Comparison of survival and complications between minimally invasive and open staging surgeries in non-endometrioid endometrial cancer.

OBJECTIVE: This study aimed to compare survival and complications between minimally invasive surgery and open surgery and evaluate related risk factors in patients with non-endometrioid endometrial cancer. METHODS: Clinicopathologic characteristics; survival outcomes; complications; and prognostic factors associated with progression-free survival and overall survival were compared among patients with non-endometrioid endometrial cancer who underwent primary staging surgery using laparoscopic, robotic, or open abdominal surgery (2004-2017). RESULTS: In total, 91 patients were included: 41 and 50 underwent minimally invasive surgery and open surgery, respectively. The minimally invasive surgery and open surgery groups showed similar progression-free survival (5-year progression-free survival rate, 58.7 % vs. 58.5 %; P = .925) and overall survival (5-year overall survival rate, 73.6 % vs. 80.3 %; P = .834). Intraoperative (7.2 % vs. 6.0 %; P = .111) and postoperative surgical complications (14.6 % vs. 26.0 %; P = .165) were similar between the groups. However, blood loss was lower (mean, 305.1 vs. 561.2 ml, P < .001) and hospital stay was shorter (mean, 8.2 vs. 15.4 days, P < .001) in the minimally invasive surgery group. Using multivariate analysis, lymphovascular space invasion was identified as poor prognostic factor for progression-free survival (adjusted hazard ratio [HR], 3.054; 95 % confidence interval [CI], 1.521-6.132; P = .002) and overall survival (adjusted HR, 3.918; 95 % CI, 1.455-10.551; P = .007), whereas age ≥ 60 years was poor prognostic factor for only overall survival (adjusted HR, 5.0953; 95 % CI, 1.660-15.378; P = .004). CONCLUSIONS: Surgical outcomes did not differ between the minimally invasive and open surgery group in patients with non-endometrioid endometrial cancer. Lymphovascular space invasion was a significant survival factor in this context.

Methotrexate might become the sole treatment option for leukemia following the occurrence of Stevens-Johnson syndrome.

INTRODUCTION: Severe cutaneous adverse reactions (SCARs) arising from drug interactions can carry life-threatening implications and result in lasting effects. SCARs can be triggered by various factors, with trimethoprim/sulfamethoxazole identified as a primary culprit. Anticonvulsants and antineoplastic agents have been noted as secondary triggers. Notably, antineoplastics linked to SCARs include immunomodulatory agents. The higher mortality rates among cancer patients with SCARs underscore the significance of comprehending cancer--specific risk factors. Our objective is to present the case of a boy with acute lymphocytic leukemia (ALL) who developed Stevens-Johnson syndrome (SJS) following MTX treatment. CASE REPORT: We present the case of a three-year-old male patient diagnosed with ALL who developed Stevens-Johnson syndrome (SJS) subsequent to the administration of MTX, following the "BFM 2009" protocol. He had undergone intrathecal MTX administration on six previous occasions. Our patient received IVIG at a dose of 2g/kg along with steroids, resulting in partial clinical improvement after 21 days. An innovative protocol was developed, involving IVIG before MTX infusion and dexamethasone before MTXi, with folinic acid rescue. Intravenous immunoglobulin (IVIG) mitigates SJS/TEN via type IV hypersensitivity down-regulation and apoptosis curbing. CONCLUSION: As far as we know, the prophylactic use of IVIG to counteract SCARs in a pediatric leukemia patient represents uncharted territory. Moreover, research into the immune system dynamics within these patients and the preservation of indispensable treatments should involve allergist-immunologists as part of the multidisciplinary team attending to neoplastic conditions.

Positive Impacts of Adolescent Involvement in Health Research: An Umbrella Review.

Despite an increased recognition of the right of adolescents to be involved in decisions that affect them, young people continue to be under-involved in health research. One of the reasons is a lack of awareness among researchers on the current evidence base around the benefits of involving adolescents. To address this, we conducted an umbrella review to synthesize the evidence on the positive impacts of adolescent involvement in health research. This umbrella review was preregistered with PROSPERO (CRD42021287467). We searched 11 databases, Google Scholar, PROSPERO, reference lists, 10 journals, websites of 472 organizations, and sought input from experts. Ultimately, we included 99 review articles. We found that adolescent involvement has many positive impacts on young people, including increased knowledge and skills; personal development; financial benefits; career and academic growth; enhanced relationships; and valuing their experience. The positive impacts of adolescent involvement on the research itself include increased relevance of the study to adolescents, improved recruitment, development of more adolescent-friendly materials, enhanced data collection and analysis, and more effective dissemination. Researchers also benefited from adolescents' involvement through increased knowledge, skills, and a shift in their attitudes. The evidence supporting the positive impacts of adolescent involvement in research is substantial but limited by a lack of rigorous evaluation, inconsistent reporting, and unclear evaluation methods.

Impact of Bevacizumab on Clinical Outcomes in Patients With Platinum-resistant Relapsed Ovarian Cancer.

BACKGROUND/AIM: Over the past several decades, new anti-cancer drugs have been developed for the treatment of epithelial ovarian cancer. The development of drugs has led to changes in improving the prognosis of ovarian cancer patients. One of these drugs, bevacizumab, is used for advanced or recurrent ovarian cancer. In this study, we aimed to evaluate survival improvement in patients with platinum-resistant relapsed epithelial ovarian cancer (PR-ROC) after introduction of bevacizumab in real world experience. PATIENTS AND METHODS: We retrospectively divided patients with PR-ROC into two groups: bevacizumab plus chemotherapy (BEV-CT group) and chemotherapy alone (CT group). Progression-free survival (PFS), the primary endpoint, between two groups was compared to evaluate whether survival outcomes were improved. In addition, overall survival (OS) was also compared. RESULTS: A total of 154 patients were included in the study: 57 and 97 patients in the BEV-CT and CT groups, respectively. OS was significantly longer in the BEV-CT group than in the CT group. The use of bevacizumab was identified as a favorable prognostic factor for OS. In a subgroup analysis confined to second-line chemotherapy, PFS and OS were statistically different between groups. More patients in the CT group suffered hematologic adverse events of grade 3 or above than patients in the BEV-CT group. CONCLUSION: In a real-world clinical setting, introduction of bevacizumab led to improvement of OS in patients with PR-ROC with a tolerable toxicity.

Optimized treatment parameter by computer simulation for high-intensity focused ultrasound treatment of uterine adenomyosis: Short-term and long-term results.

This study aimed to investigate the efficacy and safety of using optimized parameters obtained by computer simulation for ultrasound-guided high-intensity focused ultrasound (HIFU) treatment of uterine adenomyosis in comparison with conventional parameters. We retrospectively assessed a single-institution, prospective study that was registered at Clinical Research Information Service (CRiS) of Republic of Korea (KCT0003586). Sixty-six female participants (median age: 44 years) with focal uterine adenomyosis were prospectively enrolled. All participants were treated with a HIFU system by using treatment parameters either for treating uterine fibroids (Group A, first 20 participants) or obtained via computer simulation (Group B, later 46 participants). To assess the treatment efficacy of HIFU, qualitative indices, including the clinically effective dysmenorrhea improvement index (DII), were evaluated up to 3 years after treatment, whereas quantitative indices, such as the nonperfused volume ratio and adenomyosis volume shrinkage ratio (AVSR), on MRI were evaluated up to 3 months after treatment. Quantitative/qualitative indices were compared between Groups A and B by using generalized linear mixed effect model. A safety assessment was also performed. Results showed that clinically effective DII was more frequently observed in Group B than in Group A (odds ratio, 3.69; P = 0.025), and AVSR were higher in Group B than in Group A (least-squares means, 21.61; P = 0.001). However, two participants in Group B developed skin burns at the buttock and sciatic nerve pain and required treatment. In conclusion, parameters obtained by computer simulation were more effective than the conventional parameters for treating uterine adenomyosis by using HIFU in terms of clinically effective DII and AVSR. However, care should be taken because of the risk of adverse events.

Cognitive Function and Variability in Antipsychotic Drug-Naive Patients With First-Episode Psychosis: A Systematic Review and Meta-Analysis.

Importance: Cognitive impairment contributes significantly to clinical outcome and level of function in individuals with psychotic disorders. These impairments are present already at psychosis onset at a group level; however, the question of heterogeneity in cognitive function among patients has not been systematically investigated. Objective: To provide an updated quantification of cognitive impairment at psychosis onset before patients receive potentially confounding antipsychotic treatment, and to investigate variability in cognitive function compared with healthy controls. Data Sources: In this systematic review and meta-analysis, PubMed articles were searched up to September 15, 2022. Study Selection: Original studies reporting data on cognitive function in antipsychotic drug-naive patients with first-episode psychosis (FEP) were included. Data Extraction and Synthesis: Data were independently extracted by 2 researchers. Cognitive tasks were clustered according to 6 domains of the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery and the domain of executive function. Random-effects model meta-analyses of mean differences and coefficient of variation ratios (CVRs) were performed, as well as meta-regressions, assessment of study quality, and publication bias. Main Outcomes and Measures: The main outcome measure was Hedges g for mean differences in cognition and CVR for within-group variability. Results: Fifty studies were included in the analysis with a total of 2625 individuals with FEP (mean [SD] age, 25.2 [3.6] years, 60% male; 40% female) and 2917 healthy controls (mean [SD] age, 26.0 [4.6]; 55% male; 45% female). In all cognitive domains, the FEP group displayed significant impairment compared with controls (speed of processing: Hedges g = -1.16; 95% CI, -1.35 to -0.98; verbal learning: Hedges g = -1.08; 95% CI, -1.28 to -0.88; visual learning: Hedges g = -1.05; 95% CI, -1.27 to -0.82; working memory: Hedges g = -1.04; 95% CI, -1.35 to -0.73; attention: Hedges g = -1.03; 95% CI, -1.24 to -0.82; reasoning/problem solving: Hedges g = -0.90; 95% CI, -1.12 to -0.68; executive function: Hedges g = -0.88; 95% CI, -1.07 to -0.69). Individuals with FEP also exhibited a larger variability across all domains (CVR range, 1.34-1.92). Conclusions and Relevance: Results of this systematic review and meta-analysis identified cognitive impairment in FEP before the initiation of antipsychotic treatment, with large effect sizes. The high variability within the FEP group suggests the need to identify those individuals with more severe cognitive problems who risk worse outcomes and could benefit the most from cognitive remediation.

The new 2023 FIGO staging system for endometrial cancer: what is different from the previous 2009 FIGO staging system?

OBJECTIVE: The International Federation of Gynecology and Obstetrics committee modified the endometrial cancer (EC) staging system based on the histopathological feature and molecular profile. The aim is to evaluate the clinical implications of the new 2023 system compared with the previous 2009 system. METHODS: We retrospectively identified 161 patients with EC who underwent primary surgical treatment between 2014 and 2018 at Seoul National University Hospital. The droplet-digital polymerase chain reaction for POLE mutations and immunohistochemistry for MLH1, PMS2, MS2, MSH6, and p53 were performed using tissues from formalin-fixed, paraffin-embedded blocks. All patients were categorized according to the 2009 and 2023 staging systems. RESULTS: The median follow-up period was 62.9 months (range, 0.3-110.9), and the median age was 57.2 years old (range, 28.0-85.9). The 5-year progression-free survival (PFS) for the 2023 system with molecular classification was 80.3% for stage I, 75.2% for stage II, 61.2% for stage III, and 22.2% for stage IV (p<0.001). Patients with the 2009 stage I and II disease were restaged using the 2023 system. In contrast, patients with stage III and IV disease were fixed in the 2009 and 2023 systems. Molecular classification downstaged 10 patients (71.4%) to IAmPOLEmut and upstaged 6 patients (37.5%) to IICmp53abn. The 2023 system with molecular classification was associated with PFS and overall survival (p<0.001 and p=0.038). CONCLUSION: The 2023 staging system for EC subdivided stages I and II compared to the 2009 system. The 2023 system with molecular classification is a good predictor of survival.

Path analysis of perceived disease vulnerability, COVID-19 fear, and lower vaccine hesitancy within the context of protection motivation theory.

COVID-19 vaccinations have demonstrated effectiveness in reducing severe infections. However, vaccine hesitancy posed a major public health hurdle to combat the COVID-19 pandemic. Online spread of vaccine conspiracy beliefs generated unwarranted mistrust and resistance to vaccines. While numerous studies have explored the factors influencing vaccine hesitancy, there remains a lack of comprehensive understanding regarding the interplay between perceived disease vulnerability, COVID-19 fear, and vaccine hesitancy. Protection motivation theory posits citizens will evaluate perceived threats and take actions to mitigate potential harm. With a large U.S. sample, path analysis demonstrated individuals' perceived disease vulnerability was associated with lower vaccine hesitancy. Greater perceived disease vulnerability was associated with higher COVID-19 fear. Greater COVID-19 fear was associated with lower vaccine hesitancy. Greater vaccine conspiracy beliefs associated with higher vaccine hesitancy. However, in the presence of perceived vulnerability to disease, vaccine conspiracy beliefs associated with higher fear of COVID-19 and thereby lower vaccine hesitancy. We found under circumstances of higher perceived vulnerability to disease and fear of COVID-19, vaccine conspiratorial believers were less vaccine hesitant. We discuss how public health messaging can highlight personal risks to contracting COVID-19 to appeal to those who self-identify as disease prone, but may have reservations about vaccines because of misinformation. Successfully combating diseases entails reaching and gaining cooperation from misbelievers because misinformation is expected to continue in the digital age. By understand individual differences to vaccine hesitancy, it can help increase vaccinations and prevent severe illnesses in the post COVID-19 pandemic era.

MAPK/ERK and PI3K/AKT signaling pathways are activated in adolescent and adult acute lymphoblastic leukemia.

BACKGROUND: The mitogen-activated protein kinase (MAPK)/ERK signaling cascade and the phosphoinosytol-3 phosphate/Akt (PI3K/Akt) pathways are involved in proliferation and differentiation of hematopoietic cells. The frequency of PI3K/Akt and MAPK pathway activation in adult acute lymphoblastic leukemia (ALL) still need to be elucidated. AIMS: To assess the activity and prognostic implications of MAPK/ERK and PI3K/Akt pathways in adult (ALL). METHODS: We examined 28 precursor-B-cell ALL and 6 T-cell primary ALL samples. Flow cytometry was employed to analyze the expression levels of phosphorylated ERK and phosphorylated Akt. RESULTS: Ten out of 15 (67%) ALL fresh samples (7 B-cell, 3 T-cell) showed constitutive p-ERK expression. The p-ERK mean fluorescent index ratio (MFI (R)) showed a tendency to be higher in ALL than in normal T lymphocytes (1.26 [0.74-3.10] vs. 1.08 [1.02-1.21], respectively [p = .069]) and was significantly lower than in leukemic cell lines (median MFI (R) 3.83 [3.71-5.97] [p < .001]). Expression of p-Akt was found in 35% (12/34) (10 B-cell, 2 T-cell). The median MFI (R) expression for p-Akt in primary blast cell was 1.13 (0.48-9.90) compared to 1.01 (1.00-1.20) in normal T lymphocytes (p = ns) and lower than in leukemic cell lines (median MFI (R) 2.10 [1.77-3.40] [p = .037]). Moreover, expression of p-ERK was negatively associated with the expression of CD34 (1.22 [0.74-1.33] vs. 1.52 [1.15-3.10] for CD34(+) and CD34(-) group, respectively, p = .009). CONCLUSION: Our findings suggest that both MAPK/ERK and PI3K/Akt are constitutively activated in adult ALL, indicating a targeted therapy potential for ALL by using inhibitors of these pathways.

The novel use and feasibility of hemostatic oxidized regenerated cellulose agent (SurgiGuard®): multicenter retrospective study.

Background: SurgiGuard® is an absorbent hemostatic agent based on oxidized regenerated cellulose. The efficacy, effects and safety of SurgiGuard® are equivalent to existing hemostatic agents in animal experiments. This study was designed to confirm that the use of SurgiGuard® alone is effective, safe and feasible compared to combination with other hemostatic methods. Methods: We retrospectively reviewed clinical data from 12 surgery departments in seven tertiary centers in South Korea nationwide. All surgeries were performed between January and December 2018. Results: A total of 807 patients were enrolled; 447 patients (55.4%) had comorbidities. The rate of major surgery (operative time ≥4 hours) was 44% (n=355 patients). Regarding the type of SurgiGuard® used in surgery, more than 70% of minor surgeries used non-woven types. In major surgery, more than five SurgiGuards® were used in 7.3% (26 patients), and the proportion of co-usage (with four other hemostatic products) was 19.7% (70 patients). The effectiveness score was higher when SurgiGuard® was used alone in both major (5.3±0.5 vs. 5.1±0.6, P=0.048) and minor surgery (5.4±0.6 vs. 5.2±0.4, P<0.001). Seven patients had immediate re-bleeding, and all of them used SurgiGuard® and other products together. Nine patients reported adverse effects, such as abscess, bleeding, or leg swelling, but we found no direct correlation with SurgiGuard®. Conclusions: SurgiGuard® exhibited greater effectiveness when used alone. No direct adverse effects associated with SurgiGuard® use were reported, and SurgiGuard® had stable feasibility. Prospective comparative studies are needed in the future.

Clinical implications of histologic subtypes on survival outcomes in primary mucinous ovarian carcinoma.

OBJECTIVE: In 2014, the World Health Organization introduced a new histologic classification by dividing primary mucinous ovarian carcinoma (PMOC) into two: expansile (ES) or infiltrative subtypes (IS). This study investigated the clinical implications of these histological subtypes on survival outcomes. METHODS: Data from 131 patients with PMOC who underwent primary surgery between 2003 and 2021 were analyzed. The patients baseline characteristics, surgical and pathological information were collected. Survival outcomes were calculated, while factors affecting them were also investigated. RESULTS: During 55.9 months of median follow-up, 27 (20.6%) patients experienced recurrence and 20 (15.3%) died. Among 131 patients, 113 patients were classified into 87 (77%) ES and 26 (23%) IS after a slide review. Advanced stage, lymph node involvement, and residual tumors after surgery were more common in the IS, showing poorer prognosis. In multivariate analyses, advanced stage and residual tumors after surgery were associated with worse survival, while the IS showed no statistical significance. In subgroup analysis for stage I disease, survival did not vary between subtypes. Nevertheless, patients in the IS group who underwent fertility-sparing surgeries demonstrated a 5-year progression-free survival (PFS) rate of 83.3%, significantly lower than patients without fertility preservation, irrespective of histologic subtypes (5-year PFS rate: 97.9%; P = 0.002 for the ES, 5-year PFS rate: 100%; P = 0.001 for the IS). CONCLUSIONS: The IS of PMOC had poorer survival outcomes and a higher proportion of advanced-stage tumors. Although its independent prognostic significance remains uncertain, adjuvant chemotherapy should be considered for patients with fertility preservation in the IS group.

Impact of supradiaphragmatic lymphadenectomy on the survival of patients in stage IVB ovarian cancer with thoracic lymph node metastasis.

Introduction: To evaluate the survival impact of supradiaphragmatic lymphadenectomy as part of debulking surgery in stage IVB ovarian cancer with thoracic lymph node metastasis (LNM). Methods: We retrospectively enrolled patients diagnosed with stage IVB ovarian, fallopian or primary peritoneal cancer between 2010 and 2020, carrying cardiophrenic, parasternal, anterior mediastinal or supraclavicular lymph nodes ≥5 mm on axial chest computed tomography. All tumors were classified into the abdominal (abdominal tumors and cardiophrenic lymph nodes) and supradiaphragmatic (parasternal, anterior mediastinal or supraclavicular lymph nodes) categories depending on the area involved. Residual tumors were classified into <5 vs ≥5 mm in the abdominal and supradiaphragmatic areas. Based on the site of recurrence, they were divided into abdominal, supradiaphragmatic and other areas. Results: A total of 120 patients underwent primary debulking surgery (PDS, n=68) and interval debulking surgery after neoadjuvant chemotherapy (IDS/NAC, n=53). Residual tumors in the supradiaphragmatic area ≥5 mm adversely affected progression-free survival (PFS) and overall survival (OS) with marginal significance after PDS despite the lack of effect on survival after IDS/NAC (adjusted hazard ratios [HRs], 6.478 and 6.370; 95% confidence intervals [CIs], 2.224-18.864 and 0.953-42.598). Further, the size of residual tumors in the abdominal area measuring ≥5 mm diminished OS after IDS/NAC (adjusted HR, 9.330; 95% CIs, 1.386-62.800). Conclusion: Supradiaphragmatic lymphadenectomy during PDS may improve survival in patients diagnosed with stage IVB ovarian cancer manifesting thoracic LNM. Further, suboptimal debulking surgery in the abdominal area may be associated with poor OS after IDS/NAC. Trial registration: ClinicalTrials.gov (NCT05005650; https://clinicaltrials.gov/ct2/show/NCT05005650; first registration, 13/08/2021).Research Registry (Research Registry UIN, researchregistry7366; https://www.researchregistry.com/browse-the-registry#home/?view_2_search=researchregistry7366&view_2_page=1).

Tissue Expression and Prognostic Role of CXCL12 and CXCR4 in High-grade Serous Ovarian Carcinoma.

BACKGROUND/AIM: The complex of C-X-C motif chemokine receptor 4 (CXCR4) and its ligand, C-X-C motif chemokine ligand 12 (CXCL12), plays an essential role in cancer cell proliferation, invasion, and metastasis. These are emerging therapeutic targets, and recent studies have reported that inhibition of CXCL12-CXCR4 signaling pathway enhances the effects of immune checkpoint inhibitors. Thus, we aimed to investigate tissue expression of CXCL12 and CXCR4 in high-grade serous ovarian carcinoma (HGSOC) and to determine their potential as prognostic markers. PATIENTS AND METHODS: We used chemotherapy-naïve, formalin-fixed paraffin-embedded primary ovarian cancer tissues obtained from patients with advanced-stage HGSOC at the time of primary cytoreductive surgery. After histological reassessment, we constructed a tissue microarray and performed immunohistochemical staining for CXCL12 and CXCR4. Thereafter, clinicopathological characteristics and survival outcomes were compared between the high- and low-expression groups. RESULTS: A total of 97 patients with FIGO stage IIIC-IV HGSOC were included: 15 (15.5%), 66 (68.0%), and 13 (13.4%) patients showed high expression of CXCL12, CXCR4, and both, respectively. The expression level of each protein was not associated with germline BRCA1/2 mutational status, FIGO stage, or residual tumor after primary cytoreductive surgery. In multivariate analysis adjusted for confounders, high CXCL12 expression was identified as an independent poor prognostic biomarker for progression-free survival (adjusted hazards ratio, 1.990; 95% confidence interval=1.090-3.633; p=0.025). However, CXCR4 expression was not associated with patient survival outcomes. CONCLUSION: The CXCL12 expression level may represent a prognostic biomarker for HGSOC. Proteins related to the CXCL12/CXCR4 complex may serve as therapeutic targets in HGSOC treatment.

Involving adolescents in the design, implementation, evaluation and dissemination of health research: an umbrella review protocol.

INTRODUCTION: A lack of awareness on how to engage adolescents in research has been reported as one of the barriers to meaningful youth involvement in health research. Currently, available guidelines on youth involvement are limited in terms of the scope (e.g., focused on limited health research areas), content (e.g., include broad principles) and context (e.g., most guidelines are from high-income countries) for which the guidelines are applicable. To address this, we will develop a set of comprehensive guidelines based on consolidated evidence on youth involvement in health research. To inform these guidelines, we are first conducting an umbrella review to (1) summarise and synthesise findings from reviews on involving adolescents in health research, (2) consolidate the challenges experienced in youth involvement and the recommendations to mitigate these challenges, (3) identify best practices and (4) identify gaps and methodological weaknesses in the extant literature on involving adolescents in health research. METHODS AND ANALYSIS: We will include review articles exploring adolescents' involvement in studies aiming to improve their physical or mental health. Databases to be searched include Cochrane Database of Systematic Reviews, Medical Literature Analysis and Retrieval System Online (MEDLINE), Scopus, Embase, PsycINFO, PsycArticles, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Epistemonikos and Health Systems Evidence. A grey literature search will be conducted in Web of Science, ProQuest, Google Scholar and PROSPERO, supplemented by a handsearch of the reference lists of eligible reviews, relevant journals, websites of related organisations and input from experts. Data will be analysed using narrative synthesis. ETHICS AND DISSEMINATION: Ethical approval is not required as we are not collecting participant data as part of this review. The findings of this umbrella review will be disseminated through peer-reviewed publications, participatory workshops and academic conferences. PROSPERO REGISTRATION NUMBER: CRD42021287467.

Prognostic significance of L1CAM expression in addition to ProMisE in endometrial cancer.

OBJECTIVE: To investigate the prognostic significance of L1 cell-adhesion molecule (L1CAM), ß-catenin, and programmed death-ligand 1 (PD-L1) in endometrial cancer (EC) patients, with a focus on p53 wild-type subgroup, for additional risk stratification. METHODS: This retrospective cohort study included EC patients classified according to Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) who underwent primary surgical treatment at the single center between January 2014 and December 2018. Immunohistochemical staining was performed for four mismatch repair (MMR) proteins, p53, L1CAM, ß-catenin, and PD-L1. DNA polymerase epsilon (POLE) mutation was detected by hot spot sequencing via droplet digital polymerase chain reaction. Survival outcome of each subgroup of L1CAM, ß-catenin, and PD-L1 was measured according to their expression. RESULTS: A total of 162 EC patients were included. Endometrioid histologic type and early-stage disease were 140 (86.4%) and 109 (67.3%), respectively. ProMisE classification assigned 48 (29.6%), 16 (9.9%), 72 (44.4%), and 26 (16.0%) patients to MMR-deficient, POLE-mutated, p53 wild-type, and p53 abnormal subgroups, respectively. L1CAM was identified as an independent poor prognostic factor for progression-free survival (PFS; adjusted hazard ratio [aHR], 3.207; 95% confidence interval (CI), 1.432-7.187; P = 0.005), whereas ß-catenin and PD-L1 positivity were not associated with recurrence (P = 0.462 and P = 0.152, respectively). In p53 wild-type subgroup, L1CAM positivity was associated with worse PFS (aHR, 4.906; 95% CI, 1.685-14.287; P = 0.004). CONCLUSION: L1CAM positivity was associated with poor prognosis in EC and further stratified the risk of recurrence in p53 wild-type subgroup, whereas ß-catenin and PD-L1 were not informative for risk stratification.

Survival outcomes of laparoscopic versus open radical hysterectomy in early cervical cancer with incidentally identified high-risk factors.

OBJECTIVE: Previously, we suggested that patients with cervical cancer (CC) with tumors ≤2 cm on preoperative magnetic resonance imaging (MRI) are safe candidates for laparoscopic radical hysterectomy (LRH). Here, we aim to investigate whether LRH deteriorates the prognosis of patients with incidentally identified high-risk factors; lymph node metastasis (LNM) or parametrial invasion (PMI). METHODS: We identified patients with 2009 FIGO stage IB1 CC who underwent Type C LRH or open radical hysterectomy (ORH) at three tertiary hospitals between 2000 and 2019. Those with a tumor ≤2 cm on preoperative MRI who were not suspicious of LNM or PMI preoperatively were included, while those who were indicated to receive adjuvant treatment but did not actually receive it were excluded. Survival outcomes were compared between the LRH and ORH groups in the overall population, then narrowed down to those with LNM, and then to those with PMI. RESULTS: In total, 498 patients were included: 299 in the LRH group and 199 in the ORH group. The LRH and ORH groups showed similar 3-year progression-free survival (PFS) (94.0% vs. 93.6%; P = 0.615) and 5-year overall survival (OS) rates (97.2% vs. 96.8%; P = 0.439). On pathologic examination, 49 (9.8%) and 16 (3.2%) patients had LNM and PMI, respectively, and 10 (2.0%) had both. In the LNM subgroup, 5-year PFS rate was not significantly different between the LRH and ORH groups (73.2% vs. 91.7%; P = 0.169). In the PMI subgroup, no difference in PFS was observed between the two groups (P = 0.893). CONCLUSIONS: LRH might not deteriorate recurrence and mortality rates in CC patients with tumors ≤2 cm when adjuvant treatment is appropriately administered, even if pathologic LNM and PMI are incidentally identified.