DNA alterations in ovarian adult granulosa cell tumours: A scoping review protocol.

BACKGROUND: Identifying and describing molecular alterations in tumors has become common with the development of high-throughput sequencing. However, DNA sequencing in rare tumors, such as ovarian adult granulosa cell tumor (aGCT), often lacks statistical power due to the limited number of cases in each study. Questions regarding personalized treatment or prognostic biomarkers for recurrence or other malignancies therefore still need to be elucidated. This scoping review protocol aims to systematically map the current evidence and identify knowledge gaps regarding DNA alterations, actionable variations and prognostic biomarkers in aGCT. METHODS: This scoping review will be conducted based on Arksey and O'Malley's methodological framework and later modifications by JBI Evidence Synthesis. The protocol complies with Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews. All original publications describing molecular alterations of aGCT will be included. The search will be performed in May 2024 in the following databases: MEDLINE (Ovid), Embase (Ovid), Web of Science Core Collection and Google Scholar (100-top ranked). DISCUSSION: This scoping review will identify knowledge and gaps in the current understanding of the molecular landscape of aGCT, clinical trials on actionable variations and priorities for future research. As aGCT are rare, a possible limitation will be the small sample sizes and heterogenic study settings. SCOPING REVIEW REGISTRATION: The review protocol is registered at Open Science Framework under https://doi.org/10.17605/OSF.IO/PX4MF.

Sertoli-Leydig cell tumor: a clinicopathological analysis in a comprehensive, national cohort.

INTRODUCTION: Sertoli-Leydig cell tumors are rare tumors of the ovary. Moderate and poorly differentiated tumors can metastasize and have a poor outcome. A pathogenic variant in DICER1 is associated with an increased risk of developing these tumors along with other clinical phenotypes. We aimed to describe a national cohort of all Sertoli-Leydig cell tumors with regard to clinicopathological characteristics and frequency of DICER1 pathogenic variants. METHODS: In May 2018, all patients registered from January 1997 to December 2017 with the Systematized Nomenclature of Medicine code M86310 (Sertoli-Leydig cell tumor) were obtained from the Danish National Pathology Registry. Validation of the diagnosis depended on comments in the reports that two pathologists validated the initial diagnosis or revision of the pathology at another facility. We performed descriptive statistics to describe baseline characteristics, and cancer related survival was calculated using Kaplan-Meier analysis followed by a log rank test for differences between variables RESULTS: 41 women with Sertoli-Leydig cell tumors were identified. Median age was 41 years (range 6-79). The stages according to the International Federation of Gynecology and Obstetrics (FIGO) were: stage I, 85% (n=35), stage II, 2% (n=1), stage III, 5% (n=2), and stage IV, 7% (n=3). The 5 year cancer related survival was 100% for patients with localized disease (stages I-II) and 0% in advanced tumor stages (stages III-IV). Histological differentiation grade of the tumors was well differentiated in 29% (n=12), moderately differentiated in 56% (n=23), and poorly differentiated in 15% (n=6), and the 5 year cancer related survival was 100%, 96%, and 33%, respectively, according to grade. All patients underwent surgery. Twenty-two patients had fertility sparing surgery and four of these had given birth at the time of follow-up. Analysis of DICER1 was performed in eight women. Four carried a pathogenic variant. Four patients received adjuvant chemotherapy, three because of advanced tumor stage, and one because of a poorly differentiated Sertoli-Leydig cell tumor. CONCLUSION: The prognosis for women with Sertoli-Leydig cell tumors with localized disease is excellent. Women with advanced stages (III-IV) have a poor prognosis, regardless of adjuvant chemotherapy. Fertility sparing surgery seems to be a viable option for localized Sertoli-Leydig cell tumors. DICER1 screening was rarely performed in previous cohorts and concomitant organ screening programs are topics for discussion.

Effect of 24 mg dexamethasone preoperatively on surgical stress, pain and recovery in robotic-assisted laparoscopic hysterectomy.

Background: Robotic-assisted hysterectomy is an alternative to laparoscopic surgery as part of a minimal invasive regimen. Several treatment strategies are followed to improve the overall outcome and minimize surgical stress. Glucocorticoids provide significant analgesic and antiemetic effects but their role in reducing inflammatory stress in a fast-track, multi-modal setting in patients undergoing minimally invasive surgery remains to be investigated in details. Methods: This study will evaluate in a randomized trial the effect of a single dose of 24 mg dexamethasone on 100 women undergoing robotic-assisted hysterectomy with regard to surgical stress, measured by c-reactive protein as primary outcome and, further, other stress markers like white blood cell subtypes. The postoperative recovery will be registered in validated charts and questionnaires for pain and analgesic use, quality of recovery, incontinence, sexual and work life. Furthermore, in a sub-analysis, transcriptional profiling will be performed to explore the mechanism of systemic innate and adaptive immune system perturbation induced by surgical stress. Conclusion: The study will provide solid evidence on markers of immunomodulation biomarkers and in addition the subjective effects and underlying mechanisms of perioperative glucocorticoid in women undergoing robotic hysterectomy. These include important aspects of life quality like pain, fatigue, freedom of medications, resuming work and sexual activities.

Revision surgery and mortality following complex spine surgery: 2-year follow-up in a prospective cohort of 679 patients using the Spine AdVerse Event Severity (SAVES) system.

STUDY DESIGN: Prospective study. OBJECTIVE: To determine the 2-year risk of revision surgery and all-cause mortality after complex spine surgery, and to assess if prospectively registered adverse events (AE) could predict either outcome. Revision surgery and mortality are serious complications to spine surgery. Previous studies of frequency have mainly been retrospective and few studies have employed competing risk survival analyses. In addition, assessment of predictors has focused on preoperative patient characteristics. The effect of perioperative AEs on revision and all-cause mortality risks are not fully understood. METHODS: Between January 1 and December 31, 2013, we prospectively included all patients undergoing complex spine surgery at a single, tertiary institution. Complex spine surgery was defined as conditions deemed too complicated for surgery at a secondary institute, or patients with severe comorbidities requiring multidisciplinary observation and treatment. AEs were registered using the Spine Adverse Event Severity system and patients were followed for minimum 2 years regarding revision surgery and all-cause mortality. Incidences were estimated using competing risk survival analyses and correlation between AEs and either outcome was assessed using proportional odds models. RESULTS: We included a complete and consecutive cohort of 679 adult and pediatric patients. Demographics, surgical data, AEs, and events of revision or all-cause mortality were registered. The cumulative incidence of 2-year all-cause revision was 19% (16-22%) and all-cause mortality was 15% (12-18%). Deformity surgery was the surgical category with highest incidence of revision and the highest incidence of all-cause mortality was seen in the tumor group. Across surgical categories, cumulative incidences of 2-year revision ranged between 11% (tumor) and 33% (deformity), whilst 2-year all-cause mortality ranged between 3% (deformity) and 33% (tumor). We found that major intraoperative AEs were associated to increased odds of revision. Deep wound infection was associated to increased odds of all-cause mortality. CONCLUSIONS: We report the cumulative incidences of revision surgery and all-cause mortality following complex spine surgery. We found higher incidences of revision compared to previous retrospective studies. Prospectively registered AEs were correlated to increased odds of revision surgery and all-cause mortality. These results may serve as reference for future interventional studies and aid in identifying at-risk patients. LEVEL OF EVIDENCE: I.

Readmission following complex spine surgery in a prospective cohort of 679 patients - 2-years follow-up using the Spine AdVerse Event Severity (SAVES) system.

BACKGROUND CONTEXT: Recent studies suggest that prospective registration more accurately reflects the true incidence of adverse events (AEs). To our knowledge, no previous study has investigated prospectively registered AEs' influence on hospital readmission following spine surgery. PURPOSE: To determine the frequency and type of unplanned readmissions after complex spine surgery, and to investigate if prospectively registered AEs can predict readmissions. DESIGN: This is a prospective, consecutive cohort study. PATIENT SAMPLE: We conducted a single-center study of 679 consecutive patients who underwent complex spine surgery defined as conditions deemed too complicated for surgery at a secondary institute, or patients with severe comorbidities requiring multidisciplinary observation and treatment. OUTCOME MEASURES: The outcomes in this study were (1) readmission to any hospital department within 30 days of discharge and (2) readmission to a surgical spine center at any time in follow-up. METHODS: All patients undergoing complex spine surgery, at our tertiary referral center, were consecutively, and prospectively, included from January 1 to December 31, 2013. Demographics and perioperative AEs were registered using the Spine AdVerse Events Severity (SAVES) system. Patients were followed for a minimum of two years. A competing risk survival model was used to estimate rates of readmissions with death as a competing risk. Patient characteristics, surgical parameters and perioperative AEs were analyzed to identify factors associated with readmission. Analyses of 30-day readmission were performed using logistic regression models. A proportional odds model, with death as competing risk, was used for readmissions to a spine center at any time in follow-up. Results were reported as odds ratios with 95% confidence intervals (95% CI). RESULTS: Within 2 years of index discharge, 443 (65%) were readmitted. Only 20% of readmissions were to a spine center. Cumulative incidence (95% CI) of readmission was estimated to 13% (10%-16%) at 30 days, 26% (23%-30%) at 90 days, 50% (46%-54%) at 1 year, and 59% (55%-63%) at 2 years following discharge. Rates were markedly lower for readmissions to a spine center. Increased odds of 30-day readmission were correlated to intraoperative hypotension (p=.02) and major intraoperative blood loss (p<.01). Readmission to a spine center was associated with the number of instrumented vertebrae (p=.047), major intraoperative AE (p=.01), and intraoperative hypotension (p<.01). CONCLUSIONS: To the best of our knowledge, this is the first study to analyze prospectively registered AEs' association to readmission up to 2 years after complex spine surgery. We found that readmissions were more frequent than previously reported when including readmissions to any department or hospital. Factors related to major intraoperative blood loss were associated to increased odds of readmission. This should be considered during planning of postoperative observation and care.

Radiographic Predictors for Mechanical Failure After Adult Spinal Deformity Surgery: A Retrospective Cohort Study in 138 Patients.

STUDY DESIGN: Retrospective cohort study at a single institution. OBJECTIVE: We aimed at estimating the rate of revision procedures and identify radiographic predictors of mechanical failure after adult spinal deformity surgery. SUMMARY OF BACKGROUND DATA: Mechanical failure rates after adult spinal deformity surgery range 12% to 37% in literature. Although the importance of spinal and spino-pelvic alignment is well documented for surgical outcome and ideal alignment has been proposed as sagittal vertical axis (SVA) < 5 cm, pelvic tilt < 20° and lumbar lordosis (LL) = pelvic incidence ±â€Š9°, the role of radiographic sagittal spine parameters and alignment targets as predictors for mechanical failure remains uncertain. METHODS: A consecutive cohort of adult spinal deformity patients who underwent corrective surgery with at least 5 levels of instrumentation between January 2008 and December 2012 at a single tertiary spine unit were followed for at least 2 years. Time to death or failure was recorded and cause-specific Cox regressions were applied to evaluate predictors for mechanical failure or death. RESULTS: A total of 138 patients with median age of 61 years were included for analysis. Follow up ranged 2.1 to 6.8 years. In total 47% had revision and estimated failure rates were 16% at 1 year increasing to 56% at 5 years. A multivariate analysis adjusting for age at surgery showed increased hazard of failure from LL change > 30°, postoperative TK > 50°, and SS ≤30°. LL change was mostly because of 3-column osteotomy and ending the instrumentation at L5 or S1 increased the hazard of failure more than 6 fold compared with more cranial lumbar levels. CONCLUSION: Mechanical failure rate was 47% after adult spinal deformity corrective surgery. LL change > 30°, postoperative TK > 50°, and postoperative SS ≤30° were independent radiographic predictors associated with increased hazard of failure. LEVEL OF EVIDENCE: 4.

Morbidity and mortality of complex spine surgery: a prospective cohort study in 679 patients validating the Spine AdVerse Event Severity (SAVES) system in a European population.

BACKGROUND CONTEXT: Most literature on complications in spine surgery has been retrospective or based on national databases with few variables. The Spine AdVerse Events Severity (SAVES) system has been found reliable and valid in two Canadian centers, providing precise information regarding all adverse events (AEs). PURPOSE: This study aimed to determine the mortality and examine the incidence of morbidity in patients undergoing complex spinal surgery, including pediatric patients, and to validate the SAVES system in a European population. STUDY DESIGN: A prospective, consecutive cohort study was conducted using the SAVES version 2010 in the period from January 1, 2013 until December 31, 2013. A retrospective analysis was performed on all patients operated from November 1, 2011 until October 31, 2012 for comparison. PATIENT SAMPLE: Patients undergoing spinal surgery at a tertiary referral center comprised the patient sample. OUTCOME MEASURES: Morbidity and mortality were determined according to the newest version of the SAVES system and compared with the Canadian cohort. Other outcomes were length of stay, readmission, unplanned second surgery during index admission, as well as wound infections requiring revision. METHODS: All patients undergoing spinal surgery at an academic tertiary referral center in the study period were prospectively included. The newest version of SAVES system was used, and a research coordinator collected all intraoperative and perioperative data prospectively. Once a week all patients were reviewed for additional events, validation of the data, and clarification of any questions. Patients were grouped according to the type of admission (elective of emergency) and age, and subgrouped according to a major diagnostic group. The survival status was registered on January 31, 2014 to obtain 30-day survival. RESULTS: A total of 679 consecutive cases were included with 100% data completion. The in-hospital mortality was 1.3% and the 30-day mortality was 2.7%; all occurring after emergency procedures. The number of intraoperative AEs was 162 (overall incidence 20%), and the number of postoperative AEs was 1,415 (overall incidence 77%). Of the patients, 2.2% had postoperative infections requiring surgical revision. CONCLUSIONS: A prospective registration improves AE recognition, and our data confirm the generalizability of the SAVES system to pediatric and non-Canadian populations.