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Immunohistochemical Evaluation of Potential Biomarkers for Targeted Intraoperative Fluorescence Imaging in Endometriosis
Towards Optimizing Surgical Treatment
Surgical intervention for endometriosis is an important treatment modality, yet incomplete resection resulting from poor visibility of affected tissue and consequently recurrence of disease remains a prevalent challenge. Intra-operative visualization of endometriosis, enabling fluorescence-guided surgery (FGS), could help to optimize surgical treatment. A biomarker, upregulated in endometriosis compared to adjacent tissue, is required to use as a target for FGS. Immunohistochemistry was used to evaluate protein expression of a selection of previously identified potential biomarkers. Ten biomarkers were stained in a large cohort of 84 tissues, both deep and peritoneal endometriosis and tissue without endometriosis, all from patients with confirmed endometriosis. MMP11 and VCAN showed the largest upregulation in endometriosis compared to adjacent tissue and showed a membranous or extracellular staining pattern. MMP11 is a promising target for glandular and stromal visualization, VCAN for stromal visualization only. For both biomarkers, upregulation was high in both peritoneal and deep endometriosis and for patients with and without hormonal medication. Other stained biomarkers showed non-beneficial characteristics based on staining pattern or upregulation. Analysis of all endometriosis samples showed that combined glandular and stromal targeting is expected to result in optimal visualization of endometriosis. Further research is needed to determine whether targeting one biomarker is sufficient for this goal, or if dual targeting is necessary. Development of clinical tracers for VCAN and MMP11 is necessary.
Biomarker identification for endometriosis as a target for real-time intraoperative fluorescent imaging
A new approach using transcriptomic analysis to broaden the search for potential biomarkers
Intra-operative fluorescent imaging of endometriosis could help to optimize surgical treatment. Potential biomarkers to use as target for endometriosis-binding fluorescent probes were identified using a new five-phase transcriptomics-based approach to broaden the search for biomarkers. Using publicly available datasets, a differentially expressed gene (DEG) analysis was performed for endometriosis versus surgically relevant surrounding tissue (peritoneum, bladder, sigmoid, rectum, transverse colon, small intestine, vagina, and fallopian tubes) for which data was available. The remaining relevant surrounding tissues were analyzed for low expression levels. DEGs with a predicted membranous or extracellular location and with low expression levels in surrounding tissue were identified as candidate targets. Modified Target Selection Criteria were used to rank candidate targets based on the highest potential for use in fluorescent imaging. 29 potential biomarkers were ranked, resulting in Folate receptor 1 as the most potential biomarker. This is a first step towards finding a fluorescent tracer for intra-operative visualization of endometriosis. Additionally, this approach, using transcriptomics analysis to identifying candidate targets for a specific type of tissue for use in fluorescence-guided surgery could be translated to other surgical fields. Tweetable abstract: A new approach using transcriptomics analysis is shown to identify candidate targets for intra-operative fluorescent imaging for endometriosis, resulting in 29 potential candidates.
Purpose: Patients often undergo repeat surgery for endometriosis, due to recurrent or residual disease. Previous surgery is often considered a risk factor for worse surgical outcome. However, data are scarce concerning the influence of subsequent endometriosis surgery. Methods: A retrospective study in a centre of expertise for endometriosis was conducted. All endometriosis subtypes and intra-operative steps were included. Detailed information regarding surgical history of patients was collected. Surgical time, intra-operative steps and major post-operative complications were obtained as outcome measures. Results: 595 patients were included, of which 45.9% had previous endometriosis surgery. 7.9% had major post-operative complications and 4.4% intra-operative complications. The patient journey showed a median of 3 years between previous endometriosis surgeries. Each previous therapeutic laparotomic surgery resulted on average in 13 additional minutes (p = 0.013) of surgical time. Additionally, it resulted in more frequent performance of adhesiolysis (OR 2.96, p < 0.001) and in a higher risk for intra-operative complications (OR 1.81, p = 0.045), however no higher risk for major post-operative complications (OR 1.29, p = 0.418). Previous therapeutic laparoscopic endometriosis surgery, laparotomic and laparoscopic non-endometriosis surgery showed no association with surgical outcomes. Regardless of previous surgery, disc and segmental bowel resection showed a higher risk for major post-operative complications (OR 3.64, p = 0.017 respectively OR 3.50, p < 0.001). Conclusion: Previous therapeutic laparotomic endometriosis surgery shows an association with longer surgical time, the need to perform adhesiolysis, and more intra-operative complications in the subsequent surgery for endometriosis. However, in a centre of expertise with experienced surgeons, no increased risk of major post-operative complications was observed.
Background. During the COVID-19 pandemic the question arises if laparoscopy, as an aerosol forming procedure, poses a potential risk for viral transmission of SARS-CoV-2 to healthcare workers. Methods. A literature search was conducted using PubMed, Embase and MEDLINE. Articles reporting information regarding COVID-19 or other relevant viruses and laparoscopy, surgical smoke, aerosols and viral transmission were included. Results. Although aerosols produced during laparoscopy do not originate from the respiratory tract, the main transmission route of SARS-CoV-2, research did show SARS-CoV-2 to be present in other body fluids. The transmission risk via this route is however considered very low. As previous research showed potential viral transmission during laparoscopy for viruses that spread through contaminated body fluids, there might be a potential risk of SARS-CoV-2 transmission during laparoscopy, albeit considered very small. Conclusion. Due to the small risk compared to widely known benefits of laparoscopy, there is no reason to replace laparoscopy by laparotomy due to COVID-19 infection. To avoid the potential small risk of viral transmission, additional safety measures are advised.
Decline in surgeon volume after successful implementation of advanced laparoscopic surgery in gynecology
An undesired side effect?
Introduction: The implementation of advanced minimally invasive surgical (MIS) techniques has broadened. An extensive body of literature shows that high hospital and surgeon volumes lead to better patient outcomes. However, no information is available regarding volume trends in the post-implementation phase of MIS. This study investigated these trends and poses suggestions to adjust these developments. This knowledge can provide guidance to optimize patient safe performance of new surgical techniques. Material and methods: A national retrospective cohort study in the Netherlands. The number of advanced laparoscopic (level 3 and 4) and robotic procedures and the number of gynecologists performing them were collected through a web-based questionnaire to determine hospital and gynecological surgeon volume. These volumes were compared with our previously collected data from 2012. Results: The response rate was 85%. Hospitals produced larger volumes for advanced laparoscopic and robotic procedures. However, still 63% of the hospitals perform low-volume level 4 laparoscopic procedures. Additionally, gynecological surgeon volumes appeared to decrease for level 3 procedures, as the group of gynecologists performing fewer than 20 procedures expanded (64% vs. 44% in 2012), with 15% of the gynecologists performing fewer than ten procedures. Despite an increase in surgeon volumes for level 4 laparoscopy and robotic surgery, volumes continued to be low, as still 49% of gynecologists performed fewer than 10 level 4 procedures per year and 41% performed fewer than 20 robotic procedures per year. Conclusions: The broad implementation of advanced MIS procedures resulted in an increasing number of these procedures with increasing hospital volumes. However, as a side-effect, a disproportionate rise in number of gynecologists performing these procedures was observed. Therefore, surgeon volumes remain low and even decreased for some procedures. Centralization of complex procedures and training of specialized MIS gynecologists could improve surgeon volumes and therefore consequently enhance patient safety.
Reintervention risk and quality of life outcomes after uterine-sparing interventions for fibroids
A systematic review and meta-analysis
Objectives: To compare uterine-sparing treatment options for fibroids in terms of reintervention risk and quality of life. Design: Systematic review and meta-analysis according to PRISMA guidelines. Setting: Not applicable. Patient(s): Women with uterine fibroids undergoing a uterine-sparing intervention. Interventions(s): Not applicable. Main Outcome Measure(s): 1) Reintervention risk after uterine-sparing treatment for fibroids after 12, 36, and 60 months; and 2) quality of life outcomes, based on validated questionnaires. Two separate analyses were performed for the procedures that used an abdominal approach (myomectomy, uterine artery embolization [UAE], artery ligation, high-intensity focused ultrasound [HIFU], laparoscopic radiofrequency ablation [RFA]) and for the procedures managing intracavitary fibroids (hysteroscopic approach, including hysteroscopic myomectomy and hysteroscopic RFA). Result(s): There were 85 articles included for analysis, representing 17,789 women. Stratified by treatment options, reintervention risk after 60 months was 12.2% (95% confidence interval [CI] 5.2%–21.2%) for myomectomy, 14.4% (95% CI 9.8%–19.6%) for UAE, 53.9% (95% CI 47.2%–60.4%) for HIFU, and 7% (95% CI 4.8%–9.5%) for hysteroscopy. For the other treatment options, no studies were available at 60 months. For quality of life outcomes, symptoms improved after treatment for all options. The HIFU procedure had the least favorable outcomes. Conclusion(s): Despite the substantial heterogeneity of the study population, this meta-analysis provides valuable information on relative treatment efficacy of various uterine-sparing interventions for fibroids, which is relevant when counseling patients in daily practice. Furthermore, this study demonstrates that long-term data, particularly for the newest uterine-sparing interventions, are urgently needed.