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.

STUDY QUESTION: What is the additional value of the comprehensive complication index (CCI) and ClassIntra system (classification for intraoperative adverse events (ioAEs)) in adverse event (AE) reporting in (deep) endometriosis (DE) surgery compared to only using the Clavien-Dindo (CD) system? SUMMARY ANSWER: The CCI and ClassIntra are useful additional tools alongside the CD system for a complete and uniform overview of the total AE burden in patients with extensive surgery (such as DE), and with this uniform data registration, it is possible to provide greater insight into the quality of care. WHAT IS KNOWN ALREADY: Uniform comparison of AEs reported in the literature is hampered by scattered registration. In endometriosis surgery, the usage of the CD complication system and the CCI is internationally recommended; however, the CCI is not routinely adapted in endometriosis care and research. Furthermore, a recommendation for ioAEs registration in endometriosis surgery is lacking, although this is vital information in surgical quality assessments. STUDY DESIGN, SIZE, DURATION: A prospective mono-center study was conducted with 870 surgical DE cases from a nonuniversity DE expertise center between February 2019 and December 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS: Endometriosis cases were collected with the EQUSUM system, a publicly available web-based application for registration of surgical procedures for endometriosis. Postoperative adverse events (poAEs) were classified with the CD complication system and CCI. Differences in reporting and classifying AEs between the CCI and the CD were assessed. ioAEs were assessed with the ClassIntra. The primary outcome measure was to assess the additional value toward the CD classification with the introduction of the CCI and ClassIntra. In addition, we report a benchmark for the CCI in DE surgery. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 870 DE procedures were registered, of which 145 procedures with one or more poAEs, resulting in a poAE rate of 16.7% (145/870), of which in 36 cases (4.1%), the poAE was classified as severe (Grade 3b). The median CCI (interquartile range) of patients with poAEs was 20.9 (20.9-31.7) and 33.7 (33.7-39.7) in the group of patients with severe poAEs. In 20 patients (13.8%), the CCI was higher than the CD because of multiple poAEs. There were 11 ioAEs reported (11/870, 1.3%) in all procedures, mostly minor and directly repaired serosa injuries. LIMITATIONS, REASONS FOR CAUTION: This study was conducted at a single center; thus, trends in AE rates and type of AEs could differ from other centers. Furthermore, no conclusion could be drawn on ioAEs in relation to the postoperative course because the power of this database is not robust enough for that purpose. WIDER IMPLICATIONS OF THE FINDINGS: From our data, we would advise to use the Clavien-Dindo classification system together with the CCI and ClassIntra for a complete overview of AE registration. The CCI appeared to provide a more complete overview of the total burden of poAEs compared to only reporting the most severe poAEs (as with CD). If the use of the CD, CCI, and ClassIntra is widely adapted, uniform data comparison will be possible at (inter)national level, providing better insight into the quality of care. Our data could be used as a first benchmark for other DE centers to optimize information provision in the shared decision-making process.

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.

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.

Background: Surgical Process Modelling (SPM) offers the possibility to automatically gain insight in the surgical workflow, with the potential to improve OR logistics and surgical care. Most studies have focussed on phase recognition modelling of the laparoscopic cholecystectomy, because of its standard and frequent execution. To demonstrate the broad applicability of SPM, more diverse and complex procedures need to be studied. The aim of this study is to investigate the accuracy in which we can recognise and extract surgical phases in laparoscopic hysterectomies (LHs) with inherent variability in procedure time. To show the applicability of the approach, the model was used to automatically predict surgical end-times. Methods: A dataset of 40 video-recorded LHs was manually annotated for instrument use and divided into ten surgical phases. The use of instruments provided the feature input for building a Random Forest surgical phase recognition model that was trained to automatically recognise surgical phases. Tenfold cross-validation was performed to optimise the model for predicting the surgical end-time throughout the procedure. Results: Average surgery time is 128 ± 27 min. Large variability within specific phases is seen. Overall, the Random Forest model reaches an accuracy of 77% recognising the current phase in the procedure. Six of the phases are predicted accurately over 80% of their duration. When predicting the surgical end-time, on average an error of 16 ± 13 min is reached throughout the procedure. Conclusions: This study demonstrates an intra-operative approach to recognise surgical phases in 40 laparoscopic hysterectomy cases based on instrument usage data. The model is capable of automatic detection of surgical phases for generation of a solid prediction of the surgical end-time.

Background: During the implementation of new interventions (i.e., surgical devices and technologies) in the operating room, surgical safety might be compromised. Current safety measures are insufficient in detecting safety hazards during this process. The aim of the study was to observe whether surgical teams are capable of measuring surgical safety, especially with regard to the introduction of new interventions. Methods: A Surgical Safety Questionnaire was developed that had to be filled out directly postoperative by three surgical team members. A potential safety concern was defined as at least one answer between (strongly) disagree and indifferent. The validity of the questionnaire was assessed by comparison with the results from video analysis. Two different observers annotated the presence and effect of surgical flow disturbances during 40 laparoscopic hysterectomies performed between November 2010 and April 2012. Results: The surgeon reported a potential safety concern in 16% (85/520 questions). With respect to the scrub nurse and anesthesiologist, this was both 9% (46/520). With respect to the preparation, functioning, and ease of use of the devices in 37.5–47.5% (15–19/40 procedures) a potential safety concern was reported by one or more team members. During procedures after which a potential safety concern was reported, surgical flow disturbances lasted a higher percentage of the procedure duration [9.3 ± 6.2 vs. 2.9 ± 3.7% (mean ± SD), p < .001]. After procedures during which a new instrument or device was used, more potential safety concerns were reported (51.2 vs. 23.1%, p < .001). Conclusions: Potential safety concerns were especially reported during procedures in which a relatively high percentage of the duration consisted of surgical flow disturbances and during procedures in which a new instrument or device was used. The Surgical Safety Questionnaire can act as a validated tool to evaluate and maintain surgical safety during minimally invasive procedures, especially during the introduction of a new intervention.

Background: Minimally invasive surgery (MIS) is frequently compromised by surgical flow disturbances due to technology- and equipment-related failures. Compared with MIS in a conventional cart-based OR, performing MIS in a dedicated integrated operating room (OR) is supposed to be beneficial to patient safety. The aim of this study was to compare a conventional OR with an integrated OR with regard to the incidence and effect of equipment-related surgical flow disturbances during an advanced laparoscopic gynecological procedure [laparoscopic hysterectomy (LH)]. Methods: Using video recording, 40 LHs performed between November 2010 and April 2012 (20 in a conventional cart-based OR and 20 in an integrated OR) were analyzed by two different observers. Outcome measures were the number, duration and effect (on a seven-point ordinal scale) of the surgical flow disturbances (e.g., malfunctioning, intraoperative repositioning, setup device). Results: A total of 103 h and 45 min was observed. The interobserver agreement was high (kappa .85, p <.001). Procedure time was not significantly different (NS) [conventional OR vs. integrated OR, minutes ± standard deviation (SD), mean 161 ± 27 vs. 150 ± 34]. A total of 1651 surgical flow disturbances were observed (mean ± SD per procedure 40.8 ± 19.4 vs. 41.8 ± 15.9, NS). The mean number of surgical flow disturbances per procedure with regard to equipment was 6.3 ± 3.7 versus 8.5 ± 4.0, NS. No clinically relevant differences in the mean effect of these disturbances on the surgical flow between the two OR setups were observed. Conclusions: Performing LH in an integrated OR did not reduce the number of surgical flow disturbances nor the effect of these disturbances. Furthermore, in the integrated OR, repositioning of the monitors was a frequent and time-consuming source of disturbance. In order to maintain the high standard of surgical safety, the entire surgical team has to be aware that by performing surgery in an integrated OR different potential source for disruption arise.