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Fluorescence-guided surgery is an intraoperative optical imaging method that provides surgeons with real-time guidance for the delineation of tumours. Currently, in phase 1 and 2 clinical trials, evaluation of fluorescence-guided surgery is primarily focused on its diagnostic performance, although the corresponding outcome variables do not inform about the added clinical benefit of fluorescence-guided surgery and are challenging to assess objectively. Nonetheless, the effect of fluorescence-guided surgery on intraoperative decision making is the most objective outcome measurement to assess the clinical value of this imaging method. In this Review, we explore the study designs of existing trials of fluorescence-guided surgery that allow us to extract information on potential changes in intraoperative decision making, such as additional or more conservative resections. On the basis of this analysis, we offer recommendations on how to report changes in intraoperative decision making that result from fluorescence imaging, which is of utmost importance for the widespread clinical implementation of fluorescence-guided surgery.

Anesthesia awareness has potential psychological consequences. Use of the bispectral index (BIS) developed from a processed electroencephalogram has been reported to decrease anesthesia awareness. In this randomized, controlled trial comparing a BIS-based protocol with a protocol based on measurement of end-tidal anesthetic gases, two cases of definite anesthesia awareness occurred in each group. This study did not show a benefit of BIS monitoring in reducing the rate of anesthesia awareness. This trial compared a protocol based on the bispectral index (BIS) with a protocol based on measurement of end-tidal anesthetic gases. Two cases of definite anesthesia awareness occurred in each group. This study did not show a benefit of BIS monitoring in reducing the rate of anesthesia awareness. Anesthesia awareness, also known as unintended intraoperative awareness, is the explicit recall of sensory perceptions during general anesthesia. Anesthesia awareness is rare, 1 , 2 but the incidence may approach 1% in patients at high risk. 3 – 5 Anesthesia awareness can lead to anxiety and post-traumatic stress disorder. 6 The Joint Commission on Accreditation of Healthcare Organizations (JCAHO) has recommended that stringent efforts be made to prevent anesthesia awareness, 7 and the American Society of Anesthesiologists (ASA) has published guidelines on the subject. 8 According to a sentinel-event alert disseminated by the JCAHO, between 20,000 and 40,000 cases of anesthesia awareness may occur yearly in the . . .

Postoperative complications can significantly impact perioperative care management and planning. To assess machine learning (ML) models for predicting postoperative complications using independent and combined preoperative and intraoperative data and their clinically meaningful model-agnostic interpretations. This retrospective cohort study assessed 111 888 operations performed on adults at a single academic medical center from June 1, 2012, to August 31, 2016, with a mean duration of follow-up based on the length of postoperative hospital stay less than 7 days. Data analysis was performed from February 1 to September 31, 2020. Outcomes included 5 postoperative complications: acute kidney injury (AKI), delirium, deep vein thrombosis (DVT), pulmonary embolism (PE), and pneumonia. Patient and clinical characteristics available preoperatively, intraoperatively, and a combination of both were used as inputs for 5 candidate ML models: logistic regression, support vector machine, random forest, gradient boosting tree (GBT), and deep neural network (DNN). Model performance was compared using the area under the receiver operating characteristic curve (AUROC). Model interpretations were generated using Shapley Additive Explanations by transforming model features into clinical variables and representing them as patient-specific visualizations. A total of 111 888 patients (mean [SD] age, 54.4 [16.8] years; 56 915 [50.9%] female; 82 533 [73.8%] White) were included in this study. The best-performing model for each complication combined the preoperative and intraoperative data with the following AUROCs: pneumonia (GBT), 0.905 (95% CI, 0.903-0.907); AKI (GBT), 0.848 (95% CI, 0.846-0.851); DVT (GBT), 0.881 (95% CI, 0.878-0.884); PE (DNN), 0.831 (95% CI, 0.824-0.839); and delirium (GBT), 0.762 (95% CI, 0.759-0.765). Performance of models that used only preoperative data or only intraoperative data was marginally lower than that of models that used combined data. When adding variables with missing data as input, AUROCs increased from 0.588 to 0.905 for pneumonia, 0.579 to 0.848 for AKI, 0.574 to 0.881 for DVT, 0.5 to 0.831 for PE, and 0.6 to 0.762 for delirium. The Shapley Additive Explanations analysis generated model-agnostic interpretation that illustrated significant clinical contributors associated with risks of postoperative complications. The ML models for predicting postoperative complications with model-agnostic interpretation offer opportunities for integrating risk predictions for clinical decision support. Such real-time clinical decision support can mitigate patient risks and help in anticipatory management for perioperative contingency planning.

Fluorescence and photoacoustic imaging have different advantages in cancer diagnosis; however, combining effects in one agent normally requires a trade-off as the mechanisms interfere. Here, based on rational molecular design, we introduce a smart organic nanoparticle whose absorbed excitation energy can be photo-switched to the pathway of thermal deactivation for photoacoustic imaging, or to allow opposed routes for fluorescence imaging and photodynamic therapy. The molecule is made of a dithienylethene (DTE) core with two surrounding 2-(1-(4-(1,2,2-triphenylvinyl)phenyl)ethylidene)malononitrile (TPECM) units (DTE-TPECM). The photosensitive molecule changes from a ring-closed, for photoacoustic imaging, to a ring-opened state for fluorescence and photodynamic effects upon an external light trigger. The nanoparticles’ photoacoustic and fluorescence imaging properties demonstrate the advantage of the switch. The use of the nanoparticles improves the outcomes of in vivo cancer surgery using preoperative photoacoustic imaging and intraoperative fluorescent visualization/photodynamic therapy of residual tumours to ensure total tumour removal. The combination of imaging techniques in cancer treatment often involves a trade-off in properties due to the opposite working mechanisms. Here, the authors report on a material that avoids the trade-off by switching from photoacoustic imaging to fluorescence imaging upon an external light trigger

Abstract Objective To compare studies that used telepathology systems vs conventional microscopy for intraoperative consultation (frozen-section) diagnosis. Methods A total of 56 telepathology studies with 13,996 cases in aggregate were identified through database searches. Results The concordance of telepathology with the reference standard was generally excellent, with a weighted mean of 96.9%. In comparison, we identified seven studies using conventional intraoperative consultation that showed a weighted mean concordance of 98.3%. Evaluation of the risk of bias showed that most of these studies were low risk. Conclusions Despite limitations such as variation in reporting and publication bias, this systematic review provides strong support for the safety of using telepathology for intraoperative consultations.

To evaluate the associations between high and low intraoperative time-weighted average mean arterial pressures before, during and after cardiopulmonary bypass on postoperative delirium. Single center retrospective cohort study. Operating rooms and postoperative care units. 11,382 patients, 18 years of age or older who had cardiac surgery requiring cardiopulmonary bypass between January 2017 and December 2020 at the Cleveland Clinic Main Campus. All cardiac surgery requiring bypass except procedures requiring deep hypothermic circulatory arrest. Post operative delirium was assessed from 12 to 96 h postoperatively, using the Confusion Assessment Method and brief Confusion Assessment Methods. Hypotension and hypertension were defined as time-weighted average mean arterial pressure < 60 and > 80 mmHg. Postoperative delirium occurred in 678 (6.0 %) of 11,382 patients. Confounder-adjusted associations, using multivariable logistic regression models, between hypotension (time-weighted average mean arterial pressure < 60 mmHg) and hypertension (time-weighted average mean arterial pressure > 80 mmHg) and postoperative delirium were not statistically significant or clinically meaningful before, during, or after the cardiopulmonary bypass. This large single-center cohort analysis found no evidence that exposure to high or low blood pressures during various intraoperative phases of cardiac surgery are associated with postoperative delirium. [Display omitted] •There is no association between time-weighted average mean arterial pressure < 60 mmHg, during any time period, and postoperative delirium.•There is no association between time-weighted average mean arterial pressure > 80 mmHg, during any time period, and postoperative delirium.•This study does not discount the fact that intraoperative hypertension and hypotension during cardiac surgery can be associated with worst outcomes unrelated to delirium.

Background/ObjectiveIntraoperative evaluation of sentinel lymph nodes (SLNs) after neoadjuvant chemotherapy (NAC) has a higher false-negative rate than in the primary surgical setting, particularly for small tumor deposits. Additional tumor burden seen with isolated tumor cells (ITCs) and micrometastases following primary surgery is low; however, it is unknown whether the same is true after NAC. We examined the false-negative rate of intraoperative frozen section (FS) after NAC, and the association between SLN metastasis size and residual disease at axillary lymph node dissection (ALND).MethodsPatients undergoing SLN biopsy after NAC were identified. The association between SLN metastasis size and residual axillary disease was examined.ResultsFrom July 2008 to July 2017, 702 patients (711 cancers) had SLN biopsy after NAC. On FS, 181 had metastases, 530 were negative; 33 negative cases were positive on final pathology (false-negative rate 6.2%). Among patients with a positive FS, 3 (2%) had ITCs and no further disease on ALND; 41 (23%) had micrometastases and 125 (69%) had macrometastases. Fifty-nine percent of patients with micrometastases and 63% with macrometastases had one or more additional positive nodes at ALND. Among those with a false-negative result, 10 (30%) had ITCs, 15 (46%) had micrometastases, and 8 (24%) had macrometastases; 17 had ALND and 59% had one or more additional positive lymph nodes. Overall, 1/6 (17%) patients with ITCs and 28/44 (64%) patients with micrometastases had additional nodal metastases at ALND.ConclusionLow-volume SLN disease after NAC is not an indicator of a low risk of additional positive axillary nodes and remains an indication for ALND, even when not detected on intraoperative FS.

Laparoscopic cholecystectomy (LC) has a wide range of technical difficulty. Preoperative risk stratification is essential for adequate planning and patient counseling. We hypothesized that gallbladder wall thickness (GWT) is more objective marker than symptom duration in predicting complexity, as determined by operative time (OT), intraoperative events (IE), and postoperative complications. All adult patients who underwent LC during 2010–2018 were included. GWT, measured on imaging and on the histopathologic exam, was divided into three groups: <3 mm (normal), 3–7 mm and >7 mm. Univariate and multivariable analyses were performed to determine the association between GWT and 1) operative time, 2) the incidence of IE and 3) postoperative outcomes. A total of 1089 patients, subjects to LC, were included in the study. GWT was positively correlated with median OT (p < 0.001), the incidence of IE (p < 0.001) and median length of hospital stay (p < 0.001). GWT independently predicted IE (OR = 2.1 95% CI: 1.3–3.4) and outperformed symptom duration, which was not significantly associated with any of the outcomes (p = 0.7). GWT independently predicted IE and may serve as an objective marker of LC complexity. •Laparoscopic cholecystectomy (LC) is a common procedure with a wide range of operative difficulty.•The subjective report of days of symptoms is the current standard of estimating operative risk and complexity.•Gallbladder Wall Thickness (GWT) was an independent predictor of intraoperative events and length of hospital.•GWT outperformed symptom duration which was not significantly associated with any of the outcomes of our study.•GWT may serve as an objective marker of LC complexity.

Purpose Hybrid image-guided surgery technologies such as combined radio- and fluorescence-guidance are increasingly gaining interest, but their added value still needs to be proven. In order to evaluate if and how fluorescence-guidance can help realize improvements beyond the current state-of-the-art in sentinel node (SN) biopsy procedures, use of the hybrid tracer indocyanine green (ICG)- 99m Tc-nancolloid was evaluated in a large cohort of patients. Patients and methods A prospective trial was conducted (n = 501 procedures) in a heterogeneous cohort of 495 patients with different malignancies (skin malignancies, oral cavity cancer, penile cancer, prostate cancer and vulva cancer). After injection of ICG- 99m Tc-nanocolloid, SNs were preoperatively identified based on lymphoscintigraphy and SPECT/CT. Intraoperatively, SNs were pursued via gamma tracing, visual identification (blue dye) and/or near-infrared fluorescence imaging during either open surgical procedures (head and neck, penile, vulvar cancer and melanoma) or robot assisted laparoscopic surgery (prostate cancer). As the patients acted as their own control, use of hybrid guidance could be compared to conventional radioguidance and the use of blue dye ( n  = 300). This was based on reported surgical complications, overall survival, LN recurrence free survival, and false negative rates (FNR). Results A total of 1,327 SN-related hotspots were identified on 501 preoperative SPECT/CT scans. Intraoperatively, a total number of 1,643 SNs were identified based on the combination of gamma-tracing (>98%) and fluorescence-guidance (>95%). In patients wherein blue dye was used ( n  = 300) fluorescence-based SN detection was superior over visual blue dye-based detection (22–78%). No adverse effects related to the use of the hybrid tracer or the fluorescence-guidance procedure were found and outcome values were not negatively influenced. Conclusion With ICG- 99m Tc-nanocolloid, the SN biopsy procedure has become more accurate and independent of the use of blue dye. With that, the procedure has evolved to be universal for different malignancies and anatomical locations.

Intraoperative radiotherapy with electrons allows the substitution of conventional postoperative whole breast irradiation with one session of radiotherapy with the same equivalent dose during surgery. However, its ability to control for recurrence of local disease required confirmation in a randomised controlled trial. This study was done at the European Institute of Oncology (Milan, Italy). Women aged 48–75 years with early breast cancer, a maximum tumour diameter of up to 2·5 cm, and suitable for breast-conserving surgery were randomly assigned in a 1:1 ratio (using a random permuted block design, stratified for clinical tumour size [<1·0 cm vs 1·0–1·4 cm vs ≥1·5 cm]) to receive either whole-breast external radiotherapy or intraoperative radiotherapy with electrons. Study coordinators, clinicians, and patients were aware of the assignment. Patients in the intraoperative radiotherapy group received one dose of 21 Gy to the tumour bed during surgery. Those in the external radiotherapy group received 50 Gy in 25 fractions of 2 Gy, followed by a boost of 10 Gy in five fractions. This was an equivalence trial; the prespecified equivalence margin was local recurrence of 7·5% in the intraoperative radiotherapy group. The primary endpoint was occurrence of ipsilateral breast tumour recurrences (IBTR); overall survival was a secondary outcome. The main analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01849133. 1305 patients were randomised (654 to external radiotherapy and 651 to intraoperative radiotherapy) between Nov 20, 2000, and Dec 27, 2007. After a medium follow-up of 5·8 years (IQR 4·1–7·7), 35 patients in the intraoperative radiotherapy group and four patients in the external radiotherapy group had had an IBTR (p<0·0001). The 5-year event rate for IBRT was 4·4% (95% CI 2·7–6·1) in the intraoperative radiotherapy group and 0·4% (0·0–1·0) in the external radiotherapy group (hazard ratio 9·3 [95% CI 3·3–26·3]). During the same period, 34 women allocated to intraoperative radiotherapy and 31 to external radiotherapy died (p=0·59). 5-year overall survival was 96·8% (95% CI 95·3–98·3) in the intraoperative radiotherapy group and 96·9% (95·5–98·3) in the external radiotherapy group. In patients with data available (n=464 for intraoperative radiotherapy; n=412 for external radiotherapy) we noted significantly fewer skin side-effects in women in the intraoperative radiotherapy group than in those in the external radiotherapy group (p=0·0002). Although the rate of IBTR in the intraoperative radiotherapy group was within the prespecified equivalence margin, the rate was significantly greater than with external radiotherapy, and overall survival did not differ between groups. Improved selection of patients could reduce the rate of IBTR with intraoperative radiotherapy with electrons. Italian Association for Cancer Research, Jacqueline Seroussi Memorial Foundation for Cancer Research, and Umberto Veronesi Foundation.