Ultra-fast deep-learned CNS tumour classification during surgery.

Central nervous system tumours represent one of the most lethal cancer types, particularly among children1. Primary treatment includes neurosurgical resection of the tumour, in which a delicate balance must be struck between maximizing the extent of resection and minimizing risk of neurological damage and comorbidity2,3. However, surgeons have limited knowledge of the precise tumour type prior to surgery. Current standard practice relies on preoperative imaging and intraoperative histological analysis, but these are not always conclusive and occasionally wrong. Using rapid nanopore sequencing, a sparse methylation profile can be obtained during surgery4. Here we developed Sturgeon, a patient-agnostic transfer-learned neural network, to enable molecular subclassification of central nervous system tumours based on such sparse profiles. Sturgeon delivered an accurate diagnosis within 40 minutes after starting sequencing in 45 out of 50 retrospectively sequenced samples (abstaining from diagnosis of the other 5 samples). Furthermore, we demonstrated its applicability in real time during 25 surgeries, achieving a diagnostic turnaround time of less than 90 min. Of these, 18 (72%) diagnoses were correct and 7 did not reach the required confidence threshold. We conclude that machine-learned diagnosis based on low-cost intraoperative sequencing can assist neurosurgical decision-making, potentially preventing neurological comorbidity and avoiding additional surgeries.

Of rats and men.

The selective breeding of rats as physiological, behavioral, and disease models generated a wealth of variation relevant to the genetics of complex traits. In this issue, Atanur and colleagues sequence the genomes of 25 inbred rat strains to understand how artificial selection shaped their genomes.

Breast conserving surgery with intraoperative electron beam radiation therapy for low-risk breast cancer: Five-year follow-up of 306 patients.

Recent studies have reported a higher than expected risk of ipsilateral breast tumor recurrence (IBTR) after breast conserving surgery (BCS) and a single dose of electron beam intra-operative radiotherapy (IORT). This finding was the rationale to perform a retrospective single center cohort study evaluating the oncologic results of consecutive patients treated with BCS and IORT. Women were eligible if they had clinical low-risk (N0, ≤2 cm unifocal, Bloom and Richardson grade 1-2), estrogen receptor-positive and human-epidermal-growth-factor-receptor-2-negative breast cancer. Prior to BCS, pN0 status was determined by sentinel lymph node biopsy. Data on oncologic follow-up were analyzed. Between 2012 and 2019, 306 consecutive patients were treated and analyzed, with a median age of 67 (50-86) years at diagnosis. Median follow-up was 60 (8-120) months. Five-year cumulative risk of IBTR was 13.4% (95% confidence interval [CI] 9.4-17.4). True in field recurrence was present in 3.9% of the patients. In 4.6% of the patients, the IBRT was classified as a local recurrence due to seeding of tumor cells in the cutis or subcutis most likely related to percutaneous biopsy. In 2.9% of the patients, the IBRT was a new outfield primary tumor. Three patients had a regional lymph node recurrence and two had distant metastases as first event. One breast cancer-related death was observed. Estimated 5-year overall survival was 89.8% (95% CI 86.0-93.6). In conclusion, although some of IBTR cases could have been prevented by adaptations in biopsy techniques and patient selection, BCS followed by IORT was associated with a substantial risk of IBTR.

Intraoperative indocyanine green fluorescence imaging to predict early hepatic arterial complications after liver transplantation.

The purpose of this study was to propose an innovative intraoperative criterion in a liver transplantation setting that would judge arterial flow abnormality that may lead to early hepatic arterial occlusion, that is, thrombosis or stenosis, when left untreated and to carry out reanastomosis. After liver graft implantation, and after ensuring that there is no abnormality on the Doppler ultrasound (qualitative and quantitative assessment), we intraoperatively injected indocyanine green dye (0.01 mg/Kg), and we quantified the fluorescence signal at the graft pedicle using ImageJ software. From the obtained images of 89 adult patients transplanted in our center between September 2017 and April 2019, we constructed fluorescence intensity curves of the hepatic arterial signal and examined their relationship with the occurrence of early hepatic arterial occlusion (thrombosis or stenosis). Early hepatic arterial occlusion occurred in 7 patients (7.8%), including 3 thrombosis and 4 stenosis. Among various parameters of the flow intensity curve analyzed, the ratio of peak to plateau fluorescence intensity and the jagged wave pattern at the plateau phase were closely associated with this dreaded event. By combining the ratio of peak to plateau at 0.275 and a jagged wave, we best predicted the occurrence of early hepatic arterial occlusion and thrombosis, with sensitivity/specificity of 0.86/0.98 and 1.00/0.94, respectively. Through a simple composite parameter, the indocyanine green fluorescence imaging system is an additional and promising intraoperative modality for identifying recipients of transplant at high risk of developing early hepatic arterial occlusion. This tool could assist the surgeon in the decision to redo the anastomosis despite normal Doppler ultrasonography.

Intraoperative Radiation Therapy for Early-Stage Breast Cancer: Updated Outcomes from a Single-Institution Experience.

BACKGROUND: Increasingly, data have supported the use of partial-breast irradiation (PBI) for low-risk patients after breast-conserving surgery, with techniques allowing for completion of treatment in 1-3 weeks. Intraoperative radiation therapy (IORT) is an alternative to PBI. Our institution had used low-energy photon IORT (TARGIT) for more than a decade. The initial results demonstrated a 2% local recurrence rate with a short follow-up period of 2 years. This report presents updated outcomes during with 5-year follow-up. METHODS: A review of an institutional review board (IRB)-approved institutional registry was performed. The review identified 215 patients with early-stage breast cancer (stages 0-IIA) who received IORT. At the time of surgery, IORT was delivered with 20 Gy in a single fraction, with 5.1% (n = 11) of patients receiving additional whole-breast irradiation (WBI). RESULTS: The mean age at diagnosis was 71 years (range, 49-98 years), and the median follow-up was 5.7 years (interquartile range [IQR], 4.2-7.0 years). Of the 215 patients, 2.8% (n = 6) had ductal carcinoma in situ (DCIS), 90.7% (n = 195) had T1 disease, and 6.5% (n = 14) had T2 disease. Endocrine therapy was prescribed for 79% and chemotherapy for 1.4% of the patients. The 5-year rates were 5.3% for local recurrence, 6.4% for locoregional recurrence, and 2.7% for distant metastases. At 5 years, 93% of the patients were alive. CONCLUSIONS: The 5-year outcomes with TARGIT IORT demonstrated high rates of local recurrence, exceeding those seen with alternative modern approaches. The local recurrence outcomes with IORT are more consistent with studies omitting radiation following breast-conserving surgery, using endocrine therapy alone. Consistent with current guidelines and previous data, TARGIT IORT should not be used as monotherapy outside prospective clinical trials.

Continuous Wound Irrigation and Intraoperative Methadone Decreases Opioid Use and Shortens Length of Stay After CRS/HIPEC.

BACKGROUND: Epidural analgesia is resource and labor intense and may limit postoperative management options and delay discharge. This study compared postoperative outcomes after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) with epidural analgesia versus continuous wound infusion system (CWIS) with/without intraoperative methadone. METHODS: A single-institution, retrospective chart review was performed including all patients undergoing open CRS/HIPEC from 2018 to 2021. Patient demographics, surgical characteristics, length of stay, and in-hospital analgesic use were reviewed. In-hospital opioid exposure in morphine milligram equivalents (MME) was calculated. Multivariate analysis (MVA) for mean total and daily opioid exposure was conducted. RESULTS: A total of 157 patients were included. Fifty-three (34%) had epidural analgesia, 96 (61%) had CWIS, and 79 (50%) received methadone. Length of stay was significantly shorter with CWIS + methadone versus epidural (7 vs. 8 days, p < 0.01). MVA showed significantly lower mean total and daily opioid exposure with CWIS+methadone versus epidural (total: 252.8 ± 17.7 MME vs. 486.8 ± 86.6 MME; odds ratio [OR] 0.72, 95% confidence interval [CI] 0.52-0.98, p = 0.04; Daily: 32.8 ± 2.0 MME vs. 51.9 ± 5.7 MME, OR 0.72, 95% CI 0.52-0.99, p ≤ 0.05). The CWIS-only group (n = 17) had a significantly lower median oral opioid exposure versus epidural (135 MME vs. 7.5 MME, p < 0.001) and longer length of stay versus CWIS + methadone (9 vs. 7 days, p = 0.04), There were no CWIS or methadone-associated complications and one epidural abscess. CONCLUSIONS: CWIS + methadone safely offers better pain control with less in-hospital opioid use, shorter length of stay, and decreased resource utilization compared with epidural analgesia in patients undergoing CRS-HIPEC.

Reducing re-excision rates in breast conserving surgery with Margin Probe: systematic review.

INTRODUCTION: Different intraoperative techniques with varying levels of evidence are available to decrease positive surgical margins during breast conserving surgery. The aim of this review is to assess the effectiveness of the MarginProbe® device as an intraoperative adjunct tool in reducing positive surgical margins, and subsequently exploring the effect on patient re-excision rates. METHODOLOGY: A systematic review of the available medical literature was conducted from 2007 to March 2022. A literature search of Cochrane, PubMed and Embase by two independent reviewers reviwers was performed to identify eligible articles looking at the primary outcome of percentage reduction in patient re-excision rates using MarginProbe®. Secondary outcomes analysed were comparison of tissue volume removed, absolute and relative reduction in re-excision rate, cosmetic outcome, as well as MarginProbe® sensitivity and specificity. RESULTS: A total of 12 full text articles were identified. An independent samples t-test using a total of 2680 patients found a 54.68 per cent reduction in re-excision rate with the use of MarginProbe®, which was statistically significant with a large effect size (P < 0.001; d = 1.826). Secondary outcomes showed a relatively higher sensitivity of the MarginProbe® device, at the expense of decreased specificity, and no significant impact on cosmesis and volume of breast tissue excised. CONCLUSION: MarginProbe® is an effective intraoperative adjunct in breast-conservation surgery that reduces patient re-excision rates, with no adverse effects relating to breast cosmesis or increase in volume of excised tissue.

Major complications after intraoperative radiotherapy with low-energy x-rays in early breast cancer.

PURPOSE: To describe and analyze major local complications after intraoperative radiotherapy (IORT) with low-energy x­rays during breast-conserving surgery (BCS) in early breast cancer. METHODS: Ten women out of 408 who were treated with IORT between 2002 and 2017 and subsequently developed a severe local complication requiring surgical intervention were retrospectively identified and analyzed. Demographic, clinical, and surgical parameters as well as complication characteristics and treatment methods were evaluated. RESULTS: At initial presentation, eight patients (80%) showed redness, six (60%) seroma, six (60%) wound infection, six (60%) suture dehiscence, and four (40%) induration of the former surgical area. Hematoma and necrosis were observed in one case (10%) each. Time interval until appearance of the first symptoms ranged from directly postoperative until 15 years postoperatively (median 3.1 months). Initial treatment modalities comprised antibiotic therapy (n = 8/80%) and transcutaneous aspiration of seroma (n = 3/30%). In the majority of patients, smaller surgical interventions (excision of a necrotic area/fistula [n = 6/60%] or secondary suture [n = 5/50%]) were sufficient to overcome the complication, yet larger interventions such as complex flap surgery and mastectomy were necessary in one patient each. CONCLUSION: IORT is an efficient and safe treatment method as < 2.5% of all IORT patients experienced major local complications. However, it seems to pose the risk of causing severe local complications that may require lengthy and burdensome treatment. Thorough preoperative counseling, implementation of recommended intraoperative precautions, and high vigilance for first symptoms of complications during follow-up appointments are necessary measures.

Intraoperative radiotherapy (IORT) of early breast cancer with low-energy x-rays in breast-conserving surgery : Prospective identification of pre- and intraoperative factors influencing the feasibility of IORT.

PURPOSE: The aim of this study is to identify pre- and intraoperative factors indicating the feasibility of intraoperative radiotherapy (IORT) during breast-conserving surgery (BCS). MATERIALS AND METHODS: From January 2018 to December 2019, a total of 128 women undergoing BCS due to early breast cancer were included in this prospective observational study, independent of whether IORT was planned or not. Patient and tumor characteristics as well as surgical parameters that could potentially influence the feasibility of IORT were recorded for the entire collective. In addition, a preoperative senological assessment was performed and analyzed to assess the feasibility of IORT. Logistic regression was then used to identify relevant preoperative parameters and to generate a formula predicting the feasibility of IORT. RESULTS: Of the 128 included women undergoing BCS, 46 were preoperatively rated to be feasible, 20 to be questionably feasible for IORT. Ultimately, IORT was realized in 30 patients. The most frequent reasons for omission of IORT were insufficient tumor-to-skin distance and/or an excessively large tumor cavity. Small clinical tumor size and large tumor-to-skin distance according to preoperative ultrasound were significantly related to accomplishment of IORT. CONCLUSION: We observed that preoperative ultrasound-based tumor-skin distance is a significant factor in addition to already known parameters to predict feasibility of IORT. Based on our findings we developed a formula to optimize IORT planning which might serve as an additional tool to improve patient selection for IORT in early breast cancer.

Single-dose Intraoperative Methadone for Pain Management in Pediatric Tonsillectomy: A Randomized Double-blind Clinical Trial.

BACKGROUND: More than 500,000 elective tonsillectomies are performed in U.S. children annually. Pain after pediatric tonsillectomy is common, often severe, and undertreated. There is no consensus on the optimal management of perioperative tonsillectomy pain. Methadone, with an elimination half-life of 1 to 2 days, has a longer duration of effect than short-duration opioids such as fentanyl. The primary objective of this study was to investigate the intraoperative use of methadone for pediatric tonsillectomy. It tested the hypothesis that methadone would result in less postoperative opioid use compared with short-duration opioids in children after tonsillectomy. METHODS: This double-blind, randomized, parallel group trial in children (3 to 17 yr) undergoing tonsillectomy compared single-dose intravenous methadone (0.1 mg/kg then 0.15 mg/kg age-ideal body weight, in a dose escalation paradigm) versus as-needed short-duration opioid (fentanyl) controls. Opioid use, pain, and side effects were assessed in-hospital and 7 days postoperatively via electronic surveys. The primary outcome was total 7-day opioid use in oral morphine equivalents per kilogram (kg). Secondary outcomes were opioid use in the postanesthesia care unit, daily pain scores, and total number of 7-day opioid doses used. RESULTS: Data analysis included 60 children (20/group), age 5.9 ± 3.7 yr (mean ± SD; median, 4; range, 3 to 17). Total 7-day opioid use (oral morphine equivalents per kg median [interquartile range]) was 1.5 [1.2, 2.1] in controls, 0.9 [0.1, 1.4] after methadone 0.1 mg/kg (P = 0.045), and 0.5 [0, 1.4] after methadone 0.15 mg/kg (P = 0.023). Postanesthesia care unit opioid use (oral morphine equivalents per kg) in controls was 0.15 [0.1, 0.3], 0.04 [0, 0.1] after methadone 0.1 mg/kg (P = 0.061). and 0.0 [0, 0.1] after methadone 0.15 mg/kg (P = 0.021). Postoperative pain scores were not different between groups. No serious opioid-related adverse events occurred. CONCLUSIONS: This small initial study in children undergoing tonsillectomy found that single-dose intraoperative methadone at 0.15 mg/kg age ideal body weight was opioid-sparing compared with intermittent fentanyl.

Intraoperative radiotherapy combined with spinal stabilization surgery-a novel treatment strategy for spinal metastases based on a first single-center experiences.

INTRODUCTION: Current treatment of spinal metastases (SM) aims on preserving spinal stability, neurological status, and functional status as well as achieving local control. It consists of spinal surgery followed by radiotherapy and/or systemic treatment. Adjuvant therapy usually starts with a delay of a few weeks to prevent wound healing issues. Intraoperative radiotherapy (IORT) has previously been successfully applied during brain tumor, breast and colorectal carcinoma surgery but not in SM, including unstable one, to date. In our case series, we describe the feasibility, morbidity and mortality of a novel treatment protocol for SM combining stabilization surgery with IORT. METHODS: Single center case series on patients with SM. Single session stabilization by navigated open or percutaneous procedure using a carbon screw-rod system followed by concurrent 50 kV photon-IORT (ZEISS Intrabeam). The IORT probe is placed via a guide canula using navigation, positioning is controlled by IOCT or 3D-fluroscopy enabling RT isodose planning in the OR. RESULTS: 15 (8 female) patients (71 ± 10y) received this treatment between 07/22 and 09/23. Median Spinal Neoplastic Instability Score was 8 [7-10] IQR. Most metastasis were located in the thoracic (n = 11, 73.3%) and the rest in the lumbar (n = 4, 26.7%) spine. 9 (60%) patients received open, 5 (33%) percutaneous stabilization and 1 (7%) decompression only. Mean length of surgery was 157 ± 45 min. Eleven patients had 8 and 3 had 4 screws placed. In 2 patients radiotherapy was not completed due to bending of the guide canula with consecutive abortion of IORT. All other patients received 8 Gy isodoses at mdn. 1.5 cm [1.1-1.9, IQR] depth during 2-6 min. The patients had Epidural Spinal Cord Compression score 1a-3. Seven patients (46.7%) experienced adverse events including 2 surgical site infection (one 65 days after surgery). CONCLUSION: 50 kV photon IORT for SM and consecutive unstable spine needing surgical intervention is safe and feasible and can be a promising technique in selected cases.

Intraoperative radiotherapy after neurosurgical resection of brain metastases as institutional standard treatment- update of the oncological outcome form a single center cohort after 117 procedures.

PURPOSE: Stereotactic radiotherapy (SRT) is the predominant method for the irradiation of resection cavities after resection of brain metastases (BM). Intraoperative radiotherapy (IORT) with 50 kV x-rays is an alternative way to irradiate the resection cavity focally. We have already reported the outcome of our first 40 IORT patients treated until 2020. Since then, IORT has become the predominant cavity treatment in our center due to patients´ choice. METHODS: We retrospectively analyzed the outcomes of all patients who underwent resection of BM and IORT between 2013 and August 2023 at Augsburg University Medical Center (UKA). RESULTS: We identified 105 patients with 117 resected BM treated with 50 kV x-ray IORT. Median diameter of the resected metastases was 3.1 cm (range 1.3 - 7.0 cm). Median applied dose was 20 Gy. All patients received standardized follow-up (FU) including three-monthly MRI of the brain. Mean FU was 14 months, with a median MRI FU for patients alive of nine months. Median overall survival (OS) of all treated patients was 18.2 months (estimated 1-year OS 57.7%). The observed local control (LC) rate of the resection cavity was 90.5% (estimated 1-year LC 84.2%). Distant brain control (DC) was 61.9% (estimated 1-year DC 47.9%). Only 16.2% of all patients needed WBI in the further course of disease. The observed radio necrosis rate was 2.6%. CONCLUSION: After 117 procedures IORT still appears to be a safe and appealing way to perform cavity RT after neurosurgical resection of BM with low toxicity and excellent LC.

Omission of intraoperative drain placement during robotic partial nephrectomy and robotic radical prostatectomy is safe: an analysis of 18,000 patients.

PURPOSE: Placement of a drain during robotic assisted partial nephrectomy (RAPN) and robotic assisted radical prostatectomy (RARP) is standard practice for many urologists and can aid in assessment and management of complications such as urine leak, lymphocele, or bleeding. However, drain placement can cause discomfort and delay patient discharge, with questionable benefit. We aim to assess the correlation between drain placement with post operative complications. METHODS: The NSQIP targeted database was queried for patients who underwent RAPN or RARP from 2019 to 2021. Our primary outcomes included 30-day complication rates stratified by intraoperative drain placement. Secondary outcomes included procedure-specific complications, length of stay (LOS), and readmissions. Multivariable regression analyses, with Bonferroni correction, were performed for each post-operative complication. RESULTS: We identified 4738 and 13,948 patients who underwent RAPN and RARP, respectively. Drains were not placed in 2258 (47.7%) and 6700 (48%) patients, respectively. On adjusted multivariable analysis in the RAPN cohort, omission of drain placement was associated with decreased LOS (ß -0.45; 99.58% CI [-0.59, -0.32]) but no difference in overall complication rates. After adjusted analysis in the RARP cohort, omission of drain placement was associated with decreased risk of any complication (OR 0.73 [0.62-0.87]), infectious complication (OR 0.66 [0.49-0.89]), and LOS (ß -0.30 [-0.37, -0.24]). CONCLUSIONS: Using a large contemporary database, this study demonstrates that omission of drains during RAPN and RARP was safe without increased risk of postoperative complications. Despite inherent selection bias in this cohort, our data suggests that routine drain placement is not necessary for these procedures.

Preoperative and intraoperative tirofiban during endovascular thrombectomy in large vessel occlusion stroke due to large artery atherosclerosis.

BACKGROUND AND PURPOSE: The aim of this study is to investigate the efficacy and safety of preoperative versus intraoperative tirofiban in patients with large vessel occlusion (LVO) due to large artery atherosclerosis (LAA). METHODS: This is a retrospective multicenter cohort study based on the RESCUE-RE (Registration Study for Critical Care of Acute Ischemic Stroke After Recanalization) trial enrolling patients with anterior circulation LVO classified as LAA within 24 h of onset. Patients were divided into three groups: preoperative tirofiban (PT), intraoperative tirofiban (IT), and no tirofiban (NT). Propensity score matching (PSM) was used to balance baseline characteristics. The efficacy outcomes included 90-day functional independence (modified Rankin Scale score = 0-2) and early partial recanalization (EPR; defined as a modified Thrombolysis in Cerebral Infarction score = 1-2a). The safety outcomes included symptomatic intracranial hemorrhage (sICH). RESULTS: A total of 104 matched triplets were obtained through PSM. Compared with NT, PT increased 90-day functional independence (60.8% vs. 42.3%, p = 0.008) and EPR (42.7% vs. 18.3%, p < 0.001) rate, with a tendency to increase the asymptomatic intracranial hemorrhage (aICH) proportion (28.8% vs. 18.3%, p = 0.072). Compared with IT, PT had a higher 90-day functional independence (60.8% vs. 45.2%, p = 0.025) and EPR (42.7% vs. 20.2%, p = 0.001) rate, with no significant difference in sICH (14.4% vs. 7.7%, p = 0.122) and aICH (28.8% vs. 21.2%, p = 0.200). Compared with NT, IT had a lower 90-day mortality rate (9.6% vs. 24.0%, p = 0.005). CONCLUSIONS: Tirofiban shows good adjuvant therapy potential in acute ischemic stroke-LVO due to LAA patients. PT is associated with higher rates of EPR and better therapeutic efficacy. In addition, EPR may be a potential way to improve prognosis.

Intraoperative indocyanine green angiography in preventing hypoparathyroidism after thyroid cancer surgery.

BACKGROUND: The aim of this study was to determine whether the use of indocyanine green angiography to identify devascularized parathyroids during thyroidectomy for thyroid cancer would decrease the rates of postoperative hypoparathyroidism. METHODS: Retrospective study of patients who had undergone total thyroidectomy for treatment of thyroid cancer between March 2021 and March 2023. The indocyanine group included patients with all four parathyroids identified and evaluated by indocyanine green angiography at the end of the procedure. Those with parathyroid glands classified with no vascularization had the glands autotransplanted. A group without indocyanine angiography was used to compare results. RESULTS: The analysis included 100 patients in each group. Indocyanine angiography identified 14.75% of devascularized parathyroids at surgery. The number of parathyroids with a score of 2 (i.e., good vascularization) was not a safe predictor of normal parathyroid hormone levels after surgery. Indeed, 29.2% of the patients with three parathyroids with a score of 2 developed transient hypoparathyroidism. Permanent hypoparathyroidism occurred in 7% of the patients without indocyanine group and in none of the patients in the indocyanine group (p = 0.014). CONCLUSION: Intraoperative angiography with indocyanine green could contribute to reduce the occurrence of permanent hypoparathyroidism in patients undergoing surgical treatment for thyroid cancer.

The utility of intraoperative marrow margin frozen section in extremity bone sarcoma resection.

BACKGROUND AND OBJECTIVES: Intraoperative frozen section analysis is commonly used to evaluate marrow margins during extremity bone sarcoma resections, but its efficacy in the era of magnetic resonance imaging is debated. This study aimed to compare the accuracy of intraoperative frozen section assessment with final pathology, assess its correlation with gross intraoperative margin assessment, and evaluate its impact on surgical decision making. METHODS: Consecutive patients undergoing extremity bone sarcoma resections from 2010 to 2022 at a single sarcoma center were included. Intraoperative frozen section and gross margin assessments were compared to final pathology using positive predictive values (PPV) and negative predictive values (NPV). Changes in surgical decisions due to positive intraoperative margins were recorded. RESULTS: Of 166 intraoperative frozen section marrow margins, four were indeterminant/positive, with two false positive/indeterminant findings and two false negatives compared to final pathology. Gross intraoperative assessment had no false positives and two false negatives. Frozen section analysis yielded a PPV of 50% (95% confidence interval [CI]: 16%-84%) and NPV of 98.8% (95% CI: 97%-100%), while gross assessment had a PPV of 100% (95% CI: 16%-100%) and NPV of 98.8% (95% CI: 97%-100%). Positive frozen section margins led to additional resections in three of four cases. CONCLUSIONS: Intraoperative frozen section analysis did not offer added clinical value beyond gross margin assessment in extremity bone sarcoma resections. It exhibited a low PPV and led to unnecessary additional resections. Gross intraoperative assessment proved adequate for margin evaluation, potentially saving time and resources.

Intraoperative radiation therapy for pediatric sarcomas and other solid tumors.

PURPOSE: To evaluate local failure (LF) and toxicity after intraoperative radiation therapy (IORT) in pediatric solid tumors (ST). METHODS: A single-institution retrospective study of 96 pediatric patients (108 applications) with ST treated from 1995 to 2022 with IORT. LF was calculated via cumulative incidence function and overall survival (OS) by Kaplan-Meier method, both from the day of surgery. RESULTS: Median age at time of IORT was 8 years (range: 0.8-20.9 years). Median follow-up for all patients and surviving patients was 16 months and 3 years, respectively. The most common histologies included rhabdomyosarcoma (n = 42), Ewing sarcoma (n = 10), and Wilms tumor (n = 9). Most (95%) received chemotherapy, 37% had prior external beam radiation therapy to the site of IORT, and 46% had a prior surgery for tumor resection. About half (54%) were treated with upfront IORT to the primary tumor due to difficult circumstances such as very young age or challenging anatomy. The median IORT dose was 12 Gy (range: 4-18 Gy), and median area treated was 24 cm2 (range: 2-198 cm2). The cumulative incidence of LF was 17% at 2 years and 23% at 5 years. Toxicity from IORT was reasonable, with postoperative complications likely related to IORT seen in 15 (16%) patients. CONCLUSION: Our study represents the largest and most recent analysis of efficacy and safety of IORT in pediatric patients with ST. Less than one quarter of all patients failed locally with acceptable toxicities. Overall, IORT is an effective and safe technique to achieve local control in patients with challenging circumstances.

Efficacy and safety of intraoperative controlled hypotension: a systematic review and meta-analysis of randomised trials.

BACKGROUND: Intraoperative controlled hypotension improves surgical field visibility by reducing blood loss (efficacy) but poses potential risks linked to organ hypoperfusion (safety). The use of controlled hypotension persists despite increasing evidence of associations between intraoperative inadvertent hypotension and adverse outcomes. Therefore, we tested the hypothesis that the focus and results of intraoperative controlled hypertension research differ across anaesthesia and surgery investigators because of differing priorities. METHODS: We systematically reviewed randomised trials comparing controlled hypotension with usual care with trials categorised by investigators' affiliation. RESULTS: We identified 48 eligible trials, of which 37 were conducted by anaesthesia investigators and 11 by surgery investigators. For the primary outcome, 54% of the anaesthesia-led trials focused on safety, whereas all (100%) surgery-led trials focused on efficacy (P=0.004). Compared with usual care, mean arterial pressure in controlled hypotension was 23% (95% confidence interval [CI] 17-29%) lower in anaesthesia trials and 30% (95% CI 14-37%) lower in surgery trials; estimated blood loss was 44% (95% CI 30-55%) less in anaesthesia trials and 38% (95% CI 30-49%) less in surgery trials. Overall, blood loss was reduced by 43% (95% CI 32-53%), and trial sequential analysis supported an efficacy conclusion. Mean arterial pressure and estimated blood loss reductions were associated (R2=0.41, P=0.002). All trials were underpowered for safety outcomes, and none adequately evaluated myocardial or renal injury. CONCLUSIONS: Anaesthesia researchers prioritised safety outcomes, whereas surgery researchers emphasised efficacy in controlled hypotension trials. Controlled hypotension significantly reduces blood loss. In contrast, safety outcomes were poorly studied. Given increasing observational evidence linking inadvertent hypotension to myocardial and renal injury, the safety of controlled hypotension remains to be addressed. SYSTEMATIC REVIEW PROTOCOL: PROSPERO (CRD42023450397).

Intraoperative dexamethasone and chronic postsurgical pain: a propensity score-matched analysis of a large trial.

BACKGROUND: Dexamethasone has been shown to reduce acute pain after surgery, but there is uncertainty as to its effects on chronic postsurgical pain (CPSP). We hypothesised that in patients undergoing major noncardiac surgery, a single intraoperative dose of dexamethasone increases the incidence of CPSP. METHODS: We devised a propensity score-matched analysis of the ENIGMA-II trial CPSP dataset, aiming to compare the incidence of CPSP in patients who had received dexamethasone or not 12 months after major noncardiac surgery. The primary outcome was the incidence of CPSP. We used propensity score matching and inverse probability weighting to balance baseline variables to estimate the average marginal effect of dexamethasone on patient outcomes, accounting for confounding to estimate the average treatment effect on those treated with dexamethasone. RESULTS: We analysed 2999 patients, of whom 116 of 973 (11.9%) receiving dexamethasone reported CPSP, and 380 of 2026 (18.8%) not receiving dexamethasone reported CPSP, unadjusted odds ratio 0.76 (95% confidence interval 0.78-1.00), P=0.052. After propensity score matching, CPSP occurred in 116 of 973 patients (12.2%) receiving dexamethasone and 380 of 2026 patients (13.8%) not receiving dexamethasone, adjusted risk ratio 0.88 (95% confidence interval 0.61-1.27), P=0.493. There was no difference between groups in quality of life or pain interference with daily activities, but 'least pain' (P=0.033) and 'pain right now' (P=0.034) were higher in the dexamethasone group. CONCLUSIONS: Dexamethasone does not increase the risk of chronic postsurgical pain after major noncardiac surgery. CLINICAL TRIAL REGISTRATION: Open Science Framework Registration DOI https://doi.org/10.17605/OSF.IO/ZDVB5.

Intraoperative kidney replacement therapy in acute liver failure.

Paediatric acute liver failure (PALF) is often characterised by its rapidity of onset and potential for significant morbidity and even mortality. Patients often develop multiorgan dysfunction/failure, including severe acute kidney injury (AKI). Whilst the management of PALF focuses on complications of hepatic dysfunction, the associated kidney impairment can significantly affect patient outcomes. Severe AKI requiring continuous kidney replacement therapy (CKRT) is a common complication of both PALF and liver transplantation. In both scenarios, the need for CKRT is a poor prognostic indicator. In adults, AKI has been shown to complicate ALF in 25-50% of cases. In PALF, the incidence of AKI is often higher compared to other critically ill paediatric ICU populations, with reports of up to 40% in some observational studies. Furthermore, those presenting with AKI regularly have a more severe grade of PALF at presentation. Observational studies in the paediatric population corroborate this, though data are not as robust-mainly reflecting single-centre cohorts. Perioperative benefits of CKRT include helping to clear water-soluble toxins such as ammonia, balancing electrolytes, preventing fluid overload, and managing raised intracranial pressure. As liver transplantation often takes 6-10 h, it is proposed that these benefits could be extended to the intraoperative period, avoiding any hiatus. Intraoperative CKRT (IoCKRT) has been shown to be practicable, safe and may help sicker recipients tolerate the operation with outcomes analogous with less ill patients not requiring IoCKRT. Here, we provide a comprehensive guide describing the rationale, practicalities, and current evidence base surrounding IoCKRT during transplantation in the paediatric population.