The best of both worlds: a hybrid approach for optimal pre- and intraoperative identification of sentinel lymph nodes

Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas

Neoadjuvant immunotherapy with nivolumab and ipilimumab induces major pathological responses in patients with head and neck squamous cell carcinoma

Surgery for locoregionally advanced head and neck squamous cell carcinoma (HNSCC) results in 30-50% five-year overall survival. In IMCISION (NCT03003637), a non-randomized phase Ib/IIa trial, 32 HNSCC patients are treated with 2 doses (in weeks 1 and 3) of immune checkpoint blockade (ICB) using nivolumab (NIVO MONO, n = 6, phase Ib arm A) or nivolumab plus a single dose of ipilimumab (COMBO, n = 26, 6 in phase Ib arm B, and 20 in phase IIa) prior to surgery. Primary endpoints are feasibility to resect no later than week 6 (phase Ib) and primary tumor pathological response (phase IIa). Surgery is not delayed or suspended for any patient in phase Ib, meeting the primary endpoint. Grade 3-4 immune-related adverse events are seen in 2 of 6 (33%) NIVO MONO and 10 of 26 (38%) total COMBO patients. Pathological response, defined as the %-change in primary tumor viable tumor cell percentage from baseline biopsy to on-treatment resection, is evaluable in 17/20 phase IIa patients and 29/32 total trial patients (6/6 NIVO MONO, 23/26 COMBO). We observe a major pathological response (MPR, 90-100% response) in 35% of patients after COMBO ICB, both in phase IIa (6/17) and in the whole trial (8/23), meeting the phase IIa primary endpoint threshold of 10%. NIVO MONO's MPR rate is 17% (1/6). None of the MPR patients develop recurrent HSNCC during 24.0 months median postsurgical follow-up. FDG-PET-based total lesion glycolysis identifies MPR patients prior to surgery. A baseline AID/APOBEC-associated mutational profile and an on-treatment decrease in hypoxia RNA signature are observed in MPR patients. Our data indicate that neoadjuvant COMBO ICB is feasible and encouragingly efficacious in HNSCC.Immune checkpoint blockade has become standard care for patients with recurrent metastatic head and neck squamous cell carcinoma (HNSCC). Here the authors present the results of a non-randomized phase Ib/IIa trial, reporting safety and efficacy of neoadjuvant nivolumab monotherapy and nivolumab plus ipilimumab prior to standard-of-care surgery in patients with HNSCC. .Otorhinolaryngolog

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

A hybrid registration method using the mandibular bone surface for electromagnetic navigation in mandibular surgery

Purpose To utilize navigated mandibular (reconstructive) surgery, accurate registration of the preoperative CT scan with the actual patient in the operating room (OR) is required. In this phantom study, the feasibility of a noninvasive hybrid registration method is assessed. This method consists of a point registration with anatomic landmarks for initialization and a surface registration using the bare mandibular bone surface for optimization. Methods Three mandible phantoms with reference notches on two osteotomy planes were 3D printed. An electromagnetic tracking system in combination with 3D Slicer software was used for navigation. Different configurations, i.e., different surface point areas and number and configuration of surface points, were tested with a dentate phantom (A) in a metal-free environment. To simulate the intraoperative environment and different anatomies, the registration procedure was also performed with an OR bed using the dentate phantom and two (partially) edentulous phantoms with atypical anatomy (B and C). The accuracy of the registration was calculated using the notches on the osteotomy planes and was expressed as the target registration error (TRE). TRE values of less than 2.0 mm were considered as clinically acceptable. Results In all experiments, the mean TRE was less than 2.0 mm. No differences were found using different surface point areas or number or configurations of surface points. Registration accuracy in the simulated intraoperative setting was-mean (SD)-0.96 (0.22), 0.93 (0.26), and 1.50 (0.28) mm for phantom A, phantom B, and phantom C. Conclusion Hybrid registration is a noninvasive method that requires only a small area of the bare mandibular bone surface to obtain high accuracy in phantom setting. Future studies should test this method in clinical setting during actual surgery

Ultrasound aids in intraoperative assessment of deep resection margins of squamous cell carcinoma of the tongue

We wanted to find out whether ultrasound (US) can be used to assess the deep resection margins after excision of squamous cell carcinoma (SCC) of the tongue, as intraoperative feedback on their condition might help to prevent them being too close. Resected specimens of cancers of the tongue from 31 patients with SCC of the tongue were suspended in US gel and scanned with a small 5-10 MHz US probe. The tumour was readily visible and US could differentiate it from muscle tissue. The margin of normal tongue musculature surrounding the tumour was measured on the US images, and the minimal resection margin was noted and compared with that reported by the histopathologist. The mean (SD) deep resection margins measured on the US images differed by 1.1 (0.9) mm from those reported by the histopathologist (Pearson's correlation coefficient: 0.79, p < 0.01). The US measurements took a maximum of five minutes. It is feasible to use US to assess resection specimens of SCC of the tongue as an adjunct to existing strategies (such as frozen section analysis) to help achieve the desired deep surgical margins. The method is easy to incorporate into surgical routine as it does not take long

Assessment of the deep resection margin during oral cancer surgery: A systematic review

The main challenge for radical resection in oral cancer surgery is to obtain adequate resection margins. Especially the deep margin, which can only be estimated based on palpation during surgery, is often reported inadequate. To increase the percentage of radical resections, there is a need for a quick, easy, minimal invasive method, which assesses the deep resection margin without interrupting or prolonging surgery. This systematic review provides an overview of technologies that are currently being studied with the aim of fulfilling this demand. A literature search was conducted through the databases Medline, Embase and the Cochrane Library. A total of 62 studies were included. The results were categorized according to the type of technique: ‘Frozen Section Analysis’, ‘Fluorescence’, ‘Optical Imaging’, ‘Conventional imaging techniques’, and ‘Cytological assessment’. This systematic review gives for each technique an overview of the reported performance (accuracy, sensitivity, specificity, positive predictive value, negative predictive value, or a different outcome measure), acquisition time, and sampling depth. At the moment, the most prevailing technique remains frozen section analysis. In the search for other assessment methods to evaluate the deep resection margin, some technologies are very promising for future use when effectiveness has been shown in larger trials, e.g., fluorescence (real-time, sampling depth up to 6 mm) or optical techniques such as hyperspectral imaging (real-time, sampling depth few mm) for microscopic margin assessment and ultrasound (less than 10 min, sampling depth several cm) for assessment on a macroscopic scale

Surgical site complications after parotid gland surgery for benign tumors in a centralized setting: A Clavien-Dindo class cohort analysis

Background: Surgical resection is the standard of care for parotid gland tumors. Comprehensive reports on the surgical complications of parotidectomy are lacking. This study focuses on surgical wound complications of parotid gland surgery. Patients and methods: In the period 2002–2012, 390 consecutive patients (395 procedures) who underwent parotid gland surgery were selected for retrospective analysis. Based on subsequent management, the impact of surgical site complications was graded by the Clavien-Dindo Classification (CDC). Results: In 83 (21.0%) of the procedures, at least one complication was registered. In total, 118 complications were described. Rated to CDC, 61 patients (15.4%) were graded as class 2 or higher. This implies therapy was dictated. Fortyfive (11.4%) of the complications were surgical site infections (SSI). In 9 patients (2.3%) surgical complications required a surgical intervention under general anesthesia (CDC class 3b), and in 19 patients (4.8%) other invasive treatment (CDC class 3a) was needed. Conclusions: The Clavien-Dindo Classification proved to be very useful for retrospective registration of surgical complications. Of the 61 patients, 33 were managed by conservative therapy. No risk profile was found for patients at risk for direct surgical complications

c-MET receptor-targeted fluorescence on the road to image-guided surgery in penile squamous cell carcinoma patients

In penile squamous cell carcinoma (pSCC), primary surgery aims to obtain oncologically safe margins while minimizing mutilation. Surgical guidance provided by receptor-specific tracers could potentially improve margin detection and reduce unnecessary excision of healthy tissue. Here, we present the first results of a prospective feasibility study for real-time intraoperative visualization of pSCC using a fluorescent mesenchymal-epithelial transition factor (c-MET) receptor targeting tracer (EMI-137). Methods: EMI137 tracer performance was initially assessed ex vivo (n = 10) via incubation of freshly excised pSCC in a solution containing EMI137 (500 nM). The in vivo potential of c-MET targeting and intraoperative tumor visualization was assessed after intravenous administration of EMI-137 to 5 pSCC patients scheduled for surgical resection using a cyanine-5 fluorescence camera. Fluorescence imaging results were related to standard pathologic tumor evaluation and c-MET immunohistochemistry. Three of the 5 in vivo patients also underwent a sentinel node resection after local administration of the hybrid tracer indocyanine green- 99mTc-nanocolloid, which could be imaged using a near-infrared fluorescence camera. Results: No tracer-related adverse events were encountered. Both ex vivo and in vivo, EMI-137 enabled c-MET-based tumor visualization in all patients. Histopathologic analyses showed that all pSCCs expressed c-MET, with expression levels of at least 70% in 14 of 15 patients. Moreover, the highest c-MET expression levels were seen on the outside rim of the tumors, and a visual correlation was found between c-MET expression and fluorescence signal intensity. No complications were encountered when combining primary tumor targeting with lymphatic mapping. As such, simultaneous use of cyanine-5 and indocyanine green in the same patient proved to be approach.Radiolog