Differentiation of pituitary neuroendocrine tumor (PitNET) tissue from surrounding normal tissue during surgery is challenging. A number of fluorescent agents is available for visualization of tissue discrepancy, with the potential of improving total tumor resection. This review evaluates the availability, clinical and technical applicability of the various fluorescent agents within the field of pituitary surgery. According to PRISMA guidelines, a systematic review was performed to identify reports describing results of in vivo application of fluorescent agents. In this review, 15 publications were included. Sodium Fluorescein (FNa) was considered in two studies. The first study reported noticeable fluorescence in adenoma tissue, the second demonstrated the strongest fluorescence in non-functioning pituitary adenomas. 5-Aminolevulinic acid (5-ALA) was investigated in three studies. One study compared laser-based optical biopsy system (OBS) with photo-diagnostic filter (PD) and found that the OBS was able to detect all microadenomas, even when MRI was negative. The second study retrospectively analyzed twelve pituitary adenomas and found only one positive for fluorescence. The third investigated fifteen pituitary adenomas of which one displayed vague fluorescence. Indocyanine green (ICG) was researched in four studies with variable results. Second-Window ICG yielded no significant difference between functioning and non-functioning adenomas in one study, while a second study displayed 4 times higher fluorescence in tumor tissue than in normal tissue. In three studies, OTL38 showed potential in non-functioning pituitary adenomas. At present, evidence for fluorescent agents to benefit total resection of PitNETs is lacking. OTL38 can potentially serve as a selective fluorescent agent in non-functioning pituitary adenomas in the near future.

Introduction Achieving gross total resection and endocrine remission in pituitary neuroendocrine tumours (PitNET) can be challenging, especially in PitNETs with cavernous sinus (CS) invasion, defined as a Knosp grade of 3 or 4. A potential target to identify PitNET tissue is vascular endothelial growth factor A (VEGF-A), which expression is known to be significantly higher in PitNETs with CS invasion. Methods and analysis The aim of this non-randomised, non-blinded, single centre, feasibility and dose-finding phase 1 trial is to determine the feasibility of intraoperative fluorescence imaging detection of PitNET tissue during endoscopic transsphenoidal surgery using the VEGF-A targeting optical agent bevacizumab-800CW (4, 5, 10 or 25 mg). Nine to fifteen patients with a PitNET with a Knosp grade of 3 or 4 will be included. Secondary objectives are: (1) To identify the optimal tracer dose for imaging of PitNET tissue during transsphenoidal surgery for further development in a phase 2 fluorescence molecular endoscopy trial. (2) To quantify fluorescence intensity in vivo and ex vivo with multidiameter single-fibre reflectance, single-fibre fluorescence (MDSFR/SFF) spectroscopy. (3) To correlate and validate both the in vivo and ex vivo measured fluorescence signals with histopathological analysis and immunohistochemical staining. (4) To assess the (sub)cellular location of bevacizumab-800CW by ex vivo fluorescence microscopy. Intraoperative, three imaging moments are defined to detect the fluorescent signal. The tumour-to-background ratios are defined by intraoperative fluorescence in vivo measurements including MDSFR/SFF spectroscopy data and by ex vivo back-table fluorescence imaging. After inclusion of three patients in each dose group, an interim analysis will be performed to define the optimal dose. Ethics and dissemination Approval was obtained from the Medical Ethics Review Board of the University Medical Centre Groningen. Results will be disseminated through national and international journals. The participants and relevant patient support groups will be informed about the results. Trial registration number NCT04212793

Purpose: Achieving endocrine remission by gross total resection is challenging in pituitary neuroendocrine tumours (PitNETs) with cavernous sinus invasion. This study aims to assess the safety, feasibility, and optimal dose for intraoperative fluorescence imaging as an added instrument to discriminate PitNET from surrounding tissue using bevacizumab-800CW, targeting vascular endothelial growth factor A (VEGF-A). Methods: In part I, dose-escalation (0–4∙5-10-25 mg) was performed in 4 groups of 3 patients with PitNETs Knosp grade 3–4. In part II, after interim analysis, the 10 mg and 25 mg groups were expanded to a total of 6 patients. Quantitative fluoroscence molecular endoscopy consisted of wide field fluorescence molecular endoscopy and multi-diameter single fiber reflectance / single fiber fluorescence spectroscopy. Mean fluorescence intensity (MFI) of the fresh surgical specimen was calculated and VEGF-staining was performed. Results: Eighteen patients were included. All doses were well tolerated. Three serious adverse events were registered, but none were tracer-related. Part I showed an adequate in-vivo tumour-to-background ratio for both 10 mg (TBR 2∙00 [1∙86, 2∙19]) and 25 mg (TBR 2∙10, [1∙86, 2∙58]). Part II revealed a substantially higher MFI in the 25 mg group. With both 10 mg and 25 mg a statistically significant difference between tumour and surrounding tissue was detected (p < 0∙0001). All surgical specimens had VEGF-A expression. Conclusion: This study demonstrates the safety and feasibility of quantitative fluorescence molecular endoscopy during PitNET surgery. Both 10 mg and 25 mg bevacizumab-800CW result in clear differentiation in-vivo, with improved contrast ex-vivo (MFI) in the 25 mg group. Trial registration: NCT 04212793 / Study Details| Detection of PitNET Tissue During TSS Using Bevacizumab800CW| ClinicalTrials.gov.

In recent years, patient-specific spinal drill guides (3DPGs) have gained widespread popularity. Several studies have shown that the accuracy of screw insertion with these guides is superior to that obtained using the freehand insertion technique, but there are no studies that make a comparison with computer-assisted surgery (CAS). The aim of this study was to determine whether the accuracy of insertion of spinal screws using 3DPGs is non-inferior to insertion via CAS. A randomized controlled split-spine study was performed in which 3DPG and CAS were randomly assigned to the left or right sides of the spines of patients undergoing fixation surgery. The 3D measured accuracy of screw insertion was the primary study outcome parameter. Sixty screws inserted in 10 patients who completed the study protocol were used for the non-inferiority analysis. The non-inferiority of 3DPG was demonstrated for entry-point accuracy, as the upper margin of the 95% CI (−1.01 mm–0.49 mm) for the difference between the means did not cross the predetermined non-inferiority margin of 1 mm (p < 0.05). We also demonstrated non-inferiority of 3D angular accuracy (p < 0.05), with a 95% CI for the true difference of −2.30°–1.35°, not crossing the predetermined non-inferiority margin of 3° (p < 0.05). The results of this randomized controlled trial (RCT) showed that 3DPGs provide a non-inferior alternative to CAS in terms of screw insertion accuracy and have considerable potential as a navigational technique in spinal fixation.

BACKGROUND: Transsphenoidal surgery (TSS) is the primary treatment of choice in acromegaly. Tumor invasion into the medial wall of the cavernous sinus (MWCS) has been observed, even in Knosp grades 0–2, and may lead to suboptimal surgical results if not additionally resected. Removal of the MWCS may enhance the surgical outcome and result in improved endocrine remission rates. The aim of this study was to evaluate the impact of additional MWCS resection during TSS for acromegaly on endocrine remission and complication rates. The authors prospectively collected the data of acromegaly patients at a large tertiary pituitary referral center. Between January 2023 and January 2025, patients treated with TSS and additional selective resection of the MWCS were included. Patient demographics, tumor characteristics, surgical outcome, and postoperative complications were reviewed. OBSERVATIONS: Twelve patients were included (9 primary TSS, 3 re-TSS). Tumor invasion of the MWCS was confirmed in 91.7%. The median follow-up was 19 months (range 3–27 months). After primary TSS, 8 of 9 patients (88.9%) were in endocrine remission. Following re-TSS, remission was observed in 33.3%. Ultimately, disease control was achieved in 11 of 12 patients (91.7%). No carotid injuries or permanent neurological deficits were observed. LESSONS: Additional selective resection of the MWCS during TSS in acromegaly is a technique that can be safely executed, and it seems to enhance endocrine remission rates especially in primary TSS. https://thejns.org/doi/10.3171/CASE2665