Intraoperative margin assessment during radical prostatectomy: is microscopy frozen in time or ready for digital defrost?

Intraoperative frozen section (IFS) is used with the intention to improve functional and oncological outcomes for patients undergoing radical prostatectomy (RP). High resource requirements of IFS techniques such as NeuroSAFE may preclude widespread adoption, even if there are benefits to patients. Recent advances in fresh-tissue microscopic digital imaging technologies may offer an attractive alternative, and there is a growing body of evidence regarding these technologies. In this narrative review, we discuss some of the familiar limitations of IFS and compare these to the attractive counterpoints of modern digital imaging technologies such as the speed and ease of image generation, the locality of equipment within (or near) the operating room, the ability to maintain tissue integrity, and digital transfer of images. Confocal laser microscopy (CLM) is the modality most frequently reported in the literature for margin assessment during RP. We discuss several imitations and obstacles to widespread dissemination of digital imaging technologies. Among these, we consider how the 'en-face' margin perspective will challenge urologists and pathologists to understand afresh the meaning of positive margin significance. As a part of this, discussions on how to describe, categorize, react to, and evaluate these technologies are needed to improve patient outcomes. Limitations of this review include its narrative structure and that the evidence base in this field is relatively immature but developing at pace.

Accuracy of the LaserSAFE technique for detecting positive surgical margins during robot-assisted radical prostatectomy: blind assessment and inter-rater agreement analysis.

INTRODUCTION AND OBJECTIVES: Fluorescence confocal microscopy (FCM) is a new imaging modality capable of generating digital microscopic resolution scans of fresh surgical specimens, and holds potential as an alternative to frozen section (FS) analysis for intra-operative assessment of surgical margins. Previously, we described the LaserSAFE technique as an application of FCM for margin assessment in robot-assisted radical prostatectomy (RARP) using the Histolog® scanner. This study describes the accuracy and inter-rater agreement of FCM imaging compared to corresponding paraffin-embedded analysis (PA) among four blinded pathologists for the presence of positive surgical margins (PSM). MATERIALS AND METHODS: RARP specimens from patients enrolled in the control arm of the NeuroSAFE PROOF study (NCT03317990) were analysed from April 2022 to February 2023. Prostate specimens were imaged using the Histolog® scanner before formalin fixation and PA. Four trained assessors, blinded to PA, reviewed and analysed FCM images of the posterolateral prostatic surface. RESULTS: A total of 31 prostate specimens were included in the study. PA per lateral side of the prostate identified 11 instances of positive margins. Among the four histopathologists included in our study, FCM achieved a sensitivity of 73-91 and specificity of 94-100% for the presence of PSM. Fleiss' Kappa for inter-rater agreement on PSM was 0.78 (95% confidence interval = 0.64-0.92), indicating substantial agreement. CONCLUSION: This blinded analysis of FCM versus PA among histopathologists with different experience levels demonstrated high accuracy and substantial inter-rater agreement for diagnosing PSM. This supports the role of the FCM as an alternative to FS.

Protocol for a prospective study evaluating circulating tumour cells status to predict radical prostatectomy treatment failure in localised prostate cancer patients (C-ProMeta-1).

BACKGROUND: Treatment decisions in prostate cancer (PCa) rely on disease stratification between localised and metastatic stages, but current imaging staging technologies are not sensitive to micro-metastatic disease. Circulating tumour cells (CTCs) status is a promising tool in this regard. The Parsortix® CTC isolation system employs an epitope-independent approach based on cell size and deformability to increase the capture rate of CTCs. Here, we present a protocol for prospective evaluation of this method to predict post radical prostatectomy (RP) PCa cancer recurrence. METHODS: We plan to recruit 294 patients diagnosed with unfavourable intermediate, to high and very high-risk localised PCa. Exclusion criteria include synchronous cancer diagnosis or prior PCa treatment, including hormone therapy. RP is performed according to the standard of care. Two blood samples (20 ml) are collected before and again 3-months after RP. The clinical team are blinded to CTC results and the laboratory researchers are blinded to clinical information. Treatment failure is defined as a PSA ≥ 0.2 mg/ml, start of salvage treatment or imaging-proven metastatic lesions. The CTC analysis entails enumeration and RNA analysis of gene expression in captured CTCs. The primary outcome is the accuracy of CTC status to predict post-RP treatment failure at 4.5 years. Observed sensitivity, positive and negative predictive values will be reported. Specificity will be presented over time. DISCUSSION: CTC status may reflect the true potential for PCa metastasis and may predict clinical outcomes better than the current PCa progression risk grading systems. Therefore establishing a robust biomarker for predicting treatment failure in localized high-risk PCa would significantly enhance guidance in treatment decision-making, optimizing cure rates while minimizing unnecessary harm from overtreatment. TRIAL REGISTRATION: ISRCTN17332543.

Combined endoscopic transorbital and transnasal approach for the management of a solitary plasmacytoma of the sphenoid bone: A case report and literature review.

Background: Parasellar plasmacytomas are rare neurosurgical entities. Intrinsic characteristics of these tumors, such as adjacent bone erosion and symptoms resulting from invasion and mass effect, may lead to the possibility of a solitary extramedullary plasmacytoma (SEP) as a differential diagnosis. Case Description: We present the case of a 39-year-old male with a 1-month history of bilateral decreased visual acuity, retroocular pulsating pain, and chromatic vision loss. A computed tomography scan of the head revealed a parasellar lesion causing chiasmatic compression, as well as clival, orbital, sphenoidal, and ethmoidal invasion. A combined transorbital and endonasal endoscopic approach was found suitable, and gross total resection was achieved. Histological analysis of the lesion established the diagnosis of a SEP. After radiotherapy, a new magnetic resonance imaging was performed, revealing a recurrence of the lesion with a high grade of invasion. The patient was treated with palliative radiotherapy, as surgical resection did not seem feasible. Conclusion: Surgical resection and radiotherapy may achieve remission of these lesions; however, recurrence rates remain high despite any treatment modality. Patients with this condition must be followed up with a multidisciplinary team due to the high risk of multiple myeloma progression.

Implementation of streamlining measures in selecting and prioritising complex cases for the cancer multidisciplinary team meeting: a mini review of the recent developments.

In January 2020, NHS England and NHS Improvement, in the United Kingdom, issued a permissive framework for streamlining cancer multidisciplinary (MDT) meetings. Streamlining is defined as a process whereby complex cases are prioritized for full discussion by an MDT in an MDT meeting (MDM), while the management of straightforward cases is expedited using Standards of Care (SoC). SoC are points in the pathway of patient management where there are recognized guidelines and clear clinical consensus on the options for management and should be regionally agreed and uniformly applied by regional Cancer Alliances. While this report marks the first major change in cancer MDT management since the Calman-Hine report in 1995, its implementation, nationally, has been slow with now nearly four years since its publication. It is argued however that streamlining is a necessary step in ensuring the viability of MDT processes, and therefore maintaining patient care in the current socioeconomic context of rising workload and cancer incidence, financial pressures, and workforce shortages. In this mini review, we offer a succinct summary of the recent developments around the implementation of the 2020 streamlining framework, including challenges and barriers to its implementation, and the potential future directions in this field, which we propose should increase utilisation of implementation science. We conclude that ensuring successful implementation of the framework and the SOC requires securing a buy-in from key stakeholders, including MDTs and hospital management teams, with clearly defined (a) management approaches that include triage (e.g. through a mini MDT meeting), (b) assessment of case complexity (something that directly feeds into the SOC), and (c) roles of the MDT lead and the members, while acknowledging that the SOC cannot be universally applied without the consideration of individual variations across teams and hospital Trusts.

Visual outcomes in tuberculum sellae meningiomas comparing transcranial and endoscopic endonasal approaches.

Background: Tuberculum sellae meningiomas (TSM) account for 3-10% of intracranial meningiomas. Visual loss is the presenting symptom in up to 80% of cases. Surgical management poses a great challenge due to tumor proximity to neurovascular structures such as the optic nerve and the internal carotid artery (ICA); hence, there is controversy regarding the optimal approach. The aim of this study is to determine differences in visual outcomes between transcranial (TCA) and endoscopic endonasal (EEA) approaches. Methods: A retrospective study including 29 patients with TSM surgically treated by TCA or EEA between 2011 and 2023 in a single referral center was conducted. Pre-and post-operative neuro-ophthalmologic evaluations, focusing on visual acuity and campimetry, were evaluated. Results: Sixteen (55.16%) patients were intervened through a TCA and the remaining 13 (44.84%) via an EEA. The lesions in each group were similar in terms of pre- operative volume (15.12 vs 12.9 cm3, p = 0.497) and neurovascular invasion (optic canal invasion 48.26 vs 41.37%, p = 0.664; ICA 44.81 vs 31.03%, p = 0.797). There were no significant differences in visual outcomes between both approaches; TCA presented an improvement of 5.18 points in visual fields (p = 0.140), whereas EEA had an improvement of 17.39 points in visual acuity (p = 0.114). Conclusion: EEA seems to offer greater improvement in visual acuity than TCA. However, the ideal approach should be individualized; taking into account the tumor's volume and invasiveness, as well as the patient's visual complaints.

Surgical treatment of pituitary neuroendocrine tumors with coexisting intracranial lesions: A case series and review of the literature.

Background: Pituitary neuroendocrine tumors (PitNETs) are a diverse group of benign neoplasms that account for a significant proportion of intracranial tumors (13%). The coexistence of PitNET with other intracranial lesions, such as meningiomas and intracranial aneurysms, has been constantly reported in the literature; yet, the pathophysiological mechanisms remain unknown, and the appropriate management is controversial. This study aims to describe the clinical characteristics, surgical treatment, and outcomes of patients with PitNET with coexisting intracranial lesions in a single healthcare center. Methods: A retrospective analysis was conducted on 12 patients who underwent surgical treatment for PitNET and another intracranial lesion at our single tertiary referral center over 15 years from January 2008 to May 2023. Results: Among these coexisting lesions, aneurysms were the most commonly found (41.67%), followed by meningiomas (33.33%). Surgical intervention for both lesions was performed in a single-stage procedure for most cases (75%), employing transcranial, endoscopic endonasal, and combined approaches. We found low preoperative Karnofsky Performance Scale scores in three patients, with significant differences in functional outcomes. Conclusion: These findings contribute to the limited knowledge about PitNET coexisting with other intracranial lesions and emphasize the importance of patient-tailored, multidisciplinary management in these unusual scenarios.

Accuracy of Ex-vivo Fluorescence Confocal Microscopy in Margin Assessment of Solid Tumors: A Systematic Review.

Fluorescence confocal microscopy (FCM) is a novel technology that enables rapid high-resolution digital imaging of non-formalin-fixed tissue specimens and offers real-time positive surgical margin identification. In this systematic review, we evaluated the accuracy metrics of ex vivo FCM for intraoperative margin assessment of different tumor types. A systematic search of MEDLINE via PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus was performed for relevant papers (PROSPERO ID: CRD42022372558). We included 14 studies evaluating four types of microscopes in six different tumor types, including breast, prostate, central nervous system, kidney, bladder, and conjunctival tumors. Using the Quality Assessment of Diagnostic Accuracy Studies tool, we identified a high risk of bias in patient selection (21%) and index test (36%) of the included studies. Overall, we found that FCM has good accuracy metrics in all tumor types, with high sensitivity and specificity (>80%) and almost perfect concordance (>90%) against final pathology results. Despite these promising findings, the quality of the available evidence and bias concerns highlight the need for adequately designed studies to further define the role of ex vivo FCM in replacing the frozen section as the tool of choice for intraoperative margin assessment.

Endoscopic endonasal resection of a Drechslera hawaiiensis sphenoid fungal ball.

Background: Fungal infections should always be considered in difficult-to-treat paranasal sinus conditions. Sphenoid fungal balls are characterized by the presence of dense fungal masses in the sinus cavity without invasion of surrounding tissues. This case emphasizes the importance of accurate terminology and management and also highlights the involvement of rare pathogens such as Drechslera hawaiiensis. Diagnosis is typically based on imaging studies and intraoperative findings. Accurate identification of the pathogen is crucial. Fungal infections of the paranasal sinuses, including fungus balls, can present challenges in diagnosis and treatment. D. hawaiiensis, although infrequent, can cause potential life-threatening infections. Case Description: We present a 26-year-old non-HIV male patient who presented with nasal symptoms and mild headaches. The patient underwent an endoscopic exploration that revealed a soft, grayish lesion with a buttery consistency. Gross total resection was achieved and the lesion was identified as being caused by D. hawaiiensis; thus, intravenous antifungal treatment was given. Conclusion: Endoscopic surgery remains the preferred approach for disease control. Considering alternative treatments and exploring novel approaches are essential in managing complex pathologies in neurosurgical practice.

A rare case of a right infratentorial meningioma and a left giant posterior communicating thrombosed aneurysm.

Background: Giant intracranial aneurysms cause symptoms due to mass effect and can mimic other lesions in imaging studies. The coexistence of tumors and aneurysms is relatively rare, with meningiomas being the predominant tumors found in such cases. The relationship between these two entities is complex and represent a neurosurgical challenge. Case Description: A 61-year-old woman presented with intermittent headache, vertigo, right peripheral facial palsy, hearing loss, and left hemiparesis. Magnetic resonance imaging revealed two lesions: a supratentorial paraclinoid lesion in the left frontotemporal region and a right infratentorial extra-axial mass, suggestive of a meningioma. The patient underwent a two-staged surgical intervention to address both lesions. Conclusion: In this particular case, the lesions were located on different sides and in different cranial compartments, making it even rarer.

Poorly differentiated sinonasal neuroendocrine carcinoma with skull base invasion: A case report.

Background: Sinonasal neuroendocrine carcinoma is a rare head and neck tumor that represents only 5% of sinonasal neoplasms. This lesion has a high risk of invasion to adjacent structures such as the orbit, skull base, and soft tissues, with symptoms usually being nonspecific. Most cases are diagnosed in late stages, decreasing overall survival without treatment. To date, there is no consensus on management given its low prevalence; however, it has been shown that multimodal therapy, with the correct surgical approach as the mainstay, offers a better disease-free prognosis. Case Description: A 46-year-old woman presented with a 1 year history of nasal symptoms, characterized by obstruction and epistaxis. Imaging studies showed an extra-axial mass causing skull base erosion and displacement of the right fronto-orbital region, without invasion of brain parenchyma or meninges. A biopsy was performed and an unresectable poorly differentiated sinonasal neuroendocrine carcinoma was diagnosed. Treatment with radio and chemotherapy was initiated and, as the tumoral volume decreased, she was referred for neurosurgical intervention; an endonasal endoscopic approach was performed. Gross total resection was achieved and the patient was discharged without postoperative complications and no residual lesion on imaging. Conclusion: We describe the evolution of a rare advanced-stage neoplasm. It highlights that despite receiving an initial diagnosis of an unresectable mass, multimodal therapy, and an adequate surgical approach deemed the entire lesion to be resected. Despite the favorable clinical evolution, the follow-up of neuroendocrine carcinoma is prioritized as a neoplasm with a high rate of recurrence and metastasis.

Endoscopic Endonasal Approach in Craniopharyngiomas: Representative Cases and Technical Nuances for the Young Neurosurgeon.

Craniopharyngiomas (CPs) are Rathke's cleft-derived benign tumors originating most commonly in the dorsum sellae and representing 2% of intracranial neoplasms. CPs represent one of the more complex intracranial tumors due to their invasive nature, encasing neurovascular structures of the sellar and parasellar regions, making its resection a major challenge for the neurosurgeon with important postoperative morbidity. Nowadays, an endoscopic endonasal approach (EEA) provides an "easier" way for CPs resection allowing a direct route to the tumor with direct visualization of the surrounding structures, diminishing inadvertent injuries, and providing a better outcome for the patient. In this article, we include a comprehensive description of the EEA technique and nuances in CPs resection, including three illustrated clinical cases.

Microsurgical Resection of a Giant Trochlear Nerve Schwannoma: 2-Dimensional Operative Video.

We present the case of a 17-year-old male, who complained of a 1-year onset of pulsatile headache, dysphagia, speech changes, and emotional lability. Neuroimaging revealed a large left-sided contrast-enhancing tumor located at the infratentorial space consistent with a large trochlear nerve schwannoma. The tumor was compressing the brainstem, obstructing the outflow of the third and lateral ventricles causing hydrocephalus, and disturbing the cortico-bulbar pathways bilaterally leading to the diagnosis of pseudobulbar palsy. After the patient consented the surgical procedure, he was operated through a subtemporal transtentorial approach placed in the lateral position. A lumbar drain was used for brain relaxation during the procedure and image guidance to define the limits of surgical exposure. A microsurgical technique was used, aiming to preserve the cranial nerves and the vascular structures running through the perimesencephalic cisterns. Gross total resection was achieved and clinical course remained uneventful aside from a transient third nerve palsy. Symptoms improved and the three-month follow-up revealed an almost complete function of the oculomotor nerve (Video 1). Trochlear nerve schwannomas are the rarest variety of the cranial nerve schwannomas. Depending on tumor size, clinical and neuroimaging signs of mass effect and brainstem compression, treatment can be observation, microsurgical resection through cranial base approaches or radiosurgery.1-5.

Intra-aneurysmatic thrombectomy in a distal anterior cerebral artery aneurysm.

Thrombectomy procedures following intra-aneurysmatic lesions are extremely rare, and few cases have been reported. This article describes a microsurgical intra-aneurysmatic thrombectomy (MIaT) for a distal anterior cerebral artery (DACA) aneurysm. We present the case of a 48-year-old female that was admitted to the emergency room, showing neurologic deterioration with focal deficits. A computed tomography angiography (CTA) scan revealed an aneurysm located in the distal segment of the left anterior cerebral artery. During the surgical procedure, after clipping, a wellformed clot was visualized through the aneurysm's wall obstructing the left DACA flow. We proceeded to open the aneurysm's dome to remove the thrombus and clip the aneurysm neck, re-establishing the flow of the left DACA. Intra-aneurysmatic thrombosis can occur as a complication during clipping, obstructing the distal flow of vital arteries and causing fatal results in the patient's postoperative status. MIaT is a good technique for restoring the flow of the affected vessel and allows a secure aneurysm clipping after thrombus removal.

Unilateral approach for bilateral clipping of posterior communicating artery aneurysms in a hybrid operating room: A technical note.

Bilateral posterior communicating (pComm) artery aneurysms represent only 2% of mirror intracranial aneurysms. Usually, these are surgically approached through bilateral craniotomies for clipping. We present the case of a 50-year-old female presenting with headache and horizontal diplopia. Neurological examination revealed a left oculomotor palsy, with no other neurological deficits. Imaging studies revealed bilateral aneurysmatic lesions in both internal carotid arteries (ICA). A conventional left pterional approach was planned in order to treat the symptomatic aneurysm, and, if deemed feasible, a contralateral clipping through the same approach. The procedure was performed in a hybrid operating room (HOR), performing an intraoperative digital subtraction angiography (DSA) and roadmapping assistance during dissection and clipping. Transoperatively, a post-fixed optic chiasm was identified, with a wide interoptic space, which allowed us to perform the contralateral clipping through a unilateral approach. This technique for clipping bilateral pComm aneurysms can be performed when the proper anatomical features are met.

De-novo formation of neighboring intracranial aneurysm after spontaneous thrombosis of a ruptured distal anterior cerebral artery aneurysm: A case report and review of the literature.

Intracranial aneurysms arise in 1-2% of the population and usually present as hemorrhagic strokes. Spontaneous thrombosis of a ruptured intracranial aneurysm occurs in 1-3% and most commonly in giant aneurysms, with complete thrombosis in just 13-20% of the cases. Thrombosis of smaller aneurysms is rare. Here we present a case of a patient who presented with a ruptured intracranial aneurysm that subsequently thrombosed, discovering a neighboring de-novo aneurysm during follow-up. We hypothesized that after thrombosis, the hemodynamic characteristics that contributed to the formation of the first aneurysm were replicated.