Second window ICG predicts postoperative MRI gadolinium enhancement in high grade gliomas and brain metastases

A prospective trial evaluating the utility of second window indocyanine green (SWIG) in predicting postoperative MRI gadolinium enhancement was performed on high-grade gliomas (HGGs) and brain metastases. Compared to white light alone, SWIG demonstrated a higher sensitivity, negative predictive value, and accuracy in predicting residual neoplasm on MRI. The specificity of SWIG for predicting MRI enhancement was higher in HGGs than brain metastases. Clinically, near-infrared (NIR) imaging was better able to predict tumor recurrence than postoperative MRI. These results illustrate how SWIG is able to take advantage of gadolinium-like distribution properties to extravasate into the tumor microenvironment, enabling guidance in surgical resection. The video can be found here: https://stream.cadmore.media/r10.3171/2021.10.FOCVID21204

Analysis of cytology of germ cell tumors with histopathological and serum tumor marker correlation: a tertiary care centre experience

Background: Germ cell tumors are found primarily in children and young adults usually arising from gonads and rarely from extragonadal sites like mediastinum, retroperitoneum, pineal gland and sacrococcygeal region. Involvement of lymphnodes or bodycavities (pleural/peritoneal cavity) is usually associated with metastatic disease.Methods: This is a retrospective analysis of 96 cases of germ cell tumor for which a primary diagnosis of germ cell tumor was given by cytology from primary and metastatic sites. The study period is from January 1993- December 2013. Pap stained and Romanowsky stained smears and cell block sections (10cases) were studied. Serum tumor markers (LDH, BetaHCG and AFP) were correlated in all cases along with histopathology in available cases.Results: Among 96 cases 34 were diagnosed as seminoma/dysgerminoma,10 as embryonal carcinoma,9 as yolk sac tumor,6 as teratoma and 2 as mixed germ ell tumor. In 25 cases the cytology report was suggestive of germ cell tumor and in 10 cases malignant cells favouring germ cell tumor. Among the 10 cases the serum markers were high in six of the cases and the clinician after discussing with the pathologist treated them as germ cell tumors. 47 cases had histopathology and it correlated with cytology except in 14 cases which showed no residual neoplasm after chemotherapy. 15 cases expired immediately after the diagnosis or during the course of treatment 12cases were lost to follow up. Rest of the cases have completed the treatment. In our study the serum tumor markers showed a sensitivity of 92.75% and positive predictive value was 71.11%.Conclusions: The study highlights the importance of picking up the diagnosis of germ cell tumors by fine needle aspiration cytology so that patient can get an early diagnosis, effective treatment and a multidisciplinary approach is essential in diagnosing a difficult case of germ cell tumor. Previous history, radiology, clinical features and serum tumor markers all aid in the cytological diagnosis of germ cell tumor.

3248 Fluorescence-Guided Neurosurgery with 5-Aminolevulinic-Acid and Second-Window-Indocyanine-Green: A murine model and investigation into suitable cell lines.

OBJECTIVES/SPECIFIC AIMS: This study aims to understand the utility of 5-ALA and SWIG in detecting areas of neoplasm in a murine model of GBM. Primary outcome is the distribution of the two dyes in comparison to the true tumor extent; the sensitivity, specificity, PPV, and NPV of both dyes will be calculated. The secondary outcome is the suitability of existing cell-lines used for GBM research for studies in fluorescence-guided surgery. METHODS/STUDY POPULATION: Two cell lines are used for this research: U87, derived from human GBM; and GL261, derived from rodent stem cells. U87 are implanted intracranially into 6-week old athymic, nude, female mice, while GL261 are implanted intracranially into 10-week old female C57BL/6 mice. The mice are weighed every 3 days to monitor health and bioluminescence imaging is performed between 7-10 days after implantation to confirm tumor implantation and monitor tumor growth. The mice are sacrificed between 10-21 days after implantation. 5mg/kg of intravenous ICG is administered 24-hours prior to harvest and 250mg/kg of intraperitoneal 5-ALA is administered 3-hours prior to harvest. Once the mice are sacrificed, their brains are quickly harvested and placed in cold formalin. Using a high-resolution Odyssey CLx scanner, near-infrared fluorescence from ICG is captured in coronal cross sections of the brains through the tumor. Similarly, 5-ALA fluorescence is imaged using a 405nm LED excitation source and 610-690nm bandpass filter. Afterwards, slices of the brain are stained with H&E, which serves as the gold-standard of the extent of tumor. Images from ICG, 5-ALA, and H&E can then be compared using ImageJ to compare the extent of tumor to the distribution of the dyes. RESULTS/ANTICIPATED RESULTS: In separate, previous studies in humans, both 5-ALA and SWIG have demonstrated utility in detecting residual neoplasm in HGG resections. In general, 5-ALA is more specific for areas of neoplasm, while SWIG is more sensitive. Thus, I anticipate that in this study, SWIG will show a greater distribution than 5-ALA, with SWIG distributing to areas beyond the tumor and 5-ALA distributing within, but not completely covering, the tumor. SWIG’s sensitivity and NPV for detecting tumor should be >90%, while its specificity and PPV may be closer to 50%. For 5-ALA, specificity and PPV should be close to 80-90%, but its sensitivity and NPV may be <50%. In terms of cell-line, preliminary results suggest that U87 cells are not suitable for research involving 5-ALA. We suspect that this is partly due to the limited infiltrative nature of U87 cells; in fact, the cells form a spherical mass, imitating metastases rather than true HGGs. The U87 masses do not have significant vascularity, which likely limits the amount of 5-ALA that can distribute to inside the tumor. DISCUSSION/SIGNIFICANCE OF IMPACT: 5-ALA is currently the only FDA-approved agent for fluorescence-guided neurosurgery. However, it has multiple limitations, which ultimately results in its low sensitivity and NPV. Our novel technique, which has demonstrated much higher sensitivity at the cost of specificity, offers an alternative that may help surgeons better achieve total resections in the operating room. These two agents have not been compared directly in humans or mice. Thus, this experiment sets up an important precedent, on which a human clinical trial comparing the two agents’ effects on resection rates and patient outcome can be performed. Ultimately, this work will lay the foundation for future research into fluorescence-guided neurosurgery, both in the visible and NIR spectrum.

Folate Receptor Near-Infrared Optical Imaging Provides Sensitive and Specific Intraoperative Visualization of Nonfunctional Pituitary Adenomas

BACKGROUND Surgical resection is the primary treatment for nonfunctional (NF) pituitary adenomas, but gross-total resection is difficult to achieve in all cases. NF adenomas overexpress folate receptor alpha (FRα). OBJECTIVE To test the hypothesis that we could target FRα for highly sensitive and specific intraoperative detection of NF adenomas using near-infrared (NIR) imaging. METHODS Fourteen patients with NF pituitary adenoma were infused with the folate analog NIR dye OTL38 preoperatively. NIR fluorescence signal-to-background ratio (SBR) was recorded for each tumor during resection of the adenomas. Extent of surgery was not modified based on the presence or absence of fluorescence. Immunohistochemistry was performed to assess FRα expression in all specimens. Magnetic resonance imaging (MRI) was performed postoperatively to assess residual neoplasm. RESULTS Nine adenomas overexpressed FRα and fluoresced with a NIR SBR of 3.2 ± 0.52, whereas the 5 non-FRα-overexpressing adenomas fluoresced with an SBR of 1.5 ± 0.21. Linear regression demonstrated a significant correlation between intraoperative SBR and the FRα expression (P-value &lt; .001). Analysis of 14 margin samples revealed that the surgeon's impression of the tissue had 83% sensitivity, 100% specificity, 100% positive predictive value, and 89% negative predictive value, while NIR fluorescence had 100% for all values. NIR fluorescence accurately predicted postoperative MRI results in 78% of FRα-overexpressing patients. CONCLUSION Preoperative injection of folate-tagged NIR dye provides strong signal and visualization of NF pituitary adenomas. It is 100% sensitive and specific for detecting margin neoplasm and can predict postoperative MRI findings. Our results suggest that NIR fluorescence may be superior to white-light visualization alone and may improve resection rates in NF pituitary adenomas.

ASSESSMENT AND MANAGEMENT OF A PATIENT WITH PARANEOPLASTIC DERMATOMYOSITIS

Dermatomyositis (DM) is an idiopathic inflammatory myopathy, that can be associated with malignancy. We report the case of a 60-years-old woman, diagnosed and treated for left breast cancer, with residual neoplasm following treatment, who was admitted for generalized myalgias and tetraparesis with predominance of paraparesis. Clinical exam revealed heliotrope rash with bilateral palpebral edema and an erythematous eruption on both thighs and anterior thorax. Motor deficits were predominantly proximal. Paraclinical evaluation excluded other etiologies and revealed elevated serum muscle enzymes and electromyographic pattern of myopathy. An MRI was performed and showed diffuse edematous infiltration of skeletal muscles. Symptoms diminished under corticotherapy, intravenous immunoglobulins and cyclophosphamide. Left mastectomy was eventually performed, but DM symptoms reappeared a few months later. Despite extensive search, no recurrence of tumor was found. However, under treatment, the patient once again recovered, and later resumed her activity.

Cortical mapping and frameless stereotactic navigation in the high-field intraoperative magnetic resonance imaging suite

Frameless stereotactic neuronavigation provides tracking of surgical instruments on radiographic images and orients the surgeon to tumor margins at surgery. Bipolar electrical stimulation mapping (ESM) delineates safe limits for resection of brain tumors adjacent to eloquent cortex. These standard techniques could complement the capability of intraoperative MR (iMR) imaging to evaluate for occult residual disease during surgery and promote more complete tumor removal. The use of frameless neuronavigation in the high-field iMR imaging suite requires that a few pieces of standard equipment be replaced by nonferromagnetic instruments. Specific use of ESM in a high-field iMR imaging suite has not been reported in the literature. To study whether frameless neuronavigation and electrical stimulation mapping could be successfully integrated in the high-field iMR imaging suite, the authors employed these modalities in 10 consecutive cases involving patients undergoing conscious craniotomy for primary brain tumors located in or adjacent to eloquent cortices. Equipment included a custom high-field MR imaging–compatible head holder and dynamic reference frame attachment, a standard MR imaging–compatible dynamic reference frame, a standard MR imaging machine with a table top that could be translated to a pedestal outside the 5-gauss line for the operative intervention, and standard neuronavigational and cortical stimulation equipment. Both ESM and frameless stereotactic guidance were performed outside the 5-gauss line. The presence of residual neoplasm was evaluated using iMR imaging; resection was continued until eloquent areas were encountered or iMR imaging confirmed complete removal of any residual tumor. Mapping identified essential language (5 patients), sensory (6), and motor (7) areas. The combined use of frameless stereotactic navigation, ESM, and iMR imaging resulted in complete radiographic resection in 7 cases and resection to an eloquent margin in 3 cases. Postoperative MR imaging confirmed final iMR imaging findings. No patient experienced a permanent new neurological deficit. Familiar techniques such as frameless navigation and ESM can be rapidly, inexpensively, safely, and effectively integrated into the high-field iMR imaging suite.

Adult intramedullary astrocytomas of the spinal cord

✓ In this series, 25 adult patients with intramedullary astrocytomas were treated by radical excision alone. Six patients proved to have anaplastic astrocytoma; five of them died within approximately 2 years and the sixth has demonstrated disease progression. The other 19 patients were diagnosed as having low-grade astrocytoma (16 cases) or ganglioglioma (three cases); two of these had advanced preoperative neurological disability and died of medical complications. Fifteen of the remaining 17 patients have no clinical evidence of tumor recurrence after a mean follow-up period of 50.2 months; the other two have a small residual neoplasm that demonstrates no progression. Of these 17 patients, seven had previously received radiation therapy, but had clear evidence of tumor growth subsequently. This experience suggests that surgery is not beneficial for anaplastic spinal astrocytoma. However, in cases of low-grade tumor, radical excision is associated with minimal morbidity and an excellent long-term prognosis when carried out before significant disability occurs.