Aggressive Surgical Resection Research Articles

Establishment and Characterization of Three Human Ocular Adnexal Sebaceous Carcinoma Cell Lines.

Ocular adnexal sebaceous carcinoma (SebCA) represents one of the most clinically problematic periocular tumors, often requiring aggressive surgical resection. The pathobiology of this tumor remains poorly understood, and few models exist that are suitable for preclinical testing. The aim of this study was to establish new cell lines to serve as models for pathobiological and drug testing. With patient consent, freshly resected tumor tissue was cultured using conditional reprogramming cell conditions. Standard techniques were used to characterize the cell lines in terms of overall growth, clonogenicity, apoptosis, and differentiation in vitro. Additional analyses including Western blotting, short tandem repeat (STR) profiling, and next-generation sequencing (NGS) were performed. Drug screening using mitomycin-C (MMC), 5-fluorouricil (5-FU), and 6-Diazo-5-oxo-L-norleucine (DON) were performed. JHH-SebCA01, JHH-SebCA02, and JHH-SebCA03 cell lines were established from two women and one man undergoing surgical resection of eyelid tumors. At passage 15, they each showed a doubling time of two to three days, and all could form colonies in anchorage-dependent conditions, but not in soft agar. The cells contained cytoplasmic vacuoles consistent with sebaceous differentiation, and adipophilin protein was present in all three lines. STR profiling confirmed that all lines were derived from their respective patients. NGS of the primary tumors and their matched cell lines identified numerous shared mutations, including alterations similar to those previously described in SebCA. Treatment with MMC or 5-FU resulted in dose-dependent growth inhibition and the induction of both apoptosis and differentiation. MYC protein was abundant in all three lines, and the glutamine metabolism inhibitor DON, previously shown to target high MYC tumors, slowed the growth of all our SebCA models. Ocular adnexal SebCA cell lines can be established using conditional reprogramming cell conditions, and our three new models are useful for testing therapies and interrogating the functional role of MYC and other possible molecular drivers. Current topical chemotherapies promote both apoptosis and differentiation in SebCA cells, and these tumors appear sensitive to inhibition or MYC-associated metabolic changes.

Sonodynamic therapy for adult-type diffuse gliomas: past, present, and future.

Intra-axial brain tumors persist as significant clinical challenges. Aggressive surgical resection carries risk of morbidity, and the blood-brain barrier (BBB) prevents optimal pharmacological interventions. There is a clear clinical demand for innovative and less invasive therapeutic strategies for patients, especially those that can augment established treatment protocols. Focused ultrasound (FUS) has emerged as a promising approach to manage brain tumors. Sonodynamic therapy (SDT), a subset of FUS, utilizes sonosensitizers activated by ultrasound waves to generate reactive oxygen species (ROS) and induce tumor cell death. This review explores the historical evolution and rationale behind SDT, focusing on its mechanisms of action and potential applications in brain tumor management. A systematic review was conducted using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Preclinical studies have demonstrated the efficacy of various sonosensitizers, including 5-aminolevulinic acid (5-ALA), fluorescein, porphyrin derivatives, and nanoparticles, in conjunction with FUS for targeted tumor therapy and BBB disruption. Clinical trials have shown promising results in terms of safety and efficacy, although further research is needed to fully understand the potential adverse effects and optimize treatment protocols. Challenges such as skull thickness affecting FUS penetration, and the kinetics of BBB opening require careful consideration for the successful implementation of SDT in clinical practice. Future directions include comparative studies of different sonosensitizers, optimization of FUS parameters, and exploration of SDT's immunomodulatory effects. SDT represents a promising frontier in the treatment of aggressive brain tumors, offering hope for improved patient outcomes.

Molecular markers of proliferation, DNA repair, and immune infiltration defines high-risk subset of resectable retroperitoneal sarcomas

IntroductionFor retroperitoneal sarcomas (RPS), aggressive surgical resection offers the only chance for a cure; however, 5-year survival remains below 65%. Therefore, there is a critical need to identify drivers of poor clinical outcomes. Materials and methodsTo identify biomarkers of tumors likely to recur following curative intent resection, we performed genomic and transcriptomic sequencing for 47 and 34 patients, respectively, with non-metastatic RPS at a single, high-volume sarcoma center. ResultsAt the DNA level, alterations in TERT were associated with poor disease-free survival (DFS) and overall survival (OS). Increased RNA expression of gene sets related to growth signaling and DNA repair were associated with poor DFS and OS. Infiltration of CD8+ T-Cells and activated dendritic cells were associated with poor DFS and OS. ConclusionThese findings may help to better identify and treat non-metastatic, high-risk RPS.

Aggressive Surgical Management of Bilateral Metachronous Lung Metastases in Fibrolamellar Hepatocellular Carcinoma, a Case Report

Fibrolamellar hepatocellular carcinoma (FL-HCC) is a malignant primary hepatic cancer that affects mainly adolescents and young adults without underlying liver disease. Its biology remains unknown, but it is pathologically distinct from traditional HCC. Therapeutic strategies are not well defined and, as chemotherapies seem to have limited efficacy, surgical resection remains the only effective treatment. Here we report on a case of a metastatic FL-HCC in an 18-year-old man successfully treated with aggressive intra-thoracic bilateral lung metastasectomy following primary tumour resection and adjuvant chemotherapy. Survival time after initial hepatectomy is 39 months, with no recurrence of disease to date. Aggressive surgical resection and redo surgery should be considered until more effective multimodality therapies are identified. Multidisciplinary team discussion and involvement of medical and surgical specialties are essential in managing these rare entities.

Leiomyosarcoma of Inferior Vena Cava: Resection and Reconstruction

Primary leiomyosarcomas of the inferior vena cava (IVC) are rare tumors with complex anatomical relationships. Surgical resection remains the primary approach for management, with selective use of preoperative radiation and chemotherapy. Given the propensity for local invasion of these tumors, radical resection of surrounding structures is often required. Herein we describe the presentation, work-up, operative management, and outcomes of these lesions through the case of a patient with a tumor involving the middle segment of the IVC. Given the extent of involvement, IVC resection with en bloc right nephrectomy, right adrenalectomy, and partial left renal vein resection was performed with vascular reconstruction using a prosthetic graft. With appropriate preoperative planning and a well-coordinated multidisciplinary approach, aggressive surgical resection can be safely performed and patients can benefit from favorable long-term survival.

The Role of Hyperthermic Intrathoracic Chemotherapy (HITHOC) in Thoracic Tumors.

Pleural mesothelioma (PM) is a rare but aggressive thoracic tumor with a poor prognosis. Multimodal treatment-including induction chemotherapy, aggressive surgical resection, radiotherapy and immunotherapy in selected cases-currently represents the best therapeutic option. Single-center studies advocate hyperthermic intrathoracic chemotherapy (HITHOC) during surgical resection as an additional therapeutic option, although its impact on post-operative morbidity and survival has not yet been evaluated on a larger scale. HITHOC can be applied not only in the case of mesothelioma, but also in the case of thymoma with pleural involvement or-in very selected cases-in patients with secondary pleural metastases. Despite favorable outcomes and reduced clinical risks, there is no uniform approach to HITHOC, and a wide variety of indications and technical applications are still reported. Based on available data, HITHOC seems to offer a clear benefit in regard to overall survival of all mesothelioma patients; however, multicenter randomized controlled trials are required to validate and standardize this approach. The aim of this review is to focus on the present role of HITHOC in thoracic tumors with pleural involvement as well as on future challenges, particularly in the light of possible combined therapy of thoracic tumors still presenting poor prognoses.

Lumbar Chondrosarcoma in A Young Female: A Case Report and Literature Review

Introduction: Chondrosarcomas (CS) are uncommon malignant tumors that form cartilage, ranking third among primary malignant bone tumors. Although they are rare, with an incidence rate of 2%-12%, they can occur in the spine, with the lumbar region being even less common. These tumors are resistant to chemotherapy and radiotherapy, making surgical excision the treatment of choice. The extent of surgical resection is vital for the patient’s prognosis and the risk of recurrence. A unique case of lumbar CS in a young female patient is reported. Case Report: A 23-year-old female experienced progressive lower back pain and radiculopathy in both lower limbs. Laboratory tests and radiological imaging revealed an osteolytic lesion in the L5 vertebral body. Despite a biopsy that did not conclusively diagnose the lesion, a two-stage en-bloc resection was carried out. The procedure confirmed the diagnosis of grade I conventional chondrosarcoma. The patient had a successful recovery and remainedrecurrence-free after three years. Discussion: CS typically occurs in males between their 40s and 70s and can develop in various bones, with different classifications based on origin and histopathological features. Spinal CS is rare, and symptoms can be non-specific but may progress to include pain and neurological deficits. Diagnosis is primarily based on imaging, with biopsy used in some cases. Surgical resection is the mainstay of treatment due to the tumor’s resistance to other treatments. Achieving negative surgical margins is imperative but challenging, necessitating a multidisciplinary approach for optimal outcomes. Conclusion: The presented case underlines the rarity of CS in the lumbar region and the challenges in diagnosing and surgically managing such cases. Aggressive surgical resection is key to treatment, requiring careful preoperativve planning and intraoperative precision. The successful long-term disease control in our patient emphasizes the importance of complete tumor resection.

Perioperative and oncological outcomes following robotic en bloc multivisceral resection for colorectal cancer.

As multidisciplinary treatment strategies for colorectal cancer have improved, aggressive surgical resection has become commonplace. Multivisceral and extended resections offer curative-intent resection with significant survival benefit. However, limited data exist regarding the feasibility and oncological efficacy of performing extended resection via a minimally invasive approach. The aim of this study was to determine the perioperative and long-term outcomes following robotic extended resection for colorectal cancer. We describe the population of patients undergoing robotic multivisceral resection for colorectal cancer at our single institution. We evaluated perioperative details and investigated short- and long-term outcomes, using the Kaplan-Meier method to analyse overall and recurrence-free survival. Among the 86 patients most tumours were T3 (47%) or T4 (47%) lesions in the rectum (78%). Most resections involved the anterior compartment (72%): bladder (n = 13), seminal vesicle/vas deferens (n = 27), ureter (n = 6), prostate (n = 15) and uterus/vagina/adnexa (n = 27). Three cases required conversion to open surgery; 10 patients had grade 3 complications. The median hospital stay was 4 days. Resections were R0 (>1 mm) in 78 and R1 (0 to ≤1 mm) in 8, with none being R2. The average nodal yield was 26 and 48 (55.8%) were pN0. Three-year overall survival was 88% and median progression-free survival was 19.4 months. Local recurrence was 6.1% and distant recurrence was 26.1% at 3 years. Performance of multivisceral and extended resection on the robotic platform allows patients the benefit of minimally invasive surgery while achieving oncologically sound resection of colorectal cancer.

Where Do Surgical Resection and Radiosurgery Fall Short for Large Metastatic Brain Lesions?

INTRODUCTION: Stereotactic radiosurgery is established as the optimal treatment modality for metastatic disease of the brain, but there is ongoing debate about the optimal treatment for larger brain metastases. There have been few studies identifying and quantifying lesion characteristics where efficacy and local control of these lesions suffer. METHODS: We retrospectively identified patients who received surgical resection and/or hypofractionated Gamma Knife radiosurgery (HF-GKRS) between 2017 and 2022 for the treatment of metastatic brain tumors greater than 10cc. Clinical, treatment, and radiological data was collected. Local failure (LF) events were examined, and independent factors associated with subsequent local failure were identified. RESULTS: 105 lesions greater than 10cc (in 97 patients) were treated and the median patient follow-up was 10.1 months. The median gross tumor volume was 15.8cc (range 10.1-62.4). Prior surgical resection was performed on 49 lesions (54%). Tumor volume larger than 33.5cc (p = 0.029, 12-month LF rate 38%) and radioresistant histology (p=0.047, 12-month LF rate 54%) were associated with increased risk of LF (p=0.018) whereas surgical resection did not correlate with increased LC (p = 0.642, 12-month LF rate 19%). CONCLUSIONS: Patients with brain metastases that are greater than 4cm in diameter or are of radioresistant histology (primary origin of gastrointestinal adenocarcinoma, melanoma, or renal cell carcinoma) are especially prone to local failure despite aggressive surgical resection, stereotactic radiosurgery, and systemic chemotherapy. In these cases, the optimal management needs to be further elucidated and may involve preoperative stereotactic radiosurgery or intraoperative brachytherapy.

Poorly differentiated thyroid cancer: Clinical, pathological, mutational, and outcome analysis.

Poorly differentiated thyroid cancer (PDTC) remains a challenge not only for pathologists and surgeons because of the difficulties associated with the diagnostic process and the compelling need for difficult thyroidectomy, but it is also of high clinical relevance because it is responsible for mortality in non-anaplastic follicular cell-derived thyroid cancer. Cases of PDTC within a 30-year period were reviewed by two independent pathologists. Histological features like atypical mitosis, necrosis, capsular, and vascular invasion were studied. Mutation analysis was done for BRAF, RET/PTC, RAS, and PI3KCA, and P53 was performed using immunohistochemistry. There were 39 patients with a median age of 53 years; 14 patients were more than 55 years of age. At presentation, 38.4% had compressive features and the median tumor size was 9 cm. At presentation, 67.7% had an extrathyroidal extension (ETE). R0 resection was achieved in 41%, with 12 cases resulting in a difficult thyroidectomy. Necrosis was seen in 65.7% and mitosis in 73.3% with well-differentiated components in 41%. The commonest mutation was RAS (23.1%). Survival was higher in the operable group (54.26, 95% confidence interval [CI]: 30.83-77.70 vs. 20.25, 95% CI: 0-54.07) months, respectively; however, 10-year survival was only 5% and only the tumor size and presence of mitosis were independent risk factors. PDTC presents with worrisome features like large size, ETE, and rapid growth. Aggressive surgical resection with extended/radical thyroidectomy may result in better loco-regional control and improved survival. RAS was the frequent mutation detected. It is worthwhile to identify prognostic factors that can predict the course of PDTC.

Long-Term Outcomes and Survival Rates of Patients Undergoing Biopsy Vs. Maximum Safe Resection for Thalamic Lesions: A Short Review on Current Evidence

The thalamic lesion is one of the most challenging tumors with significant mortality and morbidities. Current literature highlights the importance of individualized treatment strategies tailored to the specific characteristics of the lesion and the patient. In terms of efficacy, studies have demonstrated that maximal safe resection (MSR) of thalamic lesions can lead to better tumor control, prolonged progression-free survival, and improved overall survival rates compared to biopsy alone. However, the feasibility of achieving MSR is highly dependent on the location, size, and histology of the lesion, as well as the patient's functional status and overall health. Also, surgical interventions in the thalamus carry inherent risks of neurological deficits, including sensory, motor, and cognitive impairments, depending on the extent of surgical resection and proximity to eloquent neural structures. On the other hand, biopsy remains a valuable diagnostic tool for obtaining tissue samples and establishing a definitive histological diagnosis in cases where MSR is not feasible or poses a high risk of neurological complications. Indeed, biopsy is preferred in patients with advanced age, significant comorbidities, or lesions located in eloquent regions of the thalamus where aggressive surgical resection may result in considerable morbidity. Quality of life (QoL) outcomes, including functional status, symptom burden, and overall well-being, are important endpoints in evaluating the impact of treatment approaches for thalamic lesions on patients' daily activities. While MSR may offer potential long-term benefits in terms of tumor control and survival outcomes, it may also be associated with a higher risk of neurological deficits and functional impairments that can impact QoL postoperatively. Conversely, biopsy may involve less invasive procedures and shorter recovery times, resulting in better preserved functional status and improved QoL in selected patient populations.

Factors associated with the receipt of surgery in acinar cell carcinoma of the pancreas.

668 Background: Acinar cell carcinoma of the pancreas (PACC) accounts for 1-2% of adult pancreatic tumors. Clinically, this malignancy presents as a hypersecretory syndrome as lipase is released into circulation. Median overall survival is 18 to 47 months. Aggressive surgical resection is associated with long-term survival in PACC patients. This appears to be the treatment of choice for most localized pancreatic cancers, however, there are no clear treatment guidelines or standardized protocols for PACC due to its rarity. Further, no significant study has analyzed the factors correlated with receiving this surgery. This study aims to uncover the possible factors associated with the receipt of tumor resection in patients with PACC. Methods: The National Cancer Database (NCDB) was used to identify patients diagnosed with PACC from 2004 to 2019 using the histology code 8550 as assigned by the Commission on Cancer Accreditation program. Kaplan-Meier, ANOVA Chi-Square, and Multilevel Logistic Regression were performed, and data were analyzed using SPSS version 29. Statistical significance was set at α = 0.05. Results: 1430 patients with PACC were queried. 600 (41.95%) patients received surgical resection. Surgical patients experienced longer overall survival than non-surgical patients (87.5 months vs. 25.3 months, P < 0.01). Of the surgical patients, wider surgical margins and complete tumor resection were associated with improved survival (P<0.001). Stage I and II disease, well and moderately differentiated disease, and receiving treatment at an academic/research facility were associated with an increased likelihood of receiving surgery (P<0.001). Metastasis at the time of diagnosis was associated with a decreased likelihood of receiving surgery (P<0.001). Income status, race, insurance status, and age did not appear to be significant predicting factors of surgery. Of the initial sample, 219 (15.31%) patients received adjuvant chemotherapy, 8 (0.55%) patients received adjuvant radiation, and 4 (0.28%) patients received both adjuvant chemotherapy and radiation. Adjuvant therapies did not appear to impact the overall survival of PACC patients. Conclusions: This study confirms that tumor resection is associated with increased survival in patients with PACC. Improved survival with surgery is correlated to wider surgical margins and complete tumor resection. It appears that patients with well or moderately differentiated disease, stage I or II disease, and treatment at an academic/research facility are more likely to receive surgery. PACC patients with metastasis to distant sites are less likely to receive surgery. The efficacy of adjuvant therapy remains unclear. Further studies are needed to better understand the factors involved in receiving surgery and other treatment modalities as part of PACC treatment.

Early Reconstruction with Locoregional-Free Flaps in Post-COVID-19 Rhino-orbital-cerebral Mucormycosis Craniofacial Deformities: A Single-Center Clinical Experience from India.

Aim of the Study Mucormycosis is a rare invasive and fatal fungal infection and its resurgence in coronavirus disease 2019 (COVID-19) patients has been a matter of grave concern. It is essentially a medical disease, but surgical debridement of necrotic tissues is of paramount importance leading to severe craniofacial deformities. In this case series, we present our experience with the feasibility of early reconstruction after surgical debridement. Case Series As a Dedicated COVID Center (DCH), the institute received the largest population of COVID-19 mucormycosis patients from the entire eastern region of the country between May 2021 and August 2021. More than 5,000 COVID-19 were admitted out of which 218 patients were diagnosed with mucormycosis. Nine patients, seven males and two females, with a mean age of 39 years with craniofacial mucormycosis underwent debridement and early reconstructions (2-4 weeks from first debridement and start of antifungal therapy) with free and pedicled flaps. All flaps survived and showed no evidence of recurrence. The average time of the early reconstruction after surgical debridement was 1.7 weeks once the course of systemic amphotericin B was received. Conclusion After aggressive surgical resection and a short course of antifungal therapy, early reconstruction can be done safely based on clinical criteria, as long as there is no evidence of hyphae invasion on wound edges in the intraoperative pathology examination.

Recurrent intracranial anaplastic ependymoma with late‐onset giant scalp metastasis

Key Clinical MessageEpendymomas are primary brain tumors that predominantly affect individuals between 0 and 4 years of age. Although ependymomas have a propensity for recurrence and the potential to spread within the central nervous system through cerebrospinal fluid (resulting in drop metastases), reports of extra‐neural metastatic localizations are exceedingly rare in the existing literature. This case report presents a unique and rare instance of recurrent intracranial anaplastic ependymoma with a late‐onset giant scalp metastasis.AbstractA 55‐year‐old male patient with a medical history of partial resection of an atypical supratentorial left temporal ependymoma presented with a recurrent anaplastic ependymoma, which had been managed with surgery and radiotherapy. After a 4‐year follow‐up, the patient developed a subcutaneous mass in the left parietal region of the scalp. A multidisciplinary team of neurosurgeons and plastic surgeons performed a surgical procedure, which included en bloc removal of the scalp lesion, resection of 1 cm of unaffected skin, and craniotomy to address an osteolytic area in the parietal skull bone. Skin autografts were used for reconstruction. Histological examination confirmed metastasis of anaplastic ependymoma in the scalp. After a delay in starting chemotherapy due to concerns related to the COVID‐19 pandemic, the patient eventually initiated chemotherapy, leading to disease stability at a short‐term follow‐up. Scalp metastases from ependymoma are rarely reported in the literature. Management of such cases necessitates aggressive surgical resection, followed by adjuvant chemotherapy and radiotherapy. A multidisciplinary approach is recommended to ensure effective and targeted therapy, with a focus on preserving aesthetics, particularly in pediatric cases.

GLIOMA-12 GLIOSARCOMA: A SERIES OF FOUR CASES TREATED

Abstract INTRODUCTION Gliosarcoma is a rare central nervous system malignancy, characterized by classical biphasic histological pattern with both glial and sarcomatous component. It usually affects fifth and sixth decade of life with slight male preponderance. In this report, we reviewed the clinical and radiological presentation, pathologic diagnosis, and treatment outcomes for a series of 4 patients diagnosed with gliosarcoma. MATERIAL AND METHODS We carried out a retrospective analysis of four patients with gliosarcoma diagnosed between March 2019 and March 2023. Demographic data, clinicopathological data, treatment strategies employed, details of recurrence, and survival patterns are reviewed. RESULTS Four patients, males, respectively aged of 56, 39, 54 and 57 years, presented with signs and symptoms consistent with an expanding intracranial mass,including headache, seizure, hemiparesis. Median duration of presenting symptoms was 3.5 months. The tumor was located in temporo-parieto-occipital region, fronto-parietal region, fronto-temporal region, and temporal region. All patients underwent craniotomy with attempt to achieve gross total surgical resection. Unfortunately, total resection could be achieved in only two patients; remaining two patients underwent subtotal resection. Surgery was followed by adjuvant radiotherapy and temozolomide-based chemotherapy for three patients. All patients died at 1 week, 6 months, 7 months and 10 months. CONCLUSION As gliosarcoma is considered as a variant of glioblastoma, it is treated similarly to glioblastoma but optimum treatment recommendations are yet to be defined. In this series, we have reported four cases of gliosarcoma who have been treated on the lines of glioblastoma. The prognosis is still poor despite aggressive surgical resection and adjuvant multi-modality therapy is given.

Intraductal papillary neoplasm of the bile duct: The new frontier of biliary pathology.

Intraductal papillary neoplasms of the bile duct (IPNBs) represent a rare variant of biliary tumors characterized by a papillary growth within the bile duct lumen. Since their first description in 2001, several classifications have been proposed, mainly based on histopathological, radiological and clinical features, although no specific guidelines addressing their management have been developed. Bile duct neoplasms generally develop through a multistep process, involving different precursor pathways, ranging from the initial lesion, detectable only microscopically, i.e. biliary intraepithelial neoplasia, to the distinctive grades of IPNB until the final stage represented by invasive cholangiocarcinoma. Complex and advanced investigations, mainly relying on magnetic resonance imaging (MRI) and cholangioscopy, are required to reach a correct diagnosis and to define an adequate bile duct mapping, which supports proper treatment. The recently introduced subclassifications of types 1 and 2 highlight the histopathological and clinical aspects of IPNB, as well as their natural evolution with a particular focus on prognosis and survival. Aggressive surgical resection, including hepatectomy, pancreaticoduodenectomy or both, represents the treatment of choice, yielding optimal results in terms of survival, although several endoscopic approaches have been described. IPNBs are newly recognized preinvasive neoplasms of the bile duct with high malignant potential. The novel subclassification of types 1 and 2 defines the histological and clinical aspects, prognosis and survival. Diagnosis is mainly based on MRI and cholangioscopy. Surgical resection represents the mainstay of treatment, although endoscopic resection is currently applied to nonsurgically fit patients. New frontiers in genetic research have identified the processes underlying the carcinogenesis of IPNB, to identify targeted therapies.

FRI668 Insulinoma As A Cause Of New Onset Hypoglycemic Episodes

Abstract Disclosure: S. Zahra: None. M.A. Abbas: None. R. Subramani: None. F. Manas: None. S. Yavuz: None. 37 years old female with a past medical history of hypothyroidism presented with complaints of shakiness, lightheadedness, and palpitations, relieved by eating. The physical examination was unremarkable. Fasting blood work showed low glucose of 41 mg/dl (70-99 mg/dl), normal insulin levels of 8.4 UIU/ ml (normal:1.9-23 UIU/ml), elevated proinsulin 21.1 pmol/ L (normal:<8.0 pmol/L), normal C Peptide 2.5 ng/ ml (normal:1.1-4.4 ng/ml), and negative for insulin antibody. Serum ACTH and cortisol levels were normal. Blood testing for hypoglycemia-inducing medications was negative. CT and MRI abdomen pelvis contrast was normal. She was prescribed to wear Dexcom to monitor her blood glucose round the clock. She continued to have low blood glucose, sometimes without symptoms and was rescued by the alarm. She underwent endoscopic ultrasound and was found to have a 10mm x 9mm ill-defined rounded pancreatic head mass with diffuse echogenicity of the pancreas. Biopsy of the mass revealed clusters of epithelial cells with neuroendocrine differentiation, compatible with insulinoma. She underwent surgical resection of the mass. She was also referred to genetic testing due to the association of pancreatic tumors with MEN syndrome. The diagnosis of Insulinomas is clinical as well as biochemical with presenting symptoms of Whipple’s Triad along with the presence of the following lab findings: hypoglycemia with plasma glucose of less than 50mg /dl, insulin greater than 5 UIU/L, C-Peptide greater than 0.2 nmol/L (0.6 ng/mL), Insulin/C-Peptide ratio of greater than 1.0, Proinsulin greater than 20pmol/L, and the absence of sulfonylurea metabolites in plasma or urine. Insulinoma is the most common pancreatic neuroendocrine and functional endocrine tumor of the beta cells of the pancreas with a prevalence of 1-4 people per million with equal gender distribution. They are mainly seen in the fifth decade of life but can occur at any age. They can occur sporadically or can be associated with MEN 1. Insulinomas are mostly benign, about 5-10% can be malignant. When to do medical vs surgical management? For benign insulinomas, surgical resection is preferred. For locally invasive and malignant tumors, aggressive surgical resection is performed, unless surgery is contraindicated for any other reason or patient refuses it. Medical treatment is reserved for the patients with diffuse Beta cell disease, multiple insulinoma and unresected malignant insulinoma. In the presence of unresectable metastatic disease; radiofrequency ablation, selective embolization, intraarterial chemotherapy, alone or in combination has been shown to be effective in controlling hypoglycemic episodes and improving quality of life. Octreotide, via inhibiting insulin secretion, normalizes the blood glucose levels. For better detection of hypoglycemia and adequate response to medical therapy, continuous glucose monitoring is helpful. Presentation: Friday, June 16, 2023

Hyperbaric oxygen therapy as a complementary treatment in neuroblastoma - a narrative review.

Neuroblastoma is the most frequently diagnosed cancer during the first year of life. This neoplasm originates from neural crest cells derived from the sympathetic nervous system, adrenal medulla, or paraspinal ganglia. The clinical presentation can vary from an asymptomatic mass to symptoms resulting from local invasion and/or spread of distant disease spread. The natural history of neuroblastoma is highly variable, ranging from relatively indolent biological behavior to a high-risk clinical phenotype with a dismal prognosis. Age, stage, and biological features are important prognostic risk stratification and treatment assignment prognostic factors. The multimodal therapy approach includes myeloablative chemotherapy, radiotherapy, immunotherapy, and aggressive surgical resection. Hyperbaric oxygen therapy (HBOT) has been proposed as a complementary measure to overcome tumor hypoxia, which is considered one of the hallmarks of this cancer treatment resistance. This article aims to review the relevant literature on the neuroblastoma pathophysiology, clinical presentation, and different biological and genetic profiles, and to discuss its management, focusing on HBOT.

Rapid extraction-free detection of the R132H isocitrate dehydrogenase mutation in glioma using colorimetric peptide nucleic acid-loop mediated isothermal amplification (CPNA-LAMP).

The R132H isocitrate dehydrogenase one (IDH1) mutation is a prognostic biomarker present in a subset of gliomas and is associated with heightened survival when paired with aggressive surgical resection. In this study, we establish proof-of-principle for rapid colorimetric detection of the IDH1-R132H mutation in tumor samples in under 1 hour without the need for a nucleic acid extraction. Colorimetric peptide nucleic acid loop-mediated isothermal amplification (CPNA-LAMP) utilizes 4 conventional LAMP primers, a blocking PNA probe complementary to the wild-type sequence, and a self-annealing loop primer complementary to the single nucleotide variant to only amplify the DNA sequence containing the mutation. This assay was evaluated using IDH1-WT or IDH1-R132H mutant synthetic DNA, wild-type or IDH1-R132H mutant U87MG cell lysates, and tumor lysates from archived patient samples in which the IDH1 status was previously determined using immunohistochemistry (IHC). Reactions were performed using a hot water bath and visually interpreted as positive by a pink-to-yellow color change. Results were subsequently verified using agarose gel electrophoresis. CPNA-LAMP successfully detected the R132H single nucleotide variant, and results from tumor lysates yielded 100% concordance with IHC results, including instances when the single nucleotide variant was limited to a portion of the tumor. Importantly, when testing the tumor lysates, there were no false positive or false negative results.

Coronavirus disease-19 is associated with decreased treatment access and worsened outcomes in malignant brain tumor patients.

The global coronavirus disease-19 (COVID-19) pandemic has resulted in procedural delays around the world; however, timely and aggressive surgical resection for malignant brain tumor patients is essential for outcome optimization. To investigate the association between COVID-19 and outcomes of these patients, we queried the 2020 National Inpatient Sample (NIS) for differences in rates of surgical resection, time to surgery, mortality, and discharge disposition between patients with and without confirmed COVID-19 infection. Patient data were taken from the NIS from April 2020 to December 2020. COVID-19 diagnosis was determined with the International Classification of Diseases, Tenth Revision, Clinical Modification code U07.1. A total of 30,671 malignant brain tumor patients met inclusion criteria and 738 (2.4%) patients had a confirmed COVID-19 diagnosis. COVID-19-positive patients had lower likelihood of receiving surgery (Odds ratio [OR] 0.43, 95% confidence interval [CI] 0.29-0.63, P < 0.0001), increased likelihood of mortality (OR 2.18, 95% CI 1.78-2.66, P < 0.0001), and increased likelihood of non-routine discharge (OR 1.25, 95% CI 1.13-1.39, P < 0.0001). Notably, COVID patients receiving surgery were not associated with surgical delay (P = 0.17). COVID-19 infection was associated with worse patient outcome in malignant brain tumor patients, including decreased likelihood of receiving surgery, increased likelihood of mortality, and increased likelihood of non-routine discharge. Our study highlights the need to balance the risks and benefits of delaying surgery for malignant brain tumor patients with COVID-19. Although the COVID-19 pandemic is no longer a public health emergency, understanding the pandemic's impact on outcome provides important insight in effective triage for these patients in the situations where resources are limited.