State of the neoadjuvant therapy for glioblastoma multiforme-Where do we stand?

Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor in adults. Despite several investigations in this field, maximal safe resection followed by chemoradiotherapy and adjuvant temozolomide with or without tumor-treating fields remains the standard of care with poor survival outcomes. Many endeavors have failed to make a dramatic change in the outcomes of GBM patients. This study aimed to review the available strategies for newly diagnosed GBM in the neoadjuvant setting, which have been mainly neglected in contrast to other solid tumors.

Anterior endoscopic sublabial transmaxillary access to middle cranial base lesions.

BACKGROUND: Anterior endoscopic access to middle cranial base lesions becomes feasible in the presence of infratemporal fossa (ITF) involvement. Various approaches, including endoscopic endonasal, transoral sublabial, and transorbital methods, have been described for accessing the ITF through a transmaxillary corridor. Among these approaches, endonasal access is the most commonly preferred, while the transorbital approach is a novel technique gaining popularity. The transoral sublabial approach is considered suitable for selected lesions. METHODS: Patients who underwent the anterior endoscopic transoral/sublabial transmaxillary approach to middle cranial base lesions at a single institute from 2016 to 2023 were included in this retrospective study. Malignant lesions were excluded from the study. The sublabial approach was exclusively performed in all cases, with the exception of one patient who required a combined approach. RESULTS: The anterior endoscopic transoral sublabial transmaxillary approach to the infratemporal fossa, upper parapharyngeal space, and middle cranial fossa was performed on 14 patients. The underlying conditions for these patients were as follows: trigeminal schwannomas (n = 8), meningiomas (n = 2), juvenile nasopharyngeal angiofibroma, osteochondroma, arachnoid cyst and encephalocele (n = 1 each). Gross total resection was achieved in 11 cases. The most common complication was numbness in the territory of the maxillary and mandibular nerves (n = 4). Two patients needed endoscopic maxillary antrostomy for persistent suppuration. No wound problems or CSF rhinorrhea occurred. The average follow-up time was 26.6 months. CONCLUSION: The endoscopic sublabial transmaxillary approach provides direct access to the infratemporal fossa and middle cranial base, enhancing the surgical range of maneuverability while sparing the sinonasal cavity. This procedure is safe, less invasive, and could be used as an efficient corridor for the resection of selected infratemporal fossa lesions with or without extension to the middle cranial base and parapharyngeal space.

Pituitary metastasis from renal cell carcinoma presenting with significant hyperprolactinemia, case report.

Key Clinical Message: Kidney metastasis to the pituitary gland can cause hyperprolactinemia even above 250 ng/mL. Although the treatment of metastasis is palliative, surgical decompression could play a major role in the recovery of symptoms and improve quality of life. Pituitary metastasis should be considered in the evaluation of an unusual pituitary mass. Abstract: Pituitary tumors are frequently encountered in the neurosurgical setting. Although the majority of them are pituitary adenomas, rare entities encompass pituitary metastasis. They should be differentiated from pituitary adenomas because their management and prognosis are different. We report a 53-year-old female who complained of headache and had remarkable hyperprolactinemia (271.1 ng/mL). Having considered macroprolactinoma as the initial diagnosis, medical treatment was initiated with Cabergoline. Subsequently, the patient's vision deteriorated which prompted us to perform endoscopic endonasal transsphenoidal surgery. Histologic examination of the resected tumor revealed metastatic renal cell carcinoma. Main treatment for these subjects is palliative; and unlike the pituitary adenoma, the prognosis is unfortunately poor. Pituitary metastasis should be considered in the evaluation of an unusual pituitary mass associated with hyperprolactinemia.

Skull base osteomyelitis: A case report of Garcin syndrome due to mucormycosis in COVID pandemic.

Garcin syndrome is characterized by progressive unilateral multiple cranial nerve palsy without the presence of intracranial hypertension. In this case, we present a patient who experienced lower cranial nerve (CN 9-12) involvement attributed to post-mucormycosis osteomyelitis of the skull base. The osteomyelitis resulting from mucormycosis led to the development of Garcin syndrome, which manifested as progressive paralysis of the cranial nerves. It is important to recognize this rare complication and consider it in the differential diagnosis when evaluating patients with lower cranial nerve palsy following mucormycosis-related skull base osteomyelitis.

Complications in Endoscopic Endonasal Pituitary Adenoma Surgery: An Institution Experience in 310 Patients.

Objective Endoscopic endonasal approaches (EEAs) have shown excellent results for majority of hypophyseal tumors. The aim of this study was to evaluate and report the complications of EEA in patients with pituitary adenoma (PA) who underwent surgery between 2013 and 2018. Methods We performed a retrospective review of 310 consecutive patients/325 procedures with PA treated with an EEA from May 2013 to January 2018. Minor complications including transient diabetes insipidus (DI) or new anterior pituitary hormone insufficiency in one axis and major complications including CSF leakage, hematoma needing reoperation, vascular damage, brain infection, new pan-hypopituitarism permanent DI, new visual impairment, neurological deficits, and mortality were recorded. Results We encountered 58 complications in 310 patients (18.7%) and 325 procedures (17.7%). Minor complications were 43 (13.9 and 13.2%) in 310 patients and in 325 procedures, respectively; whereas, major complications were 28 (9 and 8.6%, respectively). Total complications were associated with diameter group 2 (>30 mm), diaphragm sella violation, suprasellar extension, parasellar involvement, nonfunctional secretory type, and intraoperative arachnoid tearing. Conclusion EEA can be considered as a safe surgical treatment which has acceptable complications in the management of PAs.

Internal carotid artery injury during endoscopic endonasal surgery for skull base pathologies: an institutional incidence, management, and outcome.

BACKGROUND: Endoscopic endonasal surgery (EES) has become a popular approach to deal with skull base pathologies. The most catastrophic intra-operative complication of EES is internal carotid artery (ICA) injury. We aim to discuss and introduce our institutional experience with ICA injury during EES. METHODS: A retrospective review of patients who underwent EES from 2013 to 2022 was performed to determine the incidence and outcomes of intraoperative ICA injuries. RESULTS: There were six patients (0.56%) with intraoperative ICA injury in our institution during the last 10 years. Fortunately, there was no morbidity or mortality in our patients with intraoperative ICA injuries. The sites of injury were equally in paraclival, cavernous sinus, and preclinoidal segments of ICA. CONCLUSION: Primary prevention is the best solution for this condition. Regarding our institutional experience, the best option for primary management just after an injury is packing the surgical site. In cases where packing is not enough for temporary control of bleeding, common carotid artery occlusion should be considered. We have presented our experience and reviewed previous studies regarding different treatments and suggested our intra and post-operative management algorithm.

A case of chronic ossified hematoma presented as a skull lesion: A literature review on two rare conditions, cephalhematoma, and intradiploic hematoma.

Cephalhematoma is a frequent condition in newborn infants due to birth-related trauma, but ossified cephalhematoma (OCH) is a rare condition, especially when it presents as a skull lesion in the older pediatric population. Chronic intradiploic hematoma (CIH) is another rare condition caused by an organized hematoma between the inner and outer tables of the skull. Differentiating CIH from OCH could be difficult for young neurosurgeons. We present an 18-month-old girl with an OCH presented as a skull lesion, which was managed with craniectomy and en-bloc excision of the organized hematoma. This manuscript discusses the differences between OCH and CIH in diagnosis and management.

Can Preoperative Diffusion Tensor Imaging Tractography Predict the Visual Outcomes of Patients with Pituitary Macroadenomas? A Prospective Pilot Study.

OBJECTIVE: Visual impairment has been reported as the most common clinical manifestation of pituitary adenoma (PA) due to the compressive effect of the tumor. This prospective study aimed to evaluate the predictive role of diffusion tensor imaging (DTI) in the visual improvement of patients with PA, who were candidates for endoscopic endonasal surgery. METHODS: A total of 13 patients (male, 8; female, 5) with visual impairment due to pituitary macroadenoma were enrolled in this study. The DTI findings and visual parameters, including visual acuity (VA), visual field (VF), and visual evoked potential (VEP), were recorded for all participants before and 3 months after surgery. RESULTS: Significant recovery was reported in both VA and VF following PA surgery (P < 0.001). The results of perimetry indicated recovery in all quadrants, except for the lower nasal quadrant of the right eye. The tumor volume showed no significant association with the preoperative optic nerve, optic tract, and chiasm fractional anisotropy (FA) or mean diffusivity (MD). The VA and VF recoveries were more likely in patients with a lower preoperative optic nerve MD. Besides, increased preoperative FA of the optic nerve was associated with a higher probability of VA recovery. No significant correlation was found between the optic tract MD and FA values and visual improvement. Overall, MD values below 0.0021 and FA values above 0.1689 could predict a good prognosis of VA recovery after surgery. CONCLUSIONS: DTI may have a predictive value in estimating visual improvement in patients with PA preoperatively.

Surgical management of retrorectal tumors: a single-center 12 years' experience.

Purpose: Retrorectal tumors (RTs) are rare tumors that arise in the space between the mesorectum and the pelvic wall and often originate in embryonic tissues. The primary treatment for these tumors is complete excision surgery, and choosing the best surgical approach is very important. Methods: In this study, we retrospectively collected the data of 15 patients with RTs who underwent surgery in the surgical ward of Imam Khomeini Hospital in Tehran for 12 years to share our experiences of patients' treatment and compare different surgical approaches. Results: A total of 5 tumors were malignant, 10 were benign, and most of the tumors were congenital. Malignant tumors were seen in older patients. Three surgical procedures were performed on patients. Three patients underwent abdominal approach surgery, and 8 patients underwent posterior surgery. A combined surgical approach was performed on 4 patients. Two patients underwent laparoscopic surgery. The abdominal approach had the least long-term complication, and the combined approach had the most complications; laparoscopic surgery reduced the length of hospital stay and complications after surgery. Conclusion: A multidisciplinary team collaboration using magnetic resonance imaging details is necessary to determine a surgical treatment approach. It could reduce the need for a preoperative biopsy. However, every approach has its advantages and disadvantages. In the main, they have no superiority over each other, and individualized treatment is the key.

Post-neurosurgical meningitis; gram negative bacilli vs. gram positive cocci.

Background: Post-neurosurgical meningitis is a significant cause of mortality and morbidity. In this study we aimed to compare the differences of clinical, laboratory features and outcomes between the post-neurosurgical meningitis caused by gram-negative bacilli (GNB) and gram-positive cocci (GPC). Methods: Cases of post-neurosurgical meningitis (with positive CSF culture) were included. After classifying patients as GNB and GPC groups, clinical and paraclinical data were compared. Results: Out of 2667 neurosurgical patients, CSF culture was positive in 45 patients. 25 (54.3%) were GNB, 19 (41.3%) GPC. The most common microorganisms were Klebsiella pneumoniae (n=14, 31.1%), Coagulase negative staphylococcus (n=8, 17.8%), Staphylococcus aureus (n=6, 13.3%), Acinetobacter baumannii (n=4, 8.9%), Pseudomonas aeruginosa (n=2, 4.4%), and Escherichia coli (n=2, 4.4%). There were no correlation between CSF Leakage, Surgical site appearance, presence of drain, Age and GCS between two groups (P=0.11, P=0.28, P=0.06, P=0.86, P=0.11 respectively). The only different laboratory indexes were ESR (86.8 mm/h vs. 59.5 mm/h, P=0.01) and PCT (13.1 ng/ml vs. 0.8 ng/ml, P=0.02) which were higher in GNB cases. 20% (n=5) of patients with GNB meningitis received preoperative corticosteroid, while none of GPC cases received (P=0.03). The median length of hospitalization for GNB and GPC cases was 56 and 44.4 days respectively (P=0.3). Conclusion: The GNB antibiotic coverage should be designed more carefully in post-neurosurgical meningitis especially in patients with recent corticosteroid therapy and elevated ESR and procalcitonin.

Surgical complications of endoscopic approach to skull base: analysis of 584 consecutive patients.

PURPOSE: Endoscopic techniques have been widely applied for challenging cranial base surgeries in recent years. In this study, we evaluated the safety and efficacy of using the endoscopic endo-nasal route for various skull base pathologies in terms of postoperative complications. METHODS: A total of 584 consecutive patients who underwent endoscopic skull base surgery were studied. Peri- and post-operative complications and risk factors affecting the occurrence of these complications were evaluated. RESULTS: 648 endoscopic skull base surgical procedures were performed on 584 patients (47.8% females and 52.2% males) with the mean age of 41.2 years. Pituitary adenoma (69.3%) was the most common pathology. Post-operative mortality was 2.0%. The rates of post-operative permanent neurological deficit (one case of 6th nerve injury, two 12th nerve injuries and one hemiparesis) and visual deterioration were 0.6% and 1.5%, respectively. Ten patients (1.7%) were complicated with meningitis and it was the cause of death in 3. Systemic complications not directly attributable to skull base surgical access occurred in 2% (11 patients) with 5 mortalities. The rate of intra-operative vascular injury was 1% and among them one patient died due to PCA injury. The most common post-operative complications were diabetes insipidus (12.5%), anterior pituitary dysfunction (10.6%) and CSF leak (3.6%), respectively. In general, reoperation, malignant lesions, and level IV of surgical complexity were associated with a higher incidence of complications. CONCLUSION: Endoscopic endo-nasal approach can be a safe and less-morbid first-line treatment of patients with various skull base lesions.

Endoscopic endonasal management of skull base defects in pediatric patients.

PURPOSE: Skull base defects in children may be the result of congenital anomalies or trauma. They often present as cerebrospinal fluid (CSF) rhinorrhea, meningitis, brain abscess or nasal obstruction. Surgical intervention is predominantly the treatment of choice. Our goal is to assess the efficacy of endoscopic endonasal approach in treating skull base defects in pediatric patients. MATERIAL AND METHODS: In this retrospective study we identified 38 patients (mean age 8.7 ± 5.6 years old, ranging 2 months-18 years) who underwent endoscopic endonasal repair of skull base defects, between March 2010 and February 2020. Patients who had skull base reconstruction after tumor resection, those who were lost to follow-up or did not sign the consent forms were excluded from the study. RESULTS: The clinical indications for endoscopic endonasal repair were trauma (n = 24, 63.1%) and congenital defects (n = 14, 36.9%). Congenital skull base defects included basal meningoencephalocele (n = 5, 35.7%) and frontoethmoidal defects (n = 9, 64.3%). Mean follow up time was 32 ± 29.04 months, ranging 2-103 months. Fat graft (alone or in combination) was the most commonly used material to repair the skull base defects. Thirty-seven patients (97%) showed successful results after endoscopic endonasal surgery and were symptom free. CONCLUSION: The endoscopic endonasal repair of CSF leak and skull base defects proved to be safe and feasible with 97% success rate.

Teamwork in Cranial Base Surgery: A Feasible Task or a Utopian Dream.

In the past decade or perhaps a little earlier than that the concept of teamwork evolved among the circles of surgeons especially among those involved in complicated and time consuming surgeries. Skull base surgeries were one of those surgeries where the role of teamwork was acutely felt owing to innumerable specialties involved in the consummation of such surgeries. Although teamwork in this specialty is the need of the hour but, achieving the spirit of teamwork is not that easy and perhaps a challenging task. This manuscript tackles the much needed demand of teamwork in this arena of surgery and unveils whether such a teamwork is achievable or is just an utopian dream.

IgG4-related hypophysitis.

Hypophysitis is a rare pituitary inflammatory disorder classified in different ways. Immunoglobulin G4-related disease (IgG4-RD), also a rare disease is a systemic fibro-inflammatory condition characterized by infiltration of tissue with IgG4-positive plasma cells; however prevalence of both of them probably is underestimated. In this paper, we present an Iranian patient with biopsy-proven IgG4-related hypophysitis and then review the clinical characteristics, laboratory, imaging, pathologic findings and therapeutic management as well as prognosis of 115 published cases of hypophysitis secondary to IgG4-related disease.

Surgical Outcomes of Endoscopic Endonasal Surgery in 29 Patients with Craniopharyngioma.

Background Recently the endoscopic endonasal surgery (EES) has been introduced as a modality for the treatment of patients with craniopharyngiomas. In this study, we describe our initial experience in treatment of 29 patients with craniopharyngiomas using this approach. Methods Twenty-nine consecutive patients with craniopharyngiomas who had undergone EES in a 5-year period were studied retrospectively. Patients underwent preoperative and postoperative endocrinologic and ophthalmologic evaluations. Radiologic characteristics of tumors and extent of resection were determined. The recurrence and complications were evaluated. Results Pituitary and visual dysfunction were observed preoperatively in 89.7 and 86% of patients, respectively. After EES, visual outcome either showed an improvement or else remained unchanged in 92.3% of the cases; however, pituitary function remained unchanged and even got worsened in 34.6% of the cases. Prevalence of diabetes insipidus before and after surgery was 58.6 and 69.2%. The rate of gross total resection was 62%. Moreover, 86.2% of the tumors were almost totally resected (more than 95% of the tumor size resected). After surgery, cerebrospinal fluid (CSF) leak and meningitis occurred in four (13.8%) and two (6.9%) patients, respectively. Perioperative mortality was seen in two of the cases (6.9%). The mean follow-up was 25 months and tumor recurrence was discovered in four patients (15.3%). Conclusion The EES with the goal of maximal and safe tumor resection could be used for the treatment of most craniopharyngiomas. Although the rates of visual improvement and gross tumor resection are high, CSF leak, pituitary dysfunction, and meningitis are serious concerns.

Surgical Outcome of Endoscopic Endonasal Surgery of Large and Giant Pituitary Adenomas: An Institutional Experience from the Middle East.

OBJECTIVE: Surgical treatment of large and giant pituitary adenomas is challenging and associated with higher risk of complications and lower rate of gross total resection. We present our experience with surgical management of large and giant adenomas using the extended endoscopic transsphenoidal approach (EETA). METHODS: A total of 80 patients with large (30-39 mm) and giant (≥40 mm) pituitary adenomas who underwent tumor resection using EETA were studied. Radiologic data, hormonal and visual status, surgical outcomes, complications, and factors affecting the extent of resection were evaluated. RESULTS: Forty-five tumors (56.3%) were classified as large and 35 (43.8%) as giant adenomas. Gross total resection was achieved in 66 patients (82.5%), near-total resection in 10 (12.5%), and subtotal resection in 4 (5%). Preoperative factors including larger tumor size, multilobular shape of tumor, and higher Knosp scores significantly decrease the likelihood of gross total resection. Of patients with preoperative visual acuity impairment and visual field deficit, 76.8% and 74.1%, respectively, experienced improvement after surgery. The most common complications include new pituitary insufficiency (16.4%), permanent diabetes insipidus (7.5%), and cerebrospinal fluid leakage (5%). Two cases of meningitis (2.5%) and 3 deaths (3.8%) occurred in this cohort of patients. Mean follow-up duration was 24.2 months. CONCLUSIONS: EETA can be a safe and efficient approach as the first-line treatment of patients with large and giant pituitary adenomas and is associated with high rates of gross total resection or near-total resection, visual function improvement, and a relatively low rate of complications.

Preoperative visual evoked potential in the prediction of visual outcome after pituitary macroadenomas surgery.

OBJECTIVE: The purpose of the present study is to investigate longitudinal changes in Visual evoked potential (VEP) parameters as an objective test after transsphenoidal surgery, its correlation with subjective tests and clinical value of VEP in the prediction of visual outcome. METHODS: Fifty patients with pituitary macroadenoma who underwent surgical removal of the tumor recruited in this study. All the patients underwent ophthalmic examination, static automated perimetry (SAP), VEP and magnetic resonance imaging (MRI) preoperatively and 3 months after surgery. RESULTS: Fifty patients with pituitary macroadenoma (size: 25.1 ± 9.9 mm) were recruited in the study. Before surgery, the pattern of VEP showed a prolonged latency with reduced amplitude in eyes with abnormal visual acuity or abnormal visual field. The P100 wave latencies and amplitudes showed significant correlation with visual acuity and SAP scores. After surgery, visual acuity and visual field improvements were seen in 51% and 65.6% of eyes, respectively. Mean SAP and visual acuity scores increased significantly (p < 0.01), P100 wave latency declined and amplitude improved after surgery but not significantly. The mean age of patients, size of tumors and preoperative P100 wave latency were significantly lower in eyes with visual field and acuity improvement. CONCLUSION: VEP is a helpful quantitative and objective complementary test to visual acuity and SAP exams for assessing pre-operative visual abnormalities and post-operative visual outcome in patients with pituitary macroadenoma.

Ligamentum Flavum Buckling Causing Immediate Post-Operative Neurological Deterioration After an Anterior Cervical Discectomy: Case Report.

Neurological injury is a potential complication of anterior cervical discectomy (ACDF). Iatrogenic trauma, hypoxic-ischemic damage during surgery or epidural hematoma could cause neurological deterioration after surgery. This is the first case being reported of neurological deterioration after an anterior cervical discectomy due to ligamentum flavum buckling. The case illustrated an uncommon cause of cord compression after ACDF. Therefore, ligamentum flavum buckling should be considered as one of the potential causes for acute neurologic deterioration after an anterior cervical discectomy. While keeping this rare complication in mind, obtaining a quick post-operative imaging seems mandatory in early detection and establishing an appropriate management.

Endoscopic Endonasal Approach to the Growth Hormone-Secreting Pituitary Adenomas: Endocrinologic Outcome in 68 Patients.

BACKGROUND: The endoscopic endonasal approach has recently become an acceptable option for resection of all pituitary adenomas. We assessed biochemical outcome of endoscopic endonasal surgery in growth hormone (GH)-secreting adenomas, including remission rate, predictors of remission, and associated complications. METHODS: Sixty-eight consecutive patients with acromegaly who underwent endoscopic endonasal surgery were analyzed prospectively. Tumors were classified according to size, Knosp grade, and Hardy-Wilson classification. Biochemical remission was defined as normal serum insulin-like growth factor 1 level and either a suppressed GH serum level less than 0.4 µg/L during an oral glucose tolerance test or a random GH level less than 1.0 µg/L at least 3 months after surgery. RESULTS: Total biochemical remission rate was 64.7%. Gross total resection was achieved in 61 of the 68 patients (89.7%). Remission was achieved in 12 of 16 microadenomas (75%) and 32 of 52 macroadenomas (61.5%). Based on univariate logistic regression analysis, preoperative variables predictive of remission were age (P = 0.004), Knosp grade (P = 0.023), and preoperative GH levels (P = 0.042). Three patients (4.4%) experienced postoperative panhypopituitarism, and permanent diabetes insipidus was seen in 4 patients (5.9%). Two patients (2.9%) developed cerebrospinal fluid leaks, which were treated by lumbar puncture in one case and early surgical repair in the other case. CONCLUSIONS: Endoscopic endonasal adenoma resection leads to a high rate of endocrinologic remission in GH-secreting adenomas with a low complication rate. Patients with older age, higher preoperative GH levels, and higher Knosp grades are less likely to achieve remission.