Although the endonasal endoscopic approach has been applied to remove olfactory groove meningiomas, controversy exists regarding the efficacy and safety of this approach compared with more ...traditional transcranial approaches. The endonasal endoscopic approach was compared with the supraorbital (eyebrow) keyhole technique, as well as a combined "above-and-below" approach, to evaluate the relative merits of each approach in different situations.
Nineteen cases were reviewed and divided according to operative technique into 3 different groups: purely endonasal (6 cases); supraorbital eyebrow (microscopic with endoscopic assistance; 7 cases); and combined endonasal endoscopic with either the bicoronal or eyebrow microscopic approach (6 cases). Resection was judged on postoperative MRI using volumetric analysis. Tumors were assessed based on the Mohr radiological classification and the presence of the lion's mane sign.
The mean age at surgery was 61.4 years. The mean tumor volume was 19.6 cm(3) in the endonasal group, 33.5 cm(3) in the supraorbital group, and 37.8 cm(3) in the combined group. Significant frontal lobe edema was identified in 10 cases (52.6%). The majority of tumors were either Mohr Grade II (moderate) (42.1%) or Grade III (large) (47.4%). Gross-total resection was achieved in 50% of the endonasal cases, 100% of the supraorbital eyebrow cases with endoscopic assistance, and 66.7% of the combined cases. The extent of resection was 87.8% for the endonasal cases, 100% for the supraorbital eyebrow cases, and 98.9% for the combined cases. Postoperative anosmia occurred in 100% of the endonasal and combined cases and only 57.1% of the supraorbital eyebrow cases. Excluding anosmia, permanent complications occurred in 83.3% of the cases in the endoscopic group, 0% of the cases in the supraorbital eyebrow group, and 16.7% of cases in the combined group (p = 0.017). There were 3 tumor recurrences: 2 in the endonasal group and 1 in the combined group.
The supraorbital eyebrow approach, with endoscopic assistance, leads to a higher extent of resection and lower rate of complications than the purely endonasal endoscopic approach. The endonasal endoscopic approach by itself may be suitable for a small percentage of cases. The combined above-and-below approaches are useful for large tumors with invasion of the ethmoid sinuses.
This review provides a practical clinical perspective on the relevance of hepatic transporters in pharmacokinetics and drug‐drug interactions (DDIs). Special emphasis is placed on transporters with ...clear relevance to clinical DDIs, efficacy, and safety. Basolateral OATP1B1 and 1B3 emerged as important hepatic drug uptake pathways, sites for systemic DDIs, and sources of pharmacogenetic variability. As the first step in hepatic drug removal from the circulation, OATPs are an important determinant of systemic pharmacokinetics, specifically influencing systemic absorption, clearance, and hepatic distribution for subsequent metabolism and/or excretion. Biliary excretion of parent drugs is a less prevalent clearance pathway than metabolism or urinary excretion, but BCRP and MRP2 are critically important to biliary/fecal elimination of drug metabolites. Inhibition of biliary excretion is typically not apparent at the level of systemic pharmacokinetics but can markedly increase liver exposure. Basolateral efflux transporters MRP3 and MRP4 mediate excretion of parent drugs and, more commonly, polar metabolites from hepatocytes into blood. Basolateral excretion is an area in need of further clinical investigation, which will necessitate studies more complex than just systemic pharmacokinetics. Clinical relevance of hepatic uptake is relatively well appreciated, and clinical consequences of hepatic excretion (biliary and basolateral) modulation remain an active research area.
There is an increasing interest in transporter induction (i.e., decreased systemic drug exposure due to increased efflux‐limited absorption or transporter‐mediated clearance) as a mechanism of ...drug–drug interactions (DDIs), although evidence of clinical relevance is still evolving. Intestinal P‐glycoprotein (P‐gp) and hepatic organic anion transporting polypeptides 1B (OATP1B) can be important determinants of drug absorption and disposition, as well as targets for DDIs. Current data indicate that intestinal P‐gp protein levels can be induced up to threefold to fourfold in humans primarily with pregnane X receptor (PXR) activators, and that this induction can decrease the systemic exposure of drugs with P‐gp efflux‐limited absorption (e.g., ≤ 67% decrease in the exposure of total dabigatran following rifampin multiple oral dosing). Evaluation of the clinical relevance of P‐gp induction as a DDI mechanism must consider the induction potential of the perpetrator drug for P‐gp and attenuation of exposure of the victim drug in the context of its therapeutic window. Practical drug development recommendations are provided herein. Reports are contradictory on OATP1B induction by PXR activators in human hepatocytes and liver biopsies. Some clinical investigations demonstrated that rifampin pretreatment decreased exposure of OATP1B substrates, while other studies found no differences, and the potential involvement of other mechanisms in these observed DDIs cannot be definitively ruled out. Thus, further studies are needed to understand hepatic OATP1B induction and potential involvement of other mechanisms contributing to reduced exposure of OATP1B substrates. This review critically summarizes the state‐of‐the‐art on intestinal P‐gp and hepatic OATP1B induction, and highlights implications for drug development.
Endoscopic transsphenoidal surgery is expanding in acceptance, yet postoperative CSF leak rates remain a concern. This study presents the Cornell closure protocol, which has yielded significantly ...lower postoperative CSF leak rates compared with prior reports, as an algorithm that can be used by centers having difficulty with CSF leak.
A single closure algorithm for endoscopic surgery has been used since January 2010 at Weill Cornell Medical College. A prospective database noting intraoperative CSF leak, closure technique, and postoperative CSF leak was reviewed. The authors used a MEDLINE search to identify similar studies and compared CSF leak rates to those of patients treated using the Cornell algorithm.
The retrospective study of a prospectively acquired database included 209 consecutive patients. In 84 patients (40%) there was no intraoperative CSF leak and no postoperative CSF leak. In the 125 patients (60%) with an intraoperative CSF leak, 35 of them with high-flow leaks, there were 0 (0%) postoperative CSF leaks.
It is possible to achieve a CSF leak rate of 0% by using this closure protocol. With proper experience, endoscopic skull base surgery should not be considered to have a higher CSF leak rate than open transcranial or microscopic transsphenoidal surgery.
Craniopharyngiomas are benign parasellar tumors for which surgical removal, although potentially curative, often leads to morbidity with resulting decreases in quality of life (QOL). The endonasal ...endoscopic approach is a minimal-access technique for removing these tumors and may reduce postoperative morbidity. The QOL following this method for resection of craniopharyngiomas has not been documented.
The authors reviewed a database of consecutive endonasal endoscopic surgeries done at Weill Cornell Medical College. Adult patients with histologically proven craniopharyngiomas were included who had completed either only postoperative (> 9 months) or both pre- and postoperative QOL forms, the Anterior Skull Base Quality of Life (ASBQ) questionnaire, and the 22-Item Sinonasal Outcome Test (SNOT-22). Rates of gross-total resection (GTR), complications, and visual and endocrine function were collected. Retrospective independence (Wen score) was also assigned. A contemporaneous group of patients undergoing endonasal endoscopic pituitary macroadenoma resection was used as a control.
This study included 33 procedures performed in 31 patients. The average postoperative ASBQ score was 3.35 and the SNOT-22 score was 19.6. Better QOL was associated with GTR and postoperative radiation. Worse QOL was associated with persistent visual defects, hypopituitarism, tumor recurrence, increase in body mass index, and worsening Wen score. In a subset of 10 patients, both pre- and postoperative (> 9 months) QOL scores were obtained. Both ASBQ and SNOT-22 scores showed stability and a trend toward improvement, from 2.93 ± 0.51 to 2.96 ± 0.47 (ASBQ) and 23.7 ± 10.8 to 18.4 ± 11.6 (SNOT-22). Compared with 62 patients undergoing endoscopic pituitary macroadenoma resection, patients with craniopharyngiomas had worse postoperative QOL on the ASBQ (3.35 vs 3.80; p = 0.023) and SNOT-22 (19.6 vs 13.4; p = 0.12).
This report of validated site-specific QOL following endoscopic surgery for craniopharyngiomas shows an overall maintenance of postoperative compared with preoperative QOL. Better QOL could be seen in patients with GTR and radiation therapy, and worse QOL was found in patients with visual or endocrine deficits. Nevertheless, patients with craniopharyngiomas still had worse QOL than those undergoing similar surgery for pituitary macroadenomas, confirming the worse prognosis of craniopharyngiomas even when removed via a minimally invasive approach. These measures should serve as benchmarks for comparison with open transcranial approaches to similar tumors.
The objective of this study was the preclinical design and construction of a flexible intrasphenoid coil aiming for submillimeter resolution of the human pituitary gland.
Sphenoid sinus measurements ...determined coil design constraints for use in > 95% of adult patients. Temperature safety parameters were tested. The 2-cm-diameter coil prototype was positioned in the sphenoid sinus of cadaveric human heads utilizing the transnasal endoscopic approach that is used clinically. Signal-to-noise ratio (SNR) was estimated for the transnasal coil prototype compared with a standard clinical head coil. One cadaveric pituitary gland was explanted and histologically examined for correlation to the imaging findings.
With the coil positioned directly atop the sella turcica at a 0° angle of the B0 static field, the craniocaudal distance (21.2 ± 0.8 mm) was the limiting constraint. Phantom experiments showed no detectable change in temperature at two sites over 15 minutes. The flexible coil was placed transnasally in cadaveric specimens using an endoscopic approach. The image quality was subjectively superior at higher spatial resolutions relative to that with the commercial 20-channel head coil. An average 17-fold increase in the SNR was achieved within the pituitary gland. Subtle findings visualized only with the transnasal coil had potential pathological correlation with immunohistochemical findings.
A transnasal radiofrequency coil feasibly provides a 17-fold boost in the SNR at 3 T. The ability to safely improve the quality of pituitary imaging may be helpful in the identification and subsequent resection of small functional pituitary lesions.
Purpose
Stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (fSRT) are noninvasive therapies for vestibular schwannomas providing excellent tumor control. However, delayed ...hearing loss after radiation therapy remains an issue. One potential target to for improving hearing rates is limiting radiation exposure to the cochlea.
Methods
We retrospectively reviewed 100 patients undergoing either SRS with 12 Gy (n = 43) or fSRT with 50 Gy over 28 fractions (n = 57) for vestibular schwannoma. Univariate and multivariate analysis were carried out to identify predictors of hearing loss as measured by the Gardner Robertson scale after radiation therapy.
Results
Deterioration of hearing occurred in 30% of patients with SRS and 26% with fSRT. The overall long term (> 2 year) progression rates were 20% for SRS and 16% for fSRT. Patients with a decrease in their Gardner Robertson hearing score and those that loss serviceable hearing had significantly higher average minimal doses to the cochlea in both SRS and fSRT cohorts. ROC analysis showed that a cut off of 5 Gy and 35 Gy, for SRS and fSRT respectively, predicted hearing loss with high sensitivity/specificity.
Conclusion
Our data suggests the minimal dose of radiation that the cochlear volume is exposed to is a predictor of delayed hearing loss after either SRS or fSRT. A threshold of 5 Gy/35 Gy may lead to improved hearing preservation after radiotherapy. Further prospective multi center studies can further elucidate this mechanism.
Although primary studies have reported the safety and efficacy of LITT as a primary treatment in glioma, they are limited by sample sizes and institutional variation in stereotactic parameters such ...as temperature and laser power. The current literature has yet to provide pooled statistics on outcomes solely for primary brain tumors according to the 2021 WHO Classification of Tumors of the Central Nervous System (WHO CNS5). In the present study, we identify recent articles on primary CNS neoplasms treated with LITT without prior intervention, focusing on relationships with molecular profile, PFS, and OS. This meta-analysis includes the extraction of data from primary sources across four databases using the Covidence systematic review manager. The pooled data suggest LITT may be a safe primary management option with tumor ablation rates of 94.8% and 84.6% in IDH-wildtype glioblastoma multiforme (GBM) and IDH-mutant astrocytoma, respectively. For IDH-wildtype GBM, the pooled PFS and OS were 5.0 and 9.0 months, respectively. Similar to rates reported in the prior literature, the neurologic and non-neurologic complication rates for IDH-wildtype GBM were 10.3% and 4.8%, respectively. The neurologic and non-neurologic complication rates were somewhat higher in the IDH-mutant astrocytoma cohort at 33% and 8.3%, likely due to a smaller cohort size.
The intraoperative detection of CSF leaks during endonasal endoscopic skull base surgery is critical to preventing postoperative CSF leaks. Intrathecal fluorescein (ITF) has been used at varying ...doses to aid in the detection of intraoperative CSF leaks. However, the sensitivity and specificity of ITF at certain dosages is unknown.
A prospective database of all endoscopic endonasal procedures was reviewed. All patients received 25 mg ITF diluted in 10 ml CSF and were pretreated with dexamethasone and Benadryl. Immediately after surgery, the operating surgeon prospectively noted if there was an intraoperative CSF leak and fluorescein was identified. The sensitivity, specificity, and positive and negative predictive power of ITF for detecting intraoperative CSF leak were calculated. Factors correlating with postoperative CSF leak were determined.
Of 419 patients, 35.8% of patients did not show a CSF leak. Fluorescein-tinted CSF (true positive) was noted in 59.7% of patients and 0 false positives were encountered. CSF without fluorescein staining (false negative) was noted in 4.5% of patients. The sensitivity and specificity of ITF were 92.9% and 100%, respectively. The negative and positive predictive values were 88.8% and 100%, respectively. Postoperative CSF leaks only occurred in true positives at a rate of 2.8%.
ITF is extremely specific and very sensitive for detecting intraoperative CSF leaks. Although false negatives can occur, these patients do not appear to be at risk for postoperative CSF leak. The use of ITF may help surgeons prevent postoperative CSF leaks by intraoperatively detecting and confirming a watertight repair.
The role of P‐glycoprotein (P‐gp) and breast cancer resistance protein (BCRP) in drug–drug interactions (DDIs) and limiting drug absorption as well as restricting the brain penetration of drugs with ...certain physicochemical properties is well known. P‐gp/BCRP inhibition by drugs in the gut has been reported to increase the systemic exposure to substrate drugs. A previous International Transporter Consortium (ITC) perspective discussed the feasibility of P‐gp/BCRP inhibition at the blood–brain barrier and its implications. This ITC perspective elaborates and discusses specifically the hepatic and renal P‐gp/BCRP (referred as systemic) inhibition of drugs and whether there is any consequence for substrate drug disposition. This perspective summarizes the clinical evidence‐based recommendations regarding systemic P‐gp and BCRP inhibition of drugs with a focus on biliary and active renal excretion pathways. Approaches to assess the clinical relevance of systemic P‐gp and BCRP inhibition in the liver and kidneys included (i) curation of DDIs involving intravenously administered substrates or inhibitors; (ii) in vitro‐to‐in vivo extrapolation of P‐gp‐mediated DDIs at the systemic level; and (iii) curation of drugs with information available about the contribution of biliary excretion and related DDIs. Based on the totality of evidence reported to date, this perspective supports limited clinical DDI risk upon P‐gp or BCRP inhibition in the liver or kidneys.
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