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Clinical Lung Cancer Mar 2023Leptomeningeal metastasis (LM) is a highly fatal and debilitating complication of lung adenocarcinoma (LUAD) with limited therapeutic options. This study aimed to...
Safety, Pharmacokinetic and Clinical Activity of Intrathecal Chemotherapy With Pemetrexed via the Ommaya Reservoir for Leptomeningeal Metastases From Lung Adenocarcinoma: A Prospective Phase I Study.
INTRODUCTION
Leptomeningeal metastasis (LM) is a highly fatal and debilitating complication of lung adenocarcinoma (LUAD) with limited therapeutic options. This study aimed to evaluate the efficacy and toxicities of intrathecal chemotherapy (IC) with pemetrexed via Ommaya reservoir in LUAD with refractory LM.
METHODS
In this prospective, single-arm, phase I trial (ChiCTR2000028936), LUAD-LM patients who had progressed after at least two prior treatments were recruited. Pemetrexed from 30 mg to 50 mg was administered on Days 1 and 8 every 3 weeks via Ommaya reservoir. Serial samples of cerebrospinal fluid (CSF) and plasma were obtained for pharmacokinetic studies. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and therapeutic toxicities.
RESULTS
Twenty-three patients were enrolled and analyzed, revealing an ORR of 43.5% (95% CI, 23.2%-63.8%) and DCR of 82.6% (95% CI, 61.2%-95.0%). The median PFS and OS were 6.3 and 9.5 months, respectively. Dose-limiting toxicity was only observed in 2 patients (2/23, 8.7%), and 30 mg pemetrexed was considered as the recommended dose for IC. Pharmacokinetic analysis showed that using Ommaya reservoirs, higher pemetrexed concentrations and prolonged half-lives were achieved in the CSF compared with lumbar puncture (LP).
CONCLUSIONS
Intrathecal pemetrexed at a dose of 30 mg via Ommaya reservoirs on Days 1 and 8 every 21 days achieved promising disease control and satisfactory survival with moderate toxicities in resistant LUAD-LM, providing a feasible and effective option, especially for the patients who cannot tolerate LP.
Topics: Humans; Pemetrexed; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Prospective Studies; Adenocarcinoma of Lung; Meningeal Carcinomatosis; Antineoplastic Combined Chemotherapy Protocols
PubMed: 36588048
DOI: 10.1016/j.cllc.2022.11.011 -
Child's Nervous System : ChNS :... May 2021Labrune syndrome (LS) is a rare white matter disease characterized by leukoencephalopathy with intracranial calcification and cysts (LCC). While the intracranial cyst... (Review)
Review
PURPOSE
Labrune syndrome (LS) is a rare white matter disease characterized by leukoencephalopathy with intracranial calcification and cysts (LCC). While the intracranial cyst characteristics of LS are for the most part stable, some may require surgical intervention when they develop associated hemorrhage and/or mass effect. To date, no review of the surgical outcomes of cyst decompression in LS has been performed.
CASE PRESENTATION
We report the case of a 16-year-old girl with LS who presented with progressive right hemiparesis from an enlarging hemorrhagic left thalamic cyst. The patient underwent frameless stereotactic cyst aspiration and Ommaya reservoir placement and her hemiparesis subsequently improved. Serial monitoring demonstrated stable decompression of the cyst.
CONCLUSIONS
The pathophysiology of LS is thought to be diffuse cerebral microangiopathy and it is thought that these microhemorrhages contribute to the formation of intracranial cysts as well as diffuse calcifications. Indications for surgical intervention in LS are not well established and the heterogeneity of lesions compels them to be managed on a case-by-case basis. Based on our literature review, surgery is the standard treatment of choice for patients with progressive symptoms and growing lesions on imaging studies, with outcomes favoring less-invasive stereotactic approaches with contingencies of reservoir placement when cysts recur.
Topics: Adolescent; Calcinosis; Central Nervous System Cysts; Female; Humans; Leukoencephalopathies; Magnetic Resonance Imaging; Neoplasm Recurrence, Local
PubMed: 32789548
DOI: 10.1007/s00381-020-04861-7 -
Journal of Infection and Chemotherapy :... Mar 2021Leptomeningeal metastases (LM) from solid tumors have poor prognosis. Intrathecal chemotherapy through the Ommaya reservoir (OR) is one of the options for treating LM;...
Epidemiology and prognosis of ommaya reservoir-related bacterial meningitis in adult patients with leptomeningeal metastases from solid tumors: A 10-year retrospective single-center study in Japan.
INTRODUCTION
Leptomeningeal metastases (LM) from solid tumors have poor prognosis. Intrathecal chemotherapy through the Ommaya reservoir (OR) is one of the options for treating LM; however, OR-related bacterial meningitis (ORRBM) is a severe complication in patients who underwent OR placement. Little is known about the incidence rate and prognosis of ORRBM among patients with LM from solid tumors.
METHODS
We retrospectively reviewed the records of patients who underwent OR placement to treat LM from solid tumors at Kawasaki Municipal Kawasaki Hospital between January 2009, and December 2018.
RESULTS
Among 136 patients with OR placement (median age of 64.5 years) including 30,320 Ommaya-days, 18 (13.2%) developed ORRBM (5.9 infections per 10,000 Ommaya-days). The major primary diseases were lung cancer (65.4%). The median times from OR placement and from last OR puncture to ORRBM onset were 20 days and 4.5 days, respectively. Major clinical symptoms were fever (83.3%), headache (50.0%), disturbance of consciousness (50.0%), and nausea (38.9%). Seventeen of 18 patients underwent an OR removal operation. One patient died from ORRBM, and another patient died from heart failure during ORRBM treatment. The median duration of treatment with antibiotics was 16.5 days. The median survival period from the day of OR placement was 146.5 days among patients who developed ORRBM and 142.5 days among patients who did not develop ORRBM.
CONCLUSIONS
The rate of ORRBM among patients with LM from solid tumors in our hospital was 13.2%. ORRBM may not shorten the patients' survival period with adequate management including removal of the device.
Topics: Adult; Humans; Japan; Lung Neoplasms; Meningitis, Bacterial; Middle Aged; Prognosis; Retrospective Studies
PubMed: 33214071
DOI: 10.1016/j.jiac.2020.10.025 -
Pharmacological Research Aug 2022Cellular therapies utilizing T cells expressing chimeric antigen receptors (CARs) have garnered significant interest due to their clinical success in hematological... (Review)
Review
Cellular therapies utilizing T cells expressing chimeric antigen receptors (CARs) have garnered significant interest due to their clinical success in hematological malignancies. Unfortunately, this success has not been replicated in solid tumors, with only a small fraction of patients achieving complete responses. A number of obstacles to effective CAR-T cell therapy in solid tumors have been identified including tumor antigen heterogeneity, poor T cell fitness and persistence, inefficient trafficking and inability to penetrate into the tumor, immune-related adverse events due to on-target/off-tumor toxicity, and the immunosuppressive tumor microenvironment. Many preclinical studies have focused on improvements to CAR design to try to overcome some of these hurdles. However, a growing body of work has also focused on the use of local and/or regional delivery of CAR-T cells as a means to overcome poor T cell trafficking and inefficient T cell penetration into tumors. Most trials that incorporate locoregional delivery of CAR-T cells have targeted tumors of the central nervous system - repurposing an Ommaya/Rickham reservoir for repeated delivery of cells directly to the tumor cavity or ventricles. Hepatic artery infusion is another technique used for locoregional delivery to hepatic tumors. Locoregional delivery theoretically permits increased numbers of CAR-T cells within the tumor while reducing the risk of immune-related systemic toxicity. Studies to date have been almost exclusively phase I. The growing body of evidence indicates that locoregional delivery of CAR-T cells is both safe and feasible. This review focuses specifically on the use of locoregional delivery of CAR-T cells in clinical trials.
Topics: Humans; Immunotherapy, Adoptive; Liver Neoplasms; Neoplasms; Receptors, Chimeric Antigen; T-Lymphocytes; Tumor Microenvironment
PubMed: 35772645
DOI: 10.1016/j.phrs.2022.106329 -
Journal of Neurosurgical Sciences Jun 2023Delayed subdural fluid collections can occur after Ommaya reservoir placement and can cause neurological symptoms and interfere with treatment. We performed a...
BACKGROUND
Delayed subdural fluid collections can occur after Ommaya reservoir placement and can cause neurological symptoms and interfere with treatment. We performed a retrospective chart review to study risk factors for delayed subdural fluid collections and clinical outcomes.
METHODS
Retrospective chart review was performed for patients undergoing Ommaya reservoir placement between 2010-2019 at our institution.
RESULTS
Out of 53 patients who had Ommaya reservoir placement during the study period, 11 developed delayed subdural fluid collections (21%). HIV infection was the only statistically significant risk factor (P=0.001, Fisher's Exact Test). Thrombocytopenia, ventricle size, use of the reservoir, and suboptimal catheter placement were not associated with development of delayed subdural fluid collections. 2 patients, both HIV positive, required surgical evacuation.
CONCLUSIONS
Delayed subdural fluid collections occur in a significant minority of patients after Ommaya reservoir placement, and some patients require surgical intervention. HIV infection is associated with a higher risk of development of delayed subdural fluid collections. This patient subpopulation may benefit from closer monitoring or adjustment of management protocols.
Topics: Humans; Retrospective Studies; HIV Infections; Cerebral Ventricles; Drainage; Craniotomy
PubMed: 33297611
DOI: 10.23736/S0390-5616.20.05187-5 -
Journal of Korean Neurosurgical Society Dec 2023To evaluate the usefulness of a cranial implantable chemoport, the H-port, as an alternative to the Ommaya reservoir for intraventricular chemotherapy/cerebrospinal...
OBJECTIVE
To evaluate the usefulness of a cranial implantable chemoport, the H-port, as an alternative to the Ommaya reservoir for intraventricular chemotherapy/cerebrospinal fluid (CSF) access in patients with leptomeningeal metastasis (LM).
METHODS
One hundred fifty-two consecutive patients with a diagnosis of LM and who underwent H-port installation between 2015 and 2021 were evaluated. Adverse events associated with installation and intraventricular chemotherapy, and the rate of increased intracranial pressure (ICP) control via the port were evaluated for safety and efficacy. These indices were compared with published data of Ommaya (n=89), from our institution.
RESULTS
Time-to-install and installation-related complications of intracranial hemorrhage (n=2) and catheter malposition (n=5) were not significantly different between the two groups. Intraventricular chemotherapy-related complications of CSF leakage occurred more frequently in the Ommaya than in the H-port group (13/89 vs. 3/152, respectively, p<0.001). Intracranial hemorrhage during chemotherapy occurred only in the Ommaya group (n=4). The CSF infection rate was not statistically different between groups (14/152 vs. 12/89, respectively). The ICP control rate according to reservoir type revealed a significantly higher ICP control rate with the H-port (40/67), compared with the Ommaya result (12/58, p<0.001). Analyzing the ICP control rate based on the CSF drainage method, continuous extraventricular drainage (implemented only with the H-port), found a significantly higher ICP control rate than with intermittent CSF drainage (33/40 vs. 6/56, respectively, p<0.0001).
CONCLUSION
The H-port for intraventricular chemotherapy in patients with LM was superior for ICP control; it had equal or lower complication rates than the Ommaya reservoir.
PubMed: 38061763
DOI: 10.3340/jkns.2023.0178 -
Journal of Neuro-oncology Sep 2022Children with craniopharyngiomas (CP) can experience significant morbidities caused by extensive surgery and/or radiation. Ommaya reservoir insertion (ORI) into cystic...
INTRODUCTION
Children with craniopharyngiomas (CP) can experience significant morbidities caused by extensive surgery and/or radiation. Ommaya reservoir insertion (ORI) into cystic CP represents a minimally invasive approach allowing immediate decompression and aims to avoid additional injuries. The purpose of this study was to determine the surgical outcome and relevance of upfront ORI (± intracystic treatment) for preservation of endocrine function.
METHODS
We performed a retrospective chart review of children with CP treated at the Hospital for Sick Children between 01/01/2000 and 15/01/2020. Endocrine function was reviewed at the time of initial surgery and throughout follow-up. New endocrinological deficits related to the index procedure were defined as immediate failure (IF), whereas postoperative duration of endocrinological stability (ES) was analyzed using the Kaplan-Meier method. The rate of IF and ES was compared between the treatment groups.
RESULTS
Seventy-nine patients were included and had a median age of 8.3 years (range 2.1-18.0 years); 31 were males. Fifty-three patients with upfront surgical treatment, including 29 ORI and 24 gross total or partial resections had sufficient endocrinological follow-up data. Endocrine dysfunction occurring immediately after the index procedure (IF) was observed in 15 patients (62.5%) in the resection group compared to two patients (6.8%) in the ORI group, odds ratio: 0.05 (CI: 0.01-0.26, p < 0.0001). Excluding those with immediate endocrinological deficits, mean ES after ORI was 19.4 months (CI: 11.6-34.2), compared to 13.4 months (CI:10.6-NA) after surgical resection.
CONCLUSIONS
Endocrine function was preserved in patients with upfront ORI (± intracystic treatment), which was confirmed as a minimally invasive procedure with an overall low morbidity profile.
Topics: Adolescent; Child; Child, Preschool; Craniopharyngioma; Female; Humans; Male; Pituitary Neoplasms; Retrospective Studies; Treatment Outcome
PubMed: 35925530
DOI: 10.1007/s11060-022-04099-0 -
Neuro-Chirurgie Sep 2023Many pathologies require normal-sized ventricle cannulation, which may be technically challenging even with neuronavigation guidance. This study presents a series of...
INTRODUCTION
Many pathologies require normal-sized ventricle cannulation, which may be technically challenging even with neuronavigation guidance. This study presents a series of ventricular cannulation of normal-sized ventricles using intraoperative ultrasound (iUS) guidance and the outcomes of patients treated by this technique, for the first time.
METHODS
The study included patients who underwent ultrasound-guided ventricular cannulation of normal-sized ventricles (either ventriculoperitoneal (VP) shunting or Ommaya reservoir) between January 2020 and June 2022. All patients underwent iUS-guided ventricular cannulation from the right Kocher's point. The inclusion criteria for normal-sized ventricles were as follows: (1) Evans index <30%, and (2) widest third ventricle diameter <6mm. Medical records and pre-, intra- and post-operative imaging were retrospectively analyzed.
RESULTS
Nine of the 18 included patients underwent VP shunt placement; 6 had idiopathic intracranial hypertension (IIH), 2 had resistant cerebrospinal fluid fistula following posterior fossa surgery, and 1 had iatrogenic intracranial pressure elevation following foramen magnum decompression. Nine patients underwent Ommaya reservoir implantation, 6 of whom had breast carcinoma and leptomeningeal metastases and 3 hematologic disease and leptomeningeal infiltration. All catheter tip positions were achieved in a single attempt, and none were placed suboptimally. Mean follow-up was 10 months. One IIH patient (5.5%) had early shunt infection which necessitated shunt removal.
CONCLUSION
iUS is a simple and safe method for accurate cannulation of normal-sized ventricles. It provides an effective real-time guidance option for challenging punctures.
Topics: Humans; Treatment Outcome; Retrospective Studies; Catheterization; Cerebral Ventricles; Ventriculoperitoneal Shunt; Ultrasonography, Interventional; Hydrocephalus
PubMed: 37393990
DOI: 10.1016/j.neuchi.2023.101463 -
Heliyon Jun 2024To explore the relationship and difference between ventricular and lumbar cerebrospinal fluid(CSF), this study presents equations transforming their measures. By...
Exploring the correlation and difference between cerebrospinal fluid in the lateral ventricle and lumbar subarachnoid based on infants with intraventricular hemorrhage treated by the ommaya reservoir.
OBJECTIVE
To explore the relationship and difference between ventricular and lumbar cerebrospinal fluid(CSF), this study presents equations transforming their measures. By assessing the viability of substituting lumbar puncture, we aim to minimize the associated medical risks and trauma faced by infants with intraventricular hemorrhage(IVH) from anesthesia and lumbar puncture.
METHODS
We retrospectively analyzed CSF data from 27 infants diagnosed with IVH treated by Ommaya reservoir and lumbar puncture at our center, comprising 35 paired samples. Paired-sample and regression analyses were employed to determine test correlations, differences, and to derive transformation equations for the measurements.
RESULTS
Comparative analyses between the CSF from the lateral ventricle and the lumbar vertebrae revealed significant differences in the levels of chloride, glucose, protein, erythrocytes, total cells, and Pandy's test. Specifically:1. Levels of chloride, glucose, protein, and Pandy's test were higher in the lumbar vertebrae.2. Conversely, erythrocyte and total cell counts were higher in the lateral ventricle.There were no significant differences observed for lumbar lactate dehydrogenase(LDH), leukocytes, occult blood, clot, clarity, and color. Nevertheless, significant correlations were identified between various measures, including LDH, glucose, chloride, protein, erythrocyte, leukocyte, total cell count, Pandy's test, occult blood, clot, transparency, and color. Interestingly, the correlation strength and equation fit for each component are inversely proportional to its molecular weight.Notably, well-fitting regression equations were found for LDH, glucose, chloride, protein, leukocytes, erythrocytes, and total cells.
CONCLUSION
In infants with IVH and unobstructed CSF channels, a robust correlation was noted between ventricular CSF sourced via the Ommaya reservoir and lumbar CSF. This correlation tended to be inversely related to molecular weight, with smaller molecular weights showing lesser disparities. Ventricular CSF data could anticipate lumbar CSF trends, and using regression equations with Ommaya-obtained CSF, one can derive approximate values for lumbar CSF.
PubMed: 38912498
DOI: 10.1016/j.heliyon.2024.e32252 -
Journal of Medical Biography Sep 2023Dr Ayub Khan Ommaya (1930-2008) was a pioneering figure in the field of neurosurgery, with a particular focus on traumatic brain injury. As history books have held, he...
Dr Ayub Khan Ommaya (1930-2008) was a pioneering figure in the field of neurosurgery, with a particular focus on traumatic brain injury. As history books have held, he was a man of great intellect and vision, possessing a rare combination of scientific rigour and compassionate empathy. One of Dr Ommaya's most notable contributions was his development of the Ommaya reservoir, a device used to deliver drugs directly into the brain. This groundbreaking technology transformed the treatment of brain tumours and other neurological disorders, enabling clinicians to administer medications with unprecedented precision and efficacy. From his groundbreaking research on traumatic brain injury to his visionary invention of the Ommaya reservoir, Ommaya's legacy continues to inspire and inform the work of countless medical professionals around the world. This historical paper delves into Ommaya's remarkable life story, highlighting his extraordinary contributions to the field of neurosurgery.
PubMed: 37722807
DOI: 10.1177/09677720231198502