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Brain Pathology (Zurich, Switzerland) Nov 2016If cancer is hard to be treated, brain cancer is even more, caused by the inability of many effective drugs given systemically to cross the blood brain and blood tumor... (Review)
Review
If cancer is hard to be treated, brain cancer is even more, caused by the inability of many effective drugs given systemically to cross the blood brain and blood tumor barriers and reach adequate concentrations at the tumor sites. Effective delivery of drugs to brain cancer tissues is thus a necessary, albeit not sufficient, condition to effectively target the disease. In order to analyze the current status of research on drug delivery to high grade gliomas (HGG-WHO grades III and IV), the most frequent and aggressive brain cancers, a literature search was conducted in PubMed using the terms: "drug delivery and brain tumor" over the publication year 2015. Currently explored drug delivery techniques for HGG include the convection and permeabilization-enhanced deliveries, drug-releasing depots and Ommaya reservoirs. The efficacy/safety ratio widely varies among these techniques and the success of current efforts to increase this ratio widely varies as well.
Topics: Animals; Antineoplastic Agents; Brain Neoplasms; Convection; Drug Delivery Systems; Glioma; Humans
PubMed: 27488680
DOI: 10.1111/bpa.12423 -
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 -
Acta Neurologica Belgica Mar 2017The objective is to study the role of Ommaya reservoir in the treatment of cryptococcal meningitis. The clinical data of 42 patients with cryptococcal meningitis were...
The objective is to study the role of Ommaya reservoir in the treatment of cryptococcal meningitis. The clinical data of 42 patients with cryptococcal meningitis were retrospectively studied. The Ommaya group included 20 patients, who were treated with Amphotericin B (Am B) and Ommaya reservoir implantation. The non-Ommaya group contained 22 patients, who were just treated with Amphotericin B (Am B). In the Ommaya group (surgical group), all 20 patients with Ommaya reservoir were fully recovered, and their average hospital stay period and average treatment period with Amphotericin B were 105.3 ± 18.3 and 75.0 ± 18.1 days, respectively. In the non-Ommaya group (control group), 16 patients were fully recovered and the average hospital stay period and average treatment period with Amphotericin B of these 22 patients were 139.6 ± 29.5 and 150.0 ± 32.2 days, respectively. In the surgical group, average period of cryptococcus disappearance was 20 ± 8 days, while in the control group, that was 35 ± 10 days. The clinical efficacy was better in surgical group than control group (P < 0.05). Ommaya reservoir implantation is a valuable approach in the treatment of cryptococcal meningitis and can improve the cure rate, decrease mortality, and shorten the period of treatment.
Topics: Adult; Drainage; Female; Humans; Male; Meningitis, Cryptococcal; Middle Aged; Neurosurgical Procedures; Postoperative Complications; Retrospective Studies; Treatment Outcome
PubMed: 27492153
DOI: 10.1007/s13760-016-0682-6 -
Child's Nervous System : ChNS :... Jan 2015In this study, we investigated Ommaya reservoir among pediatric patients, its infection rate, and the predisposing factors. We also investigated its role in the...
OBJECTIVES
In this study, we investigated Ommaya reservoir among pediatric patients, its infection rate, and the predisposing factors. We also investigated its role in the reduction of CSF protein. Finally, we explored other factors that would influence the decision to insert an Ommaya in comparison to external ventricular drainage.
METHODS
This is a 6-year retrospective cohort study from a tertiary hospital in Saudi Arabia.
RESULTS
In our study, females were 48.9% (n = 22) while males were 51.1% (n = 23). The mean age at insertion was 2.9 days, SD of 1.67 day. The mean weight at insertion was 0.98 kg, SD of 0.57 kg. The total duration of Ommaya days was 2523 days. The median duration of the reservoir was 21 days. The Ommaya reservoir infection rate was 6.6%. We found an association between organisms cultured from urinary tract and the organisms cultured from the CSF. We also found that CSF protein level is lower in non-infected reservoirs in comparison to those with infection. The number of Ommaya days and the number of days of infection could not explain the mean CSF protein.
CONCLUSIONS
Ommaya reservoir has a low infection rate. Although CSF protein increased by infection, we failed to prove that Ommaya tapping provides a reduction in the CSF protein and, hence, reduction of shunt malfunctions thereafter. We conclude with expert opinions that take into account the psychological factors in addition to the clinical sense in choosing between Ommaya reservoir and external ventricular drainage (EVD).
Topics: Cerebrospinal Fluid Shunts; Cohort Studies; Female; Humans; Hydrocephalus; Infant, Newborn; Infections; Male; Postoperative Complications
PubMed: 25301010
DOI: 10.1007/s00381-014-2561-x -
Paediatric Drugs Aug 2018Prophylactic eradication of central nervous system (CNS) leukaemia is the current standard of care in treating childhood acute lymphoblastic leukaemia (ALL). This is... (Review)
Review
Prophylactic eradication of central nervous system (CNS) leukaemia is the current standard of care in treating childhood acute lymphoblastic leukaemia (ALL). This is conventionally achieved through regular lumbar punctures with intrathecal injections of methotrexate into the cerebrospinal fluid (CSF). Ommaya reservoirs are subcutaneous implantable devices that provide a secure route of drug delivery into the CSF via an intraventricular catheter. They are an important alternative in cases where intrathecal injection via lumbar puncture is difficult. Among UK Paediatric Principal Treatment Centres for ALL we found considerable variation in methotrexate dosing when using an Ommaya reservoir. We review the current safety and theoretical considerations when using Ommaya reservoirs and evidence for methotrexate dose adjustments via this route. We conclude by summarising the pragmatic consensus decision to use 50% of the conventional intrathecal dose of methotrexate when it is administered via Ommaya reservoir in front-line ALL therapy.
Topics: Antineoplastic Agents; Catheters, Indwelling; Child, Preschool; Drug Delivery Systems; Humans; Infusions, Intraventricular; Methotrexate; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 29850985
DOI: 10.1007/s40272-018-0298-9 -
Journal of Korean Neurosurgical Society Jul 2015Treatment of Leptomeningeal carcinomatosis (LMC) from solid cancers has not advanced noticeably since the introduction of intra-cerebrospinal fluid (CSF) chemotherapy in... (Review)
Review
Treatment of Leptomeningeal carcinomatosis (LMC) from solid cancers has not advanced noticeably since the introduction of intra-cerebrospinal fluid (CSF) chemotherapy in the 1970's. The marginal survival benefit and difficulty of intrathecal chemotherapy injection has hindered its wide spread use. Even after the introduction of intraventricular chemotherapy with Ommaya reservoir, frequent development of CSF flow disturbance, manifested as increased intracranial pressure (ICP), made injected drug to be distributed unevenly and thus, the therapy became ineffective. Systemic chemotherapy for LMC has been limited as effective CSF concentration can hardly be achieved except high dose methotrexate (MTX) intravenous administration. However, the introduction of small molecular weight target inhibitors for primary cancer treatment has changed the old concept of 'blood-brain barrier' as the ultimate barrier to systemically administered drugs. Conventional oral administration achieves an effective concentration at the nanomolar level. Furthermore, many studies report that a combined treatment of target inhibitor and intra-CSF chemotherapy significantly prolongs patient survival. Ventriculolumbar perfusion (VLP) chemotherapy has sought to increase drug delivery to the subarachnoid CSF space even in patients with disturbed CSF flow. Recently authors performed phase 1 and 2 clinical trial of VLP chemotherapy with MTX, and 3/4th of patients with increased ICP got controlled ICP and the survival was prolonged. Further trials are required with newly available drugs for CSF chemotherapy. Additionally, new LMC biologic/pharmacodynamic markers for early diagnosis and monitoring of the treatment response are to be identified with the help of advanced molecular biology techniques.
PubMed: 26279806
DOI: 10.3340/jkns.2015.58.1.1 -
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