Malignant glioma, or glioblastoma, is the most common and lethal form of brain tumor with a median survival time of 15 months. The established therapeutic regimen includes a tripartite therapy of ...surgical resection followed by radiation and temozolomide (TMZ) chemotherapy, concurrently with radiation and then as an adjuvant. TMZ, a DNA alkylating agent, is the most successful antiglioma drug and has added several months to the life expectancy of malignant glioma patients. However, TMZ is also responsible for inducing lymphopenia and myelosuppression in malignant glioma patients undergoing chemotherapy. Although TMZ-induced lymphopenia has been attributed to facilitate antitumor vaccination studies by inducing passive immune response, in general lymphopenic conditions have been associated with poor immune surveillance leading to opportunistic infections in glioma patients, as well as disrupting active antiglioma immune response by depleting both T and NK cells. Deletion of O6-methylguanine-DNA-methyltransferase (MGMT) activity, a DNA repair enzyme, by temozolomide has been determined to be the cause of lymphopenia. Drug-resistant mutation of the MGMT protein has been shown to render chemoprotection against TMZ. The immune modulating role of TMZ during glioma chemotherapy and possible mechanisms to establish a strong TMZ-resistant immune response have been discussed.
Purpose
The treatment of cancer has transformed over the past 40 years, with medical oncologists, radiation oncologists and surgeons working together to prolong survival times and minimize treatment ...related morbidity. With each advancement, the risk–benefit scale has been calibrated to provide an accurate assessment of surgical hazard. The goal of this review is to look back at how the role of surgery has evolved with each new medical advance, and to explore the role of surgeons in the future of cancer care.
Methods
A literature review was conducted, highlighting the key papers guiding surgical management of spinal metastatic lesions.
Conclusion
The roles of surgery, medical therapy, and radiation have evolved over the past 40 years, with new advances requiring complex multidisciplinary care.
•Spindle Cell Oncocytomas (SCO) are part of a class of tumors that includes low grade pituitary tumors such as pituicytomas and granular cell tumors (GCT).•SCO are rare tumors which are typically ...benign, with some cases having more aggressive invasion.•This is a case report of a 74-year-old woman found to have a pituitary mass treated with partial resection, diagnosed on histopathology to be a spindle cell oncocytoma.•On 6 months follow up, surveillance MRI reveals stable appearance of the tumor. No adjuvant therapy is planned.
Pituitary spindle cell oncocytomas represent a rare pathologic entity within the differential diagnosis for pituitary tumors. As part of a class of tumors that includes low grade non-endocrine pituitary tumors such as pituicytomas and granular cell tumors (GCT), these can have similar characteristics to pituitary adenomas, and are occasionally misdiagnosed as such. We present a case of a 74-year-old woman who presented for work up of persistent headaches and vertigo. MRI brain demonstrated a heterogeneously enhancing soft tissue mass at the left lateral aspect of the sella. Patient underwent a biopsy and resection of the lesion. Histopathological examination is reviewed which revealed a spindle cell oncocytoma. Follow up MRI and examination at 6 months revealed partial resection. Additionally, we present an overview of the literature on clinical characteristics of this tumor and considerations for treatment and follow up.
Malignant gliomas are very difficult neoplasms for clinicians to treat. The reason for this is multifaceted. Many treatments that are effective for systemic cancer are unable to cross the blood-brain ...barrier and/or have unacceptable systemic toxicities. Consequently, in recent years an effort has been placed on trying to develop innovative local treatments that bypass the blood-brain barrier and allow for direct treatment in the central nervous system (CNS)-interstitial treatment. In this paper, we present our extensive experience in using interstitial chemotherapy as a strategy to treat malignant brain tumors at a single institution (The Johns Hopkins Hospital). We provide a comprehensive summary of our preclinical work on interstitial chemotherapy at the Hunterian Neurosurgery Laboratory, reviewing data on rat, rabbit, and monkey studies. Additionally, we present our clinical experience with randomized placebo-controlled studies for the treatment of malignant gliomas. We compare survival statistics for those patients who received placebo versus Gliadel as initial therapy (11.6 months vs. 13.9 months, respectively) and at the time of tumor recurrence (23 weeks vs. and 31 weeks, respectively). We also discuss the positive impact of local therapy in avoiding the toxicities associated with systemic treatments. Furthermore, we provide an overview of newer chemotherapeutic agents and other strategies used in interstitial treatment. Finally, we offer insight into some of the lessons we have learned from our unique perspective.
•Neighborhood-level factors are important in healthcare utilization after surgery.•Social factors can be reliably identified pre-op engendering targeted interventions.•Area of Deprivation Index ...predicts resource utilization following spine surgery.
In the context of increased attention afforded to hospital efficiency and improved but safe patient throughput, decreasing unnecessary hospital length of stay (LOS) is imperative. Given that lumbar spine procedures may be among a hospital's most profitable services, identifying patients at risk of increased healthcare resource utilization prior to surgery is a valuable opportunity to develop targeted pre- and peri-operative intervention and quality improvement initiatives. The purpose of the present investigation was to examine patient factors that predict prolonged LOS as well as discharge disposition following elective, posterior, lumbar spine surgery.
We employed a retrospective cohort analysis on 779 consecutive patients treated with lumbar surgery without fusion. Our primary outcome measures were extended LOS (three or more midnights) and discharge disposition. Patient sociodemographic, procedural, and discharge characteristics were adjusted for in our analysis. Sociodemographic variables included Area of Deprivation Index (ADI), a comprehensive metric of socioeconomic status, utilizing income, education, employment, and housing quality based on patient zip code. Multivariable logistic regression and ordinal logistic regression analyses were performed to assess whether covariates were independently predictive of extended LOS and discharge disposition, respectively.
779 patients were studied, with a median age of 66 years (±15) and a median LOS of 1 midnight (range, 1-10 midnights). Patients in the most disadvantaged ADI quintile (adjusted odds ratio, aOR 2.48 95% CI 1.15-5.47), those who underwent a minimally-invasive or tubular retractor surgery (aOR 3.03 95% CI 1.02-8.56), those who had an intra-operative drain placed (aOR 4.46 95% CI 2.53-7.26), who had a cerebrospinal fluid leak (aOR 3.46 95% CI 1.55-7.58), who were discharged anywhere but home (aOR 17.11 95% CI 9.24-33.00), and those who were evaluated by physical therapy (aOR 7.23 95% CI 2.13-45.30) or OT (aOR 2.20 95% CI 1.13-4.22) had a significantly increased chance of an extended LOS. Preoperative opioid use was not associated with an increased LOS following surgery (aOR 1.12 95% CI 0.56-1.46). Extended LOS was not associated with post-discharge emergency department representation or unplanned readmission within 90 days following discharge (p=0.148). Patients who were older (aOR 1.99 95% CI 1.62-2.48), in higher quintiles on ADI (3rd quintile; aOR 1.90 95% CI 1.12-3.23, 4th quintile; aOR 1.79, 95% CI 1.05-3.05, 5th quintile; aOR 2.16 95% CI 1.26-3.75), who had a CSF leak (aOR 2.18 95% CI 1.22-3.86), or who had a longer procedure duration (aOR 1.38 95% CI 1.17-1.62) were more likely to require additional services or be sent to a subacute facility upon discharge.
Patient sociodemographics, along with procedural factors, and discharge disposition were all associated with an increased likelihood of prolonged LOS and resource intensive discharges following elective lumbar spine surgery. Several of these factors could be reliably identified pre-operatively and may be amenable to targeted preoperative intervention. Improving discharge disposition planning in the peri-operative period may allow for more efficient use of hospitalization and inpatient and post-acute resources.
Lateral lumbar interbody fusion (LLIF) is a minimally invasive fusion procedure that may be performed with or without supplemental instrumentation. However, there is a paucity of evidence on the ...effect of supplemental instrumentation technique on perioperative morbidity and fusion rate in LLIF.
A single-institutional retrospective review of patients who underwent LLIF for lumbar spondylosis was conducted. Patients were grouped according to supplemental instrumentation technique: stand-alone LLIF, LLIF with laterally placed instrumentation, or LLIF with posterior percutaneous pedicle screw fixation (PPSF). Outcomes included fusion rates, peri-operative complication, and reoperation; estimated blood loss (EBL); surgery duration; length of stay; and length of follow-up.
82 patients underwent LLIF at 114 levels. 35 patients (42.7%) received supplemental lateral instrumentation, 30 (36.6%) received supplemental PPSF, and 17 (20.7%) underwent stand-alone LLIF. More patients in the lateral instrumentation group had prior lumbar fusion at adjacent levels (23/35, 65.71%) versus stand-alone (3/17, 17.6%) or PPSF (2/30, 6.67%) groups (p = 0.003). 4/17 patients (23.5%) with stand-alone LLIF and 4/35 patients (11.42%) with lateral instrumentation underwent reoperation, versus 0/30 with PPSF (p = 0.030). There was no difference in fusion rates between groups (p = 0.717). Operation duration was longer in patients with PPSF (p < 0.005) and length of follow-up was longer for PPSF than lateral instrumentation (p = 0.001). Choice of instrumentation group was a statistically significant predictor of reoperation.
While rates of complete radiographic fusion on imaging follow-up didn't differ, patients receiving PPSF were less likely than stand-alone or lateral instrumentation groups to require reoperation, though operative time was significantly longer. Further study of choice of supplemental instrumentation with LLIF is indicated.
This Cervical Spine Research Society (CSRS) Study is a prospective, multicenter, nonrandomized investigation of patients with cervical spondylosis and disc disease. In this analysis, only patients ...with cervical myelopathy as the predominant syndrome were considered.
To determine demographics, surgeon treatment practices, and outcomes in patients with symptomatic myelopathy.
Current data on patient demographics and treatment practices of surgeons do not exist. There are no published prospective studies in which neurologic, functional, pain, and activities of daily living outcomes are systematically quantified.
Patients were recruited by participating CSRS surgeons. Demographic information, patients' symptoms, and patients' functional data were compiled from patient and physician surveys completed at the time of initial examination, and outcomes were assessed from patient surveys completed after treatment. Data were compiled and statistically analyzed by a blinded third party.
Sixty-two (12%) of the 503 patients enrolled by 41 CSRS surgeons had myelopathy. Patients (48.4% male; mean age, 48.7 +/- 12.03 years) had a mean duration of symptoms of 29.8 months (range, 8 weeks to 180 months). Surgery was recommended for 31 (50%) of these patients. Forty-three patients (69%) returned for follow-up and completed the questionnaire adequately for analysis. Twenty (46%) of the 43 patients on whom follow-up data are available underwent surgery, and 23 (54%) received medical treatment. Surgically treated patients had a significant improvement in functional status and overall pain, with improvement also observed in neurologic symptoms. Patients treated nonsurgically had a significant worsening of their ability to perform activities of daily living, with worsening of neurologic symptoms.
When medical and surgical treatments are compared, surgically treated patients appear to have better outcomes, despite exhibiting a greater number of neurologic and nonneurologic symptoms and having greater functional disability before treatment. Randomized studies, if feasible, should be performed to address outcome in cervical myelopathy further.
Morphological types of arbuscular mycorrhizae (AM) in crops and associated weeds were examined in agro-ecosystems. In total, 48 plant species (8 crops and 40 weeds) belonging to 43 genera in 18 ...families were examined. The number of plant species with Arum-type AM was higher than those with Paris-type AM in the examined plants. AM association was absent in 6 weeds, and the average colonization rate was 62.64% in crops and 52.92% in weeds. AM morphology has been reported in 2 crops and 21 weeds for the first time. The influence of plant identity on AM morphology was also analyzed by arranging the examined plants in a current plant phylogenetic scheme. This analysis showed there was a lack of relationship between plant classification and AM morphological type. Actually, the colonization types were not distinguished at the plant family level, but were mostly distinguished at the species level.
Successful remission in hematological cancers by CAR-T cell immunotherapy has yet to be replicated in solid tumors like GBM. A significant impediment of CAR-T immunotherapy in solid tumors is poor ...exposure of T cells to tumor antigens resulting in suboptimal CAR-T cell activation, which ultimately fails to induce a robust anti-tumor immune response. Costimulatory moieties in advanced-generation CARs, along with additional IL2 therapy has been shown to be insufficient to overcome this hurdle and have its cytotoxic limitations. GSK3 is constitutively active in naïve T cells and is transiently inactivated during T cell activation resulting in rapid T cell proliferation. Pharmacologic inhibition of GSK3 in GBM-specific CAR-T cells reduced FasL expression, increased T cell proliferation and reduced exhaustion by lowering PD-1 levels resulting in the development of CAR-T effector memory phenotype. Treatment with GSK3-inhibited CAR-T cells resulted in 100% tumor elimination during the tumor-rechallenge experiment in GBM-bearing animals and increased accumulation of memory CAR-T cells in secondary lymphoid organs. These adjuvant-like effects of GSK3 inhibition on activated CAR-T cells may be a valuable adjunct to a successful implementation of CAR-T immunotherapy against GBM and other solid tumors.
•Deficiencies in CAR-T cell immunotherapy against GBM and other solid tumors.•Restricted access to tumor antigen dampens CAR-T cell activation & limits function.•GSK3 inhibition provides “immune-boosts” in poorly activated CAR-T cells.•GSK3 inhibition lowers PD-1 levels & fosters TEM phenotype in CAR-T cells.•Increased CAR-TEM retrieval & 100% tumor clearance during in vivo GBM rechallenge.
Glioblastoma multiforme (GBM) remains one of the most lethal primary brain tumors despite surgical and therapeutic advancements. Targeted therapies of neoplastic diseases, including GBM, have ...received a great deal of interest in recent years. A highly studied target of GBM is interleukin-13 receptor α chain variant 2 (IL13Rα2). Targeted therapies against IL13Rα2 in GBM include fusion chimera proteins of IL-13 and bacterial toxins, nanoparticles, and oncolytic viruses. In addition, immunotherapies have been developed using monoclonal antibodies and cell-based strategies such as IL13Rα2-pulsed dendritic cells and IL13Rα2-targeted chimeric antigen receptor-modified T cells. Advanced therapeutic development has led to the completion of phase I clinical trials for chimeric antigen receptor-modified T cells and phase III clinical trials for IL-13-conjugated bacterial toxin, with promising outcomes. Selective expression of IL13Rα2 on tumor cells, while absent in the surrounding normal brain tissue, has motivated continued study of IL13Rα2 as an important candidate for targeted glioma therapy. Here, we review the preclinical and clinical studies targeting IL13Rα2 in GBM and discuss new advances and promising applications.
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