Predictors of survival and time to progression following operative management of intramedullary spinal cord astrocytomas.

PURPOSE: Surgical resection is considered standard of care for primary intramedullary astrocytomas, but the infiltrative nature of these lesions often precludes complete resection without causing new post-operative neurologic deficits. Radiotherapy and chemotherapy serve as potential adjuvants, but high-quality data evaluating their efficacy are limited. Here we analyze the experience at a single comprehensive cancer center to identify independent predictors of postoperative overall and progression-free survival. METHODS: Data was collected on patient demographics, tumor characteristics, pre-operative presentation, resection extent, long-term survival, and tumor progression/recurrence. Kaplan-Meier curves modeled overall and progression-free survival. Univariable and multivariable accelerated failure time regressions were used to compute time ratios (TR) to determine predictors of survival. RESULTS: 94 patients were included, of which 58 (62%) were alive at last follow-up. On multivariable analysis, older age (TR = 0.98; p = 0.03), higher tumor grade (TR = 0.12; p < 0.01), preoperative back pain (TR = 0.45; p < 0.01), biopsy [vs GTR] (TR = 0.18; p = 0.02), and chemotherapy (TR = 0.34; p = 0.02) were significantly associated with poorer survival. Higher tumor grade (TR = 0.34; p = 0.02) and preoperative bowel dysfunction (TR = 0.31; p = 0.02) were significant predictors of shorter time to detection of tumor growth. CONCLUSION: Tumor grade and chemotherapy were associated with poorer survival and progression-free survival. Chemotherapy regimens were highly heterogeneous, and randomized trials are needed to determine if any optimal regimens exist. Additionally, GTR was associated with improved survival, and patients should be counseled about the benefits and risks of resection extent.

A novel online calculator to predict nonroutine discharge, length of stay, readmission, and reoperation in patients undergoing surgery for intramedullary spinal cord tumors.

BACKGROUND CONTEXT: Intramedullary spinal cord tumors (IMSCTs) are rare tumors associated with significant morbidity and mortality. Surgical resection is often indicated for symptomatic lesions but may result in new neurological deficits and decrease quality of life. Identifying predictors of these adverse outcomes may help target interventions designed to reduce their occurrence. Nonetheless, most prior studies have employed population-level datasets with limited granularity. PURPOSE: To determine independent predictors of nonroutine discharge, prolonged length of stay (LOS), and 30 day readmission and reoperation, and to deploy these results as a web-based calculator. STUDY DESIGN: Retrospective cohort study PATIENT SAMPLE: A total of 235 patients who underwent resection of IMSCTs at a single comprehensive cancer center. OUTCOME MEASURES: Nonroutine discharge, prolonged LOS, 30 day readmission, and 30 day reoperation METHODS: Patients who underwent surgery from June 2002 to May 2020 at a single tertiary center were included. Data was collected on patient demographics, clinical presentation, tumor histology, surgical procedures, and 30 day readmission and reoperation. Functional status was assessed using the Modified McCormick Scale (MMS) and queried preoperative neurological symptoms included weakness, urinary and bowel dysfunction, numbness, and back and radicular pain. Variables significant on univariable analysis at the α≤0.15 level were entered into a stepwise multivariable logistic regression model. RESULTS: Of 235 included cases, 131 (56%) experienced a nonhome discharge and 68 (29%) experienced a prolonged LOS. Of 178 patients with ≥ 30 days of follow-up, 17 (9.6%) were readmitted within 30 days and 13 (7.4%) underwent reoperation. Wound dehiscence (29%) was the most common reason for readmission. Nonhome discharge was independently predicted by older age (OR=1.03/year; p<.01), thoracic location of the tumor (OR=2.36; p=.01), presenting with bowel dysfunction (OR=4.09; p=.03), and longer incision length (OR=1.44 per level; p=.03). Independent predictors of prolonged LOS included presenting with urinary incontinence (OR=2.65; p=.05) or a higher preoperative white blood cell count (OR=1.08 per 103/µL); p=.01), while GTR predicted shorter LOS (OR=0.40; p=.02). Independent predictive factors for 30 day unplanned readmission included experiencing ≥1 complications during the first hospitalization (OR=6.13; p<.01) and having a poor (A-C) versus good (D-E) baseline neurological status on the ASIA impairment scale (OR=0.23; p=.03). The only independent predictor of unplanned 30 day reoperation was experiencing ≥1 inpatient complications during the index hospitalization (OR=6.92; p<.01). Receiver operating curves for the constructed models produced C-statistics of 0.67-0.77 and the models were deployed as freely available web-based calculators (https://jhuspine5.shinyapps.io/Intramedullary30day). CONCLUSIONS: We found that neurological presentation, patient demographics, and incision length were important predictors of adverse perioperative outcomes in patients with IMSCTs. The calculators can be used by clinicians for risk stratification, preoperative counseling, and targeted interventions.

Diffuse midline gliomas, H3 K27M-mutant are associated with less peritumoral edema and contrast enhancement in comparison to glioblastomas, H3 K27M-wildtype of midline structures.

PURPOSE: The entity 'diffuse midline glioma, H3 K27M-mutant (DMG)' was introduced in the revised 4th edition of the 2016 WHO classification of brain tumors. However, there are only a few reports on magnetic resonance imaging (MRI) of these tumors. Thus, we conducted a retrospective survey focused on MRI features of DMG compared to midline glioblastomas H3 K27M-wildtype (mGBM-H3wt). METHODS: We identified 24 DMG cases and 19 mGBM-H3wt patients as controls. After being retrospectively evaluated for microscopic evidence of microvascular proliferations (MVP) and tumor necrosis by two experienced neuropathologists to identify the defining histological criteria of mGBM-H3wt, the samples were further analyzed by two experienced readers regarding imaging features such as shape, peritumoral edema and contrast enhancement. RESULTS: The DMG were found in the thalamus in 37.5% of cases (controls 63%), in the brainstem in 50% (vs. 32%) and spinal cord in 12.5% (vs. 5%). In MRI and considering MVP, DMG were found to be by far less likely to develop peritumoral edema (OR: 0.13; 95%-CL: 0.02-0.62) (p = 0.010). They, similarly, were associated with a significantly lower probability of developing strong contrast enhancement compared to mGBM-H3wt (OR: 0.10; 95%-CL: 0.02-0.47) (P = 0.003). CONCLUSION: Despite having highly variable imaging features, DMG exhibited markedly less edema and lower contrast enhancement in MRI compared to mGBM-H3wt. Of these features, the enhancement level was associated with evidence of MVP.

Magnetic Drug Targeting: A Novel Treatment for Intramedullary Spinal Cord Tumors.

Most applications of nanotechnology in cancer have focused on systemic delivery of cytotoxic drugs. Systemic delivery relies on accumulation of nanoparticles in a target tissue through enhanced permeability of leaky vasculature and retention effect of poor lymphatic drainage to increase the therapeutic index. Systemic delivery is limited, however, by toxicity and difficulty crossing natural obstructions, like the blood spine barrier. Magnetic drug targeting (MDT) is a new technique to reach tumors of the central nervous system. Here, we describe a novel therapeutic approach for high-grade intramedullary spinal cord tumors using magnetic nanoparticles (MNP). Using biocompatible compounds to form a superparamagnetic carrier and magnetism as a physical stimulus, MNP-conjugated with doxorubicin were successfully localized to a xenografted tumor in a rat model. This study demonstrates proof-of-concept that MDT may provide a novel technique for effective, concentrated delivery of chemotherapeutic agents to intramedullary spinal cord tumors without the toxicity of systemic administration.

Preparation, characterization and in-vivo evaluation of microemulsions containing tamoxifen citrate anti-cancer drug.

The aim of this study was to prepare and characterize a new nanocarrier for oral delivery of tamoxifen citrate (TMC) as a lipophilic oral administrated drug. This drug has low oral bioavailability due to its low aqueous solubility. To enhance the solubility of this drug, the microemulsion system was applied in form of oil-in-water. Sesame oil and Tween 80 were used as drug solvent oil and surfactant, respectively. Two different formulations were prepared for this purpose. The first formulation contained edible glycerin as co-surfactant and the second formulation contained Span 80 as a mixed surfactant. The results of characterization showed that the mean droplet size of drug-free samples was in the range of 16.64-64.62nm with a PDI value of <0.5. In a period of 6months after the preparation of samples, no phase sedimentation was observed, which confirmed the high stability of samples. TMC with a mass ratio of 1% was loaded in the selected samples. No significant size enlargement and drug precipitation were observed 6months after drug loading. In addition, the drug release profile at experimental environments in buffers with pH=7.4 and 5.5 showed that in the first 24h, 85.79 and 100% of the drug were released through the first formulation and 76.63 and 66.42% through the second formulation, respectively. The in-vivo results in BALB/c female mice showed that taking microemulsion form of drug caused a significant reduction in the growth rate of cancerous tumor and weight loss of the mice compared to the consumption of commercial drug tablets. The results confirmed that the new formulation of TMC could be useful for breast cancer treatment.

Magnetic resonance imaging localization with cod liver oil capsules for the minimally invasive approach to small intradural extramedullary tumors of the thoracolumbar spine.

OBJECT: Accurate intraoperative localization of small intradural extramedullary thoracolumbar (T-1 to L-3 level) spinal cord tumors is vital when minimally invasive techniques, such as hemilaminectomy, are used to excise these lesions. In this study, the authors describe a simple and effective method of preoperative MRI localization of small intradural extramedullary tumors using cod liver oil capsules. METHODS: Thirty-five patients with intradural tumors underwent preoperative MRI localization the evening prior to surgery. Patients were positioned prone in the MRI gantry, mimicking the intraoperative position. Nine capsules were placed in 3 rows to cover the lesion. This localization was used to guide the level for a minimally invasive approach using a hemilaminectomy to excise these tumors. RESULTS: The mean patient age was 51.5 ± 14.3 years, and the mean body mass index was 24.1 ± 3.5 kg/m(2). Twenty-two tumors involved the thoracic spine, and 13 involved the upper lumbar spine from L-1 to L-3. The mean tumor size was 2.2 ± 1.0 cm. Localization was accurate in 34 patients (97.1%). CONCLUSIONS: Accurate localization with the described method is quick, safe, cost-effective, and noninvasive with no exposure to radiation. It also reduces operating time by eliminating the need for intraoperative fluoroscopy.

Targeted therapy of spinal cord glioma with a genetically modified Salmonella typhimurium.

OBJECTIVE: Spinal cord tumours are highly malignant and often lead to paralysis and death due to their infiltrative nature, high recurrence rate and limited treatment options. In this study, we measured antitumour efficacy of the Salmonella typhimurium A1-R tumour-targeting bacterium strain, administered systemically or intrathecally, to spinal cord cancer in orthotopic mouse models. MATERIALS AND METHODS: Tumour fragments of U87-RFP were implanted by surgical orthotopic implantation into the dorsal site of the spinal cord. Five and 10 days after transplantation, eight mice in each group were treated with A1-R (2 x 10(7) CFU/200 microL i.v. injection or 2 x 10(6) CFU/10 microL intrathecal injection). RESULTS: Untreated mice showed progressive paralysis beginning at day 6 after tumour transplantation and developed complete paralysis between 18 and 25 days. Mice treated i.v. with A1-R had onset of paralysis at approximately 11 days and at 30 days; five mice developed complete paralysis, while the other three mice had partial paralysis. Mice treated by intrathecal injection of A1-R had onset of paralysis at approximately 18 days and one mouse was still not paralysed at day 30. Only one mouse developed complete paralysis at day 30 in this group. Intrathecally treated animals had a significantly better survival than the i.v. treated group as well as over the control group. CONCLUSIONS: These results suggest that S. typhimurium A1-R monotherapy can effectively treat spinal cord glioma.

Intracranial retrograde dissemination in filum terminale myxopapillary ependymomas.

Myxopapillary ependymomas (ME) are considered benign tumours (WHO grade I) of the central nervous system with long term survival rates and a tendency to local recurrence. However an aggressive course has occasionally been described, leading to CSF dissemination and even systemic metastases. We describe the case of a 23-year-old man diagnosed with intracranial subarachnoid dissemination of a filum terminale ME three years after the initial diagnosis. We have performed a careful review of the literature on CSF dissemination in ME and finally propose treatment of these cases.

Conformal rotation therapy with central axis beam block is a feasible alternative to intensity-modulated radiotherapy for chordomas of the cervical spine.

AIMS: Paraspinal tumours, such as chordoma, represent a treatment challenge for oncologists, requiring high dose to the target volume without exceeding the tolerance dose of the spinal cord. Intensity-modulated radiotherapy (IMRT) is helpful in achieving sharp dose gradients and conformation of dose to the target volume. We present a simpler technique--conformal rotation therapy with a central axis beam block (CRT + BB), which can provide similar dose distributions. MATERIALS AND METHODS: A patient with a cervical chordoma developed postoperative recurrence and was treated with high-dose palliative radiotherapy. Treatment was delivered using CRT + BB, with three fixed beams and three coplanar arcs. A dose of 62 Gy in 31 fractions was delivered to the 100% isodose, giving a maximum spinal cord dose of 49.6 Gy. The patient relapsed 2 years later, and was re-treated using the same technique to a dose of 57 Gy in 30 fractions. Estimates of spinal cord repair rates in primates were used to determine the tolerance dose of the spinal cord for re-treatment. The patient remained well for a further 25 months before developing local recurrence, which was treated with palliative chemotherapy. RESULTS: Re-treatment plans using CRT + BB and IMRT were compared. Dose-volume histograms show equivalence of dose to the spinal cord, although the IMRT plan delivered a slightly higher dose to tumour and lower dose to surrounding soft tissues. CONCLUSION: Treatment using CRT + BB requires careful planning and discussion with neurosurgeons before surgery. The normal curvature of the cervical spine must be eliminated if possible, and the patient must be immobilised with the neck horizontal. If these geometric constraints can be satisfied, then CRT + BB can be used as a safe and effective alternative treatment to IMRT for tumours at this site.

Treatment, patterns of failure, and survival of patients with Stage I nodal and extranodal non-Hodgkin's lymphomas, according to data in the population-based registry of the Comprehensive Cancer Centre West.

BACKGROUND: Primary extranodal lymphomas (EN-NHLs) are a heterogeneous category of tumors that are considered to be different from primary nodal non-Hodgkin's lymphomas (N-NHLs). To what extent these differences have clinical implications is currently not very clear, because knowledge of EN-NHL as a separate group is limited. METHODS: Using data from the Comprehensive Cancer Centre West (CCCW) population-based NHL registry in the Netherlands, N-NHL and EN-NHL patients were compared to determine differences in characteristics at diagnosis, responses to treatment, patterns of failure, and survival. RESULTS: At presentation, EN-NHL patients had poorer performance scores and more often bulky tumors compared with N-NHL patients, resulting in poorer responses to treatment (complete response rates were 72% and 84%, respectively; P=0.04) and inferior 5-year overall survival (49% and 63%, respectively; P=0.003). Among EN-NHL patients, considerable variations in response, survival, and relapse rates were observed, with gastric NHL patients having the best and central nervous system NHL patients having the worst prognosis (66% and 7% 5-year overall survival, respectively). Relapse rates for N-NHL and EN-NHL patients did not differ (39% and 36% 5-year relapse rates, respectively), whereas among EN-NHL patients considerable differences in relapse rates were noted. Relapses among N-NHL patients were mainly found in nodal sites, whereas recurrent disease in EN-NHL patients was mainly found in extranodal sites. CONCLUSIONS: In this population-based study, Stage I EN-NHL patients as a group had a poorer prognosis than N-NHL patients. However, among EN-NHL patients, considerable differences in response, relapse risk, and survival were observed. The failure analysis conducted in this study suggests that patterns of dissemination for N-NHL and EN-NHL are different.

Gangliogliomas involving the optic chiasm.

We report three patients with gangliogliomas involving the optic chiasm via distinct mechanisms. The ganglioglioma in one patient likely originated in the temporal lobe and spread medially to involve the chiasm, and diffuse spinal cord dissemination also occurred. Chiasmal involvement in this manner and dissemination at presentation are unusual for gangliogliomas. The tumor in a second patient was intrinsic to the hypothalmus and chiasm, while in the third patient, it involved both optic tracts, and a cyst compressed the chiasm laterally. Two patients developed severe bilateral visual loss, while the other had a stable bitemporal hemianopsia. Two patients received radiotherapy, but one continued to lose vision. Although gangliogliomas rarely involve chiasm, the mechanisms by which they produce chiasmal visual loss may be diverse, and the long-term visual prognosis is variable.

Preoperative shunts in suprasellar tumours.

A series of 22 cases of large suprasellar tumours was studied retrospectively. These patients had undergone a preoperative shunt to facilitate surgical exposure of the tumour and to reduce intracranial pressure in critically ill patients. Our observations on the clinical progress of these patients following the shunt is analysed. Nine patients worsened to a varying degree following insertion of the shunt. Seven patients became drowsy, one developed worsening of vision and a hemiparesis, and one became an akinetic mute. The worsening was probably related to alteration of intracranial pressure dynamics and resultant compression in the hypothalamic region by subtle superior migration of the tumour. Operative difficulties were encountered during the dissection of the tumour from the neural structures in these cases. We conclude that with the availability of modern decongestive measures and basal surgical exposures, preoperative shunting is rarely indicated and can be occasionally dangerous. In the absence of actual proof, it is postulated that the secondary ventricular enlargement appears to be a protective mechanism of the brain helping to reduce tumour pressure on the basal forebrain structures.

[Use of high performance nuclear magnetic resonance tomography in neuroradiology. Experience with 2,000 studies]. / Zur Anwendung der Hochfeld-Kernspintomographie in der Neuroradiologie.Erfahrungen mit 2000 Untersuchungen.

Experience with 2000 MRI's in the field of neuroradiology is summarized. The advantages and limits of this new modality are discussed in diseases of the brain and the spinal cord. MRI is superior to CT in detecting small lesions. Spots of demyelinization can be readily shown and the extent of a tumor can be assessed by cuts in three directions. CT is complementary to MRI in differentiating the nature of lesions. Emergency cases should be investigated with CT.

Results of a multicenter retrospective study on pediatric brain tumors in Italy.

This retrospective study was undertaken to evaluate the clinical characteristics, course and treatment of children (0-14 years of age) diagnosed with a primary CNS tumor during the period 1976-1982 in Italy. Four hundred and sixty-two patients (263 males and 199 females) were followed by 18 various neurosurgical and pediatric oncology centers. The histologic types most frequently reported were: medulloblastoma (23%), astrocytoma (16%), ependymoma (11%) and spongioblastoma (11%). Of the 388 patients who underwent surgery, radical excision was reported in 42%, partial excision in 32%, biopsy only in 6%, and unqualified surgery in 4%; 19% had no surgery. Radiotherapy and chemotherapy combined were administered in 61% of the 143 patients followed at pediatric oncology centers; 19% received radiotherapy alone, 3% chemotherapy alone, and 17% neither treatment. Forty-six percent of the patients were reported alive, 40% dead, and 14% lost to follow-up. Performance status was identified for 62 patients. The investigation revealed marked differences in the therapeutic treatment administered, thus precluding valid data analysis. This emphasizes the need to coordinate efforts among the institutions and the disciplines involved in the treatment of this form of childhood cancer.

[Primary malignant lymphoma of the central nervous system]. / Primäres malignes Lymphom des Zentralnervensystems.

Clinical and morphological observation of 56-year-old man with a primary isolated malignant non-Hodgkin's lymphoma of the central nervous system in the hypothalamus, with the formation of metastases in the space of the cerebrospinal fluid and a solitary extraneural metastasis in the epicardium. No generalised lymphoma. The histological classification is discussed. The importance of the cytology of the cerebrospinal fluid to a climical diagnosis is pointed out.

[Clinical picture and diagnosis of leptomeningeal sarcomatosis]. / Klinika i diagnostika sarkomatoza miagkikh mozgovykh obolochek

The study is based on the analysis of 10 cases of sarcomatosis of the brain and spinal pia mater. A progressive development of the disease, cachaxia, the existence of focal symptoms, radicle pain, xantochromia in the CSF, protein-cell dissociation and some other signs are characteristic of primary sarcomatosis of the pia mater. On the basis of clinical symptoms and CSF changes it is possible vitaly to perform a differential diagnosis with chronic infectious diseases and especially with tubercular meningitis and polyradiculomyelitis. Pathomorphological studies revealed tissue infiltration of the surrounding intracerebral vessels by tumors cells without proliferation into the dura mater and radicles of the spinal cord.