Prospective comparative study of intraoperative balloon electronic brachytherapy versus resection with multidisciplinary adjuvant therapy for recurrent glioblastoma.

BACKGROUND: Intraoperative balloon electronic brachytherapy (IBEB) may provide potential benefit for local control of recurrent cerebral glioblastomas (GBMs). METHODS: This is a preliminary report of an open-label, prospective, comparative cohort study conducted in two neurosurgical centers with ongoing follow-up. At recurrence, patients at one center (n = 15) underwent reresection with IBEB while, at the second center (n = 15), control subjects underwent re-resection with various accepted second-line adjuvant chemoradiotherapy options. A comparative analysis of overall survival (OS) and local progression-free survival (LPFS) following re-resection was performed. Exploratory subgroup analysis based on postoperative residual contrast-enhanced volume status was also done. RESULTS: In the IBEB group, median LPFS after re-resection was significantly longer than in the control group (8.0 vs. 6.0 months; log rank χ2 = 4.93, P = 0.026, P < 0.05). In addition, the median OS after second resection in the IBEB group was also significantly longer than in the control group (11.0 vs. 8.0 months; log rank χ2 = 4.23, P = 0.04, P < 0.05). CONCLUSION: These hypothesis-generating results from a small cohort of subjects suggest putative clinical benefit in OS and LPFS associated with maximal safe re-resection of recurrent GBM with IBEB versus re-resection and standard adjuvant therapy, a hypothesis that deserves further testing in an appropriately powered clinical trial.

The Polymorphism of Drugs: New Approaches to the Synthesis of Nanostructured Polymorphs.

Among the significant problems of modern pharmacology are the low solubility and bioavailability of drugs. One way to resolve this problem is to obtain new polymorphic forms of drugs with improved physicochemical properties. Various approaches have been developed with this aim, including the preparation of co-crystals, the use of nanoparticles, or the use of compounds in the form of a salt. A promising direction in pharmacology concerns the production of new stable polymorphic structures. In this mini-review, we consider certain aspects of drug polymorphism, methods for the synthesis of polymorphs, and the stability, size, and transformation of crystalline polymorphs. Moreover, we summarize our results from several studies demonstrating the problems associated with the synthesis of new polymorphous modifications based on inert gases and cryotemperatures. The results indicate that the problems specific to drug polymorphisms have only been partly resolved, are of current interest, and require further development.

Repeat Resection and Intraoperative Radiotherapy for Malignant Gliomas of the Brain: A History and Review of Current Techniques.

The degree of primary resection of malignant brain gliomas (MBGs) has correlated positively with progression-free and overall survival. The indications for surgery and reoperation in MBG relapse remain controversial. Surgery will not be curative and should be followed by adjuvant treatment. We reviewed the reported studies with respect to repeat resection and the various methods of intraoperative radiotherapy for MBGs from the initial experience with high-energy linear accelerators in Japan to modern, integrated brachytherapy solutions using solid and balloon applicators. Because of the findings from our review, we have begun to research into the use of intraoperative balloon brachytherapy for recurrent MBGs.

Automated Volumetric Analysis of Postoperative Magnetic Resonance Imaging Predicts Survival in Patients with Glioblastoma.

BACKGROUND: Glioblastomas (GBMs) are primary brain tumors that are very difficult to treat. Magnetic resonance imaging (MRI) is the reference tool for diagnosis, postoperative control, and follow-up of GBM. The MRI tumor contrast enhancement part serves as a target for surgery. However, there are controversial data about the influence of pre- and postoperative tumor volumetric MRI parameters on overall survival (OS). METHODS: Data of 57 patients with GBM were analyzed retrospectively. All patients had maximum safe resection and standard adjuvant treatment. All patients underwent 1.5-T MRI with contrast in the first 24 hours postoperatively. The data of pre- and postoperative volumetric parameters were analyzed using the original software. RESULTS: Correlation analysis between the postoperative volume of the tumor contrast enhancement part and the patient's OS revealed a significant level (on the Chaddock scale) of inverse correlation. Residual tumor volume associated with OS of >6 months was determined as <2.5 cm3. The mortality risk in the first 6 months after tumor resection is 3.4 times higher when the tumor remnant is >2.5 cm3 (risk ratio, 3.4; P = 0.0002). CONCLUSIONS: The volume of MRI contrast-enhancing GBM remnants after surgery, automatically measured by the software, was a significant predictor for early postoperative progression and death.

Cryochemical Synthesis of Polymorphous Nanostructures of a Steroid Neurohormone.

A new cryochemical strategy of producing nanoparticles and polymorphous nanostructures of drugs is used, which is based on the dynamic combination of high and low temperatures, gas and solid phases, and inert carrier gases. This technology is applied to the synthesis of nanoparticles of steroid neurohormone dehydroepiandrosterone (DHEA). We have optimized the conditions of synthesis of the new polymorphous DHEA structure, FVII. The molecules of DHEA in FVII structure are bound by hydrogen bonds via oxygen atoms. The grain size is 100 nm. It is shown that the yield and ratio of the resulting nanoforms of this hormone are determined by the nature and properties of the inert carrier gas. The highest yield and selectivity of FVII are observed when carbon dioxide is used as the carrier gas. In the case of helium, the FVII content decreases from 85 to 30% and other structures are formed. In experiments without carrier gas, nanoparticles are formed but no FVII is produced. The selectivity and the effect of carrier gas are considered on the basis of homogeneous and heterogeneous formation of nanoparticles and the relationship between particle selectivity and its activity. The synthesis of various polymorphous structures on the nanoscale is assumed to be the manifestation of the size effect in the synthesis of drugs.

New Software for Preoperative Diagnostics of Meningeal Tumor Histologic Types.

OBJECTIVE: Meningeal tumors are neoplasms with different histologic manifestations of both benign and malignant types that determine the prognosis of tumor recurrence and its consistency. The risk of surgical treatment depends on the location, size, and consistency of the tumor. Magnetic resonance imaging (MRI) sequences can be used to identify the features of tumors, but these MRI characteristics are not well understood. The present study describes an advanced mathematical algorithm to analyze MRI data and distinguish histologic types of meningeal tumors before surgery. METHODS: Forty-eight patients underwent surgical removal of meningeal brain tumor. All patients had preoperative MRI with a 1.5-T scanner. One radiologist and 2 neurosurgeons evaluated MRI histogram peaks of the whole tumor volume using the advanced computer algorithm. RESULTS: Three specialists received the following mean value of histogram peaks: 15.99 ± 0.23 (± standard error of the mean [SEM]) for meningoteliomatous meningiomas; 21.24 ± 0.3 (±SEM) for fibroplastic meningiomas; 19.0 ± 0.28 (±SEM) for transitional meningiomas; 10.7 ± 0.27 (±SEM) for anatypical, anaplastic meningiomas, 11.03 ± 0.51 (±SEM) for primary intracranial fibrosarcomas and 25.72 ± 0.29 (±SEM) for meningeal hemangiopericytomas. A one-way analysis of variance test proved the difference between group means: F = 70.138, P < 0.01. The Tukey test and the Games-Howell test indicated that the difference between the tumor groups was significant. Mean deviation in agreement index between specialists was 0.98 ± 0.007 (±SEM). CONCLUSIONS: The advanced algorithm proved high specificity, sensitivity, and interoperator repeatability.

ß-Polymorph of phenazepam: a powder study.

THE TITLE COMPOUND [SYSTEMATIC NAME: 7-bromo-5-(2-chloro-phen-yl)-1H-1,4-benzodiazepin-2(3H)-one] (ß-polymorph), C(15)H(10)BrClN(2)O, has been obtained via cryomodification of the known α-polymorph of phenazepam [Karapetyan et al. (1979 ▶). Bioorg. Khim.5, 1684-1690]. In both polymorphs, the mol-ecules, which differ only in the dihedral angles between the aromatic rings [75.4 (2)° and 86.2 (3)° in the α- and ß-polymorphs, respectively], are linked into centrosymmetric dimers via N-H⋯O hydrogen bonds. In the crystal structure of the ß-polymorph, weak inter-molecular C-H⋯O hydrogen bonds further link these dimers into layers parallel to bc plane.