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The vacuolar proton-translocating ATPase (V-ATPase) is a transmembrane multi-protein complex fundamental in maintaining a normal intracellular pH. In the tumoral contest, its role is crucial since the metabolism underlying carcinogenesis is mainly based on anaerobic glycolytic reactions. Moreover, neoplastic cells use the V-ATPase to extrude chemotherapy drugs into the extra-cellular compartment as a drug resistance mechanism. In glioblastoma (GBM), the most malignant and incurable primary brain tumor, the expression of this pump is upregulated, making it a new possible therapeutic target. In this work, the bafilomycin A1-induced inhibition of V-ATPase in patient-derived glioma stem cell (GSC) lines was evaluated together with temozolomide, the first-line therapy against GBM. In contrast with previous published data, the proposed treatment did not overcome resistance to the standard therapy. In addition, our data showed that nanomolar dosages of bafilomycin A1 led to the blockage of the autophagy process and cellular necrosis, making the drug unusable in models which are more complex. Nevertheless, the increased expression of V-ATPase following bafilomycin A1 suggests a critical role of the proton pump in GBM stem components, encouraging the search for novel strategies to limit its activity in order to circumvent resistance to conventional therapy. [ABSTRACT FROM AUTHOR]

Background: The exoscope is a high-definition telescope recently introduced in neurosurgery. In the past few years, several reports have described the advantages and disadvantages of such technology. No studies have compared results of surgery with standard microscope and exoscope in patients with glioblastoma multiforme (GBM). Methods: Our retrospective study encompassed 177 patients operated on for GBM (WHO 2021) between February 2017 and August 2022. A total of 144 patients were operated on with a microscope only and the others with a 3D4K exoscope only. All clinical and radiological data were collected. Progression-free survival (PFS) and overall survival (OS) have been estimated in the two groups and compared by the Cox model adjusting for potential confounders (e.g., sex, age, Karnofsky performance status, gross total resection, MGMT methylated promoter, and operator's experience). Results: IDH was mutated in 9 (5.2%) patients and MGMT was methylated in 76 (44.4%). Overall, 122 patients received a gross total resection, 14 patients received a subtotal resection, and 41 patients received a partial resection. During follow-up, 139 (73.5%) patients experienced tumor recurrence and 18.7% of them received a second surgery. After truncation to 12 months, the median PFS for patients operated on with the microscope was 8.82 months, while for patients operated on with the exoscope it was >12 months. Instead, the OS was comparable in the two groups. The multivariable Cox model showed that the use of microscope compared to the exoscope was associated with lower progression-free survival (hazard ratio = 3.55, 95%CI = 1.66–7.56, p = 0.001). Conclusions: The exoscope has proven efficacy in terms of surgical resection, which was not different to that of the microscope. Furthermore, patients operated on with the exoscope had a longer PFS. A comparable OS was observed between microscope and exoscope, but further prospective studies with longer follow-up are needed. [ABSTRACT FROM AUTHOR]

Introduction: The surgical goal in glioblastoma treatment is the maximal safe resection of the tumor. Currently the lack of consensus on surgical technique opens different approaches. This study describes the "perilesional technique" and its outcomes in terms of the extent of resection, progression free survival and overall survival. Methods: Patients included (n = 40) received a diagnosis of glioblastoma and underwent surgery using the perilesional dissection technique at "San Gerardo Hospital"between 2018 and 2021. The tumor core was progressively isolated using a circumferential movement, healthy brain margins were protected with Cottonoid patties in a "shingles on the roof" fashion, then the tumorwas removed en bloc. Intraoperative ultrasound (iOUS) was used and at least 1 bioptic sample of "healthy" margin of the resection was collected and analyzed. The extent of resection was quantified. Extent of surgical resection (EOR) and progression free survival (PFS)were safety endpoints of the procedure. Results: Thirty-four patients (85%) received a gross total resection(GTR) while 3 (7.5%) patients received a sub-total resection (STR), and 3 (7.5%) a partial resection (PR). The mean post-operative residual volume was 1.44 cm3 (range 0–15.9 cm3).During surgery, a total of 76 margins were collected: 51 (67.1%) were tumor free, 25 (32.9%) were infiltrated. The median PFS was 13.4 months, 15.3 in the GTR group and 9.6 months in the STR-PR group. Conclusions: Perilesional resection is an efficient technique which aims to bring the surgeon to a safe environment, carefully reaching the "healthy" brain before removing the tumoren bloc. This technique can achieve excellent tumor margins, extent of resection, and preservation of apatient's functions. [ABSTRACT FROM AUTHOR]

Ovarian clear cell carcinoma (OCCC) is a subtype of epithelial ovarian cancer with characteristic biological features and aggressive clinical behavior. OCCCs show a pattern of gene mutations different from other type I ovarian malignancies, notably a higher frequency of PIK3CA mutations. In low grade serous ovarian cancer, KRAS and BRAF mutations are frequent, but little data are available on the mutational status of these genes in OCCCs. To clarify this issue, we designed a clinicopathological study with the aim to establish the incidence of KRAS, NRAS, and BRAF hot spot mutations in OCCC. Between December 2006 and June 2012, 22 patients with a proven diagnosis of OCCC were admitted to our Institutions. In all cases, final diagnosis was established according to FIGO and WHO criteria. All women received complete surgical staging. The PyroMark Q24 system (Qiagen GmbH, Hilden, Germany) was used for pyrosequencing analysis of KRAS, NRAS, and BRAF hot spot regions on 2.5-μm sections of formalin-fixed paraffin-embedded tissue from primary OCCC. Pyrosequencing analysis of KRAS, NRAS, and BRAF hot spot regions revealed the presence of mutations only at codon 12 in exon 2 of KRAS in 3 of 22 (14 %) cases. We found no mutations in the hot spot regions of NRAF (exons 2, 3, 4) or BRAF (exon 15). The median age of women with a KRAS mutated OCCC was 74 years. These OCCC were unilateral FIGO stage IA lesions in two cases associated with foci of endometriosis. We conclude that in 14 % of OCCCs, a KRAS mutation occurs in codon 2 exon 2. NRAS and BRAF mutations were not found. [ABSTRACT FROM AUTHOR]

The article describes the case of a gastroesophageal reflux disease patient presenting antral gastric elastofibroma pseudotumoral lesions. Topics included are the detection of mucosal bulge and hypoechoic lesion by esophagogastroduodenoscopy and linear endoscopic ultrasound, the use of a waterjet dissecting T-Type HybridKnife for unroof biopsy via endoscopic submucosal dissection, and the revelation of acellular collagen and elastic serrated fibers. [ABSTRACT FROM AUTHOR]