Toxicity and Clinical Results after Proton Therapy for Pediatric Medulloblastoma: A Multi-Centric Retrospective Study

Medulloblastoma is the most common malignant brain tumor in children. Even if current treatment dramatically improves the prognosis, survivors often develop long-term treatment-related sequelae. The current radiotherapy standard for medulloblastoma is craniospinal irradiation with a boost to the primary tumor site and to any metastatic sites. Proton therapy (PT) has similar efficacy compared to traditional photon-based radiotherapy but might achieve lower toxicity rates. We report on our multi-centric experience with 43 children with medulloblastoma (median age at diagnosis 8.7 years, IQR 6.6, M/F 23/20; 26 high-risk, 14 standard-risk, 3 ex-infant), who received active scanning PT between 2015 and 2021, with a focus on PT-related acute-subacute toxicity, as well as some preliminary data on late toxicity. Most acute toxicities were mild and manageable with supportive therapy. Hematological toxicity was limited, even among HR patients who underwent hematopoietic stem-cell transplantation before PT. Preliminary data on late sequelae were also encouraging, although a longer follow-up is needed

Angiocentric glioma-associated seizures: The possible role of EATT2, pyruvate carboxylase and glutamine synthetase

Purpose: Our purpose was to better understand the pathogenesis of seizures associated with angiocentric glioma. Angiocentric glioma is an indolent and rare low-grade glioma. Its typical clinical presentation is with epileptic seizures. The pathogenesis of tumor-associated seizures is poorly understood. Among the possible pathomechanisms, the increased neurotoxic concentrations of the glutamate has been proposed. Glutamate transporters, pyruvate carboxylase and glutamine synthetase are involved in maintaining the physiological concentration of glutamate in the inter synaptic spaces. Methods: We evaluated the immunohistochemical expression of EAAT2 (the most important glutamate transporter), pyruvate carboxylase and glutamine synthetase in 17 angiocentric gliomas. Results: EAAT2 was never expressed (0%) in the neoplastic cells in none of the cases studied. Pyruvate carboxylase was expressed in the cytoplasm of the neoplastic cells in 16/17 cases (94 %). Glutamine synthetase was expressed in the cytoplasm of the neoplastic cells in 15/17 cases (88 %). Conclusion: The net result of this enzymatic expression, in particular considering the loss of EAAT2, could be an increased glutamate concentration in the synaptic clef, which might increase local network excitability initially involving intratumoral neurons. The observation that the angiocentric glioma-associated epilepsy might be at least in part related to EAAT2 deficiency opens up interesting therapeutic perspectives

Management of orbital and brain complications of sinusitis: A practical algorithm.

The aim of this work was to present a practical management algorithm for orbital and brain complications of sinusitis. According to the inclusion criteria, a sample of 68 patients was collected between 2008 and 2018 (39 males and 29 females). Among them, 44 were adults, with a mean age of 50.46 years, and 24 were pediatric patients, with a mean age of 10.33 years. Oral or intravenous antibiotic therapy was administered to all patients. Pharmacological resolution was observed in 14 cases. Early surgical treatment within 48 hours was necessary in 10 cases. Surgery consisted of abscess drainage, associated or not with functional endoscopic sinus surgery. Delayed surgery within 15–30 days was performed in 44 patients. The core procedure was functional endoscopic sinus surgery. Subsidiary procedures were abscess drainage, tooth extraction or cranial base repair. The combination of two or more of these procedures was case selected. Median follow-up was of 46.36 months. Sinusitis complications necessitate rapid diagnosis and prompt treatment. Antibiotic therapy alone is enough for mistreated rhinosinusitis with no anatomical predisposing factor. Surgery is mandatory for altered nasal and paranasal sinus anatomy or odontogenic infections

Multimodal treatment of peritoneal carcinomatosis and sarcomatosis

Peritoneal carcinomatosis and sarcomatosis (PCS) are short-term fatal conditions amenable only to palliative treatment. They are generally considered as a systemic disease at clinical presentation, and are resistant to standard treatments. However, there may be in the natural history a phase of loco-regional tumour spread during which the tumour may still be curable. Surgical treatment alone, or in combination with systemic chemotherapy, has yielded poor results in terms of survival and quality of life. One approach is cytoreductive surgery (CS) combined with the intraperitoneal administration of antiblastic agents. This may diminish any residual tumour following macroscopic excision and may overcome the pharmacokinetic limits of systemic chemotherapy. A further improvement in this multimodal approach may be achieved by the use of hyperthermic intraperitoneal intraoperative chemotherapy (HIIC). Results so far have been encouraging. However, series reported in the literature are relatively small and heterogeneous, and clinical and technical factors which include the selection of patients, optimal drugs dosage and temperature, evaluation of outcome and costs are still under discussion

Isolated vascular perfusion of human colon with adenocarcinoma.

Based on the premise that optimal drug delivery might improve the efficacy of locoregional treatment for solid tumors, the authors set up an experimental model for isolation perfusion in surgical specimens from patients resected for carcinoma of the colon. Ten surgical specimens were cannulated, washed internally and externally with saline solution, promptly cooled to 4 degrees C, connected to a circuit, and perfused with Krebs-Henselait modified solution, concentrated red blood cells, albumin, desamethasone, glucose, and heparin for 60 minutes at a target temperature of 37 degrees C. Organ temperature, flow rate, perfusion pressure, and metabolic and functional parameters were checked at 5, 20, and 60 minutes of perfusion. A paraphysiologic perfusion procedure was achieved. Mean values (and ranges) were as follows: temperature 37 degrees C (35.1-39.6 degrees C); flow rate 10.2 (5.6-17.9) ml/min/100 g; arterial pressure 96 (42-154) mmHg; arterial pH 73 (7.1-7.5); arterial PO2 183 (78-304) mmHg; arterial PCO2 36 (31-46) mmHg. No important signs of tissue damage were found at histology. Autonomous or stimulated peristalsis (or both) was present throughout the experiment. Mean O-2 extraction was 7.9 ml/min/100 g (range 3.1-11.0). Mean glucose consumption was 229 mg/100 g (range 174-252). The model worked well and appears promising, particularly for future use in various pharmacokinetic and pharmacodynamic studies of antiblastic agents