Therapeutic approach in glioblastoma multiforme with primitive neuroectodermal tumor components: case report and review of the literature

Glioblastoma multiforme (GBM) is the most common and aggressive malignant glioma that is treated with first-line therapy, using surgical resection followed by local radiotherapy and concomitant/adjuvant temozolomide (TMZ) treatment. GBM is characterised by a high local recurrence rate and a low response to therapy. Primitive neuroectodermal tumour (PNET) of the brain revealed a low local recurrence rate; however, it also exhibited a high risk of cerebrospinal fluid (CSF) dissemination. PNET is treated with surgery followed by craniospinal irradiation (CSI) and platinum-based chemotherapy in order to prevent CSF dissemination. GBM with PNET-like components (GBM/PNET) is an emerging variant of GBM, characterised by a PNET-like clinical behaviour with an increased risk of CSF dissemination; it also may benefit from platinum-based chemotherapy upfront or following failure of GBM therapy. The results presented regarding the management of GBM/PNET are based on case reports or case series, so a standard therapeutic approach for GBM/PNET is not defined, constituing a challenging diagnostic and therapeutic dilemma. In this report, a case of a recurrent GBM/PNET treated with surgical resection and radiochemotherapy as Stupp protocol, and successive platinum-based chemotherapy due to the development of leptomeningeal dissemintation and an extracranial metastasis, is discussed. A review of the main papers regarding this rare GBM variant and its therapeutic approach are also reported. In conclusion, GBM/PNET should be treated with a multimodal approach including surgery, chemoradiotherapy, and/or the early introduction of CSI and platinum-based chemotherapy upfront or at recurrence

GOLFIG Chemo-Immunotherapy in Metastatic Colorectal Cancer Patients. A Critical Review on a Long-Lasting Follow-Up

Background: GOLFIG is a chemo-immunotherapy regimen established in preclinical models that combines gemcitabine + FOLFOX (fluoropyrimidine backbone coupled to oxaliplatin) poly-chemotherapy with low-dose s. c. recombinant interleukin-2 (rIL-2) and granulocyte-macrophage colony stimulating factor (GM-CSF). Promising antitumor effects in metastatic colorectal cancer (mCRC) patients were obtained in previous phase II and III trials. Here we report the results of 15 years of follow-up. Methods: This is a multi-institutional retrospective analysis including 179 mCRC patients receiving GOLFIG regimen between June 2002 and June 2018. Sixty-two of them received the treatment as frontline (enrolled in the GOLFIG-2 phase III trial) and 117 as second/third line (49 enrolled in the GOLFIG-1 phase II trial and 68 as compassionate use). One hundred twelve patients showed a primary left side and 67 a primary right side; K/N-ras mutational status was available in 74 cases, and an activating mutation was detected in 33. Kaplan–Meier and Cox regression analyses were carried out to relate PFS and OS with different parameters. Results: Overall, we recorded a mean PFS and OS of 15.28 (95% CI: 10.36–20.20) and 24.6 (95% CI: 19.07–30.14) months, respectively, with 14 patients surviving free of progression for 10 years. This regimen, in our updated survey of the GOLFIG-2 trial, confirmed superiority over FOLFOX in terms of PFS (hazard ratio (HR) = 0.58, p = 0.006) with a trend to a longer OS (HR = 0.69, P = 0.06) in the first line. Our analysis also confirmed significant antitumor activity in pre-treated patients, reporting a mean PFS and OS of 12.55 (95% CI: 7.19–17.9) and 20.28 (95% CI: 14.4–26.13) months, respectively. Immune-related adverse events (irAEs) were recorded in 24% of the cases and were related to a longer survival (HR = 0.36; P = 0.0001). Finally, patients' outcome was not correlated to sex, sidedness, and MT-K/N-ras. Conclusions: The GOLFIG regimen is a reliable underestimated therapeutic option in pre-treated mCRC patients and offers a strong rationale to design further trials

Brain AVMs: An Endovascular, Surgical, and Radiosurgical Update

Brain arteriovenous malformations (bAVMs) are complex vascular lesions. Despite multiple studies, several classifications, and a great interest of the scientific community, case selection in AVM patients remains challenging. During the last few years, tremendous advancements widened therapeutic options and improved outcomes spreading indications for patients harboring lesions deemed inoperable in the past. Anatomical and biological case specific features, and natural history with a focus on presenting symptoms should be evaluated case by case and always kept in mind while planning a therapeutic management for a bAVMs. A multidisciplinary approach is strongly recommended when dealing with bAVMs and should involve physicians expertise in this kind of challenging lesions. The goal of this paper is to provide a focused review of the most recent acquisitions and therapeutic strategies regarding surgical, endovascular, and radiosurgical treatment

Atypical manifestation of direct low-flow carotid-cavernous fistula. Case report and review of the literature

Background: Carotid cavernous fistula (CCF) is a rare type of arteriovenous shunt that develops within the cavernous sinus (CS). Direct CCFs entail a direct communication between the cavernous internal carotid artery and the CS and are typically high-flow lesions. Most CCFs drain into the ophthalmic veins (typical venous drainage pattern), leading to the pathognomic ocular clinical triad associated with a CCF. When an obstruction of the typical venous outflow is present, the arterial pressure generated by the fistula is transmitted into the cerebral venous system via the sphenoparietal sinus, which might lead to intracerebral hemorrhage. We present a rare case of posttraumatic, direct, low-flow CCF associated with cerebral hemorrhage, a typical venous drainage pattern, and without ocular symptoms at presentation. Case Description: A 76-year-old woman was hospitalized for a posttraumatic frontotemporopolar hemorrhage associated with multiple fractures of the maxillofacial and cranial base skeleton and midline shift >10 mm. On neurologic examination the Glasgow Coma Scale was 8 and right anisocoria was present. Immediate surgical evacuation of the hematoma was performed. Severe arterial bleeding from the anterior third of the middle cranial fossa floor was controlled intraoperatively. Postoperative brain angio−magnetic resonance imaging and digital subtraction angiography showed a direct CCF without theft phenomenon. Ocular symptoms, and ultimately loss of function of the right eye, appeared 2 weeks from surgery. Endovascular treatment of the CCF was attempted attaining partial closure of the shunt using coils. Conclusions: Direct low-flow CCFs are exceedingly rare lesions. Five cases have been described in the literature, 4 of which were associated with spontaneous rupture of a cavernous carotid aneurysm while only 1 case was associated with posttraumatic rupture of a cavernous internal carotid artery pseudoaneurysm. In addition, despite our patient having developed an intraparenchymal hemorrhage most probably correlated to the CCF, the latter was associated with a typical venous drainage via the superior ophthalmic vein, which is uncommonly correlated to intraparenchymal bleeding

Preoperative 3D volume reconstruction of the posterior wall of the sphenoid sinus with Horos: A free, simple and reliable tool in endoscopic endonasal trans-sphenoidal surgery

Background: The purpose of the study was to create computer-aided design models of the sphenoid sinus with a free-source software in order to perform a preoperative planning during trans-sphenoidal endoscopic surgery (TES) and clarify the three-dimensional anatomical features of the sphenoid sinus and its surrounding structures. Methods: For each patient a 3D volume rendering of the sphenoid sinus was obtained from a thin slice head and maxilla-facial CT scan using a free-source DICOM viewer. The 3D models obtained preoperatively were examined preoperatively by six neurosurgeons in order to identify the boundaries of the sella. Results: For the main anatomical landmark, all of the observers were able to recognize the anatomical structure at a rate ranging from 80 to 98%, 28 to 60% and 25 to 58% for expert (n = 3), inexpert (n = 3) and the entire group of observers (n = 6), respectively. The analysis of the data shows that both observation groups presented a lower recognition rate of the following parameters: right and left medial and lateral optocarotid recesses and tumor prominence, however, the sellar prominence, clival recess, planum sphenoidalis, right and left ICA prominence, right and left optic prominences represent the main anatomical landmarks to be recognized during TES immediately before the opening of the sellar floor. Conclusions: The use of a preoperative 3D imaging is not in itself a novelty in the literature, however the fact that a simple tool obtained with a free-source software like Horos can represent a considerable help in surgical practice without resorting to the use of more complex software and expensive represents the real utility of this work

Purely Meningeal Intracranial Relapse of Melanoma Brain Metastases After Surgical Resection and Immunotherapy as a Unique Disease Progression Pattern: Our Experience and Review of the Literature.

Abstract BACKGROUND: We present a case of 72-year-old man with a history of metastatic melanoma diagnosed in 2015 presenting a stable disease in treatment with dabrafenib. CASE DESCRIPTION: The patient had been surgically treated for a presumed intracranial parietooccipital metastasis. He presented 1 month later with a meningeal lesion associated with a subdural hematoma. A second surgical treatment confirmed the diagnosis of meningeal recurrence of metastatic melanoma. CONCLUSIONS: The most recent literature lacks studies defining the clinical phenomena of an early recurrence of intracranial melanoma with de novo involvement of dural compartment in patients in treatment with a target immunotherapy. The aim of this present study is to report a case of early recurrence of intracranial melanoma metastases with evidence of fast immunohistochemical and macroscopical mutation of pathologic elements, with an analysis of literature that shows the lack of well-described occurrences

The use of piezosurgery in cranial surgery in children

Piezosurgery is an alternative surgical technique, now widely tested, that uses ultrasounds for bone cutting. This device uses ultrasounds to section hard tissues without harming surrounding soft tissues. The authors analyzed their experience in craniomaxillofacial procedures with piezosurgery. A comparison between operation timing and complication rates between piezosurgery and traditional cutting instruments has been performed. A total of 27 patients were examined (15 females and 12 males; average age, of 5.5 months) affected by craniosynostosis. The aim of this study was to analyze the advantages and disadvantages of piezosurgery in pediatric craniofacial procedures. Piezoelectric device in this study has shown being a valid instrument for bone cutting in accurate procedures, because it allows performing a more precise and safer cutting, without the risk of harming surrounding tissues