Experience, challenges and lessons learnt from microsurgical clipping of intracranial aneurysms at an emerging neurosurgical centre

Objectives: To share our experience, challenges faced, lessons learnt and analyze the results of surgical management by microsurgical clipping of intracranial aneurysms at an emerging neurosurgical centre at Guru Gobind Singh medical college and hospital (GGSMC&H) Faridkot, Punjab. India. Material and Methods: This study includes all the patients who presented with the diagnosis of intracranial aneurysm on CT angiography and were treated with the microsurgical clipping,  between March 2017 to April 2019. Results: There was a total of 23 patients 11female and 12 male. Age range 32 to 85years. On admission 22 patients had SAH on CT scan and one was admitted after incidental detection of the aneurysm without SAH. The time interval between ictus and admission was 0-3 days in 13 patients, 3-14 days in 8 patients and more than 14 days in 1 patient. WFNS grade (gd) I-15 patients, gd II-2, gd III-2, gd IV-3 patients. Fisher gd I-nil, gd II-9, gd III-4, gd IV-9 patients. In 23 patients 27 Aneurysms were clipped. Distribution of location was Anterior Communicating-12, Distal Anterior Cerebral Artery- 4, Middle cerebral artery (MCA) Bifurcation-3, MCA trifurcation-1, Anterior Choroidal-1, Posterior Communicating (P-com) -1, Ophthalmic Internal Carotid Artery (OICA)-4 and three patients had associated multiple aneurysms. Size of aneurysms varied from < 02mm diameter in 2 patients, 2-25mm - 23 and, more than 25mm-2 aneurysms. There was intra op rupture in 2 cases. Post-operatively 2 patients developed hemiparesis, which recovered, nine patients developed vasospasm. Two patients developed chest related complications. One patient developed renal failure.  There were 8 deaths. Patients are on follow up since March 2017 till date. Conclusions: Intracranial aneurysms are challenging to manage due to their proximity to vital intracranial structures, and difficulty in securing intracranial proximal control. Thorough knowledge of intracranial anatomy of adjacent relations, arachnoid planes and skilful dissection is a key element for a successful outcome. Data collected from GGSMC & Hospital may not be representative of the entire state or country’s population. Therefore, a large-scale data collection is necessary to create our own database to ascertain the risk factors and preventive measures that are exclusive to our state and nation

Gastric mucormycosis

Mucormycosis is a life-threatening fungal infection caused by mucormycetes, fungi of the Mucorales order.1 Rhino-orbital-cerebral involvement is the most common form of invasive mucormycosis. However, gastrointestinal (GI) mucormycosis cases have increased in the last two to three decades.2 Involvement of the GI tract in invasive mucormycosis is seen in 7–13% of cases.3 Out of which, involvement of the stomach is seen in 58% of the cases, and the remaining 42% involve small and large intestines. GI mucormycosis has been mostly associated with immunocompromised patients or premature infants.2 It has also been reported in immunocompetent patients.1 Many cases of GI mucormycosis are first recognized on autopsy, owing to its acute course and rapidly fatal nature.2 According to the literature, only about 25% of cases of GI mucormycosis are clinically diagnosed.4 The endoscopic appearance of gastric mucormycosis is usually a large ulcer with necrosis, eventually presenting an adherent, thick, green exudate.3 Figures 1A typically show green exudates surrounding the lesions. Autopsy diagnosis of GI mucormycosis is mostly based on gross and histopathological examination. Grossly, numerous well-circumscribed, dark red, targetoid mucosal lesions have been described in the post-mortem diagnosis of GI mucormycosis.4 Figures 1A show the so-called ‘targetoid lesion’ in the stomach mucosa. Figure 1 A - Macroscopic view of the stomach with multiple targetoid lesions of varying size, round to oval in shape with elevated margins and necrotic base (scale bar= 5 cm); B - Section from stomach depicting the transition zone between viable and necrotic tissue, left side of the image shows viable gastric tissue with patent submucosal blood vessels, while the right side shows bland necrosis with obliterated blood vessels (H&E, 20x); C and D - Gomori methenamine silver (GMS) and Periodic acid Schiff (PAS) stains highlight the angioinvasive fungal profiles within the submucosal blood vessels (400x). These hyphae are broad, aseptate foldable with right angle branching conforming to the morphology of mucormycosis.: Clinical diagnosis of GI mucormycosis is challenging. It can present an array of nonspecific symptoms, including discomfort, diarrhea, fever, gastrointestinal bleeding, necrosis, perforation, and as a necrotizing enterocolitis in premature neonates.5 The mechanism of GI tract involvement in mucormycosis is unclear. Pre-existing peptic ulcer disease, consumption of food and water contaminated with Mucorales, and use of contaminated nasogastric tubes, tongue depressors, and wooden spatula are a few factors responsible for the involvement of the GI system in mucormycosis.5,6 Mortality rate of GI mucormycosis is reported as 40 to 78%.4,5 Perforation of necrotic ulcers and peritonitis are the leading causes of death in such cases. The reported images belong to a 48-year-old man who died from septicemia seven days after a road traffic accident. At autopsy, apart from findings of traumatic injuries, the stomach showed multiple rounds to oval lesions with sizes ranging from 0.5cm X 0.5 cm to 3cm X 2 cm, over the pylorus with elevated margins and necrotic base (Figure 1A). On the formalin-fixed specimen, they were noted as ulcers with a greenish-black base and flattened edges. The periphery of the ulcer was congested. The microscopic examination showed that the ulcers were extending to the muscularis propria. They were invading underlying arteries and veins in the submucosa, indicating angioinvasion (Figure 1B). Gomori methenamine silver (GMS) and Periodic acid Schiff (PAS) stains highlighted fungal hyphae, which were broad aseptate and foldable, confirming the morphology of mucormycosis (Figure 11D, respectively). In conclusion, gastric mucormycosis cases usually go unnoticed clinically unless it becomes symptomatic or diagnosed incidentally on endoscopy. Thus, such cases are being diagnosed at autopsy

Intra-cranial malignant peripheral nerve sheath tumor of olfactory nerve: A case report and review of literature

Malignant Peripheral Nerve Sheath Tumors (MPNSTs) are one of the very rare high grade malignancies usually affecting extremities or trunk. Incidence is 1/Lac. Intra-cranial MPNSTs are even rarer, schwannomatous and commonly affecting cranial nerves VIII &VII). Intra-cranial MPNSTs are usually sporadic, arising de novo. The second most common mode of origin is from malignant transformation from pre-existing schwannomas or neurofibroma. We present an extremely rare and probably the first case of intra-cranial malignant peripheral nerve sheath tumor of the olfactory nerve in a non neurofibrosis patient with no prior history of irradiation

Cerebral pilocytic astrocytoma with spontaneous intratumoral haemorrhage in the elderly - a rare entity: A case report and review of the literature

Pilocytic astrocytomas (PA) are histologically are low-grade tumours, commonly found in the paediatric and young adult population. Although cases of adult and elderly pilocytic astrocytomas are described in the literature, they are quite uncommon. The rate of PAs with spontaneous bleeding is very less, with a high occurrence in children than in adults, moreover, that is in cerebellar PAs. Cerebral PAs with intratumoral haemorrhage in the older age group is extremely rare. We present a case of a 60-year female presenting with acute neurological compromise resulting from an acutely haemorrhagic Left temporal pilocytic astrocytoma. She was managed surgically with evacuation of tumoral haemorrhages, as well as resection of the tumour. Postoperatively the patient made a remarkable recovery

Fabrication of Variable Morphologies on Argon Sputtered PMMA Surfaces

Ion beam induced patterning and fabrication of various topographies over polymeric surfaces has drawn strong interest due to latent applications in photonics, magnetic devices, optical devices and photovoltaics etc. In this work, we report the controlled surface structuring and evolution of different morphologies in Poly(methyl methacrylate) polymer using Ar+ ion beam fabrication technique. Morphological and structural analysis has been performed by ex situ Atomic Force Microscopy (AFM) and X-ray Diffraction. The effect of oblique incidences on argon sputtered films was evaluated by various surface topography and texture parameters, such as Fast Fourier Transforms, surface roughness, skewness, kurtosis. AFM study demonstrates fabrication of transient morphologies over argon sputtered surfaces. One dimensional (1D) cross section scans of surface profiles are determined and morphological features are investigated. The results showed halo peaks in the XRD patterns, which indicate the amorphous nature of this type of polymer. The formation of these surface structures is attributed to the different degree of sputtering yield at different off-normal incidences and preferential sputtering of hydrogen in comparison to carbon in ion sputtered surfaces

Role of Exosomes in Tumor Induced Neo-Angiogenesis

Exosomes are the nanovesicles, belonging to the type of extracellular vesicles (EVs), produced by normal as well as tumor cells and function as a mode in cell-to-cell communication. Tumor cells utilize various approach to communicate with neighboring cells for facilitating tumor invasion and progression, one of these approaches has been shown through the release of exosomes. Tumor-derived exosomes (TEX) have the ability to reprogram/modulate the activity of target cells due to their genetic and molecular cargo. Such exosomes target endothelial cells (among others) in the tumor microenvironment (TME) to promote angiogenesis which is an important element for solid tumor growth and metastasis. So, exosomes play a vital role in cancer invasiveness and progression by harboring various cargoes that could accelerate angiogenesis. Here first, we will present an overview of exosomes, their biology, and their role in different cancer models. Then, we will emphasis on exosomes derived from tumor cells as tumor angiogenesis mediators with a particular importance on the underlying mechanisms in various cancer origins. In the end, we will unveil the therapeutic potential of tumor derived exosomes as drug delivery vehicles against angiogenesis

The chemopreventive polyphenol Curcumin prevents hematogenous breast cancer metastases in immunodeficient mice

Dissemination of metastatic cells probably occurs long before diagnosis of the primary tumor. Metastasis during early phases of carcinogenesis in high risk patients is therefore a potential prevention target. The plant polyphenol Curcumin has been proposed for dietary prevention of cancer. We therefore examined its effects on the human breast cancer cell line MDA-MB-231 in vitro and in a mouse metastasis model. Curcumin strongly induces apoptosis in MDA- MB- 231 cells in correlation with reduced activation of the survival pathway NF kappa B, as a consequence of diminished I kappa B and p65 phosphorylation. Curcumin also reduces the expression of major matrix metalloproteinases (MMPs) due to reduced NF kappa B activity and transcriptional downregulation of AP-1. NF kappa B/p65 silencing is sufficient to downregulate c-jun and MMP expression. Reduced NF kappa B/AP-1 activity and MMP expression lead to diminished invasion through a reconstituted basement membrane and to a significantly lower number of lung metastases in immunodeficient mice after intercardiac injection of 231 cells (p=0.0035). 68% of Curcumin treated but only 17% of untreated animals showed no or very few lung metastases, most likely as a consequence of down-regulation of NF kappa B/AP-1 dependent MMP expression and direct apoptotic effects on circulating tumor cells but not on established metastases. Dietary chemoprevention of metastases appears therefore feasible. Copyright (c) 2007 S. Karger AG, Basel

Sustained proliferation in cancer: mechanisms and novel therapeutic targets

Proliferation is an important part of cancer development and progression. This is manifest by altered expression and/or activity of cell cycle related proteins. Constitutive activation of many signal transduction pathways also stimulates cell growth. Early steps in tumor development are associated with a fibrogenic response and the development of a hypoxic environment which favors the survival and proliferation of cancer stem cells. Part of the survival strategy of cancer stem cells may manifested by alterations in cell metabolism. Once tumors appear, growth and metastasis may be supported by overproduction of appropriate hormones (in hormonally dependent cancers), by promoting angiogenesis, by undergoing epithelial to mesenchymal transition, by triggering autophagy, and by taking cues from surrounding stromal cells. A number of natural compounds (e.g., curcumin, resveratrol, indole-3-carbinol, brassinin, sulforaphane, epigallocatechin-3-gallate, genistein, ellagitannins, lycopene and quercetin) have been found to inhibit one or more pathways that contribute to proliferation (e.g., hypoxia inducible factor 1, nuclear factor kappa B, phosphoinositide 3 kinase/Akt, insulin-like growth factor receptor 1, Wnt, cell cycle associated proteins, as well as androgen and estrogen receptor signaling). These data, in combination with bioinformatics analyses, will be very important for identifying signaling pathways and molecular targets that may provide early diagnostic markers and/or critical targets for the development of new drugs or drug combinations that block tumor formation and progression