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Outcome Analysis of Surgical Clipping for Incidental Internal Carotid Posterior Communicating and Anterior Choroidal Artery Aneurysms

Mohammad AA, Yasuhiro Y, Seng LB, Rajagopal N, Yoko K

Asian J Neurosurg, 2019 5 31;14(2):415-421.
PMID: 31143255 DOI: 10.4103/ajns.AJNS_155_18

Introduction: Surgical outcome and ischemic complications of Internal carotid Posterior Communicating (IC PC) and anterior choroidal aneurysms have been questionable due to frequent occlusion of the anterior choroid artery and also due to low incidence of true anterior choroid artery aneurysms. The present series describes the postoperative outcome after clipping of such aneurysms at a single centre.
Methods: A retrospective analysis of 73 cases with IC PC and Anterior choroidal aneurysms performed at a Fujita Health University, Banbuntane Hotokukai Hospital, Nagoya, Aichi, Japan from 2014 to 2018 have been studied and emphasis is made on the demography and ischemic complications.
Results: A total of 73 patients with IC PC and anterior choroidal aneurysms were studied, out of which 57 patient had a true IC PC aneurysm, 14 patients had aneurysms involving the anterior choroidal artery and only 2 patients had aneurysms which involved both the IC PC and the anterior choroidal arteries. None of the patients had a permanent Anterior Choroidal Artery syndrome, whereas only 2 out of the 73 patients had postoperative complications in the form of transient hemiparesis.
Conclusion: Ischemic complications following surgical clipping of IC PC and anterior choroidal aneurysms can be minimised by meticulous micro dissection to identify the anterior choroidal artery thus preserving the patency of the same.
Fulltext The impact of routine histopathological examination on cholecystectomy specimens from an Asian demographic

Chin KF, Mohammad AA, Khoo YY, Krishnasamy T

Ann R Coll Surg Engl, 2012 Apr;94(3):165-9.
PMID: 22507719 DOI: 10.1308/003588412X13171221501708

INTRODUCTION: Most gallbladder carcinoma cases are suspected pre-operatively or intra-operatively. In Malaysia histopathological examination of cholecystectomy specimens has become routine practice. The aim of this study was to assess the impact of routine histological examinations on cholecystectomy specimens from an Asian demographic, which may differ from a Caucasian demographic.
METHODS: A retrospective study was performed of all histopathology reports for cholecystectomies (laparoscopic and open) undertaken over a period of 12 years (1997-2008) in a single teaching hospital.
RESULTS: A total of 1,375 gallbladder specimens were sent for histopathological analysis, with 7 (0.5%) being reported as malignant while only three (0.2%) were found to contain primary gallbladder carcinoma. Other premalignant findings included two specimens with dysplastic changes of the mucosa and one tubulovillous adenoma with a dysplastic epithelium. From the ten malignant and premalignant specimens, seven were diagnosed pre-operatively, two were suspected intra-operatively and one was diagnosed with dysplastic changes on the histopathology report post-operatively.
CONCLUSIONS: This study supports earlier research carried out in the UK and the demographic difference does not affect the impact of the histology examination on cholecystectomy specimens in diagnosing this disease. A selective policy is recommended in Malaysia.
Multimodality Techniques in Microsurgical Clipping as the Gold Standard Treatment in the Management of Basilar Tip Aneurysm: A Case Series

Seng LB, Yamada Y, Rajagopal N, Mohammad AA, Teranishi T, Miyatani K, et al.

Asian J Neurosurg, 2018 11 22;13(4):1148-1157.
PMID: 30459884 DOI: 10.4103/ajns.AJNS_159_18

Introduction: Basilar aneurysms represent 5%-7% of all intracranial aneurysms. The main goal of open surgery is to achieve complete obliteration of the aneurysmal sac using minimal invasive technique while emphasizing on avoidance of complication.
Materials and Methods: We performed a retrospective cohort study of nine cases of unruptured basilar tip aneurysm referred to the Fujita Health University Banbuntane-Hotokukai Hospital, Japan. The objective of the study was to analyze the surgical outcomes of unruptured basilar tip aneurysm.
Results: Nine patients with unruptured basilar tip aneurysm were referred to our hospital between 2015 and 2017. The median size of the aneurysm and age were 4.00 mm (interquartile range [IQR] = 3.25-6.75 mm) and 58 years (IQR = 54-70 years), respectively. Five patients (55.6%) were presented with multiple intracranial aneurysms. Surgical adjuncts such as intraoperative neuromonitoring, intraoperative indocyanine green (ICG) angiography with dual-image videoangiography (DIVA), and neuroendoscope were used. Two patients developed transient postoperative oculomotor nerve palsy which resolved spontaneously. The median duration of surgery and days of hospitalization were 292 min (IQR = 237.5-350.5 min) and 12 days (IQR = 12-25 days), respectively. There was no mortality recorded in this case series.
Conclusion: Microsurgical clipping of basilar tip aneurysm is safe in unruptured basilar tip aneurysm with a low risk of postoperative mortality or morbidity. All complications reported in this case series were transient with no long-term sequalae. The improved safety profile of microsurgical technique is due to the availability of intraoperative neuromonitoring, neuroendoscope, ICG, and DIVA. The application of multimodality technique in neurovascular surgery has also helped to achieve complication avoidance. The obliteration of the aneurysmal sac helps to restore the laminar blood flow in the bifurcation and distal blood vessels and improves the brain perfusion.
Fulltext Loss of Contralateral Upper Limb Motor Evoked Potential Due to Occlusion of the Internal Carotid Artery in Microsurgical Clipping of Basilar Tip Aneurysm

Seng LB, Yasuhiro Y, Rajagopal N, Mohammad AA, Takao T, Kyosuke M, et al.

Asian J Neurosurg, 2019 4 3;14(1):295-299.
PMID: 30937059 DOI: 10.4103/ajns.AJNS_157_18

The motor evoked potential (MEP) monitoring is routinely used as an adjunct in the microsurgical clipping of anterior circulation. We describe a case of unruptured basilar tip aneurysm treated with microsurgical clipping developed loss in MEP recording of the left abductor pollicis brevis (APB) following clipping of basilar tip aneurysm. A 58-year-old man was referred to the Fujita Health University Banbuntane-Hotokukai Hospital, Nagoya, Aichi, Japan, with incidental finding of unruptured 6.5 mm basilar tip saccular aneurysm. He underwent right anterior temporal approach of basilar tip aneurysm clipping. The internal carotid artery (ICA) was mobilized laterally to allow direct visualization of the neck of the basilar tip aneurysm. Following the application of temporary clip and subsequently permanent clip at the neck of the aneurysm, the MEP signal was lost in the left APB. The temporary clip was immediately removed. Dual-image videoangiography (DIVA) showed a filling defect in the right ICA and a branch of middle cerebral artery (MCA). The MEP was absent for about 23 minutes and the amplitude improved to only 75% of the baseline recording at 38 minutes till the end of the surgery. A repeat DIVA showed good flow within the right ICA and MCA. Glasgow coma score was 15/15 on postoperative day 1 and there was no gross motor or sensory deficit except right oculomotor nerve palsy with complete recovery at 6 months follow-up. This is the first reported ICA occlusion due to its mobilization in microsurgical clipping of basilar tip aneurysm. The use of neuromonitoring especially MEP is essential even in the posterior circulation aneurysm surgery especially when excessive manipulation of the ICA is unavoidable. When performing intraoperative angiography for aneurysm surgery, it is prudent to detect any filling defect within the surrounding vessels.
Fulltext Timing of Surgery and Surgical Strategies in Symptomatic Brainstem Cavernomas: Review of the Literature

Rajagopal N, Kawase T, Mohammad AA, Seng LB, Yamada Y, Kato Y

Asian J Neurosurg, 2019 4 3;14(1):15-27.
PMID: 30937003 DOI: 10.4103/ajns.AJNS_158_18

Brainstem cavernomas (BSCs) are angiographically occult, benign low flow vascular malformations that pose a significant surgical challenge due to their eloquent location. The present study includes an extensive review of the literature and three illustrative cases of BSC with emphasis on the timing of surgery: surgical approaches, usage of intraoperative monitoring, and complication avoidance. A systematic search was performed using the PubMed database was from January 1, 1999, to June 2018. The relevant articles were reviewed with particular attention to hemorrhage rates, timing of surgery, indications for surgery, surgical approaches, and outcome. Along with this, a retrospective analysis of three cases of symptomatic BSC, who were operated for the same, during the year 2018 in our institute was conducted. All the three patients presented with at least 1 episode of hemorrhage before surgery. Of these, one patient was operated immediately due to altered sensorium whereas the other two were operated after at least 4 weeks of the hemorrhagic episode. The patients who were operated in the subacute phase of bleed were seen to have liquefaction of hematoma, thus providing a good surgical demarcation and thereby reduced surgery-related trauma to the surrounding eloquent structures. Two patients improved neurologically during the immediate postoperative period, whereas one had transient worsening of neurological deficits during the immediate postoperative period in the form of additional cranial nerve palsies which completely improved on follow-up after 2 months. Radical resection is recommended in all patients with symptomatic BSCs. Surgery should be considered after the first or the second episode of hemorrhage as multiple rebleeds can cause exacerbation of deficits and sometimes mortality as well. Considering surgical timing, anywhere between 4 and 6 weeks or the subacute phase of the hemorrhage is considered appropriate. The aims of surgical intervention must be to improve preoperative function, minimize surgical morbidity and to reduce hemorrhagic rates. In spite of the significant surgical morbidity associated with BSCs, appropriate patient selection, meticulous surgical planning with adjuncts such as intraoperative monitoring and neuronavigation will go a long way in avoidance of major postoperative complications.
Fulltext Human cytomegalovirus may promote tumour progression by upregulating arginase-2

Costa H, Xu X, Overbeek G, Vasaikar S, Patro CP, Kostopoulou ON, et al.

Oncotarget, 2016 Jul 26;7(30):47221-47231.
PMID: 27363017 DOI: 10.18632/oncotarget.9722

BACKGROUND: Both arginase (ARG2) and human cytomegalovirus (HCMV) have been implicated in tumorigenesis. However, the role of ARG2 in the pathogenesis of glioblastoma (GBM) and the HCMV effects on ARG2 are unknown. We hypothesize that HCMV may contribute to tumorigenesis by increasing ARG2 expression.
RESULTS: ARG2 promotes tumorigenesis by increasing cellular proliferation, migration, invasion and vasculogenic mimicry in GBM cells, at least in part due to overexpression of MMP2/9. The nor-NOHA significantly reduced migration and tube formation of ARG2-overexpressing cells. HCMV immediate-early proteins (IE1/2) or its downstream pathways upregulated the expression of ARG2 in U-251 MG cells. Immunostaining of GBM tissue sections confirmed the overexpression of ARG2, consistent with data from subsets of Gene Expression Omnibus. Moreover, higher levels of ARG2 expression tended to be associated with poorer survival in GBM patient by analyzing data from TCGA.
METHODS: The role of ARG2 in tumorigenesis was examined by proliferation-, migration-, invasion-, wound healing- and tube formation assays using an ARG2-overexpressing cell line and ARG inhibitor, N (omega)-hydroxy-nor-L-arginine (nor-NOHA) and siRNA against ARG2 coupled with functional assays measuring MMP2/9 activity, VEGF levels and nitric oxide synthase activity. Association between HCMV and ARG2 were examined in vitro with 3 different GBM cell lines, and ex vivo with immunostaining on GBM tissue sections. The viral mechanism mediating ARG2 induction was examined by siRNA approach. Correlation between ARG2 expression and patient survival was extrapolated from bioinformatics analysis on data from The Cancer Genome Atlas (TCGA).
CONCLUSIONS: ARG2 promotes tumorigenesis, and HCMV may contribute to GBM pathogenesis by upregulating ARG2.
Fulltext Overexpression of endothelin B receptor in glioblastoma: a prognostic marker and therapeutic target?

Vasaikar S, Tsipras G, Landázuri N, Costa H, Wilhelmi V, Scicluna P, et al.

BMC Cancer, 2018 02 06;18(1):154.
PMID: 29409474 DOI: 10.1186/s12885-018-4012-7

BACKGROUND: Glioblastoma (GBM) is the most common malignant brain tumor with median survival of 12-15 months. Owing to uncertainty in clinical outcome, additional prognostic marker(s) apart from existing markers are needed. Since overexpression of endothelin B receptor (ETBR) has been demonstrated in gliomas, we aimed to test whether ETBR is a useful prognostic marker in GBM and examine if the clinically available endothelin receptor antagonists (ERA) could be useful in the disease treatment.
METHODS: Data from The Cancer Genome Atlas and the Gene Expression Omnibus database were analyzed to assess ETBR expression. For survival analysis, glioblastoma samples from 25 Swedish patients were immunostained for ETBR, and the findings were correlated with clinical history. The druggability of ETBR was assessed by protein-protein interaction network analysis. ERAs were analyzed for toxicity in in vitro assays with GBM and breast cancer cells.
RESULTS: By bioinformatics analysis, ETBR was found to be upregulated in glioblastoma patients, and its expression levels were correlated with reduced survival. ETBR interacts with key proteins involved in cancer pathogenesis, suggesting it as a druggable target. In vitro viability assays showed that ERAs may hold promise to treat glioblastoma and breast cancer.
CONCLUSIONS: ETBR is overexpressed in glioblastoma and other cancers and may be a prognostic marker in glioblastoma. ERAs may be useful for treating cancer patients.