Adverse Events Associated With Long-term Treatment of Epithelial Ovarian Cancer With Bevacizumab and Chemotherapy.

BACKGROUND/AIM: Adverse events associated with long-term bevacizumab administration for ovarian cancer have been poorly documented in Japan. This study aimed to evaluate the adverse events of bevacizumab combined with chemotherapy for treating primary and recurrent epithelial ovarian cancer in Japan. PATIENTS AND METHODS: In this single-center retrospective study, we analyzed data of patients with advanced and recurrent epithelial ovarian cancer treated with bevacizumab and chemotherapy between January 2013 and November 2019. Statistical analyses were performed using the Fisher's exact test and Kaplan-Meier method. RESULTS: A total of 46 patients were included and the follow-up time was 30 months. The median duration of bevacizumab treatment was 14 months, and the median total dose of bevacizumab was 247.5 mg/kg. The most common adverse events were hypertension (n=30; 65.2%) and proteinuria (n=24; 49%) in all grades. The onset of hypertension and proteinuria occurred at a median of 2 months and 14 months after treatment initiation in all grades, respectively. Gastrointestinal perforation occurred significantly more frequently in patients with a history of radiation therapy. CONCLUSION: This study included cases of primary advanced and recurrent epithelial ovarian cancer, and had a longer observation period and reported more adverse events of bevacizumab with chemotherapy than previous reports. The administration of bevacizumab therapy in patients with a history of radiation should be carefully considered due to increased chances of gastrointestinal perforation.

MicroRNAs as Potential Mediators for Cigarette Smoking Induced Atherosclerosis.

Smoking increases the risk of atherosclerosis-related events, such as myocardial infarction and ischemic stroke. Recent studies have examined the expression levels of altered microRNAs (miRNAs) in various diseases. The profiles of tissue miRNAs can be potentially used in diagnosis or prognosis. However, there are limited studies on miRNAs following exposure to cigarette smoke (CS). The present study was designed to dissect the effects and cellular/molecular mechanisms of CS-induced atherosclerogenesis. Apolipoprotein E knockout (ApoE KO) mice were exposed to CS for five days a week for two months at low (two puffs/min for 40 min/day) or high dose (two puffs/min for 120 min/day). We measured the area of atherosclerotic plaques in the aorta, representing the expression of miRNAs after the exposure period. Two-month exposure to the high dose of CS significantly increased the plaque area in aortic arch, and significantly upregulated the expression of atherosclerotic markers (VCAM-1, ICAM-1, MCP1, p22phox, and gp91phox). Exposure to the high dose of CS also significantly upregulated the miRNA-155 level in the aortic tissues of ApoE KO mice. Moreover, the expression level of miR-126 tended to be downregulated and that of miR-21 tended to be upregulated in ApoE KO mice exposed to the high dose of CS, albeit statistically insignificant. The results suggest that CS induces atherosclerosis through increased vascular inflammation and NADPH oxidase expression and also emphasize the importance of miRNAs in the pathogenesis of CS-induced atherosclerosis. Our findings provide evidence for miRNAs as potential mediators of inflammation and atherosclerosis induced by CS.

Treatment of Recurrent Intracranial Aneurysms After Clipping: A Report of 23 Cases and a Review of the Literature.

OBJECTIVE: There are no established treatment strategies for aneurysms that recur after clipping. In this study, we present cases of patients who experienced recurrent aneurysms after clipping and subsequently underwent surgical intervention. METHODS: Between 2004 and 2015, we surgically treated 23 aneurysms that recurred at a previously clipped site. Patient characteristics and clinical history were retrospectively reviewed. RESULTS: Patients included 19 women and 4 men 45-81 years old. Aneurysms recurred 3-31 years (mean, 15.4 years) after the initial operation. For 18 cases, the first clinical presentation was a subarachnoid hemorrhage; aneurysms were incidentally diagnosed in 5 patients. Aneurysm locations were as follows: 9 on the internal carotid artery; 4 on the middle cerebral artery; 7 on the anterior communicating artery; 2 on the distal anterior cerebral artery; and 1 on the basilar artery. The reasons for retreatment included subarachnoid hemorrhage (n = 9) and aneurysm regrowth detected on follow-up examinations (n = 14). Endovascular treatment was performed in 10 cases, and direct surgery was performed in 13 cases (clipping in 8, clipping or trapping with bypass in 5). Various complex vascular reconstructions, including high-flow bypass and intracranial-intracranial in situ bypass, were performed for recurrent aneurysms. CONCLUSIONS: In our experience, coil embolization is a safe and effective procedure for treating recurrent aneurysms. When cases are unsuitable for coil embolization, surgical treatment often requires neurosurgeons not only to overcome the general technical difficulty of reoperative clipping but also to perform challenging vascular reconstruction.

[Metronidazole-Induced Encephalopathy during Brain Abscess Treatment:Two Case Reports].

Metronidazole is a widely used antibiotic against anaerobic bacteria and protozoa. We report two cases of metronidazole-induced encephalopathy(MIE)during treatment of a brain abscess with metronidazole. The patients developed mental disturbance, and brain MRI showed reversible signals on DWI, FLAIR, and T2. Case 1: A 48-year-old woman was admitted to our hospital with a cerebellar abscess. We initiated treatment with oral metronidazole. After taking the medication, she developed mental disturbance, and her brain MRI showed a hyperintensity within the corpus callosum. We suspected metronidazole toxicity and discontinued metronidazole treatment. The symptoms resolved rapidly within a week, and the hyperintensity on the MRI disappeared. Case 2: A 22-year-old man was admitted to our hospital with a brain abscess. We initiated treatment with oral metronidazole. On day 38, he developed mental disturbance, and his MRI showed hyperintensities within the bilateral dentate nuclei and corpus callosum. These symptoms were consistent with MIE. After cessation of metronidazole, his symptoms and abnormal MRI signals completely disappeared.

Case Report: Trigeminal Neuralgia Caused by a Minute Meningioma with Hyperostosed Suprameatal Tubercle.

Cerebellopontine angle tumors might occasionally provoke trigeminal neuralgia but are usually large enough to be diagnosed radiographically. We present a case of trigeminal neuralgia caused by a very small meningioma covering the suprameatal tubercle that displayed hyperostosis at the entrance of Meckel's cave and was not obvious on routine magnetic resonance (MR) images. A 72-year-old woman with intractable trigeminal neuralgia in the left V3 territory was referred to our institution. Preoperative imaging studies revealed that the left trigeminal nerve was medially distorted at the entrance of Meckel's cave by a laterally seated bone bulge covered by a minute enhanced lesion. Trigeminal nerve decompression surgery was performed via a retrosigmoid intradural suprameatal approach. We found a small meningioma that had compressed and flattened the trigeminal nerve root at the entrance of Meckel's cave, which was grossly and totally removed by suprameatal tubercle resection. There was no vascular compression of the trigeminal nerve root. The trigeminal neuralgia ceased completely after the operation. Accurate preoperative determination of the causative pathologies is essential to achieve adequate surgical results after microvascular decompression for neurovascular compression syndrome. Because conventional MR sequences are inadequate for the precise interpretation of complex neurovascular anatomy in the cerebellopontine angle and such small tumors can be overlooked on routine MR studies, high-resolution thin-slice MR examinations and careful radiological interpretations are required for correct diagnosis and treatment.

Reappraisal of Microsurgical Revascularization for Anterior Circulation Ischemia in Patients with Progressive Stroke.

BACKGROUND: Intravenous thrombolysis using tissue plasminogen activator and endovascular treatment for acute ischemic stroke is becoming an established standard therapy. However, there is no consensus in the treatment of patients who are suffering from progressive neurologic symptoms in the later stages. The purpose of this study was to evaluate the safety and efficacy of microsurgical revascularization in such patients with progressive stroke. METHODS: We retrospectively reviewed the clinical and radiological records of 14 consecutive patients with progressive stroke who underwent emergency open surgery for anterior circulation occlusion within 7 days after onset. Surgical candidates were carefully selected on the basis of symptom severity, diffusion-weighted imaging, and perfusion study. Superficial temporal artery to middle cerebral artery bypass was applied for atherosclerotic occlusion, and microsurgical embolectomy was applied for embolic occlusion. RESULTS: Superficial temporal artery to middle cerebral artery bypass was performed in 12 patients, microsurgical embolectomy in 1, and the combination of these modalities in 1. As a result, complete revascularization was achieved in all patients. The National Institutes of Health Stroke Scale scores significantly improved after surgery (at third postoperative day, P < 0.05; at 14th postoperative day, P < 0.01). A favorable outcome (modified Rankin Scale 0-2) was achieved in 12 of the 14 (85.7%) patients. Minor intracerebral hemorrhage occurred in 1 patient and hyperperfusion syndrome occurred in 1 patients; however, the patients subsequently recovered without additional treatment. CONCLUSIONS: Microsurgical revascularization is a feasible treatment option for patients with progressive stroke due to anterior circulation major vessel occlusion.

[Rapid spontaneous resolution of acute epidural hematoma in an infant:a case report].

Resolution of acute epidural hematoma (AEDH) usually takes several weeks. The authors present an infantile case of AEDH that rapidly decreased within a day and review the literature. A 7-month-old boy fell from a height of approximately one meter and sustained a head injury. On presentation, a skull fracture in the right temporoparietal region was found and a small AEDH was observed on computed tomography (CT) 1 hr after the injury. He was transferred to our institute because of growing AEDH, shown by CT images taken 3 hr after the injury. We decided to treat him conservatively as he did not exhibit any neurological deficits on admission. CT images 24hr after the injury showed significant reduction of the AEDH. There was also an increase in the subcutaneous hematoma. Follow-up CT images did not show enlargement of the AEDH. The patient was discharged with no neurological deficits 3 days after admission. Rapid resolution of the AEDH might have been due to transmigration of the hematoma into the epicranial layer through the fracture gap.

[Reversible cerebral vasoconstriction syndrome associated with stroke: three case reports].

Reversible cerebral vasoconstriction syndrome(RCVS)is characterized by severe headache and diffuse segmental constriction of cerebral arteries that resolves spontaneously within a few months. Although manifestations of stroke are not included in diagnostic criteria of RCVS, it is known that some cases may be associated with stroke, including intracerebral hemorrhage, subarachnoid hemorrhage, or cerebral infarction. We present three cases of RCVS associated with various types of stroke, and then review the literature. Case 1:A 49-year-old woman presented with a headache followed by left hemiparesis and dysarthria. One month before the onset, she was transfused for severe anemia caused by uterus myoma. CT images revealed intracerebral hemorrhages in the right putamen and right occipital lobe. Angiography revealed multiple segmental constrictions of the cerebral arteries. One month after the onset, these vasoconstrictions improved spontaneously. Case 2:A postpartum 38-year-old woman who had a history of migraine presented with thunderclap headache. Imaging revealed a focal subarachnoid hemorrhage in the right postcentral sulcus and segmental vasoconstriction of the right middle cerebral artery. One week after the onset, this vasoconstriction improved spontaneously. Case 3:A 32-year-old woman who had a history of migraine presented with headache followed by left homonymous hemianopsia. Imaging revealed a cerebral infarction of the right occipital lobe and multiple constrictions of the right posterior cerebral artery. These vasoconstrictions gradually improved spontaneously.

[The result of conventional craniotomy and hematoma evacuation in striatocapsular hemorrhage].

OBJECTIVE: The aim of our study is to report the outcome of our surgical procedure of conventional craniotomy for the evacuation of striatocapsular hemorrhage. PATIENTS AND METHODS: During 2004 to 2008, 75 patients were admitted to our hospital because of striatocapsular hemorrhage. We assigned thirty one (41%) of the 75 patients to surgery. We employed prognosis-based outcome analysis. RESULTS: The average volume of hematoma in surgically treated cases was 95.2 ± 52.5 (30- 223.8) mL. Mortality rate was 16% at 6 months after the onset. In the total population, a favorable outcome was achieved in 65% assessed by using the Glasogow Outcome Scale, 37.3% by using a modified Rankin Scale and 38.7% by using the Barthel index, respectively. CONCLUSION: Our observational study indicated that the outcome through conventional craniotomy and evacuation of hematoma was superior to the outcome of typical previous studies. We also illustrated our surgical procedure to emphasize operative nuances.

Poor-grade ruptured middle cerebral artery aneurysm with intracerebral hematoma: bleeding characteristics and management.

Poor-grade ruptured middle cerebral artery aneurysm is frequently associated with intraparenchymal hemorrhage, which is associated with high morbidity rates. We analyzed the clinical presentations and surgical strategies of 23 cases of ruptured middle cerebral artery aneurysm. Hematomas were divided into three types: temporal hematoma (7 patients), sylvian hematoma (10 patients), and frontal hematoma (6 patients). In 13 of 23 patients, preoperative brainstem symptoms suggested impeding uncal herniation. Surgical procedures included external decompression in 11 patients, simple lateral temporal lobectomy in 5, and selective uncectomy in 9. Three patients died. Favorable outcome defined as upper half of severely disabled or better in the extended Glasgow Outcome Scale was achieved in 13 patients. Patients with frontal hematomas presented with both uncal herniation and brainstem signs preoperatively, but this subgroup showed unexpectedly good recovery. Patients with sylvian hematomas had relatively poor outcomes. The present series suggests that aggressive decompression and evacuation of hematoma in the acute stage may prevent significant postoperative brain swelling, and will not compromise the treatment of vasospasm.

[Basilar artery occlusion due to embolism from the vertebral artery: three case reports].

Without early recanalization, it is well known that acute basilar artery occlusion almost always results in death or severe disability. We report three cases of basilar artery occlusion due to vertebral artery thrombo-embolism. In all cases, the cause of the strokes was artery to artery embolism from the vertebral artery origin. In case 1 and 3, despite complete occlusion of the vertebral artery origin, the thrombus was drained into the basilar artery through collateral flow from the external carotid artery. Atherosclerotic lesion of the vertebral artery origin is one of the main embolic sources of basilar artery, in which case, angioplasty or stent placement of the vertebral artery origin should be considered in addition to thrombolysis of the basilar artery.

[Case allocation in the management of ruptured anterior communicating aneurysm using endovascular embolization as a first option].

OBJECTIVE: The management of ruptured anterior communicating aneurysms remains controversial since the results of ISAT have been reported. The aim of our study is to report our decision-making process and outcome in 36 consecutive cases using endovascular coil embolization as a first choice of treatment. PATIENTS AND METHODS: Thirty-six patients were studied. Since April, 2004, the treatment modality has been decided after discussion between the endovascular and cerebrovascular surgeons, taking into account the physiological status, treatment risk and morphology of the aneurysm. RESULTS: Twelve (33%) of 36 patients were allocated to coil embolization. Factors leading to the selection of clipping surgery were decided mostly by the morphology of the aneurysm, namely, tiny in 11 (47.8%), irregular shape in 6 (26.1%), broad neck in 3 (13.0%) and bleb located at the neck in 3 (13.0%). Half of the aneurysms projecting anteriorly were treated coil embolization. CONCLUSION: The allocation rate of endovascular treatment in ruptured anterior communicating aneurysms was 33%. Endovascular treatment was effective in at least half of the anterior the projecting aneurysms.

[Microsurgical exposure of middle cerebral aneurysms located at the limen recess].

OBJECTIVE: To describe techniques of exposure for middle cerebral artery (MCA) aneurysms located at the limen recess. METHODS: A retrospective review was performed of 17 patients who underwent clipping surgery, during a 3-year period, to MCA aneurysms located at the limen recess. All clinical and imaging data were reviewed. RESULTS: Techniques required in the limen recess MCA aneurysms were: 1) Wide exposure of the sylvian fissure (from the distal part to the carotid cistern), 2) Secure the M1 proximal, 3) Temporary occlusion, 4) Perpendicular clip. Temporary occlusion was employed in 13 of 17 patients. No procedure related morbidity was observed. CONCLUSION: Difficulty lies in the circumstance that the aneurysm frequently has its orifice 270 degree, while the clip has to be applied perpendicular to the M2 axis in a narrow working space. Using temporary clip and extensive exposure may be the key to avoid brain damage in the surgery of MCA aneurysms located at the limen recess.

[Ruptured P1-2 junction aneurysm associated with bilateral agenesis of the internal carotid artery].

We report a case of bilateral agenesis of the internal carotid artery which was revealed by oclulomotor palsy and subarachnoid hemorrhage. Angiography showed a ruptured aneurysm of the left P1-2 junction and bilateral absence of the internal carotid artery. In surgery, it was necessary to use temporary clipping several times to adjust the aneurismal clipping. Complete clipping easily compromised the middle cerebral circulation. This case suggested that STA-MCA bypass should be considered in the surgery of agenesis of the internal carotid artery in which the preoperative hemodynamic status is usually normal.

[The role of endovascular treatment for multiple intracranial aneurysms with subarachnoid hemorrhage].

In consideration of the treatment for multiple cerebral aneurysms occurring in association with subarachnoid hemorrhage, it is sometimes difficult to determine which therapeutic strategy should be used when it is difficult to detect the ruptured aneurysm by CT or angiography and difficult to clip all the aneurysms using one approach. This study was conducted to examine indications and problems of coil embolization in the acute stage in such a situation, based on our experience in 9 patients. The patients were aged between 29 to 91 years (mean 61.6 years), and the severity on admission was recorded according to the World Federation of Neurosurgical Societies (WFNS) Grade I in 6 patients, Grade II in 2 patients, and grade IV in 1 patient. The number of aneurysms was 2 in 5 patients, 3 in 3 patients, and 4 in 1 patient. Four patients underwent embolization for all the aneurysms simultaneously, 3 patients underwent embolization for a single aneurysm and then underwent clipping of other aneurysms, and 2 patients were considered to be eligible for surgery and underwent clipping, but since no rupture was detected, they underwent embolization for all the remaining aneurysms. Seven patients made satisfactory progress, but 1 patient developed an embolic complication. Another patient developed recurrent hemorrhage from the untreated aneurysm, so additional clipping was performed. Coil embolization is beneficial in that treatment is completed simultaneously, but has problems in that it cannot be determined whether or not the embolized aneurysm is the ruptured one, embolic complications may occur, and long-term prognosis is unknown.

[Stress response of subarachnoid hemorrhage to cardiac performance and intravascular volume evaluated by the pulse contour cardiac output (PiCCO) system].

The aim of this study was to investigate cardiac performance and volume status after subarachnoid hemorrhage (SAH). Hemodynamic and volumetric parameters including cardiac index (CL), intrathoracic blood volume index (ITBVI), and extravascular lung water index (EVLWI) were evaluated by single indicator transpulmonary thermodilution (PiCCO) from days 1 to 4 in 32 patients with SAH treated surgically or endovascularly within 24 hours. Higher CL and lower ITBVI values were observed after SAH. The mean value of Cl was 5.2 l/min/m2 on day 1, which gradually decreased to 3.4 l/min/m2 on day 4. The mean ITBVI value was 730 ml/m2 on day 1, which recovered to the reference range until day 4 by fluid administration aiming for normovolemia. Higher CL and lower ITBVI values were present in patients with poor clinical grade (WFNS grade IV, V) as compared with mild to moderate grade (I -Ill) (p < 0.05). Relationship between CL and SI were well correlated (r = 0.77, p < 0.0001). The results indicate that SAH predisposes patients to hyperdynamic and hypovolemic states associated with sympathetic hyperactivity, especially in patients with poor clinical grade. Bedside monitoring with the PiCCO system may be a powerful tool for the management of patients after SAH.