Terlipressin in combination with albumin as a therapy for hepatorenal syndrome in patients aged 65 years or older.

INTRODUCTION AND OBJECTIVES: Clinical data for older patients with advanced liver disease are limited. This post hoc analysis evaluated the efficacy and safety of terlipressin in patients aged ≥65 years with hepatorenal syndrome using data from 3 Phase III, randomized, placebo-controlled studies (OT-0401, REVERSE, CONFIRM). PATIENTS AND METHODS: The pooled population of patients aged ≥65 years (terlipressin, n = 54; placebo, n = 36) was evaluated for hepatorenal syndrome reversal-defined as a serum creatinine level ≤1.5 mg/dL (≤132.6 µmol/L) while receiving terlipressin or placebo, without renal replacement therapy, liver transplantation, or death-and the incidence of renal replacement therapy (RRT). Safety analyses included an assessment of adverse events. RESULTS: Hepatorenal syndrome reversal was almost 2-times higher in terlipressin-treated patients compared with patients who received placebo (31.5% vs 16.7%; P = 0.143). Among surviving patients, the need for RRT was significantly reduced in the terlipressin group, with an almost 3-times lower incidence of RRT versus the placebo group (Day 90: 25.0% vs 70.6%; P = 0.005). Among 23 liver-transplant-listed patients, significantly fewer patients in the terlipressin versus placebo group needed RRT by Days 30 and 60 (P = 0.027 each). Fewer patients in the terlipressin group needed RRT post-transplant (P = 0.011). More terlipressin-treated patients who were listed for and received a liver transplant were alive and RRT-free by Day 90. No new safety signals were revealed in the older subpopulation compared with previously published data. CONCLUSIONS: Terlipressin therapy may lead to clinical improvements in highly vulnerable patients aged ≥65 years with hepatorenal syndrome. CLINICAL TRIAL NUMBERS: OT-0401, NCT00089570; REVERSE, NCT01143246; CONFIRM, NCT02770716.

Volumetric analysis of intracranial arteriovenous malformations contoured for CyberKnife radiosurgery with 3-dimensional rotational angiography vs computed tomography/magnetic resonance imaging.

BACKGROUND: Accurate target delineation has significant impact on brain arteriovenous malformation (AVM) obliteration, treatment success, and potential complications of stereotactic radiosurgery. OBJECTIVE: We compare the nidal contouring of AVMs using fused images of contrasted computed tomography (CT) and magnetic resonance imaging (MRI) with matched images of 3-dimensional (3-D) cerebral angiography for CyberKnife radiosurgery (CKRS) treatment planning. METHODS: Between May 2009 and April 2012, 3-D cerebral angiography was integrated into CKRS target planning for 30 consecutive patients. The AVM nidal target volumes were delineated using fused CT and MRI scans vs fused CT, MRI, and 3-D cerebral angiography for each patient. RESULTS: The mean volume of the AVM nidus contoured with the addition of 3-D cerebral angiography to the CT/MRI fusion (9.09 cm(3), 95% confidence interval: 5.39 cm(3)-12.8 cm(3)) was statistically smaller than the mean volume contoured with CT/MRI fused scans alone (14.1 cm(3), 95% confidence interval: 9.16 cm(3)-19.1 cm(3)), with a mean volume difference of δ = 5.01 cm(3) (P = .001). Diffuse AVM nidus was associated with larger mean volume differences compared with a compact nidus (δ = 6.51 vs 2.11 cm(3), P = .02). The mean volume difference was not statistically associated with the patient's sex (male δ = 5.61, female δ = 5.06, P = .84), previous hemorrhage status (yes δ = 5.69, no δ = 5.23, P = .86), or previous embolization status (yes δ = 6.80, no δ = 5.95, P = .11). CONCLUSION: For brain AVMs treated with CKRS, the addition of 3-D cerebral angiography to CT/MRI fusions for diagnostic accuracy results in a statistically significant reduction in contoured nidal volume compared with standard CT/MRI fusion-based contouring.

Cervical disc herniation presenting with neck pain and contralateral symptoms: a case report.

INTRODUCTION: Cervical disc herniation often results in neck and arm pain in patients as a result of direct impingement of nerve roots and associated inflammatory processes. The clinical presentation usually corresponds with the side of herniation and ipsilateral symptoms predominate the clinical picture. CASE PRESENTATION: A 35-year-old Caucasian man presented to our facility with neck pain and left-sided upper and lower extremity pain. A magnetic resonance imaging scan revealed a right paramedian herniated disc at the C5 to C6 level. All other cervical levels were normal without central canal stenosis or neural foraminal stenosis. Results from magnetic reasonance imaging scans of the brain and lumbar spine were negative. An anterior cervical discectomy was performed at the C5 to C6 level, and an inter-body graft and plate were placed. Our patient had complete resolution of his neck and left arm pain. CONCLUSIONS: Anterior discectomy and fusion of the cervical spine resulted in complete resolution of our patient's neck and left arm symptoms and improvement of his contralateral left leg pain. Cervical disc herniation may present with contralateral symptoms that are different from the current perception of this disease.

Intracranial parafalcine chondroma in a pregnant patient.

BACKGROUND: Intracranial chondromas are rare benign neoplasms. We report a patient incidentally diagnosed with an intracranial chondroma during her second trimester. CASE DESCRIPTION: A 22-year-old Caucasian was diagnosed with an incidental parafalcine lesion found during admission due to a motor vehicle accident. Prior to the admission, the patient did not present with any neurological symptom. Magnetic resonance spectroscopy (MRS) suggested this intracranial lesion to be benign. A decision was made to delay the tumor excision until after delivery. Special anesthesia considerations were made to maintain stable blood pressure and euvolemia during the Cesarean section. The patient underwent a successful gross total removal of the intracranial tumor two months postpartum without any post-operative deficit. CONCLUSION: This is the first case report of an intracranial parafalcine chondroma in pregnancy. This report highlights the disease course of this rare type of tumor during pregnancy. This case illustrates relevant aspects of the management of a neurologically asymptomatic patient with an incidentally discovered intracranial tumor of which MRS suggested a benign nature.

Familial glioblastoma: A case report of glioblastoma in two brothers and review of literature.

BACKGROUND: Gliomas that aggregate in families with history of malignancy may have an inheritable genetic basis. Gliomas can occur in several well known tumor syndromes. However, their occurrence in the absence of these syndromes is quite rare. High-grade gliomas, such as glioblastoma multiforme (GBM), are the most common and most lethal primary cancers of the central nervous system (CNS). CASE DESCRIPTION: We present a case of two brothers both diagnosed with GBM. Both siblings underwent biopsy with debulking of the tumors by different surgeons. Only one sibling elected to undergo chemotherapy and radiation. Cytogenetic studies were possible only on one sibling and the tumor specimen revealed multiple chromosomal abnormalities, including triploidies 4, 8, 12, 22 and loss of heterozygosity of 1p, 9p, and 10. Histological samples for both tumors were similar, both revealing increased cellularity consisting of gemistocytic astrocytes, central necrosis, and microvascularization. CONCLUSION: We present two brothers who display a rare familial relationship in the development of their GBMs. Supplementary and improved genetic studies may allow for specific treatment modalities as certain genetic abnormalities have better response to tailored treatments and carry better prognoses.

Tectal plate glioblastoma multiforme.

BACKGROUND: Tectal plate tumors have traditionally been considered low-grade, indolent lesions. We report a patient who presented with a tectal region glioblastoma multiforme (GBM), a rare pathology in this anatomic location. CASE DESCRIPTION: This is a case report of a 45-year-old female that presented with worsening confusion, memory loss, and loss of bladder control for 3 days. There was no family history of brain malignancy. The patient presented with Parinaud's phenomenon. Pronator drift was not present. The patient had dysarthric speech. An elevated white blood cell count was also noted. Non-contrast CT scan of the head showed the presence of a tectal region mass and hydrocephalus. A follow-up MRI with and without contrast confirmed the presence of a 4.2 × 3.3 × 4.6 cm(3) mass. Magnetic Resonance Spectroscopy (MRS) demonstrated an elevated choline/N-acetylaspartate ratio and an increase in lactate suggesting an aggressive neoplasm. A ventriculoperitoneal shunt was initially placed to relieve the hydrocephalus. The patient subsequently underwent a suboccipital craniotomy for debulking of tumor and for tissue diagnosis. Pathology of the lesion was consistent with GBM. The patient declined postoperative treatment with chemotherapy and radiation. CONCLUSION: Although tectal region masses are predominantly low-grade lesions, high-grade lesions can present in this anatomical location. Furthermore, MRS can help to differentiate benign lesions from more aggressive lesions in the tectal plate. Biopsy of tectal plate lesions should be considered in select cases to establish diagnosis and prognosis in order to optimize treatment.

Technical challenges to surgical clipping of aneurysmal regrowth with coil herniation following endovascular treatment - a case report.

In recent years, technical developments have made endovascular procedures attractive therapeutic options and enabled the endovascular surgeon to redefine the management of cerebral aneurysms. However, as the number of aneurysms undergoing endovascular therapy has grown, so has the number of patients with incompletely treated aneurysms who are presenting for further management. In cases of failure of endovascular treatment caused by either incomplete occlusion or regrowth of the aneurysm, a complementary treatment is often necessary. Surgical treatment of these patients is challenging. We present a case of a ruptured posterior cerebral artery aneurysm treated initially with endovascular coiling that left behind significant residual aneurysmal sac. Regrowth of the aneurysm documented on follow-up was treated surgically. At surgery, the coil was found to have herniated through the aneurysmal sac into the subarachnoid space, and the aneurysm was successfully clipped without removing the coils. We review the regrowth of aneurysms following endovascular therapy and potential problems and challenges of surgically managing these lesions.

Internal jugular venous thrombosis as a complication after an elective anterior cervical discectomy: case report.

OBJECTIVE: Anterior cervical discectomy is one of the most common spine procedures in neurosurgery. Various complications, including hoarseness, hematoma, and dysphagia, have been reported in the literature. We report the first case of internal jugular venous thrombosis after an elective anterior cervical discectomy. CLINICAL PRESENTATION: A 35-year-old woman with past medical history significant only for hypercholesterolemia and cholecystectomy underwent an anterior cervical discectomy with fusion for a symptomatic cervical disc at the C5-C6 level. Intraoperatively, the patient had venous bleeding, which was adequately controlled. The procedure was completed with good hemostasis before closure. The patient was discharged home 1 day after the surgery. She was readmitted 5 days later with a 2-day history of a swollen right neck. The patient had no respiratory symptoms, but did report mild dysphagia. A hematoma was suspected. INTERVENTION: A computed tomographic scan of the neck was performed when the patient presented with cervical swelling. This was suggestive of a right internal jugular venous thrombosis. This diagnosis was confirmed with cervical ultrasound. The patient was seen by the vascular surgery department. The hospital course was otherwise uneventful and the patient was discharged 3 days later on oral anticoagulation with warfarin. CONCLUSION: This is the first report of internal jugular venous thrombosis after an elective anterior cervical discectomy. Internal jugular venous thrombosis should be considered in the differential diagnosis of a patient presenting with cervical swelling after an anterior cervical discectomy.

Accuracy of pedicle screw placement for lumbar fusion using anatomic landmarks versus open laminectomy: a comparison of two surgical techniques in cadaveric specimens.

OBJECTIVE: We determined whether the accuracy of lumbar pedicle screw placement is optimized by performing a laminectomy before screw placement with screw entry point and trajectory being guided by pedicle visualization and palpation (Technique 1). This technique was compared with a technique using anatomic landmarks for pedicle screw placement (Technique 2). The biomechanical stability of the instrumented constructs, in the absence and presence of a laminectomy, was also compared. METHODS: Twelve L1-L3 specimens were harvested from fresh cadavers. The intact laminectomy and instrumented spines were biomechanically tested in flexion and extension, lateral bending, and axial rotation. Laminectomies were performed in six of the 12 specimens before pedicle screw placement using Technique 1. The remaining six specimens underwent pedicle screw and rod fixation using Technique 2. Computed tomographic images were obtained for all instrumented specimens. Deviation of the screws from the ideal entry point or trajectory was analyzed to quantitatively compare the two techniques. RESULTS: Computed tomographic analysis of the specimens showed that all screw placements were within the pedicles. Scatter plot analysis demonstrated that screws placed using Technique 2 were more likely to have the combination of entry points and trajectories medial to the ideal entry point and trajectory. Laminectomy did not weaken the final pedicle screw and rod-fixated constructs. CONCLUSION: All screw placements were grossly within the confines of the pedicles, regardless of technique, as evidenced by computed tomographic analysis. Furthermore, the anatomic landmark technique and the open laminectomy technique yielded biomechanically equivalent pedicle screw and rod-fixated constructs.

Augmentation of anterior lumbar interbody fusion with anterior pedicle screw fixation: demonstration of novel constructs and evaluation of biomechanical stability in cadaveric specimens.

OBJECTIVE: Anterior lumbar interbody fusion (ALIF) has proven effective for indications including discogenic back pain, nonunion, and instability. Current practice involves posterior pedicle screw augmentation of the ALIF procedure (ALIF-PPS). This approach requires intraoperative repositioning of the patient for percutaneous posterior pedicle screw placement. We have developed a novel technique in which the ALIF procedure is augmented with anterior pedicle screws (APS; ALIF-APS). In this study, we introduce this new technique and compare the biomechanical stability of the novel ALIF-APS with the current standard ALIF-PPS. METHODS: The technique was demonstrated in a cadaveric L4-S1 specimen using neuronavigation and fluoroscopy. Plain radiographs and computed tomographic scans of the construct were obtained. Twelve cadaveric spines (7 men and 5 women) from donors with an average age of 81 years (range, 64-93 yr) were then harvested from L4-S1. Six specimens were dedicated to ALIF-APS constructs, and the remaining six were dedicated to ALIF-PPS constructs. The specimens were then studied at L5-S1 in the following steps: 1) intact form, 2) after anterior discectomy, 3) after implantation of titanium cages (ALIF), and 4) after APS or PPS fixation in conjunction with the ALIF. Measurements were obtained in axial rotation and left and right lateral bending flexion-extension. Data were normalized by calculating the ratio of the stiffness of the instrumented to the intact spine. Statistical analyses were then performed on the data. RESULTS: Radiographs and computed tomographic scans of the construct showed accurate placement of the APS at L5 and S1. The normalized data showed that ALIF-APS and ALIF-PPS had approximately equal stability in axial rotation (1.17 +/- 0.43 versus 0.85 +/- 0.14), lateral bending (0.93 +/- 0.22 versus 0.95 +/- 0.16), and flexion- extension (0.77 +/- 0.13 versus 0.84 +/- 0.2). Paired t test analysis did not show a significant difference between the biomechanical stiffness of ALIF-APS and ALIF-PPS in axial rotation, lateral bending, and flexion-extension. CONCLUSION: We demonstrate a new technique in a cadaveric specimen whereby the ALIF procedure is augmented with APS fixation using neuronavigation and fluoroscopy. Biomechanical evaluation of the constructs suggests that the ALIF-APS has comparable stability with ALIF-PPS. APS augmentation of ALIF has potential advantages over the current standard ALIF-PPS because it can 1) eliminate the patient repositioning step, 2) minimize the total number of incisions and the total operative time, and 3) protect against dislocation of the ALIF interbody graft or cage. Work is in progress to develop a low-profile system for the novel APS constructs described here.

Concomitant choroid plexus papillomas involving the third and fourth ventricles: A case report and review of the literature.

Choroid plexus papillomas (CPP) are histopathologically benign and rare central nervous system (CNS) neoplasms arising from the epithelium of the choroid plexus. The most common site of presentation of these lesions is in the fourth ventricle in adults and lateral ventricles in children. Third ventricular CPP are uncommon. In this study, we present a case of a 66-year-old woman with complaints of progressive confusion, lethargy, and weakness who was found to have concomitant third and fourth ventricular masses on imaging studies. The patient underwent a biopsy of the third ventricular mass. The biopsy was followed by staged resections of the fourth and third ventricular masses, respectively. Pathology from the biopsy and both resections was benign CPP. Multifocal concomitant CPP is rare. Concomitant CPPs may be secondary to mere coincidental tumor occurrence or to biologic seeding of cerebrospinal fluid (CSF) from a primary CPP despite otherwise benign histopathology. The primary treatment for CPP is surgical resection. Post-operative chemotherapy or radiation for CPP is of controversial benefit.

Cyclooxygenase-2 expression in brain metastases.

BACKGROUND: Elevated Cyclooxygenase-2 (COX-2) expression is thought to increase metastatic potential of many tumors. Furthermore, elevated COX-2 expression correlates with radiation resistance in many tumor types. We evaluated whether: (i) the degree of COX-2 expression correlated with either metastatic tumor type or with the presence of necrosis and whether (ii) radiation-resistant tumors (renal cell and melanoma) had higher expression of COX-2 than did relatively radiation-sensitive tumors (breast and lung). MATERIALS AND METHODS: Specimens from sixteen patients who underwent resection of brain metastases were analyzed for COX-2 expression using a COX-2 antibody-based immunoassay. Specimens consisted of brain metastases from lung tumors, breast adenocarcinomas, melanomas and renal cell carcinomas. All specimens were analyzed for the presence or absence of necrosis. RESULTS: Ten of sixteen brain metastasis specimens had ten percent or less Cox-2 immunostaining. Statistical analyses showed no correlation between Cox-2 immunostaining and metastatic tumor type or between Cox-2 immunostaining and necrosis in this study. Furthermore, renal cell carcinoma and melanoma showed variable Cox-2 immunostaining. CONCLUSION: Cox-2 is not consistently expressed in metastases to the brain. The degree of Cox-2 expression does not correlate with metastatic tumor type or with the presence of necrosis. Radioresistant tumors did not have statistically different expression of Cox-2 than radiosensitive specimens studied in this analysis.

Differential cyclooxygenase-2 enzyme expression in radiosensitive versus radioresistant glioblastoma multiforme cell lines.

BACKGROUND: Glioblastoma multiforme (GBM) is a high-grade primary brain tumor that is refractory to current forms of treatment. In cell studies, the growth rate of GBM cells correlates with the level of Cyclooxygenase-2 (COX-2) enzyme expression. COX-2 has been implicated in carcinogenesis of systemic cancers. Recently, COX-2 inhibition has been shown to increase the radiosensitivity of various tumors. We wished to assess whether the expression of COX-2 is greater in radioresistant versus radiosensitive forms of GBM. MATERIALS AND METHODS: The radiosensitive (A172) and radioresistant (T98G) Glioblastoma multiforme cell lines were assayed for COX-2 expression using standard immunofluorescence histochemistry. Fluorescence readings were recorded per field. Western blot analysis was performed on both A172 and T98G GBM cell lines. The radioresistant cells were exposed to incremental doses of radiation in the presence and absence of a COX-2-selective inhibitor. Radioresistant cells were then exposed to incremental doses of COX-2-selective inhibitor at a constant dose of radiation. RESULTS: The radioresistant cell line T98G had an approximate 1. 7-fold greater expression of COX-2 than did the radiosensitive cell line A172, as per immunofluorescence histochemistry. Western blot analysis confirmed this finding. Statistical analysis (Bonferroni/Dunn) showed the results to be significant (p<0.0001). The wells containing radioresistant cells exposed to incremental doses of radiation and COX-2 inhibitors appeared to have higher cell kill when compared to radiation alone. Furthermore, increasing the COX-2 inhibitor concentration yielded higher cell kill. CONCLUSION: The results presented here show that the radioresistant GBM cell line, T98G, has a greater expression of COX-2 than does the radiosensitive GBM cell line, A172. These results suggest that: (i) COX-2 expression may serve as a marker for assessing radioresistance in GBM, (ii) COX-2 inhibition may lower the required doses of postoperative radiation, (iii) COX-2 inhibitors may have a role in radiosensitizing otherwise radioresistant forms of GBM.