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1.
Neurourol Urodyn ; 43(5): 1217-1229, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38558173

ABSTRACT

INTRODUCTION: The pathogenesis of pelvic organ prolapse (POP), an age-related disease, has not been fully elucidated. Therapeutic targets of POP are limited. Silencing information regulator 2 related enzyme 1 (SIRT1), a gene considered capable of regulating oxidative stress and cellular senescence, has been widely demonstrated involved in aging and age-related diseases. The present study aimed to explore the role of SIRT1 in POP in vivo and in vitro. METHODS: Expression levels of SIRT1 in uterosacral ligament (USL) tissues from patients with or without POP were measured using immunohistochemical assays. SRT1720, a SIRT1 agonist, was used to upregulate SIRT1, and hydrogen peroxide (H2O2) was used to establish an oxidative stress model in human uterosacral ligament fibroblasts (hUSLFs). The effects of SIRT1 on cell viability, apoptosis, senescence, and reactive oxygen species (ROS) levels were detected, respectively. Western blot assays were used to examine expression levels of apoptosis- and senescence-associated biomarkers. Unpaired Student's t test, Mann-Whitney U test, χ2 test, and one-way ANOVA were performed for determining statistically significant differences. RESULTS: Compared to the control group, expression levels of SIRT1 were downregulated in USL tissues and hUSLFs from patients with POP, and associated with stage (p < 0.05). hUSLFs of patients with POP had lower growth rates (p < 0.0001) than those of the control group, which were improved by upregulating SIRT1 (p < 0.05). The senescent proportion was higher in the POP group than the control group (43.63 ± 10.62% vs. 4.84 ± 5.32%, p < 0.0001), which could be reduced by upregulating SIRT1 (p < 0.0001). High ROS levels in the POP group were also alleviated by SRT1720. H2O2 exposure increased ROS levels, inhibited proliferation, and triggered apoptosis and senescence in hUSLFs of patients without POP in a concentration-dependent manner. Further, these damages were alleviated by pretreatment with SRT1720. CONCLUSIONS: SIRT1 is downregulated in patients with POP, and the development of SIRT1 activators or agonists may have applications in the treatment and prevention of POP through antioxidative stress and antisenescence effects.


Subject(s)
Apoptosis , Cellular Senescence , Fibroblasts , Ligaments , Oxidative Stress , Pelvic Organ Prolapse , Reactive Oxygen Species , Sirtuin 1 , Humans , Sirtuin 1/metabolism , Oxidative Stress/drug effects , Cellular Senescence/drug effects , Female , Ligaments/drug effects , Ligaments/metabolism , Ligaments/pathology , Fibroblasts/drug effects , Fibroblasts/metabolism , Fibroblasts/pathology , Pelvic Organ Prolapse/metabolism , Pelvic Organ Prolapse/pathology , Apoptosis/drug effects , Middle Aged , Reactive Oxygen Species/metabolism , Cells, Cultured , Hydrogen Peroxide/pharmacology , Heterocyclic Compounds, 4 or More Rings/pharmacology , Cell Survival/drug effects , Aged , Sacrum/drug effects , Sacrum/pathology , Adult , Uterus/drug effects , Uterus/metabolism , Uterus/pathology
2.
Neurosurg Focus ; 49(2): E11, 2020 08.
Article in English | MEDLINE | ID: mdl-32738792

ABSTRACT

OBJECTIVE: Opportunistic Hounsfield unit (HU) determination from CT imaging has been increasingly used to estimate bone mineral density (BMD) in conjunction with assessments from dual energy x-ray absorptiometry (DXA). The authors sought to compare the effect of teriparatide on HUs across different regions in the pelvis, sacrum, and lumbar spine, as a surrogate measure for the effects of teriparatide on lumbosacropelvic instrumentation. METHODS: A single-institution retrospective review of patients who had been treated with at least 6 months of teriparatide was performed. All patients had at least baseline DXA as well as pre- and post-teriparatide CT imaging. HUs were measured in the pedicle, lamina, and vertebral body of the lumbar spine, in the sciatic notch, and at the S1 and S2 levels at three different points (ilium, sacral body, and sacral ala). RESULTS: Forty patients with an average age of 67 years underwent a mean of 20 months of teriparatide therapy. Mean HUs of the lumbar lamina, pedicles, and vertebral body were significantly different from each other before teriparatide treatment: 343 ± 114, 219 ± 89.2, and 111 ± 48.1, respectively (p < 0.001). Mean HUs at the S1 level for the ilium, sacral ala, and sacral body were also significantly different from each other: 124 ± 90.1, -10.7 ± 61.9, and 99.1 ± 72.1, respectively (p < 0.001). The mean HUs at the S2 level for the ilium and sacral body were not significantly different from each other, although the mean HU at the sacral ala (-11.9 ± 52.6) was significantly lower than those at the ilium and sacral body (p = 0.003 and 0.006, respectively). HU improvement occurred in most regions following teriparatide treatment. In the lumbar spine, the mean lamina HU increased from 343 to 400 (p < 0.001), the mean pedicle HU increased from 219 to 242 (p = 0.04), and the mean vertebral body HU increased from 111 to 134 (p < 0.001). There were also significant increases in the S1 sacral body (99.1 to 130, p < 0.05), S1 ilium (124 vs 165, p = 0.01), S1 sacral ala (-10.7 vs 3.68, p = 0.04), and S2 sacral body (168 vs 189, p < 0.05). CONCLUSIONS: There was significant regional variation in lumbar and sacropelvic HUs, with most regions significantly increasing following teriparatide treatment. The sacropelvic area had lower HU values than the lumbar spine, more regional variation, and a higher degree of correlation with BMD as measured on DXA. While teriparatide treatment resulted in HUs > 110 in the majority of the lumbosacral spine, the HUs in the sacral ala remained suggestive of severe osteoporosis, which may limit the effectiveness of fixation in this region.


Subject(s)
Bone Density Conservation Agents/administration & dosage , Lumbar Vertebrae/diagnostic imaging , Pelvic Bones/diagnostic imaging , Sacrum/diagnostic imaging , Teriparatide/administration & dosage , Absorptiometry, Photon/trends , Adult , Aged , Aged, 80 and over , Cohort Studies , Female , Humans , Lumbar Vertebrae/drug effects , Male , Middle Aged , Pelvic Bones/drug effects , Retrospective Studies , Sacrum/drug effects , Treatment Outcome
3.
JBJS Case Connect ; 10(1): e0126, 2020.
Article in English | MEDLINE | ID: mdl-32224679

ABSTRACT

CASE: We report a patient with hypereosinophilia-associated massive osteolytic lesion of the sacrum who was admitted to our hospital. Genetic analysis revealed that atypical eosinophilic cells were positive for FIP1-like-1-platelet-derived growth factor receptor-alpha (FIP1L1-PDGFRA) fusion gene. Treatment was initiated with oral administration of imatinib mesylate. The patient responded rapidly to this medication with a marked reduction in eosinophilia both from the peripheral blood and FIP1L1-PDGFRA fusion gene in the bone marrow within 2 weeks, followed by gradual osteosclerotic repair of the sacrum. CONCLUSIONS: This case study found that the drug imatinib proved very effective in the treatment of this rare condition.


Subject(s)
Antineoplastic Agents/therapeutic use , Hypereosinophilic Syndrome/complications , Imatinib Mesylate/therapeutic use , Osteolysis/drug therapy , Sacrum/diagnostic imaging , Adult , Antineoplastic Agents/pharmacology , Humans , Imatinib Mesylate/pharmacology , Male , Osteolysis/diagnostic imaging , Osteolysis/etiology , Sacrum/drug effects , Tomography, X-Ray Computed
4.
Nihon Hinyokika Gakkai Zasshi ; 111(2): 48-52, 2020.
Article in Japanese | MEDLINE | ID: mdl-33883359

ABSTRACT

A 66-year-old man with buttock pain and intermittent claudication visited a nearby doctor. Magnetic resonance imaging revealed a tumor of 8 cm in diameter in his sacrum. He was referred to our hospital. Abdominal contrast enhanced computed tomography revealed a small mass of 2.5 cm in diameter on his left kidney and he was diagnosed with metastatic bone disease after needle tumor biopsy. However, needle biopsy of the renal tumor demonstrated no evidence of malignancy. As he rejected further examination, we started treatment using the tyrosine kinase inhibitor sunitinib. However, it had little effect on his sacral metastasis and he developed massive bowel bleeding twice. Extensive invasion from the sacral metastasis to the back side of the rectum was found on colonoscopy. The patient died 2 months after the introduction of sunitinib. The final diagnosis based on pathological autopsy was renal cell carcinoma with sacral metastasis.


Subject(s)
Bone Neoplasms/secondary , Carcinoma, Renal Cell/pathology , Kidney Neoplasms/pathology , Sacrum/pathology , Aged , Bone Neoplasms/diagnostic imaging , Bone Neoplasms/drug therapy , Bone Neoplasms/pathology , Carcinoma, Renal Cell/diagnostic imaging , Fatal Outcome , Humans , Image-Guided Biopsy/methods , Kidney Neoplasms/diagnostic imaging , Magnetic Resonance Imaging , Male , Sacrum/drug effects , Sunitinib/therapeutic use , Tomography, X-Ray Computed
5.
Neuropharmacology ; 170: 107815, 2020 06 15.
Article in English | MEDLINE | ID: mdl-31634501

ABSTRACT

Descending neuromodulators from the brainstem play a major role in the development and regulation of spinal sensorimotor functions. Here, the contribution of serotonergic signaling in the lumbar spinal cord was investigated in the context of the generation of locomotor activity. Experiments were performed on in vitro spinal cord preparations from newborn rats (0-5 days). Rhythmic locomotor episodes (fictive locomotion) triggered by tonic electrical stimulations (2Hz, 30s) of a single sacral dorsal root were recorded from bilateral flexor-dominated (L2) and extensor-dominated (L5) ventral roots. We found that the activity pattern induced by sacral stimulation evolves over the 5 post-natal (P) day period. Although alternating rhythmic flexor-like motor bursts were expressed at all ages, the locomotor pattern of extensor-like bursting was progressively lost from P1 to P5. At later stages, serotonin (5-HT) and quipazine (5-HT2A receptor agonist) at concentrations sub-threshold for direct locomotor network activation promoted sacral stimulation-induced fictive locomotion. The 5-HT2A receptor antagonist ketanserin could reverse the agonist's action but was ineffective when fictive locomotion was already expressed in the absence of 5-HT (mainly before P2). Although inhibiting 5-HT7 receptors with SB266990 did not affect locomotor pattern organization, activating 5-HT1A receptors with 8-OH-DPAT specifically deteriorated extensor phase motor burst activity. We conclude that during the first 5 post-natal days in rat, serotonergic signaling in the lumbar cord becomes increasingly critical for the expression of fictive locomotion. Our findings therefore further underline the importance of both descending serotonergic and sensory afferent pathways in shaping locomotor activity during postnatal development. This article is part of the special issue entitled 'Serotonin Research: Crossing Scales and Boundaries'.


Subject(s)
Locomotion/drug effects , Sacrum/drug effects , Serotonin 5-HT2 Receptor Agonists/pharmacology , Serotonin 5-HT2 Receptor Antagonists/pharmacology , Serotonin/pharmacology , Spinal Nerve Roots/drug effects , Animals , Animals, Newborn , Electric Stimulation/methods , Female , Locomotion/physiology , Male , Organ Culture Techniques , Rats , Rats, Sprague-Dawley , Sacrum/innervation , Sacrum/physiology , Spinal Nerve Roots/physiology
6.
Probl Radiac Med Radiobiol ; 24: 537-551, 2019 Dec.
Article in English, Ukrainian | MEDLINE | ID: mdl-31841494

ABSTRACT

We present a rare case report of a bilateral avascular necrosis of lateral sacral masses in a patient who developed a sustainable complete clinical and radiological response after chemoradiotherapy for locally advanced rectal cancer. It is shown that despite the standardized and precise planning and fractioning for neoadjuvant chemoradiation therapy for locally advanced rectal cancer, the biological effects of ionizing radiation on critical organs can be va- ried both in time of occurrence and in structure. Evaluating the effect of neoadjuvant chemoradiation therapy, one should take into account the possibility of the development of even very rare effects of ionizing radiation on criti- cal organs and include their early detection in the diagnostic algorithm.


Subject(s)
Adenocarcinoma/therapy , Chemoradiotherapy/methods , Necrosis/therapy , Neoadjuvant Therapy/methods , Neoplasm Recurrence, Local/therapy , Rectal Neoplasms/therapy , Adenocarcinoma/diagnostic imaging , Adenocarcinoma/pathology , Aged , Antineoplastic Agents/therapeutic use , Humans , Magnetic Resonance Imaging , Male , Necrosis/diagnostic imaging , Necrosis/pathology , Neoplasm Recurrence, Local/diagnostic imaging , Neoplasm Recurrence, Local/pathology , Radiation, Ionizing , Rectal Neoplasms/diagnostic imaging , Rectal Neoplasms/pathology , Rectum/diagnostic imaging , Rectum/drug effects , Rectum/pathology , Rectum/radiation effects , Remission Induction , Sacrum/diagnostic imaging , Sacrum/drug effects , Sacrum/pathology , Sacrum/radiation effects , Treatment Outcome
7.
J Orthop Surg Res ; 13(1): 251, 2018 Oct 11.
Article in English | MEDLINE | ID: mdl-30305126

ABSTRACT

BACKGROUND: Pedicle screws can be augmented with polymethylmethacrylate (PMMA) cement through cannulated and fenestrated pedicle screws to improve screw anchorage. To overcome the drawbacks of PMMA, a modified augmentation technique applying a self-curing elastomeric material into a balloon-created cavity prior to screw insertion was developed and evaluated. The aim of the study was to compare the effect of the established and novel augmentation technique on pedicle screw anchorage in a biomechanical in vitro experiment. METHODS: In ten lumbar vertebral bodies, the right pedicles were instrumented with monoaxial cannulated and fenestrated pedicle screws and augmented in situ with 2 ml PMMA. The left pedicles were instrumented with monoaxial cannulated pedicle screws. Prior to left screw insertion, a balloon cavity was created and filled with 3 ml of self-curing elastomer (silicone). Each screw was subjected to a cranio-caudal cyclic load starting from - 50 to 50 N while the upper load was increased by 5 N every 100 load cycles until loosening or 11,000 cycles (600 N). After cyclic loading, a pullout test of the screws was conducted. RESULTS: The mean cycles to screw loosening were 9824 ± 1982 and 7401 ± 1644 for the elastomer and PMMA group, respectively (P = 0.012). The post-cycling pullout test of the loosened screws showed differences in the failure mode and failure load, with predominantly pedicle/vertebrae fractures in the PMMA group (1188.6 N ± 288.1) and screw pullout through the pedicle (671.3 N ± 332.1) in the elastomer group. CONCLUSION: The modified pedicle screw augmentation technique involving a balloon cavity creation and a self-curing elastomeric silicone resulted in a significantly improved pedicle screw anchorage under cyclic cranio-caudal loading when compared to conventional in situ PMMA augmentation.


Subject(s)
Bone Cements , Elastomers/administration & dosage , Lumbar Vertebrae/physiology , Pedicle Screws , Polymethyl Methacrylate/administration & dosage , Weight-Bearing/physiology , Aged , Aged, 80 and over , Biomechanical Phenomena/physiology , Female , Humans , Lumbar Vertebrae/drug effects , Lumbar Vertebrae/pathology , Male , Materials Testing/methods , Sacrum/drug effects , Sacrum/pathology , Sacrum/physiology , Skull/drug effects , Skull/pathology , Skull/physiology
8.
J BUON ; 23(2): 453-459, 2018.
Article in English | MEDLINE | ID: mdl-29745092

ABSTRACT

PURPOSE: Denosumab, a new monoclonal antibody that inhibits receptor activator for nuclear factor Kß ligand (RANKL), has recently been approved by FDA for the treatment of aggressive giant cell tumor of bone (GCTB). So we initiated this study to evaluate the clinical benifits of denosumab used preoperatively or postoperatively. METHODS: Patients diagnosed with classic sacral GCT without metastasis were included in this study. Patients were assigned into 3 groups according to the use of denosumab: control group 1, post-operative group 2 and neoadjuvant group 3. The latter two groups were treated with 120 mg of subcutaneous denosumab every 4 weeks with loading doses on days 8 and 15 of the first cycle. The primary endpoints were event-free-survival (EFS) and objective response rate (OPR) based on RECIST criteria. A system (MUD system) proposed by our center was applied to score the sacral nerve deficit changes before surgery in group 3. RESULTS: A total 30 patients (13 men and 17 women, mean age 34.7 years, range 15-56) were enrolled from April 2014 to July 2016. Group 1 included 10 patients, group 2 9 and group 3 11. The study ended in March 01, 2017, and followup ranged from 3 to 36 months (mean 18.3). Two patients with PET-CT showed SUV max uptake down to muscle tissue level. In the neoadjuvant group 3 7 patients had partial responses and 4 stable disease (ORR 63.6%; 95% CI 35-92). Most (80%) patients achieved significant improvement in pain and great relief in the bladder and bowel functions. In 4 patients the urocatheter was removed after neoadjuvant denosumab. CONCLUSION: Neoadjuvant therapy with denosumab can significantly relieve the symptoms and neurologic deficits.


Subject(s)
Denosumab/administration & dosage , Giant Cell Tumor of Bone/drug therapy , Neoadjuvant Therapy , Pain/drug therapy , Adolescent , Adult , Denosumab/adverse effects , Disease-Free Survival , Female , Gene Expression Regulation, Neoplastic/drug effects , Giant Cell Tumor of Bone/genetics , Giant Cell Tumor of Bone/pathology , Humans , Male , Middle Aged , Neoplasm Metastasis , Pain/genetics , Pain/pathology , Postoperative Period , RANK Ligand/genetics , Sacrum/drug effects , Sacrum/pathology , Treatment Outcome , Young Adult
9.
Anesth Analg ; 124(5): 1674-1677, 2017 05.
Article in English | MEDLINE | ID: mdl-28431427

ABSTRACT

Intrathecal local anesthetic maldistribution is a well-known cause of spinal anesthesia failure (SAF). This could potentially result in sensory blockade restricted to the sacral dermatomes. We sought to determine the overall incidence of SAF and the role of sacral dermatomes in differentiating between total and partial failures. Of the 3111 spinals prospectively examined, 194 (6.2%) were classified as failures. Of the 72 presumed total failures based on the initial assessment, evaluation of the sacral dermatomes revealed sensory blockade in 32 (44%; 95% confidence interval, 32.7%-56.6%). Sacral dermatome assessment after SAF may be important in safely guiding subsequent anesthetic management.


Subject(s)
Anesthesia, Spinal/adverse effects , Anesthetics, Local/adverse effects , Bupivacaine/adverse effects , Motor Activity/drug effects , Sacrum/drug effects , Sensory Thresholds/drug effects , Adult , Anesthetics, Local/administration & dosage , Bupivacaine/administration & dosage , Female , Humans , Male , Middle Aged , Neurologic Examination , Pain Threshold/drug effects , Prospective Studies , Sacrum/physiology , Thermosensing/drug effects , Treatment Failure
11.
Article in English | MEDLINE | ID: mdl-27997083

ABSTRACT

BACKGROUND: Sacral nerve stimulation (SNS) is a surgical treatment of fecal and urinary incontinence that consists of inserting a stimulating electrode into one of the s3 or s4 sacral holes. In addition to the benefit of SNS in the treatment of incontinence, recent studies showed that SNS is effective in the treatment of irritable bowel syndrome as well as bladder pain syndrome. The aim of this study was to evaluate the effect of SNS on visceral mechanosensitivity in a cross-organ sensitization rat model. METHODS: Hypersensitive model was obtained by instillation of acetic acid into the bladder of rats during 5 minutes, 30 minutes before the start of the experiments. Visceral sensitivity was assessed by monitoring the change in mean arterial pressure in response to graded isobaric colorectal distension series. To decipher the mechanisms underlying SNS effect, rats were administered intravenously either a nonselective opioid receptor antagonist (naloxone) or a nitric oxide synthesis antagonist (L-NAME). Neuronal activation in the dorsal horn of the sacral spinal cord was measured by counting c-fos immunoreactive cells in response to colorectal distension and NMS. KEY RESULTS: Intravesical acetic acid instillation increased mean arterial pressure variation in response to colorectal distension when compared to saline group. SNS reduced the variation in arterial pressure. Colorectal distension induced a rise in c-fos immunoreactive cells in the dorsal horn of the spinal cord. This effect was reduced by SNS. CONCLUSIONS & INFERENCES: SNS reduces visceral mechanosensitivity in a cross-organ sensitization model.


Subject(s)
Colon/physiology , Mechanotransduction, Cellular/physiology , Rectum/physiology , Sacrum/physiology , Spinal Nerves/physiology , Visceral Pain/physiopathology , Animals , Colon/drug effects , Colon/innervation , Electric Stimulation/methods , Enzyme Inhibitors/pharmacology , Male , Mechanotransduction, Cellular/drug effects , Narcotic Antagonists/pharmacology , Rats , Rats, Sprague-Dawley , Rectum/drug effects , Rectum/innervation , Sacrum/drug effects , Sacrum/innervation , Visceral Pain/drug therapy
12.
Vet Radiol Ultrasound ; 57(2): 180-90, 2016.
Article in English | MEDLINE | ID: mdl-26626409

ABSTRACT

Radiopaque gelified ethanol preparation has been described as a useful agent for treatment of humans with intervertebral disc protrusion. The material is injected into the nucleus pulposus under image guidance with intention to cause the protruded disc material to recede. Because treatment options for dogs with chronic protrusions are limited, new and minimally invasive treatments are desirable. The aim of this experimental, descriptive, prospective study was to assess the feasibility and safety of percutaneous injection of gelified ethanol into the lumbosacral intervertebral disc of dogs. Lumbosacral intervertebral discs of normal dogs (n = 9) were imaged with magnetic resonance imaging and then injected with gelified ethanol using image guidance. The accuracy of gelified ethanol placement in the nucleus pulposus and presence of leakage of the injected material were documented. Postinjection computed tomography (CT) findings (n = 9), short-term (n = 9) and long-term (n = 4) follow-up magnetic resonance imaging and CT findings were compared to document the distribution of the injected preparation and identify effects on adjacent tissues. Percutaneous injection of the intervertebral disc was successful in delivering radiopaque gelified ethanol to the nucleus pulposus in all dogs. Leakage of the injected material into the vertebral canal was present in three dogs immediately following injection and in another additional dog at 1 year following injection. All dogs tolerated the injection well and had no clinical adverse reactions within the study period. Findings indicated that injection of the nucleus pulposus of healthy dogs was well tolerated, even in the presence of mild leakage of material from the intervertebral disc.


Subject(s)
Ethanol/administration & dosage , Intervertebral Disc/drug effects , Lumbar Vertebrae/drug effects , Sacrum/drug effects , Administration, Cutaneous , Animals , Dogs , Female , Gels/administration & dosage , Male , Prospective Studies , Reference Values , Time Factors
13.
J Oral Maxillofac Surg ; 72(4): 702-16, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24397946

ABSTRACT

Osteonecrosis of the jaws (ONJ) is a complex disease involving multiple tissue and cell-type responses to wound healing or infection. AAOMS defines bisphosphonate related ONJ (BRONJ) as exposed, necrotic bone in the maxillofacial region that has persisted for more than 8 weeks in a patient with current or previous antiresorptive treatment, without a history of radiation therapy to the jaws. Since the first reported ONJ cases in 2003 and 2004, there has been little advancement in understanding the etiology and pathophysiology of ONJ. Many hypotheses have been proposed, including bisphosphonate (BP) toxicity to oral epithelium, altered wound healing after tooth extraction, high turnover of the mandible and maxilla, oral biofilm formation, infection and inflammation, and suppression of angiogenesis and bone turnover. The current classification system of ONJ involves stages 0 to 3 and is based on patient clinical presentation. This report describes a case of stage 0 ONJ in a patient on denosumab and indicates the full-spectrum similarities between BP- and denosumab-associated ONJ clinically, radiographically, and histologically.


Subject(s)
Antibodies, Monoclonal, Humanized/adverse effects , Mandibular Diseases/chemically induced , Osteonecrosis/chemically induced , RANK Ligand/antagonists & inhibitors , Adult , Bisphosphonate-Associated Osteonecrosis of the Jaw/diagnosis , Cone-Beam Computed Tomography/methods , Denosumab , Diagnosis, Differential , Giant Cell Tumors/drug therapy , Humans , Male , Sacrum/drug effects , Spinal Neoplasms/drug therapy
14.
Neuro Oncol ; 16(1): 72-80, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24366975

ABSTRACT

BACKGROUND: Chordomas are rare and indolent bone tumors that arise in the skull base and mobile spine. Distant metastases occur in >20% of cases, but morbidity and mortality are mainly related to local relapses that affect the majority of patients. Standard chemotherapy has modest activity, whereas new targeted therapies (alone or in combination) have some activity in controlling disease progression. However, the scarcity of preclinical models capable of testing in vivo responses to these therapies hampers the development of new medical strategies. METHODS: In this study, 8 chordoma samples taken from 8 patients were implanted in nude mice. Four engrafted successfully and gave rise to tumor masses that were analyzed histologically, by means of fluorescence in situ hybridization and biochemical techniques. The data relating to each of the mouse tumors were compared with those obtained from the corresponding human tumor. RESULTS: All 4 engraftments retained the histological, genetic and biochemical features of the human tumors they came from. In one epidermal growth factor receptor(EGFR)-positive xenograft, responsiveness to lapatinib was evaluated by comparing the pre- and post treatment findings. The treatment induced a low-level, heterogeneous switching off of EGFR and its downstream signaling effectors. CONCLUSIONS: Overall, this model is very close to human chordoma and represents a new means of undertaking preclinical investigations and developing tailored therapies.


Subject(s)
Antineoplastic Agents/therapeutic use , Biomarkers, Tumor/analysis , Bone Neoplasms/drug therapy , Chordoma/drug therapy , Quinazolines/therapeutic use , Sacrum/pathology , Animals , Blotting, Western , Bone Neoplasms/metabolism , Bone Neoplasms/pathology , Chordoma/metabolism , Chordoma/pathology , ErbB Receptors/antagonists & inhibitors , ErbB Receptors/metabolism , Female , Humans , Immunoenzyme Techniques , In Situ Hybridization, Fluorescence , Lapatinib , Magnetic Resonance Imaging , Mice , Mice, Nude , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/metabolism , Neoplasm Recurrence, Local/pathology , Sacrum/drug effects , Sacrum/metabolism , Signal Transduction/drug effects , Transplantation, Heterologous , Tumor Cells, Cultured , Xenograft Model Antitumor Assays
15.
Spine (Phila Pa 1976) ; 37(20): 1785-9, 2012 Sep 15.
Article in English | MEDLINE | ID: mdl-22472808

ABSTRACT

STUDY DESIGN: A retrospective cohort study. OBJECTIVE: To compare the incidence of retrograde ejaculation (RE) after anterior lumbar spine surgery with disc replacement versus fusion with the use of recombinant human bone morphogenetic protein-2 (BMP). SUMMARY OF BACKGROUND DATA: Anterior lumbar interbody fusion (ALIF) has become a popular choice for treating a number of pathologies, largely because it preserves the posterior paravertebral muscles and ligaments. Despite these advantages, the anterior approach is also associated with various complications, one of which is RE. A recent study has questioned whether the risk of RE is increased by the use of BMP in ALIF procedures rather than by the approach alone. METHODS: We conducted a retrospective review of all male patients who received ALIF using BMP or artificial disc replacement (ADR) on at least the L5-S1 level between 2004 and 2011. Medical records were evaluated for the occurrence of RE, and patients were contacted via the phone to obtain current information. The incidence of RE was then compared between the 2 anterior lumbar surgery procedures. RESULTS: Of the 95 cases of anterior surgery including L5-S1, 54 patients underwent ALIF with BMP (56.8%) and 41 patients were treated with ADR (43.2%). Postoperative RE occurred in 4 of the 54 ALIF patients (7.4%) and in 4 of the 41 ADR patients (9.8%). The incidence of RE was not significantly different between groups (P = 0.7226). At latest follow-up, 1 ALIF and 1 ADR patient reported resolution of the RE. CONCLUSION: This study found that RE occurred at a similar rate in patients treated with ADR and ALIF with BMP. The overall rate of RE after retroperitoneal anterior lumbar surgery was higher than expected, which underscores the importance of counseling patients about this risk and specifically questioning patients about the symptoms of RE at postoperative visits.


Subject(s)
Ejaculation/physiology , Genital Diseases, Male/physiopathology , Lumbar Vertebrae/surgery , Postoperative Complications/physiopathology , Spinal Fusion/adverse effects , Total Disc Replacement/adverse effects , Adult , Aged , Bone Morphogenetic Protein 2/adverse effects , Bone Morphogenetic Protein 2/therapeutic use , Genital Diseases, Male/etiology , Humans , Lumbar Vertebrae/drug effects , Male , Middle Aged , Outcome Assessment, Health Care/statistics & numerical data , Postoperative Complications/etiology , Retrospective Studies , Sacrum/drug effects , Sacrum/surgery , Spinal Diseases/surgery , Spinal Fusion/methods , Total Disc Replacement/methods , Young Adult
17.
Anesth Analg ; 105(1): 263-6, 2007 Jul.
Article in English | MEDLINE | ID: mdl-17578985

ABSTRACT

BACKGROUND: In this prospective, randomized, double-blind study, we compared the tibial and the peroneal evoked motor response with regard to efficacy of sciatic nerve block using the parasacral approach. METHODS: Twenty-six ASA I-III patients scheduled for elective lower limb surgery were randomized to receive a parasacral sciatic block, using a nerve stimulator technique seeking either a tibial (n = 14) or peroneal (n = 12) motor response. After the evoked motor response was obtained, a solution of 10 mL 2% lidocaine with epinephrine and 10 mL 0.75% ropivacaine (actual final concentration of epinephrine, 1/160,000) was slowly injected through the needle. Sensory and motor blocks were assessed every 5 min for 30 min by an anesthesiologist blinded to the elicited motor response. If the block was not complete 30 min after injection of the local anesthetics, it was considered as failed, and general anesthesia was supplemented. RESULTS: Time to perform the block and level of minimal and maximal stimulation were not different between groups. The success rate of complete block was significantly higher in the tibial compared to the peroneal group (11 of 14 vs 2 of 12; P = 0.002). CONCLUSIONS: Eliciting a tibial motor response predicts a higher success rate than eliciting a peroneal motor response with parasacral sciatic nerve block.


Subject(s)
Evoked Potentials, Motor/physiology , Nerve Block/methods , Sciatic Nerve/physiology , Adult , Aged , Anesthetics, Local/administration & dosage , Double-Blind Method , Evoked Potentials, Motor/drug effects , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Prospective Studies , Sacrum/drug effects , Sacrum/physiology , Sciatic Nerve/drug effects
18.
AJNR Am J Neuroradiol ; 28(1): 38-41, 2007 Jan.
Article in English | MEDLINE | ID: mdl-17213421

ABSTRACT

BACKGROUND AND PURPOSE: Sacral insufficiency fractures are an infrequent but often disabling cause of severe low back pain. We report our results of a sacroplasty technique, using CT for needle placement and fluoroscopy to monitor the polymethylmethacrylate injection in a group of patients with sacral insufficiency fractures. METHODS: All patients had a history of chronic back pain and had an osteoporotic sacral insufficiency fracture documented by imaging before the procedure. With the patient under conscious sedation, a bone biopsy needle was placed under CT guidance; the patient was then transferred to the fluoroscopy suite, where a polymethylmethacrylate mixture was injected into the sacrum under real-time fluoroscopy. Clinical outcome was assessed by telephone. RESULTS: The procedure was performed on 13 female patients with an average age of 76 years (range, 60-88 years). A bilateral procedure was performed in 11 patients and a unilateral procedure was performed in 2 patients. An average of 4.1 mL of cement was injected for each treatment. There were no instances of cement extravasation into the central canal or sacral foramina. Long-term follow-up, averaging 15 months, was available in 6 patients. Five patients (83%) reported no symptoms of pain at all. The final patient, in whom a bilateral procedure was performed, was completely asymptomatic on the left side but reported persistent unilateral pain on the right. CONCLUSION: Sacroplasty is a safe and effective procedure in the treatment of sacral insufficiency fractures that can provide substantial pain relief and lead to a better quality of life.


Subject(s)
Fluoroscopy , Fractures, Spontaneous/therapy , Osteoporosis, Postmenopausal/complications , Polymethyl Methacrylate/administration & dosage , Radiology, Interventional , Sacrum/injuries , Spinal Fractures/therapy , Tomography, X-Ray Computed , Aged , Back Pain/etiology , Back Pain/therapy , Bone Cements , Female , Fractures, Spontaneous/diagnosis , Humans , Middle Aged , Osteoporosis, Postmenopausal/diagnosis , Osteoporosis, Postmenopausal/therapy , Sacrum/drug effects , Sacrum/pathology , Spinal Fractures/diagnosis , Treatment Outcome
19.
Rofo ; 178(11): 1105-14, 2006 Nov.
Article in German | MEDLINE | ID: mdl-17133671

ABSTRACT

PURPOSE: To study the influence of (Modic) signal alterations (SA) of the cartilage endplate (CEP) of vertebrae L3-S1 on the outcome of an in-patient minimally invasive treatment (MIT) using epidural injections on patients with lumbar disc herniation (LDH). MATERIALS AND METHODS: The MR images of 59 consecutive patients with LDH within segments L3/L4 - L5/S1 undergoing in-patient minimally invasive treatment with epidural injections were evaluated in a clinical study. The (Modic) signal alterations of the CEP were recorded using T1- and T2-weighted sagittal images. On the basis of the T2-weighted sagittal images, the extension and distribution of the SA were measured by dividing each CEP into 9 areas. The outcome of the MIT was recorded using the Oswestry Disability Index (ODI) before and after therapy and in a 3-month follow-up. Within a subgroup of patients (n = 35), the distribution and extension of the signal alterations were correlated with the development of the ODI. RESULTS: Segments with LDH showed significantly more (p < 0.001) SA of the CEP than segments without LDH. Although the extension of the SA was not dependent on sex, it did increase significantly with age (p = 0.017). The outcome after MIT did not depend on the sex and age of the patients nor on the type of LDH. The SA extension tended to have a negative correlation with the outcome after MIT after 3 months (p = 0.071). A significant negative correlation could be established between the SA extension in the central section of the upper endplate and the outcome after 3 months (p = 0.019). CONCLUSION: 1. Lumbar disc herniation is clearly associated with the prevalence of (Modic) signal alterations. 2. Extensive signal alterations tend to correlate with a negative outcome of an MIT using epidural injections. 3. Such SA in the central portion of the upper CEP correlate significantly with a negative treatment result. 4. The central portion of the upper CEP being extensively affected by (Modic) SA is a negative predictor for the success of a minimally invasive pain therapy.


Subject(s)
Anesthetics, Local , Anti-Inflammatory Agents/administration & dosage , Intervertebral Disc Displacement/drug therapy , Intervertebral Disc/drug effects , Lumbar Vertebrae/drug effects , Magnetic Resonance Imaging , Mepivacaine/administration & dosage , Sacrum/drug effects , Triamcinolone/administration & dosage , Adolescent , Adult , Aged , Bone Marrow/drug effects , Bone Marrow/pathology , Disability Evaluation , Female , Follow-Up Studies , Hospitalization , Humans , Injections, Epidural , Intervertebral Disc/pathology , Intervertebral Disc Displacement/diagnosis , Lumbar Vertebrae/pathology , Male , Middle Aged , Nerve Compression Syndromes/diagnosis , Nerve Compression Syndromes/drug therapy , Osteochondritis/diagnosis , Osteochondritis/drug therapy , Outcome Assessment, Health Care , Sacrum/pathology , Spinal Nerve Roots/drug effects , Spinal Nerve Roots/pathology , Statistics as Topic
20.
J Spinal Disord Tech ; 19(5): 373-5, 2006 Jul.
Article in English | MEDLINE | ID: mdl-16826012

ABSTRACT

STUDY DESIGN: Case report describing augmentation of a loosened sacral screw with percutaneous injection of polymethylmethacrylate. OBJECTIVE: To highlight the advantages of percutaneous injection of polymethylmethacrylate in treatment of loosened pedicle screws. SETTING: Turkey. SUMMARY OF BACKGROUND DATA: Lumbosacral instrumentation with pedicle screws is a commonly used procedure for correcting deformity and stabilizing the spine until bony fusion occurs. Loosening of the screws is a complication of this procedure and is seen more frequently in multilevel instrumentation, particularly in those instrumentations using sacral screws. METHOD: We present the case of a woman who had had L3-L4-L5-S1 instrumentation with pedicle screws who developed severe low back pain radiating to the left hip 2 months after the operation. Radiologic and clinical examination revealed that the left pedicle screw of the sacrum had loosened, and revision surgery was planned. The left sacral screw was augmented with percutaneous injection of polymethylmethacrylate. RESULTS: The patient was free of pain after the operation. CONCLUSIONS: We suggest that percutaneous polymethylmethacrylate injection around a loosened screw may be an alternative to major open revision surgery in cases of sacral screw failure in multisegmental instrumentation.


Subject(s)
Bone Screws/adverse effects , Lumbar Vertebrae/surgery , Polymethyl Methacrylate/administration & dosage , Sacrum/surgery , Female , Humans , Low Back Pain/diagnostic imaging , Low Back Pain/etiology , Low Back Pain/surgery , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/drug effects , Radiography , Reoperation , Sacrum/diagnostic imaging , Sacrum/drug effects
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