Interleukin-6 (IL-6) is thought to play a crucial role in the radicular pain caused by lumbar spinal stenosis. However, efficacy of inhibition of IL-6 for sciatica in patients with lumbar spinal stenosis has not been clarified. The purpose of the current study was to examine the effect of the anti-IL-6 receptor monoclonal antibody, tocilizumab, on radicular pain by its epidural administration onto spinal nerves in patients with lumbar spinal stenosis.
Sixty patients with low back and radicular leg pain caused by spinal stenosis were investigated. In 30 patients, we infiltrated 2.0 mL of lidocaine and 80 mg of tocilizumab onto the affected spinal nerve, and 2.0 mL of lidocaine and 3.3 mg of dexamethasone were used in 30 patients. Low back pain, leg pain, and leg numbness were evaluated during 1 month after spinal nerve infiltration.
Infiltration of tocilizumab was more effective than dexamethasone for leg pain (3 days, 1, 2, and 4 weeks), low back pain (3 days, 1, 2 and 4 weeks), and leg numbness (3 days, 1 and 2 weeks). No adverse event was observed in either group.
Our results indicate that the epidural administration of an anti-IL-6 receptor monoclonal antibody, tocilizumab, onto the spinal nerve produced reduction of radicular leg pain, numbness, and low back pain without adverse event. IL-6 may be one of the inducers of pain caused by spinal stenosis in humans.
Anti-interleukin-6 receptor monoclonal antibody; Sciatica; Lumbar spinal stenosis; Pain; Tocilizumab
Developing sensory neurons require neurotrophic support for survival, neurite outgrowth and myelination. The low-density lipoprotein receptor-related protein-1 (LRP1) transactivates Trk receptors and thereby functions as a putative neurotrophin. Herein, we show that LRP1 is abundantly expressed in developing dorsal root ganglia (DRG) and that LRP1-dependent cell signaling supports survival, neurite extension and receptivity to Schwann cells even in the absence of neurotrophins. Cultured embryonic DRG neurons (E15) were treated with previously characterized LRP1 ligands, LRP1-receptor binding domain of α2-macroglobulin (RBD), hemopexin domain of MMP-9 (PEX) or controls (GST) for two weeks. These structurally diverse LRP1 ligands significantly activated and sustained extracellular signal-regulated kinases (ERK1/2) 5-fold (p<0.05), increased expression of growth-associated protein-43(GAP43) 15-fold (P<0.01), and increased neurite outgrowth 20-fold (P<0.01). Primary sensory neurons treated with LRP1 ligands survived > 2 weeks in vitro, to an extent equaling NGF, a finding associated with canonical signaling mechanisms and blockade of caspase-3 cleavage. LRP1 ligand-induced survival and sprouting were blocked by co-incubation with the LRP1 antagonist, receptor associated protein (RAP), whereas RAP had no effect on NGF-induced activity. Site directed mutagenesis of the LRP1 ligand, RBD, in which Lys1370 and Lys1374 are converted to alanine to preclude LRP1 binding, were ineffective in promoting cell signaling, survival or inducing neurite extension in primary sensory neurons, confirming LRP1 specificity. Furthermore, LRP1-induced neurite sprouting was mediated by Src-family kinase (SFK) activation, suggesting transactivation of Trk receptors. Co-cultures of primary embryonic neurons and Schwann cells showed that LRP1 agonists promoted axonal receptivity to myelination to Schwann cells. Collectively, these findings identify LRP1 as a novel and perhaps essential trophic molecule for sensory neuronal survival and development.
Introduction. Spinal scoliosis and kyphosis in elderly people sometimes cause severe low back pain. Surgical methods such as osteotomy are useful for correcting the deformity. However, complications during and after surgery are associated with the osteotomy procedure. In particular, it is difficult to manage deformity correction surgery for patients with Parkinson's disease. Here, we present two cases of combined anterior and posterior surgery for deformity in patients with adult scoliosis and kyphosis due to Parkinson's disease. Case Presentation. Two 70-year-old women had spinal scoliosis and kyphosis due to Parkinson's disease. They had severe low back pain, and conservative treatment was not effective for the pain. Surgery was planned to correct the deformity in both patients. We performed combined posterior and anterior correction surgery. At first, posterior fusions were performed from T4 to the ilium using pedicle screws. Next, cages and autograft from the iliac crest were used in anterior lumbar surgery. The patients became symptom free after surgery. Bony fusion was observed 12 months after surgery. Conclusions. Combined posterior and anterior fusion surgery is effective for patients who show scoliosis and kyphosis deformity, and symptomatic low back pain due to Parkinson's disease.
Osteoarthritic pain is largely considered to be inflammatory pain. Sensory nerve fibers innervating the knee have been shown to be significantly damaged in rat models of knee osteoarthritis (OA) in which the subchondral bone junction is destroyed, and this induces neuropathic pain (NP). Pregabalin was developed as a pain killer for NP; however, there are no reports on pregabalin use in OA patients. The purpose of this study was to investigate the efficacy of pregabalin for pain in OA patients.
Materials and Methods
Eighty-nine knee OA patients were evaluated in this randomized prospective study. Patients were divided into meloxicam, pregabalin, and meloxicam+pregabalin groups. Pain scores were evaluated before and 4 weeks after drug application using a visual analogue scale (VAS), and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Pain scales among groups were compared using a Kruskal-Wallis test.
Before drug application, there was no significant difference in VAS and WOMAC scores among the three groups (p>0.05). Significant pain relief was seen in the meloxicam+pregabalin group in VAS at 1, 2, and 4 weeks, and WOMAC score at 4 weeks, compared with the other groups (p<0.05). No significant pain relief was seen in the meloxicam only group in VAS during 4 weeks and WOMAC score at 4 weeks compared with the pregabalin only group (p>0.05).
Meloxicam+pregabalin was effective for pain in OA patients. This finding suggests that OA pain is a combination of inflammatory and NP.
Pain; osteoarthritis; knee; nerve; pregabalin; inflammatory; neuropathic
Prospective study of changes in intervertebral disc degeneration after injection of bupivacaine.
To examine whether injection of bupivacaine into human intervertebral discs accelerates their degeneration.
Overview of Literature
Bupivacaine is commonly used for therapy and diagnosis of discogenic low back pain. However, several in vitro studies have reported toxic effects of bupivacaine to disc cells. We sought to evaluate whether this finding is clinically relevant.
We selected 46 patients with low back pain who showed disc degeneration at only one level (L4-L5 or L5-S1) on magnetic resonance imaging (MRI) (discography group, n=18), discoblock group (injection of bupivacaine, n=18), and a control group, n=10). There were no significant differences in baseline characteristics across the 3 groups. The two experimental groups underwent either discography or anesthetic discoblock, respectively. All three groups were followed up 5 years after the examination.
At 5 years follow-up, there was no significant difference in the rate of disc degeneration among the 3 groups (p>0.1). Moreover, X-ray images showed that there was no significant difference in disc height, range of motion, or translation between flex and extension position (p>0.1).
In conclusion, radiologic and MRI findings did not show acceleration of intervertebral disc degeneration at 5 years after a single injection of bupivacaine into human discs.
Lumbar vertebrae; Intervertebral disc degeneration; Bupivacaine
We present a rare case of delayed onset of epidural hematoma after lumbar surgery whose only presenting symptom was vesicorectal disturbance. A 68-year-old man with degenerative spinal stenosis underwent lumbar decompression and instrumented posterolateral spine fusion. The day after his discharge following an unremarkable postoperative course, he presented to the emergency room complaining of difficulty in urination. An MRI revealed an epidural fluid collection causing compression of the thecal sac. The fluid was evacuated, revealing a postoperative hematoma. After removal of the hematoma, his symptoms disappeared immediately, and his urinary function completely recovered. Most reports have characterized postoperative epidural hematoma as occurring early after operation and accompanied with neurological deficits. But it can happen even two weeks after spinal surgery with no pain. Surgeons thus may need to follow up patients for at least a few weeks because some complications, such as epidural hematomas, could take that long to manifest themselves.
A 26-year-old paraplegic schizophrenic Japanese woman suffered from severe kyphosis and back pain derived from lumbar burst fractures caused by jumping. She had already undergone resection of the L1 and L2 spinous processes for sharp angular kyphosis, but she still had severe kyphosis and back pain at the L1 and L2. Radiographical examination revealed fused anterior columns at L1 and L2 with severe local kyphosis and a significantly decreased percutaneous distance in the back. The patient underwent anterior instrumented bony resection including an L2 vertebral osteotomy: bilateral L2-L3 facetectomy and partial posterior osteotomy of the L2 vertebrae via a posterior approach followed by an anterior corpectomy of the L2 vertebrae and insertion of a cylindrical cage. No posterior instrumentation was used owing to the presence of atrophied paraspinal soft tissues. Lumbar interbody fusion was performed with vertebral body screws extending from T12 to L4 and corresponding anterior distension and posterior compression. The procedure corrected the kyphosis by 15° and enhanced local stability. Postsurgical visual analogue scale improved from 9.0 to 2.0 and Oswestry Disability Index from 40 to 17.8, respectively. In conclusion, we have demonstrated that anterolateral interbody fusion using extended fixation can compensate for posterior corrective surgery.
The pathological mechanism of lumbar spinal stenosis is reduced blood flow in nerve roots and degeneration of nerve roots. Exercise and prostaglandin E1 is used for patients with peripheral arterial disease to increase capillary flow around the main artery and improve symptoms; however, the ankle-brachial index (ABI), an estimation of blood flow in the main artery in the leg, does not change after treatment. Lumbar spinal nerve roots contain somatosensory, somatomotor, and unmyelinated autonomic nerves. Improved blood flow by medication with prostaglandin E1 and decompression surgery in these spinal nerve roots may improve the function of nerve fibers innervating muscle, capillary, and main vessels in the lower leg, resulting in an increased ABI. The purpose of the study was to examine whether these treatments can improve ABI.
Materials and Methods
One hundred and seven patients who received conservative treatment such as exercise and medication (n=56) or surgical treatment (n=51) were included. Low back pain and leg pain scores, walking distance, and ABI were measured before treatment and after 3 months of conservative treatment alone or surgical treatment followed by conservative treatment.
Low back pain, leg pain, and walking distance significantly improved after both treatments (p<0.05). ABI significantly increased in each group (p<0.05).
This is the first investigation of changes in ABI after treatment in patients with lumbar spinal stenosis. Improvement of the spinal nerve roots by medication and decompression surgery may improve the supply of blood flow to the lower leg in patients with lumbar spinal stenosis.
Ankle-brachial index; pain; lumbar; spinal stenosis
Adult presentation of neglected congenital muscular torticollis (CMT) is rare. Therefore, efficacy of surgical treatment for adult CMT is unclear. We experienced a case of neglected CMT in a 28-year-old male patient and report the surgical result here. We conducted unipolar resection at the distal end of the sternocleidomastoid muscle (SCM). After surgery, the range of neck movement and head tilt improved, and his appearance was cosmetically improved despite the long-standing nature of the deformity. We concluded that surgical management of adult patients with neglected congenital muscular torticollis may be a treatment option.
Although N-ERC/mesothelin (N-ERC) is an attractive diagnostic and treatment monitoring biomarker for malignant pleural mesothelioma (MPM), its clinical utility for predicting the prognosis has not yet been clarified. The aim of this study is to investigate whether the serum N-ERC level can accurately predict the outcome in patients with MPM.
Twenty-six patients with MPM were enrolled. Serum N-ERC level was measured before and after chemotherapy. The N-ERC index was determined by the logarithm of the division of the N-ERC level after two courses of chemotherapy by the prior level.
The median N-ERC index in the partial response (PR) group was significantly lower than that in patients with the stable disease (SD) plus the progressive disease (PD) group. The overall survival in the group whose median N-ERC index was lower than its median value was significantly longer than the group whose median N-ERC index was higher than its median value.
The N-ERC index is therefore considered to be a useful biomarker for predicting not only the chemotherapeutic response, but also the prognosis in patients with advanced MPM.
Mesothelioma; biomarker; N-ERC index; response; prognosis
We report an 85-year-old woman with an L3 vertebral body fracture who presented with back pain, bilateral leg pain, and weakness after four months of conservative treatment. Because of unstable pseudoarthrosis, the L3 vertebral body collapsed in the standing position and the L3 nerve root was compressed. The indicated surgery decompressed the L3-L4 foramen and fused the unstable segment. The back pain and neurologic symptoms improved significantly following surgery. We propose that delayed neurologic deficit following an osteoporotic fracture of the lumbar body may be caused not only by retropulsion of vertebral body fragments with significant canal compromise, but also by foraminal stenosis with the late collapse of the vertebral fracture. This new pathomechanism for delayed neurologic deficit has not been previously described. If a collapse takes place in the caudal part of the vertebral body below the base of the pedicle, spine surgeons should be aware of the possibility of foraminal stenosis.
Based on the neuroprotective effects of granulocyte colony-stimulating factor (G-CSF) on experimental spinal cord injury, we initiated a clinical trial that evaluated the safety and efficacy of neuroprotective therapy using G-CSF for patients with worsening symptoms of compression myelopathy.
We obtained informed consent from 15 patients, in whom the Japanese Orthopaedic Association (JOA) score for cervical myelopathy decreased two points or more during a recent 1-month period. G-CSF (5 or 10 μg/kg/day) was intravenously administered for five consecutive days. We evaluated motor and sensory functions of the patients and the presence of adverse events related to G-CSF therapy.
G-CSF administration suppressed the progression of myelopathy in all 15 patients. Neurological improvements in motor and sensory functions were obtained in all patients after the administration, although the degree of improvement differed among the patients. Nine patients in the 10-μg group (n = 10) underwent surgical treatment at 1 month or later after G-CSF administration. In the 10-μg group, the mean JOA recovery rates 1 and 6 months after administration were 49.9 ± 15.1 and 59.1 ± 16.3%, respectively. On the day following the start of G-CSF therapy, the white blood cell count increased to more than 22,700 cells/mm3. It varied from 12,000 to 50,000 and returned to preadministration levels 3 days after completing G-CSF treatment. No serious adverse events occurred during or after treatment.
The results indicate that G-CSF administration at 10 μg/kg/day is safe for patients with worsening symptoms of compression myelopathy and may be effective for their neurological improvement.
Neuroprotective therapy; Granulocyte colony-stimulating factor; Compression myelopathy; Clinical trial
Patients with Parkinson’s disease have higher risk of complications and revision surgery following spine surgery. Spinal fracture in an ankylosed spine is also difficult to treat. We recently treated a case of thoracic spine fracture in a patient with Parkinson’s disease complicating a severely ankylosed spine. There is no report describing surgical treatment of spine fracture in such a difficult condition, thus, we firstly report the case and discuss the reasons for a successful result.
A 68-year-old man with Parkinson’s disease had a pathologic thoracic spine fracture at T11. Four days after onset, he was referred to a local hospital because of gradually increasing back pain, but no spinal fracture was pointed out at that time. Because he developed lower extremity bilateral numbness and weakness, he was transported to our hospital, eight days after onset. When referred to our hospital, he exhibited severe back pain and paralysis of the lower extremities due to spinal cord involvement. Emergency surgery was performed. Decompression of T10-11 was performed followed by instrumented spinal fusion from T8 to L2. A dramatic neurological improvement was observed following surgery, and complete bony fusion was achieved. At the final two-year postoperative follow-up, the patient had no pathological symptoms related to spinal fracture and no instrument failure was observed.
This patient had Parkinson’s disease and a severely ankylosed spine, both of which may lead to unsatisfactory surgical results from spinal surgery. Generally, patients with Parkinson’s disease have an increased risk for adjacent segment disease and instrument failure. In this patient, fusion surgery did not change the number of fused segments because operated segments were already ankylosed. Because no stress force exists between adjacent vertebral bodies, a severely ankylosed spine may help prevent screw pullout. Thus, treatment of a spinal fracture in an ankylosed spinal segment is a less adverse condition for patients with Parkinson’s disease. Our experience led us to think that a combination of Parkinson’s disease with severely ankylosed spine does not necessarily suggest unsatisfactory outcomes after surgical treatment of spinal fracture.
Parkinson’s disease; Spinal fracture; Ankylosed spine; Ankylosis; Fusion surgery
Recently, driver oncogenes in adenocarcinoma of the lung were identified, and several molecular target agents were introduced in the clinical setting. However, there are few reports on the frequency of gene abnormalities in young patients with lung cancer.
Materials and methods
Twelve patients with lung adenocarcinoma aged 40 or younger at Juntendo University Urayasu Hospital or Juntendo University Hospital from July 2004 to March 2010 were analyzed for driver oncogene status including EGFR activating mutation, EML4-ALK fusion gene, and K-ras mutation.
Four patients showed EGFR gene mutation. Five out of 7 EGFR mutation-negative patients showed positive results for EML4-ALK gene fusion. One case whose EGFR mutation was indeterminate.
Driver oncogene including EGFR mutation and EML4-ALK fusion gene was identified in 9 of 12 cases (75%). Examination of gene abnormalities is essential in young patients with non-small cell lung cancer to provide the best treatment.
Young patients; driver oncogene; lung cancer; EGFR; EML4-ALK
There have been few reports of patients with bilateral cervical facet dislocations that remain untreated for eight weeks or more. We report the case of a 76-year-old man with an old bilateral cervical facet joint dislocation fracture that was treated by posterior-anterior reduction and fixation.
A 76-year-old Asian man was involved in a road traffic accident. He presented with neck pain and arm pain on his right side, but motor weakness and paralysis were not observed. He was treated conservatively; however, instability and spondylolisthesis at the C5 to C6 joint increased eight weeks after the injury. We performed a posterior-anterior reduction and fixation. After surgery, bony union was achieved, and his neck pain and arm pain disappeared.
We recommend reduction and fixation surgery if a patient has an old bilateral facet joint dislocation fracture in the cervical spine.
Cachexia, a major cause of cancer-related death, is characterized by depletion of muscle and fat tissues, anorexia, asthenia, and hypoglycemia. Recent studies indicate that secretions of proinflammatory cytokines such as interleukin-6 (IL-6) play a crucial role in cachexia development, and that these cytokines are secreted from not only cancer cells but also host cells such as macrophages. In this study, we investigated the therapeutic effects of hochuekkito, a Kampo formula, on cachexia induced by colon 26 adenocarcinoma in mice. Hochuekkito treatment did not inhibit tumor growth, but significantly attenuated the reduction in carcass weight, food and water intake, weight of the gastrocnemius muscle and fat tissue around the testes, and decrease of serum triglyceride level compared with controls. Furthermore, hochuekkito treatment significantly reduced serum IL-6 level and IL-6 expression level in macrophages in tissues surrounding the tumor. In vitro studies showed that hochuekkito suppressed the production of IL-6 by THP-1 or RAW264.7 macrophage cells, although it did not affect IL-6 production by colon 26 carcinoma cells. These results suggest that hochuekkito inhibits the production of proinflammatory cytokines, particularly IL-6, by host cells such as macrophages. Therefore, hochuekkito may be a promising anticachectic agent for the treatment of patients with cancer.
The aim of this study was to examine the effect of hydration with magnesium and mannitol without furosemide on the nephrotoxocity accompanying combination chemotherapy using cisplatin and pemetrexed in patients with advanced non-small cell lung cancer (NSCLC).
Fifty patients with NSCLC who received cisplatin plus pemetrexed, using either old hydration protocol including normal saline with mannitol and furosemide, or a new one including normal saline with magnesium and mannitol without furosemide were retrospectively analyzed. Nephrotoxicity was compared between patients treated using the old protocol and those treated with the new protocol. Univariate and multivariate analyses were performed to identify the independent factors associated with protection against nephrotoxicity in patients with NSCLC who received cisplatin plus pemetrexed.
Thirty patients received the old hydration protocol, while 20 patients were treated using the new hydration protocol. The patients treated using the new hydration protocol showed a significantly greater increase in creatinine clearance (P=0.0004) and a decrease in the serum creatinine level (P=0.0148) after one course of chemotherapy compared with those treated using the old hydration protocol. There were no differences in the chemotherapeutic response or overall survival between the groups (P=0.572). The new hydration protocol with supplemented magnesium with mannitol without furosemide was an independent factor for the protection against nephrotoxicity induced by cisplatin and pemetrexed in patients with advanced NSCLC [HR 0.232 (95% CI: 0.055-0.986), P=0.039].
These results demonstrate that the new hydration protocol comprising supplementation with magnesium without furosemide could prevent the nephrotoxicity induced by cisplatin and pemetrexed without affecting the treatment outcome.
Lung cancer; cisplatin; magnesium; nephrotoxicity; pemetrexed
Granulocyte colony-stimulating factor (G-CSF) is a protein that stimulates differentiation, proliferation, and survival of cells in the granulocytic lineage. Recently, a neuroprotective effect of G-CSF was reported in a model of cerebral infarction and we previously reported the same effect in studies of murine spinal cord injury (SCI). The aim of the present study was to elucidate the potential therapeutic effect of G-CSF for SCI in rats.
Adult female Sprague-Dawley rats were used in the present study. Contusive SCI was introduced using the Infinite Horizon Impactor (magnitude: 200 kilodyne). Recombinant human G-CSF (15.0 µg/kg) was administered by tail vein injection at 1 h after surgery and daily the next four days. The vehicle control rats received equal volumes of normal saline at the same time points.
Using a contusive SCI model to examine the neuroprotective potential of G-CSF, we found that G-CSF suppressed the expression of pro-inflammatory cytokine (IL-1 beta and TNF- alpha) in mRNA and protein levels. Histological assessment with luxol fast blue staining revealed that the area of white matter spared in the injured spinal cord was significantly larger in G-CSF-treated rats. Immunohistochemical analysis showed that G-CSF promoted up-regulation of anti-apoptotic protein Bcl-Xl on oligpodendrocytes and suppressed apoptosis of oligodendrocytes after SCI. Moreover, administration of G-CSF promoted better functional recovery of hind limbs.
G-CSF protects oligodendrocyte from SCI-induced cell death via the suppression of inflammatory cytokines and up-regulation of anti-apoptotic protein. As a result, G-CSF attenuates white matter loss and promotes hindlimb functional recovery.
Background. In patients with bronchial asthma, spirometry could identify the airflow limitation of small airways by evaluating the concave shape of the maximal expiratory flow-volume (MEFV) curve. As the concave shape of the MEFV curve is not well documented, we reevaluated the importance of this curve in adult asthmatic patients. Methods. We evaluated spirometric parameters, the MEFV curve, and its concave shape (scoop between the peak and endpoint of expiration) in 27 nonsmoking asthmatic patients with physician-confirmed wheeze and positive bronchial reversibility after a short-acting β2-agonist inhalation. We also calculated angle β and shape factors (SF25% and SF50%) to quantitate the curvilinearity of the MEFV curve. Results. The MEFV curve was concave in all patients. Along with improvements in standard spirometric parameters, curvilinear parameters, angle β, SF25%, and SF50% were significantly improved after bronchodilator inhalation. There were significant correlations between improvements in angle β, and FEF50%, and FEF25-75%, and between improvements in SF25%, and SF50%, and FEF75%. Conclusions. The bronchodilator greatly affected the concave shape of the MEFV curve, correlating with spirometric parameters of small airway obstructions (FEF50%, FEF75%, and FEF25-75%). Thus, the concave shape of the MEFV curve is an important indicator of airflow limitation in adult asthmatic patients.
Because we have a clinical impression that elderly patients have low back pain while in motion and standing, but less pain when sitting, we investigate characteristics of nonspecific low back pain (NSLBP), using a new detailed visual analog scale (VAS) scoring system. One hundred eighty-nine patients with NSLBP were divided into an elderly group (≥65 years old, n = 56) and a young group (<65 years old, n = 133). Low back pain was evaluated by a traditional VAS scoring system, the Oswestry Disability Index (ODI), and a new detailed VAS scoring system in which pain is independently evaluated in three different postural situations (in motion, standing, and sitting). No significant differences were observed in traditional VAS and ODI scores between the two groups. The results of the detailed VAS showed no significant differences between the two groups while in motion and standing. However, the elderly group showed significantly lower VAS score while sitting compared to the young group. In this study of the first use of a new detailed VAS scoring system, differences in characteristics of NSLBP between elderly and young patients were successfully detected. This minor modification of the traditional VAS may be useful for characterizing and evaluating low back pain.
In the present case of postoperative lumbar spinal stenosis after non-instrumented intertransverse fusion with granules of hydroxyapatite (HA), bone union was not completed and the patient felt the recurrence of his symptoms within two years. We performed re-decompression with fusion, and in hematoxylin and eosin staining of HA granulation harvested during revision surgery, fibrous tissue with hyaline degeneration surrounded the cavity where the HA had existed. Multinuclear giant cells and lymphocytes infiltrated some parts of the marginal layer of the cavity, and no obvious bony bridge had regenerated from autologous bone. No tartrate-resistant acid phosphate (TRAP) -positive osteoclasts could be seen in the new bone, suggesting that the activity of osteoclasts in the new bone decreased during the seven years after the primary surgery.
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/3483360258050263
Nonunion; Lumbar spine; Intertransverse fusion; Hydroxyapatite
Intermittent claudication is a common symptom of both lumbar spinal stenosis (LSS) and peripheral arterial disease (PAD) in middle-aged and elderly people. However, the prevalence and clinical characteristics of LSS with PAD (LSSPAD) have not been investigated in a multicenter study. The aim of this study was to investigate the prevalence and clinical characteristics of LSS associated with PAD.
570 patients diagnosed with LSS using a clinical diagnostic support tool and MRI at 64 facilities were enrolled. We evaluated each patient’s medical history, physical findings, ankle brachial index, Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) score, and the Short Form 36 (SF-36) score. Statistical analyses were performed to compare LSSPAD patients and LSS patients without PAD using the t test, Mann–Whitney’s U test, and multivariate recurrence analysis. p values of <0.05 were considered statistically significant.
The LSSPAD group comprised 38 patients (6.7 %); 20 (3.5 %) had pre-diagnosised PAD while 18 (3.2 %) had undetected PAD. The clinical characteristics of these patients were advanced age, diabetes, and a history of ischemic heart disease and cerebrovascular disorder. 570 patients enrolled, and 448 (78.6 %) of those patients were followed up at three months after enrollment. Pain in buttocks and legs improved less in the LSSPAD group than in the LSS group (p < 0.05). Improvements in the “general health” score in SF-36 were lower in the LSSPAD group than in the LSS group (p < 0.05).
Advanced age, diabetes, and a history of cerebrovascular disorder and ischemic heart disease were associated with LSSPAD. Because LSSPAD patients show less improvement in QOL than patients with LSS but without PAD do, clinicians should consider the coexistence of PAD in LSS patients.
Obesity is a risk factor for ossification of the posterior longitudinal ligament (OPLL) of the spine, which is characterized by heterotopic bone formation in the posterior longitudinal spinal ligament. Hyperleptinemia is a common feature of obese people and leptin is believed to be an important factor in the pathogenesis of OPLL. However, the association between leptin and bone metabolism and the development of OPLL is not understood fully. The objective of the present study was to determine the association between serum leptin concentration and bone metabolic markers and the extent of heterotopic ossification of the spinal ligament in patients with OPLL. The serum concentrations of leptin, insulin, fructosamine, bone-specific alkaline phosphatase, and carboxyterminal propeptide of type I procollagen, urine deoxypyridinoline levels, and the number of vertebrae with OPLL involvement were measured in 125 (68 males and 57 females) patients with OPLL. The correlation between leptin and these other factors was then examined. Serum leptin and insulin concentrations were increased significantly in OPLL females compared to non-OPLL female controls. In the females with OPLL, serum leptin concentrations corrected for body mass index correlated positively with the number of vertebrae with OPLL involvement. In females, serum leptin levels were significantly higher in patients in whom OPLL extended to the thoracic and/or lumbar spine than in patients in whom OPLL was limited to the cervical spine. Our results suggest that hyperleptinemia, in combination with hyperinsulinemia, may contribute to the development of heterotopic ossification of the spinal ligament in female patients with OPLL.
Leptin; Ossification of the posterior longitudinal ligament (OPLL); Insulin; Gender; Bone metabolic markers
Among all types of cancer, incidence of lung cancer remains the highest with regard to cancer-related mortality. Problems contributing to recurrence of the disease include metastasis and drug resistance. Mounting evidence has demonstrated involvement of epithelial mesenchymal transition (EMT) in cancer progression. EMT is a critical mechanism ensuring tissue remodeling during morphogenesis of multicellular organisms. Therefore, understanding of the biology of this process for identification of potential EMT-targeted therapeutic strategies for the benefit cancer patients is necessary. This review describes recent evidence of EMT involvement in drug resistance and metastasis of cancers, with an emphasis on lung cancer.
Epithelial-mesenchymal transition; Drug resistance; Neoplasm metastasis; Lung neoplasms