High Serum Alkaline Phosphatase Research Articles

DIAGNOSTIC ASPECTS OF PAGET’S DISEASE OF BONE IN CLINICAL PRACTICE

Paget’s disease of bone (PDB) is a chronic localized skeletal disease that belongs to a group of metabolic osteopathies and is characterized by impaired bone remodeling to form foci of increased bone resorption followed by replacement with an excessive amount of defective, less durable bone that is prone to deformities and pathologic fractures. The course of PDB shows three stages: rarefaction, compaction, and coarse-trabecular remodeling – each of which is characterized by certain clinical, biochemical, and radiological manifestations. The majority of the clinical manifestations of the disease are associated with skeletal injury. The disease is characterized by the appearance of bone and joint pain in case of secondary osteoarthritis, bone deformities, pathological fractures, hearing loss due to damage to the skull bones, etc. In many patients, the disease is asymptomatic and detected incidentally after finding a high serum alkaline phosphatase activity or during bone X-ray for any pathological processes, but it can be diagnosed fairly late in the development of complications, as shown in the clinical examples. A combination of clinical, biochemical, morphological data and radiological findings allows for a diagnosis. The use of bisphosphonates is the method of choice for the treatment of PDB.

Survival After Palliative Radiotherapy in Patients with Breast Cancer and Bone-only Metastases.

Patients with bone-only metastases survive longer than patients with widespread visceral disease. We analyzed the prognostic impact of different baseline parameters, such as abnormal blood tests and receptor status in patients who received local radiotherapy, in addition to contemporary systemic treatment, according to national guidelines. Retrospective uni- and multivariate analyses of 57 consecutive female patients treated in the time period 2007-2014 (median follow-up=29 months). The median age was 59 years and the median time interval from the initial diagnosis of breast cancer was 57 months. The median survival was 23 months from radiotherapy and 32 months from initial diagnosis of metastatic disease. Five-year survival rates were 13 and 21%, respectively. Survival after radiotherapy was significantly longer in patients who were prescribed higher radiation doses; 29 months after ≥30 Gy and 10 months after <30 Gy, p=0.02. Multivariate analysis confirmed 4 independent prognostic factors for shorter survival: triple-negative histology (p=0.0001), high serum lactate dehydrogenase (LDH) (p=0.001), high serum alkaline phosphatase (ALP) (p=0.015) and intended radiation dose <30 Gy (p=0.028). A 3-tiered prognostic score with median survival of 48, 21 and 12 months was developed. Prognosis varied widely with many patients surviving for several years. The results of simple blood tests provided important prognostic information. Prospective studies are necessary to confirm that more aggressive radiotherapy improves survival in patients with bone-only disease suitable for local therapy.

Elevated liver enzymes

Elevated liver enzymes are a frequent finding in both symptomatic and asymptomatic patients necessitating further evaluation to clarify the underlying disease. Three different patterns of increased liver enzymes can be defined to allow for a more precise and rational further diagnostic approach. A predominant increase in transaminase activities reflects a disturbance of hepatocellular integrity which can be found in patients with viral hepatitis, genetic liver diseases like Wilson`s disease or hemochromatosis, and drug-induced liver diseases. A second pattern is characterized by high serum alkaline phosphatase and γ-glutamyltranspeptidase activities indicating cholestatic liver diseases. The next important diagnostic measure in this group is an ultrasound study discerning intra- from extrahepatic cholestasis. Intrahepatic cholestatic diseases include primary and secondary sclerosing cholangitis, genetic disturbances of canalicular membrane transporters or drug-induced liver dieseases. Extrahepatic cholestasis involves obstruction of the large bile ducts by gall stones or tumors. The third enzym pattern is defined by a predominant rise in γ-glutamyl transpeptidase which is observed in alcoholic or non-alcoholic fatty liver disease and infiltrating liver diseases. A rise in liver enzymes is not necessarily indicative of a primary hepatic origin. Extrahepatic diseases often cause similarly increased serum activities. In addition even higher values can be observed under normal conditions during pregnancy or in adolescens. Lower values in asymptomatic patients should only be controlled since more than 30% of elevated transaminases spontaneously normalize during follow-up.

High Serum Alkaline Phosphatase Levels in Relation to Multi-Cerebral Microbleeds in Acute Ischemic Stroke Patients with Atrial Fibrillation and/or Rheumatic Heart Disease.

Elevated alkaline phosphatase (ALP) levels are associated with cerebral small vascular diseases, such as silent brain infarction and cerebral white matter hyperintensity (cWMH), but few prospective data are available for cerebral microbleeds (CMBs). The aim of the study was to investigate associations between serum ALP levels and CMBs in acute ischemic stroke patients with atrial fibrillation and/or rheumatic heart disease. This prospective study involved consecutively recruited acute ischemic stroke patients with atrial fibrillation and/or rheumatic heart disease treated at two large tertiary care hospitals in southwestern China. We used logistic regression to examine the relationships between ALP levels and CMBs. Of 128 patients (56 males; mean age, 68 years) included, 71 (55.5%) patients had CMBs. Compared with the first tertile of ALP concentration, participants in the third tertile were 3.59 times more likely to have multi-CMBs (≥2) [95% confidence interval (CI): 1.21-10.71; P = 0.02] after adjusting for age, gender, smoking habits, drinking habits, ALT (alanine transaminase) levels, AST (aspartate transaminase) levels, renal impairment and cWMH.

Osteomalacia induced by long-term low-dose adefovir dipivoxil: Clinical characteristics and genetic predictors

ContextAdefovir dipivoxil (ADV) was an important cause of adult-onset hypophosphatemic osteomalacia. However, its clinical characteristics and mechanisms have not been well defined. ObjectiveThe objective of the study was to summarize the clinical characteristics of ADV-induced osteomalacia and to explore the association between ADV-associated tubulopathy and polymorphisms in genes encoding drug transporters. Design, setting, patients, and main outcome measureSeventy-six affected patients were clinically studied. The SLC22A6 and ABCC2 genes were screened and compared with healthy people from the HapMap. ResultsHypophosphatemia, high serum alkaline phosphatase (ALP) levels, hypouricemia, nondiabetic glycosuria, proteinuria, metabolic acidosis and high bone turnover markers were the main metabolic characteristics. Fractures and pseudofractures occurred in 39 patients. Stopping ADV administration, supplementing calcitriol and calcium was effective during the follow-up period. Single SNP analysis revealed a higher percentage of the G/A genotype at c.2934 in exon 22 of the ABCC2 gene (rs3740070) in patients than in healthy people (12% [7 of 58 patients] vs. 0% [0 of 45 patients]; P=0.017), while there was no subject with homozygosity for the A allele at c.2934. ConclusionsADV can be nephrotoxic at a conventional dosage. The G/A genotype at c.2934 of the ABCC2 gene may be a predictor of patients at greater risk for developing ADV-associated tubulopathy. Larger case-control studies are needed to further verify this finding.

Outcome of Long-Term Bisphosphonate Therapy in McCune-Albright Syndrome and Polyostotic Fibrous Dysplasia.

McCune-Albright syndrome (MAS) is a rare bone disorder characterized by fibrous dysplasia (FD), endocrinopathies, and café-au-lait patches. FD patients have been shown to respond favorably to treatment with bisphosphonates, but data are scarce in the more severe polyostotic form (PFD), including MAS, and factors determining treatment outcome are not known, particularly in the long-term. We evaluated the biochemical (bone turnover markers [BTMs]) and clinical (pain reduction) outcome of bisphosphonate therapy in 11 patients with MAS and 30 patients with PFD: median duration of treatment 6 years (range, 2 to 25 years). Prognostic factors for treatment outcome were identified in both groups. Patients with MAS were younger at diagnosis (p = 0.001), all had precocious puberty, and four (36%) had additional growth hormone (GH) excess associated with severe craniofacial FD. Extent of skeletal disease was more severe in MAS compared to PFD. MAS patients had higher serum alkaline phosphatase (ALP) concentrations (p = 0.005), higher skeletal burden scores (p < 0.001), and more fractures (p = 0.021). MAS patients had also higher levels of FGF-23 (p = 0.008) and higher prevalence of hypophosphatemia (p = 0.013). Twenty-four of 30 PFD patients (80%) demonstrated a complete clinical and biochemical response within a year of starting treatment (p = 0.015), compared to only four of 11 MAS patients (36%). There were no nonresponders. In the whole group, FGF-23, total ALP, P1NP, and CTX positively correlated with skeletal burden scores (all p ≤ 0.001), which was the only significant risk factor for an incomplete response to bisphosphonate therapy (p < 0.01). Our data suggest a beneficial and safe outcome of long-term bisphosphonate therapy in the majority of patients with PFD, although response to therapy was limited by the higher skeletal disease burden in MAS patients. In the PFD/MAS population studied, the only identified prognostic factor that influenced the outcome of bisphosphonate therapy was a high skeletal burden score. © 2016 American Society for Bone and Mineral Research.

Hematological and Serum Biochemical Abnormalities Associated with a Suspected Case of Genital Squamous Cell Carcinoma in a Gray Nigerian Mare

An 18-year-old gray mare (a crossbred Nigerian horse) was observed to have a proliferative tissue growth with multiple necrotic areas, which was suspected to be a genital squamous cell carcinoma. The mucous membrane of the eyes and gingiva of the mare were pale, and the animal was dull and insensitive, had an abnormal posture and gait, with conspicuous protruding proliferative tissue mass around the vagina and vulva. Blood samples for hematology analysis and serum biochemistry were collected from the jugular vein and determinations followed standard procedures. Hematological examination revealed that the mare had macrocytic anaemia, leukocytosis, neutrophilia, monocytosis, higher than normal erythrocyte sedimentation rate. Serum biochemical assays showed that serum activities of aspartate aminotransferase and alanine aminotransferase were slightly lower than normal. High serum alkaline phosphatase activity was recorded, with high serum total protein level that was mainly due to high serum globulin level. The mare also had a lower than normal total cholesterol. High serum creatinine level was observed. These hematological and serum biochemical findings are commonly associated with genital squamous cell carcinomas in animals and humans.

Outcomes of Percutaneous Cholecystostomy for Acute Cholecystitis

Acute cholecystitis (AC) is an important cause of emergency admissions among the elderly. The use of percutaneous cholecystostomy (PC) as bridging therapy among high-risk patients is widely accepted. However, the use of PC as definitive treatment is controversial. To determine the characteristics, clinical outcomes and predictors of recurrence of AC among patients who underwent PC. A retrospective case series of 71 consecutive patients [73 (38-96) years, 43/71 males] treated with PC for AC at a tertiary hospital from 2007 to 2013, with data collected from case records. Patients were followed up for 37.0 (0.1-110.8) months after PC. Mortality rate was 8.5% (6/71) during the index admission and 32.4% (23/71) at the end of follow-up. Recurrence rate for AC was 11.9% (7/59). Median time to recurrence was 62 (13-464) days. PC was definitive treatment in 33/59. Predictors of recurrence were higher serum alkaline phosphatase (ALP) at diagnosis (OR=1.01, 95% CI 1.00-1.02, p=0.021) and acute myocardial infarction (AMI) during index admission (OR=8.00, 95% CI 1.19-54.0, p=0.033). Fifteen patients (26.3%, 15/71) had post-procedural complications including dislodgement (14%, 10/71), tube obstruction (7.0%, 5/71), bile leaks (2.8%, 2/71), gallbladder perforation (1.4%, 1/71), bowels perforation (1.4%, 1/71) and severe post-procedural haemorrhage (1.4%, 1/71). PC is effective and relatively safe in high-risk patients with AC. However, patients with higher ALP or AMI during index admission have higher risk of recurrence and might benefit from definitive cholecystectomy.

Pituitary-dependent hyperadrenocorticism in a terrier dog: A case report

We report a case of pituitary-dependent hyperadrenocorticism in a 10-year-old, female, terrier dog. The animal was admitted due to polyphagia, weight gain, polyuria, polydipsia, hair loss, exercise intolerance and panting at rest. On physical examination, abdominal distention, truncal and bilaterally symmetric alopecia, thin hypotonic skin, comedones, bruising, hyperpigmentation and calcinosis cutis on the dorsal midline were observed. Hematologic investigations showed stress leukogram, high serum alkaline phosphatase activity, mild to moderate alanine aminotransferase activity, hypercholesterolemia, hypertriglyceridemia and hyperglycemia. Mild generalized interstitial lung patterns and hepatomegaly were detected in the radiographs. Bilaterally symmetric normal-sized adrenal glands were also diagnosed in ultrasonography. Diagnosis of pituitary-dependent hyperadrenocorticism was confirmed with low-dose dexamethasone suppression test. The dog was successfully treated with mitotane.

Hepatocutaneous syndrome in Shih Tzus: 31 cases (1996-2014).

To characterize findings in Shih Tzus with progressive superficial necrolytic dermatitis and degenerative vacuolar hepatopathy consistent with hepatocutaneous syndrome. Retrospective case series. 31 Shih Tzus. Medical records were reviewed to obtain information on signalment, history, treatment, outcome, and results of clinicopathologic testing, abdominal ultrasonography, and histologic examination of skin and liver specimens. A pedigree analysis was performed. There were 16 males and 15 females. Median age at the time of diagnosis was 8 years (range, 5 to 14 years). Common clinical signs included lethargy, inappetence, weight loss, and lameness. Twenty-five dogs had cutaneous lesions consistent with hepatocutaneous syndrome; the remaining 6 initially only had hepatic abnormalities, but 3 of the 6 subsequently developed cutaneous lesions. Common clinicopathologic abnormalities included microcytosis (15/24 [63%] dogs) and high serum alkaline phosphatase activity (24/24 [100%] dogs). Hepatic ultrasonographic findings included a hyperechoic or heteroechoic appearance to the parenchyma with innumerable hypoechoic nodules. Histologic hepatic lesions consisted of degenerative vacuolar (glycogen and lipid) hepatopathy associated with minimally fibrotic to nonfibrotic, noninflammatory, proliferative nodules. Pedigree analysis confirmed a common ancestry in 12 of 18 dogs. Median survival time was 3 months (range, 1 to 36 months). Results suggested that HCS may have a heritable component in Shih Tzus, although the condition may also be identified in Shih Tzus without affected relatives. Clinical, clinicopathologic, ultrasonographic, and histologic abnormalities in affected Shih Tzus were similar to those previously reported for dogs of other breeds with HCS.

KIAA0101 mRNA expression in the peripheral blood of hepatocellular carcinoma patients: Association with some clinicopathological features

ObjectivesThe development of hepatocellular carcinoma (HCC) is multi-factorial, multi-step and involving many genes. Recent studies have revealed the involvement of KIAA0101 in HCC development and progression. KIAA0101 is involved in the regulation of DNA repair, cell cycle progression, and cell proliferation.This study aims to elucidate the clinicopathological significance of KIAA0101 mRNA expression in the whole blood of HCC patients. Design and methodsThis study was conducted on 77 patients with proven HCC who presented to the outpatient clinic at the National Cancer Institute — Cairo University over a period of 8 consecutive months. Thirty patients with cirrhosis and forty apparently healthy volunteers were included as control groups.Detection of KIAA0101 mRNA was done on whole blood collected on EDTA for all patients and control subjects using real-time PCR. ResultsKIAA0101 mRNA was over-expressed in the HCC group compared to the control groups. Overexpression of KIAA0101 mRNA was significantly associated with distant metastasis, advanced stage, high serum alkaline phosphatase and low serum albumin levels. Both sensitivity and specificity of KIAA0101 mRNA were higher than those of AFP and CEA. ConclusionBeing associated with some of the prognostic factors of HCC which reflect tumor progression; as advanced stage, distant metastasis, hypoalbuminemia and elevated serum alkaline phosphatase, together with its relatively high diagnostic performance; KIAA0101 mRNA might be nominated to play a probable role in the diagnosis and prognosis prediction of HCC. Further studies on a wider scale are recommended to confirm these results.

Prognostic Factors and Skeletal-Related Events in Patients with Small Cell Lung Cancer with Bone Metastases at the Time of Diagnosis

Background/Objective: The aim of this study was to evaluate the characteristics and prognostic factors of small cell lung cancer (SCLC) with bone metastases. We also investigated the characteristics and predictive factors of skeletal-related events (SREs) in these patients. Materials and Methods: Sixty-one patients who were first diagnosed with SCLC with bone metastases at our institution were included in this retrospective analysis. Results: The overall survival (OS) of patients with bone metastases was shorter than that of patients without bone metastases (4.13 vs. 6.17 months, p = 0.015). Poor Eastern Cooperative Oncology Group (ECOG) performance status (PS; ≥2) and higher serum alkaline phosphatase (ALP; above upper normal limit × 2) were independent poor prognostic factors (p = 0.027 for ECOG PS, p = 0.002 for ALP). More than 1 SRE occurred in 21 patients (34.4%). Cervical spine metastasis, thoracic spine metastasis, pelvic bone metastasis, more than 5 bone metastatic regions and higher serum lactate dehydrogenase were correlated with the occurrence of SREs. Thoracic spinal metastasis was a strong predictive factor for the occurrence of SREs (odds ratio = 5.475; 95% CI: 1.080-27.755). Conclusion: Our study demonstrates the poor prognosis of SCLC patients with bone metastases. Physicians should treat SCLC patients with bone metastases with caution.

Serum Alkaline Phosphatase Levels are Not Associated with Increased Death Risk in Prevalent Hemodialysis Patients: 5-Year Experience in a Single Hemodialysis Center

Background/Aims: Although high serum alkaline phosphatase (ALP) levels were reported as predictive factors for death risk in dialysis patients on the basis of large databank analyses, the real scenario in a single hemodialysis (HD) center is unknown. Methods: In this study, a 5-year cohort of 1126 prevalent HD patients in the largest HD center in Taiwan was studied. The associations of ALP levels expressed as baseline, time-average, and time-dependent with all-cause mortality and cardiovascular mortality were evaluated by using adjusted Cox regression models. Results: At baseline, levels of serum parathyroid hormone, calcium, and liver enzymes are increased in parallel with ALP quartiles. The hazard ratio (HR) for all-cause mortality was significantly increased in time-average and time-dependent ALP quartile in the unadjusted Cox analysis. The significance disappeared when multivariate adjusted Cox analysis was used. Similarly, HR was not significantly increased for cardiovascular mortality with ALP quartile expressed as baseline, time-average, and time-dependent in three models of Cox analyses. Conclusion: Our study demonstrated that serum ALP levels were not associated with increased death risk in prevalent HD patients over a 5-year interval.

Osteoblast-Specific Overexpression of Human WNT16 Increases Both Cortical and Trabecular Bone Mass and Structure in Mice.

Previous genome-wide association studies have identified common variants in genes associated with bone mineral density (BMD) and risk of fracture. Recently, we identified single nucleotide polymorphisms (SNPs) in Wingless-type mouse mammary tumor virus integration site (WNT)16 that were associated with peak BMD in premenopausal women. To further identify the role of Wnt16 in bone mass regulation, we created transgenic (TG) mice overexpressing human WNT16 in osteoblasts. We compared bone phenotypes, serum biochemistry, gene expression, and dynamic bone histomorphometry between TG and wild-type (WT) mice. Compared with WT mice, WNT16-TG mice exhibited significantly higher whole-body areal BMD and bone mineral content (BMC) at 6 and 12 weeks of age in both male and female. Microcomputer tomography analysis of trabecular bone at distal femur revealed 3-fold (male) and 14-fold (female) higher bone volume/tissue volume (BV/TV), and significantly higher trabecular number and trabecular thickness but lower trabecular separation in TG mice compared with WT littermates in both sexes. The cortical bone at femur midshaft also displayed significantly greater bone area/total area and cortical thickness in the TG mice in both sexes. Serum biochemistry analysis showed that male TG mice had higher serum alkaline phosphatase, osteocalcin, osteoprotegerin (OPG), OPG to receptor activator of NF-kB ligand (tumor necrosis family ligand superfamily, number 11; RANKL) ratio as compared with WT mice. Also, lower carboxy-terminal collagen cross-link (CTX) to tartrate-resistant acid phosphatase 5, isoform b (TRAPc5b) ratio was observed in TG mice compared with WT littermates in both male and female. Histomorphometry data demonstrated that both male and female TG mice had significantly higher cortical and trabecular mineralizing surface/bone surface and bone formation rate compared with sex-matched WT mice. Gene expression analysis demonstrated higher expression of Alp, OC, Opg, and Opg to Rankl ratio in bone tissue in the TG mice compared with WT littermates. Our data indicate that WNT16 is critical for positive regulation of both cortical and trabecular bone mass and structure and that this molecule might be targeted for therapeutic interventions to treat osteoporosis.

Association between Serum Alkaline Phosphatase Level and Cerebral Small Vessel Disease.

BackgroundSerum alkaline phosphatase (ALP) is a marker of vascular calcification. A high serum ALP level is associated with an increase in cardiovascular events, and predicts poor functional outcome in patients with stroke. We investigated whether serum ALP was associated with cerebral small vessel disease (cSVD) and large cerebral artery stenosis (LCAS).MethodsWe evaluated vascular risk factors, brain magnetic resonance images (MRIs), and MR angiograms from 1,011 neurologically healthy participants. The presence of silent lacunar infarction (SLI) and moderate-to-severe cerebral white matter hyperintensities (MS-cWMH) were evaluated as indices of cSVD on brain MRIs. Findings of extracranial arterial stenosis (ECAS) or intracranial arterial stenosis (ICAS) were considered to be indices of LCAS on MR angiograms.ResultsSubjects with SLI (odds ratio [OR]: 2.09; 95% confidence interval [CI]: 1.27–3.42; p = 0.004) and MS-cWMH (OR: 1.48; 95% CI; 1.03–2.13, p = 0.036) were significantly more likely to have ALP levels in the third tertile (ALP ≥ 195 IU/L) than the first tertile (ALP ≤ 155 IU/L), after adjusting for cardiovascular risk factors. The mean serum ALP level was significantly higher in patients with SLI or MS-cWMH compared to patients without those findings. After adjustment for confounding factors, the multivariate model found that the statistical significance of serum ALP remained when the presence of SLI (OR: 1.05 per 10 IU/L increase in ALP; 95% CI: 1.02–1.08; p = 0.003) or MS-cWMH (OR: 1.03 per 10 IU/L increase in ALP; 95% CI: 1.00–1.06; p = 0.025) were added to the model. There were no differences in the proportions of patients with LCAS, ICAS, and ECAS across the serum ALP tertiles.ConclusionsOur study of neurologically healthy participants found a positive association between serum ALP level and indicators of cSVD, but no association between serum ALP level and the indicators of LCAS.

Relative factors analysis of type 2 diabetes mellitus complicated with osteoporosis in elderly men

Objective To investigate and analyze the relative factors in elderly men with type 2 diabetes mellitus(T2DM) complicated with osteoporosis(OP), thus to provide guidance for prevention of OP complicated with T2DM in elderly men. Methods Dual X-ray absorptiometry determination of bone mineral density (BMD) of 67 cases of elderly men with diabetes, men were divided into OP group (n=32), NOP group (n=35). Then, we compared differences in body mass index(BMI), diabetes duration, fasting plasma glucose (FPG), glycosylated hemoglobin(HbA1c), patients' age, fasting insulin(FINS), insulin sensitivity index(ISI), quantitative of urinary albumin (ALb), quantitative of urinary protein in 24 hours and alkaliphosphatase level(ALP), low density lipoprotein cholesterin(LDL-C), triglyceride(TG), and made correlation analysis. Results Compared with those in NOP group, patients in OP group had older age, longer disease course, smaller baric index, lower BMD, higher ALP, lower FINS, lower ISI, higher HbA1c, higher quantitative of urinary protein in 24 hours and urinary albumin, higher LDL-C, which were significantly different (P<0.05); BMD of elderly men with T2DM was negatively correlated to patients' age, disease course, HbA1c, quantitative of urinary protein in 24 hours, ALb, ALP and LDL-C, but positively correlated to BMI, FINS and ISI. Conclusion Many factors, such as elderly, low body weight, long duration of the disease, high level of blood sugar, insulin dysfunction, low insulin sensitivity, high level of blood suger, insulin dysfunction, low insulin sensitivity, high serum alkalinephosphatase, high LDL-C and diabetic nephropathy, contribute to osteoporosis in elderly men with T2DM. Key words: Diabetes mellitus, type 2; Bone mineral density; Osteoporosis; Men (male) sex; Aged; Factor analysis

A rare case of scapular metastasis from bronchogenic carcinoma with ipsilateral malignant pleural effusion.

A rare case of scapular metastasis from bronchogenic carcinoma with ipsilateral malignant pleural effusion.

Prognostic Significance of Serum Alkaline Phosphatase Level in Osteosarcoma: A Meta-Analysis of Published Data.

Background. Serum alkaline phosphatase (SALP) is commonly elevated in osteosarcoma patients. A number of studies have investigated the prognostic role of SALP level in patients with osteosarcoma but yielded inconsistent results. Method. Systematic computerized searches were performed in PubMed, Embase, and Web of Science databases for relevant original articles. The pooled hazard ratios (HRs) and relative risks (RRs) with corresponding confidence intervals (CIs) were calculated to assess the prognostic value of SALP level. Results. Finally, 21 studies comprising 3228 patients were included. Overall, the pooled HRs of SALP suggested that elevated level had an unfavorable impact on osteosarcoma patients' overall survival (OS) (HR = 1.82; 95% CI: 1.61–2.06; p < 0.001) and event-free survival (EFS) (HR = 1.97; 95% CI: 1.61–2.42; p < 0.001). Combined RRs of SALP indicated that elevated level was associated with presence of metastasis at diagnosis (RR = 5.55; 95% CI: 1.61–9.49; p = 0.006). No significantly different results were obtained after stratified by variables of age range, cancer stage, sample size, and geographic region. Conclusion. This meta-analysis demonstrated that high SALP level is significantly associated with poor OS or EFS rate and presence of metastasis at diagnosis. SALP level is a convenient and effective biomarker of prognosis for osteosarcoma.

A novel assessment method of serum alkaline phosphatase for the diagnosis of osteosarcoma in children and adolescents

Background A high serum alkaline phosphatase (ALP) level is valuable for the diagnosis of osteosarcoma in adults, but its use in teenagers is problematic because ALP levels are affected by age, gender, and pubertal stage. Because serum acid phosphatase (ACP) shows the same tetraphasic pattern as serum ALP in children and adolescents, we presumed that serum levels of ALP and ACP would have a strong correlation and that the ratio of ALP to ACP (ALP/ACP) would show little variation and would be useful for the diagnosis of osteosarcoma in teenagers. The purpose of this study was to evaluate the correlation between the serum levels of ALP and ACP and to investigate the validity of ALP/ACP in the differential diagnosis of osteosarcoma in children and adolescents.Methods We retrospectively examined 538 patients aged 1–18 years, including 24 with osteosarcomas, 8 with other malignant bone tumors, 56 with benign bone tumors, and with 450 non-tumor lesions (controls). We evaluated the serum levels of ALP and ACP, both obtained by preoperative examination.Results There were significant correlations between the serum ALP and ACP levels in the controls (r = 0.805 in males and r = 0.860 in females). The ratios of ALP to ACP in the controls showed little variation with age. In ROC curve analysis, to discriminate between the osteosarcomas and the controls, the cutoff levels of serum ALP and ALP/ACP were 956 (U/l) and 50.9 in males and 748 (U/l) and 43.3 in females, respectively. The sensitivity and specificity of serum ALP and ALP/ACP in the differential diagnosis of osteosarcoma were 50.0 and 89.0 %, and 60.0 and 94.1 %, respectively in males, and 61.5 and 72.7 %, and 69.2 and 84.2 %, respectively, in females.Conclusions The results suggest that ALP/ACP is more useful than the serum ALP level in diagnosing osteosarcoma because it is little affected by the age.

PO-0102 Transcutanous Intrahepatic Portosystemic Shunt (tipss) In Children

Background Variceal haemorrhage is a major cause of mortality and morbidity in patients with portal hypertension. Transcutaneous intrahepatic portosystemic shunt (TIPSS) is a procedure which is widely used in adults with limited experience in children. Objectives The aim of this study is to analyse the use of pre- and post-operative laboratory results as predictors for TIPSS failure in the given sample. Methods This is a retrospective study of children who underwent TIPSS from 1998 to 2013. Data were obtained within 1 month before TIPSS placement. The variables are shown in (Table 1). Failure of TIPSS was defined as requirement of revision within 36 months after the procedure. Patients were divided into two groups post-operatively according to the procedure success; those who did not require revision within 36 months after procedure were considered to have successful TIPSS, while those who needed revision within 36 months after procedure had a failed TIPSS procedure. Results A total of 10 children (7 females) underwent TIPSS. The primary indication was variceal haemorrhage in all the patients with different diagnoses (Table-1). Congenital Hepatic Fibrosis was the most common aetiology (50%). Three patients (30%) needed revision in a mean of 24.2 month post-procedure. 7 patients (70%) did not require revision 36 month post procedure, with a mean follow up of 60.5 month. Pre-operative high serum alkaline phosphatase (ALP) was associated with TIPSS failure (p value =0.027) and thus, can be used as a pre-operative predictor for failed TIPSS. Other variables did not show significant association with TIPSS procedure including patients age and weight. Conclusion This study involves the association of multiple variables with TIPSS outcomes in children. ALP showed a relative association as a predictor to TIPSS failure. Further studies are needed with a larger sample.