Long Bone Fractures in Fibrous Dysplasia/McCune-Albright Syndrome: Prevalence,Natural History,and Risk Factors

Fibrous dysplasia/McCune-Albright syndrome (FD/MAS) is a rare bone and endocrine disorder arising along a broad spectrum. Long-bone fractures are a common, painful, and potentially disabling complication. However, fracture prevalence and risk factors have not been well-established, making it difficult to predict which patients are at risk for a severe course. Clinical and imaging data were reviewed from two large, well-phenotyped cohorts (National Institutes of Health [NIH] in the United States and the Leiden University Medical Center [LUMC] in the Netherlands) to identify long-bone fractures at FD sites. Skeletal burden score was quantified using bone scintigraphy. Multiple linear regressions were performed to identify clinical associations with fractures. A total of 419 patients were included (186 NIH, 233 LUMC); 194 (46%) had MAS endocrinopathies. Median age at last follow-up was 30.2 years (range 3.2–84.6, interquartile range [IQR] 25.5), and median skeletal burden score was 16.6 (range 0–75, IQR 33). A total of 48 (59%) patients suffered one or more lifetime fracture (median 1, range 0–70, IQR 4). Median age at first fracture was 8 years (range 1–76, IQR 10). Fracture rates peaked between 6 and 10 years of age and decreased thereafter. Lifetime fracture rate was associated with skeletal burden score (β = 0.40, p < 0.01) and MAS hyperthyroidism (β = 0.22, p = 0.01). Younger age at first fracture was associated with skeletal burden score (β = −0.26, p = 0.01) and male sex (β = −0.23, p = 0.01). Both skeletal burden score >25 and age at first fracture ≤7 years were associated with a higher total number of lifetime fractures (median 4, range 1–70, IQR 5 versus median 1, range 1–13, IQR 1) (p < 0.01). In conclusion, higher skeletal burden score and MAS hyperthyroidism are associated with long-bone fractures in FD/MAS. Both skeletal burden score ≥25 and age at first fracture ≤7 years are associated with a higher lifetime long-bone fracture risk and may predict a more severe clinical course. These results may allow clinicians to identify FD/MAS patients at risk for severe disease who may be candidates for early therapeutic interventions. © 2021 American Society for Bone and Mineral Research (ASBMR). This article has been contributed to by US Government employees and their work is in the public domain in the USA.     

Skeletal Disease Acquisition in Fibrous Dysplasia: Natural History and Indicators of Lesion Progression in Children

Fibrous dysplasia (FD) is a rare mosaic disorder resulting in fractures, pain, and disability. Bone lesions appear during childhood and expand during skeletal growth. The rate at which FD lesions progress and the biochemical determinants of FD lesion formation have not been established, making it difficult to investigate and implement preventative therapies. The purpose of this study was to characterize FD lesion progression in children, and to identify clinical variables associated with progressive disease. Clinical data and imaging from an ongoing natural history study at the National Institutes of Health (NIH) were reviewed. 99m-Technetium methylene diphosphonate (99Tc-MDP) scans were used to determine Skeletal Burden Score (SBS), a validated quantitative scoring system. FD progression rate was determined by the change in the SBS in each patient per year. Thirty-one children had serial 99Tc-MDP scans, with a median age at first scan of 6 years (interquartile range [IQR] 4–8, range 2–10), and median follow-up 1.1 years (IQR 1.1–2.1, range 0.7–11.2). The median FD progression rate for the total group was 2.12 SBS units/year (IQR 0.81–2.94, range 0.05–7.81). FD progression rates were highest in children under age 8 years and declined with age (p = 0.03). Baseline disease severity was associated with subsequent disease progression (p = 0.009), with the highest FD progression rates in patients with moderate disease (baseline SBS 16–30), and lowest progression rates in those with severe disease (SBS ≥50). Serum levels of the bone formation marker osteocalcin were positively correlated with subsequent FD progression rate (p = 0.01, R = 0.58). There was no association between FD progression and baseline endocrinopathies, fractures, or surgery rates. FD lesions progress during childhood, particularly in younger children and those with moderate involvement. Osteocalcin may potentially serve as a biomarker for progressive disease. These findings may allow clinicians to investigate preventative therapies, and to identify children with FD who are candidates for early interventions. Published 2022. This article is a U.S. Government work and is in the public domain in the USA.     

18F-FDG PET/CT评价初诊T细胞淋巴瘤代谢活性与免疫表型的相关性

目的观察初诊T细胞淋巴瘤~(18)F-FDG代谢活性与淋巴瘤免疫表型的关系。方法回顾性分析64例初诊T细胞淋巴瘤患者,均于治疗前接受~(18)F-FDG PET/CT检查且经病理学确诊。测量活检部位PET/CT最大标准摄取值(SUV_(max)),分析其与免疫表型之间的相关性。结果 64例活检部位SUV_(max)为2.23～24.42,中位SUV_(max)为8.02,与Ki-67、CD5表达呈正相关(r_s=0.31、P=0.02,r_s=0.81、P0.01),而与其他免疫学指标均无相关性(P均0.05)。结论 T细胞淋巴瘤代谢活性与Ki-67和CD5表达呈正相关;~(18)F-FDG PET/CT可作为无创评估Ki-67和CD5免疫表达的影像学手段。     

18F-FDG PET/CT诊断腹膜后纤维化

目的探讨~(18 )F-FDG PET/CT诊断腹膜后纤维化(RPF)的价值。方法回顾性分析因RPF接受~(18 )F-FDG PET/CT检查的12例患者,分析其病灶形态、分布范围和葡萄糖代谢活性最大标准摄取比值(SUV_(max))。结果 12例患者中,7例为初诊患者,5例为治疗后患者。7例初诊RPF患者中4例为继发性,病因分别为IgG4相关疾病、乳腺癌和前列腺癌。12例患者均可见腹主动脉和/或髂血管旁软组织密度病灶,91.67%(11/12)患者可见输尿管受累。初诊RPF患者腹膜后病灶SUV_(max)(4.21±1.76)显著高于治疗后患者(1.46±0.25;P0.05)。依据PET/CT检查结果,3例有代谢活性病灶的特发RPF患者接受激素和/或他莫昔芬等免疫抑制治疗,4例具有活性病灶的继发RPF患者接受针对病因治疗;5例治疗后患者,3例继续当前激素维持剂量治疗,2例未接受其他治疗。结论 PET/CT可用于评价RPF病灶活性和分布范围。     

Multimodal [18F]FDG PET/CT Is a Direct Readout for Inflammatory Bone Repair: A Longitudinal Study in TNFα Transgenic Mice

In rheumatoid arthritis (RA), chronic joint inflammation leading to bone and cartilage damage is the major cause of functional impairment. Whereas reduction of synovitis and blockade of joint damage can be successfully achieved by disease modifying antirheumatic therapies, bone repair upon therapeutic interventions has only been rarely reported. The aim of this study was to use fluorodeoxyglucose ([¹⁸F]FDG) and [¹⁸F]fluoride µPET/CT imaging to monitor systemic inflammatory and destructive bone remodeling processes as well as potential bone repair in an established mouse model of chronic inflammatory, erosive polyarthritis. Therefore, human tumor necrosis factor transgenic (hTNFtg) mice were treated with infliximab, an anti-TNF antibody, for 4 weeks. Before and after treatment period, mice received either [¹⁸F]FDG, for detecting inflammatory processes, or [¹⁸F]fluoride, for monitoring bone remodeling processes, for PET scans followed by CT scans. Standardized uptake values (SUV_mean) were analyzed in various joints and histopathological signs of arthritis, joint damage, and repair were assessed. Longitudinal PET/CT scans revealed a significant decrease in [¹⁸F]FDG SUVs in affected joints demonstrating complete remission of inflammatory processes due to TNF blockade. In contrast, [¹⁸F]fluoride SUVs could not discriminate between different severities of bone damage in hTNFtg mice. Repeated in vivo CT images proved a structural reversal of preexisting bone erosions after anti-TNF therapy. Accordingly, histological analysis showed complete resolution of synovial inflammation and healing of bone at sites of former bone erosion. We conclude that in vivo multimodal [¹⁸F]FDG µPET/CT imaging allows to quantify and monitor inflammation-mediated bone damage and reveals not only reversal of synovitis but also bone repair upon TNF blockade in experimental arthritis. © 2019 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc.     

Evaluation of the diagnostic performance of 18F-NaF positron emission tomography/computed tomography in patients with suspected ankylosing spondylitis according to the Assessment of SpondyloArthritis International Society criteria

BACKGROUND CONTEXTPositron emission tomography (PET) is a potential imaging technique for the diagnosis of AS. The visualization of physiological change makes PET potentially suitable for early detection of inflammatory processes, even before anatomical changes occur. Thus, PET might provide specificity via the use of receptor targeting tracers and allows quantification of disease activity in order to accurately monitor therapeutic effects.PURPOSETo examine fluorine-18 sodium fluoride (¹⁸F-NaF) PET/computed tomography (PET/CT) findings in patients with inflammatory low back pain and evaluate the utility of this modality in the diagnosis of ankylosing spondylitis (AS) according to the Assessment of SpondyloArthritis International Society (ASAS) criteria.STUDY DESIGNRetrospective cohort study.PATIENTS SAMPLESixty-eight patients who underwent ¹⁸F-NaF PET/CT imaging between April 2015 and April 2017 for evaluation of inflammatory low back pain.OUTCOME MEASURESWe defined AS-positive lesions on PET/CT as symmetric sacroiliac joint uptake that suggests sacroiliitis, syndesmophytes on the spine, and enthesopathy at any site.METHODSAll patients were evaluated using the ASAS criteria and assigned to either the AS or the control group. The diagnostic criteria of AS on PET/CT images were defined as ¹⁸F-NaF PET/CT images with at least one of AS-positive findings.RESULTSThe diagnostic rate of AS was 72.1% among the 68 patients according to the ASAS criteria. The baseline characteristics between the two groups differed significantly in terms of serum C-reactive protein levels and the presence of human leucocyte antigen-B27. Compared to the control group, in the AS group, 39 patients (79.5%) exhibited typical ¹⁸F-NaF PET/CT-positive findings, such as enthesopathy (65.3%, p=.003), syndesmophytes (61.2%, p=.006) and symmetric sacroiliitis (67.3%, p=.001). PET-positive findings had significantly higher area under the curve values than did single ¹⁸F-NaF PET/CT- positive findings, and they had the best performance for concordant diagnosis according to the ASAS criteria.CONCLUSIONS¹⁸F-NaF PET/CT yielded significantly different findings between the two groups according to the ASAS criteria and is useful for diagnosing AS.     

Distributions of Microdamage Are Altered Between Trabecular Rods and Plates in Cancellous Bone From Men With Type 2 Diabetes Mellitus

Individuals with type 2 diabetes mellitus (T2DM) have an increased risk of fragility fracture despite exhibiting normal to high bone mineral density (BMD). Conditions arising from T2DM, such as reduced bone turnover and alterations in microarchitecture, may contribute to skeletal fragility by influencing bone morphology and microdamage accumulation. The objectives of this study were (i) to characterize the effect of T2DM on microdamage quantity and morphology in cancellous bone, and (ii) relate the accumulation of microdamage to the cancellous microarchitecture. Cancellous specimens from the femoral neck were collected during total hip arthroplasty (T2DM: n = 22, age = 65 ± 9 years, glycated hemoglobin [HbA1c] = 7.00% ± 0.98%; non-diabetic [non-DM]: n = 25, age = 61 ± 8 years, HbA1c = 5.50% ± 0.4%), compressed to 3% strain, stained with lead uranyl acetate to isolate microdamage, and scanned with micro–computed tomography (μCT). Individual trabeculae segmentation was used to isolate rod-like and plate-like trabeculae and their orientations with respect to the loading axis. The T2DM group trended toward a greater BV/TV (+27%, p = 0.07) and had a more plate-like trabecular architecture (+8% BV_plates, p = 0.046) versus non-DM specimens. Rods were more damaged relative to their volume compared to plates in the non-DM group (DV_rods/BV_rods versus DV_plates/BV_plates: +49%, p < 0.0001), but this difference was absent in T2DM specimens. Longitudinal rods were more damaged in the non-DM group (DV_{longitudinal rods}/BV_{longitudinal rods}: +73% non-DM versus T2DM, p = 0.027). Total damage accumulation (DV/BV) and morphology (DS/DV) did not differ in T2DM versus non-DM specimens. These results provide evidence that cancellous microarchitecture does not explain fracture risk in T2DM, pointing to alterations in material matrix properties. In particular, cancellous bone from men with T2DM may have an attenuated ability to mitigate microdamage accumulation through sacrificial rods. © 2022 American Society for Bone and Mineral Research (ASBMR).     

Quantitative in vivo assessment of bone allograft viability using 18F-fluoride PET/CT after glenoid augmentation in reverse shoulder arthroplasty: a pilot study

Background

Success after glenoid bone augmentation in total shoulder arthroplasty depends on osseous integration and non-resorption. Standard imaging techniques, such as computed tomography (CT) and X-rays, cannot quantify bone viability. Therefore, we introduce a new technique to assess graft viability using ¹⁸F-sodium fluoride (¹⁸F-NaF) PET–CT for femoral allografts in reverse total shoulder arthroplasty (RSA).

Materials and methods

Patient charts were reviewed following glenoid augmentation using femoral allografts in reverse total shoulder arthroplasty. A total of seven patients were included in this study. ¹⁸F-NaF PET–CT was used to assess graft viability and graft fusion. Semiquantitative assessment of ¹⁸F-NaF uptake was performed by means of a standardized uptake value (SUV). Radiographs were used to assess fusion. The mean age of the patients at the time of follow-up was 83.4 years (range 79–92), and the mean follow-up was 44.4 months.

Results

Viability and fusion were confirmed in all allografts using semiquantitative analysis of ¹⁸F-NaF PET–CT by means of standardized uptake value (SUVmax). Metabolic activity of medullary region of a vertebral spine was defined as a reference background. The mean value of maximum tracer activity in the allograft was not statistically different from native bone in the reference vertebrae (p = 0.14).

Conclusions

¹⁸F-NaF PET–CT is a practicable tool to quantitatively assess viability in large bone allografts after glenoid augmentation in RSA. The study shows viability and fusion in all allografts.

Level of Evidence

Level IV, treatment study.

     

Assessment of Bone Health in Patients With Type 1 Gaucher Disease Using Impact Microindentation

Gaucher disease (GD), one of the most common lysosomal disorders (a global population incidence of 1:50,000), is characterized by beta‐glucocerebrosidase deficiency. Some studies have demonstrated bone infiltration in up to 80% of patients, even if asymptomatic. Bone disorder remains the main cause of morbidity in these patients, along with osteoporosis, avascular necrosis, and bone infarcts. Enzyme replacement therapy (ERT) has been shown to improve these symptoms. This cross‐sectional study included patients with type 1 Gaucher disease (GD1) selected from the Catalan Study Group on GD. Clinical data were collected and a general laboratory workup was performed. Bone mineral density (BMD) was measured at the lumbar spine and hip using dual‐energy X‐ray absorptiometry (DXA). Patients with bone infarcts or any other focal lesion in the area of indentation visible on imaging were excluded. Bone Material Strength index (BMSi) was measured by bone impact microindentation using an Osteoprobe instrument. Analysis of covariance (ANCOVA) models were fitted to adjust for age, sex, weight, and height. Sixteen patients with GD1 and 29 age‐ and sex‐matched controls were included. GD1 was associated with significantly lower BMSi (adjusted beta –9.30; 95% CI, –15.18 to –3.42; p = 0.004) and reduced lumbar BMD (adjusted beta –0.14; 95% CI, –0.22 to –0.06; p = 0.002) and total hip BMD (adjusted beta –0.09; 95% CI, –0.15 to –0.03; p = 0.006), compared to GD1‐free controls. Chitotriosidase levels were negatively correlated with BMSi (linear R² = 51.6%, p = 0.004). Bone tissue mechanical characteristics were deteriorated in patients with GD1. BMSi was correlated with chitotriosidase, the marker of GD activity. Bone disorder requires special consideration in this group of patients, and microindentation could be an appropriate tool for assessing and managing their bone health. © 2017 American Society for Bone and Mineral Research.     

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.     

18F-FDG PET/CT半定量参数在非小细胞肺癌预后判断中的研究进展

肺癌是目前世界上发病率最高的恶性肿瘤,非小细胞肺癌(NSCLC)约占其中的80%～85%,手术切除仍是首选治疗方法,因此,术前的准确分期和预后评估至关重要。~(18)F-FDG PET/CT检查相关的葡萄糖代谢半定量参数,包括最大标准化摄取值(SUV_(max))、最大标准化摄取峰值(SUV_(peak))、平均标准化摄取值(SUV_(mean))、肿瘤代谢体积(MTV)、总糖酵解量(TLG)等,可为判断肿瘤预后提供重要信息。本文对以上葡萄糖代谢半定量参数判断NSCLC预后的临床进展进行综述。     

Assessment of Bone Fragility in Patients With Multiple Myeloma Using QCT‐Based Finite Element Modeling

Multiple myeloma (MM) is a malignant plasma cell disease associated with severe bone destruction. Surgical intervention is often required to prevent vertebral body collapse and resulting neurological complications; however, its necessity is determined by measuring lesion size or number, without considering bone biomechanics. Finite element (FE) modeling, which simulates the physiological loading, may improve the prediction of fragility. To test this, we developed a quantitative computed tomography (QCT)‐based FE model of the vertebra and applied it to a dataset of MM patients with and without prevalent fracture. FE models were generated from vertebral QCT scans of the T₁₂ (T₁₁ if T₁₂ was fractured) of 104 MM patients, 45 with fracture and 59 without, using a low‐dose scan protocol (1.5 mm slice thickness, 4.0 to 6.5 mSv effective dose). A calibration phantom enabled the conversion of the CT Hounsfield units to FE material properties. Compressive loading of the vertebral body was simulated and the stiffness, yield load, and work to yield determined. To compare the parameters between fracture and nonfracture groups, t tests were used, and standardized odds ratios (sOR, normalized to standard deviation) and 95% confidence intervals were calculated. FE parameters were compared to mineral and structural parameters using linear regression. Patients with fracture showed lower vertebral stiffness (–15.2%; p = 0.010; sOR = 1.73; 95% CI, 1.11 to 2.70), yield force (–21.5%; p = 0.002; sOR = 2.09; 95% CI, 1.27 to 3.43), and work to yield (–27.4%; p = 0.001; sOR = 2.28; 95% CI, 1.33 to 3.92) compared to nonfracture patients. All parameters correlated significantly with vBMD (stiffness: R² = 0.57, yield force: R² = 0.59, work to yield: R² = 0.50, p < 0.001), BV/TV (stiffness: R² = 0.56, yield force: R² = 0.58, work to yield: R² = 0.49, p < 0.001), and Tb.Sp (stiffness: R² = 0.51, yield force: R² = 0.53, work to yield: R² = 0.45, p < 0.001). FE modeling identified MM patients with compromised mechanical integrity of the vertebra. Higher sOR values were obtained for the biomechanical compared to structural or mineral measures, suggesting that FE modeling improves fragility assessment in these patients. © 2016 American Society for Bone and Mineral Research.     

18F-FDG PET/CT动态评价单纯125I粒子植入或联合顺铂化学治疗兔VX2肺癌效果

目的 分析¹⁸F-FDG PET/CT动态观察单纯¹²⁵I粒子植入术及联合化学治疗（化疗）对兔VX2肺癌的干预效果的价值。方法 将VX2肿瘤组织接种于3~4月龄新西兰大耳白兔右肺下叶,制成兔VX2肺癌模型。将30只模型兔随机分为3组,每组10只。对A组通过治疗计划系统（TPS）植入25.9 MBq（0.7 mCi）¹²⁵I粒子,B组经耳缘静脉注射顺铂7 mg/kg体质量,C组予以上2种干预。分别于治疗前及治疗后第3、7、14天对实验兔行全身PET/CT扫描,于右肺肿瘤部位及肝右叶勾画ROI,检测其最大标准摄取值（SUV_max）,计算肿瘤SUV_max/肝脏SUV_max（SUV_T/L）;于治疗前及治疗后第3、7天完成PET/CT检查后分别处死2只,治疗后第14天PET/CT检查后处死4只动物,取肿瘤组织进行病理学检查。结果 3组间及A、B组内治疗前及治疗后不同时间点肿瘤最大径差异均无统计学意义（P均>0.05）。C组治疗后第14天肿瘤最大径较治疗前缩小（P<0.05）。治疗后第7、14天,C组SUV_T/L值较A、B组均降低（P均<0.05）;A、B组治疗后第7、14天SUV_T/L值均较治疗前降低,C组治疗后第3、7、14天SUV_T/L值均较治疗前降低（P均<0.05）。病理学检查发现3组治疗后肿瘤细胞均逐渐减少,A、C组炎症细胞及肿瘤坏死区较B组更多;C组治疗后第14天仅见少量肿瘤细胞,炎症细胞及纤维组织增多。结论 ¹⁸F-FDG PET/CT可动态监测并早期评价单纯¹²⁵I粒子植入术及联合化疗对兔VX2肺癌的干预效果。     

RANKL Inhibition in Fibrous Dysplasia of Bone: A Preclinical Study in a Mouse Model of the Human Disease

Fibrous dysplasia of bone/McCune-Albright syndrome (Polyostotic FD/MAS; OMIM#174800) is a crippling skeletal disease caused by gain-of-function mutations of G_sα. Enhanced bone resorption is a recurrent histological feature of FD and a major cause of fragility of affected bones. Previous work suggests that increased bone resorption in FD is driven by RANKL and some studies have shown that the anti-RANKL monoclonal antibody, denosumab, reduces bone turnover and bone pain in FD patients. However, the effect of RANKL inhibition on the histopathology of FD and its impact on the natural history of the disease remain to be assessed. In this study, we treated the EF1α-G_sα^R201C mice, which develop an FD-like phenotype, with an anti-mouse RANKL monoclonal antibody. We found that the treatment induced marked radiographic and microscopic changes at affected skeletal sites in 2-month-old mice. The involved skeletal segments became sclerotic due to the deposition of new, highly mineralized bone within developing FD lesions and showed a higher mechanical resistance compared to affected segments from untreated transgenic mice. Similar changes were also detected in older mice with a full-blown skeletal phenotype. The administration of anti-mouse RANKL antibody arrested the growth of established lesions and, in young mice, prevented the appearance of new ones. However, after drug withdrawal, the newly formed bone was remodelled into FD tissue and the disease progression resumed in young mice. Taken together, our results show that the anti-RANKL antibody significantly affected the bone pathology and natural history of FD in the mouse. Pending further work on the prevention and management of relapse after treatment discontinuation, our preclinical study suggests that RANKL inhibition may be an effective therapeutic option for FD patients. © 2019 American Society for Bone and Mineral Research.     

淋巴瘤PET/CT最大标准摄取值与临床分期、病理分型及Ki-67表达相关性

目的探讨淋巴瘤18F-FDG PET/CT中最大标准摄取值(SUVmax)与临床分期、病理分型及Ki-67表达的相关性。方法回顾性分析135例经病理证实、18F-FDG PET/CT和Ki-67免疫组化资料完整的淋巴瘤患者,分析SUVmax与临床分期和Ki-67表达的相关性,比较不同病理分型淋巴瘤SUVmax差异,绘制ROC曲线,获得SUVmax诊断侵袭性淋巴瘤的界值。结果 SUVmax与淋巴瘤临床分期无相关(r=0.04,P=0.544)。霍奇金淋巴瘤和非霍奇金淋巴瘤SUVmax分别为11.53±5.58和11.84±6.82(Z=-0.256,P=0.798);侵袭性淋巴瘤SUVmax(13.02±6.53)高于惰性淋巴瘤(6.81±5.71,Z=-4.226,P0.001);以SUVmax=8.4为预测侵袭性淋巴瘤的界值,其灵敏度和特异度分别为75.5%和77.3%。早期和晚期淋巴瘤SUVmax与Ki-67指数均呈正相关(r=0.44,P0.001;r=0.43,P=0.002)。结论淋巴瘤18F-FDG PET/CT SUVmax与临床分期不相关,与Ki-67表达呈正相关,可预测侵袭性淋巴瘤。     

Nerves in Bone: Evolving Concepts in Pain and Anabolism

The innervation of bone has been described for centuries, and our understanding of its function has rapidly evolved over the past several decades to encompass roles of subtype-specific neurons in skeletal homeostasis. Current research has been largely focused on the distribution and function of specific neuronal populations within bone, as well as their cellular and molecular relationships with target cells in the bone microenvironment. This review provides a historical perspective of the field of skeletal neurobiology that highlights the diverse yet interconnected nature of nerves and skeletal health, particularly in the context of bone anabolism and pain. We explore what is known regarding the neuronal subtypes found in the skeleton, their distribution within bone compartments, and their central projection pathways. This neuroskeletal map then serves as a foundation for a comprehensive discussion of the neural control of skeletal development, homeostasis, repair, and bone pain. Active synthesis of this research recently led to the first biotherapeutic success story in the field. Specifically, the ongoing clinical trials of anti-nerve growth factor therapeutics have been optimized to titrated doses that effectively alleviate pain while maintaining bone and joint health. Continued collaborations between neuroscientists and bone biologists are needed to build on this progress, leading to a more complete understanding of neural regulation of the skeleton and development of novel therapeutics. © 2019 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc.     

Correlation between mechanical stress by finite element analysis and 18F‐fluoride PET uptake in hip osteoarthritis patients

¹⁸F‐fluoride positron emission tomography (¹⁸F‐fluoride PET) is a functional imaging modality used primarily to detect increased bone metabolism. Increased ¹⁸F‐fluoride PET uptake suggests an association between increased bone metabolism and load stress at the subchondral level. This study therefore examined the relationship between equivalent stress distribution calculated by finite element analysis and ¹⁸F‐fluoride PET uptake in patients with hip osteoarthritis. The study examined 34 hips of 17 patients who presented to our clinic with hip pain, and were diagnosed with osteoarthritis or pre‐osteoarthritis. The hips with trauma, infection, or bone metastasis of cancer were excluded. Three‐dimensional models of each hip were created from computed tomography data to calculate the maximum equivalent stress by finite element analysis, which was compared with the maximum standardized uptake value (SUV_max) examined by ¹⁸F‐fluoride PET. The SUV_max and equivalent stress were correlated (Spearman's rank correlation coefficient ρ = 0.752), and higher equivalent stress values were noted in higher SUV_max patients. The correlation between SUV_max and maximum equivalent stress in osteoarthritic hips suggests the possibility that ¹⁸F‐fluoride PET detect increased bone metabolism at sites of stress concentration. This study demonstrates the correlation between mechanical stress and bone remodeling acceleration in hip osteoarthritis. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:78–83, 2015.     

18F-FDG PET/CT在胆道系统恶性肿瘤中的应用

目的探讨~(18)F-FDG PET/CT诊断胆道系统恶性肿瘤的价值。方法回顾性分析34例临床疑似胆道恶性肿瘤患者的PET/CT影像资料,均获得术后病理结果,其中12例经手术切除淋巴结或淋巴结穿刺活检对18枚淋巴结获得病理诊断;与病理结果对照,计算PET/CT对胆道恶性病变原发灶、淋巴结转移的灵敏度、特异度、阳性预测值、阴性预测值及准确率。结果 34例中,31例为恶性病变,3例为良性病变。PET/CT诊断胆道恶性肿瘤原发灶的灵敏度100%(31/31),特异度66.67%(2/3),阳性预测值96.88%(31/32),阴性预测值100%(2/2),准确率97.06%(33/34)。胆道恶性病变原发灶最大标准摄取值(SUV_(max))为8.42±4.27;3例胆道良性疾病SUV_(max)分别为12.90、2.00及1.90。共18枚淋巴结获得病理结果,包括转移性淋巴结13枚,良性增生5枚。PET/CT诊断淋巴结转移的灵敏度76.92%(10/13),特异度60.00%(3/5),阳性预测值83.33%(10/12),阴性预测值50.00%(3/6),准确率72.22%(13/18)。结论 PET/CT对胆道系统恶性肿瘤的诊断具有重要价值。     

Association Between Vertebral Cross‐sectional Area and Vertebral Wedging in Children and Adolescents: A Cross‐sectional Analysis

A small vertebral cross‐sectional area (CSA) imparts a mechanical disadvantage that escalates the risk for vertebral fractures in elderly populations. We examined whether a small vertebral CSA is also associated with a greater degree of vertebral wedging in children. Measurements of vertebral CSA, lumbar lordosis (LL) or thoracic scoliosis angle, and vertebral wedging were obtained in 100 healthy adolescents (50 boys and 50 girls) and 25 girls with adolescent idiopathic scoliosis (AIS) using magnetic resonance imaging. Vertebral CSA of the lumbar vertebrae negatively correlated to the degree of posteroanterior vertebral wedging at L₅ (r = –0.49; p < 0.0001); this was true whether all subjects were analyzed together or boys and girls independently. In contrast, we found a positive correlation between the degree of LL and vertebral wedging (r = 0.57; p < 0.0001). Multiple regression analysis showed that the association between vertebral CSA and wedging was independent of age and body mass index. In girls with AIS, vertebral CSA negatively correlated to the degree of lateral thoracic vertebral wedging (r = –0.66; p = 0.0004), an association that persisted even after accounting for age and body mass index. Additionally, Cobb angle positively correlated to lateral thoracic vertebral wedging (r = 0.46; p = 0.021). Our cross‐sectional results support the hypothesis that smaller vertebral CSA is associated with greater vertebral deformity during growth, as in adulthood. © 2017 American Society for Bone and Mineral Research.     

Molecular Imaging of Proliferation and Glucose Utilization: Utility for Monitoring Response and Prognosis after Neoadjuvant Therapy in Locally Advanced Gastric Cancer

Background

Metabolic imaging of gastric cancer is limited due to the 30% of primary tumors that are not ¹⁸F-fluorodeoxyglucose (FDG) avid. In contrast, the proliferation marker ¹⁸F-fluorothymidine (FLT) has been shown to visualize also non-FDG-avid gastric tumors. In this study we tested whether FLT-positron emission tomography (PET) can improve the predictive potential of molecular imaging for assessing response to neoadjuvant therapy in gastric cancer compared with FDG-PET.

Methods

45 patients with gastric cancer underwent FDG- and FLT-PET before and 2 weeks after initiation of chemotherapy. FDG/FLT-PET findings and Ki67 immunohistochemistry were correlated with clinical and histopathological response and survival.

Results

14 patients had non-FDG-avid tumors, whereas all tumors could be visualized by FLT-PET. No significant association of clinical or histopathological response with any of the analyzed metabolic parameters [initial standardized uptake value (SUV), SUV after 2 weeks, change of SUV for FDG/FLT] was found. Univariate Cox regression analysis for Ki67 and metabolic parameters revealed significant prognostic impact for survival only for FLT SUV_mean day 14 (p = 0.048) and Ki67 (p = 0.006). Multivariate Cox regression analysis (including clinical response, Lauren type, ypN category, and FLT SUV_mean day 14) revealed Lauren type and FLT SUV_mean day 14 as the only significant prognostic factors (p = 0.006, p = 0.002).

Conclusions

FLT uptake 2 weeks after initiation of therapy was shown to be the only imaging parameter with significant prognostic impact. Neither FLT-PET nor FDG-PET were correlated with histopathological or clinical response. However, these data must be interpreted with caution due to the single-center trial study design, relatively short follow-up, poor response rates, and unfavorable prognosis.