Low serum vitamin D among community-dwelling healthy women in Sri Lanka

Background: Although hypovitaminosis D is prevalent among healthy adults in Asia and other regions, available data among Sri Lankans are not consistent with this finding. We studied vitamin D level among healthy community-dwelling women and examined its effects on parathyroid hormone (PTH) level and bone mineral status. Methods: Females of 20-40 years (n = 434) who were employed in southern Sri Lanka were recruited to the study. Bone mineral density and content (pBMD and pBMC) of the middle phalanx of the middle finger of the non-dominant hand were measured in all subjects and 5.0 ml of venous blood was collected from each subject after an overnight fast for biochemical assessment of serum vitamin D, parathyroid hormone and total alkaline phosphatase. Results: Mean (SD) pBMD of the women studied was 0.493 (0.060) g/cm2 and pBMC was 1.49 (0.28) g. Severe vitamin D deficiency (jects, whereas 19.1% subjects had moderate (12.5-25.0 nmol/L) and 15.7% had mild (25.1 -35.0 nmol/L) vitamin D deficiency. Serum vitamin D showed significant positive correlations with pBMD (r = 0.13, p = 0.008) and pBMC (r = 0.12, p = 0.01). In regression analysis, vitamin D showed a positive association with pBMD (regression coefficient 0.0003, SEM 0.0001, p = 0.007). Conclusions: Vitamin D insufficiency/deficiency is prevalent among healthy young and middle-aged women in this study group selected from southern Sri Lanka. The accompanying rise of PTH indicates the biological significance of low vitamin D level. The negative effects observed on bone mineral status suggest the clinical importance of this finding.

Amyloid positron emission tomography and cognitive reserve

Alzheimer's disease(AD) is characterized by a nonlinear progressive course and several aspects influence the relationship between cerebral amount of AD pathology and the clinical expression of the disease. Brain cognitive reserve(CR) refers to the hypothesized capacity of an adult brain to cope with brain damage in order to minimize symptomatology. CR phenomenon contributed to explain the disjunction between the degree of neurodegeneration and the clinical phenotype of AD. The possibility to track brain amyloidosis(Aβ) in vivo has huge relevance for AD diagnosis and new therapeutic approaches. The clinical repercussions of positron emission tomography(PET)-assessed Aβ load are certainly mediated by CR thus potentially hampering the prognostic meaning of amyloid PET in selected groups of patients. Similarly, amyloid PET and cerebrospinal fluid amyloidosis biomarkers have recently provided new evidence for CR. The present review discusses the concept of CR in the framework of available neuroimaging studies and specifically deals with the reciprocal influences between amyloid PET and CR in AD patients and with the potential consequent interventional strategies for AD.

FDG-PET/CT and parathyroid carcinoma:Review of literature and illustrative case series

Parathyroid cancer is an uncommon malignant cancer and is associated with a poor prognosis.The staging of parathyroid cancer represents an important issue both at initial diagnosis and after surgery and medical treatment.The role of positron emission tomography/computed tomography(PET/CT)with 18F-Fluorodeoxyglucose(18F-FDG)as an imaging tool in parathyroid cancer is not clearly reported in the literature,although its impact in other cancers is well-defined.The aim of the following illustrative clinical cases is to highlight the impact of PET/CT in the management of different phases of parathyroid cancer.We describe five patients with parathyroid malignant lesions,who underwent FDG PET/CT at initial staging,restaging and post-surgery evaluation.In each patient we report the value of PET/CT comparing its findings with other common imaging modalities(e.g.,CT,planar scintigraphy with 99mTcsestamibi,magnetic resonance imaging)thus determining the complementary benefit of FDG PET/CT in parathyroid carcinoma.We hope to provide an insight into the potential role of PET/CT in assessing the extent of disease and response to treatment which are the general principles used to correctly evaluate disease status.

Correlation between thoracic aorta 18F-natrium fluoride uptake and cardiovascular risk

AIM: To investigating the relationship between thoracic and cardiac 18F-Natrium-Fluoride (18F-NaF) uptake, as a marker of ongoing calcification and cardiovascular risk factors.METHODS: Seventy-eight patients (44 females, mean age 63, range 44-83) underwent whole body 18F-NaF positron emission tomography/computed tomography. Cardiovascular risk (CVR) was used to divide these patients in three categories: Low (LR), medium (MR) and high risk (HR). 18F-NaF uptake was measured by manually drawing volumes of interest on the ascending aorta, on the aortic arch, on the descending aorta and on the myocardium; average standardized uptake value was normalized for blood-pool, to obtain target-to-background ratio (TBR). Values from the three aortic segments were then averaged to obtain an index of the whole thoracic aorta.RESULTS: A significant difference in whole thoracic aorta TBR was detected between HR and LR (1.84 ± 0.76 vs 1.07 ± 0.3, P < 0.001), but also between MR and HR-LR (1.4 ± 0.4, P < 0.02 and P < 0.01, respectively). Significance of this TBR stratification strongly varied among thoracic aorta subsegments and the lowest P values were reached in the descending aorta (P < 0.01). Myocardial uptake provided an effective CVR classes stratification (P < 0.001).Correlation between TBR and CVR was appreciable when the whole thoracic aorta was considered (R = 0.67), but it peaked when correlating the descending thoracic segment (R = 0.75), in comparison with the aortic arch and the ascending segment (R = 0.55 and 0.53, respectively).CONCLUSION: Fluoride uptake within the thoracic aorta wall effectively depicts patients’ risk class and correlates with cardiovascular risk. Descending aorta is the most effective in CVR determination.

Evaluation of response to immune checkpoint inhibitors: Is there a role for positron emission tomography?

Strategies targeting intracellular negative regulators such as immune checkpoint inhibitors (ICPIs) have demonstrated significant antitumor activity across a wide range of solid tumors. In the clinical practice, the radiological effect of immunotherapeutic agents has raised several more relevant and complex challenges for the determination of their imaging-based response at single patient level. Accordingly, it has been suggested that the conventional Response Evaluation Criteria in Solid Tumors assessment alone, based on dimensional evaluation provided by computed tomography (CT), tends to underestimate the benefit of ICPIs at least in a subset of patients, supporting the need of immune-related response criteria. Different from CT, very few data are available for the evaluation of immunotherapy by means of 18F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET). Moreover, since the antineoplastic activity of ICPIs is highly related to the activation of T cells against cancer cells, FDG accumulation might cause false-positive findings. Yet, discrimination between benign and malignant processes represents a huge challenge for FDG-PET in this clinical setting. Consequently, it might be of high interest to test the complex and variegated response to ICPIs by means of PET and thus it is worthwhile to ask if a similar introduction of immune-related PET-based criteria could be proposed in the future. Finally, PET might offer a new insight into the biology and pathophysiology of ICPIs thanks to a growing number of non-invasive immune-diagnostic approaches based on non-FDG tracers.

Successful multidisciplinary clinical approach and molecular characterization by whole transcriptome sequencing of a cardiac myxofibrosarcoma: A case report

BACKGROUND Cardiac tumors are rare and complex entities.Surgery represents the cornerstone of therapy,while the role of adjuvant treatment remains unclear and,in case of relapse or metastatic disease,the prognosis is very poor.Lack of prospective,randomized clinical trials hinders the generation of high level evidence for the optimal diagnostic workup and multimodal treatment of cardiac sarcomas.Herein,we describe the multidisciplinary clinical management and molecular characterization of a rare case of cardiac myxofibrosarcoma in an elderly woman.CASE SUMMARY A 73-year-old woman presented signs and symptoms of acute left-sided heart failure.Imaging examination revealed a large,left atrial mass.With suspicion of a myxoma,she underwent surgery,and symptoms were promptly relieved.Histology showed a cardiac myxofibrosarcoma,a rare histotype of cardiac sarcoma.Eight months later,disease unfortunately relapsed,and after a multidisciplinary discussion,a chemotherapy with doxorubicin and then gemcitabine was started,achieving partial radiologic and complete metabolic response,which was maintained up to 2 years and is still present.This report is focused on the entire clinical path of our patient from diagnosis to follow-up,through surgery and strategies adopted at relapse.Moreover,due to their rarity,very little is known about the molecular landscape of myxofibrosarcomas.Thus,we also performed and described preliminary genome analysis of the tumor tissue to get further insight on mechanisms involved in tumor growth,and to possibly unveil new clinically actionable targets.CONCLUSION We report a case of cardiac myxofibrosarcoma that achieved a very good prognosis due to an integrated surgical,cardiac and oncologic treatment strategy.

Role of molecular imaging in the management of patients affected by inflammatory bowel disease:State-of-the-art

AIM To present the current state-of-the art of molecular imaging in the management of patients affected by inflammatory bowel disease(IBD).METHODS A systematic review of the literature was performed in order to find important original articles on the role of molecular imaging in the management of patients affected by IBD. The search was updated until February 2016 and limited to articles in English.RESULTS Fifty-five original articles were included in this review, highlighting the role of single photon emission tomography and positron emission tomography. CONCLUSION To date, molecular imaging represents a useful tool to detect active disease in IBD. However, the available data need to be validated in prospective multicenter studies on larger patient samples.

Metformin and cancer: Technical and clinical implications for FDG-PET imaging

Metformin is the most widely used hypoglycemic agent. Besides its conventional indications, increasing evidence demonstrate a potential efficacy of this biguanide as an anticancer drug. Possible mechanisms of actions seem to be independent from its hypoglycemic effect and seemto involve the interference with key pathways in cellular proliferation and glycolysis. To date, many clinical trials implying the use of metformin in cancer treatment are on-going. The increasing use of 18F-2-fluoro-2-deoxyd-glucose positron emission tomography(FDG-PET) in cancer evaluation raises a number of questions about the possible interference of the biguanide on FDG distribution. In particular, the interferences exerted by metformin on AMP-activated protein kinase pathway(the cellular energy sensor), on insulin levels and on Hexokinase could potentially have repercussion on glucose handling and thus on FDG distribution. A better comprehension of the impact of metformin on FDG uptake is needed in order to optimize the use of PET in this setting. This evaluation would be useful to ameliorate scans interpretation in diabetic patients under chronic metformin treatment and to critically interpret images in the context of clinical trials. Furthermore, collecting prospective data in this setting would help to verify whether FDG-PET could be a valid tool to appreciate the anticancer effect of this new therapeutic approach.

Radium-223 and metastatic castration-resistant prostate cancer: All that glitters is not gold

After being approved by the National Drug Agency in several countries, Radium-223 (Ra-223) is gaining wide acceptance in the treatment of bone metastatic castration resistant prostate cancer. The exact mechanism of action remain unclear: The established model of direct alpha-particle irradiation from the remodelling bone surface, where Ra-223 accumulates, surrounding the tumor foci can explain a lethal effect only on metastatic microdeposits, but not on higher tumor burden. According to the &#x0201c;pre-metastatic niche model&#x0201d;, it is likely that Ra-223 targets several non-tumoral cell types of the tumor microenvironment involved in the complex mechanism of cancer bone homing and colonization. A deeper insight into this hypothetical mechanism will lead to a more accurate dosimetric approach and to find optimal sequencing and/or combination with the other therapeutic options.

Standardized Semi-Quantitative Evaluation of [123I]FP-CIT SPECT in a Multicenter Study

To the best of our knowledge no multicenter studies have been published using standardized semi-quantitative evaluation of [123I]FP-CIT scan (DAT-SPECT). The aims of this study were: 1) to cross-compare semi-quantitative software-assisted evaluations of DAT-SPECTs performed in three centers with different equipments;2) to assess the accuracy of semi-quantitative evaluations of DAT-SPECT and 3) to identify the threshold with the best accuracy, sensitivity and specificity in a patient population with suspected parkinsonian syndrome. Materials and Methods: Two hundred twenty patients (mean age at the time of SPECT acquisition, 67.4 ± 9.5 yy) acquired in three centers (Ospedale San Luigi Gonzaga;Ospedale San Giovanni Battista Molinette;Ospedale Mauriziano Umberto I) were included. All of them underwent DAT-SPECT from January 2006 to July 2010. All exams were analyzed with the freely available software BASGAN and semi-quantitative data were used to predict disease. In particular, analyses were based on the values from the most deteriorated putamen and caudate, normalized for age and corrected for equipment. ROC analysis was performed and area under the curve (AUC) was estimated. Results: Analysis showed high AUCs (0.898, 0.864, 0.900 and 0.891 for each center and for the multicenter setting, respectively) confirming the very good accuracies reached. The best cut-off were 0.72 and 0.82 for putamen and caudate respectively. These thresholds allowed sensitivities and specificities in each center and in the multicenter setting of 76% and 96%, 91% and 82%, 93% and 90%, 86% and 89% respectively. No significant differences were observed between sensibility and specificity in each center. Conclusion: A unique threshold useful for all centers with high and similar sensitivities and specificities is possible after correction for age and equipments. The high accuracy reached in this multicenter trial by the semi-quantitative analysis seems similar to accuracies from qualitative analysis in other multicenter studies.

Short Term Prognostic Utility of Tc-99m DMSA Renal Imaging in Sepsis Induced Acute Renal Failure;Provisional Data

Background: Sound prognostic data in sepsis induced acute renal failure (SARF) are lacking especially on the short term outcome [STO] in the intensive care unit [ICU]. We addressed the use of Tc-99m DMSA [2,3-dimercaptosuccinicacid] renal cortical imaging as a prognostic tool in SARF. Methods: Forty patients with acute renal failure due to sepsis [age range 15-74 years;median 44.5] were subjected for full history taking complete physical examination, routine ICU monitoring, routine laboratory investigations, APACHE II [Acute Physiology and Chronic Health Evaluation] and SOFA [Sequential Organ Failure Assessment] together with Tc-99m DMSA cortical renal scintigraphy. Patients’ death in the ICU or discharge was considered as the end point of the study representing the so-called short term outcome [STO]. Results: 25% mortality rate [10/40] was found along the admission period in the ICU. All non-survivors were abnormal with DMSA imaging [NPV & PPV 100% & 66.7% respectively]. Abnormal DMSA cases showed significant positive associations with serum creatinine at admission [r = 0.5;P 0.02];admission duration [r = 0.4;P 0.002];APACHE II score [r = 0.5;P 0.004] and STO [r = 0.4;P 0.03]. Statistically significant difference was elicited between subjects with normal and abnormal DMSA regarding the same parameters. Conclusion: This preliminary data could raise Tc-99m DMSA renal imaging as a prognostic tool in SARF that could allow influential interference to prohibit dramatic outcomes as mortality.

Unexpected hypercalcemia in a diabetic patient with kidney disease

We report a case of a diabetic patient with progressive chronic kidney disease and unexplained hypercalcemia. This unusual presentation and the investigation of all possible causes led us to perform a renal biopsy. The systemic sarcoidosis diagnosis was confirmed by the presence of interstitial multiple granulomas composed of epithelioid and multinucleated giant cells delimited by a thin fbrous reaction, and by pulmonary computed tomography finding of numerous lumps with ground-glass appearance. Sarcoidosis most commonly involves lungs, lymph nodes, skin and eyes, whilst kidney is less frequently involved. When it affects males it is characterized by hypercalcemia, hypercalciuria, and progressive loss of renal function. Early treatment with steroids allows for a gradual improvement in renal function and normalization of calcium serum values. Otherwise, the patient would quickly progress to end stage renal disease. Finding of hypercalcemia in a patient with renal failure must alert physicians because it may be a sign of several pathological entities.

轻度认知障碍转变为痴呆与APOE基因型关系的FDG-PET预测研究

Objectives: To investigate whether the combination of fluoro-2-deoxy-D-glu cose (FDG) PET measures with the APOE genotype would improve prediction of the c onversion frommild cognitive impairment (MCI) to Alzheimer disease (AD).Method: After 1 year, 8 of 37 patients with MCI converted to AD (22%). Differences in b aseline regional glucose metabolicrate (rCMRglc) across groups were assessed on a voxel-based basis using a two-factor analysis of variance with outcome (conv erters[n = 8] vs nonconverters [n = 29]) and APOE genotype (E4 carriers [E4+] [ n = 16] vs noncarriers [E4-] [n = 21]) asgrouping factors. Results were conside red significant at p < 0.05, corrected for multiple comparisons. Results: All co nverters showed reduced rCMRglc in the inferior parietal cortex(IPC) as compared with the nonconverters. Hypometabolismin AD-typical regions, that is, temporop arietal and posteriorcingulate cortex, was found for the E4+as compared with th e E4-patients, with the E4+/converters (n = 5) having additional rCMRglc reduc tions within frontal areas, such as the anterior cingulate (ACC) and inferior fr ontal (IFC) cortex. For the whole MCI sample, IPC rCMRglc predicted conversion t o AD with 84%overall diagnostic accuracy (p = 0.003). Moreover,ACC and IFC rCMR glc improved prediction for the E4+group,yielding 100%sensitivity, 90%specifi city, and 94%accuracy (p < 0.0005), thus leading to an excellent discrimination . Conclusion:Fluoro-2-deoxy-D-glucose-PET measures may improve prediction o f the conversion to Alzheimer disease, especially in combination with the APOE g enotype.

A new era for hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is one of the most frequent cancers worldwide among patients with cirrhosis,and its management and treatment is in continuous evolution due to the introductions of new therapeutic option.It represents most common primary malignancy of the liver,developing in 90%of cases of un underlying liver disease(1)[chronic HBV and HCV hepatitis,dysmetabolic liver disease].

Usefulness of PET-CT scan in recurrent thyroid cancer

The aim of this paper is to discuss the risk of recurrence in patients with differentiated thyroid cancer and emphasize the importance of risk-group stratification,early recurrence identification and application of new imaging modalities,what is the PET-CT.Moreover,follow-up of patients with thyroid carcinoma should be carried out by specialized teams throughout life.Therefore,interdisciplinary case discussions in tumor conferences may improve the use of multimodal therapy especially in patients with poorly differentiated thyroid carcinomas.After baseline follow-up,if there is a suspicion of thyroid carcinoma,early PET-CT should be used for early detection and appropriate planning.Fortunately,due to the good localization possibility,the PET-CT enables a focused surgical procedure with avoidance of an unnecessary tumor search and thereby a reduction of the risk of injury of neighboring structures which is a concern with reoperative neck surgery.

Role of ^(18)F-FDG PET/CT in detection of hematogenous metastases of advanced differentiated thyroid carcinoma: a systematic review and meta-analysis

The aim of this study was to collect the evidence on the performance of 2-deoxy-2-[^(18)F]fluoro-D-glucose(^(18)F-FDG)Positron Emission Tomography/Computed Tomography(PET/CT)in terms of detection rate(DR)and diagnostic accuracy in identifying hematogenous metastases in patients with differentiated thyroid cancer and compare its performance with that of other imaging techniques.A comprehensive PubMed/MEDLINE database research was carried out to retrieve studies documenting the performance of^(18)F-FDG PET/CT in depicting hematogenous metastases in patients with differentiated thyroid cancer.Statistical analysis was performed on a per-patient and per-lesion basis.The literature search yielded 15 articles to be included in the systematic review.^(18)F-FDG PET/CT showed a pooled DR of 85.08%on a per-patient analysis and 89.70%on a per-lesion analysis.For bone lesions,a high DR(81.78%)was found for^(18)F-FDG PET/CT.For the sub-group analysis of lung lesions,pooled DR was 92.77%for^(18)F-FDG PET/CT,95.02%for CT,and 64.93%for magnetic resonance imaging(MRI).On a per-patient analysis,^(18)F-FDG PET/CT demonstrated a pooled sensitivity(SS)of 87.3%[95%confidence interval(CI):77.3%-94%]and a pooled specificity(SP)of 95.6%(95%CI:87.6-99.1).On a per-lesion analysis(328 metastases),PET/CT showed a pooled SS and SP of 86.3%(95%CI:73.5%-93.5%)and 93.4%(95%CI:71.7%-98.8%)in the detection of hematogenous metastases.The presented systematic review and meta-analysis favor the use of^(18)F-FDG PET/CT in the detection of hematogenous metastases in patients with differentiated thyroid cancer.The limited literature warrants further studies to confirm our findings.

^(18)F-fluorodeoxyglucose positron emission tomography for intrahepatic cholangiocarcinoma N-and M-staging:should guidelines recommend it at last?

We really appreciated Lin et al.’s“The influence of ^(18)F-fluorodeoxyglucose positron emission tomography/computed tomography on the N-and M-staging and subsequent clinical management of intrahepatic cholangiocarcinoma”in HepatoBiliary Surgery and Nutrition(1).A 291-patient population affected by intrahepatic cholangiocarcinoma(ICC)was retrospectively analyzed with the aim of assessing the accuracy of preoperative staging and treatment reallocation by ^(18)F-fluorodeoxyglucose positron emission tomography/computed tomography(^(18)F-FDG PET/CT)(1).