Prevention of postoperative nausea and vomiting after orthognathic surgery: a scoping review.

INTRODUCTION: Postoperative nausea and vomiting (PONV) is one of the most common adverse events following orthognathic surgery. It's a distressing feeling for patients and continues to be the cause of postoperative complications such as bleeding, delayed healing, and wound infection. This scoping review aims to identify effective PONV prophylaxis strategies during orthognathic surgery that have emerged in the past 15 years. METHODS: We searched Pubmed, Cochrane Controlled Register of Trials, and Embase from 2008 to May 2023. Studies meeting the following criteria were eligible for inclusion: (1) recruited patients undergo any orthognathic surgery; (2) evaluated any pharmacologic or non-pharmacologic method to prevent PONV. Studies meeting the following criteria were excluded: (1) case series, review papers, or retrospective studies; (2) did not report our prespecified outcomes. RESULTS: Twenty-one studies were included in this review. Pharmacological methods for PONV prevention include ondansetron and dexamethasone (3 studies), peripheral nerve block technique (4 studies), dexmedetomidine (1 study), pregabalin (2 studies), nefopam (2 studies), remifentanil (1 study), propofol (2 studies), and penehyclidine (1 study). Non-pharmacologic methods include capsicum plaster (1 study), throat packs (2 studies) and gastric aspiration (2 studies). CONCLUSIONS: Based on current evidence, we conclude that prophylactic antiemetics like dexamethasone, ondansetron, and penehyclidine are the first defense against PONV. Multimodal analgesia with nerve block techniques and non-opioid analgesics should be considered due to their notable opioid-sparing and PONV preventive effect. For the non-pharmacological methods, throat packs are not recommended for routine use because of their poor effect and serious complications. More prospective RCTs are required to confirm whether gastric aspiration can prevent PONV effectively for patients undergoing orthognathic surgery.

Cooperation of MLL1 and Jun in controlling H3K4me3 on enhancers in colorectal cancer.

BACKGROUND: Enhancer dysregulation is one of the important features for cancer cells. Enhancers enriched with H3K4me3 have been implicated to play important roles in cancer. However, their detailed features and regulatory mechanisms have not been well characterized. RESULTS: Here, we profile the landscape of H3K4me3-enriched enhancers (m3Es) in 43 pairs of colorectal cancer (CRC) samples. M3Es are widely distributed in CRC and averagely possess around 10% of total active enhancers. We identify 1322 gain variant m3Es and 367 lost variant m3Es in CRC. The target genes of the gain m3Es are enriched in immune response pathways. We experimentally prove that repression of CBX8 and RPS6KA5 m3Es inhibits target gene expression in CRC. Furthermore, we find histone methyltransferase MLL1 is responsible for depositing H3K4me3 on the identified Vm3Es. We demonstrate that the transcription factor AP1/JUN interacts with MLL1 and regulates m3E activity. Application of a small chemical inhibitor for MLL1 activity, OICR-9429, represses target gene expression of the identified Vm3Es, enhances anti-tumor immunity and inhibits CRC growth in an animal model. CONCLUSIONS: Taken together, our study illustrates the genome-wide landscape and the regulatory mechanisms of m3Es in CRC, and reveals potential novel strategies for cancer treatment.

Inter-pass motion correction for whole-body dynamic PET and parametric imaging.

Whole-body dynamic FDG-PET imaging through continuous-bed-motion (CBM) mode multi-pass acquisition protocol is a promising metabolism measurement. However, inter-pass misalignment originating from body movement could degrade parametric quantification. We aim to apply a non-rigid registration method for inter-pass motion correction in whole-body dynamic PET. 27 subjects underwent a 90-min whole-body FDG CBM PET scan on a Biograph mCT (Siemens Healthineers), acquiring 9 over-the-heart single-bed passes and subsequently 19 CBM passes (frames). The inter-pass motion correction was executed using non-rigid image registration with multi-resolution, B-spline free-form deformations. The parametric images were then generated by Patlak analysis. The overlaid Patlak slope Ki and y-intercept Vb images were visualized to qualitatively evaluate motion impact and correction effect. The normalized weighted mean squared Patlak fitting errors (NFE) were compared in the whole body, head, and hypermetabolic regions of interest (ROI). In Ki images, ROI statistics were collected and malignancy discrimination capacity was estimated by the area under the receiver operating characteristic curve (AUC). After the inter-pass motion correction was applied, the spatial misalignment appearance between Ki and Vb images was successfully reduced. Voxel-wise normalized fitting error maps showed global error reduction after motion correction. The NFE in the whole body (p = 0.0013), head (p = 0.0021), and ROIs (p = 0.0377) significantly decreased. The visual performance of each hypermetabolic ROI in Ki images was enhanced, while 3.59% and 3.67% average absolute percentage changes were observed in mean and maximum Ki values, respectively, across all evaluated ROIs. The estimated mean Ki values had substantial changes with motion correction (p = 0.0021). The AUC of both mean Ki and maximum Ki after motion correction increased, possibly suggesting the potential of enhancing oncological discrimination capacity through inter-pass motion correction.

Epidemiology of liver cirrhosis and associated complications: Current knowledge and future directions.

Cirrhosis causes a heavy global burden. In this review, we summarized up-to-date epidemiological features of cirrhosis and its complications. Recent epidemiological studies reported an increase in the prevalence of cirrhosis in 2017 compared to in 1990 in both men and women, with 5.2 million cases of cirrhosis and chronic liver disease occurring in 2017. Cirrhosis caused 1.48 million deaths in 2019, an increase of 8.1% compared to 2017. Disability-adjusted life-years due to cirrhosis ranked 16th among all diseases and 7th in people aged 50-74 years in 2019. The global burden of hepatitis B virus and hepatitis C virus-associated cirrhosis is decreasing, while the burden of cirrhosis due to alcohol and nonalcoholic fatty liver disease (NAFLD) is increasing rapidly. We described the current epidemiology of the major complications of cirrhosis, including ascites, variceal bleeding, hepatic encephalopathy, renal disorders, and infections. We also summarized the epidemiology of hepatocellular carcinoma in patients with cirrhosis. In the future, NAFLD-related cirrhosis will likely become more common due to the prevalence of metabolic diseases such as obesity and diabetes, and the prevalence of alcohol-induced cirrhosis is increasing. This altered epidemiology should be clinically noted, and relevant interventions should be undertaken.

Systemic inflammation enhances stimulant-induced striatal dopamine elevation in tobacco smokers.

Immune-brain interactions influence the pathophysiology of addiction. Lipopolysaccharide (LPS)-induced systemic inflammation produces effects on reward-related brain regions and the dopamine system. We previously showed that LPS amplifies dopamine elevation induced by methylphenidate (MP), compared to placebo (PBO), in eight healthy controls. However, the effects of LPS on the dopamine system of tobacco smokers have not been explored. The goal of Study 1 was to replicate previous findings in an independent cohort of tobacco smokers. The goal of Study 2 was to combine tobacco smokers with the aforementioned eight healthy controls to examine the effect of LPS on dopamine elevation in a heterogenous sample for power and effect size determination. Eight smokers were each scanned with [11C]raclopride positron emission tomography three times-at baseline, after administration of LPS (0.8 ng/kg, intravenously) and MP (40 mg, orally), and after administration of PBO and MP, in a double-blind, randomized order. Dopamine elevation was quantified as change in [11C]raclopride binding potential (ΔBPND) from baseline. A repeated-measures ANOVA was conducted to compare LPS and PBO conditions. Smokers and healthy controls were well-matched for demographics, drug dosing, and scanning parameters. In Study 1, MP-induced striatal dopamine elevation was significantly higher following LPS than PBO (p = 0.025, 18 ± 2.9 % vs 13 ± 2.7 %) for smokers. In Study 2, MP-induced striatal dopamine elevation was also significantly higher under LPS than under PBO (p < 0.001, 18 ± 1.6 % vs 11 ± 1.5 %) in the combined sample. Smoking status did not interact with the effect of condition. This is the first study to translate the phenomenon of amplified dopamine elevation after experimental activation of the immune system to an addicted sample which may have implications for drug reinforcement, seeking, and treatment.

Multifaceted regulation of enhancers in cancer.

Enhancer is one kind of cis-elements regulating gene transcription, whose activity is tightly controlled by epigenetic enzymes and histone modifications. Active enhancers are classified into typical enhancers, super-enhancers and over-active enhancers, according to the enrichment and location of histone modifications. Epigenetic factors control the level of histone modifications on enhancers to determine their activity, such as histone methyltransferases and acetylases. Transcription factors, cofactors and mediators co-operate together and are required for enhancer functions. In turn, abnormalities in these trans-acting factors affect enhancer activity. Recent studies have revealed enhancer dysregulation as one of the important features for cancer. Variations in enhancer regions and mutations of enhancer regulatory genes are frequently observed in cancer cells, and altering the activity of onco-enhancers is able to repress oncogene expression, and suppress tumorigenesis and metastasis. Here we summarize the recent discoveries about enhancer regulation in cancer and discuss their potential application in diagnosis and treatment.

Dynamic Chromatin States Coupling with Key Transcription Factors in Colitis-Associated Colorectal Cancer.

Inflammation is one of the critical risk factors for colorectal cancer (CRC). However, the mechanisms for transition from colitis to CRC remain elusive. Recently, epigenetic changes have emerged as important regulatory factors for colitis-associated cancer. Here, a systematic epigenomic study of histone modifications is performed, including H3K4me1, H3K4me3, H3K27ac, H3K27me3 and H3K9me3, in an AOM-DSS-induced CRC mouse model. In combination with transcriptomic data, the authors generate a dataset of 105 deep sequencing files and illustrate the dynamic landscape of chromatin states at five time points during inflammation-cancer transition. Functional gene clusters are identified based on dynamic transcriptomic and epigenomic information, and key signaling pathways in the process are illustrated. This study's results reveal that enhancer state regions play important roles during inflammation-cancer transition. It predicts novel transcription factors based on enhancer information, and experimentally proves OTX2 as a critical tumor suppressive transcription factor. Taken together, this study provides comprehensive epigenomic data and reveals novel molecular mechanisms for colitis-associated cancer.

Deep learning-based attenuation correction for whole-body PET - a multi-tracer study with 18F-FDG, 68 Ga-DOTATATE, and 18F-Fluciclovine.

A novel deep learning (DL)-based attenuation correction (AC) framework was applied to clinical whole-body oncology studies using 18F-FDG, 68 Ga-DOTATATE, and 18F-Fluciclovine. The framework used activity (λ-MLAA) and attenuation (µ-MLAA) maps estimated by the maximum likelihood reconstruction of activity and attenuation (MLAA) algorithm as inputs to a modified U-net neural network with a novel imaging physics-based loss function to learn a CT-derived attenuation map (µ-CT). METHODS: Clinical whole-body PET/CT datasets of 18F-FDG (N = 113), 68 Ga-DOTATATE (N = 76), and 18F-Fluciclovine (N = 90) were used to train and test tracer-specific neural networks. For each tracer, forty subjects were used to train the neural network to predict attenuation maps (µ-DL). µ-DL and µ-MLAA were compared to the gold-standard µ-CT. PET images reconstructed using the OSEM algorithm with µ-DL (OSEMDL) and µ-MLAA (OSEMMLAA) were compared to the CT-based reconstruction (OSEMCT). Tumor regions of interest were segmented by two radiologists and tumor SUV and volume measures were reported, as well as evaluation using conventional image analysis metrics. RESULTS: µ-DL yielded high resolution and fine detail recovery of the attenuation map, which was superior in quality as compared to µ-MLAA in all metrics for all tracers. Using OSEMCT as the gold-standard, OSEMDL provided more accurate tumor quantification than OSEMMLAA for all three tracers, e.g., error in SUVmax for OSEMMLAA vs. OSEMDL: - 3.6 ± 4.4% vs. - 1.7 ± 4.5% for 18F-FDG (N = 152), - 4.3 ± 5.1% vs. 0.4 ± 2.8% for 68 Ga-DOTATATE (N = 70), and - 7.3 ± 2.9% vs. - 2.8 ± 2.3% for 18F-Fluciclovine (N = 44). OSEMDL also yielded more accurate tumor volume measures than OSEMMLAA, i.e., - 8.4 ± 14.5% (OSEMMLAA) vs. - 3.0 ± 15.0% for 18F-FDG, - 14.1 ± 19.7% vs. 1.8 ± 11.6% for 68 Ga-DOTATATE, and - 15.9 ± 9.1% vs. - 6.4 ± 6.4% for 18F-Fluciclovine. CONCLUSIONS: The proposed framework provides accurate and robust attenuation correction for whole-body 18F-FDG, 68 Ga-DOTATATE and 18F-Fluciclovine in tumor SUV measures as well as tumor volume estimation. The proposed method provides clinically equivalent quality as compared to CT in attenuation correction for the three tracers.

The impact of proton pump inhibitors in liver diseases and the effects on the liver.

In this systematic and comprehensive overview, we aimed to evaluate the impact of proton pump inhibitors (PPIs) on chronic liver diseases, especially on cirrhosis. A manual and comprehensive search of the PubMed database was conducted to obtain relevant literatures. PPIs altered the composition and function of the intestinal microflora and might lead to small intestinal bacterial overgrowth and bacterial translocation, which were associated with adverse effects in liver diseases. They might increase the risk of hepatic encephalopathy, spontaneous bacterial peritonitis, infections, and are related to an increased mortality in cirrhosis. PPIs might lead to an increased risk of hepatocellular carcinoma, although the mechanism is unknown, and the results are controversial. PPIs also had an impact on the direct-acting antiviral regimen in patients with chronic hepatitis C. They were associated with an increased risk of liver abscess and increased mortality. Additionally, PPIs might lead to metabolic risk events, such as liver steatosis and weight gain. PPIs are associated with several adverse outcomes in liver diseases. Cautious use of PPIs is recommended and clinicians should be aware of the indications for their use in patients with liver diseases.

Synaptic density and cognitive performance in Alzheimer's disease: A PET imaging study with [11 C]UCB-J.

INTRODUCTION: For 30 years synapse loss has been referred to as the major pathological correlate of cognitive impairment in Alzheimer's disease (AD). However, this statement is based on remarkably few patients studied by autopsy or biopsy. With the recent advent of synaptic vesicle glycoprotein 2A (SV2A) positron emission tomography (PET) imaging, we have begun to evaluate the consequences of synaptic alterations in vivo. METHODS: We examined the relationship between synaptic density measured by [11 C]UCB-J PET and neuropsychological test performance in 45 participants with early AD. RESULTS: Global synaptic density showed a significant positive association with global cognition and performance on five individual cognitive domains in participants with early AD. Synaptic density was a stronger predictor of cognitive performance than gray matter volume. CONCLUSION: These results confirm neuropathologic studies demonstrating a significant association between synaptic density and cognitive performance, and suggest that this correlation extends to the early stages of AD.

Nicotine Patch Alters Patterns of Cigarette Smoking-Induced Dopamine Release: Patterns Relate to Biomarkers Associated With Treatment Response.

INTRODUCTION: Tobacco smoking is a major public health burden. The first-line pharmacological treatment for tobacco smoking is nicotine replacement therapy (eg, the nicotine patch (NIC)). Nicotine acts on nicotinic-acetylcholine receptors on dopamine terminals to release dopamine in the ventral and dorsal striatum encoding reward and habit formation, respectively. AIMS AND METHODS: To better understand treatment efficacy, a naturalistic experimental design combined with a kinetic model designed to characterize smoking-induced dopamine release in vivo was used. Thirty-five tobacco smokers (16 female) wore a NIC (21 mg, daily) for 1-week and a placebo patch (PBO) for 1-week in a randomized, counter-balanced order. Following 1-week under NIC and then overnight abstinence, smokers participated in a 90-minute [11C]raclopride positron emission tomography scan and smoked a cigarette while in the scanner. Identical procedures were followed for the PBO scan. A time-varying kinetic model was used at the voxel level to model transient dopamine release peaking instantaneously at the start of the stimulus and decaying exponentially. Magnitude and spatial extent of dopamine release were estimated. Smokers were subcategorized by nicotine dependence level and nicotine metabolism rate. RESULTS: Dopamine release magnitude was enhanced by NIC in ventral striatum and diminished by NIC in dorsal striatum. More-dependent smokers activated more voxels than the less-dependent smokers under both conditions. Under PBO, fast metabolizers activated more voxels in ventral striatum and fewer voxels in dorsal striatum compared to slow metabolizers. CONCLUSIONS: These findings demonstrate that the model captured a pattern of transient dopamine responses to cigarette smoking which may be different across smoker subgroup categorizations. IMPLICATIONS: This is the first study to show that NIC alters highly localized patterns of cigarette smoking-induced dopamine release and that levels of nicotine dependence and nicotine clearance rate contribute to these alterations. This current work included a homogeneous subject sample with regards to demographic and smoking variables, as well as a highly sensitive model capable of detecting significant acute dopamine transients. The findings of this study add support to the recent identification of biomarkers for predicting the effect of nicotine replacement therapies on dopamine function which could help refine clinical practice for smoking cessation.

Generation of parametric Ki images for FDG PET using two 5-min scans.

PURPOSE: The net uptake rate constant (Ki ) derived from dynamic imaging is considered the gold standard quantification index for FDG PET. In this study, we investigated the feasibility and assessed the clinical usefulness of generating Ki images for FDG PET using only two 5-min scans with population-based input function (PBIF). METHODS: Using a Siemens Biograph mCT, 10 subjects with solid lung nodules underwent a single-bed dynamic FDG PET scan and 13 subjects (five healthy and eight cancer patients) underwent a whole-body dynamic FDG PET scan in continuous-bed-motion mode. For each subject, a standard Ki image was generated using the complete 0-90 min dynamic data with Patlak analysis (t* = 20 min) and individual patient's input function, while a dual-time-point Ki image was generated from two 5-min scans based on the Patlak equations at early and late scans with the PBIF. Different start times for the early (ranging from 20 to 55 min with an increment of 5 min) and late (ranging from 50 to 85 min with an increment of 5 min) scans were investigated with the interval between scans being at least 30 min (36 protocols in total). The optimal dual-time-point protocols were then identified. Regions of interest (ROI) were drawn on nodules for the lung nodule subjects, and on tumors, cerebellum, and bone marrow for the whole-body-imaging subjects. Quantification accuracy was compared using the mean value of each ROI between standard Ki (gold standard) and dual-time-point Ki , as well as between standard Ki and relative standardized uptake value (SUV) change that is currently used in clinical practice. Correlation coefficients and least squares fits were calculated for each dual-time-point protocol and for each ROI. Then, the predefined criteria for identifying a reliable dual-time-point Ki estimation for each ROI were empirically determined as: (1) the squared correlation coefficient (R2 ) between standard Ki and dual-time-point Ki is larger than 0.9; (2) the absolute difference between the slope of the equality line (1.0) and that of the fitted line when plotting standard Ki versus dual-time-point Ki is smaller than 0.1; (3) the absolute value of the intercept of the fitted line when plotting standard Ki versus dual-time-point Ki normalized by the mean of the standard Ki across all subjects for each ROI is smaller than 10%. Using Williams' one-tailed t test, the correlation coefficient (R) between standard Ki and dual-time-point Ki was further compared with that between standard Ki and relative SUV change, for each dual-time-point protocol and for each ROI. RESULTS: Reliable dual-time-point Ki images were obtained for all the subjects using our proposed method. The percentage error introduced by the PBIF on the dual-time-point Ki estimation was smaller than 1% for all 36 protocols. Using the predefined criteria, reliable dual-time-point Ki estimation could be obtained in 25 of 36 protocols for nodules and in 34 of 36 protocols for tumors. A longer time interval between scans provided a more accurate Ki estimation in general. Using the protocol of 20-25 min plus 80-85 or 85-90 min, very high correlations were obtained between standard Ki and dual-time-point Ki (R2  = 0.994, 0.980, 0.971 and 0.925 for nodule, tumor, cerebellum, and bone marrow), with all the slope values with differences ≤0.033 from 1 and all the intercept values with differences ≤0.0006 mL/min/cm3 from 0. The corresponding correlations were much lower between standard Ki and relative SUV change (R2  = 0.673, 0.684, 0.065, 0.246). Dual-time-point Ki showed a significantly higher quantification accuracy with respect to standard Ki than relative SUV change for all the 36 protocols (p < 0.05 using Williams' one-tailed t test). CONCLUSIONS: Our proposed approach can obtain reliable Ki images and accurate Ki quantification from dual-time-point scans (5-min per scan), and provide significantly higher quantification accuracy than relative SUV change that is currently used in clinical practice.

Assessment of population-based input functions for Patlak imaging of whole body dynamic 18F-FDG PET.

BACKGROUND: Arterial blood sampling is the gold standard method to obtain the arterial input function (AIF) for quantification of whole body (WB) dynamic 18F-FDG PET imaging. However, this procedure is invasive and not typically available in clinical environments. As an alternative, we compared AIFs to population-based input functions (PBIFs) using two normalization methods: area under the curve (AUC) and extrapolated initial plasma concentration (CP*(0)). To scale the PBIFs, we tested two methods: (1) the AUC of the image-derived input function (IDIF) and (2) the estimated CP*(0). The aim of this study was to validate IDIF and PBIF for FDG oncological WB PET studies by comparing to the gold standard arterial blood sampling. METHODS: The Feng 18F-FDG plasma concentration model was applied to estimate AIF parameters (n = 23). AIF normalization used either AUC(0-60 min) or CP*(0), estimated from an exponential fit. CP*(0) is also described as the ratio of the injected dose (ID) to initial distribution volume (iDV). iDV was modeled using the subject height and weight, with coefficients that were estimated in 23 subjects. In 12 oncological patients, we computed IDIF (from the aorta) and PBIFs with scaling by the AUC of the IDIF from 4 time windows (15-45, 30-60, 45-75, 60-90 min) (PBIFAUC) and estimated CP*(0) (PBIFiDV). The IDIF and PBIFs were compared with the gold standard AIF, using AUC values and Patlak Ki values. RESULTS: The IDIF underestimated the AIF at early times and overestimated it at later times. Thus, based on the AUC and Ki comparison, 30-60 min was the most accurate time window for PBIFAUC; later time windows for scaling underestimated Ki (- 6 ± 8 to - 13 ± 9%). Correlations of AUC between AIF and IDIF, PBIFAUC(30-60), and PBIFiDV were 0.91, 0.94, and 0.90, respectively. The bias of Ki was - 9 ± 10%, - 1 ± 8%, and 3 ± 9%, respectively. CONCLUSIONS: Both PBIF scaling methods provided good mean performance with moderate variation. Improved performance can be obtained by refining IDIF methods and by evaluating PBIFs with test-retest data.

Geniposide ameliorated fluoxetine-suppressed neurite outgrowth in Neuro2a neuroblastoma cells.

AIM: Fluoxetine (FXT), a selective serotonin reuptake inhibitor (SSRI), is one of the most common psychiatric medications clinically prescribed; while over-produced serotonin may suppress neurite development. The role of major iridoids like geniposide (GPS) and genipin (GNP) from Gardenia jasminoides Ellis fruit (family Rubiaceae) in ameliorating the anti-neurite outgrowth effect of FXT is poorly understood. In this study, the effects of these iridoids on FXT-suppressed neurite outgrowth in Neuro2a neuroblastoma cells were investigated. MAIN METHODS: Neuro2a cells were treated with FXT and GPS. The effect of GPS-FXT co-treatment on neurite outgrowth was observed using inverted phase-contrast microscope imaging system, while neurite outgrowth markers - microtubule-associated protein-2 (MAP2) and growth-associated protein 43 (GAP43) were analyzed using RT-PCR, Western blot and immunofluorescence staining. The transcription factor-cAMP response element binding (CREB), and signaling pathways - mitogen-activated protein kinase (MAPK) and protein kinase B/mammalian target of rapamycin (AKT/mTOR) were also analyzed with the help of Western blot. KEY FINDINGS: The results showed that FXT decreased the neurite outgrowth in Neuro2a cells and also downregulated gene and protein expression of MAP2 and GAP43. It also downregulated the protein expression of phosphorylated-CREB, MAPK, and AKT/mTOR signaling pathways. In contrast, GPS counteracted the effects of FXT. GPS-FXT co-treatment increased the percentage of neurite-bearing cells by 3.6-fold at 200 µM as compared to FXT treatment only. SIGNIFICANCE: This study has provided the possible molecular mechanism showing how FXT exerted its detrimental side-effects on the neurite differentiation, and via the same mechanism how GPS attenuated these side effects.

Improved discrimination between benign and malignant LDCT screening-detected lung nodules with dynamic over static 18F-FDG PET as a function of injected dose.

Lung cancer mortality rate can be significantly reduced by up to 20% through routine low-dose computed tomography (LDCT) screening, which, however, has high sensitivity but low specificity, resulting in a high rate of false-positive nodules. Combining PET with CT may provide more accurate diagnosis for indeterminate screening-detected nodules. In this work, we investigated low-dose dynamic 18F-FDG PET in discrimination between benign and malignant nodules using a virtual clinical trial based on patient study with ground truth. Six patients with initial LDCT screening-detected lung nodules received 90 min single-bed PET scans following a 10 mCi FDG injection. Low-dose static and dynamic images were generated from under-sampled list-mode data at various count levels (100%, 50%, 10%, 5%, and 1%). A virtual clinical trial was performed by adding nodule population variability, measurement noise, and static PET acquisition start time variability to the time activity curves (TACs) of the patient data. We used receiver operating characteristic (ROC) analysis to estimate the classification capability of standardized uptake value (SUV) and net uptake constant K i from their simulated benign and malignant distributions. Various scan durations and start times (t *) were investigated in dynamic Patlak analysis to optimize simplified acquisition protocols with a population-based input function (PBIF). The area under curve (AUC) of ROC analysis was higher with increased scan duration and earlier t *. Highly similar results were obtained using PBIF to those using image-derived input function (IDIF). The AUC value for K i using optimized t * and scan duration with 10% dose was higher than that for SUV with 100% dose. Our results suggest that dynamic PET with as little as 1 mCi FDG could provide discrimination between benign and malignant lung nodules with higher than 90% sensitivity and specificity for patients similar to the pilot and simulated population in this study, with LDCT screening-detected indeterminate lung nodules.

What is the role of dosimetry in patients with advanced thyroid cancer?

PURPOSE OF REVIEW: Pretreatment dosimetry prior to I-131 treatment for patients with advanced differentiated thyroid cancer will provide critical information for optimizing dosing regimen for effectiveness and safety. The review briefly summarizes relevant information and updates the current advances. RECENT FINDINGS: I-124 positron emission tomography-computed tomography (PET-CT) with anatomical cross-section imaging provides a better assessment of lesional dosimetry in contrast to traditional I-131 whole body scan with planar imaging. The introduction of Thyrogen (Genzyme, Cambridge, Massachusetts, USA) primed dosimetry also provides an easy way to stimulate the uptake of iodine without prolonged withdrawal of thyroid hormone, although the impact of reducing lesional dosimetry requires attention and further investigation. Lower radioactivities of I-131 could provide similar outcomes in treatment of intermediate risk patients with thyroid cancer compared with traditional high doses. Despite a wide range of lesional doses being noted using fixed 100 mCi radioactivities of I-131, no dose-effective relationship can be established because of an overwhelming success in ablation. SUMMARY: Pretreatment dosimetry remains important to optimize the I-131 treatment dosages for patients with advanced or metastatic thyroid cancer, elderly patients with renal insufficiency or patients with renal failure. Modern I-124 PET-CT and Thyrogen may provide further improvement of this assessment although these advances may require further validation.

Differential diagnosis of intestinal tuberculosis from Crohn's disease and primary intestinal lymphoma in China.

BACKGROUND/AIMS: There are many similarities and overlaps in clinical, radiological, endoscopic, and histological features among intestinal tuberculosis (ITB), Crohn's disease (CD), and primary intestinal lymphoma (PIL), and the differential diagnosis of ITB can be very challenging for clinicians. PATIENTS AND METHODS: The clinical, radiologic, endoscopic, and pathological data of 213 patients were analyzed retrospectively. According to the diagnostic criteria and exclusive criteria of ITB, CD, and PIL, 83 patients were recruited and divided into three groups, including 30 cases in the ITB group, 38 cases in the CD group, and 15 cases in the PIL group, and the medical data and statistical analysis were recorded. RESULTS: Rural patients with abdominal pain as the first symptom and with transverse ulcer and caseating granulomas were more common in the ITB group than the CD group, whereas urban patients with stool change as the first symptom, moderate or severe anemia, thickening of intestinal wall, rectal involvement, skipping distribution, prominent lymphoid aggregates, and irregular glands were more common in CD group than ITB group (P < 0.05). Young patients (age < 30 years) with fever, weakness, fatigue, abdominal mass, intestinal perforation, and emergent operation were more common in ITB group than PIL group, whereas thickening of intestinal wall, malignant lymphocytes, limited distribution, and involvement of small intestine occurred more in PIL group than ITB group (P < 0.05). CONCLUSION: The differential diagnosis of ITB from CD and PIL can be made by a combination of clinical manifestation, endoscopy, and pathological examinations.

Use of (18)F-fluorodeoxyglucose positron emission tomography-computed tomography to aid in diagnosing intestinal adenocarcinoma in 2 rhesus macaques (Macaca mulatta).

Two aged female rhesus macaques (Macaca mulatta) presented with weight loss and intermittent inappetence. The signalment and constellation of clinical signs led clinicians to suspect the presence of intestinal adenocarcinoma. Because of each animal's advanced age and inconclusive radiographic findings, a noninvasive diagnostic tool was preferred over exploratory laparotomy to assist in determining a diagnosis. Consequently, 2-[(18)F]fluoro-2-deoxy-d-glucose (FDG) positron emission tomography-CT (FDG-PET-CT) was chosen to aid in confirming a suspicion of gastrointestinal adenocarcinoma in both animals. FDG is a glucose analogue labeled with fluorine-18 and is taken up by highly metabolically active cells, as observed in many cancers. Tomography revealed an annular constriction of the small intestine with focal FDG uptake in one animal, and an FDG avid transmural mass in the ascending colon of the second animal. Necropsy later confirmed both sites to be adenocarcinomas. This report supports the use of FDG-PET-CT as an adjunct to conventional radiography in the diagnosis of intestinal adenocarcinoma in nonhuman primates.

The utility of I-123 pretherapy scan in I-131 radioiodine therapy for thyroid cancer.

BACKGROUND: There is a growing belief that a pretherapy scan yields little or no additional information that would impact on radioiodine ablation dosing. In addition, there is some concern regarding on the stunning effect of a pretherapy scan, especially when I-131 radioisotope is used for imaging. We hypothesized that a pretherapy scan provides invaluable information on the amount of thyroid remnant, sometimes indicating the need for two-step I-131 ablation. It may also detect unsuspected local lymph node involvement or distant metastases, indicating the requirement for a higher I-131 dose after thyroidectomy. The aim of this study was to evaluate how effective pretherapy scans are for guiding I-131 therapy planning and augmenting information provided in the pathology reports for thyroidectomy specimens. METHODS: We reviewed 122 patients who underwent I-123 pretherapy scan and I-131 radioablation at Yale New Haven Hospital between January 2006 and August 2007. The percentage of neck uptake and whole-body images were acquired 24 hours following the administration of 51.8 MBq (1.4 mCi) of I-123 NaI. A 24-hour uptake of >3% was used as the cutoff to determine whether there was a greater than desired quantity of thyroid remnant, which would require a two-step treatment protocol. Furthermore, attention was paid to identifying cervical lymph nodes, which may not have presented themselves in the euthyroid state at the time of thyroidectomy. Additional clinical information provided by pretherapy scans was computed as percentages with 95% confidence intervals by using adjusted Wald intervals. RESULTS: Overall, the pretherapy scans provided additional critical information in 25% of the cases (31/122; 95% CI: 18%-34%). For cases demonstrating >3% uptake with midline lymph nodes, the pretherapy scan provided additional information in 50% of the cases (8/16; 95% CI: 28%-72%). CONCLUSIONS: Our study demonstrated that I-123 pretherapy scans provide valuable information with regard to unsuspected lymph nodes or distant metastases, indicating the requirement for a significantly higher I-131 dose, and unexpected large thyroid remnants, suggesting the need for two-step ablation. We should take advantage of stimulated pretherapy scans and adjust the treatment dosing accordingly.