Role of the Clinical Features and MRI Parameters on Ki-67 Expression in Hepatocellular Carcinoma Patients: Development of a Predictive Nomogram.

PURPOSE: To develop a nomogram using clinical features and the MRI parameters for preoperatively predicting the expression of Ki-67 in patients with hepatocellular carcinoma (HCC). METHODS: One hundred and forty patients (training cohorts: n = 108; validation cohorts: n = 32) with confirmed HCC were investigated. Mann-Whitney U test, independent sample t-test, and chi-squared test were used to analyze the continuous and categorical variables. Univariate and multivariate logistic regression analyses were performed to examine the clinical variables and parameters from MRI associated with Ki-67 expression. As a result, a nomogram was developed based on these associations in patients with HCC. The performance of the nomogram was evaluated using the area under the receiver operating characteristic curve (AUC) and calibration curves. RESULTS: In the training set, multivariable logistic regression analysis revealed that lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (AFP-L3) levels, protein induced by vitamin K absence or antagonist-II (PIVKA-II) levels, and tumor shape were independent predictors for Ki-67 expression (p < 0.05). These three variables and the apparent diffusion coefficient (ADC) value were used to establish a nomogram, while the ADC value was found to be a marginal significant predictor. The model demonstrated a strong ability to discriminate Ki-67 expression in both the training and validation cohorts (AUC = 0.862, 0.877). CONCLUSION: A non-invasive preoperative prediction method, which incorporates MRI variables and clinical features was developed, and showed effectiveness in evaluating Ki-67 expression in HCC patients.

Lactobacillus Intestinalis Primes Epithelial Cells to Suppress Colitis-Related Th17 Response by Host-Microbe Retinoic Acid Biosynthesis.

Gut microbiome is integral to the pathogenesis of ulcerative colitis. A novel probiotic Lactobacillus intestinalis (L. intestinalis) exerts a protective effect against dextran sodium sulfate-induced colitis in mice. Based on flow cytometry, colitis-associated Th17 cells are the target of L. intestinalis, which is supported by the lack of protective effects of L. intestinalis in T cell-null Rag1-/- mice or upon anti-IL-17-A antibody-treated mice. Although L. intestinalis exerts no direct effect on T cell differentiation, it decreases C/EBPA-driven gut epithelial SAA1 and SAA2 production, which in turn impairs Th17 cell differentiation. Cometabolism of L. intestinalis ALDH and host ALDH1A2 contributed to elevated biosynthesis of retinoic acid (RA), which accounts for the anti-colitis effect in RAR-α -mediated way. In a cohort of ulcerative colitis patients, it is observed that fecal abundance of L. intestinalis is negatively associated with the C/EBPA-SAA1/2-Th17 axis. Finally, L. intestinalis has a synergistic effect with mesalazine in alleviating murine colitis. In conclusion, L. intestinalis and associated metabolites, RA, have potential therapeutic effects for suppressing colonic inflammation by modulating the crosstalk between intestinal epithelia and immunity.

Lactobacillus johnsonii alleviates colitis by TLR1/2-STAT3 mediated CD206+ macrophagesIL-10 activation.

Imbalance of gut microbiota homeostasis is related to the occurrence of ulcerative colitis (UC), and probiotics are thought to modulate immune microenvironment and repair barrier function. Here, in order to reveal the interaction between UC and gut microbiota, we screened a new probiotic strain by 16S rRNA sequencing from Dextran Sulfate Sodium (DSS)-induced colitis mice, and explored the mechanism and clinical relevance. Lactobacillus johnsonii (L. johnsonii), as a potential anti-inflammatory bacterium was decreased colonization in colitis mice. Gavage L. johnsonii could alleviate colitis by specifically increasing the proportion of intestinal macrophages and the secretion of Il-10 with macrophages depleted model and in Il10-/- mice. We identified this subset of immune cells activated by L. johnsonii as CD206+ macrophagesIL-10. Mechanistically, L. johnsonii supplementation enhanced the mobilization of CD206+ macrophagesIL-10 through the activation of STAT3 in vivo and in vitro. In addition, we revealed that TLR1/2 was essential for the activation of STAT3 and the recognition of L. johnsonii by macrophages. Clinically, there was positive correlation between the abundance of L. johnsonii and the expression level of MRC1, IL10 and TLR1/2 in UC tissues. L. johnsonii could activate native macrophages into CD206+ macrophages and release IL-10 through TLR1/2-STAT3 pathway to relieve experimental colitis. L. johnsonii may serve as an immunomodulator and anti-inflammatory therapeutic target for UC.

Determining the suitability of definitive radiation therapy in patients with metastatic nasopharyngeal carcinoma based on PET/CT: a large cohort study.

OBJECTIVES: To determine patients with de novo metastatic nasopharyngeal carcinoma (mNPC) who would benefit from receiving definitive radiation therapy (DRT) along with their pre-existing palliative chemotherapy (PCT) by evaluating their post-PCT Deauville scores and EBV DNA. METHODS: A total of 570 mNPC patients, treated with PCT or PCT+DRT, were studied. EBV DNA levels, along with post-PCT Deauville scores, were used to stratify risk based on the recursive partitioning analysis (RPA). RESULTS: Significant differences were observed in the survival rates of patients with Deauville scores of 1-3 and 4-5 (2-year progression-free survival (PFS): 23.4% versus 8.5%, p < 0.001; 2-year overall survival (OS): 56.8% versus 18.8%, p < 0.001). RPA yielded three distinct groups in the increasing order of risk (Deauville scores of all RPA I-II were within the range of 1-3): (1) RPA I: EBV DNA levels at a pretreatment concentration ≤ 4000 copies/mL and undetectable post-PCT; (2) RPA II: EBV DNA levels either at a pretreatment concentration > 4000 copies/mL or at a pretreatment concentration ≤ 4000 copies/mL and detectable post-PCT; (3) RPA III: Deauville scores 4-5. While patients in RPA I and RPA II had significantly PFS rates when treated with PCT+DRT than when treated with PCT alone (RPA I: 72.7% versus 13.4%, RPA II: 37.8% versus 6.3%), those in RPA III did not experience such PFS benefits (6.5% versus 9.7%). CONCLUSION: PCT+DRT might improve the survival rates in mNPC patients in the low- and mid-risk strata but not those of patients in the high-risk strata. KEY POINTS: We use the Deauville scores and the concentrations of the Epstein-Barr virus (EBV) DNA to determine those patients with de novo metastatic NPC who would benefit from radiation therapy.

The prognostic value of end-of-treatment FDG-PET/CT in diffuse large B cell lymphoma: comparison of visual Deauville criteria and a lesion-to-liver SUVmax ratio-based evaluation system.

PURPOSE: The aim of this study was to determine a better criterion for end-of-treatment PET (EoT-PET) assessment and prognostic evaluation of patients with diffuse large B cell lymphoma (DLBCL). METHOD: EoT-PET scans were assessed using the visual Deauville 5-point scale (5PS) and LLR, the maximum standard uptake value ratio between the lesion and the liver. The cutoff value of LLR was obtained by receiver operator characteristic curve analysis. Patient outcomes were compared using Kaplan-Meier survival analysis. Prognostic indexes of different criteria were compared. Multivariate Cox regression analysis was performed to evaluate the prognostic factors. RESULTS: Four hundred forty-nine newly diagnosed DLBCL patients who received rituximab-based immunochemotherapy were included, and the median follow-up duration was 41.4 months. Patients with Deauville score (DS) 4 displayed significantly longer PFS and OS compared with patients with DS 5 (both p < 0.001), and they had significantly shorter PFS (p < 0.01) but similar OS (p = 0.057) compared with patients with DS 1-3. The differences in PFS and OS between groups were all significant whether positive EoT-PET was defined as DS 4-5 or DS 5 (all p < 0.001). The optimal cutoff of LLR was 1.83, and both PFS and OS were significantly different between EoT-PET-positive and EoT-PET-negative patients as defined by the cutoff (both p < 0.001). LLR-based criterion displayed higher specificity, positive predictive value, and accuracy than 5PS-based criterion in the prediction of disease progression and death events. In the multivariate analysis, positive EoT-PET (as defined by LLR) was related to unfavorable PFS and OS (both p < 0.001). Additional treatment was not correlated with outcomes of EoT-PET-negative patients either defined by LLR or 5PS or EoT-PET-positive patients classified by 5PS, but it was the only beneficial factor for OS (p < 0.05) in EoT-PET-positive patients with LLR ≥ 1.83. CONCLUSION: The optimal cutoff of LLR may be superior to Deauville criteria in identifying low-risk DLBCL patients with negative EoT-PET after the first-line immunochemotherapy and sparing them the cost and toxicity of additional treatment.

Immune checkpoint blocking impact and nomogram prediction of COVID-19 inactivated vaccine seroconversion in patients with cancer: a propensity-score matched analysis.

BACKGROUND: Patients with cancer on active immune checkpoint inhibitors therapy were recommended to seek prophylaxis from COVID-19 by vaccination. There have been few reports to date to discuss the impact of progression cell death-1 blockers (PD-1B) on immune or vaccine-related outcomes, and what risk factors that contribute to the serological status remains to be elucidated. The study aims to find the impact of PD-1B on vaccination outcome and investigate other potential risk factors associated with the risk of seroconversion failure. METHODS: Patients with active cancer treatment were retrospectively enrolled to investigate the interaction effects between PD-1B and vaccination. Through propensity score matching of demographic and clinical features, the seroconversion rates and immune/vaccination-related adverse events (irAE and vrAE) were compared in a head-to-head manner. Then, a nomogram predicting the failure risk was developed with variables significant in multivariate regression analysis and validated in an independent cohort. RESULTS: Patients (n=454) receiving either PD-1B or COVID-19 vaccination, or both, were matched into three cohorts (vac+/PD-1B+, vac+/PD-1B-, and vac-/PD-1B+, respectively), with a non-concer control group of 206 participants. 68.1% (94/138), 71.3% (117/164), and 80.5% (166/206) were seropositive in vac+/PD-1B+cohort, vac+/PD-1B- cohort, and non-cancer control group, respectively. None of irAE or vrAE was observed to be escalated in PD-1B treatment except for low-grade rash.The vaccinated patients with cancer had a significantly lower rate of seroconversion rates than healthy control. A nomogram was thus built that encompassed age, pathology, and chemotherapy status to predict the seroconversion failure risk, which was validated in an independent cancer cohort of 196 patients. CONCLUSION: Although patients with cancer had a generally decreased rate of seroconversion as compared with the healthy population, the COVID-19 vaccine was generally well tolerated, and seroconversion was not affected in patients receiving PD-1B. A nomogram predicting failure risk was developed, including age, chemotherapy status, pathology types, and rheumatic comorbidity.

Image quality and lesion detectability in low-dose pediatric 18F-FDG scans using total-body PET/CT.

PURPOSE: To investigate the effects of dose reduction on image quality and lesion detectability of oncological 18F-FDG total-body PET/CT in pediatric oncological patients and explore the minimum threshold of administered tracer activity. METHODS: A total of 33 pediatric patients (weight 8.5-58.5 kg; age 0.8-17.6 years) underwent total-body PET/CT using uEXPLORER scanner with an 18F-FDG administered dose of 3.7 MBq/kg and an acquisition time of 600 s were retrospectively enrolled. Low-dose images (0.12-1.85 MBq/kg) were simulated by truncating the list-mode PET data to reducing count density. Subjective image quality was rated on a 5-point scale. Semi-quantitative uptake metrics for low-dose images were assessed using region-of-interest (ROI) analysis of healthy liver and suspected lesions and were compared with full-dose images. The micro-lesion detectability was compared among the dose-dependent PET images. RESULTS: Our analysis shows that sufficient subjective image quality and lesion conspicuity could be maintained down to 1/30th (0.12 MBq/kg) of the administered dose of 18F-FDG, where good image quality scores were given to 1/2- and 1/10- dose groups. The image noise was significantly more deranged than the overall quality and lesion conspicuity in 1/30- to 1/10-dose groups (all p < 0.05). With reduced doses, quantitative analysis of ROIs showed that SUVmax and SD in the liver increased gradually (p < 0.05), but SUVmax in the lesions and lesion-to-background ratio (LBR) showed no significant deviation down to 1/30-dose. One hundred percent of the 18F-FDG-avid micro-lesions identified in full-dose images were localized down to 1/15-dose images, while 97% of the lesion were localized in 1/30-dose images. CONCLUSION: The total-body PET/CT might significantly decrease the administered dose upon maintaining the image quality and diagnostic performance of micro-lesions in pediatric patients. Data suggests that using total-body PET/CT, optimal image quality could be achieved with an administered dose-reduction down to 1/10-dose (0.37 MBq/kg).

Evaluation of Low-Dose Multidetector Computed Tomography Whole Gastroenterography With Oral Administration of Contrast Agents.

PURPOSE: To evaluate the degree of gastric, enteric, colonic, and rectal filling in multidetector computed tomography (MDCT) whole gastroenterography. METHODS: In this prospective study involving 124 patients, 78 and 46 patients underwent MDCT whole gastroenterography using positive and neutral oral contrast agents, respectively. The degree of filling of the stomach, small and large bowel, was qualitatively analyzed by experienced radiologists using a 3-point scoring system. RESULTS: The majority of patients received a score of ≥2 for small intestine filling using both positive and neutral contrast agents (90.5% and 78.2%, respectively), and <9% of the patients had a score of 0. The highest score for the degree of filling in the small intestine was observed in the ileum, followed by the duodenum and jejunum. There was a significant difference in the degree of filling achieved with positive and neutral contrast agents in the duodenum (P = .013) and jejunum (P = .047). More than 74% of cases had an optimal filling of the stomach, whereas >80% of the cases had an optimal filling of the colorectal segments. Only ≤5.1% had a score of 0 for the analyzed segments of the colorectum. Positive and neutral contrast agents were associated with similar degree of filling in the stomach and colon segments without a significant difference in the extent of contrast agent filling (P > .05). CONCLUSIONS: Multidetector computed tomography whole gastroenterography was found to be a simple, safe, noninvasive, painless, and effective modality for the diagnosis of stomach and bowel complications in clinical settings.

Rebound adenotonsillar and thymic uptake of 18F-FDG in paediatric patients with lymphoma.

PURPOSE: To evaluate the treatment-dependent changes in FDG uptake in the adenoid, palatine tonsils, and thymus in paediatric patients with lymphoma. METHODS: Eight hundred PET/CT scans of 212 paediatric patients between 2007 and 2019 (mean age, 11.9 years; median follow-up, 26.2 months) were retrospectively reviewed for discernible FDG uptake in the adenoid (A+), palatine tonsils (P+), and thymus (T+). The distribution of metabolic activity in the interested lymphoid organs was examined. Statistical analysis was performed using SPSS packages. RESULTS: There were 513 (64 %) A + scans, 548 (69 %) P + scans, 270 (48 %) T + scans identified. The percentage of A + was 88 % at baseline, decreased to 48 % at the end of treatment, and then rebounded to 73 % during follow up; P + went from 79 % to 45 % then to 82 %; and for T + was 75 %, 21 %, 72 %. SUVmax was significantly higher (P < 0.001) in scans performed during follow-up than that of the baseline (A + 7.0 ±â€¯3.5 vs. 5.8 ±â€¯2.5; P + 9.4 ±â€¯3.5 vs. 8.2 ±â€¯2.8; T + 4.0 ±â€¯1.4 vs. 3.4 ±â€¯1.1). A + and P + peaked between 6-12 months of follow-up with a SUVmax of 7.6 ±â€¯3.2, 10.6 ±â€¯3.2, accordingly; T + peaked within 3-12 months with a SUVmax of 4.4 ±â€¯1.4. Despite that A + and T + were more commonly seen in younger patients at any given study time, evident uptake rebound persisted in patients aged ≥16. CONCLUSIONS: In paediatric patients with lymphoma, evident and benign rebound adenotonsillar and thymic 18F-FDG uptake commonly occur during post-treatment surveillance.

Subclassification of skull-base invasion for nasopharyngeal carcinoma using cluster, network and survival analyses: A double-center retrospective investigation.

PURPOSE: To investigate the prognostic value of skull-base invasion (SBI) for nasopharyngeal carcinoma (NPC), propose a subclassification of SBI. METHODS: 792 and 433 patients with pathologically proven NPC and complete clinical and magnetic resonance imaging records at Sun Yat-sen University Cancer Center and Foshan Hospital were enrolled, and investigated using heat map/cluster, network and survival analyses. RESULTS: The results of heat map/cluster analyses and network analysis showed that T3 patients with pterygoid process and/or base of the sphenoid bone invasion (T3 slight) had better treatment outcomes than those with other SBIs (T3 severe). Significant differences were observed between T3-slight and T3-severe groups with regard to 5-year overall survival (OS) (93.0% vs. 83.5%, p = 0.014) and progression-free survival (PFS) (82.5% vs. 74.1%, p = 0.044) rates. No significant difference was observed between T3-slight group and T2 patients with regard to 5-year OS (93.0% vs. 84.7%, p = 0.062) and PFS (82.5% vs. 78.9%, p = 0.459) rates. Therefore, we downgraded patients with T3 slight to T2, yielding a new T classification sample. The survival curves of the 5-year OS and PFS rates of T2 and T3 were more reasonable after sample redistribution than those before sample redistribution. The differences in the 5-year OS and PFS rates between T2 and T3 patients after sample redistribution approached significance (p = 0.075 and 0.051, respectively). CONCLUSIONS: Different types of SBIs had different effects on the prognosis for NPC. We recommend patients with T3 slight not be defined as T3 but, rather, as T2.

Glycine Protects against Hypoxic-Ischemic Brain Injury by Regulating Mitochondria-Mediated Autophagy via the AMPK Pathway.

Hypoxic-ischemic encephalopathy (HIE) is detrimental to newborns and is associated with high mortality and poor prognosis. Thus, the primary aim of the present study was to determine whether glycine could (1) attenuate HIE injury in rats and hypoxic stress in PC12 cells and (2) downregulate mitochondria-mediated autophagy dependent on the adenosine monophosphate- (AMP-) activated protein kinase (AMPK) pathway. Experiments conducted using an in vivo HIE animal model and in vitro hypoxic stress to PC12 cells revealed that intense autophagy associated with mitochondrial function occurred during in vivo HIE injury and in vitro hypoxic stress. However, glycine treatment effectively attenuated mitochondria-mediated autophagy. Additionally, after identifying alterations in proteins within the AMPK pathway in rats and PC12 cells following glycine treatment, cyclosporin A (CsA) and 5-aminoimidazole-4-carboxamide-1-b-4-ribofuranoside (AICAR) were administered in these models and indicated that glycine protected against HIE and CoCl2 injury by downregulating mitochondria-mediated autophagy that was dependent on the AMPK pathway. Overall, glycine attenuated hypoxic-ischemic injury in neurons via reductions in mitochondria-mediated autophagy through the AMPK pathway both in vitro and in vivo.

Predictors for reactive thymic hyperplasia and its prognostic value in children and adolescents with lymphoma.

BACKGROUND: Reactive thymic hyperplasia (RTH) is seen in children and adolescents receiving chemotherapy for various malignancies. However, it is not clear why this occurs only in some patients. The aim of this study was to identify the predictors for RTH in children and adolescents receiving chemotherapy for lymphoma and to determine the effect of RTH on prognosis. METHODS: We reviewed the medical records of 126 lymphoma patients (October 2007-October 2012). The patients were divided into two groups according to different criteria, i.e., age at initial diagnosis (2-12 years vs. 13-18 years); presence of thymic infiltration at baseline (yes vs. no); and receipt of mediastinal radiotherapy (yes vs. no). The Kaplan-Meier method and multivariate Cox regression model analysis were used to analyze predictors for RTH. Further, patients were divided into two groups according to the occurrence of RTH during follow-up, and Kaplan-Meier survival analysis was used to analyze the prognostic value of RTH. RESULTS: The 2-12-year-old group had a shorter duration from the end of therapy to RTH than the 13-18-year-old group (median: 3 months vs. 16 months) and a higher rate of RTH (97.1% vs. 60.3%, P < 0.001). The lymphoma thymic non-infiltration group had a shorter duration from the end of therapy to RTH than the lymphoma infiltration group (median: 4 months vs. 22 months), and a higher rate of RTH (88.2% vs. 57.6%, P < 0.001). The non-mediastinal radiotherapy group had higher rate of RTH than the mediastinal radiotherapy group (84.7% vs. 12.5%, P < 0.001). Low age, absence of thymic infiltration by lymphoma at baseline, and absence of mediastinal radiation were predictors for RTH by multivariate Cox regression analysis (P < 0.05). The RTH group had a lower recurrence rate than the non-RTH group (13.9% vs. 40%), and a longer duration from the end of therapy to recurrence (median: 10 months vs. 5 months, P < 0.001). CONCLUSIONS: Younger age, absence of thymic infiltration by lymphoma at baseline and absence of mediastinal radiotherapy are predictors for RTH in children and adolescents. RTH may be a positive prognostic factor.

The conditioned medium of human mesenchymal stromal cells reduces irradiation-induced damage in cardiac fibroblast cells.

Recently, multipotent mesenchymal stromal cell (MSC) treatment has attracted special attention as a new alternative strategy for stimulating regeneration. Irradiation myocardial fibrosis (IMF) is a major complication associated with total body irradiation for hematopoietic stem cell transplantation, nuclear accidents, and thoracic radiotherapy for lung cancer, esophageal cancer, proximal gastric cancer, breast cancer, thymoma, and lymphoma. The aim of the present study was to assess the therapeutic paracrine effects of human umbilical cord-derived mesenchymal stromal cells (UC-MSCs) in the cell model of IMF. For this purpose, primary human cardiac fibroblasts (HCF) cells were irradiated and cultured with the conditioned medium of UC-MSCs (MSCCM). MSCCM promoted cell viability, reduced collagen deposition as measured by Sircol assay and qPCR (Col1A1 and Col1A2), prevented oxidative stress and increased antioxidant status (as measured by malondialdehyde content and the activities and mRNA levels of antioxidant enzymes), and reduced pro-fibrotic TGF-ß1, IL-6 and IL-8 levels (as examined by ELISA kit and qPCR). Pretreatment with inhibitor of NF-κB led to a decrease in the levels of TGF-ß1 in cell lysate of HCF cells by ELISA kit. Furthermore, we also found that MSCCM prevented NF-κB signaling pathway activation for its proinflammatory actions induced by irradiation. Taken together, our data suggest that MSCCM could reduce irradiation-induced TGF-ß1 production through inhibition of the NF-κB signaling pathway. These data provide new insights into the functional actions of MSCCM on irradiation myocardial fibrosis.

Knockdown of PKM2 and GLS1 expression can significantly reverse oxaliplatin-resistance in colorectal cancer cells.

Clinical treatment for colorectal cancer (CRC) thus far encounters a huge challenge due to oxaliplatin-resistance. As crucial rate-limiting enzymes in aerobic glycolysis and glutaminolysis, pyruvate kinase M2 type (PKM2) and kidney-type glutaminase (GLS1) are proposed to carry important implications in colorectal carcinogenesis and drug-resistance. This study aimed to explore the possible association of oxaliplatin-resistance with aerobic glycolysis/glutaminolysis indexed by PKM2/GLS1 expression. PKM2 and GLS1 expression was quantified by polymerase chain reaction (PCR) and Western blot techniques in CRC cell lines. The abilities of cell formation, kinetics, migration, invasion, survival and apoptosis, as well as permeability glycoprotein (Pgp) expression were inspected before and after knocking-down PKM2/GLS1 expression. In addition, the influence of knocking-down PKM2/GLS1 expression was evaluated in vivo. Differentiated PKM2 and GLS1 expression in both THC8307 and THC8307/Oxa cell lines was identified. In the THC8307 cell line, PKM2 and GLS1 can accelerate malignant behaviors, increase oxaliplatin-resistance, upregulate Pgp expression, and inhibit cell apoptosis. Contrastingly in the THC8307/Oxa cell line, knockdown of PKM2/GLS1 expression can restrain malignant behaviors, reestablish oxaliplatin-sensitivity, downregulate Pgp expression, and induce cell apoptosis. In xenograft, knockdown of PKM2/GLS1 expression can significantly inhibit tumor growth, reduce Pgp expression, and increase tumor apoptosis. Taken together, the present findings enriched our knowledge by demonstrating a significant association of PKM2 and GLS1 with oxaliplatin-resistance in CRC. We further propose that knockdown of PKM2/GLS1 expression may constitute a novel therapeutic strategy toward effective treatment for CRC.

Diagnostic performance of magnifying narrow-band imaging for early gastric cancer: A meta-analysis.

AIM: To investigate the performance of magnifying endoscopy with narrow-band imaging (ME-NBI) in the diagnosis of early gastric cancer (EGC). METHODS: Systematic literature searches were conducted until February 2014 in PubMed, EMBASE, Web of Science, Ovid, Scopus and the Cochrane Library databases by two independent reviewers. Meta-analysis was performed to calculate the pooled sensitivity, specificity and diagnostic odds ratio and to construct a summary receiver operating characteristic (ROC) curve. Subgroup analyses were performed based on the morphology type of lesions, diagnostic standard, the size of lesions, type of assessment, country and sample size to explore possible sources of heterogeneity. A Deeks' asymmetry test was used to evaluate the publication bias. RESULTS: Fourteen studies enrolling 2171 patients were included. The pooled sensitivity, specificity and diagnostic odds ratio for ME-NBI diagnosis of EGC were 0.86 (95%CI: 0.83-0.89), 0.96 (95%CI: 0.95-0.97) and 102.75 (95%CI: 48.14-219.32), respectively, with the area under ROC curve being 0.9623. Among the 14 studies, six also evaluated the diagnostic value of conventional white-light imaging, with a sensitivity of 0.57 (95%CI: 0.50-0.64) and a specificity of 0.79 (95%CI: 0.76-0.81). When using "VS" (vessel plus surface) ME-NBI diagnostic systems in gastric lesions of depressed macroscopic type, the pooled sensitivity and specificity were 0.64 (95%CI: 0.52-0.75) and 0.96 (95%CI: 0.95-0.98). For the lesions with a diameter less than 10 mm, the sensitivity and specificity were 0.74 (95%CI: 0.65-0.82) and 0.98 (95%CI: 0.97-0.98). CONCLUSION: ME-NBI is a promising endoscopic tool in the diagnosis of early gastric cancer and might be helpful in further target biopsy.

Qualitative visual trichotomous assessment improves the value of fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography in predicting the prognosis of diffuse large B-cell lymphoma.

INTRODUCTION: Fluorine-18 fluorodeoxyglucose (18 F-FDG) positron emission tomography/computed tomography (PET/CT) is a powerful tool for monitoring the response of diffuse large B-cell lymphoma (DLBCL) to therapy, but the criteria to interpret PET/CT results remain under debate. We investigated the value of post-treatment PET/CT in predicting the prognosis of DLBCL patients when interpreted according to qualitative visual trichotomous assessment (QVTA) criteria compared with the Deauville criteria. METHODS: In this retrospective study, final PET/CT scans of DLBCL patients treated with rituximab-based regimens between October 2005 and November 2010 were interpreted using the Deauville and QVTA criteria. Survival curves were estimated using Kaplan-Meier analysis and compared using the log-rank test. RESULTS: A total of 253 patients were enrolled. The interpretation according to the Deauville criteria revealed that 181 patients had negative PET/CT scan results and 72 had positive results. The 3 year overall survival (OS) rate was significantly higher in patients with negative scan results than in those with positive results (91.6% vs. 57.5%, P<0.001). The 72 patients with positive scan results according to the Deauville criteria were divided into two groups by the interpretation according to the QVTA criteria: 29 had indeterminate results, and 43 had positive results. The 3 year OS rate was significantly higher in patients with indeterminate scan results than in those with positive results (91.2% vs. 33.5%, P<0.001) but was similar between patients with negative and indeterminate scan results (91.6% vs. 91.2%, P=0.921). CONCLUSIONS: Compared with the Deauville criteria, using the QVTA criteria for interpreting post-treatment PET/CT scans of DLBCL patients is likely to reduce the number of false positive results. The QVTA criteria are feasible for therapeutic outcome evaluation and can be used to guide risk-adapted therapy.

Cervical lymph node hyperplasia on [(18)F]-fluorodeoxyglucose positron emission tomography/computed tomography scan after treatment of children and adolescents with malignant lymphoma.

PURPOSE: To define imaging manifestations and clinical prognosis of cervical lymph node hyperplasia using [(18)F]-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) scanning after treatment of children and adolescents with malignant lymphoma. METHODS: Children and adolescent patients with malignant lymphoma who had high FDG uptake in their cervical lymph nodes via PET/CT after treatment, which was not due to tumor recurrence or residue, were retrospectively analyzed. RESULTS: Twenty-seven patients with a median age of 12 years were included; 11 had Hodgkin's disease and 16 had non-Hodgkin's lymphoma. The time from PET/CT scan to completion of therapy was 1-36 months, 85.2% (23/27) of which took place within 12 months. Three patients had confirmed lymph node follicular hyperplasia by biopsy, while all 27 patients achieved disease-free survival during the follow-up period. The maximum standardized uptake values (SUVmax) of cervical lymph nodes were 2.2-16.2 and the maximum short axis ranged from 0.3 to 1.2 cm. Cervical lymph node hyperplasia was noted in neck levels I-V, and neck level II bilaterally had the highest incidence (100%). Bilateral cervical lymph node hyperplasia was symmetrical in terms of both the SUVmax and affected locations. Thymic hyperplasia and nasopharyngeal lymphoid hyperplasia were both observed in 24 patients (88.9%). There was no relationship in terms of the SUVmax between cervical lymph nodes and thymic tissue, cervical nodes or nasopharyngeal lymphoid tissue. CONCLUSION: Cervical lymph node hyperplasia with high FDG uptake on PET/CT scans found after treating children and adolescents with malignant lymphoma can be benign processes. Awareness of this possibility may help avoid invasive procedures and over-treatment.

A Mutation in CTSK Gene in an Autosomal Recessive Pycnodysostosis Family of Chinese Origin.

Pycnodysostosis is a rare autosomal recessive skeletal dysplasia characterized by short stature, osteosclerosis, acro-osteolysis, frequent fractures, and skull deformities. Mutation in the gene encoding cathepsin K (CTSK), which is a lysosomal cysteine protease, has been found to be responsible for this disease. Here we reported a consanguineous Chinese family with 1 affected individual demonstrating autosomal recessive pycnodysostosis with recurrent kidney stone, a new clinical manifestation which has not been reported in patients of pycnodysostosis before. To identify the pathogenic mutation, we evaluated the patient clinically, biochemically, and radiographically. To screen for mutations in the CTSK gene of the patient and his family members, all of its exons and exon-intron junctions were PCR amplified from genomic DNA and sequenced. Sequence analysis of the patient's CTSK gene revealed homozygosity for a missense mutation (c.746T>C) in exon 6, which leads to amino change (p.Ile249Thr) in the mature CTSK protein. This mutation was firstly reported by Michela Donnarumma and his colleagues in 2007 in a Spanish family. Our study strengthens the role of this particular mutation in the pathogenesis of pycnodysostosis.

Complementary Roles of Squamous Cell Carcinoma Antigen and (18)F-FDG PET/CT in Suspected Recurrence of Cervical Squamous Cell Cancer.

PURPOSE: To assess the clinical value of FDG PET/CT and evaluate the complementary roles of serum squamous cell carcinoma antigen (SCCAg) and FDG PET/CT in the diagnosis of suspected recurrent of cervical squamous cell cancer. METHODS: Serum SCCAg levels were retrospectively reviewed in patients previously treated for cervical squamous cell carcinoma, who had suspected recurrence of cervical cancer and who had undergone FDG PET/CT scans. The clinical impact of elevated SCCAg (>1.5 ng/ml) and negative SCCAg (≤1.5 ng/ml) levels were analyzed based on the results of PET/CT and final diagnosis. RESULTS: The overall patient-based sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of PET/CT for the detection of tumor recurrence or malignancy were 100% (86/86), 80.8% (21/26), 95.5% (107/112), 94.5% (86/91) and 100% (21/21), respectively. Of the 112 patients included in this study, recurrence or malignancy was detected by PET/CT in 62 of the 64 patients with elevated SCCAg, compared to 24 of the 48 patients with negative SCCAg levels. The overall patient-based PPV, NPV, sensitivity and accuracy of SCCAg for the detection of tumor recurrence or malignancy were 96.9% (62/64), 50% (24/48), 72.1% (62/86) and 76.8% (86/112), respectively. The five false-positive PET/CT results were all associated with patients with negative SCCAg levels. The PPV of positive PET/CT-associated elevated SCCAg for the detection of tumor recurrence or malignancy was 100% (62/62). The NPV of negative SCCAg-associated negative PET/CT was 100% (19/19). CONCLUSIONS: Serum SCCAg evaluation and FDG PET/CT imaging can be complementary techniques in cases of suspected recurrent cervical squamous cancer. Positive PET/CT with elevated SCCAg can predict recurrence. Although PET/CT cannot confidently be deferred due to a negative SCCAg test, the possibility of a false-positive PET/CT in those cases may have diagnostic importance.

Use of subsequent PET/CT in diffuse large B-cell lymphoma patients in complete remission following primary therapy.

Interim 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (I-PET/CT) is a powerful tool for monitoring the response to therapy in diffuse large B-cell lymphoma (DLBCL). This retrospective study aimed to determine when and how to use I-PET/CT in DLBCL. A total of 197 patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) were enrolled between October 2005 and July 2011; PET/CT was performed at the time of diagnosis (PET/CT0), after 2 and 4 cycles of chemotherapy (PET/CT2 and PET/CT4, respectively), and at the end of treatment (F-PET/CT). According to the International Harmonization Project for Response Criteria in Lymphoma, 110 patients had negative PET/CT2 scans, and 87 had positive PET/CT2 scans. The PET/CT2-negative patients had significantly higher 3-year progression-free survival rate (75.8% vs. 38.2%) and 3-year overall survival rate (93.5% vs. 55.6%) than PET/CT2-positive patients. All PET/CT2-negative patients remained negative at PET/CT4, but 3 were positive at F-PET/CT. Among the 87 PET/CT2-positive patients, 57 remained positive at F-PET/CT, and 32 progressed during chemotherapy (15 at PET/CT4 and 17 at F-PET/CT). Comparing PET/CT4 with PET/CT0, 7 patients exhibited progression, and 8 achieved partial remission. Comparing F-PET/CT with PET/CT0, 10 patients exhibited progression, and 7 achieved partial remission. In conclusion, our results indicate that I-PET/CT should be performed after 2 rather than 4 cycles of immunochemotherapy in DLBCL patients. There is a limited role for subsequent PET/CT in the detection of relapse in PET/CT2-negative patients, but repeat PET/CT is required if the PET/CT2 findings are positive.