Medial and dorsal lateral septum involving social disruption stress-primed escalation in acid-induced writhes.

Introduction: Stress may cause prospective escalations in abdominal pain magnitude and accumbal TRPV1 expression, while central neural circuits mediating these stress effects remain unclear. Methods: Using retrograde tracing methods, we first demonstrated the existence of a medial septal-dorsal lateral septal -accumbal circuit very likely involving social disruption stress-primed escalations in acid-induced writhes and accumbal TRPV1 level. An intersectional viral strategy and virus-carrying hM3Dq and hM4Di DREADDs were, then, employed to selectively modulate GABAergic and cholinergic neuronal activity in medial and dorsal lateral septum. Results: Exciting medial septal GABAergic neuron was found to prevent social disruption stress-primed escalations in acid-induced writhes and accumbal TRPV1 and PKCε expressions. Likewise, inactivating dorsal lateral septal cholinergic neurons was also effective in abolishing these stress-primed escalations. Inactivating GABAergic neuron in non-stressed animals' medial septum was found to reproduce the stress-primed effects in causing heightened acid-induced writhes and accumbal TRPV1 and PKCε levels. Discussion: These results, taken together, prompt us to conclude that social disruption stress may produce plastic changes in a newly-identified medial septal-dorsal lateral septal-accumbal circuit. Moreover, medial septal GABAergic hypoactivity and dorsal lateral septal cholinergic hyperactivity are, at least, two likely causes reflecting such stress-produced escalations in abdominal pain magnitude and pain transduction-related protein over-expression in nucleus accumbens.

Stress while lacking of control induces ventral hippocampal autophagic flux hyperactivity and a depression-like behavior.

BACKGROUND: Stressed animals may perform depression-like behavior insomuch as stress-provoking blood-brain barrier (BBB) disruption, central immune activation, and autophagic flux changes. This study was undertaken to assess whether adult mice having (executive) vs. lacking (yoke) of behavioral control in otherwise equivalent stress magnitude condition, may display differences in their BBB integrity, ventral hippocampal (VH) interleukin-6 (IL-6) and autophagic flux level and VH-related depression-like behavior. To further understand the causative relation of enhanced autophagic flux and stress-primed depression-like behavior, we assessed the effects of bilateral intra-VH 3-methyladenine (3-MA), an autophagic flux inhibitor, infusion in stressed mice. METHODS: Adult mice used had comparable genetic background and housing condition. Executive/yoke pairs of mice received a 10-day (1 h/day) footshock stressor regimen. Throughout the regimen, the ongoing footshock was terminated immediately contingent on the executive mouse', while irrelevant to the respective yoke mouse' voluntary behavior, or lasting for 7 s. Each dyad's cage-mate receiving no such regimen served as no stressor controls. RESULTS: Yoke mice displayed disrupted BBB integrity (escalated Evans blue extravasation and decreased VH ZO-1, claudin-5 expression), increases in VH autophagic flux (increased LC3II/LC3I and decreased p62) and immobility duration in forced swimming test. Most of these indices remained unaltered in executive mice. Administration of 3-MA did not affect immobility duration in control mice, while prevented the increases in immobility duration in yoke mice. CONCLUSIONS: (1) stress susceptibility may be determined by their differences in stress-coping results; (2) VH autophagic flux increase plays a permissive role in priming the stressed animals susceptible to exhibit depression-like behavior.

Verification of the Efficacy of New Diagnostic Criteria for Retropharyngeal Nodes in a Cohort of Nasopharyngeal Carcinoma Patients.

Purpose: A multistage approach to diagnose lateral retropharyngeal nodes (LRPNs) of nasopharyngeal carcinoma (NPC) had been proposed and warranted for validation. Methods: Between 2012 and 2017, the patients with newly diagnosed NPC were enrolled. The responsive nodes or those that progressed during follow-up were positive. The criteria for the multistage approach delimited LRPNs with a minimal axial diameter (MIAD) ≥ 6.1 mm were assessed as positive and if the mean standard uptake value ≥ 2.6, or if the maximal coronal diameter ≥ 25 mm and maximal axial diameter ≥ 8 mm with nodes MIAD < 6.1 mm were also considered as positive. The outcomes were compared with the MIAD cutoff value ≥ 6 mm (traditional method). A chi-squared test was used to compare two areas under the curve of the receiver operating characteristic curves. Results: A total of 67 eligible NPC cases and 155 LRPNs (72 positive and 83 negative) were analyzed. The accuracy, specificity, and sensitivity of the traditional method were 0.91, 0.93, and 0.89, respectively. The values for the multistage approach all reached 0.94. The area under the curve was significantly greater for the multistage approach compared with the traditional method (p = 0.023). Conclusion: The results support the advantage of the multistage approach.

Observer's adrenal corticosterone secretion involvement in vicarious fear conditioning.

Vicarious learning represents a far-reaching value for the survival of social animals. Adrenal hormones are known to affect many forms of learning, yet the roles of adrenal hormones in vicarious learning remain unexplored. This study was undertaken to assess whether observation-stimulated corticosterone (CORT) secretion may affect the magnitude of a vicarious fear conditioning. Mouse observers were individually subjected to an observational compartment next to the training compartment wherein three their cage-mate demonstrators received (1) 5 days of 15 randomly-scheduled footshocks (0.5 mA, 2 s in duration over a 30 min session) (G1); (2) a 30-min presentation of vanilla odors (G2); or (3) footshock delivery and vanilla odors in combination (G3). Demonstrator mice receiving G3 training session and their respective observer mice were found to exhibit greater training-induced and slightly greater observation-stimulated CORT secretion, greater vanilla odors-induced fear responses (FR) and conditioned place aversion (CPA), as compared with the observers vicariously learning from demonstrators receiving G1 or G2 sessions. Observers held in their home cages during demonstrators' trainings and those receiving null demonstrator (No Demonstrator) failed to exhibit vanilla odors-induced FR. Moreover, observers undergoing adrenalectomy (ADX) and G3 sessions exhibited lower vanilla odors-induced FR and CPA as compared to sham surgical (Sham) observers observing G3 sessions. Furthermore, systemic metyrapone injections (50 and 100 mg/kg) prior to daily vicarious G3 training session resulted in decreases in vanilla odors-induced FR and CPA magnitudes in observers. Finally, CORT (1 mg/kg)-pretreated G2 observers failed to display odors-induced FR escalation. These results, taken together, suggest that observation-stimulated CORT secretion is necessary for reliable establishment of vicarious fear conditioning in observer mice.

A pilot study on the association between the blood oxygen level-dependent signal in the reward system and dopamine transporter availability in adults with attention deficit hyperactivity disorder.

BACKGROUND: It is well-known that attention deficit hyperactivity disorder (ADHD) is associated with changes in the dopaminergic system. However, the relationship between central dopaminergic tone and the blood oxygen level-dependent (BOLD) signal during receipt of rewards and penalties in the corticostriatal pathway in adults with ADHD is unclear. METHODS: Single-photon emission computed tomography with [99mTC]TRODAT-1 was used to assess striatal dopamine transporter (DAT) availability. Event-related functional magnetic resonance imaging was conducted on subjects performing the Iowa Gambling Test. RESULT: DAT availability was found to be associated with the BOLD response, which was a covariate of monetary loss, in the medial prefrontal cortex (r = 0.55, P = .03), right ventral striatum (r = 0.69, P = .003), and right orbital frontal cortex (r = 0.53, P = .03) in adults with ADHD. However, a similar correlation was not found in the controls. CONCLUSIONS: The results confirmed that dopaminergic tone may play a different role in the penalty-elicited response of adults with ADHD. It is plausible that a lower neuro-threshold accompanied by insensitivity to punishment could be exacerbated by the hypodopaminergic tone in ADHD.

Availability of Striatal Dopamine Transporter in Healthy Individuals With and Without a Family History of ADHD.

OBJECTIVE: ADHD is the most prevalent neurodevelopmental disorder. It is highly heritable and multifactorial, but the definitive causes remain unknown. Abnormal dopamine transporter (DAT) availability has been reported, but the data are inconsistent. The aim of this study was to examine whether DAT availability differs between healthy parents with and without ADHD offspring. METHOD: Eleven healthy parents with ADHD offspring and 11 age- and sex-matched healthy controls without ADHD offspring were recruited. The availability of DAT was approximated using single-photon emission computed tomography, with [99mTc] TRODAT-1 as the ligand. RESULTS: DAT availability in the basal ganglia, caudate nucleus, and putamen was significantly lower in the parents with ADHD offspring than in the healthy controls without ADHD offspring. CONCLUSION: The results suggest that ADHD could be heritable via abnormal DAT activities.

Prefrontal cortex modulates the correlations between brain-derived neurotrophic factor level, serotonin, and the autonomic nervous system.

Top-down regulation in the human brain and anatomical connections between the prefrontal cortex (PFC) and specific catecholamine-related regions have been well-studied. However, the way in which the PFC modulates downstream neuro-networks in terms of serotonin and the autonomic nervous system (ANS) by variation in the level of brain-derived neurotrophic factor (BDNF) is still unclear. We recruited sixty-seven healthy subjects. Serotonin transporter (SERT) availability was examined by SPECT with [123I]ADAM analysis; heart rate variability (HRV) testing was performed, and the BDNF level was measured. The Wisconsin card-sorting test (WCST), which assesses PFC activation, was also conducted. The interactions of BDNF level and SERT availability were significant in relation to the HRV indexes of low frequency, high frequency, total power, and mean heart rate range. Moderate to significant positive correlations between SERT availability and the above-mentioned HRV indexes existed only in subjects with a low BDNF level. Furthermore, in the low BDNF level group, only those with high WCST perseveration errors or low category completions exhibited significant positive correlations between SERT availability and HRV indexes. A lower BDNF level and poorer PFC function might modulate the synergistic effects of serotonergic and ANS systems in order to maintain brain physiological and psychological homeostasis.

Availability of dopamine transporters and auditory P300 abnormalities in adults with attention-deficit hyperactivity disorder: preliminary results.

OBJECTIVE: Previous studies have indicated that there is dopamine transporter (DAT) dysregulation and P300 abnormality in adults with attention-deficit hyperactivity disorder (ADHD); however, the correlations among the three have not been fully explored. METHODS: A total of 11 adults (9 males and 2 females) with ADHD and 11 age-, sex-, and education-level-matched controls were recruited. We explored differences in DAT availability using single-photon emission computed tomography and P300 wave of event-related potentials between the two groups. The correlation between DAT availability and P300 performance was also examined. RESULTS: DAT availability in the basal ganglia, caudate nucleus, and putamen was significantly lower in the ADHD group. Adults with ADHD had lower auditory P300 amplitudes at the Pz and Cz sites, as well as longer Fz latency than controls. DAT availability was negatively correlated to P300 latency at Pz and Fz. CONCLUSIONS: Adults with ADHD had both abnormal DAT availability and P300 amplitude, suggesting that ADHD is linked to dysfunction of the central dopaminergic system and poor cognitive processes related to response selection and execution.

Role of adiponectin gene variants, adipokines and hydrometry-based percent body fat in metabolically healthy and abnormal obesity.

OBJECTIVE: Metabolically healthy obesity (MHO) subjects have better metabolic parameters than metabolically abnormal obesity (MAO) subjects, but the possible mechanisms underlying this remain unknown. Our study was designed to investigate the interrelationships among genes, adipokines, body fat and its distribution in MHO and MAO. METHODS: From 2007 to 2009, 103 males and 131 females aged 18-50 years were enrolled by an intention-to-treat design in a weight management clinic. Participants were divided into MHO and MAO groups. Percent body fat (PBF) was measured by a deuterium oxide dilution method. Four polymorphic variants, including PPARγ2 (Pro12Ala and C1431T) and adiponectin (T45G and G276T) genes, and three adipokines (adiponectin, leptin and resistin) were obtained. RESULTS: Of the 234 obese subjects, 130 (55.6%) were MHO. In the univariate analysis, the MAO group has significantly higher anthropometric, metabolic indices and leptin levels than the MHO group. Logistic regression analysis revealed that age, male gender, the T allele of adiponectin T45G polymorphism, leptin and PBF were positively associated with MAO. ANCOVA analysis revealed that the T allele of adiponectin T45G polymorphism was associated with higher fasting and postprandial glucose levels. We further found that TT genotype has a lower high molecular weight (HMW)/low molecular weight (LMW) adiponectin ratio than GG genotype. CONCLUSIONS: The factors associated with MAO are age, male gender, the T allele of adiponectin T45G polymorphism, leptin, and PBF. The net effects of T45G polymorphism on the MAO phenotype may be achieved by changes in the adiponectin oligomer ratio and glucose levels.

Comparison of brain serotonin transporter using [I-123]-ADAM between obese and non-obese young adults without an eating disorder.

Cerebral serotonin metabolism has an important but controversial role in obesity. However, it is not given enough attention in morbidly obese young adults. We used single photon emission computed tomography (SPECT) with [I-123]-labeled 2-((2-((dimethylamino)methyl)phenyl)thio)-5-iodophenylamine (ADAM) to investigate changes in serotonin transporter (SERT) availability in 10 morbidly obese young adults without an eating disorder (M/F = 5/5, body mass index (BMI): 40.3 ± 4.1 kg/m2, percentage of body fat (BF%): 46.0 ± 3.9%) and 10 age- and sex-matched non-obese controls (BMI: 20.3 ± 1.2 kg/m2, BF%: 20.6 ± 8.9%). All participants underwent SPECT at 10 min and 6 h after an injection of 200 MBq of [I-123]-ADAM. The SERT binding site (midbrain) was drawn with cerebellum normalization. The BF% and fat distribution were measured using dual-energy X-ray absorptiometry. The midbrain/cerebellum SERT binding ratios (2.49 ± 0.46 vs. 2.47 ± 0.47; p = 0.912) at 6 h were not significantly different between groups, nor was the distribution of the summed images at 10 min (1.36 ± 0.14 vs. 1.35 ± 0.11; p = 0.853). There were no significant correlations between midbrain/cerebellum SERT binding ratio and age, BMI, BF%, or fat distribution. No significant difference in SERT availability in the midbrain between morbidly obese and non-obese young adults without an eating disorder indicates an unmet need for investigating the role of cerebral serotonin in obesity.

Unaltered Dopamine Transporter Availability in Drug-Naive Patients With Schizophrenia After 6 Months of Antipsychotics Treatment: A Naturalistic Study.

BACKGROUND: Dopaminergic dysfunction, namely, dopamine transporter (DAT) availability variations in patients with drug-naive schizophrenia after long-term treatment, is still not well understood. The aims of the study were to explore (i) whether the DAT availability in patients with drug-naive schizophrenia differed after antipsychotic treatment and (ii) whether treatment with different generations of antipsychotics influenced the DAT availability after follow-up for 6 months. METHODS: Twenty-four first-episode, drug-naive patients with schizophrenia were divided into first- and second-generation antipsychotic groups naturalistically. After 6 months of follow-up, 7 patients who received first-generation antipsychotic treatment and 17 patients who received second-generation antipsychotic treatment completed the study. The patients underwent premedication and 6-month follow-up measurements using single-photon emission computed tomography with technetium Tc 99m (Tc) TRODAT-1. Psychopathological evaluations and adverse effects were recorded using appropriate scales. RESULTS: Both of the treatment groups significantly improved according to Positive and Negative Symptoms Scale evaluation. However, no significant difference was noticed between the premedication and 6-month follow-up DAT scans. Nonsignificant differences existed even in the groups of different generations of antipsychotics. CONCLUSIONS: Improvements in psychotic symptoms in patients with schizophrenia may not be influenced by DAT availability, even under treatment with different antipsychotics for a sufficient treatment period.

Can Parameters Other than Minimal Axial Diameter in MRI and PET/CT Further Improve Diagnostic Accuracy for Equivocal Retropharyngeal Lymph Nodes in Nasopharyngeal Carcinoma?

PURPOSE: Minimal axial diameter (MIAD) in magnetic resonance imaging (MRI) was recognized as the most useful parameter in diagnosing lateral retropharyngeal lymph (LRPL) nodes in nasopharyngeal carcinoma (NPC). This study aims to explore the additional nodal parameters in MRI and positron emission tomography-computed tomography for increasing the prediction accuracy. MATERIALS AND METHODS: A total of 663 LRPL nodes were retrospectively collected from 335 patients with NPC. The LRPL nodes ascertained on follow-up MRI were considered positive for metastases. First, the optimal cutoff value of each parameter was derived for each parameter. In addition, neural network (NN) nodal evaluation was tested for all combinations of three parameters, namely MIAD, maximal axial diameter (MAAD), and maximal coronal diameter (MACD). The optimal approach was determined through brute force attack, and the results of two methods were compared using a bootstrap sampling method. Second, the mean standard uptake value (NSUVmean) was added as the fourth parameter and tested in the same manner for 410 nodes in 219 patients. RESULTS: In first and second analysis, the accuracy rate (percentage) for the MIAD was 89.0% (590/663) and 89.0% (365/410), with the optimal cutoff values being 6.1 mm and 6.0 mm, respectively. With the combination of all three and four parameters, the accuracy rate of the NN was 89% (288/332) and 88.8% (182/205), respectively. In prediction, the optimal combinations of the three and four parameters resulted in correct identification of three (accuracy: 593/663, 89.4%) and six additional nodes (371/410, 90.5%), representing 4% (3/73) and 13.3% (6/45) decreases in incorrect prediction, respectively. CONCLUSION: NPC LRPL nodes with an MIAD ≥ 6.1 mm are positive. Among nodes with an MIAD < 6.1 mm, if the NSUVmean ≥ 2.6 or MACD ≥ 25 mm and MAAD ≥ 8 mm, the nodes are positive; otherwise, they are negative.

Serotonin transporter availability may moderate the association between perceiving stress and depressive tendencies - A SPECT with 5-HTTLPR genotyping study.

It was found that serotonin transporter (SERT) gene (5-HTTLPR) polymorphism may moderate the association between perceiving stress and depressive tendency. Although SERT availability in the central nervous system could be associated with 5-HTTLPR polymorphism, whether SERT availability moderates the association between stress and depressive tendency is unclear. This study aimed to investigate whether there is a SERT availability×environmental stress interaction effect, as well as a gene-by-environmental (G×E) interaction effect, using single-photon emission computed tomography (SPECT) with a serotonin transporter radiotracer, [(123)I]ADAM. 87 healthy volunteers were enrolled. The SERT availability was approximated using SPECT with [(123)I]ADAM. Stress and depressive tendencies were measured by the Recent Life Change Questionnaire (RLCQ) and the Taiwanese Depression Questionnaire (TDQ), respectively. A significant interaction of sex×RLCQ×thalamic SERT availability on the TDQ was found, and this effect was robust after controlling for the effect of the SS genotype. The interaction of RLCQ×thalamic SERT availability on the TDQ was significant among males. In particular, a significant association between RLCQ and TDQ (Spearman correlation, ρ=0.64, p<0.01) was found among male subjects with a lower level of thalamic SERT availability. SERT availability may play a role in depressive tendency when under perceived stress among healthy individuals, independent of G×E. This finding provides new evidence that confirms the role of the serotonergic system in the association between stress and depression. Males with lower levels of SERT availability may be more vulnerable to the effects of negative life events.

Lower availability of striatal dopamine transporter in generalized anxiety disorder: a preliminary two-ligand SPECT study.

Dopamine and serotonin have been indirectly found to be associated with generalized anxiety disorder (GAD). The aims of this study were to examine the availabilities of the striatal dopamine transporter (DAT) and the midbrain serotonin transporter (SERT) in patients with GAD. 12 patients with GAD and 12 sex-matched, age-matched, and smoking status-matched healthy controls were recruited. The availabilities of DAT and SERT were approximated using single-photon emission computed tomography, with [Tc]TRODAT-1 and [I]ADAM as the ligands. There were several missing data for six participants with GAD in the ADAM study because of a lack of the radioligand at the time of the experiment. The DAT availability in the striatum was significantly lower in the patients with GAD than in the healthy controls. However, the SERT availability did not differ between the two groups. The results with respect to the striatal DAT level suggested a potential role in the pathophysiology of GAD.

Which demographic variables are necessary to correct in neuroimaging studies of serotonin transporter availability? A SPECT study with [¹²³I]ADAM.

Previous studies have shown that many demographic variables influence serotonin transporter (SERT) availability as assessed by single photon emission computed tomography (SPECT). The aim of this study was to explore which demographic variables influenced the SERT availability most in a SPECT study with [(123)I]ADAM. Ninety-five healthy volunteers were recruited. Age, sex, smoking, alcohol intake, educational level, body mass index, seasonal change, and SERT availability were recorded and then analyzed by multivariate linear regression. Age was the only variable that was significantly associated with SERT availability (calculate: (midbrain-cerebellum)/cerebellum). Furthermore, the inverse correlation of age and SERT availability may be present only before the age of 47. Age should be a covariate in SERT-related neuroimaging analyses, particularly in participants under the age of 47 years.

Oxytocin receptor gene rs53576 polymorphism modulates oxytocin-dopamine interaction and neuroticism traits--a SPECT study.

Brain oxytocin and dopamine systems interact to modulate social cognitive behavior. Whether the interactions are modulated by oxytocin receptor (OXTR) gene variations remains unclear. Considering the dopamine transporter (DAT) availability as an endophenotype and the degree of dopamine-mediated neuroticism as a phenotype of the OXTR genotypes, the current molecular imaging study used [(99m)Tc]TRODAT-1 single photon emission computed tomography (SPECT) to measure the striatal DAT availability and the 57-item Maudsley Personality Inventory to measure neuroticism personality traits in healthy individuals to investigate (A) the correlation between the rs53576 (G/A) of OXTR and the striatal DAT availability, (B) the correlation between the peripheral oxytocin level and striatal DAT availability among different OXTR rs53576 (G/A) genotypes, and (C) whether neuroticism traits could be modified by oxytocin in certain OXTR rs53576 genotypes. The results showed that the striatal DAT availability in the AG+GG group was significantly lower than that in the AA group (2.08±0.47 vs. 1.90±0.32, p=0.04). Only individuals with one or two copies of the G allele of rs53576 showed a negative correlation between DAT availability and oxytocin level (r=-0.41, p=0.002). Furthermore, the oxytocin×DAT interaction was significantly correlated with the MPI neuroticism score in the AA group. Further analyses showed that the DAT availability was correlated with the neuroticism score only in the AA group with a low oxytocin level (r=0.74, p=0.002). The results indicated that the OXTR rs53576 is connected with the striatal DAT availability in vivo and modulates the interactions between the oxytocinergic and dopaminergic systems. Carriers with a specific rs53576 OXTR genotype may present a greater biological sensitivity as well as stress reactivity in terms of environmental adaptation.

Probing the association between dexamethasone-induced cortisol suppression and serotonin transporter availability among drug-free patients with major depressive disorder--a small-sample SPECT study with [¹²³I]ADAM.

The association between hypothalamo-pituitary-adrenal (HPA) axis function and the serotonergic system could be involved in the mechanism of depression. However, neuroimaging evidence is scarce. The aim of the present study was to probe the association between dexamethasone suppression test response and serotonin transporter (SERT) availability in drug-free patients with major depressive disorder (MDD). Seventeen MDD patients (five males and twelve females) were recruited. SPECT with [(123)I] ADAM was used to measure the midbrain SERT availability, and HPA axis function was measured by the dexamethasone suppression test (DST). The association was significant when considering all participants (ρ=0.69, p=0.002). This association may have clinical implications for the treatment of MDD.

The increment in standardized uptake value determined using dual-phase 18F-FDG PET is a promising prognostic factor in non-small-cell lung cancer.

PURPOSE: We aimed to determine whether the increment in the maximal standardized uptake value (SUVmax) of the primary lung tumour between the initial and delayed imaging by dual-phase (18)F-FDG PET has prognostic value in patients with non-small-cell lung cancer (NSCLC). METHODS: We reviewed the records of patients with NSCLC who underwent pretreatment dual-phase (18)F-FDG PET/CT scans acquired at 1 h and 2 h after injection. The SUVmax increment (SUVinc) of the primary lung tumour was the 2-h SUVmax minus the 1-h SUVmax. Univariate and multivariate analyses were used to assess the prognostic significance of SUVinc, retention index, whole-body total metabolic tumour volume, whole-body total lesion glycolysis (TLGwb), 1-h SUVmax, 2-h SUVmax, gender, age, performance status, histological subtype, T stage, N stage and clinical stage. RESULTS: The records of 187 consecutive patients were reviewed. The median follow-up time was 3.9 years. The estimated median progression-free survival (PFS) and overall survival (OS) were 1.3 years and 4.4 years, respectively. An SUVinc cut-off value of >1 had the best discriminative yield for PFS. The 3-year PFS and OS were 61.6 % and 87.8 % in patients with SUVinc ≤ 1 versus 21.1 % and 46.2 % in patients with SUVinc >1 (all P < 0.01). Using the forward stepwise multivariate Cox proportional hazards model, SUVinc, TLGwb, and clinical stage were significant factors for PFS (all P < 0.01). A subgroup analysis of 117 patients treated with surgery showed that SUVinc (P = 0.02) and clinical stage (P < 0.01) were significant prognostic factors for PFS. Furthermore, in stage I patients treated with surgery alone, SUVinc was the only significant prognostic factor (HR 28.07; 95 % CI 2.42 - 326.41). CONCLUSION: SUVinc determined from dual-phase (18)F-FDG PET is a promising prognostic factor for NSCLC. It adds to the value of dual-phase (18)F-FDG PET.

Validation of Memorial Sloan-Kettering Cancer Center nomogram for prediction of non-sentinel lymph node metastasis in sentinel lymph node positive breast cancer patients an international comparison.

BACKGROUND: Current guidelines for breast cancer treatment recommend completion axillary lymph node dissection (CALND) following in case of positive sentinel lymph node (SLN) metastasis, which only in 35%-70% shows additional nodal metastases. Several nomograms and scoring systems have been created to predict the risk of metastasis in non-SLNs. The aim of the study was to identify individual patient risk for non-sentinel lymph node metastasis by validating with MSKCC nomogram and to evaluate the variability within a group of SLN-positive breast cancer patients with the final goal of avoiding unnecessary CALND. PATIENTS AND METHODS: We retrospectively evaluated 1496 primary breast cancer patients. 324 women with a positive SLN who underwent CALND were identified. The predictive accuracy was measured and compared with the MSKCC nomogram by the area under the receiver operating characteristic curve. Receiver operating characteristic (ROC) curve was drawn on the basis of the sensitivity and specificity, and the area under the curve (AUC) was calculated. RESULTS: At least one metastatic non-SLN were identified in 88/324 (27.2%) patients. Tumor size, tumor type, tumor grade, number of positive SLNs and number of negative SLNs were significantly associated with non-SLN status in multivariate analyses. The MSKCC nomogram showed an AUC value of 0.738 (95% confidence interval = 0.682-0.793) after the validation for our collectives. CONCLUSIONS: The MSKCC nomogram showed a good prediction for the non-SLN metastasis and performed adequately in our patient collective. Therefore, for the use of nomogram, validation with other populations of patients is strongly suggested.