Gastroparesis might not be uncommon in patients with diabetes mellitus in a real-world clinical setting: a cohort study.

BACKGROUND: This study investigated the frequency of diabetic gastroparesis and associated risk factors in a real-world clinical setting. METHODS: This retrospective cross-sectional study included patients who underwent assessments of solid gastric emptying time (GET) by technetium-99 m scintigraphy between May 2019 and December 2020. We categorized patients into three groups according to gastric retention of technetium-99 m: rapid (< 65% at 1 h or < 20% at 2 h), normal (≤60% at 2 h and/or ≤ 10% at 4 h), and delayed (> 60% at 2 h and/or > 10% at 4 h). RESULTS: Patients with diabetes mellitus (DM) were more likely to show abnormal GET than those without DM (119 [70.8%] vs. 16 [44.4%]). The mean glycated A1c was 10.3% in DM patients. DM patients with normal GET were significantly younger (57.2 years, P = 0.044) than those with delayed (65.0 years) or rapid GET (60.2 years). Fasting glucose levels were the lowest in the normal GET group and the highest in the rapid GET group (delayed: 176.3 mg/dL, normal: 151.2 mg/dL, rapid: 181.0 mg/dL, P = 0.030). However, glycated A1c was not significantly different among the delayed, normal, and rapid GET groups in patients with DM. Patients with delayed and rapid GET showed a higher frequency of retinopathy (6.0 vs. 15.5%, P = 0.001) and peripheral neuropathy (11.3 vs. 24.4%, P = 0.001) than those with normal GET. In the multinomial logistic regression analysis, retinopathy demonstrated a positive association with delayed GET, while nephropathy showed a significant negative correlation. CONCLUSION: DM gastroparesis in the clinical setting was not uncommon. Abnormal GET, including delayed and rapid GET, was associated with DM retinopathy or peripheral neuropathy.

The Adenylyl Cyclase Activator Forskolin Increases Influenza Virus Propagation in MDCK Cells by Regulating ERK1/2 Activity.

Vaccination is the most effective method for preventing the spread of the influenza virus. Cell-based influenza vaccines have been developed to overcome the disadvantages of egg-based vaccines and their production efficiency has been previously discussed. In this study, we investigated whether treatment with forskolin (FSK), an adenylyl cyclase activator, affected the output of a cell-based influenza vaccine. We found that FSK increased the propagation of three influenza virus subtypes (A/H1N1/California/4/09, A/H3N2/Mississippi/1/85, and B/Shandong/7/97) in Madin-Darby canine kidney (MDCK) cells. Interestingly, FSK suppressed the growth of MDCK cells. This effect could be a result of protein kinase A (PKA)-Src axis activation, which downregulates extracellular signal-regulated kinase (ERK)1/2 activity and delays cell cycle progression from G1 to S. This delay in cell growth might benefit the binding and entry of the influenza virus in the early stages of viral replication. In contrast, FSK dramatically upregulated ERK1/2 activity via the cAMP-PKA-Raf-1 axis at a late stage of viral replication. Thus, increased ERK1/2 activity might contribute to increased viral ribonucleoprotein export and influenza virus propagation. The increase in viral titer induced by FSK could be explained by the action of cAMP in assisting the entry and binding of the influenza virus. Therefore, FSK addition to cell culture systems could help increase the production efficiency of cell-based vaccines against the influenza virus.

Prognostic value of TLR from FDG PET/CT in patients with margin-negative stage IB and IIA non-small cell lung cancer.

OBJECTIVES: To evaluate the prognostic value of TLR from PET/CT in patients with resection margin-negative stage IB and IIA non-small cell lung cancer (NSCLC) and compare high-risk factors necessitating adjuvant treatment (AT). METHODS: Consecutive FDG PET/CT scans performed for the initial staging of NSCLC stage IB and IIA were retrospectively reviewed. The maximum standardized uptake value (SUVmax) of the primary tumor and mean SUV of the liver were acquired. The tumor-to-liver SUV ratio (TLR) was also calculated. Charts were reviewed for basic patient characteristics and high-risk factors for considering AT (poor differentiation, visceral pleura invasion, vascular invasion, tumors > 4 cm, and wedge resection). Statistical analysis was performed using Cox regression analysis and the Kaplan-Meier method. RESULTS: Of the 112 patients included, 15 (13.4%) died, with a median overall survival (OS) of 43.8 months. Twenty-two patients (19.6%) exhibited recurrence, with median disease-free survival (DFS) of 36.0 months. In univariable analysis, pathology, poor differentiation, and TLR were associated with shorter DFS and OS. In multivariable analysis, TLR (hazard ratio [HR] = 1.263, p = 0.008) and differentiation (HR = 3.087, p = 0.012) were associated with shorter DFS. Also, TLR (HR = 1.422, p < 0.001) was associated with shorter OS. CONCLUSION: TLR from FDG PET/CT was an independent prognostic factor for recurrence and survival. PET parameters constitute risk factors for consideration in the decision-making for AT in margin-negative stage IB and IIA NSCLC. CLINICAL RELEVANCE STATEMENT: In this study, TLR from FDG PET/CT was an independent prognostic factor in stage IB-IIA non-small cell cancer patients. Although additional validation studies are warranted, TLR has the potential to be used to determine the need for adjuvant therapy. KEY POINTS: • High TLR is an independent poor prognostic factor in stage IB-IIA NSCLC. • Adjuvant treatment should be considered in patients with high TLR following complete tumor resection.

Prognostic impact of 18F-FDG PET/CT in pathologic stage II invasive ductal carcinoma of the breast: re-illuminating the value of PET/CT in intermediate-risk breast cancer.

BACKGROUND: The aim of this study is to investigate the impact of 18F-FDG PET/CT on prognosis of stage II invasive ductal carcinoma (IDC) of the breast primarily treated with surgery. METHODS: The clinical records of 297 consecutive IDC with preoperative PET/CT and pathologically staged II in surgery from 2013 to 2017 were retrospectively reviewed. The maximum standardized uptake value (SUVmax), peak standardized uptake value (SUVpeak), tumor-to-liver ratio (TLR), and metabolic tumor volume (MTV) were measured. Association of clinicopathologic factors (age, T stage, N stage, AJCC pathologic stage of IIA or IIB, pathologic prognostic stage, grade, hormonal receptor status, HER2 status, Ki-67, and adjuvant therapy) and PET parameters with DFS was assessed using the Cox proportional hazards model. RESULTS: There were 35 recurrences and 10 deaths at a median follow-up of 49 months (range 0.8 ~ 87.3). All PET parameters were significantly associated with DFS in univariate analysis but in multivariate analysis, SUVpeak was the only factor significantly associated with DFS (hazard ratio 2.58, 95% confidence interval 1.29-5.15, P = 0.007). In cohorts with higher values of SUVpeak or TLR, patients who received adjuvant chemotherapy had significantly superior DFS. CONCLUSION: Metabolic parameters derived from preoperative PET/CT was significantly associated with recurrence in stage II IDC primarily treated with surgery. PET/CT can be a powerful prognostic tool in conjunction with novel staging systems and current biomarkers for patients undergoing contemporary therapy. Our results urge to reconsider the currently underestimated value of PET/CT confined to diagnostic aspect and to newly recognize its prognostic impact in these intermediate-risk breast cancer.

Predictive Value of 18F-Fluorodeoxyglucose Positron-Emission Tomography Metabolic and Volumetric Parameters for Systemic Metastasis in Tonsillar Cancer.

Although the prognosis of tonsillar cancer (human papillomavirus-positive oropharyngeal squamous cell carcinoma) is improving, disease control failure (distant metastasis) still occurs in some cases. We explored whether several 18F-fluorodeoxyglucose (FDG) positron-emission tomography (PET) parameters can predict metastasis. We retrospectively reviewed the medical records of 55 patients with tonsil squamous cell carcinoma who underwent pretreatment 18F-FDG positron-emission tomography/computed tomography (PET/CT) followed by primary surgery. During the follow-up period, systemic metastases were found in 7 of the 55 patients. The most common sites were the lungs (33%), bone (22%), brain/skull base (22%), small bowel (11%), and liver (11%). Pathologically, P53 mutation was less common in patients with systemic metastasis (41.7% vs. 14.3%, p = 0.054) than without systemic metastasis. In terms of PET parameters, the metabolic tumor volume (MTV2.5) and total lesion glycolysis (TLG2.5) values were lower in the primary tumor, and higher in the metastatic lymph nodes, of human papillomavirus (HPV)-positive compared to HPV-negative patients (all p < 0.05). The MTV2.5, TLG2.5, and tumor−to−liver uptake ratio were 36.07 ± 54.24 cm3, 183.46 ± 298.62, and 4.90 ± 2.77, respectively, in the systemic metastasis group, respectively; all of these values were higher than those of the patients without systemic metastasis (all p < 0.05). The MTV2.5 value was significantly different between the groups even when the values for the primary tumor and metastatic lymph nodes were summed (53.53 ± 57.78 cm3, p = 0.036). The cut-off value, area under the curve (95% confidence interval), sensitivity, and specificity of MTV2.5 for predicting systemic metastasis were 11.250 cm3, 0.584 (0.036−0.832), 0.571, and 0.565, respectively. The MTV2.5 of metastatic lymph nodes and summed MTV2.5 values of the primary tumor and metastatic lymph nodes were significantly higher in tonsillar cancer patients with than without systemic metastases. We suggest PET/CT scanning for pre-treatment cancer work-up and post-treatment surveillance to consider additional systemic therapy in patients with a high risk of disease control failure.

Prognostic Impact of Total Lesion Glycolysis (TLG) from Preoperative 18F-FDG PET/CT in Stage II/III Colorectal Adenocarcinoma: Extending the Value of PET/CT for Resectable Disease.

We investigated the prognostic role of metabolic parameters from preoperative 18F-FDG PET/CT in stage II/III colorectal adenocarcinoma. A total of 327 stage II/III colorectal adenocarcinoma patients who underwent curative resection were included. The maximal standard uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were analyzed for optimal cut-offs and their effect on DFS. Differences in DFS rates and hazard ratios for DFS between cut-offs were statistically significant in SUVmax, MTV2.5, MTV3, TLG 2.5, TLG3, and TLG30%. Factors significantly related to DFS in univariate Cox regression were age, sex, stage, preoperative CEA, SUVmax, MTV2.5, MTV3, TLG2.5, TLG3, and TLG30%. Age, sex, preoperative CEA, and TLG2.5 (p = 0.009) sustained statistically significant difference in multivariate analysis. The 1-, 3-, and 5-year DFS rates for TLG2.5 ≤ 448.5 were 98.1%, 79.6%, and 74.8%, significantly higher than 78.4%, 68.5%, and 61.1% of TLG2.5 > 448.5, respectively (p = 0.012). TLG, a parameter indicating both the metabolic activity and metabolic volume, was the strongest predictor independently associated with DFS, among several PET parameters with statistical significance. These results suggest the potential prognostic value of preoperative 18F-FDG PET/CT in stage II/III resectable colorectal cancer.

Cognitive decline according to amyloid uptake in patients with poststroke cognitive impairment.

BACKGROUND AND PURPOSE: Poststroke cognitive impairment (PSCI) is common, but the impact of ß-amyloid (Aß) on PSCI is uncertain. The proposed study will investigate amyloid pathology in participants with PSCI and how differently their cognition progress according to the amyloid pathology. METHODS: This multicenter study was designed to be prospective and observational based on a projected cohort size of 196 participants with either newly developed cognitive impairment, or rapidly aggravated CI, within 3 months after acute cerebral infarction. They will undergo 18F-flutemetamol positron emission tomography at baseline and will be categorized as either amyloid-positive (A+) or amyloid-negative (A-) by visual rating. The primary outcome measures will be based on Korean Mini-Mental State Examination changes (baseline to 12 months) between the A+ and A- groups. The secondary outcome measures will be the dementia-conversion rate and changes in the Korean version of the Montreal Cognitive Assessment (baseline to 12 months) between the A+ and A- groups. CONCLUSIONS: This study will provide a broadened perspective on the impact of Aß on the cause and outcomes of PSCI in clinical practice. Identifying amyloid pathology in patients with PSCI will help select patients who need more focused treatments such as acetylcholinesterase inhibitors. TRIAL REGISTRATION: Clinical Research Information Service identifier: KCT0005086.

Clinical Characteristics and Outcome of Pathologic N0 Non-small Cell Lung Cancer Patients With False Positive Mediastinal Lymph Node Metastasis on FDG PET-CT.

BACKGROUND/AIM: Preoperative fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET-CT) is a non-invasive and useful diagnostic tool to evaluate mediastinal lymph node (LN) metastasis in lung cancer. However, there are often false-positive LN cases in FDG PET-CT. This study aimed to explore the clinical characteristics and outcome of pathologic N0 non-small cell lung cancer patients with false-positive mediastinal LN on FDG PET-CT. PATIENTS AND METHODS: We enrolled 147 patients who underwent preoperative FDG PET-CT scan and mediastinal LN dissection. These patients were re-evaluated for post-operative pathologic nodal metastasis and divided into a false-positive group and a group of others. RESULTS: Among 40 patients diagnosed with clinical N1-3 on FDG PET-CT, 19 (47.5%) patients were pathologic N0, meaning false-positive LN by PET-CT. Preoperative absolute platelet count and platelet-lymphocyte ratio were significantly higher in patients with pathologic N0. The presence of lymphatic invasion was significantly lower in patients with pathologic N0 than in the group of others. Recurrence-free survival was significantly shorter in patients with false positive LN than in patients with true positive LN or true negative LN at the same pathologic stage. CONCLUSION: Higher absolute platelet count and PLR, lower proportion of lymphatic invasion and shorter recurrence-free survival were associated with false positive mediastinal LN on preoperative FDG PET-CT.

Feasibility of Iodine-131 6ß-Methyl-Iodo-19 Norcholesterol (NP-59) Scintigraphy to Complement Adrenal Venous Sampling in Management of Primary Aldosteronism: A Case Series.

PURPOSE: Primary aldosteronism (PA) is mainly comprised of aldosterone-producing adenoma and bilateral idiopathic adrenal hyperplasia. Current guidelines recommend adrenal venous sampling (AVS) as a gold standard method to classify the subtypes. However, because of technical challenges in AVS including invasiveness of AVS and a wide range of success rate for cannulation, it is not uncommon that appropriate decisions could not be made depending on AVS. The aim of this study is to elucidate the proper role of I­131­6ß­iodomethyl­norcholesterol (NP-59) scintigraphy in management of PA. PATIENTS AND METHODS: Between January 2009 and October 2018, patients with PA were retrospectively reviewed for the study. Five patients were included in the study who had NP-59 scintigraphy with non-conclusive AVS results or without AVS. We described the clinical outcome of patients in whom clinical decisions were made according to NP-59 scintigraphy results. RESULTS: Patients in the presenting cases were diagnosed for PA. AVS, the most reliable test to identify unilateral APA, were not applicable because of hypersensitivity to contrast dye (patient 1), and use of antiplatelet agents after acute cerebral infarction (patient 2). NP-59 scintigraphy was performed in patients 3 and 4 whose result of AVS and CT scan were inconsistent. In patient 5, who had bilateral adrenal adenomas (two in the left and one in the right adrenal gland), both unsuccessful catheterization and coexistence of cortisol overproduction made AVS results unreliable. CONCLUSION: Based on clinical outcomes of these case series, it is noticeable that NP-59 scintigraphy could play a substantial role in management of PA in selected cases.

Early Interim Chemotherapy Response Evaluation by F-18 FDG PET/CT in Diffuse Large B Cell Lymphoma.

Fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) after one cycle of standard chemotherapy in patients with diffuse large B cell lymphoma (DLBCL) was assessed. Prospectively enrolled 51 patients had four PET/CT studies using the same protocol and system: at baseline and after one, three, and six cycles of chemotherapy (PET0, PET1, PET3, PET6). The PET1 and PET6 Deauville five-point score (D5PS) agreed in 60.8%, while PET3 and PET6 D5PS agreed in 90.2%. The absolute and percent changes of peak standard uptake value corrected for lean body mass (SULpeak) compared to baseline were significantly different between PET1 and PET3 (p = 0.001, p < 0.001) and PET1 and PET6 (p = 0.002, p = 0.001), but not between PET3 and PET6 (p = 0.276, p = 0.181). The absolute SULpeak from PET1 predicted treatment failure with accuracy of 78.4% (area under the curve 0.73, p = 0.023). D5PS, SULpeak, and metabolic tumor volume (MTV) were not statistically different between responders versus non-responders, or the one year disease-free versus relapse groups. D5PS and PERCIST responses showed 100% agreement at end-of-therapy. In conclusion, the responses after three and six cycles of therapy showed high degree of agreement. D5PS or MTV after one cycle of chemotherapy could not predict response or one-year disease-free status, but the SULpeak from PET1 was associated with response to first line therapy in DLBCL. Deauville and PERCIST criteria show high concordance.

KSNM/KSID/KOSHIC Guidance for Nuclear Medicine Department Against the Coronavirus Disease 2019 (COVID-19) Pandemic.

The dramatic spread of Coronavirus Disease 2019 (COVID-19) has profound impacts on every continent and life. Due to human-to-human transmission of COVID-19, nuclear medicine staffs also cannot escape the risk of infection from workplaces. Every staff in the nuclear medicine department must prepare for and respond to COVID-19 pandemic which tailored to the characteristics of our profession. This article provided the guidance prepared by the Korean Society of Nuclear Medicine (KSNM) in cooperation with the Korean Society of Infectious Disease (KSID) and Korean Society for Healthcare-Associated Infection Control and Prevention (KOSHIC) in managing the COVID-19 pandemic for the nuclear medicine department. We hope that this guidance will support every practice in nuclear medicine during this chaotic period.

The clinical value of F-18 FDG PET/CT in differentiating malignant from benign lesions in pneumoconiosis patients.

OBJECTIVES: We reviewed PET/CT findings of pneumoconiosis and determined the ability of PET/CT to differentiate lung cancer from progressive massive fibrosis (PMF), and metastatic lymph nodes (LNs) from underlying reactive LN hyperplasia. METHODS: This was a retrospective study of patients with pneumoconiosis and suspected lung cancer. Maximum standardized uptake value (SUVmax), long- and short-axis diameters (DL and DS), ratio of DL to DS (DL/S), and Hounsfield unit (HU) from the lung mass and mediastinal LNs were measured. The cutoff values of each parameter were obtained by ROC analysis, and we evaluated the diagnostic sensitivity. RESULTS: Forty-nine pneumoconiosis patients were included. Eighty-three lung masses were detected, of which 42 were confirmed as lung cancer (23 squamous cell carcinomas, 12 adenocarcinomas, and 7 small cell carcinomas) and 41 were PMF. There were significant differences between lung cancer and PMF in terms of SUVmax, DS, DL/S, and HU (all p < 0.05). The sensitivity, specificity, and accuracy for diagnosis of lung cancer were 81.0%, 73.2%, and 77.1%, respectively, with an SUVmax cutoff value of 7.4; and 92.8%, 87.8%, and 90.4%, respectively, with a HU cutoff value of 45.5. Among the 40 LNs with available pathological results, 7 were metastatic. Metastatic LNs showed higher SUVmax, larger DS, and lower HU than benign lesions (all p < 0.05). The sensitivity, specificity, and accuracy for predicting metastatic LNs by PET/CT were 85.7%, 93.9%, and 92.5%, respectively. CONCLUSION: By applying PET and CT parameters in combination, the accuracy for differentiating malignant from benign lesions could be increased. PET/CT can play a central role in the discrimination of lung cancer and PMF. KEY POINTS: • Lung cancer showed significantly higher SUVmax than PMF. • Lung cancer showed similar D L but longer D S , resulting in a smaller D L/S than PMF. • SUVmax demonstrated additive value in differentiating lung cancer from PMF, compared with HU alone.

Clinicopathologic risk factors of radioactive iodine therapy based on response assessment in patients with differentiated thyroid cancer: a multicenter retrospective cohort study.

PURPOSE: We investigated whether predictive clinicopathologic factors can be affected by different response criteria and how the clinical usefulness of radioactive iodine (RAI) therapy should be evaluated considering variable factors in patients with differentiated thyroid carcinoma (DTC). METHODS: A total of 1563 patients with DTC who underwent first RAI therapy after total or near total thyroidectomy were retrospectively enrolled from 25 hospitals. Response to therapy was evaluated with two different protocols based on combination of biochemical and imaging studies: (1) serum thyroglobulin (Tg) and neck ultrasonography (US) and (2) serum Tg, neck US, and radioiodine scan. The responses to therapy were classified into excellent and non-excellent or acceptable and non-acceptable to minimize the effect of non-specific imaging findings. We investigated which factors were associated with response to therapy depending on the follow-up protocols as well as response classifications. Multivariate logistic regression analysis was performed to identify factors significantly predicting response to therapy. RESULTS: The proportion of patients in the excellent response group significantly decreased from 76.5 to 59.6% when radioiodine scan was added to the follow-up protocol (P < 0.001). Preparation method (recombinant human TSH vs. thyroid hormone withdrawal) was a significant factor for excellent response prediction evaluated with radioiodine scan (OR 2.129; 95% CI 1.687-2.685; P < 0.001) but was not for other types of response classifications. Administered RAI activity, which was classified as low (1.11 GBq) or high (3.7 GBq or higher), significantly predicted both excellent and acceptable responses regardless of the follow-up protocol. CONCLUSIONS: The clinical impact of factors related to response prediction differed depending on the follow-up protocol or classification of response criteria. A high administered activity of RAI was a significant factor predicting a favorable response to therapy regardless of the follow-up protocol or classification of response criteria.

Role of F-18 FDG PET/CT in non-conjunctival origin ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphomas.

BACKGROUND: Despite the widespread use of F-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) in the diagnosis and response assessment of patients with lymphoma, few studies have assessed its value in ocular adnexal lymphomas. The purpose of this study was to evaluate the role of FDG PET/CT in staging of non-conjunctival origin ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphomas (OAML). In addition, the diagnostic sensitivity of FDG PET/CT was compared with magnetic resonance imaging (MRI). FDG PET/CT of 123 consecutive patients with pathologically proven OAML between January 2009 and February 2016 were retrospectively reviewed. The patients with MALT lymphoma originating from conjunctiva were excluded. A total 50 patients with non-conjunctival origin OAML were assessed. Maximum standardized uptake value (SUVmax) and additional PET parameters were measured for all lesions. Sensitivity for primary tumor detection was compared with MRI. RESULTS: Ten patients had bilateral OAML and total 60 OAML lesions were analyzed. MRI was missing in one patient. The tumor locations were as follows: eyelid, 9; lacrimal gland, 18; orbit, 33. Fifty lesions (83.3%) were FDG-avid tumors with mean ± SD SUVmax 4.8 ± 2.4 (range 2.0~11.1). The mean SUVmax according to tumor location were as follows: eyelid, 3.7 ± 1.1 (2.8~5.3); lacrimal gland, 3.6 ± 1.4 (2.1~6.4); orbit, 5.7 ± 2.6 (2.0~11.1). Mean SUVmax among the 3 locations were statistically different (P = 0.010). The sensitivity was calculated as 83.1% (49/59) for FDG PET/CT and 89.8% (53/59) for MRI, which were statistically comparable (P = 0.219 by McNemar's test). Seven of 50 patients (14%) were upstaged by detection of extraocular lesions by FDG PET/CT (1 kidney and lung, 1 tonsil, 4 cervical LNs, 1 sacral foramen). CONCLUSION: 83.3% of the non-conjunctival origin OAML were FDG-avid tumors, with FDG PET/CT showing comparable sensitivity to that of MRI. FDG PET/CT detected unsuspected extraocular lymphoma involvement in 14% of the patients. FDG PET/CT performed for staging of non-conjunctival origin OAML may thus guide therapeutic management.

CYFRA 21-1 in Lymph Node Fine Needle Aspiration Washout Improves Diagnostic Accuracy for Metastatic Lymph Nodes of Differentiated Thyroid Cancer.

Fine needle aspiration cytology (FNAC) and washout thyroglobulin (Tg) measurements are the standard for evaluating a metastatic lymph node (LN) in thyroid cancer. However, patients rarely benefit from these procedures due to false results. This study aims to identify a reliable biomarker that significantly improves the diagnosis of metastatic LNs, in addition to FNAC and washout Tg. This study analyzed 130 LNs that were suspected to have metastases on thyroid ultrasonography, from June 2016 to December 2017. All subjects underwent FNAC, washout Tg measurements and a new biomarker, washout Cytokeratin fragment 21-1 (CYFRA 21-1) measurement. The final LN outcomes were confirmed by surgical histology, repeat FNAC, or follow-up image. The diagnostic values of the presence of washout CYFRA 21-1 for diagnosing metastatic LNs were evaluated according to final LN outcomes. Among the 130 LNs, 42 were metastatic lesions and 88 were benign. The washout CYFRA 21-1 levels were significantly higher in metastatic LNs than in benign LNs. In contrast to the findings of washout Tg, washout CYFRA 21-1 showed little overlap between benign and malignant LNs, and its diagnostic cutoff values were not affected by surgery. The combinations of FNAC and washout CYFRA 21-1 showed higher sensitivity (91.9%), specificity (96.5%), negative predictive value (98.8%), and diagnostic accuracy (94.2%) than FNAC with washout Tg. The combination of FNAC, washout Tg, and washout CYFRA 21-1 showed the best sensitivity (98.8%). When washout CYFRA 21-1 was applied to the discordant results that were observed between FNAC and washout Tg, 20 of 22 LNs were correctly diagnosed. Washout CYFRA 21-1 measurements in thyroid LNs provide a diagnostic modality.

Does FDG PET/CT have a role in determining adjuvant chemotherapy in surgical margin-negative stage IA non-small cell lung cancer patients?

PURPOSE: To evaluate the prognostic value of FDG PET/CT metabolic parameter compared to clinico-pathological risk factors in surgical margin-negative stage IA non-small cell lung cancer (NSCLC) patients. METHODS: 167 patients with consecutive FDG PET/CT scans from 2009 to 2015 performed for staging of NSCLC stage IA with plans for curative surgery were retrospectively reviewed. Maximum standardized uptake value (SUVmax) of primary tumor and mean SUV of liver were acquired from PET/CT. Tumor-to-liver SUV ratio (TLR) was calculated. Charts were reviewed to obtain basic patient characteristics (age, sex, smoking history, LDH, histologic subtype) and high-risk factors for adjuvant chemotherapy (tumor size, poorly differentiation, vascular invasion, and sub-lobar resection). Patients were dichotomized into two groups using optimal cut-off from receiver operating characteristic curve analysis of TLR to predict recurrence. Statistical analysis was done using Cox regression analysis and Kaplan-Meier method. Factors with P < 0.2 in univariate analysis were included in multivariate analysis. RESULTS: Recurrence rate was 12.6% (21/167). Median disease-free survival (DFS) was 47.2 months while 2-year and 5-year DFS rates were 93% and 86%, respectively. The optimal cut-off for TLR was 2.3. In univariate analysis, P value of sex, vascular invasion, and TLR were less than 0.2. In multivariable analysis, high TLR was the only factor that showed significant association with tumor recurrence (hazard ratio 3.795, P = 0.0048). CONCLUSIONS: TLR was an independent prognostic factor for recurrence and TLR could be an important risk factor to be considered in decision-making for adjuvant chemotherapy, even for those with stage IA NSCLC.

Heterologous prime-boost vaccination with adenoviral vector and protein nanoparticles induces both Th1 and Th2 responses against Middle East respiratory syndrome coronavirus.

The Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic and zoonotic virus with a fatality rate in humans of over 35%. Although several vaccine candidates have been developed, there is still no clinically available vaccine for MERS-CoV. In this study, we developed two types of MERS-CoV vaccines: a recombinant adenovirus serotype 5 encoding the MERS-CoV spike gene (Ad5/MERS) and spike protein nanoparticles formulated with aluminum (alum) adjuvant. Next, we tested a heterologous prime-boost vaccine strategy, which compared priming with Ad5/MERS and boosting with spike protein nanoparticles and vice versa, with homologous prime-boost vaccination comprising priming and boosting with either spike protein nanoparticles or Ad5/MERS. Although both types of vaccine could induce specific immunoglobulin G against MERS-CoV, neutralizing antibodies against MERS-CoV were induced only by heterologous prime-boost immunization and homologous immunization with spike protein nanoparticles. Interestingly, Th1 cell activation was induced by immunization schedules including Ad5/MERS, but not by those including only spike protein nanoparticles. Heterologous prime-boost vaccination regimens including Ad5/MERS elicited simultaneous Th1 and Th2 responses, but homologous prime-boost regimens did not. Thus, heterologous prime-boost may induce longer-lasting immune responses against MERS-CoV because of an appropriate balance of Th1/Th2 responses. However, both heterologous prime-boost and homologous spike protein nanoparticles vaccinations could provide protection from MERS-CoV challenge in mice. Our results demonstrate that heterologous immunization by priming with Ad5/MERS and boosting with spike protein nanoparticles could be an efficient prophylactic strategy against MERS-CoV infection.

Prognostic Value of Pre- and Post-Treatment FDG PET/CT Parameters in Small Cell Lung Cancer Patients.

PURPOSE: To evaluate the prognostic value of PET parameters obtained from pre- and post-treatment FDG PET/CT examinations in patients with SCLC. METHODS: Fifty-nine patients with initially diagnosed SCLC from 2009 to 2014 were included and had chemotherapy and/or concurrent chemoradiotherapy. FDG PET/CT examinations were performed before (PET1) and after (PET2) treatment to evaluate treatment response. A region of interest was placed over the primary lesion and metastatic lymph nodes within the thoracic cavity. PET parameters including change from PET1 to PET2 (Δ in %) were acquired: SUVmax, SUVpeak, MTV2.5, TLG, ΔSUVmax, ΔSUVpeak, ΔMTV and ΔTLG. Patient characteristics including staging, age, sex, LDH and response evaluation by RECIST were surveyed. Statistical analysis was done using Kaplan-Meier method and Cox regression analysis with respect to OS and PFS. RESULTS: The median follow-up was 9.6 months (2.5-80.5 months). 27 patients were LD and 32 were ED. Forty-six patients (78.0%) had died, and median OS was 8.6 months; 51 patients (86%) showed disease progression, and median PFS was 2.5 months. On univariate analysis, patients with ED, high interval change (ΔSUVmax and ΔSUVpeak) and low PET2 parameters showed longer OS and PFS. Multivariate analyses demonstrated that ΔSUVpeak (HR 2.6, P = 0.002) was an independent prognostic factors for OS, and MTV2.5 of PET2 (HR 2.8, P = 0.001), disease stage (HR 2.7, P = 0.003) and RECIST (HR 2.0, P = 0.023) were independent prognostic factors for PFS. CONCLUSIONS: Metabolic and volumetric PET parameters obtained from pre- and post-treatment FDG PET/CT examinations in patients with SCLC have significant prognostic information.

18F-fluorodeoxyglucose uptake of hepatocellular carcinoma as a prognostic predictor in patients with sorafenib treatment.

PURPOSE: Sorafenib, an oral multikinase inhibitor, is a recommended treatment option available for patients with Barcelona Clinic Liver Cancer (BCLC)-C stage hepatocellular carcinoma (HCC). This study aimed to evaluate the performance of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) for predicting tumour progression during sorafenib treatment. METHODS: We formed a retrospective cohort comprising patients treated with sorafenib for at least 30 days and undergoing 18F-FDG PET/CT within 1 month before treatment. For statistical analyses, the tumour-to-liver standardised uptake value (SUV) ratio (TLR) of the most hypermetabolic lesion was measured. RESULTS: Among a total of 35 patients, two obtained partial remission, and 11 showed stable disease after the first response evaluation. Patients with a TLR ≥ 2.9 (n = 17) had a median overall survival (OS) of 3.7 months after sorafenib treatment, whereas patients with a TLR < 2.9 (n = 18) had median OS of 12.2 months (P < 0.001), although the disease control rate was not significantly different between the two groups. Pretreatment TLR ≥ 2.9 (hazard ratio [HR] = 6.318, P = 0.002) and Child-Pugh class B (HR = 4.316, P = 0.044) were poor prognostic factors for OS, and a TLR ≥ 2.9 (HR = 2.911, P = 0.024) was the only poor prognostic factor for progression-free survival in a multivariate analysis. CONCLUSION: Pretreatment tumour metabolic activity assessed by 18F-FDG PET is an independent prognostic factor for survival in patients with BCLC-C stage HCC receiving sorafenib monotherapy, although it may not predict tumour response to the treatment.

Clinical utility of 18F-FDG PET/CT in low 18F-FDG-avidity breast cancer subtypes: comparison with breast US and MRI.

OBJECTIVE: The aim of this study was to evaluate the diagnostic performance of fluorine-18-fluorodeoxyglucose (F-FDG) PET/CT in initial axillary lymph node (ALN) staging and tumor recurrence in breast cancer subtypes with low F-FDG avidity in comparison with breast ultrasonography (US) and/or MRI. PATIENTS AND METHODS: A total of 491 PET/CT exams from 192 patients with biopsy-proven breast cancer subtypes with low F-FDG avidity were enrolled retrospectively. Nodal status on staging and locoregional recurrence or metastasis on surveillance was confirmed either by pathology or by further clinical follow-up. Comparison was made with recent US and/or MRI. RESULTS: A total of 142 scans were for staging and 349 scans were for surveillance. For the staging, 127 tumors had perceptible F-FDG uptake. For the detection of ALN metastasis, the sensitivity, specificity, and accuracy were calculated to be 51.5, 94.6, and 84.7% for F-FDG PET/CT, 42.4, 90.1, and 79.2% for US, and 51.5, 88.3, and 79.9% for MRI, respectively. PET/CT showed significantly higher specificity than MRI. In the surveillance, the total recurrence rate was 4.3%. There were no cases of recurrence of mucinous or tubular carcinoma. PET/CT showed comparable diagnostic performance for locoregional recurrence compared with US in invasive lobular carcinoma. Distant metastasis developed in five patients (one stage II, four stage III), and all of these were identified by PET/CT alone. CONCLUSION: PET/CT showed comparable diagnostic performance with US and/or MRI for ALN staging and detecting tumor recurrence even when the primary breast cancer has low F-FDG avidity. F-FDG PET/CT also detected unsuspected distant metastasis in 36.4% of stage III patients. Surveillance PET/CT should be considered in advanced-stage invasive lobular carcinoma for early detection of recurrence.